UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-K

(Mark One)

☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the fiscal year ended December 31, ~~2024~~2025

☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the transition period from ______to______

Commission File No. 001-37590

AVALO THERAPEUTICS, INC.

(Exact name of registrant as specified in its charter)


Delaware (State or other jurisdiction of incorporation or organization)			45-0705648 (I.R.S. Employer Identification No.)

~~540~~1500 ~~Gaither~~Liberty ~~Road~~Ridge Drive, Suite ~~400~~321

~~Rockville~~Wayne, ~~Maryland~~Pennsylvania ~~20850~~19087

(Address of principal executive offices)

Telephone: (410) 522-8707

(Registrant’s telephone number, including area code)

Securities registered pursuant to Section 12(b) of the Act:


Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock, $0.001 Par Value	AVTX	Nasdaq Capital Market

Securities registered pursuant to section 12(g) of the Act: None

Indicate by check mark if the registrant is a well‑known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒

Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ☒

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and

(2) has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐

Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S‑T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes ☒ No ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule12b-2 of the Exchange Act.

Large accelerated filer ☐

Accelerated filer ☐

Non-accelerated filer ☒

Smaller reporting company ☒

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☐

If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐

Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b‑2 of the Act). Yes ☐ No ☒

The aggregate market value of the registrant’s shares of common stock held by non-affiliates of the registrant as of June 2830, ~~2024~~2025 (which is the last business day of the registrant's most recently completed second fiscal quarter) based upon the closing market price of such stock on the Nasdaq Capital Market on that date was approximately $1253.97 million. Shares of common stock held by each officer and directors and by each person

known to be the registrant who owned 10% or more of the outstanding common stock have been excluded in that such person may be deemed to be affiliates. This determination of affiliate status is not necessarily a conclusive determination for other purposes.

As of March 1718, ~~2025~~2026, there were 1022,~~671~~788,~~934~~452 outstanding shares of the registrant’s common stock, par value $0.001 per share.

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TABLE OF CONTENTS

			Page
PART I			ii
Item 1. Business			1
Item 1A. Risk Factors			1216
Item 1B. Unresolved Staff Comments			4458
Item 1C. Cybersecurity			4458
Item 2. Properties			4559
Item 3. Legal Proceedings			4559
Item 4. Mine Safety Disclosures			4659
PART II			4760
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities			4760
Item 6. Reserved			4861
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations			4962
Item 7A. Quantitative and Qualitative Disclosures About Market Risk			5870
Item 8. Financial Statements and Supplementary Data			5870
Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure			5870
Item 9A. Controls and Procedures			5870
Item 9B. Other Information			5971
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspection			5972
PART III			6073
Item 10. Directors, Executive Officers and Corporate Governance			6073
Item 11. Executive Compensation			6479
Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters			7288
Item 13. Certain Relationships and Related Transactions, and Director Independence			7592
Item 14. Principal Accountant Fees and Services			7793
PART IV			7895
Item 15. Exhibits; Financial Statement Schedules			7895
Item 16. Form 10-K Summary			84100

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PART I

SPECIAL NOTE REGARDING FORWARD‑LOOKING STATEMENTS

This report and the information incorporated herein by reference contain forward-looking statements that involve a number of risks and uncertainties, as well as assumptions that, if they never materialize or if they prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Although our forward-looking statements reflect the good faith judgment of our management, these statements can only be based on facts and factors currently known by us. Consequently, forward-looking statements are inherently subject to risks and uncertainties, and actual results and outcomes may differ materially from results and outcomes discussed in the forward-looking statements.

Forward-looking statements can be identified by the use of forward-looking words such as “projects,” “may,” “might,” “will,” “could,” “would,” “should,” “continue,” “seeks,” “aims,” “predicts,” “believes,” “expects,” “anticipates,” “estimates,” “intends,” “plans,” “potential,” “pro forma” or other similar words (including their use in the negative), or by discussions of future matters such as: the future financial and operational outlook; the development of product candidates; and other statements that are not historical. These statements include but are not limited to statements under the captions “Business,” “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” as well as other sections in this report. You should be aware that the occurrence of any of the events discussed under the caption “Risk Factors” and elsewhere in this report could substantially harm our business, results of operations and financial condition and cause our results to differ materially from those expressed or implied by our forward-looking statements. If any of these events occurs, the trading price of our common stock and the price or value of our other securities could decline and you could lose all or a part of the value of your investment in our Company.

The cautionary statements made in this report are intended to be applicable to all related forward-looking statements wherever they may appear in this report. We urge you not to place undue reliance on these forward-looking statements, which speak only as of the date of this report. Except as required by law, we assume no obligation to update or revise these forward-looking statements for any reason, even if new information becomes available in the future.

As used in this report, the terms “Avalo,” “Company,” “we,” “us,” and “our” mean Avalo Therapeutics, Inc. and its subsidiaries unless the context indicates otherwise.

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SUMMARY OF PRINCIPAL RISK FACTORS

This summary briefly states the principal risks and uncertainties facing our business that could affect our securities, which are only a select portion of those risks. A more complete statement of those risks and uncertainties is set forth under Part I, Item 1A “Risk Factors” of this ~~annual~~Annual ~~report~~Report on Form 10-K. This summary is qualified in its entirety by that more complete statement. You should carefully read the entire “Risk Factors” section when considering the risks and uncertainties as part of your evaluation of our business and your investment in our company.

•If clinical trials of our product candidates fail to demonstrate safety and efficacy to the satisfaction of regulatory authorities or do not otherwise produce positive results, we may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of our product candidates.

•If we ~~are~~experience ~~unable~~delays ~~to enroll appropriate subjects~~ in clinical ~~trials~~testing, orwe ~~retain~~will ~~patients~~be delayed in ~~the~~obtaining ~~clinical~~regulatory ~~trials~~approvals weand ~~perform,~~commercializing weour ~~may~~product ~~not~~candidates, beour ~~able~~costs tomay ~~complete~~increase ~~these~~and ~~trials~~our onbusiness amay ~~timely~~be ~~basis, or at all~~harmed.

•Even if we complete the necessary clinical trials, we cannot predict when or if we will obtain marketing approval to commercialize a product candidate or the approval may be for a narrower indication than we expect or may be conditioned on costly post-approval obligations.

•We rely on third parties to conduct and monitor our clinical trials. The failure of these third parties to successfully carry out their contractual duties or meet expected deadlines could hinder our ability to commercialize or obtain marketing approval for our product candidates in a timely manner, or at all.

•Our product candidates that we intend to commercialize are in early to mid-stages of development. If we do not successfully complete nonclinical testing and clinical development of our product candidates or experience significant delays in doing so, our business may be materially harmed. Our focus and reliance on abdakibart (AVTX-009) increases the risk of such exposure.

•We may expend our limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success. Our focus and reliance on abdakibart (AVTX-009) increases the risk of such exposure.

•The marketing approval processes of the United States Food and Drug Administration (the “FDA”) and ~~comparable~~other ~~foreign~~ regulatory authorities are lengthy, time‑consuming, costly and inherently unpredictable. Our inability to obtain regulatory approval for our product candidates would substantially harm our business and prospects.

•We use third parties to manufacture all of our product candidates. This may increase the risk that we will not have sufficient clinical or commercial quantities of our product candidates, ~~to conduct our clinical trials~~ or ~~for commercial production or whether we can acquire~~ such quantities at an acceptable cost, which could result in the delay, prevention, or impairment of clinical development and commercialization of our product candidates and could harm our business, financial condition and results of operations.

•We expect to require additional capital in the future to continue to fund our operations and to finance the further advancement of our product candidates, which might not be available to us on acceptable terms, or at all. Failure to obtain any necessary capital could force us to delay, limit or terminate our product development efforts or significantly curtail or cease our operations altogether.

•IfEven if we ~~are~~receive ~~unable~~marketing toapproval ~~obtain~~for orabdakibart ~~maintain~~(AVTX-009) ~~intellectual~~or ~~property~~future ~~rights~~product candidates, orour ifcurrent ~~the~~or ~~scope~~future ofproduct ~~patent~~candidates ~~protection~~may is not ~~sufficiently~~achieve broad, ~~competitors~~market ~~could~~acceptance, ~~develop~~which ~~and~~would ~~commercialize~~limit ~~products~~the ~~similar~~revenue orthat ~~identical to ours, and~~ we ~~might~~generate ~~not~~from betheir ~~able~~sales toand ~~compete~~could ~~effectively~~prevent inus ~~that~~from ~~market.~~achieving ~~Furthermore,~~or ~~our~~sustaining ~~patent for AVTX-009 is set to expire in 2026~~profitability.

•If we are unable to obtain or maintain intellectual property rights, or if the scope of patent protection is not sufficiently broad, competitors could develop and commercialize products similar or identical to ours, and we might not be able to compete effectively in that market. Furthermore, our US composition-of-matter patent for abdakibart (AVTX-009) expired in February 2026.

iii

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•If we breach the license and development agreements related to our product candidates, we could lose the ability to develop and commercialize our product candidates.

•If we fail to attract and keep management and other key personnel, as well as members of our board of directors, we may be unable to develop our product candidates or otherwise implement our business plan.

•The ~~market~~ price of our common stock iscould ~~volatile,~~be subject to rapid and ~~you~~substantial ~~could~~volatility. ~~lose~~Such ~~all~~volatility, including any stock run-ups, may be unrelated to our actual or ~~part~~expected operating performance and financial condition or prospects, making it difficult for prospective investors to assess the rapidly changing value of ~~your~~our ~~investment~~common stock. Volatility in our common stock price may subject us to securities litigation or regulatory scrutiny.

•We have incurred significant net losses in most periods since our inception and we expect to continue to incur net losses in the future.

~~iii~~•We or the third parties upon whom we depend may be adversely affected by unforeseen global events, natural disasters, and our business continuity and disaster recovery plans may not adequately protect us from a serious disaster.

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PART I

Item 1. Business.

Overview

~~Avalo~~We ~~Therapeutics,~~are ~~Inc. (the “Company”, “Avalo” or “we”) is~~ a clinical stage biotechnology company ~~focused~~fully ondedicated ~~the~~to ~~treatment~~developing ofIL-1β-based treatments for immune-mediated ~~dysregulation~~inflammatory diseases. ~~Avalo’s~~Our lead ~~asset~~product iscandidate, abdakibart (AVTX-009), an anti-IL-1β monoclonal antibody (“mAb”), ~~targeting~~is ~~inflammatory~~in ~~diseases~~a Phase 2 clinical trial for hidradenitis suppurativa (“HS”). We are also exploring additional opportunities to make an impact in prevalent indications that have significant remaining unmet needs.

~~Avalo~~Our ~~was~~current ~~incorporated~~focus inis ~~Delaware~~on ~~and~~completing ~~commenced~~the ~~operation~~Phase 2 (“LOTUS”) trial evaluating abdakibart (AVTX-009) in ~~2011~~HS, ~~and~~preparing ~~completed~~for ~~its~~the ~~initial~~anticipated ~~public~~topline ~~offering~~data readout in ~~October~~the ~~2015.~~second quarter of 2026, and planning for our Phase 3 trial(s).

Our Strategy

Our strategy for increasing stockholder value includes:

•Advancing our pipeline through development to regulatory approval~~. Most~~ —notably and in the near term, by completing our Phase 2 LOTUS trial in ~~hidradenitis suppurativa~~HS, preparing ~~for~~to ~~the~~initiate ~~next~~our ~~stage~~pivotal trial(s) pending the readout of ~~development~~the ~~for~~Phase ~~that~~2 ~~indication~~LOTUS trial results and considering further indication expansion for abdakibart (AVTX-009);

•Acquiring or in-licensing rights to and/or developing targeted, complementary differentiated preclinical and clinical stage compounds that treat immune -mediated inflammatory disease; and

•Opportunistically out-~~license~~licensing rights to compounds, indications or geographies.

~~There~~Pipeline is no guarantee that our products will obtain regulatory approval by the United States Food and Drug Administration (the “FDA”) or comparable foreign regulatory authorities. The FDA approval process is complex, time-~~consuming,~~ ~~and expensive. Prior to submitting a new drug application (“NDA”) or biologics license application (“BLA”)~~Overview, ~~the FDA approval process typically involves the following: preclinical laboratory and animal testing~~Competition, ~~submission of an Investigational New Drug (“IND”) application,~~ and ~~human~~Intellectual clinical trials to establish safety and efficacy. Human clinical trials typically include: Phase 1 studies to evaluate the safety and tolerability of the drug, generally in normal, healthy volunteers; Phase 2 studies to evaluate safety and efficacy, as well as appropriate doses; these studies are typically conducted in patient volunteers who suffer from the particular disease condition that the drug is designed to treat; and Phase 3 studies to evaluate the safety and efficacy of the product at specific doses in one or more larger pivotal trials. Upon submission of an NDA or BLA, the FDA reviews the application, which potentially involves an FDA advisory committee review, and typically inspects manufacturing facilities and clinical study sites. Even if the FDA approves a product, it may impose post-approval requirements or withdraw approval if safety or efficacy issues arise. The processes for obtaining marketing approvals in foreign countries, along with subsequent compliance with applicable statutes and regulations, require the expenditure of substantial time and financial resources. Property

~~Pipeline~~We —are ~~Overview,~~advancing ~~Competition,~~a pipeline that emphasizes a high-value and ~~Intellectual~~potentially ~~Property~~best-in-class and best-in-disease biologics for immune mediated inflammatory diseases.

~~AVTX-009:~~The ~~Anti-IL-1β~~following ~~monoclonal~~table ~~antibody~~summarizes ~~(“mAb”)~~certain ~~targeting~~key ~~inflammatory~~information ~~diseases.~~about our lead product candidate:

~~Overview:~~Abdakibart (AVTX-009 ~~is a humanized monoclonal antibody (IgG4~~): ~~that binds to interleukin~~Anti-~~1β (“~~IL-1β”) ~~with~~mAb ~~high~~targeting ~~affinity and neutralizes its activity. IL-1β is a central driver in the~~ inflammatory ~~process. Overproduction or dysregulation of IL-1β is implicated in many autoimmune and inflammatory~~ diseases. IL-1β is a major, validated target for therapeutic intervention. There is evidence that inhibition of IL-1β could be effective in hidradenitis suppurativa, a chronic, often debilitating inflammatory skin disease that causes painful lumps, abscesses and tunnels to form under the skin (“HS”), and a variety of other inflammatory diseases in dermatology, gastroenterology, and rheumatology. Note that AVTX-009 has previously been referred to as FL-101 and LY2189102, when rights in it were held by Leap Therapeutics (previously Flame Biosciences) and Eli Lilly and Company, respectively.

InOur ~~October~~lead ~~2024~~product candidate, ~~Avalo~~abdakibart ~~dosed~~(AVTX-009), ~~its~~is ~~first~~a ~~patient~~high inaffinity, ~~its~~highly ~~Phase~~potent 2humanized IgG mAb designed to specifically inhibit IL-1β and block downstream inflammatory pathways. Abdakibart (AVTX-009) is a humanized monoclonal antibody (IgG4) that binds to interleukin-1β (“~~LOTUS~~IL-1β”) ~~trial~~with ofhigh ~~AVTX~~affinity and neutralizes its activity. IL-~~009~~1β is a pro-inflammatory cytokine that plays a central role in HSthe pathogenesis of a wide range of human diseases. ~~The~~It ~~LOTUS~~activates ~~Trial~~immune iscells athat ~~randomized~~generate proinflammatory cytokines, ~~double~~including IL-~~blind~~6, ~~placebo~~TNF-~~controlled~~α, ~~parallel~~and IL-~~group~~17. ~~Phase~~Dysregulated 2IL-1β ~~trial~~signaling ~~with~~is ~~two~~a major driver of inflammation, contributing to the progression of autoimmune disorders. IL-1β inhibition has proven effective in multiple immune-mediated inflammatory diseases. Abdakibart (AVTX-009) ~~dose~~has ~~regimens~~previously been referred to ~~evaluate~~as ~~the~~FL-101 ~~efficacy~~and LY2189102, when rights in it were held by Leap Therapeutics (previously Flame Biosciences) and ~~safety~~Eli ofLilly and Company, respectively. Abdakibart (AVTX-009) is currently being studied in ~~approximately~~the ~~180~~LOTUS ~~adults~~Phase ~~with~~2 ~~moderate~~trial toin ~~severe~~participants with HS. ~~Subjects~~In ~~are~~October ~~randomized~~2025, ~~(1:1:1)~~we announced that we completed enrollment in the Phase 2 LOTUS trial and expect to report topline data in the second quarter of 2026.

Phase 2 LOTUS Trial

The LOTUS trial (NCT06603077) is a randomized, double-blind, placebo-controlled, parallel-group Phase 2 trial with two abdakibart (AVTX-009) dosing regimens to evaluate the efficacy, safety and tolerability of abdakibart (AVTX-009) in approximately 250 adults with moderate to severe hidradenitis suppurativa. Subjects were randomized (1:1:1) to receive either one of two dosing regimens of abdakibart (AVTX-009) or placebo during a 16-week treatment phase. The primary efficacy endpoint is the proportion of subjects achieving Hidradenitis Suppurativa Clinical Response 75 (HiSCR75) at Week 16. Secondary objectives include but are not limited to: the proportion of patients achieving HiSCR50 and HiSCR90 as well as

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~~receive~~change ~~either~~from ~~one~~baseline ofin: ~~two~~International ~~doses~~HS ofSeverity ~~AVTX-009~~Score orSystem ~~placebo~~(IHS4), ~~during~~draining afistula ~~16-week~~count, ~~treatment~~abscess ~~phase.~~and ~~The~~inflammatory ~~primary~~nodule ~~efficacy~~(AN) ~~endpoint~~count, isand ~~the~~patients ~~proportion~~achieving ofat ~~subjects~~least ~~achieving~~a ~~Hidradenitis~~30% ~~Suppurativa~~reduction ~~Clinical~~on ~~Response~~a ~~(HiSCR75)~~numerical atrating ~~Week~~scale 16in Patient's Global Assessment of Skin Pain (PGA Skin Pain). We are the study sponsor and ~~the~~ current trial site locations include the United States, Canada, France, Germany, Italy, Spain, Bulgaria, Czech Republic, Greece, Poland, Australia, Turkey, and Slovakia.

~~Secondary~~Development ~~endpoints~~Opportunity ~~include~~in ~~the following:~~ HS

~~•Incidence~~IL-1β ofis ~~adverse~~a ~~events~~pro-inflammatory ~~(“AEs”),~~cytokine ~~and~~that ~~changes~~plays ~~from~~a ~~Baseline~~central role in ~~vital~~the ~~signs~~pathogenesis of a wide range of human diseases. IL-1β activates immune cells that generate proinflammatory cytokines, ~~physical~~including ~~examinations~~IL-6, TNF-α, and ~~clinical~~IL-17. ~~laboratory~~Dysregulated ~~tests~~IL-1β signaling is a major driver of inflammation, contributing to the progression of autoimmune disorders.

~~•The~~ ~~proportion~~IL-1β ofinhibition ~~subjects~~has ~~achieving~~proven ~~HiSCR50~~effective in multiple immune-mediated inflammatory diseases. IL-1β also has a well-established class safety and tolerability profile supported by ~~visit~~ILARIS® (canakinumab), an IL-1β blocker approved for use in multiple indications.

~~•The~~HS ~~proportion~~is ofa ~~subjects~~chronic, ~~achieving~~progressive, ~~HiSCR90~~often debilitating inflammatory skin disease that causes painful nodules, abscesses, and tunnels to form under the skin. Areas commonly affected by ~~visit~~HS include the nape of the neck, breasts, chest, armpits, abdomen, buttocks and anus, groin and genitals, and inner thighs. If not adequately or promptly treated, the chronic inflammation characteristic of HS may progress to tissue destruction and permanent scarring. HS typically first presents in late adolescence or early adulthood and is estimated to affect 0.7–1.2% of the U.S. population, though some sources suggest the prevalence may be as high as 2–4%.

~~•Change~~There ~~from~~is ~~Baseline~~a substantial unmet need for more effective and durable treatment options in ~~International~~HS. Currently approved biologics for HS ~~Severity~~(adalimumab ~~Score~~(anti-TNF-α), ~~System~~secukinumab (~~“IHS4”~~anti-IL-17A) , and bimekizumab (dual anti-IL-17A/F)) achieve HiSCR50 (an efficacy measure) only ~50% of the time, with more stringent thresholds (HiSCR75/90) achieved in even fewer individuals. Long-term disease control remains a challenge with established biologics and an area of uncertainty with newer agents (secukinumab and bimekizumab), as data on sustained efficacy are still emerging. In addition, people with HS often have comorbidities that can limit access to current treatment options.

~~•Change~~There ~~from~~were ~~Baseline~~an estimated 3.4 million people in ~~Abscess~~the United States with HS in 2024 with such number expected to rise to 3.5 million by 2035. Additionally, it is estimated that HS affects approximately 1-4% of the population worldwide. Of the 3.4 million people who were estimated to have HS in the United States in 2024, only approximately 1.0 million were diagnosed and ~~Inflammatory~~treated, ~~Nodule~~with ~~(“AN”)~~this ~~count~~number projected to rise to 1.6 million by 2035. The global HS market is expected to grow to >$10 billion by 2035.

•Change from Baseline in draining fistula count

•Percentage of subjects achieving at least a 30% reduction and at least a 1 unit reduction from Baseline on a Numerical Rating Scale (“NRS”) in Patient’s Global Assessment of Skin Pain (“PGA Skin Pain”) among subjects with Baseline NRS ≥3 (“NRS30”)

•Percentage of subjects with flares defined as ≥25% increase in AN count plus an increase of ≥2 in AN count compared to Baseline

•Incidence of AVTX-009 anti-drug antibodies (“ADA”) at specified timepoints

In addition to HS, Avalo intends to develop AVTX-009 in at least one other chronic inflammatory indication.

Competition: We face substantial competition from major pharmaceutical companies and biotechnology companies worldwide. In particular, pharmaceutical and biotechnology companies that develop and/or market products targeting IL-1β or the indications we are pursuing, including HS, are likely to represent substantial competition.

As of the date of this report, and to our knowledge, there is one company with an approved anti-IL-1β antibody (Novartis AG or “Novartis”) and Avalo is one of four additional companies with novel, non-biosimilar antibodies specifically targeting IL-1β in clinical development worldwide (such as Novartis and Sunshine Guojian Pharmaceutical Co Ltd, or “Sunshine Guojian”), inclusive of all approved indications and indications in development. There are additional companies developing and/or marketing known or investigational therapeutic agents that target IL-1α as well as IL-1β through interactions with IL-1 receptors, engineered bispecific antibodies, or through adjacent mechanistic targets (such as IL-1RAP and NLRP3).

Worldwide, several companies currently market TNF alpha inhibitors (such as AbbVie Inc., or “AbbVie”, and additional companies marketing biosimilars) and IL-17 inhibitors (such as Novartis and UCB) for HS. As of the date of this report, five additional companies have phase 3 development programs in HS with IL-17 inhibitors (Moonlake Immunotherapies, Inc.), JAK inhibitors (Incyte Corporation, AbbVie), BTK inhibitors (Novartis), and dual IL-1α/β inhibitors (AbbVie). There are multiple additional companies pursuing phase 2, phase 1, and preclinical development programs in HS.

License: AVTX-009 is subject to a world-wide exclusive license from Eli Lilly and Company (“Lilly”) (the “Lilly License Agreement”), as well as an agreement under which AlmataBio, Inc. (“AlmataBio”) purchased rights to the compound from Leap Therapeutics, Inc. (“Leap” and the “Leap Agreement”). Avalo obtained the rights to AVTX-009, including the Lilly License Agreement and Leap Agreement, pursuant to its acquisition of AlmataBio in the first quarter of 2024 (the “AlmataBio Transaction”). Avalo is responsible for the development and commercialization of the program.

Avalo is required to pay Lilly up to $70 million based on the achievement of specified development and regulatory milestones. Upon commercialization, the Company is required to pay sales-based milestones aggregating up to $650 million payable to Lilly and up to $70 million to Leap.

Additionally, Avalo is required to pay royalties to Lilly of between 5% and 15% of Avalo or its sublicenees’ annual net sales, beginning on first commercial sale of a licensed product in a given territory and expiring on a county-by-country basis, on the latest of (a) the tenth (10th) anniversary of the date of the first commercial sale, (b) the expiration of the last-to-expire licensed patent in the given country, or (c) the expiration of any data exclusivity period for the licensed product in the given territory.

Avalo has not paid any milestones, royalties or any other amounts under the Lilly License Agreement or the Leap Agreement as of the date of this report. Additionally, there are no annual or maintenance fees payable under the Lilly License Agreement or the Leap Agreement.

The Lilly License Agreement remains in effect until the expiration of the last-to-expire royalty term of any licensed products. Each party may terminate for cause, and though the Company may terminate at its sole discretion by giving one-hundred twenty

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(120) days’ prior written notice to Lilly, all licenses and rights granted pursuant to the agreement shall automatically terminate and revert to Lilly. There are no termination or expiration provisions under the Leap Agreement.

Pursuant to the AlmataBio Transaction, the Company made a cash payment of $7.5 million due to the former AlmataBio stockholders upon the initial closing of the private placement investment, which closed on March 28, 2024. Further, a portion of the consideration for the AlmataBio Transaction includes development milestones to the former AlmataBio stockholders including $5.0 million due upon the first patient dosed in a Phase 2 trial in patients with hidradenitis suppurativa for AVTX-009 and $15.0 million due upon the first patient dosed in a Phase 3 trial for AVTX-009, both of which are payable in cash or Avalo stock at the election of the former AlmataBio stockholders, subject to the terms and conditions of the definitive merger agreement. In October 2024, the first development milestone was met and the Company made the $5.0 million payment in cash.

Market, Data, and Patent Exclusivity: If we receive marketing approval, we expect to receive biologics reference product exclusivity in the United States, which may provide twelve years of data exclusivity in the United States from the date of FDA approval and ten years of combined data and market exclusivity in Europe (the EU and UK) from the date of approval. We plan to primarily rely on biologics data or market exclusivity; however, the table below sets forth details of a patent related to AVTX-009 that might provide additional protection that the Company considers material:

Product

Jurisdiction

Owned/Licensed

Status

Expiration Date

Protection Type

AVTX-009

United States

Licensed

Issued

2026

Composition of Matter

Legacy Programs

We are not currently pursuing the clinical development of the following ~~Company~~ legacy programs and are exploring strategic alternatives for them.

Quisovalimab (AVTX-002): Quisovalimab is fully human mAb, directed against human LIGHT (Lymphotoxin-like, exhibits Inducible expression, and competes with HSV Glycoprotein D for Herpesvirus Entry Mediator, a receptor expressed by T lymphocytes; also referred to as TNFSF14).

•AVTX-006: AVTX-006 is a dual mTORc1/c2 small molecule inhibitor.

•AVTX-008: AVTX-008 is a fully human B and T Lymphocyte Attenuator agonist fusion protein.

•AVTX-913: AVTX-913 is a nucleotide prodrug for the treatment of a mitochondrial disorder and is a preclinical asset.

Licensing and Partnerships

Eli Lilly License Agreement

Abdakibart (AVTX-009) is subject to a world-wide exclusive license from Eli Lilly and Company (“Lilly”) (the “Lilly License Agreement”), as well as an agreement under which AlmataBio, Inc. (“AlmataBio”) purchased rights to the compound from Leap Therapeutics, Inc. (“Leap” and the “Leap Agreement”). We obtained the rights to abdakibart (AVTX-009), including the Lilly License Agreement and Leap Agreement, pursuant to our acquisition of AlmataBio in the first quarter of 2024 (the “AlmataBio Transaction”). We are responsible for the development and commercialization of the program.

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We are required to pay Lilly up to $70 million based on the achievement of specified development and regulatory milestones. Upon commercialization, we are required to pay sales-based milestones aggregating up to $650 million payable to Lilly and up to $70 million to Leap.

Additionally, we are required to pay royalties to Lilly of between 5% and 15% of Avalo or its sublicensees’ annual net sales, beginning on first commercial sale of a licensed product in a given territory and expiring on a country-by-country basis, on the latest of (a) the tenth (10th) anniversary of the date of the first commercial sale, (b) the expiration of the last-to-expire licensed patent in the given country, or (c) the expiration of any data exclusivity period for the licensed product in the given territory.

We have not paid any milestones, royalties or any other amounts under the Lilly License Agreement or the Leap Agreement as of the date of this report. Additionally, there are no annual or maintenance fees payable under the Lilly License Agreement or the Leap Agreement.

The Lilly License Agreement remains in effect until the expiration of the last-to-expire royalty term of any licensed products. Each party may terminate for cause, and though we may terminate at our sole discretion by giving one-hundred twenty (120) days’ prior written notice to Lilly, all licenses and rights granted pursuant to the agreement shall automatically terminate and revert to Lilly. There are no termination or expiration provisions under the Leap Agreement.

AlmataBio Transaction

Pursuant to the AlmataBio Transaction, we paid $7.5 million to the former AlmataBio stockholders upon the initial closing of the private placement investment, which closed on March 28, 2024. Further, a portion of the consideration for the AlmataBio Transaction includes development milestones to the former AlmataBio stockholders including $5.0 million due upon the first patient dosed in a Phase 2 trial in patients with hidradenitis suppurativa for abdakibart (AVTX-009) and $15.0 million due upon the first patient dosed in a Phase 3 trial for abdakibart (AVTX-009), both of which are payable in cash or our stock at the election of the former AlmataBio stockholders, subject to the terms and conditions of the definitive merger agreement. In October 2024, the first development milestone was met and we paid $5.0 million in cash.

Intellectual Property Overview

Our success depends in part on our ability to obtain and maintain proprietary protection for the technology and know-how upon which our product candidates are based, to operate without infringing the proprietary rights of ~~others~~third parties and to prevent ~~others~~third parties from infringing our proprietary rights.

We ~~hold~~own ~~ownership,~~a ~~trademark~~combination of in-licensed intellectual property rights, including patent applications, know-how and~~/or~~ trademarks, and, in certain cases, regulatory exclusivity rights, if we receive marketing approval for abdakibart (AVTX-009) to develop and commercialize our product candidates covered by patents and patent applications. Our ~~portfolio~~intellectual ofproperty ~~patents~~portfolio includes ~~patents or~~ patent applications with claims directed to compositions of matter, including compounds, pharmaceutical formulations, ~~methods~~ of ~~use~~compounds, and methods of ~~manufacturing~~use of ~~the~~such compounds, or a combination of these claims. We also rely on trade secrets and proprietary know-how, including manufacturing and formulation know-how, as well as confidentiality agreements and other contractual protections, to protect aspects of our technology and product candidates that may not be patentable or that we elect not to patent. Depending upon the timing, duration and specifics of FDA approval of the use of a compound for a specific indication, some of our U.S. patents may be eligible for a limited patent term extension, also called marketing exclusivity, under U.S. patent term extension provisions including under the Drug Price Competition and Patent Term Restoration Act of 1984, ~~referred~~and torelated asstatutory ~~the~~authority, ~~Hatch-Waxman~~and ~~Act.~~similar ~~Similar~~patent term extensions toor ~~patent~~supplementary ~~term~~protection may be available in other countries for particular patents in our portfolio. including, where applicable, Supplementary Protection Certificates (“SPCs”) in Europe (including the EU and the UK).

WeWhen possible, we plan to augment our portfolio of ~~compounds~~product candidates by focusing on the development ~~(when possible)~~ of new ~~chemical entities (“NCEs”) or~~ biologics, which have not previously received FDA approval. Upon approval by the FDA, ~~NCEs~~new biologics are entitled to ~~market~~marketing ~~and data~~ exclusivity in the United States with respect to generic drug competition for a maximum period of five years from the date of FDA approval, even if the related patents have expired. Similarly, upon approval by the FDA, biologics are entitled to reference product exclusivity, also called regulatory exclusivity, for a period of twelve years from the date of FDA approval, even if the related patents have expired.

~~Intellectual~~If ~~property~~we receive marketing approval for abdakibart (AVTX-009), we expect to receive biologics reference product exclusivity in the United States, which may provide twelve years of regulatory exclusivity in the United States from the date of FDA approval and a period of regulatory data protection, as well as a minimum of 9 years, and potentially up to 11 years based certain criteria as required, of regulatory exclusivity legislation in Europe , the scope and duration of which is ~~discussed~~jurisdiction-specific ~~above~~and may be subject to legislative or regulatory change. As the composition of matter patent covering abdakibart (AVTX-009) expired in February 2026, we plan to primarily rely on biologics regulatory exclusivity for abdakibart (AVTX-009); however, the table

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~~Competition~~below ~~Overview~~sets forth details of patent applications related to abdakibart (AVTX-009) that might provide additional protection that we consider material:

Jurisdiction

Owned/Licensed

Status

Expiration Date

Protection Type

United States Non-Provisional

Owned

Pending

2045

Methods of Treating HS

Worldwide (PCT)

Owned

Pending

2045

Methods of Treating HS

United States Non-Provisional

Owned

Pending

2045

Formulations

Worldwide (PCT)

Owned

Pending

2045

Formulations

Competition for AVTX-009 is discussed above.

Manufacturing

We do not have any manufacturing facilities. We ~~rely~~currently onutilize, and expect to continue to utilize third-party contract development and manufacturing organizations (CDMOs) to, among other things, supply and manufacture raw materials, components, parts and consumables, and to perform quality testing for our preclinical and clinical supply for all of our biologic product candidates. We currently rely on a single CDMO to manufacture clinical supply for abdakibart (AVTX-009). Further, we rely on and expect to continue to rely on such CDMOs to produce our ~~drug~~biologic candidates in accordance with applicable ~~provisions~~regulations, ofincluding ~~the~~manufacturing ~~FDA’s~~activities ~~and~~performed ~~EMA~~in accordance with FDA’s current good manufacturing practices (“cGMP”) regulations, ~~for~~and ~~use~~similar inregulations ~~our~~and ~~clinical~~standards ~~studies~~in other jurisdictions. The manufacture of ~~pharmaceuticals~~biological products is subject to extensive cGMP regulations, which impose various procedural and documentation requirements and also govern ~~all areas of~~ record keeping, production processes and controls, personnel and quality control.

Sales and Marketing

Given our stage of development as a company, we have limited resources dedicated to sales, distribution and marketing. To successfully commercialize any products that may result from our development programs, we will need to further develop sales and marketing capabilities, either on our own or with third parties in the respective jurisdictions where marketing approval has been obtained. We may retain or partner with third parties onfor ~~the~~ commercialization rights and to develop sales and marketing capabilities~~, when needed~~. If we develop our own sales force, we may complement it with co‑promotion agreements with partners in and outside of the United States.

Overall Competitive Climate and Regulatory Risks

Competitors may have a variety of drugs in development or awaiting FDA approval that could reach the market and become established before we have an approved product to sell. Our competitors may also develop alternative therapies that could limit the market for any approved drugs that we may develop. Many of our competitors are using technologies or methods different or similar to ours to identify and validate drug targets and to discover novel small compound drugs. Many of our competitors and their collaborators may have significantly greater experience than we do in the following:Competition

We face, and will continue to face, intense competition from pharmaceutical and biotechnology companies, as well as numerous academic and research institutions and governmental agencies, both in the United States and abroad. We compete, or will compete, with existing and new products being developed by our competitors. Some of these competitors are pursuing the development of pharmaceuticals that target the same diseases and conditions that our research and development programs target or might target. Some of these competitors also have greater resources and more experience than we do in research and development and marketing. Competitors may have a variety of drugs in development or awaiting FDA approval that could reach the market and become established before we have an approved product to sell. Our competitors may also develop alternative therapies that could limit the market for any approved drugs that we may develop. Many of our competitors are using technologies or methods different or similar to ours to identify and validate drug targets and to discover novel small compound drugs.

In particular, pharmaceutical and biotechnology companies that develop and/or market products targeting IL-1β or the indications we are pursuing, including HS, are likely to represent substantial competition.

As of the date of this report, and to our knowledge, there are two companies with approved anti-IL-1β antibodies (Novartis AG or “Novartis” and Changchun GeneScience Pharmaceuticals Co., Ltd. or “GenSci”) and we are one of three additional companies with novel, non-biosimilar antibodies specifically targeting IL-1β in clinical development worldwide (Sunshine Guojian Pharmaceutical Co Ltd, or “Sunshine Guojian”, and TavoTek), inclusive of all approved indications and indications in development. There are additional companies developing and/or marketing known or investigational therapeutic agents that target IL-1β and/or IL-1α through interactions with IL-1 receptors, engineered bispecific antibodies, or through adjacent mechanistic targets (such as IL-1RAP and NLRP3).

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Worldwide, several companies currently market TNF alpha inhibitors (such as AbbVie Inc., or “AbbVie”, and additional companies marketing biosimilars) and IL-17 inhibitors (such as Novartis and UCB) for HS. As of the date of this report, six additional companies have ongoing or completed phase 3 development programs in HS with IL-17 inhibitors (Moonlake Immunotherapies, Inc.), JAK inhibitors (Incyte Corporation, AbbVie), BTK inhibitors (Novartis), and dual IL-1α/β inhibitors (AbbVie). There are multiple additional companies pursuing phase 2, phase 1, and preclinical development programs in HS.

Competition in the inflammatory disease market is intense. We face competition from many large pharmaceutical companies. There are numerous other companies that have commercialized or are developing treatments for HS and inflammatory diseases that we will compete with, including AbbVie, Lilly, Merck, Novartis, Pfizer, Sanofi, Takeda, UCB and others. Many of our competitors and their collaborators may have significantly greater experience than we do in the following:

•identifying and validating targets;

•screening compounds against targets;

•preclinical and clinical trials of potential pharmaceutical products; and

•obtaining FDA and other regulatory clearances.

In addition, many of our competitors and their collaborators have substantially greater advantages in the following areas:

•capital resources;

•research and development resources;

•manufacturing capabilities; and

•sales and marketing resources.

Smaller companies might also prove to be significant competitors, particularly through proprietary research discoveries and collaborative arrangements with large pharmaceutical and established biotechnology companies.

Many of our competitors have products that have been approved or are in advanced development. We face competition from other companies, academic institutions, governmental agencies and other public and private research organizations for collaborative arrangements with pharmaceutical and biotechnology companies, in recruiting and retaining highly qualified scientific and management personnel and for licenses to additional technologies. Our competitors, either alone or with their collaborators, may succeed in developing technologies or drugs that are more effective, safer, and more affordable or more easily administered than our product candidates and may achieve patent protection or commercialize drugs sooner than us. Developments by others may render our product candidates or our technologies obsolete. Our failure to compete effectively could have a material adverse effect on our business.Regulatory

~~Government~~There ~~Regulation~~is no guarantee that our products will obtain regulatory approval by the United States Food and ~~Product~~Drug ~~Approval~~Administration (the “FDA”) or comparable foreign regulatory authorities. The FDA approval process is complex, time-consuming, and expensive. Prior to submitting a new drug application (“NDA”) or biologics license application (“BLA”), the FDA approval process typically involves the following: preclinical laboratory and animal testing, submission of an Investigational New Drug (“IND”) application, and human clinical trials to establish safety and efficacy. Human clinical trials typically include: Phase 1 studies to evaluate the safety and tolerability of the drug, generally in normal, healthy volunteers (although for biologics and certain serious or inflammatory diseases, first-in-human studies may be conducted in patients); Phase 2 studies to evaluate safety and efficacy, as well as appropriate doses; these studies are typically conducted in patient volunteers who suffer from the particular disease condition that the drug is designed to treat; and Phase 3 studies to evaluate the safety and efficacy of the product at specific doses in one or more larger pivotal trials.

4As a biologics-focused company, our product candidates are subject to additional regulatory scrutiny, including requirements related to manufacturing process validation, product consistency, immunogenicity, and ongoing comparability assessments, and the FDA may require extensive chemistry, manufacturing and controls (“CMC”) data both before and after approval. Because biologics are derived from living systems, changes to manufacturing processes, facilities or suppliers may require additional regulatory review or approval.

Upon submission of an NDA or BLA, the FDA reviews the application, which potentially involves an FDA advisory committee review, and typically inspects manufacturing facilities and clinical study sites. The FDA has substantial discretion in the approval process and may require additional clinical studies, new or modified endpoints, expanded safety data, or longer follow-up periods as a condition to approval, even if earlier trials produce favorable results. Even if the FDA approves a product, it may impose post-approval requirements, such as risk evaluation and mitigation strategies, post-marketing studies or enhanced pharmacovigilance obligations, or withdraw approval if safety or efficacy issues arise.

We are currently conducting clinical development programs, including Phase 2 clinical trials, and success in earlier-stage trials does not ensure that later-stage trials will be successful or that regulatory approval will be obtained. The FDA may determine that additional studies are required prior to advancing to later-stage trials or submitting an NDA or BLA.

The processes for obtaining marketing approvals in foreign countries, along with subsequent compliance with applicable statutes and regulations, require the expenditure of substantial time and financial resources. Regulatory approval in foreign jurisdictions is generally independent of FDA approval and may require additional clinical data, different endpoints, or separate manufacturing inspections. Regulatory authorities in the European Union, the United Kingdom and other jurisdictions may apply standards that differ from those of the FDA, and clinical trial data generated in one jurisdiction may not be accepted by

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~~Government~~regulatory authorities in ~~the~~another. ~~United~~Delays ~~States~~or ~~and~~failures in ~~other~~obtaining ~~countries~~foreign ~~extensively~~regulatory ~~regulate,~~approvals ~~among~~could ~~other~~adversely ~~things,~~affect the ~~research,~~timing ~~development, testing, manufacturing, packaging, storage, recordkeeping, labeling, advertising, promoting, distributing, marketing, importing~~ and ~~exporting,~~scope ~~pricing,~~of ~~and~~any ~~government~~potential ~~contracting~~commercialization ~~related~~outside tothe ~~pharmaceutical~~United ~~products such as those we are developing~~States.

Government Regulation and Product Approval

Government authorities in the United States and in other countries extensively regulate, among other things, the research, development, testing, manufacturing, packaging, storage, recordkeeping, labeling, advertising, promotion, distribution, marketing, import and export, pricing, and government contracting related to biological products such as those we are developing.

United States Government Regulation

In the United States, the FDA regulates ~~drugs~~biologics under the Federal Food, Drug, and Cosmetic Act (“FDCA”), the Public Health Service Act, and its implementing regulations. The process of obtaining marketing approvals and ~~the~~ subsequent compliance with appropriate federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources. Failure to comply with the applicable United States requirements at any time during the product development process, approval process or after approval, may subject an applicant to a variety of administrative or judicial sanctions, ~~or other actions,~~ such as the FDA’s ~~delay in review of or~~ refusal to approve a pending ~~new~~ NDA or BLA, withdrawal of an approval, imposition of a clinical hold or study termination, issuance of Warning Letters or Untitled Letters, mandated modifications to promotional materials or issuance of corrective information, ~~requests for~~ product recalls, consent decrees, corporate integrity agreements, deferred prosecution agreements, product seizures or detentions, refusal to allow product import or export, total or partial suspension, restriction, or imposition of other requirements relating to production or distribution, injunctions, consent decrees, fines, debarment from government contracts and refusal of future orders under existing contracts, exclusion from participation in federal and state healthcare programs, FDA debarment, restitution, disgorgement or civil or criminal penalties, including fines and imprisonment (and, in certain cases, the imposition of compliance obligations pursuant to settlements or similar arrangements).

~~FDA~~Clinical ~~Marketing~~Development ~~Approval~~in the U.S.

Obtaining FDA marketing approval for a new ~~products~~product may take many years and require the expenditure of substantial financial resources. For the FDA to determine that a product is safe and effective for the proposed indication, the product must first undergo testing in animals (nonclinical studies). The data generated from nonclinical studies is used to support the filing of an ~~IND~~Investigational ~~under~~New ~~which~~Drug ~~human~~application ~~studies~~(“IND”), ~~are~~which ~~conducted.~~must ~~Human~~become ~~testing~~effective isbefore ~~generally~~human ~~conducted~~clinical ~~under~~studies anmay ~~IND~~begin. ~~in three phases following Good Clinical Practices (“GCP”) regulations:~~

~~•Phase~~Clinical 1:development ~~Studies~~involves ~~evaluate~~the administration of the investigational product to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control, in accordance with good clinical practice (“GCP”) requirements, which include the requirement that all patients provide their informed consent for their participation in any clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria and the parameters to be used to monitor subject safety and ~~tolerability~~assess efficacy. Each protocol, and any subsequent amendments to the protocol, must be submitted to the FDA as part of the ~~drug~~IND. Furthermore, ~~generally~~each clinical trial must be reviewed and approved by an IRB for each institution at which the clinical trial will be conducted to ensure that the risks to individuals participating in ~~normal~~the clinical trials are minimized and are reasonable in relation to anticipated benefits. The IRB also approves the informed consent form that must be provided to each clinical trial subject or his or her legal representative, ~~healthy~~and ~~volunteers;~~must monitor the clinical trial until completed. There also are requirements governing the reporting of ongoing clinical trials and completed clinical trial results to public registries.

~~•Phase~~A 2:sponsor ~~Studies~~that ~~evaluate~~wishes ~~safety~~to ~~and~~conduct ~~efficacy~~a clinical trial outside of the U.S. may, asbut ~~well~~need asnot, ~~appropriate~~obtain ~~doses;~~FDA ~~these~~authorization ~~studies~~to ~~are~~conduct ~~typically~~the clinical trial under an IND. If a foreign clinical trial is not conducted inunder ~~patient~~an ~~volunteers~~IND, ~~who~~the ~~suffer~~sponsor may submit data from the ~~particular~~clinical ~~disease~~trial ~~condition~~to ~~that~~the FDA in support of a BLA. The FDA will accept a well‑designed and well‑conducted foreign clinical study not conducted under an IND if the ~~drug~~study was conducted in accordance with GCP requirements, and the FDA is ~~designed~~able to ~~treat;~~validate ~~and~~the data through an onsite inspection if deemed necessary.

~~•Phase~~Clinical 3:trials ~~Studies~~are ~~evaluate~~generally ~~safety~~conducted ~~and~~in ~~efficacy~~three ofsequential ~~the~~phases, ~~product~~which atmay ~~specific~~overlap ~~doses in one~~ or ~~more~~be ~~larger pivotal trials.~~ combined:

In•Phase ~~addition~~1: toStudies ~~human~~in ~~testing,~~a ~~the~~small ~~manufacturing~~number ~~process~~ of ~~the~~subjects ~~potential product must be developed in accordance~~ with ~~cGMP regulations. Prior to~~ the ~~approval~~primary purpose of aassessing ~~new~~the ~~product~~metabolism, ~~the~~pharmacologic ~~FDA~~action, ~~may~~side ~~inspect~~effect ~~the~~tolerability ~~facilities~~and atsafety ~~which~~of the ~~proposed drug~~ product iscandidate, togenerally bein ~~manufactured~~normal, tohealthy ~~ensure~~volunteers ~~cGMP~~but ~~compliance.~~sometimes ~~FDA~~for ~~may~~certain ~~also~~biologics ~~inspect~~and ~~clinical~~serious ~~trial~~diseases, ~~sites~~in ~~and applicable laboratories.~~patients;

In•Phase ~~addition~~2: toStudies ~~the~~generally ~~cumulative~~designed ~~safety~~to ~~and~~evaluate ~~efficacy~~proof ~~data~~of ~~generated~~concept ~~from~~and determine the ~~clinical~~dosing ~~trials~~regimen(s) ~~described~~for ~~above,~~subsequent ~~chemistry~~investigations, ~~manufacturing~~ and ~~control~~further ~~(“CMC”)~~assess ~~information,~~safety ~~nonclinical study data~~ and ~~proposed~~PK/PD ~~labeling~~in ~~form~~patients ~~the~~who ~~basis~~have ~~to support approval of an NDA or BLA to~~ the ~~FDA.~~particular ~~The~~disease ~~preparation~~condition ofthat ~~an NDA or BLA requires~~ the ~~expenditure~~drug ~~of substantial funds and the commitment of substantial resources. Additionally, at the time of an NDA or BLA submission a user fee~~ is ~~required~~designed to ~~be paid unless the product has orphan drug designation (“ODD”)~~treat. ~~The~~Multiple ~~FDA~~Phase ~~conducts~~2 aclinical ~~preliminary~~trials ~~administrative~~may ~~review~~be ~~upon~~conducted ~~receipt~~to ofobtain ~~the~~information ~~NDA~~prior ~~or BLA submission and decides whether~~ to ~~accept~~beginning ~~the~~larger ~~NDA or BLA submission. If the application is not accepted for review by the FDA, the Sponsor of the application must resolve the deficiencies~~ and ~~re-submit~~more ~~the~~expensive ~~application,~~Phase ~~re-starting~~3 ~~the~~clinical ~~review~~trials; ~~clock.~~and

~~After~~•Phase ~~evaluating~~3: ~~the~~Studies ~~NDA~~in ~~or BLA and all related information, including if there is~~ an ~~advisory~~expanded ~~committee~~patient ~~recommendation,~~population ~~and~~to ~~inspection~~provide ~~reports~~statistically ~~regarding~~significant ~~the~~evidence ~~manufacturing~~of orclinical ~~laboratory~~efficacy ~~facilities~~ and ~~clinical~~to ~~trial~~further ~~sites,~~test ~~the~~for ~~FDA may issue an approval letter~~safety, ~~or, in some cases, a complete response letter (“CRL”). A CRL~~ generally ~~contains~~conducted aat ~~statement~~multiple ofgeographically ~~specific~~dispersed ~~conditions that must be met to secure final approval of the NDA or BLA and may require additional~~ clinical ortrial ~~nonclinical studies, or other information, in order for FDA approval~~sites. ~~Even~~These ~~with~~clinical submission of this additional information, the FDA may decide that the NDA or BLA does not satisfy the regulatory criteria for approval. If and when those conditions have been met to the FDA’s satisfaction, the FDA may issue an approval letter. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.

~~For purposes of BLA approval, human clinical trials are typically conducted in three sequential phases that may overlap.~~6

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~~•Phase~~trials ~~1: The investigational product is initially introduced into healthy human subjects or patients with the target disease or condition. These studies~~ are ~~designed~~intended to ~~test~~establish the ~~safety,~~overall ~~dosage~~risk/benefit ~~tolerance,~~ratio ~~absorption, metabolism and distribution~~ of ~~the~~an investigational product inand ~~humans,~~to ~~the~~provide ~~side~~an ~~effects~~adequate ~~associated~~basis ~~with~~for ~~increasing~~labeling ~~doses,~~ and, ifproduct ~~possible, to gain early evidence on effectiveness~~approval.

~~•Phase~~Post‑approval 2:trials, ~~The~~sometimes ~~investigational~~referred ~~product is administered~~ to aas ~~limited~~Phase ~~patient~~4 ~~population~~clinical ~~with~~trials, amay ~~specified~~be ~~disease~~conducted orafter ~~condition~~initial tomarketing ~~evaluate~~approval. ~~the~~These ~~preliminary~~trials ~~efficacy,~~are ~~optimal~~used ~~dosages~~to ~~and~~gain ~~dosing~~additional ~~schedule~~experience ~~and~~from tothe ~~identify~~treatment ~~possible~~of ~~adverse~~patients ~~side~~in ~~effects~~the ~~and~~intended ~~safety~~therapeutic ~~risks~~indication. ~~Multiple~~In ~~Phase~~certain 2instances, ~~clinical~~the ~~trials~~FDA may bemandate ~~conducted~~the toperformance ~~obtain~~of ~~information~~Phase ~~prior~~4 toclinical ~~beginning~~trials ~~larger~~as ~~and~~a ~~more~~condition ~~expensive~~of ~~Phase~~approval 3of ~~clinical~~a ~~trials~~BLA.

~~•Phase~~Progress 3:reports ~~The~~detailing ~~investigational~~the ~~product~~results isof ~~administered~~the clinical trials, among other information, must be submitted at least annually to anthe ~~expanded~~FDA ~~patient~~and ~~population~~written IND safety reports must be submitted to ~~further~~the ~~evaluate~~FDA ~~dosage~~and the investigators for serious and unexpected suspected adverse events, tofindings ~~provide~~from ~~statistically~~other studies or animal or in vitro testing that suggest a significant ~~evidence~~risk offor ~~clinical~~human ~~efficacy~~subjects and toany ~~further~~clinically ~~test~~important ~~for~~increase ~~safety,~~in ~~generally~~the atrate ~~multiple~~of ~~geographically~~a ~~dispersed~~serious ~~clinical~~suspected ~~trial~~adverse ~~sites~~reaction over that listed in the protocol or investigator brochure. Additionally, ~~These~~some clinical trials are ~~intended~~overseen toby ~~establish~~an ~~the~~independent ~~overall~~group ~~risk/benefit~~of ~~ratio~~qualified ofexperts organized by the ~~investigational~~clinical ~~product~~trial ~~and~~sponsor, toknown ~~provide~~as ana ~~adequate~~data ~~basis~~safety monitoring board or committee. This group provides authorization for ~~product~~whether ~~approval~~a trial may move forward at designated check points based on access to certain data from the trial.

~~The~~Concurrent ~~development~~with ~~and~~clinical ~~approval of new drugs requires substantial time~~trials, ~~effort~~companies ~~and~~usually ~~financial~~complete ~~resources.~~additional ~~Data~~animal ~~obtained~~studies ~~from a development program is not always conclusive~~ and ~~may~~also bemust ~~susceptible~~develop toadditional ~~varying~~information ~~interpretations.~~about ~~These~~the ~~instances may delay~~chemistry, ~~limit~~manufacturing orand ~~prevent~~controls ~~regulatory~~(“CMC”) ~~approval.~~for ~~The~~the ~~FDA~~investigational ~~may~~product ~~not~~as ~~grant~~well ~~approval~~as onfinalize a ~~timely~~process ~~basis,~~for ormanufacturing atthe ~~all.~~product Wein ~~may~~commercial ~~encounter~~quantities ~~difficulties or unanticipated costs~~ in ~~our~~accordance ~~efforts~~with tocGMP ~~secure~~requirements ~~necessary~~and, ~~governmental~~as ~~approvals~~applicable, ~~which~~demonstrate ~~could~~process ~~delay~~consistency orand ~~preclude~~comparability usas ~~from~~manufacturing ~~marketing any approved product candidates~~scales. ~~The FDA may limit the indications for use or place other conditions on any approvals that could restrict the commercial application of the approved product.~~

Under the Pediatric Research Equity Act (“PREA”), as amended, a BLA or supplement to a BLA must contain data to assess the safety and efficacy of the biological product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The FDA may grant deferrals for submission of pediatric data or full or partial waivers. Unless otherwise required by regulation, PREA does not apply to any biological product for an indication for which orphan designation has been granted. A sponsor who is planning to submit a marketing application for a drug that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration must submit an initial Pediatric Study Plan (“PSP”) within 60 days of an end‑of‑Phase 2 meeting or, if there is no such meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 study. The initial PSP must include an outline of the pediatric study or studies that the sponsor plans to conduct, including study objectives and design, age groups, relevant endpoints and statistical approach, or a justification for not including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting information. The FDA and the sponsor must reach an agreement on the PSP. A sponsor can submit amendments to an agreed‑upon initial PSP at any time if changes to the pediatric plan need to be considered based on data collected from preclinical studies, early phase clinical trials and/or other clinical development programs.

The preparation of an NDA or BLA requires the expenditure of substantial funds and the commitment of substantial resources. Additionally, at the time of an NDA or BLA submission a user fee is required to be paid unless the product has orphan drug designation (“ODD”) or another waiver or reduction applies. The FDA conducts a preliminary administrative review upon receipt of the NDA or BLA submission and decides whether to accept the NDA or BLA submission. If the application is not accepted for review by the FDA through a “refuse-to-file” determination, the Sponsor of the application must resolve the deficiencies and resubmit the application, restarting the review clock.

After evaluating the NDA or BLA and all related information, including if there is an advisory committee recommendation, and inspection reports regarding the manufacturing or laboratory facilities and clinical trial sites, the FDA may issue an approval letter, or, in some cases, a complete response letter (“CRL”). A CRL generally contains a statement of specific conditions that must be met to secure final approval of the NDA or BLA and may require additional clinical or nonclinical studies, or other information. Even with submission of this additional information, the FDA may decide that the NDA or BLA does not satisfy the regulatory criteria for approval. The FDA will not approve an application until issues identified in any complete response letters have been addressed. Even if such data and information are submitted, the FDA may decide that the application does not satisfy the criteria for approval. Failure to respond to a complete response letter may be considered by the FDA as a request to withdraw the application. If and when those conditions have been met to the FDA’s satisfaction, the FDA may issue an approval letter. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.

Even if the FDA approves a new product, the approval may be limited to specific disease states, patient populations and dosages, and the indications for use may otherwise be limited. The FDA may also require that contraindications, warnings, or precautions be included in the product labeling. The FDA may prevent or limit further marketing of a product based on the results of post-market studies or surveillance programs. After approval, many types of changes to the approved product, such as adding new indications, certain manufacturing changes and additional labeling claims, are subject to further testing requirements and FDA review and approval.

FDA Review Process

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Following completion of clinical trials, the data are analyzed to assess whether the investigational product is safe and effective for the proposed indicated use or uses. The results of preclinical studies and clinical trials are then submitted to the FDA as part of a BLA, along with proposed CMC and manufacturing information to ensure product quality and other relevant data. The BLA is a request for approval to market the biologic for one or more specified indications and must contain preclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, efficacy,, purity and potency for a biologic candidate. The application may include both negative and ambiguous results of preclinical studies and clinical trials, as well as positive findings. Data may come from company‑sponsored clinical trials intended to test the safety and efficacy of a product’s use or from a number of alternative sources, including studies initiated by investigators. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of the investigational product to the satisfaction of the FDA. FDA approval of a BLA must be obtained before a biologic may be marketed in the U.S.

Under the Prescription Drug User Fee Act (“PDUFA”) as amended, each BLA must be accompanied by a user fee. The FDA adjusts the PDUFA user fees on an annual basis. Fee waivers or reductions are available in certain circumstances, including a waiver of the application fee for the first application filed by a small business. Additionally, no user fees are assessed on BLAs for products designated as orphan drugs, unless the product also includes a non‑orphan indication.

The FDA reviews all submitted BLAs before it accepts them for filing, and may request additional information rather than accepting the BLA for filing. The FDA must make a decision on accepting a BLA for filing within 60 days of receipt, and such decision could include a refusal to file by the FDA. Once the submission is accepted for filing, the FDA begins an in‑depth review of the BLA. Under the goals and policies agreed to by the FDA under PDUFA, the FDA has 10 months from the filing date in which to complete its initial review of an original BLA and respond to the applicant, and six months from the filing date of an original BLA designated for priority review. The FDA does not always meet its PDUFA goal dates for standard and priority BLAs, and the review process is often extended by FDA requests for additional information or clarification.

Before approving a BLA, the FDA generally will conduct a pre‑approval inspection of the manufacturing facilities for the new product to determine whether they comply with cGMP requirements. The FDA will not approve the product unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. The FDA also may audit data from clinical trials to ensure compliance with GCP requirements. In certain circumstances, the FDA may require a Risk Evaluation and Mitigation Strategy (“REMS”) to assure the safe use of the product. If the FDA concludes a REMS is needed, the sponsor of the BLA must submit a proposed REMS, and the FDA will not approve the BLA without an approved REMS. A REMS could include medication guides, physician communication plans or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools.

After the FDA evaluates a BLA, it will issue an approval letter or a complete response letter. An approval letter authorizes commercial marketing of the biologic with specific prescribing information for specific indications. A complete response letter indicates that the review cycle of the application is complete and the application will not be approved in its present form. A complete response letter usually describes all of the specific deficiencies in the BLA identified by the FDA. The complete response letter may require additional clinical data, additional pivotal Phase 3 clinical trial(s) and/or other significant and time‑consuming requirements related to clinical trials, preclinical studies or manufacturing. If a complete response letter is issued, the applicant may either resubmit the BLA, addressing all of the deficiencies identified in the letter, or withdraw the application. Even if such data and information are submitted, the FDA may decide that the BLA does not satisfy the criteria for approval.

Data obtained from a development program is not always conclusive and may be susceptible to varying interpretations, which may delay, limit or prevent regulatory approval. The FDA may not grant approval on a timely basis, or at all. We may encounter difficulties or unanticipated costs in our efforts to secure necessary governmental approvals, which could delay or preclude us from marketing any approved product candidates. The FDA may limit the indications for use or place other conditions on any approvals that could restrict the commercial opportunity of the approved product.

FDA Post‑Approval Considerations

Drugs manufactured or distributed pursuant to FDA approval are subject to continuing regulation by the FDA, including, among other things, requirements relating to recordkeeping, manufacturing, periodic reporting, product sampling and distribution, advertising and promotion, and reporting of adverse experiences with the product and drug shortages. During the approval process, the FDA and the sponsor may agree that specific studies or clinical trials should be conducted as post-marketing commitments, ~~but they are not required by statute~~ or ~~regulation. The FDA may also impose~~ post-marketing requirements as a condition of approval of ana ~~NDA or~~ BLA. ~~For~~The ~~example, the~~ FDA may require post-marketing testing, including Phase 4 clinical trials and surveillance, to further assess and monitor the product’s safety and effectiveness after commercialization. Once an approval is granted, the FDA may withdraw ~~the~~ approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product becomes available in the market. Other potential consequences include, among other things:

•restrictions on the marketing or manufacturing of a product, ~~complete withdrawal of the product from the market~~ or product recalls;

•fines, warning letters or holds on post-approval clinical studies;

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•refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of existing product approvals;

•product seizure or detention, or refusal of the FDA to permit the import or export of products;

•consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs;

•mandated modification of promotional materials and labeling and the issuance of corrective information;

•the issuance of safety alerts, Dear Healthcare Provider letters, press releases and other communications containing warnings or other safety information about the product; or

•injunctions or the imposition of civil or criminal penalties.

After approval, ~~most~~many changes to the approved product, such as manufacturing changes and adding new indications or other labeling claims, are subject to FDA review and approval. There are also annual user fee requirements for ~~any~~ marketed ~~product~~products and ~~new~~ application fees for supplemental applications with clinical data. Additionally, the FDA strictly regulates the labeling, advertising and promotion of products under an approved ~~NDA or~~ BLA. The FDA and other agencies ~~actively~~ enforce the laws and regulations prohibiting the promotion of off‑label uses, and a company that improperly markets or promotes off‑label uses may be subject to significant liability, including criminal and civil penalties under the FDCA and False Claims Act, exclusion from participation in federal healthcare programs, debarment from government contracts, refusal of future orders under existing contracts and mandatory compliance programs under corporate integrity agreements or deferred prosecution agreements.

Other Regulations of the Healthcare Industry

In addition to FDA regulations governing the marketing of pharmaceutical products, there are various state and federal laws that may restrict business practices in the biopharmaceutical industry. These include the following:

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•The federal Anti-Kickback laws and implementing regulations, which prohibit persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce either the referral of an individual, or furnishing or arranging for a good or service, for which payment may be made under federal healthcare programs such as the Medicare and Medicaid programs;

•Other Medicare laws, regulations, rules, manual provisions and policies that prescribe the requirements for coverage and payment for pharmaceutical products and services, including the amount of such payment;

•The federal False Claims Act, which imposes civil and criminal liability on individuals and entities who submit, or cause to be submitted, false or fraudulent claims for payment to the government;

•The Foreign Corrupt Practices Act (“FCPA”), which prohibits certain payments made to foreign government officials; and

•State and foreign law equivalents of the foregoing and state laws regarding pharmaceutical company marketing compliance, reporting and disclosure obligations.

If our agents or operations are found to be in violation of any of these laws, regulations, rules or policies or any other law or governmental regulation, or if interpretations of the foregoing change, we may be subject to civil and criminal penalties, damages, fines, exclusion from participating in the Medicare and Medicaid programs and the curtailment or restructuring of our operations.

To the extent that any of our product candidates are approved for sale in a foreign country, we may be subject to similar foreign laws and regulations, which may include, for instance, applicable post‑marketing requirements, including safety surveillance, anti‑fraud and abuse laws, and implementation of corporate compliance programs and reporting of payments or transfers of value to healthcare professionals.

Coverage and Reimbursement

~~Our~~The ~~ability to commercialize and, the commercial~~ success of, ~~any~~our ~~approved~~ product candidates, ~~will~~if ~~depend~~approved, independs ~~part~~ on the ~~extent~~availability toof ~~which governmental authorities, private health insurers and other third‑party payers provide~~ coverage ~~for~~ and ~~establish~~ adequate reimbursement ~~levels~~from ~~for~~third-party ~~our therapeutic product candidates~~payors. InWe ~~the~~cannot ~~United~~be ~~States,~~sure ~~the~~that ~~European~~coverage ~~Union~~ and ~~other~~reimbursement ~~potentially~~will ~~significant~~be ~~markets~~available for our product candidates, ~~government~~nor ~~authorities~~can ~~and~~we ~~third‑party~~accurately ~~payers~~estimate ~~are increasingly imposing more stringent requirements and restrictions on coverage, attempting to limit reimbursement levels or regulate~~ the ~~price~~potential ofrevenue ~~drugs~~from ~~and other medical products and services~~them. Similarly, ~~particularly~~we ~~for~~cannot ~~new~~assure ~~and~~that ~~innovative~~coverage ~~products~~ and ~~therapies,~~reimbursement ~~which~~will ~~often has resulted in average selling prices lower than they would otherwise~~ be. ~~For~~available example, in the United States, federal and state governments reimburse covered prescription drugs at varying rates generally below average wholesale price. Federal programs also impose price controls through mandatory ceiling prices on purchases by federal agencies and federally funded hospitals and clinics and mandatory rebates on retail pharmacy prescriptions paid by Medicaid and Tricare. These restrictions and limitations influence the purchase of healthcare services and products. Legislative proposals to reform healthcare or reduce costs under government programs may result in lower reimbursement for ~~our~~any product ~~candidates~~that orwe ~~exclusion~~may ~~of our product candidates from coverage. Moreover, the Medicare and Medicaid programs increasingly are used as models for how private payers and other governmental payers~~ develop ~~their coverage and reimbursement policies~~.

InPatients ~~addition,~~who ~~the~~are ~~increased~~provided ~~emphasis~~medical ontreatment ~~managed~~for ~~healthcare~~their inconditions ~~the~~generally ~~United~~rely ~~States and~~ on ~~country~~third-party ~~and~~payors ~~regional~~to ~~pricing~~reimburse ~~and~~all ~~reimbursement~~or ~~controls~~part inof the ~~European~~costs ~~Union~~associated ~~will~~with ~~put~~their ~~additional~~treatment. ~~pressure~~Coverage onand ~~product~~adequate ~~pricing,~~ reimbursement ~~and utilization, which may adversely affect any future product sales and our results of operations. These pressures can arise~~ from ~~rules~~governmental ~~and~~healthcare ~~practices of managed care groups~~programs, ~~competition~~such ~~within~~as ~~therapeutic classes, availability of generic equivalents, judicial decisions and governmental laws and regulations related to~~ Medicare, ~~Medicaid~~ and ~~healthcare reform~~Medicaid, ~~coverage~~ and ~~reimbursement~~commercial ~~policies~~payors ~~and~~is ~~pricing~~critical in general. The cost containment measures that healthcare payers and providers are instituting and any healthcare reform implemented in the future could significantly reduce our revenues from the sale of any approved products. We cannot provide any assurances that we will be able to ~~obtain~~new ~~and~~product ~~maintain third‑party coverage or adequate reimbursement for our approved products in whole or in part~~acceptance.

~~Healthcare~~Government ~~Reform~~authorities and other third-party payors, such as private health insurers and health maintenance organizations, decide which drugs and treatments they will cover and the amount of reimbursement. Coverage and reimbursement by a third-party payor may depend upon a number of factors, including the third-party payor’s determination that use of a product is:

~~The~~•a ~~United~~covered ~~States~~benefit ~~and~~under ~~many~~its ~~foreign~~health ~~jurisdictions~~plan; have enacted or proposed legislative and regulatory changes affecting the healthcare system. The United States government, state legislatures and foreign governments also have shown significant interest in implementing cost-containment programs to limit the growth of government-paid healthcare costs, including price controls, restrictions on reimbursement and requirements for substitution of generic products for branded prescription drugs.

~~In recent years~~•safe, ~~Congress~~effective has considered reductions in Medicare reimbursement levels for drugs administered by physicians. Further, the Center for Medicare & Medicaid Services (“CMS”), the agency that administers the Medicare and ~~Medicaid~~medically necessary;

7•appropriate for the specific patient;

• cost-effective; and

•neither experimental nor investigational.

In the United States, no uniform policy of coverage and reimbursement for products exists among third-party payors. As a result, obtaining coverage and reimbursement approval of a product from a government or other third-party payor is a time-consuming and costly process that could require us to provide to each payor supporting scientific, clinical and cost-effectiveness data for the use of our products on a payor-by-payor basis, with no assurance that coverage and adequate reimbursement will be obtained. In the United States, the principal decisions about reimbursement for new medicines are typically made by CMS. CMS decides whether and to what extent a new medicine will be covered and reimbursed under Medicare and private payors tend to follow CMS to a substantial degree. Even if we obtain coverage for a given product, the resulting reimbursement payment rates might not be adequate for us to achieve or sustain profitability or may require co-payments that patients find unacceptably high. Additionally, third-party payors may not cover, or provide adequate reimbursement for, long-term follow-up evaluations required following the use of product candidates, once approved. Patients are unlikely to use our product candidates, once approved, unless coverage is provided and reimbursement is adequate to cover a significant portion of their cost. There is significant uncertainty related to insurance coverage and reimbursement of newly approved products. It is difficult to predict at this time what third-party payors will decide with respect to the coverage and reimbursement for our product candidates.

Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for medical products. We cannot be sure that reimbursement will be available for any product candidate that we commercialize and, if reimbursement is available, the level of reimbursement. In addition, many pharmaceutical manufacturers must calculate and report certain price reporting metrics to the government, such as average sales price and best price. Penalties may apply in some cases when such metrics are not submitted accurately and timely. Further, these prices for drugs may be reduced by mandatory discounts or rebates required by

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~~programs,~~government ~~also~~healthcare ~~has~~programs. ~~authority~~Payment tomethodologies ~~revise~~may ~~reimbursement~~be ~~rates~~subject ~~and~~ to ~~implement coverage restrictions for some drugs. Cost reduction initiatives and~~ changes in ~~coverage~~healthcare ~~implemented through~~ legislation ~~or regulation could decrease utilization of~~ and ~~reimbursement~~regulatory ~~for any approved products~~initiatives. While Medicare regulations apply only to drug benefits for Medicare beneficiaries, private payers often follow Medicare coverage policy and payment limitations in setting their own reimbursement rates. Therefore, any reduction in reimbursement that results from federal legislation or regulation may result in a similar reduction in payments from private payers.

~~The~~Moreover, ~~Patient~~increasing ~~Protection~~efforts by governmental and ~~Affordable~~other ~~Care~~third-party ~~Act~~payors ofin ~~2010,~~the asUnited ~~amended~~States ~~(the~~and ~~“Affordable~~abroad ~~Care~~to ~~Act”~~cap or ~~“ACA”),~~reduce ~~substantially~~healthcare ~~changed~~costs ~~the~~may ~~way~~cause ~~healthcare~~such isorganizations ~~financed~~to bylimit both ~~governmental~~coverage and ~~private insurers, and significantly impacts~~ the ~~pharmaceutical~~level ~~industry.~~of ~~The~~reimbursement ~~ACA~~for ~~was~~newly ~~intended~~approved toproducts ~~broaden access to health insurance~~and, ~~reduce~~as ora ~~constrain the growth of healthcare spending~~result, ~~enhance~~they ~~remedies~~may ~~against~~not ~~healthcare~~cover ~~fraud~~or ~~and~~provide ~~abuse,~~adequate ~~add~~payment ~~new transparency requirements~~ for ~~healthcare~~our ~~and~~product ~~health~~candidates. ~~insurance~~There ~~industries,~~has ~~impose~~been ~~new~~increasing ~~taxes~~legislative and ~~fees~~enforcement oninterest ~~pharmaceutical~~in ~~and~~the ~~medical~~United ~~device~~States ~~manufacturers,~~with ~~and~~respect ~~impose~~to ~~additional~~specialty ~~health~~drug ~~policy~~pricing ~~reforms~~practices. ~~Since its passage~~Specifically, there have been ~~persistent~~several ~~efforts~~recent toU.S. ~~modify~~Congressional orinquiries ~~eliminate~~and ~~the~~proposed ~~ACA.~~and ~~These~~enacted ~~have,~~federal ~~among~~and ~~other~~state ~~things,~~legislation ~~reduced~~designed ~~Medicare payments~~ to, ~~several~~among ~~types~~other ~~of providers~~things, ~~including~~bring ~~hospitals,~~more ~~imaging~~transparency ~~centers~~to ~~and~~drug ~~cancer treatment centers~~pricing, ~~and~~reduce ~~increased~~ the ~~statute~~cost of ~~limitations~~prescription ~~period~~drugs ~~for~~under ~~the~~Medicare, ~~government~~review ~~to recover overpayments to providers. These efforts are unlikely to abate in~~ the ~~near~~relationship ~~term,~~between ~~with~~pricing ~~new~~and ~~challenges~~manufacturer topatient ~~the~~programs ~~individual~~and ~~mandate~~reform orgovernment toprogram ~~the~~reimbursement ~~ACA~~methodologies asfor ~~a whole likely~~drugs.

~~The~~At ~~Inflation Reduction Act of 2022, enacted on August 16, 2022 (“IRA”), includes several provisions to lower prescription drug costs for Medicare patients and reduce drug spending by~~ the ~~federal~~state ~~government~~level, ~~which~~legislatures ~~could~~have ~~affect~~increasingly ~~the~~passed ~~pricing~~legislation and ~~reimbursement~~implemented ofregulations ~~our~~designed ~~product candidates if they are approved for commercial sale. Pursuant~~ to ~~this,~~control ~~the~~pharmaceutical ~~CMS announced in August 2023 that it had selected the first ten drugs covered under Medicare Part D for negotiation,~~ and ~~selected~~biological anproduct additional fifteen drugs for negotiation in January 2025. However, recent announcements from the second Trump administration call into question the administration’s commitment to enforcing the IRA going forward, and CMS’ drug pricing policies have engendered patent abuse lawsuits that call into question the limits of the government’s pricing control efforts. It is unknown what this negotiation will yield or what form any future changes or any law would take, ~~and~~including ~~how~~price or ~~whether~~patient itreimbursement ~~may affect our business in the future. We expect that changes or additions to the ACA~~constraints, ~~the Medicare and Medicaid programs~~discounts, ~~changes~~restrictions ~~allowing~~on ~~the~~certain ~~federal~~product ~~government~~access toand ~~directly~~marketing ~~negotiate~~cost ~~drug~~disclosure ~~prices~~ and ~~changes~~transparency ~~stemming from other healthcare reform~~ measures, ~~especially with regard to healthcare access~~and, ~~financing or other legislation~~ in ~~individual~~some ~~states~~cases, ~~could~~designed ~~have~~to aencourage ~~material~~importation ~~adverse~~from ~~effect~~other oncountries ~~the~~and ~~healthcare~~bulk ~~industry~~purchasing.

~~Payment~~We ~~methodologies~~expect that healthcare reform measures that may be ~~subject~~adopted toin ~~further~~the ~~changes~~future may result in ~~healthcare~~more ~~legislation~~rigorous coverage criteria and ~~regulatory~~in ~~initiatives~~additional asdownward ~~well~~pressure on the price that we receive for any approved product. InThe ~~addition,~~implementation atof ~~the~~cost ~~state~~containment ~~level,~~measures ~~legislatures~~or ~~have~~other ~~passed~~healthcare ~~and~~reforms ~~implemented~~may prevent us from being able to generate revenue, ~~and~~attain ~~may~~profitability, inor ~~the~~commercialize ~~future~~our ~~pass~~products. Legislative and ~~implement~~regulatory ~~legislation~~proposals ~~and~~have ~~regulations~~been ~~designed~~made to ~~control~~expand ~~pharmaceutical~~post-approval ~~product~~requirements ~~pricing,~~and ~~including~~restrict ~~price~~sales orand ~~patient~~promotional ~~reimbursement~~activities ~~constraints,~~for ~~discounts,~~pharmaceutical ~~restrictions~~products. onWe ~~certain~~cannot ~~product~~be ~~access~~sure ~~and~~whether ~~marketing~~additional ~~cost~~legislative ~~disclosure~~changes ~~and~~will ~~transparency~~be ~~measures~~enacted, ~~and~~or whether existing regulations, inguidance ~~some~~or ~~cases~~interpretations will be changed, ~~designed~~or towhat ~~encourage~~the ~~importation~~impact ~~from~~of ~~other~~such ~~countries~~changes ~~and~~on ~~bulk~~the ~~purchasing.~~marketing approvals or clearances of our product candidates, if any, may be.

~~The~~In ~~second~~addition, ~~Trump~~in ~~administration~~some ~~has~~foreign ~~granted~~countries, the Uproposed pricing for a drug must be approved before it may be lawfully marketed.S. ~~DOGE~~The ~~Service~~requirements ~~Temporary~~governing ~~Organization,~~drug ~~led~~pricing byvary ~~Elon~~widely ~~Musk~~from country to country. For example, ~~broad~~the ~~discretionary~~European ~~authority~~Union provides options for its Member States to ~~eliminate~~restrict ~~perceived~~the ~~inefficiency,~~range ~~fraud,~~of ~~waste,~~medicinal ~~and~~products ~~abuse~~for inwhich ~~government~~their national health insurance systems provide reimbursement and to ~~eliminate~~control ~~excessive~~the ~~regulation~~prices of medicinal products for human use. ItTo isobtain ~~unclear~~reimbursement ~~what~~or ~~effect~~pricing approval, some of these ~~efforts~~countries atmay ~~overhauling~~require the ~~federal~~completion ~~administrative~~of ~~state~~clinical ~~will~~trials ~~have~~that oncompare the ~~administration~~cost effectiveness of a particular product candidate to currently available therapies. A Member State may approve a specific price for the medicinal product or ~~viability~~it may instead adopt a system of ~~federal~~direct ~~healthcare~~or ~~programs~~indirect ~~and~~controls ~~FDA~~on the profitability of the company placing the medicinal product on the market. There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and ~~CMS’~~pricing ~~ability~~arrangements tofor ~~oversee~~any of our product candidates. Historically, products launched in the European Union do not follow price structures of the United States and ~~administer~~generally ~~these~~prices ~~programs~~tend to be significantly lower.

WeOther ~~expect~~Healthcare ~~that~~Laws ~~additional federal, state~~ and ~~foreign~~Compliance ~~healthcare~~Requirements reform measures could be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in limited coverage and reimbursement and reduced demand for our products, once approved, or additional pricing pressures.

~~Exclusivity~~Pharmaceutical companies are subject to additional healthcare regulation and ~~Approval~~enforcement by the federal government and by authorities in the states and foreign jurisdictions in which they conduct their business that may constrain the financial arrangements and relationships through which we research, as well as sell, market and distribute any products for which we obtain marketing authorization. Arrangements with third-party payors and customers can expose pharmaceutical manufactures to broadly applicable fraud and abuse and other healthcare laws and regulations, including, without limitation, the federal Anti-Kickback Statute and the federal False Claims Act (FCA) which may constrain the business or financial arrangements and relationships through which companies research, sell, market and distribute pharmaceutical products. In addition, transparency laws and patient privacy laws can apply to the activities of ~~Competing~~pharmaceutical ~~Products~~manufactures. The applicable federal, state and foreign healthcare laws and regulations that can affect a pharmaceutical company’s operations include without limitation:

~~Hatch‑Waxman~~•The ~~Patent~~federal ~~Exclusivity~~Anti-Kickback Statute, which prohibits, among other things, knowingly and willfully soliciting, receiving, offering or paying any remuneration (including any kickback, bribe, or rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce, or in return for, either the referral of an individual, or the purchase, lease, order or recommendation of any good, facility, item or service for which payment may be made, in whole or in part, under the Medicare and Medicaid programs, or other federal healthcare programs. A person or entity can be found guilty of violating the statute without actual knowledge of the statute or specific intent to violate it. Violations are subject to civil and criminal fines and penalties for each violation, plus up to three times the remuneration involved, imprisonment, and exclusion from government healthcare programs. In addition, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the FCA or federal civil monetary penalties. The Anti-Kickback Statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers, and formulary managers on the other. There are a number of statutory exceptions and regulatory safe harbors protecting some common activities from prosecution, but such exceptions and safe harbors are drawn narrowly and require strict compliance in order to offer protection;

In seeking approval for a drug through an NDA, applicants are required to list with the FDA each patent with claims that cover the applicant’s product or a method of using the product. Upon approval of a NDA, each of the patents listed in the application for the drug is then published in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book. Drugs listed in the Orange Book can, in turn, be cited by potential competitors in support of approval of an abbreviated new drug application (“ANDA”) or 505(b)(2) NDA. Generally, an ANDA provides for marketing of a drug product that has the same active ingredients in the same strengths, dosage form and route of administration as the listed drug and has been shown to be bioequivalent through in vitro or in vivo testing or otherwise to the listed drug. ANDA applicants are not required to conduct or submit results of preclinical or clinical tests to prove the safety or effectiveness of their drug product, other than the requirement for bioequivalence testing. Drugs approved in this way are commonly referred to as 10

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~~“generic~~•The ~~equivalents”~~federal civil and criminal false claims laws, including the FCA, and civil monetary penalty laws, which prohibit any person or entity from, among other things, knowingly presenting, or causing to be presented, a false, fictitious or fraudulent claim for payment to, or approval by, the ~~listed~~federal ~~drug~~government ~~and~~or ~~can~~knowingly ~~often~~making, using or causing to be ~~substituted~~made or used a false record or statement, including providing inaccurate billing or coding information to customers or promoting a product off-label, material to a false or fraudulent claim to the federal government. As a result of a modification made by ~~pharmacists~~the ~~under~~Fraud ~~prescriptions~~Enforcement ~~written~~and Recovery Act of 2009, a claim includes “any request or demand” for money or property presented to the ~~reference~~federal ~~listed~~government. ~~drug~~In addition, manufacturers can be held liable under the FCA even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. The FCA also permits a private individual acting as a “whistleblower” to bring actions on behalf of the federal government alleging violations of the FCA and to share in any monetary recovery;

•The ~~ANDA~~federal orHealth ~~505~~Insurance Portability and Accountability Act of 1996 (bHIPAA)~~(2)~~, ~~NDA~~which ~~applicant~~created isfederal ~~required~~criminal statutes that prohibit, among other things, knowingly and willfully executing, or attempting to ~~provide~~execute, a ~~certification~~scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the ~~FDA~~money inor property owned by, or under the ~~product~~custody ~~application~~or ~~concerning~~control of, any ~~patents~~healthcare ~~listed~~benefit ~~for~~program, regardless of the ~~approved~~payor ~~product~~(e.g., inpublic ~~the~~or ~~FDA’s~~private) ~~Orange~~and ~~Book,~~knowingly ~~except~~and ~~for~~willfully ~~patents~~falsifying, concealing or covering ~~methods~~up by any trick or device a material fact or making any materially false statements in connection with the delivery of, ~~use~~or payment for, ~~which~~healthcare ~~the~~benefits, ~~applicant~~items isor ~~not~~services ~~seeking~~relating ~~approval~~to healthcare matters. ~~Specifically,~~Similar to the ~~applicant~~federal ~~must~~Anti-Kickback ~~certify~~Statute, ~~with~~a ~~respect~~person toor ~~each~~entity ~~patent~~can ~~that:~~be found guilty of violating HIPAA without actual knowledge of the statute or specific intent to violate it;

•HIPAA, as amended by the ~~required~~Health ~~patent~~Information Technology for Economic and Clinical Health Act of 2009 (HITECH), and their respective implementing regulations, which impose, among other things, specified requirements relating to the privacy, security and transmission of individually identifiable health information ~~has~~held ~~not~~by ~~been~~covered ~~filed~~entities and their business associates as well as their covered subcontractors. HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions;

•The federal legislation commonly referred to as the ~~listed~~Physician ~~patent~~Payments ~~has~~Sunshine ~~expired~~Act, created under the ACA, and its implementing regulations, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to CMS, information related to payments or other transfers of value made to physicians, other licensed care professionals and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members;

•~~the~~Federal ~~listed~~government ~~patent~~price ~~has~~reporting ~~not expired~~laws, ~~but~~which ~~will~~require ~~expire~~us onto acalculate ~~particular~~and ~~date~~report ~~and~~complex ~~approval~~pricing ismetrics ~~sought~~in ~~after~~an ~~patent~~accurate ~~expiration;~~and ortimely manner to government programs;

•~~the~~Federal ~~listed~~consumer ~~patent~~protection isand ~~invalid,~~unfair ~~unenforceable~~competition laws, orwhich ~~will~~broadly ~~not~~regulate bemarketplace ~~infringed~~activities byand ~~the~~activities ~~new~~that ~~product.~~potentially harm consumers; and

~~Generally~~Additionally, we are subject to state and foreign equivalents of each of the ~~ANDA~~healthcare orlaws ~~505(b)(2)~~and ~~NDA~~regulations ~~cannot~~described above, among others, some of which may be ~~approved~~broader ~~until~~in ~~all~~scope ~~listed~~and ~~patents~~may apply regardless of the payor. Many U.S. states have ~~expired,~~adopted ~~except~~laws ~~when~~similar to the ~~ANDA~~federal orAnti-Kickback ~~505(b)(2)~~Statute ~~NDA~~and ~~applicant~~False ~~challenges~~Claims aAct, ~~listed~~and ~~patent~~may orapply ifto ~~the~~our ~~listed~~business ~~patent~~practices, isincluding, abut ~~patented~~not ~~method~~limited ofto, ~~use~~research, ~~for~~distribution, ~~which~~sales ~~approval~~or ismarketing ~~not~~arrangements ~~being~~and ~~sought~~claims involving healthcare items or services reimbursed by non-governmental payors, including private insurers. AIn ~~certification~~addition, some states have passed laws that require pharmaceutical companies to comply with the ~~proposed~~April ~~product~~2003 ~~will~~Office ~~not~~of ~~infringe~~Inspector General Compliance Program Guidance for Pharmaceutical Manufacturers and/or the ~~already~~Pharmaceutical ~~approved~~Research ~~product~~and Manufacturers of America’s ~~listed~~Code ~~patents~~on Interactions with Healthcare Professionals. Several states also impose other marketing restrictions or ~~that~~require ~~such~~pharmaceutical ~~patents~~companies ~~are~~to ~~invalid~~make marketing or ~~unenforceable~~price isdisclosures ~~called~~to athe ~~Paragraph IV~~state ~~Certification.~~and Ifrequire the ~~applicant~~registration ~~does~~of ~~not~~pharmaceutical ~~challenge~~sales representatives. State and foreign laws, including for example the ~~listed~~European ~~patents~~Union orGeneral ~~does~~Data ~~not~~Protection ~~indicate~~Regulation, ~~that~~which itbecame iseffective ~~not~~May ~~seeking~~2018 ~~approval~~also ofgovern athe ~~patented~~privacy ~~method~~and security of ~~use~~health information in some circumstances, ~~the~~many ~~ANDA~~of orwhich ~~505(b)(2)~~differ ~~NDA~~from ~~application~~each ~~will~~other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts. There are ambiguities as to what is required to comply with these state requirements and if we fail to comply with an applicable state law requirement we could be ~~approved~~subject ~~until~~to ~~all~~penalties. ~~the~~Finally, ~~listed~~there ~~patents~~are ~~claiming~~state and foreign laws governing the ~~referenced~~privacy ~~product~~and ~~have~~security ~~expired~~of health information, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

IfThe ~~the~~scope ~~ANDA~~and orenforcement ~~505(b)(2)~~of ~~NDA~~each ~~applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice~~ of ~~the~~these ~~Paragraph IV~~laws ~~certification~~is touncertain ~~the NDA~~ and ~~patent~~subject ~~holders~~to ~~once~~rapid ~~the~~change ~~application~~in ~~has been accepted for filing by~~ the ~~FDA.~~current ~~The~~environment ~~NDA~~of ~~and~~healthcare ~~patent~~reform, ~~holders~~especially ~~may then initiate a patent infringement lawsuit~~ in ~~response~~light ~~to the notice~~ of the ~~Paragraph IV~~lack ~~certification. The filing~~ of aapplicable ~~patent~~precedent ~~infringement~~and ~~lawsuit~~regulations ~~within~~with ~~45 days~~respect ~~after~~to ~~the~~certain ~~receipt~~laws. ofFederal ~~notice~~and ofstate ~~the~~enforcement ~~Paragraph IV~~bodies ~~certification~~have ~~automatically~~recently ~~prevents~~increased ~~the~~their ~~FDA~~scrutiny ~~from approving the ANDA or 505(b)(2) NDA until the earlier~~ of ~~30 months,~~interactions ~~expiration~~between ofhealthcare ~~the~~companies ~~patent,~~and ~~settlement~~healthcare ~~of the lawsuit, a decision in the infringement case that is favorable to the ANDA applicant or other period determined by a court.~~

~~Hatch‑Waxman Non‑Patent Exclusivity~~11

Market and data exclusivity provisions under the FDCA also can delay the submission or the approval of certain applications for competing products. The FDCA provides a five‑year period of non‑patent data exclusivity within the United States to the first applicant to gain approval of an NDA for a NCE. A drug is a NCE if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the therapeutic activity of the drug substance. During the exclusivity period, the FDA may not accept for review an ANDA or a 505(b)(2) NDA submitted by another company that contains the previously approved active moiety. However, an ANDA or 505(b)(2) NDA may be submitted after four years if it contains a certification of patent invalidity or non‑infringement.

The FDCA also provides three years of marketing exclusivity for an NDA, 505(b)(2) NDA, or supplement to an existing NDA or 505(b)(2) NDA, if new clinical investigations other than bioavailability studies that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application or supplement. Three‑year exclusivity may be awarded for changes to a previously approved drug product, such as new indications, dosages, strengths or dosage forms of an existing drug. This three‑year exclusivity covers only the conditions of use associated with the new clinical investigations and, as a general matter, does not prohibit the FDA from approving ANDAs or 505(b)(2) NDAs for generic versions of the original, unmodified drug product. Five‑year and three‑year exclusivity will not delay the submission or approval of a full NDA; however, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well‑controlled clinical trials necessary to demonstrate safety and effectiveness.

Approval of Biosimilars and Biologic Exclusivity

The Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), which was enacted as part of the ACA, created an abbreviated approval pathway for biological products that are demonstrated to be “biosimilar” or “interchangeable” with an FDA-licensed reference biological product via an approved BLA. Biosimilarity is established by demonstrating that there are no clinically meaningful differences between the biological product and its reference product in terms of safety, purity, and potency. This determination is typically based on analytical studies, animal studies, and one or more clinical studies. Interchangeability, on the other hand, requires that a product is biosimilar to the reference product and must further show that it is expected to produce the same clinical results in any given patient. Additionally, for products administered multiple times, the reference biologic and the interchangeable biologic must be able to be switched or alternated without increasing safety risks or compromising efficacy compared to exclusive use of the reference biologic.

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Aproviders, ~~product~~which ~~designated~~has asled ~~biosimilar~~to ora ~~interchangeable~~number toof aninvestigations, ~~FDA-approved~~prosecutions, ~~reference~~convictions ~~biological~~and ~~product~~settlements ~~may~~in ~~rely~~the onhealthcare ~~the~~industry. ~~FDA’s~~Prohibitions ~~prior~~or ~~determination~~restrictions on sales or withdrawal of ~~safety~~future ~~and~~marketed ~~effectiveness~~products ~~for~~could ~~that~~materially ~~reference~~affect ~~product~~our business in an adverse way. ~~This~~Changes ~~reliance~~in ~~can~~regulations, ~~reduce~~statutes ~~both~~or the ~~cost~~interpretation ~~and~~of ~~time~~existing ~~required~~regulations tocould ~~obtain~~impact ~~market~~our ~~approval.~~business ~~However~~in the future by requiring, ~~due~~for example: (i) changes to ~~the~~our ~~larger~~manufacturing ~~and~~arrangements; ~~more~~(ii) ~~complex~~additions ~~structures~~or modifications to product labeling; (iii) the recall or discontinuation of ~~biological~~our products; ~~and~~or ~~the~~(iv) ~~intricate~~additional ~~manufacturing~~record-keeping ~~processes~~requirements. ~~involved~~If any such changes were to be imposed, they could adversely affect the ~~abbreviated~~operation ~~approval~~of ~~pathway~~our ~~remains~~business. ~~challenging~~Ensuring toour ~~implement,~~business arrangements comply with ~~many~~applicable ~~regulatory~~healthcare ~~details~~laws, ~~still~~as ~~being~~well ~~refined~~as responding to possible investigations by government authorities, can be time- and resource-consuming and can divert a company’s attention from the ~~FDA~~business.

~~Under~~The ~~the~~failure ~~BPCIA,~~to ancomply ~~application~~with ~~for~~any aof ~~biosimilar~~these ~~cannot~~laws beor ~~submitted~~regulatory requirements subjects companies to ~~the~~possible ~~FDA~~legal ~~until~~or ~~four~~regulatory ~~years~~action. ~~after~~Depending on the ~~reference~~circumstances, ~~product~~failure ~~was~~to ~~first~~meet ~~licensed.~~applicable ~~Furthermore,~~regulatory ~~the~~requirements ~~FDA~~can ~~cannot~~result ~~approve~~in asignificant ~~biosimilar~~penalties, ~~until~~including 12civil, ~~years~~criminal ~~after~~and ~~the~~administrative ~~reference~~penalties, ~~product's~~damages, ~~initial~~fines, ~~approval.~~disgorgement, ~~During~~imprisonment, ~~this~~possible ~~12-year~~exclusion ~~exclusivity~~from ~~period,~~participation ain ~~competing~~federal ~~product~~and ~~may~~state ~~still~~funded behealthcare ~~marketed~~programs, ifcontractual damages and the ~~FDA~~curtailment ~~approves~~or arestricting ~~full~~of ~~BLA~~our ~~containing~~operations, ~~the~~as ~~applicant’s~~well ~~own~~as ~~preclinical~~additional reporting obligations and ~~clinical~~oversight ~~trial~~if ~~data~~we ~~demonstrating~~become ~~safety,~~subject ~~purity,~~to ~~and~~a ~~potency.~~corporate ~~Additionally,~~integrity ~~the~~agreement ~~BPCIA~~or ~~provides~~other ~~certain~~agreement ~~exclusivity~~to ~~periods~~resolve ~~for~~allegations ~~biosimilars~~of ~~designated~~non-compliance aswith ~~interchangeable~~these ~~products~~laws. ~~However~~Any action for violation of these laws, iteven ~~remains~~if ~~uncertain~~successfully ~~whether~~defended, ~~FDA-approved~~could ~~interchangeable~~cause ~~products~~a ~~will~~pharmaceutical becompany ~~readily~~to ~~substituted~~incur bysignificant ~~pharmacies,~~legal asexpenses ~~state~~and ~~pharmacy~~divert ~~laws~~management’s ~~ultimately~~attention ~~govern~~from ~~substitution~~the ~~practices~~operation of the business.

~~Upon~~Healthcare ~~approval~~Reform of a BLA, the biologic is listed by the FDA in its Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Purple Book, along with the date it was licensed; whether the FDA has determined that the licensed biological product is biosimilar to or interchangeable with a reference biological product (an already-licensed FDA biological product) and the date of expiration of applicable exclusivity. Under the BPCIA, a reference biologic is granted 12 years of exclusivity from the time of first licensure of the reference product. This 12-year period includes 4 years before the FDA may accept for filing an application for a biologic that references a branded (reference) product. The BPCIA is complex and continues to be interpreted and implemented by the FDA. In addition, government proposals have sought to reduce the 12-year reference product exclusivity period. Other ~~aspects~~Regulatory ofChanges the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the subject of recent litigation. As a result, the ultimate implementation and impact of the BCPIA is subject to significant uncertainty.

In the United States and some foreign jurisdictions, there have been, and likely will continue to be, a number of legislative and regulatory changes and proposed changes regarding the healthcare system directed at broadening the availability of healthcare, improving the quality of healthcare, and containing or lowering the cost of healthcare.

For example, in 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, each as amended, collectively known as the ACA was enacted in the United States. The ACA includes measures that have significantly changed, and are expected to continue to significantly change, the way healthcare is financed by both governmental and private insurers. The ACA contained a number of provisions, including those governing enrollment in federal healthcare programs, reimbursement adjustments and changes to fraud and abuse laws. Among the provisions of the ACA of greatest importance to the pharmaceutical industry are that the ACA:

•subjects biological products to potential competition by biosimilars;

•made several changes to the Medicaid Drug Rebate Program, including increasing pharmaceutical manufacturers’ rebate liability; and

•extended a manufacturer’s Medicaid rebate liability to covered drugs dispensed to individuals who are enrolled in Medicaid managed care organizations.

•

Other legislative changes have been proposed and adopted in the United States since the Affordable Care Act was enacted include the following:

•The Budget Control Act of 2011, among other things, created measures for spending reductions by Congress. This includes aggregate reductions of Medicare payments to providers of 2% per fiscal year. Subsequent legislation extended the 2% reduction which remains in effect through 2031.

•On January 2, 2013, the American Taxpayer Relief Act of 2012 was signed into law, which further reduced Medicare payments to several types of providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

•On April 13, 2017, CMS published a final rule that gives states greater flexibility in setting benchmarks for insurers in the individual and small group marketplaces, which may have the effect of relaxing the essential health benefits required under the ACA for plans sold through such marketplaces.

•On May 23, 2019, CMS published a final rule to allow Medicare Advantage Plans the option of using step therapy for Part B drugs beginning January 1, 2020.

•On March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminated the statutory Medicaid drug rebate cap, previously set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, effective January 1, 2024. These laws and regulations may result in additional reductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain for any of our product candidates for which we may obtain regulatory approval or the frequency with which any such product candidate is prescribed or used.

•Further, on May 30, 2018, the Right to Try Act, was signed into law. The law, among other things, provides a federal framework for certain patients to access certain investigational new drug products that have completed a Phase 1 clinical trial and that are undergoing investigation for FDA approval. Under certain circumstances, eligible patients can seek treatment without enrolling in clinical trials and without obtaining FDA permission under the FDA expanded access program. There is no obligation for a pharmaceutical manufacturer to make its drug products available to eligible patients as a result of the Right to Try Act.

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•The Inflation Reduction Act of 2022 (IRA) includes several provisions that may impact our business to varying degrees, including provisions that reduce the out-of-pocket spending cap for Medicare Part D beneficiaries from $7,050 to $2,000 starting in 2025, thereby effectively eliminating the coverage gap; impose new manufacturer financial liability on certain drugs under Medicare Part D, allow the U.S. government to negotiate Medicare Part B and Part D price caps for certain high-cost drugs and biologics without generic or biosimilar competition; require companies to pay rebates to Medicare for certain drug prices that increase faster than inflation; and delay until January 1, 2032 the implementation of the HHS rebate rule that would have limited the fees that pharmacy benefit managers can charge. Further, under the IRA, orphan drugs are exempted from the Medicare drug price negotiation program, but only if they have one orphan designation and for which the only approved indication is for that disease or condition.  Under the One Big Beautiful Bill Act of 2025, this restriction was eliminated; and effective for the 2028 initial price applicability year, all orphan drugs, regardless of the number of orphan drug designations or indications, are exempt from the Medicare drug price negotiation program. The implementation of the IRA is currently subject to ongoing litigation challenging the constitutionality of the IRA’s Medicare drug price negotiation program. Although the effects of the IRA on our business and the healthcare industry in general are not yet known, we are taking into consideration the potential impact of the IRA on our development and commercialization activities. The implementation of the IRA is currently subject to ongoing litigation challenging the constitutionality of the IRA’s Medicare drug price negotiation program. The effects of the IRA on our business and the healthcare industry in general is not yet known.

The costs of prescription drugs and biological products have also been the subject of considerable discussion in the United States. At a federal level, President Trump reversed some of President Biden’s executive orders including rescinding Executive Order 14087 entitled “Lowering Prescription Drug Costs for Americans." President Trump may issue new executive orders designed to impact prescription product pricing. A number of these and other proposed measures may require authorization through additional legislation to become effective. Congress and the Trump administration have indicated that they will continue to seek new legislative measures to control prescription product costs.

On April 15, 2025, the Trump Administration published Executive Order 14273, “Lowering Drug Prices by Once Again Putting Americans First,” which generally directs the federal government to take measures to reduce drug prices, including eliminating the so-called “pill penalty” under the Inflation Reduction Act that creates a distinction between small molecule and large molecule products for purposes of determining when a drug may be eligible for drug price negotiation. On May 12, 2025, the Trump Administration published Executive Order 14297, “Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients” which generally, among other things, directs the federal government to establish and communicate most-favored-nation (“MFN”) price targets to pharmaceutical manufacturers to bring prices for American patients in line with comparably developed nations. Further, the Executive Order directs the federal government to support regulatory paths to allow direct-to-patient sales for companies that meet these targets. It also states that the Administration will take additional aggressive action (for example, examining whether marketing approvals should be modified or rescinded or opening the door for individual drug importation waivers) should manufacturers fail to offer American consumers the MFN lowest price or otherwise meet the Administration’s pricing objectives. It also directs the Secretary of Commerce and the U.S. Trade Representative to “take all necessary and appropriate action to ensure foreign countries are not engaged in any act, policy, or practice that may be unreasonable or discriminatory or that may impair United States national security . . . including by suppressing the price of pharmaceutical products below fair market value in foreign countries.” Notably, a similar “Most Favored Nation” pricing rule enacted under the first Trump Administration was subject to an injunction resulting from judicial challenges to the rule, which was formally rescinded by the former Biden Administration in August 2021. We cannot predict whether, when, or in what form the current Executive Orders or related agency actions will be implemented, challenged, modified, delayed or enjoined.

On December 19, 2025, CMS released two proposed rules that would incorporate MFN pricing principles into federal reimbursement for prescription drugs. The first proposal, the Global Benchmark for Efficient Drug Pricing Model (“GLOBE”) for Medicare Part B, would require manufacturers of specified single source drugs and sole source biologics to pay incremental rebates based on international benchmark prices, with participation triggered for products meeting CMS’s spending and eligibility criteria. The second proposal, the Guarding U.S. Medicare Against Rising Drug Costs (“GUARD”) model for Medicare Part D, would similarly mandate manufacturer rebates for qualifying sole source drugs where the Medicare net price exceeds an MFN benchmark derived from international reference pricing methodologies. As proposed, GLOBE would begin a five year performance period on October 1, 2026 and GUARD would begin its performance period in 2027. These proposals will likely be subject to legal challenges that could delay their implementation or modify their impact on manufacturer pricing and revenue. Additionally, in November 2025, CMS introduced the GENErating cost Reductions for U.S. Medicaid (“GENEROUS”) Model, a voluntary MFN framework for manufacturers participating in the Medicaid Drug Rebate Program. Although it is voluntary, the GENEROUS Model could also impact the drug pricing landscape for manufacturers.

In addition, at the state level, legislatures have increasingly passed legislation and implemented regulations similar to those under consideration at the federal level, as well as laws designed to control pharmaceutical and biotherapeutic product pricing, including restrictions on pricing or reimbursement at the state government level, limitations on discounts to patients, marketing cost disclosure and transparency measures, restrictions or other limitations on patient assistance, and, in some cases, policies to encourage importation from other countries (subject to federal approval) and bulk purchasing. Certain states are also pursuing

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cost containment efforts through Prescription Drug Affordability Boards (“PDABs”) and similar entities. While many PDABs have been granted authority to promote drug price transparency and reporting, some states have granted PDABs more expansive authority, including to set Upper Payment Limits (UPLs) on select, high price drugs. The adoption and implementation of UPLs may put downward pressure on drug prices and impact our company’s future revenues.

Exclusivity and Approval of Competing Products

Approval of Biosimilars and Biologic Exclusivity

The Biologics Price Competition and Innovation Act of 2009 (“BPCIA”) created an abbreviated approval pathway for biological products that are demonstrated to be “biosimilar” or “interchangeable” with an FDA-licensed reference biological product. Biosimilarity is established by demonstrating that there are no clinically meaningful differences between the biological product and its reference product in terms of safety, purity, and potency. This determination is typically based on analytical studies, animal studies, and in some cases, clinical studies. Interchangeability requires that a product is biosimilar to the reference product and must further show that it is expected to produce the same clinical results in any given patient. For products administered multiple times, the reference biologic and the interchangeable biologic must be able to be switched or alternated without increasing safety risks or compromising efficacy compared to exclusive use of the reference biologic.

A product designated as biosimilar or interchangeable to an FDA-approved reference biological product may rely on the FDA’s prior determination of safety and effectiveness for that reference product. This reliance can reduce both the cost and time required to obtain market approval. However, due to the larger and more complex structures of biological products and the intricate manufacturing processes involved, the biosimilar pathway remains challenging to implement.

Under the BPCIA, an application for a biosimilar cannot be submitted to the FDA until four years after the reference product was first licensed. Furthermore, the FDA cannot approve a biosimilar until 12 years after the reference product's initial approval. During this 12-year exclusivity period, a competing product may still be marketed if the FDA approves a full BLA containing the applicant’s own preclinical and clinical trial data demonstrating safety, purity, and potency. Additionally, the BPCIA provides certain exclusivity periods for biosimilars designated as interchangeable products. State pharmacy laws govern whether FDA-approved interchangeable products can be readily substituted for the reference product .

Pediatric Exclusivity

Pediatric exclusivity is another type of non‑patent regulatory and marketing exclusivity in the United States and, if granted, provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity, including the non‑patent exclusivity period described above. ~~A biological product can also obtain pediatric market exclusivity in the United States. Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms.~~ This six-month exclusivity, ~~which runs from the end of other exclusivity protection or patent term,~~ may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued “Written Request” for such a study.

Foreign Regulation

In order to market any product outside of the United States, we would need to comply with numerous and varying regulatory requirements of other countries regarding biologic and drug development, approval and commercialization. The approval process varies by country and can involve additional product testing and additional administrative review periods. The time required to obtain approval in other countries might differ from and be longer than that required to obtain FDA approval. Regulatory approval in one country does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country may negatively impact the regulatory process in others. The processes for obtaining marketing approvals in foreign countries, along with subsequent compliance with applicable statutes and regulations, require the expenditure of substantial time and financial resources.

European Union Drug Approval Process

To obtain a marketing authorization offor a ~~drug~~medicinal product, including a biologic,in the European Union, we may submit marketing authorization applications (“MAAs”) either under the so‑called centralized, decentralized, mutual recognition or national authorization procedures.

Centralized procedure

The centralized procedure provides for the grant of a single marketing authorization following a favorable opinion by the European Medicines Agency (“EMA”) that is valid in all European Union member states, as well as Iceland, Liechtenstein and Norway. The centralized procedure is compulsory for medicines produced by specified biotechnological processes, products designated as orphan medicinal products, and products with a new active substance indicated for the treatment of specified diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative disorders or autoimmune diseases and other immune dysfunctions and viral diseases. The centralized procedure is optional for products that represent a significant therapeutic, scientific or technical innovation, or whose authorization would be in the interest of public health.

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dysfunctions and viral diseases. The centralized procedure is optional for products that represent a significant therapeutic, scientific or technical innovation, or whose authorization would be in the interest of public health.

National authorization procedures

There are also three other possible routes to authorize medicinal products in several European Union countries, which are available for investigational medicinal products that fall outside the scope of the centralized procedure.

•National authorization procedure. This procedure involves submitting an MAA to an individual EU country’s competent authority for approval. Each EU Member State has its own national authorization procedures.

•Decentralized procedure. Using the decentralized procedure, an applicant may apply for simultaneous authorization in more than one European Union country of medicinal products that have not yet been authorized in any European Union country and that do not fall within the mandatory scope of the centralized procedure.

•Mutual recognition procedure. In the mutual recognition procedure, a medicine is first authorized in one European Union Member State, in accordance with the national procedures of that country. Following this, further marketing authorizations can be sought from other European Union countries in a procedure whereby the countries agree to recognize the validity of the original, national marketing authorization.

In the European Union, new products authorized for marketing (i.e., reference products) qualify for eight years of data exclusivity and an additional two years of market exclusivity upon marketing authorization. The data exclusivity period prevents generic applicants from relying on the preclinical and clinical trial data contained in the dossier of the reference product when applying for a ~~generic~~follow-on marketing authorization in the EU during a period of eight years from the date on which the reference product was first authorized in the EU. The market exclusivity period prevents a successful ~~generic~~follow-on applicant from commercializing its product in the EU until ten years have elapsed from the initial authorization of the reference product in the EU. The ten‑year market exclusivity period can be extended to a maximum of eleven years if, during the first eight years of those ten years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.

Employees and Human Capital Management

As of December 31, ~~2024~~2025, we had ~~twenty-three~~33 employees, all of whom were full-time. ~~Thirteen~~18 of our employees are primarily engaged in research and development activities. None of our employees are represented by a labor union or covered by a collective bargaining agreement. We consider our relationship with our employees to be good.

We believe that our future success largely depends upon our ability to scale and to attract and retain highly skilled and qualified personnel. We believe that we provide our employees with competitive salaries and bonuses, opportunities for equity ownership, and an employment package that promotes well-being across all aspects of their lives, including health care, retirement planning and paid time off. We ~~value~~believe ~~diversity~~that much of our success is rooted in the variety of backgrounds represented in our teams and ~~inclusiveness~~our atcommitment ~~all~~to ~~levels~~inclusion. We focus on extending our inclusion initiatives across our entire workforce.

Corporate Information

We were incorporated in Delaware in 2011 and commenced operations in the second quarter of 2011. We completed our initial public offering in October 2015. Our principal executive offices are located at ~~540~~1500 ~~Gaither~~Liberty ~~Road~~Ridge Drive, Suite ~~400~~321, ~~Rockville~~Wayne, ~~Maryland~~PA ~~20850~~19087, and our phone number is (410) 522-8707. Our website address is www.avalotx.com. The information on, or that can be accessed through, our website is not part of this report. We have included our website address in this report solely as an inactive textual reference.

Available Information

Our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934 (the “Exchange Act”), are available free of charge on our website at www.avalotx.com as soon as reasonably practicable after electronically filing or furnishing such material to the Securities and Exchange Commission. The Securities and Exchange Commission maintains a website (www.sec.gov) that includes our reports, proxy statements and other information.

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Item 1A. Risk Factors.

You should consider carefully the following information about the risks described below, together with the other information contained in this Annual Report on Form 10-K and in our other public filings, in evaluating our business. If any of the following risks actually occurs, our business, financial condition, results of operations and future growth prospects would likely be materially and adversely affected. In these circumstances, the market price and value of our securities would likely decline. Additional risks or uncertainties not presently known to us or that we currently deem immaterial may also harm our business. Moreover, some of the factors, events and contingencies discussed below may have occurred in the past, but the disclosures below are not representations as to whether or not the factors, events or contingencies have occurred in the past and instead reflect our beliefs and opinions as to the factors, events, or contingencies that could materially and adversely affect us in the future.

Risks Related to Our Financial Position and Capital Needs

We expect to require additional capital in the future to continue to fund our operations and to finance the further advancement of our product candidates, which might not be available to us on acceptable terms, or at all. Failure to obtain any necessary capital could force us to delay, limit or terminate our product development efforts or significantly curtail or cease our operations altogether.

AtAs ~~December~~a ~~31,~~research ~~2024~~and development company, weour ~~had~~operations ~~$134.5~~have ~~million~~consumed insubstantial amounts of cash since inception. Identifying potential product candidates and ~~cash~~conducting ~~equivalents~~preclinical testing and ~~$7.0~~clinical ~~million~~trials inis ~~current~~a ~~liabilities.~~time‑consuming, Asexpensive ofand ~~the~~uncertain ~~date~~process ofthat ~~this~~takes ~~Report~~years to complete, and we ~~believe~~expect weour ~~have~~research ~~sufficient~~and ~~funds~~development expenses to ~~finance~~increase ~~our~~substantially ~~continuing~~in ~~operations~~connection ~~into~~with atour ~~least~~ongoing ~~2027~~activities, toparticularly ~~further~~as we advance our current product candidates. ~~However,~~through weor ~~will~~into ~~likely~~clinical ~~need~~trials toand ~~raise~~prepare ~~additional~~for ~~funds~~later-stage ~~prior~~development toactivities, ~~any~~including ~~phase~~manufacturing 3scale-up, ~~development~~regulatory engagement, and~~/or~~ ~~indication~~commercialization ~~expansion~~planning. ~~Additionally,~~Circumstances ifmay ~~there~~cause ~~are~~us ~~significant~~to ~~unexpected~~consume ~~delays and/~~or ~~cost~~require ~~overruns~~capital inmore rapidly than we currently anticipate. Historically, our ~~current~~capital ~~Phase~~constraints 2have ~~LOTUS~~required ~~trial~~us to prioritize certain development programs over others, orincluding ~~other~~deferring, ~~negative~~out-licensing ~~deviations~~or ~~from~~discontinuing ~~cash~~certain ~~forecast~~candidates, and we ~~might~~may ~~require~~be required to do so again in the future. We will need to raise additional funds ~~prior~~or otherwise obtain funding through collaborations to complete the ~~Phase~~development 2of ~~LOTUS~~abdakibart ~~trial read~~(AVTX-~~out~~009) and any other product candidates and to continue our operations.

AsWe aplan ~~research~~to ~~and~~finance ~~development company,~~ our operations ~~have~~through ~~consumed~~a ~~substantial~~combination ~~amounts~~ of ~~cash~~equity ~~since~~offerings, ~~inception.~~debt ~~Identifying~~financings, ~~potential~~collaborations, ~~product~~licensing ~~candidates~~arrangements and ~~conducting~~other ~~preclinical~~similar ~~testing~~arrangements. ~~and~~We ~~clinical~~do ~~trials~~not ishave aany ~~time‑consuming,~~committed ~~expensive~~sources ~~and~~of ~~uncertain~~external ~~process~~financing. ~~that~~Our ~~takes~~ability ~~years~~ to ~~complete,~~raise ~~and~~additional wefunds ~~expect~~may ~~our~~be ~~research~~adversely ~~and~~impacted ~~development~~by ~~expenses~~global toeconomic ~~increase~~conditions, ~~substantially~~disruptions into, ~~connection~~and ~~with~~volatility ~~our ongoing activities~~in, ~~particularly~~the ascredit weand ~~advance~~financial ~~our~~markets ~~current~~in ~~product~~the ~~candidates~~United ~~through~~States orand ~~into~~worldwide, ~~clinical~~and ~~trials.~~diminished ~~Circumstances~~liquidity ~~may~~and ~~cause~~credit usavailability, toand ~~consume~~biotechnology-specific ormarket ~~require~~conditions, ~~capital~~including ~~more~~reduced ~~rapidly~~investor ~~than~~appetite wefor ~~currently~~clinical-stage ~~anticipate~~companies. AsIf anthe ~~example,~~equity ~~our~~and ~~cash~~credit ~~position~~markets indeteriorate, ~~the~~it ~~past~~may ~~has~~make ~~caused~~any usnecessary todebt ~~prioritize~~or ~~product~~equity ~~candidates~~financing ~~for~~more ~~development~~difficult, ~~out-license~~more ~~certain~~costly ~~product candidates~~ and tomore ~~defer the development of other candidates~~dilutive. WeIf ~~will~~we ~~need~~are unable to raise ~~additional~~capital ~~funds~~when needed or ~~otherwise~~on ~~obtain~~attractive ~~funding~~terms, ~~through~~we ~~collaborations~~would tobe ~~complete~~forced ~~the development of any of our product candidates and~~ to ~~continue our operations.~~:

~~Additional~~•Significantly ~~fundraising efforts may divert our management from our day‑to‑day activities~~delay, ~~which~~scale ~~may~~back adversely affect our ability to develop and commercialize our product candidates. In addition, we do not have any committed external sources of funding, and cannot guarantee that future financing will be available in sufficient amounts or ondiscontinue ~~terms acceptable to us, if at all. Furthermore, our ability to raise capital on a timely basis through~~ the ~~issuance~~development ~~and~~or ~~sale~~commercialization of ~~equity~~abdakibart ~~securities might be limited by Nasdaq’s listing rules on transactions that do not qualify as “public offerings”~~ (~~as defined in Nasdaq listing rules~~AVTX-009), ~~which might require us to obtain stockholder approval prior to the issuance of common stock (~~or ~~securities~~other ~~convertible~~product ~~into~~candidates or ~~exercisable~~cease ~~for~~operations ~~common stock) at a price per share that is less than the “Minimum Price” if the issuance would equal 20% or more of our common stock outstanding before the issuance.~~ altogether;

We•Seek ~~may~~strategic ~~need~~alliances tofor ~~seek~~research ~~additional~~and ~~funds~~development ~~sooner~~programs ~~than~~at ~~anticipated~~an ~~through~~earlier ~~public~~stage orthan ~~private~~we ~~equity~~would ~~offerings,~~otherwise ~~debt~~desire ~~financings, collaborations, licensing agreements,~~ or ~~other~~on ~~sources.~~terms ~~Such~~less ~~financing~~favorable ~~could~~than ~~dilute~~might ~~our~~otherwise ~~shareholders,~~be ~~and~~available; ~~failure to secure adequate funding may limit our operational activities.~~ or

If•Relinquish, ~~we raise additional capital through the sale of equity~~ or ~~convertible~~license ~~debt~~on ~~securities,~~unfavorable ~~your ownership interest may be diluted, and the~~ terms ~~of such financing could include liquidation preference~~, ~~anti-dilution~~our ~~provisions, or other~~ rights ~~that~~to ~~may~~technologies ~~negatively~~or ~~impact~~any ~~your~~future ~~position~~product ascandidates athat ~~shareholder.~~we ~~Debt~~otherwise ~~financing~~would ~~could~~seek ~~impose~~to ~~restrictive~~develop ~~covenants, increase fixed payment obligations,~~ or ~~introduce~~commercialize ~~other constraints that could affect our business operations~~ourselves.

IfAt December 31, 2025, we ~~secure~~had ~~additional~~$98.3 ~~funds~~million ~~through~~in ~~upfront~~cash orand ~~milestone~~cash ~~payment~~equivalents asand ~~part~~short-term investments and $12.9 million in current liabilities. As of ~~future~~the ~~collaborations~~date ~~with~~of ~~third~~this ~~parties~~Report, we ~~may~~believe bewe ~~required~~have sufficient funds to ~~relinquish~~finance ~~valuable~~our ~~rights~~continuing operations into 2028 to further advance abdakibart (AVTX-009) orand ~~grant~~other ~~licenses~~product ~~under~~candidates. ~~terms~~This ~~that~~estimate ~~are~~is ~~not~~based ~~favorable~~on toassumptions ~~us.~~regarding ~~Our~~our ~~ability~~operating toplan, ~~raise~~clinical ~~additional~~timelines, ~~capital~~and expenditures that may prove to be ~~negatively~~inaccurate. ~~affected~~We bycould ~~macro~~use ~~events~~our capital resources sooner than we currently expect due to unanticipated delays, ~~such~~cost asoverruns, ~~worsening~~changes ~~global~~in ~~economic~~regulatory ~~conditions~~strategy, ~~disruptions~~or other factors. We will likely need to ~~financial~~raise ~~markets~~additional funds prior to any phase 3 development and/or indication expansion. Additionally, if there are significant unexpected delays and/or ~~volatility~~cost overruns in ~~credit~~our ~~markets~~current inPhase ~~the~~2 ~~United~~LOTUS ~~States~~trial, ~~and~~or ~~worldwide~~other negative deviations from cash forecast, aswe ~~well~~might asrequire ~~biotechnology~~additional ~~specific~~funds ~~industry~~prior ~~events~~to ~~and~~the ~~trends~~Phase 2 LOTUS trial read-out.

We may never achieve or sustain profitability.

To become and remain profitable, we must succeed in developing, obtaining regulatory approvals for, and eventually commercializing products that generate significant revenue. This will require us to be successful in a range of challenging activities, including completing clinical trials and preclinical studies and obtaining regulatory approval for one or more of our current and future product candidates, and manufacturing, marketing, and selling any products for which we may obtain regulatory approval. We may never succeed in these activities and, even if we do, may never generate revenue that is significant enough to achieve profitability. Because

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of the numerous risks and uncertainties associated with biopharmaceutical product development, we are unable to accurately predict the timing or amount of increased expenses or when, or if, we will be able to achieve profitability. Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our failure to become and remain profitable may have an adverse effect on the value of our company and could impair our ability to raise capital, expand our business, maintain our research and development efforts, diversify our product candidates, achieve our strategic objectives or even continue our operations.

Raising additional capital may cause dilution to our stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates.

Additional fundraising efforts may divert our management from our day‑to‑day activities, which may adversely affect our ability to develop and commercialize our product candidates. In addition, we do not have any committed external sources of funding and cannot guarantee that future financing will be available in sufficient amounts or on terms acceptable to us, if at all.

We may need to seek additional funds sooner than anticipated through public or private equity offerings, debt financings, collaborations, licensing agreements, or other sources. Such financing could dilute our stockholders, and failure to secure adequate funding may limit our operational activities.

If we raise additional capital through the sale of equity or convertible debt securities, your ownership interest may be diluted, and the terms of such financing could include liquidation preference, anti-dilution provisions, or other rights that may negatively impact stockholders. Debt financing could impose restrictive covenants, increase fixed payment obligations, or introduce other constraints that could affect our business operations.

If we secure additional funds through upfront or milestone payment as part of future collaborations with third parties, we may be required to relinquish valuable rights to abdakibart (AVTX-009) or grant licenses under terms that are not favorable to us. Our ability to raise additional capital may be negatively affected by macro events, such as worsening global economic conditions, disruptions to financial markets, and volatility in credit markets in the United States and worldwide, as well as biotechnology specific industry events and trends.

We might never progress to the point where we have commercially successful product sales or other revenue sufficient to sustain operations. Accordingly, we may seek to raise needed funds through public or private equity offerings, debt financings, credit facilities, partnering or other corporate collaborations and licensing arrangements. If adequate funds are not available or are not available on acceptable terms, our ability to fund our operations, take advantage of opportunities, develop products and technologies, and otherwise respond to competitive pressures could be significantly delayed or limited, and we might need to downsize or halt our operations.

IfWe wehave doincurred ~~not~~significant ~~raise~~net ~~additional~~losses ~~capital~~in ~~when~~most ~~required~~periods orsince onour ~~acceptable~~inception ~~terms,~~and we ~~may~~expect ~~need~~to continue to: incur net losses for the foreseeable future.

12Investment in biopharmaceutical product development is highly speculative because it entails substantial upfront capital expenditures and significant risk that any potential product candidate will fail to demonstrate an adequate effect or acceptable safety profile, gain marketing approval and become commercially viable. We are a clinical-stage biotechnology company with a limited operating history upon which you can evaluate our business and prospects. We commenced operations in 2011, have no products approved for commercial sale and have not generated any revenue from product sales. Since our inception, we have devoted substantially all our resources to building our organization, including an acquisition, raising capital, researching, discovering and developing potential drug candidates, establishing and maintaining our intellectual property portfolio, conducting preclinical studies and clinical trials, organizing and staffing our company, business planning and providing general and administrative support for these operations. We have not yet demonstrated the ability to successfully obtain regulatory approvals, manufacture products at commercial scale, establish reliable third-party manufacturing capabilities, or conduct sales and marketing activities necessary for successful product commercialization. Consequently, any predictions made about our future success or viability may not be as accurate as they could be if we had a history of successfully developing and commercializing biopharmaceutical products.

Historically, we have financed our operations primarily through public and private equity offerings. We incurred a net loss of $78.3 million for the year ended December 31, 2025. As of December 31, 2025, we had an accumulated deficit of $448.5 million. Substantially all of our operating losses have resulted from costs incurred in connection with our research and development program and from general and administrative costs associated with supporting our operations. We expect that our existing cash and cash equivalents and short-term investments will allow us to advance the clinical development of abdakibart (AVTX-009) and other product candidates, and we expect that the remainder will be utilized to fund other research and development activities as well as working capital and other general corporate needs. We have based these estimates on assumptions that may prove to be wrong, and we could use our capital resources sooner or differently than we currently expect.

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~~•Significantly~~Our ~~delay~~operating plans and other demands on our cash resources may change as a result of many factors currently unknown to us, ~~scale~~including ~~back~~but not limited to including clinical trial delays or ~~discontinue~~failures, ~~the~~changes ~~development~~in regulatory requirements, manufacturing challenges, strategic decisions, or ~~commercialization~~competitive ~~of AVTX~~developments and we may need to seek additional funds sooner than planned. Our existing cash and cash equivalents and short-~~009~~term investments may not be sufficient to complete development of any of our current or ~~other~~future product candidates. orWe ~~cease~~will ~~operations~~require ~~altogether;~~substantial capital in order to advance any of our current and future product candidates through clinical trials, regulatory approval and commercialization.

•Seek strategic alliances for research and development programs at an earlier stage than we would otherwise desire or on terms less favorable than might otherwise be available; or

•Relinquish, or license on unfavorable terms, our rights to technologies or any future product candidates that we otherwise would seek to develop or commercialize ourself.

Our future funding requirements, both short and long term, will depend on many factors, including:

•The initiation, progress, timing, costs and results of preclinical and clinical studies for abdakibart (AVTX-009) and any future product candidates we may develop;

•The level of research and development investment required to develop product candidates through clinical development and prepare for later stage trials;

•The rate and level of patient recruitment into clinical trials~~, including particularly the ongoing LOTUS Trial~~;

•The timing and amount of milestone payments we are required to make under license agreements;

•Changes in product development plans needed to address any difficulties that may arise in manufacturing, preclinical activities, clinical trials, regulatory interactions, or commercialization;

•The outcome, timing and cost of seeking and obtaining regulatory approvals from the FDA and other regulatory authorities, including the potential for such authorities to require that we perform more studies than currently expected;

•The initiation and completion of all required safety and efficacy studies necessary for obtaining regulatory approval in the U.S. including additional clinical trials or studies beyond those currently planned to support abdakibart (AVTX-009)’s approval and commercialization;

•Providing sufficient evidence to the FDA, and other global regulatory bodies demonstrating the safety, efficacy, and an acceptable risk-benefit profile of abdakibart (AVTX-009) or any future other product candidates;

•Our ability to promptly submit and secure ~~approval~~clearance of IND applications for our programs to initiate planned or future clinical trials;

•Effectively monitor and manage the occurrence, duration, and severity of any potential side effects or safety concerns associated with our product candidates, if any arise;

•Securing timely marketing approvals from the FDA, and other relevant regulatory authorities;

•The cost to establish, maintain, expand and defend the scope of our intellectual property portfolio and patent claims, including the amount and timing of any payments we may be required to make, or that we may receive, in connection with licensing, preparing, filing, prosecuting, defending and enforcing any patents or other intellectual property rights;

•~~The~~Competitive ~~effect~~dynamics, including the timing of ~~competing~~competitor ~~technological~~data readouts, approvals, and ~~market~~commercial ~~developments~~launches;

•The cost and timing of selecting, auditing and potentially validating a manufacturing site for commercial‑scale manufacturing;

•The cost of future commercialization activities including, developing our sales, marketing., manufacturing and distribution capabilities to accommodate any of our product candidates for which we receive marketing approval and that we determine to commercialize ourselves or in collaboration with our partners;

•Market acceptance of any approved product candidates;

•The effect of competing product and market developments;

•The ability and willingness to enter into new agreements with strategic partners, and the terms of these agreements; and

•The costs of acquiring, licensing or investing in additional businesses, products, product candidates and technologies.

We ~~have~~expect ~~incurred~~to ~~significant~~continue ~~net~~to incur losses in ~~most~~the ~~periods~~future ~~since~~and ~~our~~we ~~inception~~might never achieve profitability on an annual basis. We may also encounter unforeseen expenses, difficulties, complications, delays and other unknown factors that may adversely affect our business. Our future profitability will depend, in part, on the rate of future growth of our expenses as we ~~expect~~develop toour ~~continue~~product candidates and the successful completion of clinical development and regulatory approval, and our ability to ~~incur~~generate ~~net~~revenues from any approved products. Our prior losses inand ~~the~~expected future losses have had and will continue to have an adverse effect on our stockholders’ equity and working capital.

~~Investment~~Risks in biopharmaceutical product development is highly speculative because it entails substantial upfront capital expenditures and significant risk that any potential product candidate will fail to demonstrate an adequate effect or acceptable safety profile, gain marketing approval and become commercially viable. Historically, we have financed our operations primarily through public and private equity offerings. We incurred a net loss of $35.1 million for the year ended December 31, 2024. As of December 31, 2024, we had an accumulated deficit of $370.3 million. Substantially all of our operating losses have resulted from costs incurred in connection with our research and development program and from general and administrative costs associated with ~~our~~short-term ~~operations~~liquid investments.

WeAt ~~expect~~December to31, ~~continue~~2025, towe ~~incur~~had ~~losses~~$98.3 million in ~~the~~cash ~~future~~and cash equivalents and weshort-term ~~might~~investments. ~~never~~We ~~achieve~~historically ~~profitability~~have oninvested anour ~~annual~~cash ~~basis.~~in Wemoney ~~may~~market ~~also~~funds ~~encounter~~and ~~unforeseen~~investment-grade ~~expenses~~marketable securities such as corporate and government bonds, ~~difficulties~~commercial paper, ~~complications~~asset-backed securities, ~~delays~~U.S. ~~and~~treasury ~~other~~securities, ~~unknown~~money ~~factors~~market ~~that~~funds, ~~may~~and ~~adversely~~other ~~affect~~cash equivalents, consistent with our ~~business~~investment policy. ~~Our~~These ~~future~~investments ~~profitability~~are ~~will~~intended ~~depend,~~to inpreserve ~~part,~~principal onvalue ~~the~~and ~~rate~~maintain ofa ~~future~~high ~~growth~~degree of ~~our~~liquidity ~~expenses~~while asproviding wecurrent ~~develop~~income. ~~our~~However, ~~product~~these ~~candidates~~instruments ~~and~~are ~~our~~subject ~~ability~~ to ~~obtain~~general ~~approval~~credit, ofliquidity, ~~one~~market orand ~~more~~interest ofrate ~~our~~risks. ~~product~~We ~~candidates~~may torealize ~~generate~~losses ~~revenues.~~in ~~Our~~the ~~prior~~fair ~~losses~~value ~~and~~of ~~expected~~these ~~future~~investments, ~~losses~~which ~~have~~could ~~had~~include ~~and~~a ~~will~~complete ~~continue~~loss toof these investments, which would have ana ~~adverse~~negative effect on our ~~stockholders’~~consolidated ~~equity~~financial ~~and~~statements. ~~working~~In ~~capital~~extreme market conditions, such losses could be material.

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WeIn ~~face~~addition, ~~risks~~should ~~associated~~our ~~with~~investments ~~short-term~~cease ~~liquid~~paying or reduce the amount of interest paid to us, our interest income would decrease. Interest rate fluctuations can negatively impact the returns on our fixed-income investments, particularly during periods of rising interest rates.

~~At December 31~~Further, ~~2024,~~these wetypes ~~had~~of ~~$134.5~~investments ~~million~~are innot ~~cash~~insured ~~and~~against ~~cash~~loss ~~equivalents.~~of Weprincipal, ~~historically~~and ~~have~~cash ~~invested~~and ~~our~~ cash inequivalents ~~money market funds~~ and ~~intend~~short-term toinvestments ~~invest~~held in adeposit ~~variety~~accounts ofbear ~~investment-grade~~the ~~marketable~~risk ~~securities~~of ~~such~~bank asfailure ~~corporate~~to ~~and~~the ~~government~~extent ~~bonds,~~balances ~~commercial~~exceed ~~paper,~~applicable ~~asset-backed~~government ~~securities,~~insurance Ulimits.S. ~~treasury~~There ~~securities,~~is ~~money~~no ~~market~~guarantee ~~funds,~~that ~~and~~investments ~~other~~in ~~cash~~these ~~equivalents,~~assets ~~that~~will ~~are~~be ~~intended~~redeemable toat ~~preserve~~par ~~principal~~ value. ~~and~~Once ~~maintain~~invested, aif ~~high~~we ~~degree~~cannot ofliquidate ~~liquidity~~our ~~while providing current income. However~~investments, ~~these~~or ~~instruments~~redeem ~~are~~them ~~subject~~at topar, ~~general~~we ~~credit,~~could ~~liquidity,~~incur ~~market~~losses and ~~interest~~experience ~~rate~~liquidity ~~risks~~issues. WeA ~~may~~decline ~~realize losses~~ in the ~~fair~~ value of ~~these~~our investments, ~~which~~or ~~could include~~ a ~~complete~~delay ~~loss~~or suspension of ~~these~~our ~~investments,~~right ~~which~~to ~~would~~redeem may have a ~~negative~~material adverse effect on our ~~consolidated~~results ~~financial~~of ~~statements.~~operations ~~In addition, should our investments cease paying~~ or ~~reduce~~financial ~~the amount of interest paid to us, our interest income would decrease~~condition. ~~Interest rate fluctuations can negatively impact the returns on our fixed-income investments.~~

Further, these types of investments are not insured against loss of principal, and cash and cash equivalents held in deposit accounts bear the risk of bank failure. There is no guarantee that investments in these assets will be redeemable at par value. Once invested, if we cannot liquidate our investments, or redeem them at par, we could incur losses and experience liquidity issues. A decline in the value of our investments or a delay or suspension of our right to redeem may have a material adverse effect on our results of operations or financial condition.

Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited.

We have a significant amount of gross net operating losses (“NOLs”) for federal and state purposes. The Company has accumulated $3.4 million of NOLs through the end of 2017, which will begin to expire in 2031. Unused NOLs for the current tax year and prior tax years will carry forward to offset future taxable income, if any, until such unused losses expire. Unused NOLs generated after December 31, 2017 of $~~183~~255.0 million, will not expire and may be carried forward indefinitely, but will be only deductible to the extent of 80% of current year taxable income in any given year. In addition, both the deductibility of current and future unused NOL carryovers may be subject to limitation under Sections 382 and 383 of the Internal Revenue Code (“IRC”). Sections 382 and 383 of the IRC subject the future utilization of NOLs and certain other tax attributes, such as research and experimental tax credits, to an annual limitation in the event of certain ownership changes. In general, an “ownership change” is defined as a greater than 50% change (by value) in equity ownership over a three-year period. As of December 31, ~~2024~~2025, the Company had various research tax credits of $67.37 million that will begin to expire in 2038. If we experience an ownership change, or if we do not generate sufficient taxable income before the expiration of these attributes, some or all of our NOLs or tax credits could expire unused. To the extent there is a limitation, there could be a reduction in the $78.04 million deferred tax asset related to Federal loss carryforwards and tax credits that may have expired unutilized with an offsetting reduction in the valuation allowance.

Our operating results fluctuate from quarter to quarter and year to year, making future operating results difficult to predict.

Our quarterly and annual operating results historically have fluctuated and are likely to continue to fluctuate depending on several factors, many of which are beyond our control, including but not limited to the timing and outcome of clinical trials, regulatory interactions, financing activities, changes in operating plans, and macroeconomic or industry conditions. Accordingly, our quarterly and annual results are difficult to predict prior to the end of the quarter or year, and we may be unable to confirm or adjust expectations with respect to our operating results for a particular period until that period has closed. In addition, period-to-period comparisons of our operating results may not be meaningful due to the episodic nature of clinical development activities. In the event we provide cash projections or other guidance, any failure to meet such targets or failure to meet the expectations of analysts could adversely impact the market price of our securities. Therefore, you should not rely upon the results of any quarterly or annual periods as indications of future operating performance.

Our role as a guarantor of certain obligations assigned to Aytu exposes us to risk of loss or illiquidity.

In connection with the Aytu Divestiture, as defined in the Notes to our Consolidated Financial Statements, we assigned payment obligations (“TRIS Obligations”) to Aytu under a supply and distribution agreement (the “Karbinal Agreement”) with TRIS Pharma Inc. (“TRIS”), which includes a per-unit royalty make whole payment for each unit sold under an annual minimum sales commitment through 2025. The total future make-whole payments to be made by Aytu are unknown as the amount owed to TRIS is dependent on the number of units sold.

As a part of the assignment, we became a guarantor to the TRIS Obligations. If Aytu defaults under the terms of the Karbinal Agreement, we could be liable as a guarantor for unpaid amounts of the TRIS Obligation. Any amount we would be required to pay under the TRIS Obligation would limit the amount of cash available for development of our clinical pipeline and may expose us to significant losses, which would materially and adversely affect our results of operations.

We have no approved commercial products.

~~Our~~With ~~supply~~no ~~and~~commercial ~~license~~products, ~~agreement~~our ~~for~~operations ~~our~~are ~~only~~not ~~commercial~~expected ~~pharmaceutical~~to ~~product,~~produce ~~Millipred®,~~revenues ~~which~~for the ~~Company~~foreseeable ~~considered a non-core asset~~future, ~~expired,~~or asat ~~planned~~all, onwhich ~~September~~might ~~30,~~harm ~~2023.~~our ~~The~~ability ~~product revenue from Millipred® was not sufficient~~ to ~~provide~~obtain ~~adequate~~additional ~~capital~~financing ~~for~~and ~~the~~might ~~continued~~require ~~development~~us ofto ~~our~~reduce ~~product~~or ~~candidates.~~discontinue ~~With no commercial products,~~ our operations ~~are not expected to~~ .

14Our ability to generate revenue in the future will depend on developing and commercializing our current and future product candidates. Identifying, developing, obtaining regulatory approval and commercializing product candidates are prone to the risks of failure inherent in clinical development. Developing product candidates is expensive, and we expect to spend substantial amounts as we fund our product development. We cannot provide any assurance that we will be able to successfully advance any product candidate through the development process or successfully commercialize any product candidate, or that any such product candidate will be widely accepted in the marketplace or be more effective than other commercially available alternatives. Any failure to develop or commercialize a product candidate in our current clinical pipeline could require us to raise additional financing.

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produce revenues for the foreseeable future, or at all, which might harm our ability to obtain additional financing and might require us to reduce or discontinue our operations.

Our ability to increase revenue in the future will depend on developing and commercializing our current and future product candidates. Identifying, developing, obtaining regulatory approval and commercializing product candidates are prone to the risks of failure inherent in clinical development. Developing product candidates is expensive, and we expect to spend substantial amounts as we fund our product development. We cannot provide any assurance that we will be able to successfully advance any product candidate through the development process or successfully commercialize any product candidate, or that any such product candidate will be widely accepted in the marketplace or be more effective than other commercially available alternatives. Any failure to develop or commercialize a product candidate in our current clinical pipeline could require us to raise additional financing.

Risks Related to Development of Our Product Candidates

We are substantially dependent on the success of abdakibart (AVTX-009), and our ongoing and anticipated clinical trials of abdakibart (AVTX-009) may not be successful.

We acquired abdakibart (AVTX-009) in March 2024 and have focused our resources on abdakibart (AVTX-009) thereby increasing our exposure to risks associated with a single lead product candidate. Our future success, including financial condition and results of operations, relies heavily on our ability to successfully develop abdakibart (AVTX-009) for marketing approval and eventual commercialization. We are dedicating the majority of our efforts and financial resources to the research and development of ~~AVTX-009. In October 2024 we announced the first patient enrolled in our global Phase 2 LOTUS clinical trial.~~

AVTX-009 will require further clinical development, assessment of clinical, preclinical, and manufacturing activities, regulatory approval in multiple jurisdictions, substantial investment, and significant marketing efforts before we can generate any revenue from product sales. We are not allowed to market or promote AVTX-009 until we receive marketing approval from the FDA, and other comparable foreign regulatory authorities, and we may never obtain such approvals.19

~~The~~Table ~~success~~ of AVTX-009 will depend on various factors, many of which are beyond our control. These include aspects of clinical development, the regulatory submission process, potential challenges to our intellectual property rights, and the manufacturing, marketing, distribution, and sales activities of any third parties with whom we may collaborate in the future. Therefore, we cannot guarantee that we will ever generate revenue from the sale of AVTX-009, even if it receives regulatory approval. If we are unable to successfully commercialize AVTX-009, or if there are significant delays in doing so, our business will be materially impacted.Contents

abdakibart (AVTX-009). In October 2024 we announced the first patient enrolled in our global Phase 2 LOTUS clinical trial and in October 2025 we announced that we completed enrollment.

Abdakibart (AVTX-009) will require further clinical development, generation and assessment of clinical and preclinical data, manufacturing activities, regulatory approval in multiple jurisdictions, substantial investment, additional scale, and significant marketing efforts before we can generate any revenue from product sales. We are not allowed to market or promote abdakibart (AVTX-009) until we receive marketing approval from the FDA and other comparable foreign regulatory authorities, and we may never obtain such approvals.

The success of abdakibart (AVTX-009) will depend on various factors, many of which are beyond our control. These include aspects of clinical development, the regulatory submission process, potential challenges to our intellectual property rights, and the manufacturing, marketing, distribution, and sales activities of any third parties with whom we may collaborate in the future. It could take years until abdakibart (AVTX-009) may receive marketing approval, and we may never obtain such marketing approval. Moreover, we cannot guarantee that we will ever generate revenue from the sale of abdakibart (AVTX-009), even if it receives regulatory approval. If we are unable to successfully commercialize abdakibart (AVTX-009), or if there are significant delays in doing so, our business will be materially impacted.

Any setback for or failure of abdakibart (AVTX-009) during its clinical development could cause material delays in and costs to its further development and commercialization. Any such delays or costs could have a material adverse effect on our financial condition and results of operations and could require us to raise more capital, turn to third-party collaborators to continue the development of abdakibart (AVTX-009) or cease operations. In addition, our focus on abdakibart (AVTX-009) may negatively impact the planned development of our other product candidates. Drug development is unpredictable and we could encounter toxicity, safety, adverse reactions or other concerns with abdakibart (AVTX-009) as we continue its development. There can be no assurances that we will successfully develop abdakibart (AVTX-009).

Interim, “topline,” and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data. Such data are inherently preliminary and should not be relied upon as definitive or predictive of final results.

From time to time, we may publicly disclose preliminary or topline data from our preclinical studies and clinical trials, which is based on an initial analysis of then-available data, and the results and related findings and conclusions are subject to change following a more comprehensive review of the data related to the particular study or trial. There can be no assurance that the final topline data from our trials will be consistent with such results or otherwise viewed as positive. We also may make assumptions, estimations, calculations and conclusions as part of our analyses of preliminary or topline data, and we may not have received or had the opportunity to fully and carefully evaluate all data. As a result, the topline or preliminary results that we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated.

Topline data also remain subject to audit and verification procedures including data cleaning, source verification, and protocol-specified analyses, that may result in the final data being materially different from the preliminary data we previously published. As a result, topline data should be viewed with caution until the final data are available. From time to time, we may also disclose interim data from our clinical trials. Interim data from clinical trials that we may complete, including data from of our clinical trials, are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available or as patients from our clinical trials continue other treatments for their diseases. Early trends observed in interim analyses may not persist through trial completion. Adverse differences between preliminary or interim data and final data could significantly harm our business prospects. Further, disclosure of interim data by us or by our competitors could result in volatility in the price of our common stock.

Further, others, including regulatory agencies, may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular product candidate or product and our company in general. In addition, the information we choose to publicly disclose regarding a particular study or clinical trial, is based on what is typically extensive information, and you or others may not agree with what we determine is material or otherwise appropriate information to include in our disclosure.

If the interim, topline, or preliminary data that we report differ from actual results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain approval for, and commercialize, our product candidates may be harmed, which could harm our business, results of operations, prospects or financial condition.

If clinical trials of our product candidates fail to demonstrate safety and efficacy to the satisfaction of regulatory authorities or do not otherwise produce positive results, we may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of our product candidates.

Before obtaining required approvals from regulatory authorities for the sale of product candidates, we alone, or with a partner, must conduct extensive clinical trials to demonstrate the safety and efficacy of the product candidates in humans. Clinical testing is expensive and difficult to design and implement, can take many years to complete and is uncertain as to outcome. A failure of one or more clinical trials can occur at any stage of testing. The outcome of preclinical studies and early clinical trials might not predict the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results. A number of companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in advanced clinical trials due to lack of efficacy or unacceptable safety profiles, notwithstanding promising results in earlier trials. Our product candidates will require additional clinical and preclinical development, management of clinical, preclinical and manufacturing activities, regulatory approval in multiple jurisdictions, obtaining manufacturing supply on our own or from a third party, expansion of our commercial organization, and substantial investment and significant marketing efforts before we could generate any revenues from sales of any of those product candidates approved for marketing. We do not know whether the clinical trials we or our partners may conduct will demonstrate adequate efficacy and safety data resulting in regulatory approval enabling us to market any of our product candidates in any particular country. If later stage clinical trials do not produce favorable results, our ability to achieve regulatory approval for any of our product candidates would be adversely impacted, which could cause a sharp decline in our stock price and/or lead to insolvency of the Company.20

Our product candidates that we intend to commercialize are in early to mid-stages of development. If we do not successfully complete nonclinical testing and clinical development of our product candidates or experience delays in doing so, our business may be materially harmed. Our focus and reliance on AVTX-009 increases the risk of such exposure.

We have invested a significant portion of our efforts and financial resources in the identification and preclinical and clinical development of product candidates, including AVTX-009. Our ability to generate significant product revenues will depend on our ability to advance our clinical product candidates toward approval and our preclinical product candidates into clinical development. The outcome of preclinical studies and earlier clinical trials might not predict the success of future clinical trials. Preclinical data and

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~~clinical~~Before ~~trial~~obtaining ~~data~~required ~~may~~approvals befrom ~~susceptible~~regulatory toauthorities ~~varying~~for ~~interpretations~~the ~~and~~sale ~~analyses~~of product candidates, we alone, or with a partner, must conduct extensive clinical trials to demonstrate the safety and ~~many~~efficacy of the product candidates ~~that~~in ~~performed~~humans. ~~satisfactorily~~Clinical intesting is expensive and difficult to design and implement, can take many years to complete and is uncertain as to outcome. A failure of one or more clinical trials can occur at any stage of testing. The outcome of preclinical studies and early clinical trials may not predict the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results. A number of companies in the pharmaceutical and biotechnology industries have ~~nonetheless~~suffered ~~failed~~significant setbacks in ~~later~~advanced clinical trials due to lack of efficacy or unacceptable safety profiles, notwithstanding promising results in earlier trials. Our product candidates will require additional clinical and preclinical development, management of clinical, preclinical and manufacturing activities, regulatory approval in multiple jurisdictions, obtaining manufacturing supply on our own or from a third party, expansion of our commercial organization, and substantial investment and significant marketing efforts before we could generate any revenues from sales of any of those product candidates approved for marketing.

We cannot be certain whether the clinical trials we or our partners may conduct will demonstrate adequate efficacy and safety data to support regulatory approval that would enable us to market any of our product candidates in any particular country. We also cannot be certain whether the efficacy and safety profile shown in clinical trials of any of our product candidates will be regarded by investors as competitive relative to marketed products and/or product candidates in development by third parties. If later stage clinical trials do not produce favorable results, our ability to achieve regulatory approval for any of our product candidates would be adversely impacted, which could cause a sharp decline in our stock price and materially impair our ability to continue our operations. If clinical trials do not produce sufficiently favorable results, our ability to raise capital to fund our operations and complete the development and commercialization of our product candidates could be adversely impacted.

We have invested significant efforts and financial resources in the identification and preclinical and clinical development of product candidates, including abdakibart (AVTX-009). Our ability to generate significant product revenues will depend on our ability to advance our clinical product candidates toward approval and our preclinical product candidates into clinical development. The outcome of preclinical studies and earlier clinical trials might not predict the success of future clinical trials. Preclinical data and clinical trial data may be susceptible to varying interpretations and analyses, and many product candidates that performed satisfactorily in preclinical studies and early clinical trials have nonetheless failed in later clinical development.

If we experience delays in clinical testing, we will be delayed in obtaining regulatory approvals and commercializing our product candidates, our costs may increase and our business may be harmed.

We may experience delays in obtaining or maintaining the FDA’s authorization to initiate clinical trials under future INDs and to complete ongoing clinical studies of our product candidates due to a variety of reasons. Our product development costs will increase if we experience delays in clinical testing. Significant clinical trial delays also could shorten any periods during which we may have the exclusive right to commercialize our product candidates or allow our competitors to bring products to market before we do, which would impair our ability to successfully commercialize our product candidates and may harm our business, results of operations and prospects.

~~Events~~Factors which may result in a delay or unsuccessful completion of clinical development include:

•Delays in ~~reaching an agreement with~~ or failure into ~~obtaining~~obtain authorization from the FDA, other regulatory authorities or institutional review boards (“IRBs”) or ethics committees (“ECs”) to commence or amend a clinical trial;

•Delays in reaching ~~agreements~~alignment with the FDA or other regulatory authorities regarding requisite trial design or endpoints sufficient to establish a clinically meaningful benefit of our product candidates, given there might not be well-established development paths and outcomes in the indications we pursue;

•~~Inability~~Imposition toof ~~agree~~a ~~with~~clinical hold or trial termination by regulatory authorities or us for any reason, including following an inspection of our clinical trial operations or trial sites by the FDA or other regulatory authorities onor ~~operationally~~a ~~viable~~decision ~~endpoints~~by the FDA, other regulatory authorities, IRBs, ECs or ~~trial~~us, ~~design~~or recommendation by a data safety monitoring board;

•~~Imposition~~Delays ofin areaching ~~clinical~~agreement ~~hold~~on oracceptable ~~trial~~terms ~~termination~~with ~~following~~prospective ancontract ~~inspection~~research oforganizations ~~our~~(“CROs”) and clinical trial ~~operations or trial~~ sites ~~by the FDA or other regulatory authorities~~, ~~or due to concerns about trial design, or a decision by~~ the ~~FDA,~~terms ~~other~~of ~~regulatory~~which ~~authorities,~~may ~~IRBs,~~vary ~~ECs~~significantly oramong ~~us,~~different orCROs ~~recommendation~~and byclinical ~~a data safety monitoring board, to place the~~ trial ~~on hold or otherwise suspend or terminate clinical trials at any time for safety issues or for any other reason~~sites;

•~~Delays~~Deviations infrom ~~reaching~~the ~~agreement~~trial onprotocol ~~acceptable~~by ~~terms~~clinical ~~with~~trial ~~prospective~~sites ~~contract~~and ~~research~~investigators, ~~organizations~~or ~~(“CROs”)~~failure ~~and~~to ~~clinical~~conduct the trial ~~sites;~~in accordance with regulatory requirements;

•Deviations from the trial protocol by clinical trial sites and investigators, or failing to conduct the trial in accordance with regulatory requirements;

•Failure of our third parties, such as CROs, to satisfy their contractual duties or meet expected deadlines;

•Failure to enter into agreements with third parties to obtain the results of clinical trials;

•Delays in the importation and manufacture of clinical supply;

•Delays in the testing, validation and delivery of the clinical supply of the product candidates to the clinical sites;

•For clinical trials in selected subject populations, delays in identification and auditing of central or other laboratories and the transfer and validation of assays or tests to be used to identify selected subjects;21

~~•Delays~~Table ~~due to the world-wide shortage~~ of ~~animal testing subjects, including monkeys;~~Contents

•~~Delays~~For clinical trials in ~~recruiting~~selected ~~suitable~~subject ~~subjects~~populations, delays in identification and auditing of central or other laboratories and the transfer and validation of assays or tests to ~~participate~~be inused ato ~~trial~~identify eligible subjects;

•Delays in recruiting eligible subjects to participate in a trial;

•Delays in having subjects complete participation in a trial or return for post‑treatment follow‑up;

•Delays caused by subjects dropping out of a trial due to side effects, or disease progression, or other reasons;

•Delays in adding new investigators and clinical trial sites;

•Delays resulting from national or global health or geopolitical situations, including military conflict, trade barriers, or governmental budget dynamics;

•Withdrawal of clinical trial sites from our clinical trials as a result of changing standards of care or the ineligibility of a site to participate in our clinical trials; or

•Changes in government regulations or administrative actions; or ~~lack of adequate funding to continue the clinical trials.~~

•Lack of adequate funding to continue or complete the clinical trials.

Any inability by us or our partners to complete clinical development in a timely manner could result in additional costs to us relating to product development and obtaining marketing approval and impair our ability to generate product revenues and commercialization and sales milestone payments and royalties on product sales.

If we are unable to enroll appropriate subjects in clinical trials or retain patients in the clinical trials we perform, we may not be able to complete these trials on a timely basis, or at all.

Identifying and qualifying a sufficient number of eligible subjects to participate in clinical trials of our product candidates, and retaining the subjects once qualified, is critical to our ~~regulatory~~ success. The timing of our clinical trials depends on the speed at which we can recruit appropriate subjects to participate in testing our product candidates as well as completion of required follow‑up periods. If subjects are unwilling to participate in our trials or complete the required follow-up periods, the timeline for recruiting subjects, conducting trials and obtaining marketing approval of potential products may be delayed.

16Difficulty or delays in patient recruitment into our trials could result in increased costs, delays in advancing our product development, revisions to trial design or endpoints, or termination of the clinical trials altogether. Many factors affect subject enrollment and retention, including:

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Difficulty or delays in patient recruitment into our trials could result in increased costs, delays in advancing our product development, delays in testing the effectiveness of our technology or termination of the clinical trials altogether. Many factors affect subject enrollment, including:

•The size and nature of the subject population;

•The number and location of clinical sites we ~~enroll~~activate;

•The proximity of subjects to clinical sites;

•Perceived risks and benefits of the product candidate under trial;

•Competition with other companies for clinical sites or subjects;

•The eligibility and exclusion criteria for the trial;

•The design of the clinical trial;

•Doctor, patient and public awareness of the clinical trials;

•~~Inability~~Ability to obtain and maintain subject consent;

•Ability to monitor subjects adequately during and after the administration of the product candidate and the ability of subjects to comply with the clinical trial requirements;

•Risk that enrolled subjects will drop out or be withdrawn before completion; and

•Clinicians’ and subjects’ perceptions as to the potential advantages of the drug being studied in relation to other available therapies, including any new drugs that may be approved for the indications we are investigating.

We rely on CROs and clinical trial sites to ensure the proper and timely conduct of our clinical trials,. ~~and~~Although ~~while~~ we have agreements governing their committed activities, we have limited ~~influence~~control over their ~~actual~~ performance, resources, or prioritization of our trials. If we are unable to enroll sufficient subjects in our clinical trials, if enrollment is slower than we anticipate, or if our clinical trials require more subjects than we anticipate, our clinical trials may be delayed or might not be completed. If we experience delays in our clinical trials, the commercial prospects of our product candidates will be harmed. In addition, any delays in completing our clinical trials ~~will~~may increase our costs, slow down our product candidate development and approval process and jeopardize our ability to commence product sales and generate revenues. In addition, many of the factors that could cause a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of any of our product candidates.

Disruptions to the FDA, the SEC and other governmental agencies and regulatory authorities caused by funding shortages or global health concerns could hinder the ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.

The ability of the FDA to review regulatory filings and our ability to commence human clinical trials can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory and policy changes. Average review times at the agency have fluctuated in recent years as a result. In addition, government funding of the SEC, and other governmental agencies on which our operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable.

Disruptions at the FDA and other agencies or comparable foreign regulatory authorities, may also slow the time necessary for the review and approval of applications for clinical trials or marketing authorization, which would adversely affect our business. For example, in recent years, including 2018 and 2019, the U.S. government shut down several times and certain regulatory agencies, such as the FDA and the SEC, had to furlough critical employees and stop critical activities. Additionally, action by the new Trump Administration to limit federal agency budgets or personnel may result in reductions to the FDA’s budget, employees, and operations, which may lead to slower response times and longer review periods, potentially affecting our ability to progress development of our product candidates or obtain regulatory approval for our product candidates. If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business. Further, future government shutdowns could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations.

If a prolonged government shutdown occurs, or if global health concerns prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews, or other regulatory activities, it could significantly impact the ability of the FDA or other regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business.

We may fail to successfully identify, in‑license, acquire, develop or commercialize potential product candidates.

The success of our business has in the past and is expected to continue depend in part upon our ability to identify and validate new therapeutic targets and identify, develop and commercialize therapeutics, which we may develop ourselves, in‑license or acquire from others. Research programs designed to identify product candidates require substantial technical, financial and human resources, whether or not any product candidates are ultimately identified. Our research efforts may initially show promise in identifying potential therapeutic targets or candidates, yet fail to yield product candidates for clinical development for a number of reasons, including:

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others. Research programs designed to identify product candidates require substantial technical, financial and human resources, whether or not any product candidates are ultimately identified. Our research efforts may initially show promise in identifying potential therapeutic targets or candidates, yet fail to yield product candidates for clinical development for a number of reasons, including:

•Our methodology, including our screening technology, might not successfully identify medically relevant potential product candidates;

•Our competitors may develop alternatives that render our product candidates obsolete;

•We may encounter product manufacturing difficulties that limit yield or produce undesirable characteristics that increase the cost of goods, cause delays or make the product candidates unmarketable;

•Our product candidates may cause adverse effects in subjects, even after successful initial toxicology studies, or not be tolerable, which may make the product candidates unmarketable;

•Other drugs in the same drug class as our product candidates could develop unforeseen adverse effects that could negatively impact development, approval and/or future sales of our product candidates;

•Our product candidates might not be capable of being produced in commercial quantities at an acceptable cost, or at all;

•Our product candidates might not demonstrate a meaningful benefit to subjects; and

•Our reliance on third ~~party~~parties ~~clinical~~for ~~trials~~research, ~~may~~preclinical ~~cause~~studies, usor toclinical betrials ~~denied~~may limit our access to ~~clinical~~data, ~~results~~delay ~~that~~development, ~~may~~or berestrict ~~significant~~our ability to ~~further~~independently ~~clinical~~analyze or control development decisions.

Additionally, we may focus our efforts and resources on potential programs or product candidates that ultimately prove to be unsuccessful. If any of these events occur, we may be forced to abandon our development efforts for a program or programs, which would have a material adverse effect on our business, operating results and prospects and could potentially cause us to cease operations.

Our current or future product candidates may cause undesirable side effects or have other properties that could delay or prevent their marketing approval, limit ~~the~~their commercial ~~profile of an approved label~~potential, or result in significant negative consequences following any marketing approval.

Undesirable side effects caused by our product candidates in clinical trials could cause us or regulatory authorities to ~~issue~~interrupt, delay, or halt one or more clinical trials, including issuing a clinical hold, and could result in a more restrictive label or the delay or denial of marketing approval by the FDA or other regulatory authorities. Clinical trial results may reveal safety signals that are dose-dependent, population-specific, or cumulative over time, Results of our trials could reveal a high and unacceptable severity and prevalence of side effects or unexpected characteristics.

Should our clinical trials of our product candidates reveal undesirable side effects, we could suspend or terminate our trials or the FDA or other regulatory authorities as well as IRBs or ECs could order us to suspend or cease clinical trials. The FDA or other regulatory authorities could also deny approval of our product candidates for any or all targeted indications or only for a limited indication or patient population or could require label warnings and/or precautions, contraindications, including black box warnings, additional wording regarding adverse reactions, post‑market studies, testing and surveillance programs or other conditions including distribution restrictions or other risk management mechanisms under a risk evaluation and mitigation strategy (“REMS”). Drug‑related side effects could affect subject recruitment or the ability of enrolled subjects to complete the trial or result in potential product liability claims. Any ofsuch ~~these~~outcomes ~~occurrences~~could ~~may~~materially ~~harm~~and adversely affect our ~~business~~development timelines, ~~financial~~costs, ~~condition~~ and prospects ~~significantly~~.

Further, clinical trials by their nature utilize a sample of the potential patient population. With a limited number of patients and limited duration of exposure, rare and severe side effects of our current or future product candidates may only be uncovered with a significantly larger number of patients exposed to the product candidate. Additionally, if one or more of our product candidates receives marketing approval, and we or others (regulatory agencies, consumers, etc.) later identify undesirable side effects caused by such products, a number of potentially significant negative consequences could result, including:

•We may suspend marketing of, or withdraw or recall, such product;

•Regulatory authorities may withdraw approvals of such product;

•Regulatory authorities may require additional warnings on the label or other label modifications;

•Regulatory authorities may issue safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings about such product;

•Regulatory authorities may require the establishment or modification of a REMS or other restrictions on marketing and distribution, or may require the establishment or modification of a similar strategy that may, for instance, require us to issue a medication guide outlining the risks of such side effects for distribution to patients or restrict distribution of our products and impose burdensome implementation requirements on us;

•Regulatory authorities may require that we conduct post‑marketing studies; and

•We could be sued and held liable for harm caused to subjects or patients.

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Any of these events could prevent us from achieving or maintaining market acceptance of the particular product candidate or otherwise materially harm the commercial prospects for the product candidate, if approved, and could significantly harm our business, financial condition, results of operations and prospects.

Changes in product candidate manufacturing or formulation may result in additional costs or delay.

As product candidates are developed through preclinical studies to late‑stage clinical trials toward regulatory approval and commercialization, it is common that various aspects of the development program, such as manufacturing methods and formulation, are altered in an effort to optimize processes and results. Such changes carry the risk that they will not achieve these intended objectives. Any of these changes could cause our product candidates to perform differently and affect the results of planned clinical trials or other future clinical trials conducted with the optimized materials. Such changes may also require additional testing, FDA or other regulatory authorities’ notification or approval.23

~~Similarly,~~Table ~~changes in the location~~ of manufacturing or addition of manufacturing facilities may increase our costs and require additional studies and FDA approval. This may require us to ensure that the new facility meets all applicable regulatory requirements, is adequately validated and qualified, and conduct additional studies of product candidates manufactured at the new location. Any of the above could delay completion of clinical trials, require the conduct of bridging clinical trials or the repetition of one or more clinical trials, increase clinical trial costs, delay regulatory approval of our product candidates and jeopardize our ability to commence product sales and generate revenue.Contents

~~Biologic~~As ~~products~~product candidates are ~~highly~~developed ~~complex~~through preclinical studies to late‑stage clinical trials toward regulatory approval and ~~expensive~~commercialization, ~~and~~it ifis common that various aspects of the ~~third-party~~manufacturing ~~manufacturers~~process, wesuch ~~contract~~as ~~with~~methods and formulation, are ~~unable~~altered in an effort to ~~provide~~optimize ~~quality~~processes and ~~timely~~results. ~~offerings~~Such tochanges may introduce comparability risk and carry the risk that they will not achieve these intended objectives. Any such changes could cause our product candidates to perform differently, affect the results of planned clinical ~~trial~~trials ~~sites~~or other future clinical trials conducted with the optimized materials, and limit our ability to rely on data from clinical trials ~~might~~conducted bewith ~~delayed~~an earlier version of our product candidate Manufacturing or formulation changes may require additional nonclinical testing, clinical bridging studies, regulatory notifications, or regulatory approvals.

~~Our~~Similarly, ~~product~~changes ~~candidate,~~in ~~AVTX-009,~~the islocation aof ~~biologic.~~manufacturing ~~The~~or ~~process~~addition of manufacturing ~~biologics~~facilities may increase our costs and ~~their~~require ~~components~~additional studies and FDA approval. This may require us to ensure that the new facility meets all applicable regulatory requirements, is ~~complex~~adequately validated and qualified, ~~expensive~~and conduct additional studies of product candidates manufactured at the new location. Any of the above could delay completion of clinical trials, ~~highly-regulated~~require bridging clinical trials or the repetition of one or more clinical trials, increase clinical trial costs, delay regulatory approval of our product candidates and ~~subject~~jeopardize our ability to ~~multiple~~commence ~~risks~~product sales and generate revenue.

~~Manufacturing~~Biological ~~biologics~~products isare highly ~~susceptible~~complex toand ~~product loss due to contamination~~expensive, ~~equipment failure, improper installation or operation of equipment, vendor or operator error, inconsistency in yields, variability in product characteristics~~ and ~~difficulties~~if ~~in scaling~~ the ~~production~~third-party ~~process.~~manufacturers ~~Even~~we ~~minor~~contract ~~deviations~~with ~~from~~are ~~normal~~unable ~~manufacturing~~to ~~processes~~provide ~~could~~quality ~~result in reduced production yields, product defects~~ and ~~other~~timely ~~supply~~offerings ~~disruptions.~~to ~~Furthermore,~~our ~~the~~clinical ~~development~~trial ~~of biologic products involves a lengthy and expensive process with an uncertain outcome~~sites, ~~which might require us to incur additional unforeseen costs to complete~~ our clinical trials might be delayed.

~~Although~~Our ~~we are working with third parties to develop reproducible and commercially viable manufacturing processes for our biologic~~ product ~~candidates~~candidate, ~~doing~~abdakibart so(AVTX-009), is a ~~difficult~~biologic. ~~and~~The ~~uncertain~~process ~~task,~~of ~~and~~manufacturing ~~there~~biologics ~~are~~and ~~risks~~their ~~associated~~components ~~with~~is ~~scaling to the level required for advanced clinical trials or commercialization~~complex, ~~including~~expensive, ~~among others, cost overruns, potential problems with process scale~~highly-~~out,~~regulated ~~process reproducibility, stability issues, lot consistency,~~ and ~~timely~~subject ~~availability~~to ofmultiple ~~reagents or raw materials~~risks.

WeManufacturing ~~may~~biologics ~~make~~is ~~changes~~susceptible ~~as we continue~~ to ~~evolve~~product ~~the~~loss ~~manufacturing~~due ~~processes~~to ~~for~~contamination, ~~our~~equipment ~~biologic~~failure, ~~product~~improper ~~candidates~~installation ~~for~~or ~~advanced~~operation ~~clinical~~of ~~trials and commercialization~~equipment, ~~and~~vendor weor ~~cannot~~operator beerror, ~~sure~~inconsistency ~~that~~in ~~even~~yields, ~~minor~~variability ~~changes~~ in ~~these~~product ~~processes~~characteristics ~~will~~and ~~not~~difficulties ~~cause~~in ~~our~~scaling ~~product~~the ~~candidates~~production toprocess. ~~perform~~Even ~~differently~~minor ~~and~~deviations ~~affect~~from ~~the~~normal ~~results~~manufacturing ofprocesses ~~our~~could ~~ongoing~~result ~~clinical~~in ~~trials,~~reduced ~~future~~production ~~clinical trials~~yields, orproduct ~~the~~defects ~~performance~~and ofother ~~the~~supply ~~product once commercialized~~disruptions. InFurthermore, ~~some~~the ~~circumstances,~~development ~~changes~~of inbiological ~~manufacturing~~products ~~operations,~~involves ~~including~~a tolengthy ~~our~~and ~~protocols,~~expensive ~~processes,~~process ~~materials~~with oran ~~facilities~~uncertain ~~used~~outcome, ~~may~~which might require us to ~~perform~~incur additional ~~preclinical~~unforeseen orcosts ~~comparability studies, or~~ to ~~collect~~complete ~~additional~~our clinical ~~data~~trials. Such ~~from~~issues ~~patients~~may ~~prior~~require toinvestigation, ~~undertaking~~remediation, ~~additional clinical studies~~ or ~~filing for~~ regulatory ~~approval~~reporting, ~~for~~further aincreasing ~~product~~costs ~~candidate. These requirements might lead to delays in our clinical development~~ and ~~commercialization plans for our biologic product candidates and might increase our development costs substantially~~delays.

Although we are working with third parties to develop reproducible and commercially viable manufacturing processes for our biological product candidates, doing so is a difficult and uncertain task, and there are risks associated with scaling to the level required for advanced clinical trials or commercialization, including, among others, cost overruns, potential problems with process scale-up, process reproducibility, stability issues, lot consistency, and timely availability of reagents or raw materials. Any failure by our third-party manufacturers could materially delay our clinical trials, regulatory submissions, or commercialization efforts and materially harm our business.

We face substantial competition and rapid technological change and the possibility that others may discover, develop or commercialize products before or more successfully than us.

Competitive timing risk is heightened by our clinical-stage status and limited commercial infrastructure. The biotechnology and pharmaceutical industries are intensely competitive and subject to rapid and significant technological change. We face competition with respect to our current product candidates and will face competition with respect to any future product candidates from major pharmaceutical companies, specialty pharmaceutical companies, governmental agencies, research institutions and biotechnology companies worldwide. Many of our competitors have significantly greater financial, technical manufacturing, regulatory, commercial, and human resources and may be better positioned to withstand market volatility or invest across multiple programs simultaneously. Smaller and early‑stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

Our competitors may obtain marketing approval of their products more rapidly than we may or secure regulatory exclusivity, pricing advantages, or preferred formulary placement or may obtain patent protection or other intellectual property rights that limit our ability to develop or commercialize our product candidates. Our competitors may also develop drugs that are more effective, more convenient, more widely used and less costly or have a better safety profile and better tolerability than our products and these competitors may also be more successful than us in manufacturing and marketing their products.

19Our competitors will also compete with us in recruiting and retaining qualified scientific, management and commercial personnel, establishing clinical trial sites and subject registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Competition for clinical trial sites and patient populations may intensify as additional trials are initiated in overlapping indications.

Additionally, many of our competitors and their collaborators may have significantly greater experience than we do in the following:

•Identifying and validating targets;

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~~tolerability~~•Screening ~~than~~compounds ~~our~~against ~~products and these competitors may also be more successful than us in manufacturing and marketing their products.~~targets;

~~Our~~•Manufacturing ~~competitors~~pharmaceutical ~~will also compete with us in recruiting~~ and ~~retaining~~biological ~~qualified~~products ~~scientific,~~at management and commercial personnel, establishing clinical trial sites and subject registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.scale;

~~There~~•Preclinical ~~are now~~ and ~~could~~clinical betrials ~~future numerous approved therapies for treating the conditions our product candidates seek to address and, consequently, competition in these markets is intense. Many~~ of ~~these~~potential ~~approved~~pharmaceutical ~~drugs are or may become well-established therapies or~~ products; and widely accepted by physicians, patients and third‑party payors. Some of these drugs are or may become branded and subject to patent protection and non‑patent regulatory exclusivity, and others are or may become available on a generic basis.

•Obtaining FDA and other regulatory clearances.

There are now approved therapies to treat the conditions our product candidates seek to address and there could be other approved therapies in the future, consequently, competition in these markets is intense. Many of these approved products are or may become well-established therapies and widely accepted by physicians, patients and third‑party payors. Some of these therapies are protected by patents and regulatory exclusivities, while others are available or may become available as generic or biosimilar products, which could further limit market opportunity.

Our products might not achieve adequate market acceptance among physicians, patients, third‑party payors and others in the medical community necessary for commercial success.

Even if our product candidates have or receive marketing approval, they might not gain adequate market acceptance among physicians, patients and others in the medical community. Our commercial success also depends on coverage and adequate reimbursement of our product candidates by third‑party payors, including government payors, generally, which may be difficult or time‑consuming to obtain, may be limited in scope or might not be obtained in all jurisdictions in which we may seek to market our products. The degree of market acceptance of any of our approved product candidates will depend on a number of factors, including:

•The efficacy and safety profile of our product candidates, including relative to marketed products and product candidates in development by third parties;

•Prevalence and severity of any side effects of our product candidates;

•Relative convenience and ease of administration of our product candidates;

•Cost effectiveness of our product candidates;

•The claims we may make for our product candidates based on the approved label or any restrictions placed upon our marketing and distribution of our product candidates;

•The time it takes for our product candidates to complete clinical development and receive marketing approval;

•How quickly and effectively we alone, or with a partner, can market, launch, and distribute any of our product candidates that receive marketing approval relative to competing products;

•The ability to commercialize any of our product candidates that receive marketing approval;

•The adequacy of our or our partners’ sales, medical affairs, and market-access capabilities;

•The price of our approved product candidates, including in comparison to branded or generic competitors and relative to alternative treatments;

•Potential or perceived advantages or disadvantages of our approved product candidates over alternative treatments;

•The ability to collaborate with others in the development and commercialization of new products;

•Whether coverage and adequate levels of reimbursement are available under private and governmental health insurance plans, including Medicare;

•The ability to establish, maintain and protect intellectual property rights related to our product candidates;

•The entry of generic versions of any of our approved products onto the market;

•The number of products in the same therapeutic class as our product candidates;

•The effect of current and future healthcare laws on our drug candidates;

•The ability to secure favorable managed care formulary positions for our approved product candidates, including federal healthcare program formularies;

•The ability to manufacture commercial quantities of any of our product candidates that receive marketing approval;

•Acceptance of any of our product candidates that receive marketing approval by physicians and other healthcare providers; and

•Potential post‑marketing commitments and post-marketing requirements imposed on an approved product candidate by regulatory authorities, such as patient registries.

If any product candidate is approved but does not achieve an adequate level of acceptance by physicians, hospitals, third‑party payors and patients, we might not generate or derive sufficient revenue from that product ~~candidate and might not become or remain profitable.~~

Weand may ~~expend~~not ~~our~~achieve ~~limited~~or ~~resources~~sustain toprofitability, ~~pursue~~which acould ~~particular~~materially ~~product candidate or indication~~ and ~~fail~~adversely toaffect ~~capitalize~~our onbusiness, ~~product~~financial ~~candidates~~condition, orresults ~~indications that may be more profitable or for which there is a greater likelihood~~ of ~~success.~~operations, ~~Our focus~~ and ~~reliance on AVTX-009 increases the risk of such exposure~~prospects.

20We may expend our limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success. Our concentration of resources and reliance on abdakibart (AVTX-009) materially increases our exposure to this risk.

Given our limited resources, we have prioritized certain product candidates over others at our management’s discretion. These prioritization decisions necessarily involve significant judgment based on incomplete information. We have also de-prioritized development of certain product candidates. We continually evaluate our capital allocation for each product candidate, and, in the

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Given our limited resources, we have prioritized certain product candidates over others at our management’s discretion. We have also de-prioritized development of certain product candidates. We continually evaluate our capital allocation for each product candidate, and, in the future, may de-prioritize or cancel the development of certain product candidates. IfOur ~~the~~decisions ~~development~~concerning ~~of our product candidates is unsuccessful or, if successful but~~ the ~~products~~allocation ~~do not achieve an adequate level~~ of ~~market~~research, ~~acceptance~~collaboration, wemanagement, ~~may~~and nofinancial ~~longer~~resources ~~have~~toward ~~the~~particular ~~ability~~proprietary ormolecules ~~resources~~in toour ~~further~~library, ~~develop other~~ product candidates. ~~Our~~or ~~resource~~therapeutic ~~allocation~~areas ~~decisions~~ may cause us to fail to capitalize on viable commercial products or profitable market opportunities. Our spending on current and future research and development programs and product candidates for specific indications might not ~~yield any commercially viable products. If we do not~~ accurately ~~evaluate~~reflect ~~the~~their ultimate commercial potential orand ~~target market for a particular product candidate, we~~ may ~~relinquish~~divert ~~valuable~~resources ~~rights~~away tofrom ~~that~~better product candidate through collaboration, licensing or other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization rights to such product candidateopportunities. ~~Our focus and reliance on AVTX-009 increases the risk of this exposure.~~

~~Our~~Similarly, ~~focus~~our ~~and~~decisions ~~reliance~~to ondelay, ~~AVTX-009~~terminate ~~exposes~~or collaborate with third parties in respect of certain product development programs may limit our future strategic flexibility and could cause us to ~~risk~~miss valuable opportunities. If the development of our product candidates is unsuccessful or, if ~~AVTX-009~~successful ~~does~~but the products do not ~~perform~~achieve inan ~~clinical~~adequate ~~trials~~level of market acceptance, we may lack the financial or ~~receive~~operational ~~FDA~~capacity ~~approval~~to ~~and~~pursue alternative programs. Our resource allocation decisions may cause us to fail to capitalize on viable commercial products or profitable market ~~acceptance~~opportunities.

WeOur ~~acquired~~spending ~~AVTX-009~~on incurrent ~~March~~and ~~2024~~future research and ~~have~~development ~~focused~~programs ~~our~~and ~~resources~~product oncandidates ~~AVTX-009~~for atspecific ~~the~~indications ~~expense~~might ofnot ~~allocating~~yield ~~those~~any ~~resources~~commercially toviable ~~other assets~~products. ~~Consequently,~~If ~~our~~we ~~future~~do ~~financial~~not ~~condition~~accurately ~~and~~evaluate ~~results~~the ofcommercial ~~operations~~potential ~~will~~or ~~primarily~~target ~~depend~~market ~~on AVTX-009. Any setback~~ for ora ~~failure~~particular ofproduct ~~AVTX-009~~candidate, ~~during~~we ~~its~~may ~~clinical~~relinquish ~~development~~valuable ~~could~~rights ~~cause material delays in and costs~~ to ~~its~~that ~~further~~product ~~development~~candidate ~~and~~through ~~commercialization.~~collaboration, ~~Any~~licensing ~~such delays~~ or ~~costs~~other ~~could~~royalty ~~have~~arrangements ain ~~material~~cases ~~adverse~~in ~~effect~~which onit ~~our~~would ~~financial~~have ~~condition~~been ~~and~~more ~~results~~advantageous offor ~~operations and could require~~ us to ~~raise~~retain ~~more~~sole ~~capital,~~development ~~turn~~and tocommercialization ~~third-party~~rights ~~collaborators~~ to ~~continue~~such ~~the~~product ~~development of AVTX-009 or cease operations~~candidate. InOur ~~addition,~~focus ~~our~~and ~~focus~~reliance on abdakibart (AVTX-009) ~~may~~increases ~~negatively impact~~ the ~~planned~~risk ~~development~~ of ~~our~~this ~~other product candidates~~exposure.

Drug development is unpredictable and we could encounter toxicity, safety, adverse reactions or other concerns with AVTX-009 as we continue its development. There can be no assurances that we will successfully develop AVTX-009.

Risks Related to Regulatory Approval of Our Product Candidates

The marketing approval processes of the FDA and other regulatory authorities are lengthy, time‑consuming, costly and inherently unpredictable. Our inability to obtain regulatory approval for our product candidates would substantially harm our business and prospects.

The time required to develop and to obtain approval from regulatory authorities to market a new drug or biological product is unique to each product and indication. It typically takes many years in nonclinical and clinical development and depends upon numerous factors including but not limited to the severity of the target disease, the availability of alternative therapies, and evolving regulatory expectations. In addition, regulatory guidance, laws and regulations as well as interactions with regulatory authorities may change the course of development for a product candidate. Further, the type and amount of preclinical and clinical data necessary to gain approval may change during the course of product candidates development and may vary among countries. Securing regulatory approval requires the submission of extensive preclinical and clinical data and supporting information to the various regulatory authorities for each therapeutic indication to establish the product candidate’s safety and efficacy. Securing regulatory approval also requires the submission of information about the drug manufacturing process to, and inspection of manufacturing facilities and often clinical sites by, the relevant regulatory authority. Our current or future product candidates may not be effective, may be only moderately effective or may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude our obtaining marketing approval or prevent or limit commercial use. We have not obtained regulatory approval for any product candidate and it is possible that none of our existing product candidates or any future product candidates will ever obtain regulatory approval. Submission of an NDA or BLA to the FDA (igenerally requires an application fee.~~e.,~~ ~~for~~We ~~new~~may ~~indications,~~also ~~dosing~~be ~~regimen,~~required ~~etc.)~~to ~~requires~~pay ansignificant ~~application~~fees ~~fee~~for regulatory advice, inspections, and post-approval commitments. The filing of an NDA or BLA for any of our product candidates may be delayed due to our lack of financial resources to pay such user fee or otherwise support the regulatory review process.

The FDA may refuse to accept any application for filing, may place a clinical hold on a clinical trial at any stage, or may decide that our data are insufficient for approval and require additional preclinical, clinical or other studies. The U.S. Supreme Court’s decision in July 2024 to overturn established case law giving deference to regulatory agencies’ interpretations of ambiguous statutory language has introduced uncertainty regarding the extent to which FDA’s regulations, policies and decisions may become subject to increasing legal challenges, delays or changes and may result in inconsistent regulatory outcomes or extended review timeline. Our product candidates could fail to receive regulatory approval from the FDA or a other regulatory authorities for many reasons, including:

•Such regulatory authorities may disagree on the design or conduct of our key phase 2 and pivotal phase 3 clinical trials, including the overall study design, primary and secondary endpoints, number of patients, statistical analysis plan, or our proposed product indication. For instance, the FDA may find that the study designs we are utilizing in a planned clinical trial do not ~~support~~constitute an adequate and well‑controlled study supportive of approval. The FDA also might not agree with the proposed quality of life scales and other evaluation tools that we may use in a clinical trial to assess the efficacy of a product candidate;

•Such regulatory authorities may disagree with our development plans, ~~specifically~~including the number of studies and types of studies planned to support approval for each product and indication;

•Our failure to demonstrate to the satisfaction of the FDA or other regulatory authorities that a product candidate is safe and effective for each proposed indication;

•Our clinical trials may fail to meet statistical significance on their primary endpoints, which is required for a positive study;

•We may fail to demonstrate that a product candidate’s benefits outweigh its risks, including due to better than expected performance of placebo arms;

•The FDA or other regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials;

•Data collected from clinical trials of our product candidates may be insufficient to support the submission of a marketing application, other submission or to obtain marketing approval, and the FDA or other regulatory authority may require additional studies to show a product candidate is safe and/or effective;26

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•The FDA or other regulatory authorities may require an advisory committee review and the advisory committee may recommend against approval;

•Our product candidates may fail to qualify for, or maintain, accelerated approval, priority review, breakthrough therapy, fast track or similar regulatory designations;

•Data collected from clinical trials of our product candidates may be insufficient to support the submission of a marketing application or to obtain marketing approval, and the FDA or other regulatory authority may require additional studies to show a product candidate is safe and/or effective;

•We may fail to obtain approval of the manufacturing processes or facilities of third‑party manufacturers with whom we contract for clinical and commercial supplies; or

•There may be changes in ~~precedence~~precedent, regulatory guidance, laws and regulations that render our preclinical and clinical data insufficient for approval.

The FDA or other regulatory authority may require more information, including additional preclinical or clinical studies to support approval, which may delay or prevent approval and our commercialization plans, or we may decide to abandon the development program. This lengthy approval process, as well as the unpredictability of future clinical trial results, may result in our failing to obtain approval to market our product candidates, which would significantly harm our business, results of operations and prospects. In addition, even if we were to obtain approval, regulatory authorities may approve any or all of our product candidates for fewer or more limited indications than we request, may require that contraindications, warnings or precautions be included in the product labeling, including a black‑box warning, may grant approval with a requirement of post‑marketing clinical trials or other post‑market requirements, or post-marketing commitments or may approve a product candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that product candidate or impose restrictions that materially limit market adoption. Any of the foregoing scenarios could materially harm the commercial prospects for our product candidates.

Even if we complete the necessary clinical trials, we cannot predict when or if we will obtain marketing approval to commercialize a product candidate or the approval may be for a narrower indication than we expect or may be conditioned on costly post-approval obligations.

We cannot commercialize a product candidate until the appropriate regulatory authorities have reviewed and approved the product candidate. Even if our product candidates demonstrate safety and efficacy in clinical trials, regulatory agencies might not complete their review processes in a timely manner, or we might not be able to obtain marketing approval. Additional delays may result if the FDA or other regulatory authority, ~~or an FDA Advisory Committee~~ recommends non‑approval or restrictions on approval. In addition, we may experience delays or rejections based upon additional government regulation from future legislation or administrative action, or changes in regulatory agency policy during the period of product development, clinical trials and the review process. Further, regulatory agencies may not approve the labeling claims that are necessary or desirable for the successful commercialization of our product candidates. Regulatory authorities may approve a product candidate for fewer or more limited indications than requested, may impose significant limitations in the form of narrow indications, warnings, including black‑box warnings, precautions or contra‑indications with respect to conditions of use, additional adverse reactions information or may grant approval subject to the performance of post‑marketing clinical trials or other post‑marketing requirements, including a REMS. Our drugs, if approved, may be required to carry warnings comparable to this and other class‑wide warnings. Any of the foregoing scenarios could materially harm the commercial prospects for our product candidates.

Even if our product candidates receive marketing approval, we will still be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expense and diversion of management attention. Additionally, our product candidates, if approved, could be subject to labeling and other restrictions and ~~market withdrawal and~~ we may be subject to administrative sanctions or penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our products.

Even if we obtain marketing approval for a product candidate, we would be subject to ongoing requirements by the FDA and other regulatory authorities governing the manufacturing, quality control, further development, labeling, packaging, storage, distribution, safety surveillance, import, export, advertising, promotion, recordkeeping and annual reporting of safety and other post‑market information. The FDA and other regulatory authorities will continue to closely monitor the safety profile of any product even after approval. If the FDA or other regulatory authorities become aware of new safety information after approval of any of our product candidates, they may withdraw approval, require labeling changes or establishment of a REMS or similar strategy, impose significant restrictions on a product’s indicated uses or marketing, or impose ongoing requirements for potentially costly post‑approval studies or post‑market surveillance. In addition, any marketing approvals that we obtain for our product candidates may be subject to limitations on the approved indicated uses for which the product may be marketed or to the conditions of approval or contain requirements for potentially costly post‑marketing testing and other requirements, including phase 4 clinical trials, imposition of a REMS and surveillance to monitor the safety and efficacy of the product candidate for an extended period of time.

In addition, manufacturers of drug products and their facilities, including contracted facilities, are subject to periodic inspections by the FDA and other regulatory authorities for compliance with cGMP regulations and standards. If we or a regulatory agency discover previously unknown problems with the facility where the product is manufactured, we may be subject to reporting obligations and a regulatory agency may impose restrictions on that product, the manufacturing facility, us, or our suppliers, including requesting recalls or withdrawal of the product from the market or suspension of manufacturing. If we, our product candidates, our contractors, the manufacturing facilities for our product candidates or others working on our behalf fail to comply with applicable regulatory requirements, either before or after marketing approval, a regulatory agency may:

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or withdrawal of the product from the market or suspension of manufacturing or distribution. If we, our product candidates, our contractors, the manufacturing facilities for our product candidates or others working on our behalf fail to comply with applicable regulatory requirements, either before or after marketing approval, a regulatory agency may:

•Issue Warning Letters, Untitled Letters, or FDA Form 483s, all of which document compliance issues identified by the FDA;

•Mandate modifications to promotional materials or labeling, or require us to provide corrective information to healthcare practitioners;

•Require us to enter into a consent decree, which can include imposition of various fines, reimbursements for inspection costs, required due dates for specific actions and penalties for noncompliance;

•Seek an injunction or impose civil or criminal penalties or monetary fines, restitution or disgorgement, as well as imprisonment;

•Suspend or withdraw marketing approval;

•Suspend or terminate any ongoing clinical studies;

•Refuse to approve pending applications or supplements to applications filed by us;

•Debar us from submitting marketing applications, exclude us from participation in federal healthcare programs, require a corporate integrity agreement or deferred prosecution agreements, debar us from government contracts and refuse future orders under existing contracts;

•Suspend or impose restrictions on operations, including restrictions on marketing, distribution or manufacturing of the product, or the imposition of costly new manufacturing requirements or use of alternative suppliers; or

•Seize or detain products, refuse to permit the import or export of products, or request that we initiate a product recall.

The occurrence of any event or penalty described above may inhibit our ability to continue our development programs, commercialize our products and generate revenue and may require us to incur substantial remediation costs.

Advertising and promotion of any product candidate that obtains approval in the United States will be heavily scrutinized by the FDA and other federal agencies, state attorneys general and the public. While the FDA does not restrict physicians from prescribing approved drugs for uses outside of the drugs’ approved labeling, known as off‑label use, pharmaceutical manufacturers are strictly prohibited from promoting and marketing their products for such uses. Violations, including promotion of products for off‑label uses, are subject to enforcement letters, inquiries, investigations, civil and criminal sanctions by the government, corporate integrity agreements, deferred prosecution agreements, debarment from government contracts and refusal of future orders under existing contracts, and exclusion from participation in federal healthcare programs. Additionally, other regulatory authorities will heavily scrutinize advertising and promotion of any product candidate that obtains approval outside of the United States under their respective national laws.

In the United States, engaging in the impermissible promotion of any products for off‑label uses can also subject a company to false claims litigation under federal and state statutes, which can lead to civil and criminal penalties and fines, debarment from government contracts and refusal of future orders under existing contracts, deferred prosecution agreements, and corporate integrity agreements with governmental authorities that materially restrict the manner in which a company promotes or distributes drug products. These false claims statutes include the federal civil False Claims Act, which allows any individual to bring a lawsuit against a pharmaceutical company on behalf of the federal government alleging submission of false or fraudulent claims, or causing to present such false or fraudulent claims, for payment by a federal program such as Medicare or Medicaid. If the government decides to intervene and prevails in the lawsuit, the individual will share in any fines or settlement funds. If the government does not intervene, the individual may proceed on his or her own. Since 2004, these False Claims Act lawsuits against pharmaceutical companies have increased significantly in volume and breadth, leading to several substantial civil and criminal settlements, such as settlements regarding certain sales practices promoting off‑label drug uses involving significant fines. This growth in litigation has increased the risk that a pharmaceutical company will have to defend a false claim action, pay settlement fines or restitution, agree to comply with burdensome reporting and compliance obligations, and be excluded from Medicare, Medicaid and other federal and state healthcare programs. If we do not lawfully promote our approved products, we may become subject to such litigation and, if we do not successfully defend against such actions, those actions may have a material adverse effect on our business, financial condition, results of operations and prospects.

The FDA’s or other regulatory authorities policies may change, and additional government guidance, laws and regulations may be enacted that could prevent, limit or delay marketing approval, and the sale and promotion of our product candidates or increase the costs associated with regulatory compliance. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained, which would adversely affect our business, prospects and ability to achieve or sustain profitability.

WeDisruptions ~~are~~to ~~conducting~~the ~~clinical~~FDA, ~~trials~~the ~~for~~SEC ~~AVTX-009~~and atother ~~sites~~governmental inagencies ~~foreign~~and ~~jurisdictions~~regulatory authorities caused by funding shortages, changes in leadership and policy, or global health concerns could hinder the ~~FDA~~ability ~~might~~to ~~not~~hire ~~accept~~and ~~data~~retain key leadership and other personnel, prevent new products and services from ~~trials~~being ~~conducted~~developed or commercialized in ~~such~~a ~~locations~~timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business and results of operations.

InThe ~~addition~~ability of the FDA to review regulatory filings and our ~~sites~~ability ~~within~~to ~~the~~commence ~~United~~human ~~States,~~clinical wetrials ~~are~~can ~~conducting~~be ~~our~~affected ~~phase~~by 2a ~~trial~~variety of ~~AVTX-009~~factors, ~~for~~including ~~the~~government ~~treatment~~budget ofand HSfunding atlevels, ~~sites~~ability into ~~foreign~~hire ~~jurisdictions.~~and ~~Although~~retain key personnel and contractors, the FDA’s ~~may~~ability to accept ~~data~~and ~~from~~process ~~clinical~~the ~~trials~~payment ~~conducted~~of ~~outside~~user fees and accept the ~~United~~payment ~~States~~of user fees, ~~acceptance~~and ofstatutory, ~~this~~regulatory, ~~data~~leadership isand ~~subject~~policy tochanges. ~~certain~~Average ~~conditions~~review ~~imposed~~times byat the ~~FDA.~~agency ~~Generally,~~have ~~the~~fluctuated ~~patient~~recently ~~population~~and ~~for~~may ~~any~~continue ~~clinical~~to ~~trials~~fluctuate ~~conducted~~in ~~outside~~the offuture. In addition,

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~~the~~government ~~United~~funding ~~States must be representative~~ of the ~~population~~SEC, ~~for whom we intend to seek approval in the United States~~ and ~~the~~other ~~data~~governmental ~~must~~agencies beon ~~applicable~~which toour ~~the~~operations ~~U.S.~~may ~~population~~rely, ~~and~~including ~~medical~~those ~~practice in ways~~ that ~~the~~fund ~~FDA~~research ~~deems~~and ~~clinically~~development ~~meaningful. In addition~~activities, ~~while~~is ~~these clinical trials are~~ subject to the ~~applicable~~political ~~local laws~~process, ~~FDA~~which ~~acceptance~~is ofinherently ~~the~~fluid ~~data~~and ~~will~~unpredictable ~~be dependent upon its determination that the trials also complied with all applicable U.S. laws~~ and ~~regulations.~~may ~~There can~~ be noaffected ~~assurance~~by ~~that~~changes the FDA will accept data from trials conducted outside of the United States. If the FDA does not accept the data from any of our clinical trials that we conduct outside the United States, it would likely result in ~~the~~congressional ~~need for additional trials, which would be costly and time‑consuming and delay~~ or ~~permanently~~executive ~~halt our development of the product candidate~~priorities. ~~In addition, any clinical trials outside of the United States might be subject to delays and risks surrounding geopolitical events.~~

~~Our~~Disruptions ~~failure~~at tothe ~~obtain~~FDA and other agencies or comparable foreign regulatory ~~approval~~authorities, inmay ~~international~~also ~~jurisdictions~~slow ~~would~~the ~~prevent~~time usnecessary ~~from~~for the review and approval of applications for clinical trials or marketing authorization, which would adversely affect our ~~product~~business. ~~candidates~~For ~~outside~~example, action by the ~~United~~Trump ~~States~~Administration to limit federal agency budgets and personnel has led to reductions to the FDA’s budget, employees, and operations, which ~~would~~in ~~limit~~certain ~~our~~circumstances ~~market~~has ~~opportunities~~led to slower response times and ~~adversely~~longer review periods and inspection backlogs. These factors may affect our ability to progress development of our product candidates or obtain regulatory approval for our product candidates. If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business.

InIf ~~order~~a toprolonged ~~market~~government ~~and~~shutdown ~~sell~~occurs, ~~our~~or ~~products~~if inglobal ~~other~~health ~~jurisdictions,~~concerns weor ~~must~~other beemergencies ~~granted~~prevent ~~approval~~the ~~and~~FDA ~~comply~~or ~~with~~other ~~numerous and varying~~ regulatory ~~requirements.~~authorities ~~The approval procedure varies among countries and can involve additional testing. The time required to obtain approval may differ substantially~~ from ~~that~~conducting ~~required~~their toregular ~~obtain~~inspections, ~~FDA~~reviews ~~approval.~~or ~~The~~other regulatory ~~approval~~activities, ~~process outside~~ the ~~United~~ability ~~States generally includes all~~ of the ~~risks associated with obtaining~~ FDA ~~approval.~~or Inother ~~addition, in many countries outside the United States, we must secure product reimbursement approvals before~~ regulatory authorities ~~will~~to ~~approve~~timely ~~the~~review ~~product~~and ~~for~~process ~~sale~~our inregulatory ~~that~~submissions, ~~country.~~conduct ~~Obtaining~~manufacturing ~~foreign~~or ~~regulatory~~clinical ~~approvals~~site ~~and~~inspections, ~~compliance~~or ~~with~~hold ~~foreign~~advisory ~~regulatory~~committee ~~requirements~~meetings could ~~result~~be insignificantly ~~significant delays~~impacted, ~~difficulties~~which ~~and costs for us and~~ could ~~delay~~have ora ~~prevent~~material ~~the~~adverse ~~introduction~~effect ofon our ~~products in certain countries~~business. Further, ~~clinical~~future ~~trials~~government ~~conducted~~shutdowns incould ~~one~~impact ~~country might not be accepted by regulatory authorities in other countries. If we fail to comply with the regulatory requirements in international markets and receive applicable marketing approvals,~~ our ~~target market will be reduced and our~~ ability to ~~realize~~access the ~~full~~public ~~market~~markets ~~potential of our product candidates will be harmed~~ and ~~our business will be adversely affected. We might not~~ obtain ~~foreign~~necessary ~~regulatory~~capital ~~approvals on a timely basis, if at all. Approval by the FDA does not ensure approval by regulatory authorities~~ in ~~other~~order countries or jurisdictions. Approval by one regulatory authority outside the United States does not ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA. Also, regulatory approval for any of our product candidates may be withdrawn. The failure to ~~obtain~~properly ~~approval~~capitalize inand ~~one~~continue ~~jurisdiction may negatively impact~~ our ~~ability~~operations toor delay ~~obtain~~SEC ~~approval~~effectiveness ~~in another jurisdiction. Our failure to obtain approval~~ of ~~any~~registration ofstatements ~~our~~or ~~product~~other ~~candidates by regulatory authorities in another country may significantly diminish the commercial prospects of that product candidate and our business prospects could decline~~filings.

~~Risks~~There ~~Related~~is substantial uncertainty as to how and to what extent the ~~Commercialization~~leadership of ~~Our~~the ~~Product~~FDA ~~Candidates~~and the Trump Administration will continue to seek to modify or revise the requirements and policies of the FDA and other regulatory agencies with jurisdiction over our product candidates and any products for which we obtain approval. Additionally, the administration could issue or promulgate executive orders, regulations, policies or guidance that adversely affect us or create a more challenging or costly environment to pursue the development of new therapeutic candidates or alter regulatory standards in ways that increase development timelines or costs.

We ~~might~~are ~~not~~conducting beclinical ~~successful~~trials infor ~~our~~abdakibart ~~efforts~~(AVTX-009) toat ~~develop~~sites in foreign jurisdictions, and ~~commercialize~~the ~~our~~FDA ~~product~~might ~~candidates~~not accept data from trials conducted in such locations.

~~Our~~In ~~continued~~addition ~~development~~to ofour sites within the United States, we are conducting our ~~product~~phase ~~candidates~~2 ~~will~~trial beof ~~dependent~~abdakibart on(AVTX-009) ~~receiving~~for ~~positive~~the ~~data~~treatment ~~that,~~of HS at sites in ~~our~~foreign ~~judgment~~jurisdictions. Although the FDA may accept data from clinical trials conducted outside the United States, ~~merits~~acceptance ~~advancing~~of ~~such~~this ~~programs~~data is subject to certain conditions imposed by the FDA. ~~Even~~Generally, ifthe patient population for any clinical trials conducted outside of the United States must be representative of the population for whom we ~~are~~intend ~~successful~~to seek approval in ~~continuing~~the United States and the data must be applicable to ~~build~~the U.S. population and ~~expand~~medical ~~our~~practice ~~pipeline~~in ways that the FDA deems clinically meaningful. In addition, while these clinical trials are subject to the ~~product~~applicable ~~candidates~~local ~~that~~laws, weFDA ~~identify~~acceptance ~~might~~of ~~not~~the data will be ~~suitable~~dependent ~~for~~upon ~~clinical~~its ~~development~~determination that the trials also complied with all applicable U.S. laws and ~~commercialization,~~regulations including asbut anot ~~result~~limited ofto ~~being~~including ~~shown~~requirements relating to ~~have~~good ~~harmful~~clinical ~~side~~practice, ~~effects~~trial ormonitoring, ~~other~~and ~~characteristics~~data ~~that~~integrity. ~~indicate~~There can be no assurance that ~~they~~the ~~are~~FDA ~~unlikely~~will toaccept ~~receive~~data ~~marketing~~from ~~approval~~trials ~~and~~conducted ~~achieve~~outside ~~market~~of ~~acceptance.~~the ~~Similarly,~~United ~~even~~States. ifIf the FDA ~~accepts~~does ~~our~~not ~~INDs,~~accept ~~there~~the isdata nofrom ~~guarantee~~any of our clinical trials that we ~~will~~conduct beoutside ~~successful~~the United States, it would likely result in ~~our~~the ~~efforts~~need tofor ~~advance~~additional trials, which would be costly and time‑consuming and delay or permanently halt our development of the product ~~candidates~~candidate. ~~through~~In ~~development~~addition, orany ifclinical ~~approved,~~trials outside of the United States might be subject to ~~commercialization~~delays and risks surrounding geopolitical events or differences in regulatory enforcement practices.

IfWe wemay ~~obtain~~fail ~~approval~~ to ~~commercialize~~achieve our ~~product~~development ~~candidates,~~and ~~the~~regulatory ~~markets~~milestones inon ~~which~~expected wetimelines, ~~will~~or beat ~~selling~~all, ~~are~~which ~~highly~~could ~~competitive~~materially and weadversely ~~might~~affect beour ~~unable~~business, tofinancial ~~compete~~condition, ~~successfully~~results ~~against~~of ~~new~~operations ~~entrants~~and ~~or established companies~~prospects.

~~Competition~~As ina the pharmaceutical industry is intense and is characterized by costly sales and marketing infrastructures as well as extensive research efforts and rapid technological progress. We are aware of several pharmaceutical companies who commercially market products for the same condition or conditions we are targeting for AVTXclinical-~~009.~~stage ~~There~~biopharmaceutical ~~may~~company, ~~also be companies who are actively engaged in~~ the ~~development~~value of ~~therapies~~our orbusiness ~~products~~depends ~~for at least some of these same conditions. Many of these companies have~~ substantially ~~greater~~on ~~research~~our ~~and~~ability ~~development~~to ~~capabilities~~advance asour ~~well~~product ascandidate(s) ~~substantially~~through ~~greater~~preclinical ~~marketing, financial~~ and ~~human resources than we do. In addition, many of these companies have significantly greater experience than us in undertaking pre-~~clinical ~~testing,~~development ~~clinical trials~~ and ~~other~~to obtain regulatory approval ~~procedures.~~in ~~Our~~a ~~competitors~~timely ~~may develop technologies and products that are more effective than those we are researching and developing~~manner. ~~Such~~Our ~~developments~~development ~~could~~programs ~~render our product candidates, if approved, less competitive or possibly obsolete. We~~ are ~~also~~subject ~~competing with respect~~ to ~~marketing~~significant ~~capabilities~~risks and ~~manufacturing efficiency~~uncertainties, ~~areas in which we have no current capabilities~~ and ~~in which~~ we ~~have no experience as a company, even though our executive officers do have pharmaceutical commercialization and launch experience. Mergers, acquisitions, joint ventures and similar events~~ may ~~also~~fail ~~significantly~~to ~~increase~~meet ~~the~~publicly ~~competition~~disclosed weor ~~face.~~internally Inanticipated ~~addition,~~milestones ~~new~~for ~~developments, including the development of other drug technologies and methods of preventing the incidence of disease, occur in the pharmaceutical and medical technology industries at~~ a ~~rapid~~variety ~~pace. These developments may render AVTX-009 or any~~ of ~~our product candidates obsolete or noncompetitive. Compared to us~~reasons, many of ~~our~~which ~~potential~~are ~~competitors~~outside ~~have substantially greater capital resources as well as greater access to strategic partners. As a result~~ of ~~these~~our control.

24We establish development milestones based on a variety of assumptions, including patient enrollment rates, clinical site initiation timelines, manufacturing readiness, data availability, regulatory review periods, and the performance of third-party service providers. These assumptions may prove to be inaccurate. Clinical trials are inherently unpredictable and may be delayed or terminated due to, among other things: slower-than-expected patient enrollment or higher screen failure rates; delays in clinical site activation or staffing shortages at clinical sites; protocol amendments, safety concerns, or unfavorable interim data; variability in trial results or failure to achieve trial endpoints; manufacturing delays, supply chain disruptions, or product quality issues; delays in the release, analysis or validation of clinical data; feedback from regulatory authorities requiring additional data, modifications to trial design, or additional trials; challenges in scaling manufacturing processes or transferring manufacturing to third parties; and reliance on CROs, contract manufacturing organizations (“CMOs”), and other third parties over whom we have limited control. If we are unable to meet anticipated milestones for our clinical development programs, including timing of trial initiation, enrollment, data readouts, regulatory submissions, or regulatory approvals, our business may be materially harmed. Delays in achieving milestones may result in increased development costs, require us to raise additional capital sooner than expected, and divert management’s attention and resources. In addition, failure to meet publicly disclosed milestones or guidance could result in significant volatility in our stock price, loss of

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~~factors~~investor confidence, ~~our~~increased ~~competitors~~litigation risk, and diminished ability to access capital on favorable terms, or at all. We may ~~obtain~~revise, ~~regulatory~~suspend, ~~approval~~or ofterminate ~~their~~one ~~products~~or more ~~rapidly~~of ~~than~~our wedevelopment ~~can~~programs if interim or ~~may~~final ~~obtain~~data ~~patent~~are ~~protection~~negative or ~~other~~inconclusive, ~~intellectual~~if ~~property~~regulatory ~~rights~~authorities ~~that~~impose ~~limit~~additional ~~our~~requirements, ~~ability~~or toif ~~develop~~we ordetermine ~~commercialize~~that ~~our~~the ~~product~~program ~~candidates~~is no longer commercially viable. ~~Our~~Even ~~competitors~~if ~~might~~we ~~also~~ultimately ~~develop~~complete ~~products~~a ~~that~~clinical ~~are~~trial, ~~more~~delays ~~effective~~in data analysis, ~~more~~regulatory ~~useful~~review, ~~and~~or ~~less~~manufacturing ~~costly~~scale-up ~~than~~may prevent us from achieving regulatory approval or commercialization within expected timeframes. Because our ~~products~~operating ~~and~~expenses ~~might~~are ~~also~~primarily bedriven ~~more~~by ~~successful~~development activities, delays in ~~manufacturing~~our clinical programs may materially impact our cash runway and ~~marketing~~require ~~their~~us ~~products.~~to Inseek ~~addition~~additional financing, ~~our~~which ~~competitors~~may ~~might~~not be ~~more~~available ~~effective~~on inacceptable ~~commercializing~~terms ~~their~~or ~~products~~at ~~and~~all. asAny aof ~~result,~~these events could materially and adversely affect our business, ~~and~~financial ~~prospects~~condition, ~~might~~results beof ~~materially~~operations ~~harmed~~and prospects.

IfOur wefailure to obtain regulatory approval toin ~~commercialize~~international jurisdictions would prevent us from marketing our product candidates outside of the United States, awhich ~~variety~~would oflimit ~~risks~~our ~~associated~~market ~~with~~opportunities ~~international~~and ~~operations could materially~~ adversely affect our business.

IfIn ~~any~~order ofto market and sell our products in other jurisdictions, we must be granted approval and comply with numerous and varying regulatory requirements. The approval procedure varies among countries and can involve additional product ~~candidates~~candidate ~~are~~testing ~~approved~~and ~~for~~additional ~~commercialization~~administrative review periods. The time required to obtain approval may differ substantially from that required to obtain FDA approval. The regulatory approval process outside the United States generally includes all of the risks associated with obtaining FDA approval as well as other risks. In addition, in many countries outside the United States, we ~~may~~must ~~enter~~secure ~~into~~product ~~agreements~~reimbursement approvals before regulatory authorities will approve the product for sale in that country. Obtaining foreign regulatory approvals and compliance with ~~third~~foreign ~~parties~~regulatory requirements could result in significant delays, difficulties and costs for us and could delay or prevent the introduction of our products in certain countries. Further, clinical trials conducted in one country might not be accepted by regulatory authorities in other countries. If we fail to comply with the regulatory requirements in international markets and receive applicable marketing approvals, our target market ~~them~~will be reduced and our ability to realize the full market potential of our product candidates will be harmed and our business will be adversely affected. We might not obtain foreign regulatory approvals on a ~~worldwide~~timely basis, if at all. Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions. Approval by one regulatory authority outside the United States does not ensure approval by regulatory authorities in ~~more~~other ~~limited~~countries ~~geographical~~or ~~regions~~jurisdictions or by the FDA. WeAlso, ~~expect~~regulatory ~~that~~approval wefor ~~would~~any of our product candidates may be ~~subject~~withdrawn or conditioned on post-approval obligations. The failure to ~~additional~~obtain ~~risks~~approval ~~related~~in one jurisdiction may negatively impact our ability to ~~entering~~obtain ~~into~~approval ~~international~~in another jurisdiction. Our failure to obtain approval of any of our product candidates by regulatory authorities in another country may significantly diminish the commercial prospects of that product candidate and our business ~~relationships,~~prospects ~~including:~~could decline.

~~•Different~~Our ~~regulatory~~future ~~requirements~~growth ~~for~~may ~~approval~~depend, ~~advertising~~in ~~and~~part, ~~promotion~~on ofour ~~drugs~~ability into penetrate foreign ~~countries;~~markets, where we would be subject to additional regulatory burdens and other risks and uncertainties that could materially adversely affect our business and profitability.

~~•Challenges~~We ~~enforcing~~are not permitted to market or promote any of our ~~contractual~~current ~~and~~or ~~intellectual~~future ~~property~~product ~~rights~~candidates before we receive regulatory approval from the applicable regulatory authority in that market, ~~especially~~and we may never receive such regulatory approval for any of our current or future product candidates. To obtain separate regulatory approval in ~~those~~many ~~foreign~~other countries ~~that~~we domust ~~not~~comply ~~respect~~with numerous and ~~protect~~varying ~~intellectual~~regulatory ~~property~~requirements ~~rights~~of tosuch ~~the~~countries ~~same~~regarding ~~extent~~safety asand ~~the~~efficacy ~~United~~and ~~States;~~governing, among other things, clinical trials and commercial sales, pricing and distribution of our current or future product candidates, and we cannot predict success in these jurisdictions. If we obtain approval of our current or future product candidates and ultimately commercialize our current or future product candidates in foreign markets, we would be subject to additional risks and uncertainties, including:

•Differing regulatory requirements in foreign countries, such that obtaining regulatory approvals outside of the U.S. may take longer and be more costly than obtaining approval in the U.S.;

•Challenges enforcing our contractual and intellectual property rights, especially in those foreign countries that do not respect and protect intellectual property rights to the same extent as the U.S.;

•Our customers’ ability to obtain reimbursement for our current or future product candidates in foreign markets;

•The burden of complying with complex and changing foreign regulatory, tax, accounting and legal requirements;

•Foreign reimbursement, pricing and insurance regimes;

•Unexpected changes in tariffs, trade barriers and regulatory requirements;

•Different medical practices and customs in foreign countries affecting acceptance in the marketplace;

•Import or export licensing requirements;

•Longer accounts receivable collection times;

•Longer lead times for shipping;

•Language barriers for technical training;

•Reduced protection of intellectual property rights in some foreign countries;

•The existence of additional potentially relevant third-party intellectual property rights;

•Economic weakness, including inflation, or political instability in particular foreign economies and markets;

•Compliance with tax, employment, immigration and labor laws for employees living or traveling abroad;

•Foreign ~~currency fluctuations~~taxes, ~~which~~including ~~could~~withholding ~~result~~of inpayroll ~~increased operating expenses and reduced revenues, and other obligations incident to doing business in another country~~taxes;

•Foreign ~~taxes~~currency fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to doing business in another country;

•Difficulties staffing and managing foreign operations;

~~•Workforce uncertainty in countries where labor unrest is more common than in the United States;~~30

~~•Potential~~Table ~~liability~~of ~~under the FCPA or comparable foreign regulations;~~Contents

•Workforce uncertainty in countries where labor unrest is more common than in the U.S.;

•Potential liability under the Foreign Corrupt Practices Act of 1977 (the “FCPA”) or comparable foreign regulations;

•The interpretation of contractual provisions governed by foreign laws in the event of a contract dispute;

•Production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and

•Business interruptions resulting from ~~geopolitical~~geo-political actions, including war and terrorism~~, natural disasters, including earthquakes, typhoons, floods and fires, or pandemics~~.

~~These~~Foreign ~~and~~sales ~~other~~of ~~risks~~our ~~associated~~current ~~with~~or ~~any~~ future ~~international~~product ~~operations~~candidates could ~~materially~~also be adversely ~~affect~~affected ~~our~~by ~~ability~~the toimposition ~~attain~~of governmental controls, political and economic instability, trade restrictions and changes in tariffs (including tariffs that have been or ~~maintain~~may ~~profitable~~in ~~operations~~the future be imposed by the United States or other countries or by sanctions regimes that limit cross-border transactions.

~~Even~~We ifare wesubject ~~commercialize~~to ~~any~~certain ofU.S. ~~our~~and ~~product~~foreign ~~candidates~~anti-corruption, ~~these~~anti-money ~~products~~laundering, ~~may~~export ~~become~~control, ~~subject~~sanctions, toand ~~unfavorable~~other ~~third‑party~~trade ~~coverage~~laws and ~~reimbursement policies, healthcare reform initiatives, or pricing~~ regulations,. ~~any~~We ofcan ~~which~~face ~~could~~serious ~~negatively~~consequences ~~impact~~for ~~our business~~violations.

~~Our~~Among ~~ability~~other tomatters, ~~commercialize~~U.S. ~~any~~and ~~product~~foreign ~~candidates~~anti-corruption, ~~successfully~~including ~~will~~the ~~depend~~FCPA, inanti-money ~~part~~laundering, onexport ~~the~~control, ~~extent~~sanctions, toand ~~which~~other ~~coverage~~trade laws and ~~adequate~~regulations, ~~reimbursement~~which ~~for~~we ~~these~~collectively ~~product~~refer ~~candidates~~to ~~will~~as be“Trade ~~available~~Laws,” ~~from~~prohibit ~~government~~companies ~~authorities,~~and ~~private~~their ~~health~~employees, ~~insurers~~agents, ~~health~~clinical ~~maintenance~~research organizations, legal counsel, accountants, consultants, contractors, and other ~~entities.~~partners ~~These~~from ~~third‑party~~authorizing, ~~payors~~promising, ~~determine~~offering, ~~which~~providing, ~~medications~~soliciting, ~~they~~or ~~will~~receiving ~~cover~~directly ~~and~~or ~~establish~~indirectly, ~~reimbursement~~corrupt ~~levels,~~or ~~and~~improper ~~increasingly~~payments ~~attempt~~or toanything ~~control~~else ~~costs~~of byvalue ~~limiting~~to ~~coverage~~or ~~and~~from recipients in the ~~amount~~public or private sector (including government officials and employees of ~~reimbursement~~government-owned ~~for~~or ~~particular~~government-controlled ~~medications~~entities). ~~Several~~Anti-corruption ~~third‑party~~and ~~payors~~anti-bribery ~~require~~laws ~~drug~~have ~~companies~~been toenforced ~~provide~~aggressively ~~them~~in ~~with~~recent ~~predetermined~~years ~~discounts~~and ~~from~~are ~~list~~interpreted ~~prices~~broadly. In addition, U.S. export control and ~~use~~sanctions ~~preferred~~laws ~~drug~~(including ~~lists~~those toadministered ~~leverage~~by ~~greater~~the ~~discounts~~U.S. inDepartment ~~competitive~~of ~~classes~~the Treasury’s Office of Foreign Assets Control and the U.S. InDepartment ~~addition~~of Commerce) can restrict, ~~federal~~prohibit ~~programs~~or impose ~~penalties~~licensing requirements on ~~drug~~certain ~~manufacturers~~transactions inand ~~certain~~dealings ~~instances~~with designated countries, entities and individuals. Violations of trade laws can result in substantial criminal fines and civil penalties, imprisonment, the ~~form~~loss of ~~mandatory~~trade ~~additional~~privileges, ~~rebates~~debarment, ~~and/or~~tax ~~discounts~~reassessments, ~~which~~breach ~~can~~of becontract ~~substantial~~and fraud litigation, reputational harm, and ~~could~~other ~~impact~~consequences. ~~our~~As ~~ability~~we toincrease ~~raise~~our ~~commercial~~activities ~~prices~~outside the U.S., Wewhich ~~cannot~~may beinclude ~~sure~~increased ~~that~~interactions ~~coverage~~with officials and ~~reimbursement~~employees ~~will~~of begovernment ~~available~~agencies ~~for~~or ~~any~~state-owned ~~product~~or ~~candidate~~-affiliated ~~that~~entities, weour ~~commercialize~~risks ~~and,~~under ifthese ~~coverage~~laws ismay ~~available~~increase. Noncompliance with these laws could subject us to investigations, ~~what~~sanctions, ~~the~~settlements, ~~level~~prosecution, other enforcement actions, disgorgement of ~~reimbursement~~profits, ~~will~~significant ~~be.~~fines, ~~Coverage~~damages, other civil and ~~reimbursement~~criminal ~~may~~penalties ~~impact~~or ~~the~~injunctions, ~~demand~~adverse ~~for~~media coverage, orand other consequences. We may be held liable for the ~~price~~actions of our third-party intermediaries, ~~any~~including ~~product~~CROs, ~~candidate~~investigators, ~~for~~consultants, ~~which~~contractors and partners, even if we ~~obtain~~did ~~marketing~~not ~~approval~~authorize or have actual knowledge of the improper conduct. Any Ifinvestigations, ~~coverage~~actions or sanctions could harm our business, results of operations, and ~~reimbursement~~financial ~~are~~condition. ~~not~~We ~~available~~have direct or ~~available~~indirect ~~only~~interactions towith ~~limited~~officials ~~levels,~~and weemployees ~~might~~of ~~not~~government ~~successfully~~agencies ~~commercialize~~or ~~any~~government-affiliated ~~product~~hospitals, ~~candidate~~universities, ~~for~~and ~~which~~other weorganizations ~~obtain~~in ~~marketing~~connection ~~approval~~with our clinical development activities.

~~There~~Governments ~~may~~outside bethe ~~significant~~United ~~delays~~States intend ~~obtaining~~to ~~coverage~~impose ~~and~~strict ~~reimbursement~~price ~~for newly approved drugs~~controls, ~~and~~which ~~coverage~~ may beadversely ~~more~~affect limited than the purposes for which the drug is approved by the FDA or other regulatory authorities. Moreover, eligibility for coverage and reimbursement does not imply that a drug will be paid for in all cases or at a rate that covers our ~~costs~~revenues, ~~including research, development, manufacture, sale and distribution. Interim reimbursement levels for new drugs,~~ if ~~applicable, may also not be sufficient to cover our costs and may only be temporary~~any. Reimbursement rates for a drug may vary according to the clinical setting in which it is used and may be based on reimbursement levels already set for lower cost drugs and may be incorporated into existing payments for other services. Prices paid for a drug also vary depending on the class of trade. Prices charged to government customers are subject to price controls and private entities obtain discounts through group purchasing organizations. Net prices for drugs may be further

25In some countries, the pricing of prescription pharmaceuticals is subject to governmental control. In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a product. To obtain coverage and reimbursement or pricing approval in some countries, we may be required to conduct a clinical trial that compares the cost-effectiveness of our product candidate to other available therapies. In addition, many countries outside the U.S. have limited government support programs that provide for reimbursement of products such as our product candidates, with an emphasis on private payors for access to commercial products. If reimbursement of our product candidates is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our business could be materially harmed.

Current and future healthcare legislative reform measures may have a material adverse effect on our business and results of operations.

In the U.S. and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and affect our ability to profitably sell any product candidates for which we obtain marketing approval. The pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by legislative initiatives. Current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that we receive for any FDA approved product. If reimbursement of our products is unavailable or limited in scope, our business could be materially harmed. For more information, please see “Business—Government Regulation and Product Approval—Healthcare Reform and Other Regulatory Changes.”

Third party payors, whether domestic or foreign, or governmental or commercial, are developing increasingly sophisticated methods of controlling healthcare costs. In the U.S. and certain other jurisdictions, there have been, and are expected to continue to be, a number of legislative and regulatory changes to the healthcare system that could impact our ability to sell our products profitably. In addition, significant uncertainty exists in the U.S. and certain other jurisdictions regarding the provision and financing of healthcare because the elected administrations in such countries have publicly declared their intention to review and potentially significantly modify the current legal and regulatory framework for the healthcare system including through drug pricing and reimbursement reforms.

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~~reduced~~We bycannot ~~mandatory~~predict ~~discounts~~the orinitiatives ~~rebates required by government healthcare programs and demanded by private payors, and by any future relaxation of laws~~ that ~~presently restrict imports of drugs from countries where they~~ may be ~~sold~~adopted ~~at lower prices than~~ in the ~~United States~~future. ~~Our~~The ~~inability~~continuing toefforts ~~promptly~~of ~~obtain~~the ~~coverage~~government, ~~and~~insurance ~~profitable~~companies, ~~reimbursement~~managed ~~rates~~care ~~from~~organizations ~~both government‑funded~~ and ~~private~~other ~~payors~~payers ~~for~~of ~~any~~healthcare ~~approved~~services ~~products that we develop could have a material adverse effect on our operating results, our ability~~ to ~~raise~~contain ~~capital~~or ~~needed~~reduce tocosts ~~commercialize~~of ~~product~~healthcare ~~candidates~~may ~~and~~adversely ~~our overall financial condition.~~affect:

~~Moreover,~~•The ~~the~~demand ~~regulations that govern pricing, coverage and reimbursement~~ for ~~new~~any ~~drug~~of products abroad vary widely from country to country. Current and future U.S. or foreign legislation may significantly change the pricing, coverage and reimbursement in ways that could involve additional costs and cause delays in obtaining approvals. Adverse pricing limitations may hinder our ~~ability to recoup our investment in one or more~~ product candidates, ~~even~~ if ~~our product candidates obtain marketing approval.~~approved;

•The ability to set a price that we believe is fair for any of our product candidates, if approved;

•Our ability to generate revenues and achieve or maintain profitability;

•The level of taxes that we are required to pay; and

•The availability of capital.

For example, recent CMS proposals from November 2025 and December 2025, including the GLOBE, GUARD, and GENEROUS, could materially impact the Company’s revenue. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors, which may adversely affect our future profitability and could materially reduce net realized prices.

The FDA announced in July 2025 a fast-track priority review voucher for drugs whose manufacturers commit to setting a price in line with drug pricing offered in economically similarly situated countries around the world. For example, the FDA has announced a “national priority” voucher pilot program intended to accelerate development and review of certain drugs and biologics aligned with U.S. national health priorities. The effects of these proposals and how these proposals will be implemented are not yet known and could depend on future guidance and agency discretion.

Further, the Inflation Reduction Act of 2022 (the “IRA”) was recently revised to broaden the exemption from the drug price negotiation program for drugs with orphan designations. Previously under the IRA, orphan drugs were exempted from the Medicare drug price negotiation program; but this exemption was restricted to drugs with only one orphan designation and for which the only approved indication is for that rare disease or condition. If a product were to receive multiple orphan designations or had multiple approved indications, it would not have qualified for the orphan drug exemption. Under the One Big Beautiful Bill Act of 2025, this restriction was eliminated; and effective for the 2028 initial price applicability year, all orphan drugs, regardless of the number of orphan designations or indications, are exempt from the Medicare drug price negotiation program, provided that all approved indications are for rare diseases.

Any of the foregoing measures (and related implementing guidance, rulemaking, enforcement activity or private litigation) could materially reduce pricing flexibility, increase rebates or discounts, narrow coverage, delay patient access, and adversely affect our ability to commercialize abdakibart (AVTX-009) or any future product candidates, if approved.

If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could have a material adverse effect on the success of our business.

We are subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. Our operations involve the use of hazardous and flammable materials, including chemicals and biological and radioactive materials. Our operations also produce hazardous waste products. We generally contract with third parties for the disposal of these materials and wastes. We cannot eliminate the risk of contamination or injury from these materials. In the event of contamination or injury resulting from our use of hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties.

Although we maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage against potential liabilities. We do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us in connection with our storage or disposal of biological, hazardous or radioactive materials. In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations. Current or future environmental laws and regulations may impair our research, development and production efforts, which could harm our business, prospects, financial condition or results of operations.

Our employees, principal investigators, CROs and consultants may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements and insider trading laws.

We are exposed to the risk that our employees, principal investigators, CROs and consultants may engage in fraudulent conduct or other illegal activity. Misconduct by these parties could include intentional, reckless and/or negligent conduct or disclosure of unauthorized activities to us that violate the regulations of the FDA and other regulatory authorities, including those laws requiring the reporting of true, complete and accurate information to such authorities; healthcare fraud and abuse laws and regulations in the U.S. and abroad; or laws that require the reporting of financial information or data accurately or compliance with securities laws, including laws relating to insider trading and selective disclosure. In particular, sales, marketing, patient support and business arrangements in

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the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements. Other activities subject to these laws include the improper use of information obtained in the course of clinical trials or creating fraudulent data in our preclinical studies or clinical trials, which could result in regulatory sanctions and cause serious harm to our reputation. We have adopted a code of conduct applicable to all of our employees, but it is not always possible to identify and deter misconduct by employees and other third parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations. Additionally, we are subject to the risk that a person could allege such fraud or other misconduct, even if none occurred. If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of civil, criminal and administrative penalties, damages, monetary fines, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, and curtailment of our operations, any of which could adversely affect our ability to operate our business and our results of operations.

Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs. Because of the breadth of these laws and the narrowness of the statutory exceptions and safe harbors available, it is possible that some of our business activities could be subject to challenge under one or more of such laws. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant criminal, civil and administrative sanctions including monetary penalties, damages, fines, disgorgement, individual imprisonment, reputational harm, exclusion from participation in government funded healthcare programs, such as Medicare and Medicaid, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations.

The risk of our being found in violation of these laws is increased by the fact that many of them have not been fully interpreted by the regulatory authorities or the courts, and their provisions are open to a variety of interpretations. Any action against us for violation of these laws, even if we successfully defend against it, could cause us to incur significant legal expenses and divert our management’s attention from the operation of our business. The shifting compliance environment and the need to build and maintain robust and expandable systems to comply with multiple jurisdictions with different compliance and/or reporting requirements increases the possibility that a healthcare company may run afoul of one or more of the requirements.

Ongoing changes to healthcare laws and regulations may increase the difficulty of and costs associated with commercializing our products and may affect the prices we are paid for those products and the demand for such products.

Coverage and reimbursement may be limited or unavailable in certain market segments for our product candidates, if approved, which could make it difficult for us to sell any product candidates or therapies profitably. The success of our product candidates, if approved, depends on the availability of adequate coverage and reimbursement from third party payors, including government agencies, private health insurers and health maintenance organizations. There is significant uncertainty related to the insurance coverage and reimbursement of any newly approved product, novel biologic therapies and drugs approved based on limited or surrogate endpoints or requiring specialized administration. All the therapeutic indications approved by the relevant authorities may not be covered or reimbursed. In addition, we cannot be sure that coverage and reimbursement will be available for, or accurately estimate the potential revenue from, our product candidates because they are new therapies in evolving reimbursement environments, and payors may adopt new or more restrictive coverage policies following approval. For more information “Business—Government Regulation and Product Approval—Coverage and Reimbursement.”

In the U.S. and some other jurisdictions, patients generally rely on third party payors to reimburse all or part of the costs associated with their treatment. Adequate coverage and reimbursement from governmental healthcare programs, such as Medicare and Medicaid in the U.S., and commercial payors are critical to new product uptake and commercial success.

Government authorities and other third party payors, such as private health insurers and health maintenance organizations, decide which drugs and treatments they will cover and the amount of reimbursement. In the U.S., the principal decisions about reimbursement for new medicines are typically made by the CMS, an agency within the U.S. Department of Health and Human Services. CMS decides whether and to what extent a new medicine will be covered and reimbursed under Medicare, and private payors often follow CMS’s coverage decisions. Other jurisdictions have agencies, such as the National Institute for Health and Care Excellence in the U.K., that evaluate the use and cost-effectiveness of therapies, which impact the utilization and price of the medicine in such jurisdiction and may impose additional evidence development requirements.

In the U.S., no uniform policy of coverage and reimbursement for products exists among third party payors. As a result, obtaining coverage and reimbursement approval of a product from a third party payor is a time-consuming and costly process that could require

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us to provide supporting scientific, clinical and cost-effectiveness data for the use of our products to each potential payor, with no assurance that coverage and adequate reimbursement will be obtained from all or any of them. Even if we obtain coverage for a given product, the resulting reimbursement payment rates might be insufficient or may require co-insurance or co-payments that patients find unacceptably high, which may prevent us from achieving or sustaining profitability. Additionally, third party payors may not cover, or provide adequate reimbursement for, long-term follow-up evaluations required following the use of our genome editing products.

In addition, each country in which we seek approval to market our product candidates has unique laws and market practices regulating coverage and reimbursement for human therapeutics. Market acceptance and sales of our products in each country will depend on our ability to meet each of these jurisdiction’s requirements for coverage and reimbursement. Further, changes to the country’s existing requirements may also affect our ability to commercialize our products in the future, or achieve profitability from their sale. In many jurisdictions, payors may require head-to-head comparative effectiveness data, real-world evidence, or additional post-approval studies as a condition of coverage or favorable reimbursement.

We may be subject to certain regulations, including federal and state healthcare fraud and abuse laws, physician payment transparency laws, anti-bribery and anti-corruption laws and health information privacy and security laws. Any actual or perceived failure to comply with these regulations could have a material adverse effect on our business and financial condition.

If we obtain FDA approval for any of our product candidates and begin commercializing those products in the United States, our operations may be subject to various federal and state healthcare laws, including, without limitation, fraud and abuse laws, false claims laws, data privacy and security laws, as well as transparency laws regarding payments or other items of value provided to healthcare providers and patients. These laws may impact, among other things, our proposed sales, marketing and education programs. Additionally, we may be subject to state and foreign equivalents of such healthcare laws and regulations, some of which may be broader in scope and may apply regardless of the payor, as well as patient privacy regulation by both the federal government and the states in which we conduct our business. Because of the breadth of these laws and the narrowness of the statutory exceptions and safe harbors available, it is possible that some of our business activities could be subject to challenge and may not comply under one or more of such laws, regulations, and guidance. Law enforcement authorities are increasingly focused on enforcing fraud and abuse laws, and it is possible that some of our practices may be challenged under these laws. Efforts to ensure that our current and future business arrangements with third parties, and our business generally, will comply with applicable healthcare laws and regulations will involve substantial costs. If our operations, including our arrangements with physicians and other healthcare providers are found to be in violation of any of such laws or any other governmental regulations that apply to us, we may be subject to penalties, including, without limitation, administrative, civil and criminal penalties, damages, fines, disgorgement, contractual damages, reputational harm, diminished profits and future earnings, the curtailment or restructuring of our operations, exclusion from participation in federal and state healthcare programs (such as Medicare and Medicaid), and imprisonment, as well as additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance with these laws, any of which could adversely affect our ability to operate our business and our financial results. For more information, please see “Business—Government Regulation and Product Approval—Other Healthcare Laws and Compliance Requirements.”

The scope and enforcement of these laws is uncertain and subject to rapid change in the current environment of healthcare reform, especially in light of the lack of applicable precedent and regulations. Federal and state enforcement has led to a number of investigations, prosecutions, convictions and settlements in the healthcare industry. Ensuring that our internal operations and future business arrangements with third parties comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes, regulations, agency guidance or case law involving applicable fraud and abuse or other healthcare laws and regulations.

The provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order or use of medicinal products is prohibited in the European Union. The provision of benefits or advantages to physicians is also governed by the national anti-bribery laws of European Union Member States, such as the UK Bribery Act 2010. Infringement of these laws could result in substantial fines and individual imprisonment.

Payments made to physicians in certain European Union Member States must be publicly disclosed. Moreover, agreements with physicians often must be the subject of prior notification and approval by the physician’s employer, his or her competent professional organization and/or the regulatory authorities of the individual European Union Member States. These requirements are provided in the national laws, industry codes or professional codes of conduct, applicable in the European Union Member States. Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or individual imprisonment.

Risks Related to the Commercialization of Our Product Candidates

We might not be successful in our efforts to develop and commercialize our product candidates.

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Our continued development of our product candidates will be dependent on receiving positive data that, in our judgment, merits advancing such programs. Even if we are successful in continuing to build and expand our pipeline, the product candidates that we identify might not be suitable for clinical development and commercialization, including as a result of being shown to have harmful side effects or other characteristics that indicate that they are unlikely to receive marketing approval and achieve market acceptance. Similarly, even if the FDA accepts our INDs, there is no guarantee that we will be successful in our efforts to advance our product candidates through development, or if approved, to commercialization.

If, in the future, we are unable to establish sales, marketing and distribution capabilities or enter into licensing or collaboration agreements for these purposes, we might not be successful in commercializing our product candidates.

There are risks involved with both establishing our own sales and marketing and patient support capabilities and entering into arrangements with third parties to perform these services. For example, recruiting and training a sales force is expensive and time consuming and could delay any drug launch. If the commercial launch of a product candidate for which we recruit a sales force and establish marketing capabilities is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialization expenses. This may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketing personnel.

For product candidates for which we decide to perform sales, marketing and distribution functions ourselves, we could face a number of additional risks, including:

•Our inability to recruit and retain adequate numbers of effective sales and marketing personnel;

•Inability of marketing personnel to develop effective marketing materials;

•The inability of sales personnel to obtain access to physicians or educate adequate numbers of physicians on the clinical benefits of our products to achieve market acceptance;

•The lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines;

•The costs associated with training sales personnel on legal compliance matters and monitoring their actions;

•Liability for sales personnel failing to comply with applicable legal requirements; and

•Unforeseen costs and expenses associated with creating an independent sales and marketing organization.

Where and when appropriate, we may elect to utilize contract sales forces or strategic partners to assist in the commercialization of our product candidates. If we enter into arrangements with third parties to perform sales, marketing and distribution services for our products, the resulting revenues or the profitability from these revenues to us are likely to be lower than if we had sold, marketed and distributed our products ourselves. In addition, we might not be successful in entering into arrangements with third parties to sell, market and distribute our product candidates or may be unable to do so on terms that are favorable to us. We likely will have little control over such third parties, and any of these third parties may fail to devote the necessary resources and attention to sell, market and distribute our products effectively. Such third parties may also not comply with the applicable regulatory requirements, which could potentially expose us to regulatory and legal enforcement actions and reputational harm.

Even if we receive marketing approval for abdakibart (AVTX-009) or future product candidates, our current or future product candidates may not achieve broad market acceptance, which would limit the revenue that we generate from their sales and could prevent us from achieving or sustaining profitability.

The commercial success of our current or future product candidates, if approved by the FDA or other applicable regulatory authorities, will depend upon the awareness and acceptance of our current or future product candidates among the medical community, including physicians, patients and healthcare payors. Market acceptance of our current or future product candidates, if approved, will depend on a number of factors, including, among others:

•The efficacy of our current or future product candidates as demonstrated in clinical trials, and, if required by any applicable regulatory authority in connection with the approval for the applicable indications, to provide patients with incremental health benefits, as compared with other available medicines;

•Limitations or warnings contained in the labeling approved for our current or future product candidates by the FDA or other applicable regulatory authorities; Including but not limited to any boxed warning, contraindications, limitations of use, or requirements for a REMS;

•The clinical indications for which our current or future product candidates are approved including the breadth of the indicated patient population;

•Availability of alternative treatments already approved or expected to be commercially launched in the near future;

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•The potential and perceived advantages of our current or future product candidates over current treatment options or alternative treatments, including future alternative treatments;

•The willingness of the target patient population to try new therapies or treatment methods and of physicians to prescribe these therapies or methods;

•The need to dose such product candidates in combination with other therapeutic agents, and related costs;

•The strength of marketing and distribution support and timing of market introduction of competitive products;

•Publicity concerning our products or competing products and treatments;

•Pricing and cost effectiveness;

•The effectiveness of our sales and marketing strategies;

•Our ability to increase awareness of our current or future product candidates;

•Our ability to obtain sufficient third-party coverage or reimbursement; including the adequacy of reimbursement for administration, monitoring and other ancillary services; or

•The willingness of patients to pay out-of-pocket in the absence of third-party coverage.

If our current or future product candidates are approved but do not achieve an adequate level of acceptance by patients, physicians and payors, we may not generate sufficient revenue from our current or future product candidates to become or remain profitable. Before granting reimbursement approval, healthcare payors may require us to demonstrate that our current or future product candidates, in addition to treating these target indications, also provide incremental health benefits to patients including comparative effectiveness versus existing therapies and real-world evidence of value. Our efforts to educate the medical community, patient organizations and third-party payors about the benefits of our current or future product candidates may require significant resources and may never be successful.

Product liability lawsuits against us could cause us to incur substantial liabilities and limit commercialization of any product candidates that we may develop.

We face an inherent risk of product liability exposure related to the testing of our product candidates in human clinical trials and related to the commercial sale of any approved products. Product liability claims may be brought against us by subjects enrolled in our clinical trials, patients, healthcare providers or others using, administering or selling our product candidates or any approved product. For example, we may be sued if any product candidate we test or, if approved, sell allegedly causes injury or is found to be otherwise unsuitable during product testing, manufacturing, marketing or sale. Any such product liability claims may include allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product, negligence, strict liability and a breach of warranties. Claims could also be asserted under state consumer protection acts. If we cannot successfully defend ourselves against claims that our product candidates or products caused injuries, we could incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:

•Decreased demand for any product candidates or approved products;

•Termination of clinical trial sites or entire trial programs;

•Injury to our reputation and significant negative media attention;

•Withdrawal of clinical trial participants;

•Significant costs to defend the related litigation;

•Substantial monetary awards to trial subjects or patients;

•Loss of revenue;

•Product recalls, withdrawals or labeling, marketing or promotional restrictions;

•Diversion of management and scientific resources from our business operations;

•The inability to commercialize any product candidates that we may develop; and

•A decline in our stock price.

We currently hold product and clinical trial liability insurance coverage, but it might not adequately cover all liabilities that we incur. We might not be able to maintain clinical trial insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise. WeIf ~~also~~we ~~maintain~~obtain ~~insurance~~marketing ~~coverage~~approval for any of our ~~commercially~~product ~~available~~candidates and commercialize any products, ~~which~~we ~~might~~may ~~not~~seek ~~adequately~~to ~~cover~~obtain ~~all~~additional ~~liabilities~~insurance ~~that~~coverage wefor such products; however, such coverage may ~~incur~~be unavailable on acceptable terms, or at all, or may not provide adequate coverage against potential liabilities. We might not be able to maintain insurance coverage for our product candidates and our approved products at a reasonable cost or in an amount adequate to satisfy any liability that may arise. Large judgments have been awarded in class action lawsuits based on drugs that had unanticipated side effects. A product liability claim or series of claims brought against us, whether or not successful, but particularly if judgments exceed our insurance coverage, could decrease our cash and adversely affect our reputation and business.

We do not currently have a sales or marketing infrastructure. To develop our internal sales, distribution and marketing capabilities for product candidates, we will have to invest significant financial and management resources, some of which will be committed prior to any confirmation that any product candidates will be approved. For product candidates for which we decide to perform sales, marketing and distribution functions ourselves, we could face a number of additional risks, including:

•Our inability to recruit and retain adequate numbers of effective sales and marketing personnel;

•Inability of marketing personnel to develop effective marketing materials;

•The inability of sales personnel to obtain access to physicians or educate adequate numbers of physicians on the clinical benefits of our products to achieve market acceptance;

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•The lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines;

•The costs associated with training sales personnel on legal compliance matters and monitoring their actions;

•Liability for sales personnel failing to comply with applicable legal requirements; and

•Unforeseen costs and expenses associated with creating an independent sales and marketing organization.

Risks Related to Our Dependence on Third Parties

We rely on third parties to conduct and monitor our clinical trials. The failure of these third parties to successfully carry out their contractual duties or meet expected deadlines could hinder our ability to commercialize or obtain marketing approval for our product candidates in a timely manner or at all.

We rely upon third‑party CROs to monitor and manage data for our clinical programs. We rely on these parties for execution of our clinical trials and, while we have agreements governing their activities, we have limited influence over their actual performance and control only certain aspects of their activities. Nevertheless, we are responsible for ensuring that each of our studies is conducted in accordance with the applicable protocol, legal, regulatory and scientific standards, and our reliance on the CROs does not relieve us of our regulatory responsibilities. We, our clinical trial sites, and our CROs are required to comply with GCP requirements, which are regulations and guidelines enforced by the FDA that govern clinical trials. Similar requirements are imposed by comparable foreign regulatory authorities for all of our product candidates in clinical development. Regulatory authorities enforce these GCP requirements through periodic inspections of trial sponsors, principal investigators and trial sites. If we, any of our CROs or clinical trial sites fail to comply with applicable GCP requirements, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or other regulatory authorities may require us to perform additional clinical trials before approving our marketing applications, if at all. In addition, we are required to report certain financial interests of our third‑party investigators if these relationships exceed certain financial thresholds or meet other criteria. The FDA or comparable foreign regulatory authorities may question the integrity of the data from those clinical trials conducted by principal investigators who previously served or currently serve as scientific advisors or consultants to us from time to time and receive cash compensation in connection with such services or otherwise receive compensation from us that could be deemed to impact study outcome, proprietary interests in a product candidate, certain company equity interests, or significant payments of other sorts. We cannot assure you that upon inspection by a given regulatory authority, such regulatory authority will determine that any of our clinical trials comply with GCP requirements. In addition, we must conduct our clinical trials with product produced under applicable cGMP requirements for drug manufacturing. Failure to comply with these regulations may require us to repeat preclinical and clinical trials, which would delay the marketing approval process.36

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We rely upon and expect to continue to rely upon third‑party CROs, CDMOs and other partners for execution of our clinical trials and, while we have agreements governing their activities, we have limited influence over their actual performance and control only certain aspects of their activities. Nevertheless, we are responsible for ensuring that each of our studies is conducted in accordance with the applicable protocol, legal, regulatory and scientific standards, and our reliance on the CROs does not relieve us of our regulatory responsibilities. For any violations of laws and regulations during the conduct of our preclinical studies or clinical trials, we could be subject to untitled and warning letters or enforcement action that may include civil penalties up to and including criminal prosecution and could delay or prevent regulatory approval of our product candidates.

We, our clinical trial sites, and our CROs are required to comply with GCP requirements, which are regulations and guidelines enforced by the FDA that govern clinical trials. Similar requirements are imposed by comparable foreign regulatory authorities for all of our product candidates in clinical development. Regulatory authorities enforce these GCP requirements through periodic inspections of trial sponsors, principal investigators and trial sites. If we, any of our CROs or clinical trial sites fail to comply with applicable GCP requirements, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or other regulatory authorities may require us to perform additional clinical trials before approving our marketing applications, if at all. In addition, if regulatory authorities determine that we or our third parties have not complied with applicable requirements, they may impose a clinical hold, refuse to consider data from a study, or delay or deny approval. In addition, we are required to report certain financial interests of our third‑party investigators if these relationships exceed certain financial thresholds or meet other criteria. The FDA or comparable foreign regulatory authorities may question the integrity of the data from those clinical trials conducted by principal investigators who previously served or currently serve as scientific advisors or consultants to us from time to time and receive cash compensation in connection with such services or otherwise receive compensation from us that could be deemed to impact study outcome, proprietary interests in a product candidate, certain company equity interests, or significant payments of other sorts. We cannot assure you that upon inspection by a given regulatory authority, such regulatory authority will determine that any of our clinical trials comply with GCP requirements. In addition, we must conduct our clinical trials with current or future product produced under applicable cGMP requirements for drug manufacturing. Failure to comply with these regulations may require us to repeat preclinical and clinical trials, which would delay the marketing approval process. Our failure or the failure of third parties that we may contract with to comply with these regulations may require us to repeat some aspects of a specific, or an entire, clinical trial, which would delay the marketing approval process and could also subject us to enforcement action. We also are required to register certain ongoing clinical trials and provide certain information, including information relating to the trial’s protocol, on a government-sponsored database, ClinicalTrials.gov, within specific timeframes. Failure to do so can result in fines, adverse publicity and civil and criminal sanctions.

Our CROs and clinical trial site personnel are not our employees, and, except for remedies available to us under our agreements with such CROs and clinical trial sites, we cannot control whether they devote sufficient time and resources to our ongoing clinical, nonclinical and preclinical programs. These CROs and clinical trial sites may also have relationships with other commercial entities, including our competitors, for whom they may also be conducting clinical trials or other drug development activities that could harm our competitive position. If CROs or clinical trial sites do not successfully carry out their contractual duties or obligations or meet expected deadlines, or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated and we might not be able to obtain marketing approval for or successfully commercialize our product candidates or we may be subject to regulatory enforcement actions. As a result, our results of operations and the commercial prospects for our product candidates would be harmed, our costs could increase and our ability to generate revenues could be delayed. To the extent we are unable to successfully identify and manage the performance of third‑party service providers in the future, our business may be adversely affected.

~~Switching~~Our orreliance ~~adding~~on ~~CROs~~third ~~involves~~parties ~~substantial~~to ~~cost~~conduct ~~and~~clinical ~~requires~~trials ~~extensive~~will ~~management~~also ~~time~~result ~~and~~in ~~focus.~~less Indirect ~~addition,~~control ~~there~~over isthe amanagement ~~natural~~of ~~transition~~data ~~period~~developed ~~when~~through aclinical ~~new~~trials ~~CRO~~than ~~commences~~would ~~work.~~be Asthe acase ~~result,~~if ~~delays~~we ~~occur,~~were ~~which~~relying ~~can~~entirely ~~materially~~upon ~~impact~~ our ~~ability~~own ~~to meet our desired clinical development timelines~~staff. ~~Though~~Communicating ~~we carefully manage our relationships~~ with ~~our~~outside ~~CROs,~~parties ~~there~~ can also be nochallenging, ~~assurance~~potentially ~~that~~leading weto ~~will~~mistakes ~~not~~as ~~encounter~~well ~~similar~~as ~~challenges~~difficulties ~~or delays~~ in ~~the~~coordinating ~~future~~activities. orOutside ~~that~~parties ~~these delays or challenges will not have a material adverse impact on our business, prospects, financial condition and results of operations.~~may:

27•Have staffing difficulties;

•Fail to comply with contractual obligations;

•Experience regulatory compliance issues; and

•Form relationships with other entities, some of which may be our competitors.

These factors may materially adversely affect the willingness or ability of third parties to conduct our clinical trials and may subject us to unexpected cost increases that are beyond our control. If our CROs do not perform clinical trials in a satisfactory manner, breach their obligations to us, fail to comply with regulatory requirements, or if they need to be replaced, any clinical trials such CROs are associated with may be extended, delayed or terminated, the development, marketing approval and commercialization of our current or future product candidates may be delayed, we may not be able to obtain marketing approval and commercialize our current or future product candidates, or our development programs may be materially and irreversibly harmed. If we are unable to rely on clinical data collected by our CROs, we could be required to repeat, extend the duration of, or increase the size of clinical trials we conduct and this could significantly delay commercialization and require significantly greater expenditures. If any of our relationships with these third-party CROs terminate, we may not be able to enter into arrangements with alternative CROs on commercially reasonable terms, or at

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Weall. ~~use~~If ~~third~~our ~~parties~~CROs todo ~~manufacture~~not ~~all~~successfully ofcarry ~~our~~out ~~product~~their ~~candidates.~~contractual ~~This~~duties ~~may~~or ~~increase~~obligations ~~the~~or ~~risk~~meet ~~that~~expected wedeadlines, ~~will~~if ~~not~~they ~~have~~need ~~sufficient~~to ~~clinical~~be replaced or ~~commercial~~if ~~quantities~~the quality or accuracy of ~~our~~the ~~product~~clinical ~~candidates~~data orthey ~~such~~obtain ~~quantities~~is atcompromised andue ~~acceptable~~to ~~cost,~~the ~~which~~failure ~~could~~to ~~result~~adhere into ~~the~~our ~~delay,~~clinical ~~prevention~~protocols, regulatory requirements or ~~impairment~~for ofother reasons, any clinical ~~development~~trials such CROs are associated with may be extended, delayed or terminated, and ~~commercialization~~we ofmay not be able to obtain marketing approval for or successfully commercialize our current or future product candidates.

WeSwitching door ~~not~~adding ~~own~~CROs orinvolves ~~operate,~~substantial cost and ~~have~~requires noextensive ~~plans~~management totime ~~establish~~and focus. In addition, ~~any~~there ~~manufacturing~~is ~~facilities~~a ~~for~~natural transition period when a new CRO commences work. As a result, delays occur, which can materially impact our ~~product~~ability ~~candidates~~to meet our desired clinical development timelines. WeThough ~~have~~we ~~limited~~carefully ~~personnel~~manage our relationships with ~~experience~~our inCROs, ~~drug~~there ~~manufacturing~~can ~~and~~be no assurance that we ~~lack~~will ~~the~~not ~~resources~~encounter ~~and~~similar challenges or delays in the ~~capabilities~~future toor ~~manufacture~~that ~~any~~these ofdelays ~~our~~or ~~product~~challenges ~~candidates~~will onnot have a ~~clinical~~material oradverse ~~commercial~~impact ~~scale~~on our business, prospects, financial condition and results of operations.

We ~~currently~~use ~~outsource~~third ~~all~~parties ~~manufacturing~~to manufacture all of our product candidates. toThis ~~third~~may ~~parties~~increase ~~typically~~the ~~without~~risk ~~any guarantee~~ that ~~there~~we will benot have sufficient ~~supplies~~clinical toor ~~fulfill~~commercial ~~our~~quantities ~~requirements~~of orour ~~that~~product wecandidates ~~may~~or ~~obtain~~ such ~~supplies~~quantities onat an acceptable ~~terms.~~cost, ~~Any~~which ~~delays~~could result in ~~obtaining~~the ~~adequate~~delay, ~~supplies~~prevention, ~~with~~or ~~respect~~impairment toof clinical development and commercialization of our product candidates ~~may~~and ~~delay~~could ~~the~~harm ~~development~~our orbusiness, ~~commercialization~~financial ofcondition ~~our~~and ~~other~~results ~~product~~of ~~candidates~~operations.

We do not own or operate, and have no plans to establish, any manufacturing facilities for our product candidates. We have limited personnel with experience in drug manufacturing and we lack the resources and the capabilities to manufacture any of our product candidates on a clinical or commercial scale. As a result, we depend on third parties for the development, testing, scale-up, manufacture, fill-finish, quality control, labeling, packaging, storage and distribution of our product candidates.

We currently outsource all manufacturing of our product candidates to third parties typically without any guarantee that there will be sufficient supplies to fulfill our requirements or that we may obtain such supplies on acceptable terms. Any delays in obtaining adequate supplies with respect to our product candidates may delay the development or commercialization of our other product candidates or require us to incur additional costs to secure alternative suppliers.

In addition, we do not currently have agreements with all third‑party manufacturers for the long‑term commercial supply of our product candidates. We may be unable to enter agreements for commercial supply with third‑party manufacturers, or may be unable to do so on acceptable terms. Even if we enter into these agreements, the various manufacturers of each product candidate will likely be single source suppliers to us for a significant period of time.

The facilities used by our contract manufacturers to manufacture our product candidates may be inspected by the FDA after we submit ana ~~NDA or~~ BLA and prior to approval thereof. While we are ultimately responsible for the manufacture of our product candidates, other than through our contractual arrangements, we do not control the manufacturing process of, and are completely dependent on, our contract manufacturing partners for compliance with cGMP requirements for manufacture of both active drug substances and finished drug products for clinical supply and eventually for commercial supply, if we receive regulatory approval. If our contract manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or other regulatory authorities, we will not be able to secure and/or maintain regulatory approval for their manufacturing facilities. Failure of our contract manufacturers to comply with the applicable regulatory requirements may also subject us to regulatory enforcement actions. In addition, other than through our contractual agreements, we have no control over the ability of our contract manufacturers to maintain adequate quality control, quality assurance and qualified personnel. If the FDA or other regulatory authorities do not approve these facilities for the manufacture of our product candidates or if approval is withdrawn in the future, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, obtain marketing approval for or market our product candidates, if approved.

Reliance on third‑party manufacturers subjects us to risks that would not affect us if we manufactured the product candidates ourselves, including:

•Reliance on the third parties for regulatory compliance and quality assurance;

•The possible breach of the manufacturing agreements by the third parties because of factors beyond our control;

•The possible misappropriation of our proprietary information, including trade secrets and know‑how;

•The possibility of termination or nonrenewal of the agreements by the third parties because of our breach of the manufacturing agreement or based on our own business priorities;

•The disruption and costs associated with changing suppliers, including additional regulatory filings.;

•Failure to satisfy our contractual duties or obligations;

•Inability to meet our product specifications and quality requirements consistently;

•Delay or inability to procure or expand sufficient manufacturing capacity;

•Manufacturing and/or product quality issues related to manufacturing development and scale‑up or technology transfer;

•Costs and validation of new equipment and facilities required for scale‑up;

•Failure to comply with applicable laws, regulations, guidance and standards, including cGMP and similar foreign standards;

•Deficient or improper record‑keeping or data integrity issues;

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•Contractual restrictions on our ability to engage additional or alternative manufacturers;

•Inability to negotiate manufacturing agreements with third parties under commercially reasonable terms;

•Termination or nonrenewal of manufacturing agreements with third parties in a manner or at a time that is costly or damaging to us;

•Reliance on a limited number of sources, and in some cases, single sources for product components, such that if we are unable to secure a sufficient supply of these product components, we would be unable to manufacture and sell our product candidates or any future product candidate in a timely fashion, in sufficient quantities or under acceptable terms;

•Lack of qualified backup suppliers for those components that are currently purchased from a sole or single source supplier;

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•Lack of access or licenses to proprietary manufacturing methods used by third‑party manufacturers to make our product candidates;

•Operations of our third‑party manufacturers or suppliers could be disrupted by conditions unrelated to our business or operations, including the bankruptcy of the manufacturer or supplier or regulatory sanctions related to the manufacturer;

•Carrier and import disruptions or increased costs that are beyond our control; ~~and~~

•Failure to deliver our products under specified storage conditions and in a timely manner. including but not limited to any required cold-chain or other specialized handling conditions;

~~Our~~•Potential ~~product~~changes ~~candidates~~by ~~may~~third ~~compete~~parties ~~with other products and product candidates for access~~ to ~~manufacturing facilities. There are a limited number of manufacturers that operate under cGMP regulations and that are both capable of manufacturing for us and willing to do so. In addition~~materials, ~~the manufacture of biologics requires significant expertise~~processes, including the development of advanced manufacturing techniques and process controls. The process is highly complex and we may encounter difficulties in production. These issues may include difficulties with production coststesting, ~~production~~facilities ~~yields~~or ~~and quality control~~equipment, ~~including~~which ~~stability~~could ~~of the product candidate. Further, our product candidates may~~ require ~~new~~us ~~or specialized manufacturing with limited third-party manufacturers available~~ to ~~provide~~demonstrate ~~these~~comparability, ~~services. The occurrence of any of these problems~~ could ~~significantly~~lead ~~delay our clinical trials or the commercial availability of our product candidates. If our existing third‑party manufacturers, or the third parties that we engage in the future~~ to ~~manufacture a product for commercial sale or for our clinical trials~~delays, ~~should cease to continue to do so for any reason, we likely would experience delays in obtaining sufficient quantities of our product candidates for us to advance our clinical trials~~ or tocould ~~meet~~adversely ~~commercial~~affect ~~demand while we identify and qualify replacement suppliers. If for any reason we are unable to obtain adequate supplies of our~~ product ~~candidates~~quality or ~~the~~regulatory ~~drug~~compliance; ~~substances used to manufacture them, it will be more difficult for us to develop~~ and ~~commercialize our product candidates and compete effectively.~~

~~Our~~•Limited ~~suppliers~~availability ~~are~~or ~~subject~~long tolead ~~regulatory~~times ~~requirements~~for ~~covering~~critical ~~manufacturing,~~raw ~~testing~~materials, ~~quality control~~components, ~~manufacturing,~~or ~~and~~specialized ~~record keeping relating to our product candidates~~testing, ~~and~~including ~~subject~~due to ongoing inspections by the regulatory agencies. Failure by any of our suppliers to comply with applicable regulations may result in long delays and interruptions to our manufacturing capacity while we seek to secure another supplier ~~that~~constraints ~~meets~~or ~~all~~allocation ~~regulatory~~decisions ~~requirements,~~favoring aslarger ~~well as market disruption related to any necessary recalls or other corrective actions~~customers.

~~National~~Our product candidates may compete with other products and ~~global~~product ~~health~~candidates for access to manufacturing facilities. There are a limited number of manufacturers that operate under cGMP regulations and that are both capable of manufacturing for us and willing to do so. In addition, the manufacture of biologics requires significant expertise, including the development of advanced manufacturing techniques and process controls. The process is highly complex and we may encounter difficulties in production. These issues may include difficulties with production costs, production yields and quality control, including stability of the product candidate. Further, our product candidates may require new or ~~geopolitical~~specialized ~~situations~~manufacturing with limited third-party manufacturers available to provide these services. The occurrence of any of these problems could ~~have~~significantly adelay ~~negative~~our ~~adverse~~clinical ~~impact~~trials onor the commercial availability of our ~~suppliers~~product candidates. If our existing third‑party manufacturers, ~~which~~or ~~could~~the ~~impede~~third parties that we engage in the ~~development~~future to manufacture a product for commercial sale or ~~commercialization~~for our clinical trials, should cease to continue to do so for any reason, we likely would experience delays in obtaining sufficient quantities of our product candidates for us to advance our clinical trials or to meet commercial demand while we identify and qualify replacement suppliers including delays associated with technology transfer, qualification, validation and regulatory submissions. If for any reason we are unable to obtain adequate supplies of our product candidates or the drug substances used to manufacture them, it will be more difficult for us to develop and commercialize our product candidates and compete effectively and our business, financial condition and results of operations could be materially adversely affected.

Our suppliers are subject to regulatory requirements covering manufacturing, testing, quality control, and record keeping relating to our product candidates, and subject to ongoing inspections by the regulatory agencies. Failure by any of our suppliers to comply with applicable regulations may result in long delays and interruptions to our manufacturing capacity while we seek to secure another supplier that meets all regulatory requirements, as well as market disruption related to any necessary recalls or other corrective actions, including potential clinical holds, delays in regulatory review, or refusal to approve marketing applications.

National and global health or geopolitical situations could have a material adverse impact on our suppliers, which could impede the development or commercialization of our product candidates. including through disruptions in transportation, import/export restrictions, sanctions, labor shortages, inflationary cost pressures, or allocation of manufacturing capacity.

Our manufacturing process needs to comply with FDA regulations relating to the quality and reliability of such processes. Any failure to comply with relevant regulations could result in delays in or termination of our preclinical and clinical programs and suspension or withdrawal of any regulatory approvals or could limit our ability to supply product for clinical trials or, if approved, for commercial sale.

To commercially produce our products either at our own facility or at a third party’s facility, we will need to comply with the FDA’s cGMP regulations and guidelines. We may encounter difficulties in achieving quality control and quality assurance and may experience shortages in qualified personnel. We are subject to inspections by the FDA and comparable foreign regulatory authorities to confirm compliance with applicable regulatory requirements. Any failure to follow cGMP or other regulatory requirements or delay, interruption or other issues that arise in the manufacture, fill-finish, packaging, or storage of our product candidates as a result of a failure of our facilities or the facilities or operations of third parties to comply with regulatory requirements or pass any regulatory authority inspection could significantly impair our ability to develop and commercialize our current or future product candidates, including leading to significant delays in the availability of our product candidates for our clinical trials or the termination of or suspension of a clinical trial, or the delay or prevention of a filing or approval of marketing applications for our current or future product candidates. Significant non-compliance could also result in the imposition of sanctions, including warning or untitled letters, fines, injunctions, civil penalties, failure of regulatory authorities to grant marketing approvals for our current or future product candidates, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of products, operating restrictions

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and criminal prosecutions, any of which could damage our reputation and our business and could result in significant additional costs and the diversion of management time and attention.

If our third-party manufacturers use hazardous and biological materials in a manner that causes injury or violates applicable law, we may be liable for damages.

Our research and development activities involve the controlled use of potentially hazardous substances, including chemical materials, by our third-party manufacturers. Our manufacturers are subject to federal, state and local laws and regulations in the U.S. governing the use, manufacture, storage, handling and disposal of medical and hazardous materials. Although we believe that our manufacturers’ procedures for using, handling, storing and disposing of these materials comply with legally prescribed standards, we cannot completely eliminate the risk of contamination or injury resulting from medical or hazardous materials. As a result of any such contamination or injury, we may incur liability or local, city, state or federal authorities may curtail the use of these materials and interrupt our business operations. In the event of an accident, we could be held liable for damages or penalized with fines, and the liability could exceed our resources. We do not have any insurance for liabilities arising from medical or hazardous materials. Compliance with applicable environmental laws and regulations is expensive, and current or future environmental regulations may impair our research, development and production efforts, which could harm our business, prospects, financial condition or results of operations.

We might not succeed in establishing and maintaining development collaborations, which could adversely affect our ability to develop and commercialize product candidates.

A part of our strategy is to enter ~~into~~ product development collaborations in the future, including collaborations with major biotechnology or pharmaceutical companies for the development or commercialization of our current and future product candidates. We also face significant competition in seeking appropriate development partners and the negotiation process is time‑consuming and complex. We might not succeed in our efforts to establish development collaborations or other alternative arrangements for any of our existing or future product candidates and programs because our research and development pipeline may be insufficient, our product candidates and programs may be deemed to be at too early a stage of development for collaborative effort and/or third parties might not view our product candidates and programs as having the requisite potential to demonstrate safety and efficacy or a commercially attractive risk-return profile.

Furthermore, any collaborations that we enter into might not be successful. The success of our development collaborations will depend heavily on the efforts and activities of our collaborators over which we have limited control. Our relationship with any future collaborations may pose several risks, including the following:

•Collaborators have significant discretion in determining the amount and timing of the efforts and resources that they will apply to these collaborations and may prioritize their own internal programs or other third-party collaborations over ours;

•Collaborators might not perform their obligations as expected;

•The nonclinical studies and clinical trials conducted as part of these collaborations might not be successful or may generate results that do not support continued development or commercialization;

•Collaborators might not pursue development and commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew development or commercialization programs based on nonclinical study or clinical trial results, changes in the collaborators’ strategic focus or available funding or external factors, such as an acquisition, that divert resources or create competing priorities including changes in management or corporate strategy;

•Collaborators may delay nonclinical studies and clinical trials, provide insufficient funding for nonclinical studies and clinical trials, stop a nonclinical study or clinical trial or abandon a product candidate, repeat or conduct new nonclinical studies or clinical trials or require a new formulation of a product candidate for nonclinical studies or clinical trials which could increase our development costs or delay regulatory timelines;

•Collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours;

29•Product candidates developed in collaboration with us may be viewed by our collaborators as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the commercialization of our product candidates or to exercise contractual rights in a manner adverse to us;

~~Table~~•A collaborator with marketing and distribution rights to one or more of ~~Contents~~our product candidates that achieve regulatory approval might not commit sufficient resources to the marketing and distribution of any such product candidate or may fail to achieve anticipated commercial performance;

•Product candidates developed in collaboration with us may be viewed by our collaborators as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the commercialization of our product candidates;

•A collaborator with marketing and distribution rights to one or more of our product candidates that achieve regulatory approval might not commit sufficient resources to the marketing and distribution of any such product candidate;

•Disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development of any product candidates, may cause delays or termination of the research, development or commercialization of such product candidates, may lead to additional responsibilities for us with respect to such product candidates or may result in litigation or arbitration, any of which would be time consuming and expensive;

•Collaborators might not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation or loss of exclusivity;

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•Disputes may arise with respect to the ownership or inventorship of intellectual property developed pursuant to our collaborations;

•Collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability or require us to seek alternative development pathways;

•The terms of our collaboration agreement may restrict us from entering into certain relationships with other third parties, thereby limiting our opportunities or strategic opportunities; and

•Collaborations may be terminated for the convenience of the collaborator and, if terminated, we could be required to raise additional capital to pursue further development or commercialization of the applicable product candidates or to assume development, manufacturing, or commercialization responsibilities previously borne by the collaborator.

Even if we are successful in our efforts to establish development collaborations, the terms that we agree upon might not be favorable to us and we might not be able to maintain such development collaborations if, for example, development or approval of a product candidate is delayed or sales of an approved product candidate are disappointing or fail to meet the collaborator’s internal expectations. Any delay in entering into development collaboration agreements related to our product candidates could delay the development and commercialization of our product candidates and reduce their competitiveness if they reach the market. Additionally, collaborations with pharmaceutical or biotechnology companies and other third parties often are terminated or allowed to expire by the other party sometimes for reasons outside our control. Any such termination or expiration would adversely affect us financially and could harm our business reputation and stock price.

If we fail to establish and maintain additional development collaborations related to our product candidates:

•The development of certain of our product candidates may be terminated or delayed;

•Our cash expenditures related to development of certain of our product candidates would increase significantly and we may need to seek additional financing, which might not be available on favorable terms, or at all;

•We may be required to hire additional employees or otherwise develop expertise, such as sales and marketing expertise, for which we have not budgeted;

•We would bear all of the risk related to the development of any such product candidates including but not limited to including regulatory, manufacturing, and commercialization risks;

•We may have to expend unexpected efforts and funds if we are unable to obtain the results of third‑party clinical trials or access collaboration-generated data; and

•The competitiveness of any product candidate that is commercialized could be reduced or eliminated entirely.

Risks Related to Intellectual Property

If we are unable to obtain or maintain intellectual property rights, or if the scope of ~~patent~~our ~~protection~~issued ispatents are not sufficiently broad, competitors could develop and commercialize products similar or identical to ours, and we might not be able to compete effectively in our market. Furthermore, our US composition-of-matter patent for abdakibart (AVTX-009) isexpired ~~set to expire~~ in February 2026.

Our success depends in significant part on our and our licensors’, licensees’ or collaborators’ ability to ~~establish~~file and prosecute patent applications, maintain ~~and~~patents, diligently protect ~~patents~~our patent rights and other intellectual property rights and operate without infringing the intellectual property rights of ~~others~~any third party (including patents and other proprietary rights relating to biologics, antibody sequences, manufacturing processes, formulations, methods of treatment, dosing regimens, and delivery). We have filed numerous patent applications both in the United States and in foreign jurisdictions to obtain patent rights to ~~inventions~~our ~~we have discovered~~inventions. We have also licensed ~~from~~ third parties’ ~~rights~~patent portfolios relevant to ~~patent~~our ~~portfolios~~technology and may in the future in-license additional intellectual property or enter into other strategic arrangements.

The patent prosecution process is expensive, ~~and~~ time‑consuming, and uncertain, and we and our current or future licensors, licensees or collaborators might not be able to prepare, file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. It is also possible that we or our licensors, licensees or collaborators will fail to identify patentable aspects of inventions made in the course of development and commercialization activities before it is too late to obtain patent protection on them or before any third party files patent applications covering such inventions. Moreover, in some circumstances, we might not have the right to control the preparation, filing and prosecution of patent applications, or to maintain the patents, covering technology that we license from or license to third parties and are reliant on our licensors, licensees or collaborators. ~~Therefore,~~to ~~these~~secure ~~patents~~ and ~~applications~~maintain ~~might~~adequate ~~not~~patent beprotection ~~prosecuted~~to cover our technology to further our efforts to commercialize our product candidate. Therefore, these licensed patents and ~~enforced~~patent applications in a manner consistent with the best interests of our business including because of budget constraints, competing priorities, or differing enforcement strategies. If our current or future licensors, licensees or collaborators fail to ~~establish~~file, ~~maintain~~prosecute, or ~~protect~~maintain such patents and other intellectual property, such intellectual property rights may be reduced or eliminated. If our licensors, licensees or collaborators are not fully cooperative or disagree with us as to the prosecution, maintenance or enforcement of any patent rights, such patent rights could be compromised and we may not have adequate contractual remedies or practical ability to cure these issues.

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The patent position of biotechnology and ~~other~~pharmaceutical ~~intellectual~~companies ~~property~~generally ~~rights~~is highly uncertain, ~~such~~involves ~~rights~~complex ~~may~~legal beand ~~reduced~~factual orquestions ~~eliminated~~and has in recent years been the subject of much costly litigation. IfAs a result, the issuance, scope, validity, enforceability and commercial value of our and our current or future licensors’, licensees’ or collaborators’ patent rights are highly uncertain. Our and our licensors’, licensees’ or collaborators’ pending and future patent applications might not ~~fully~~result ~~cooperative~~in patents being issued which protect our technology or ~~disagree~~products, ~~with~~in uswhole asor in part, or which effectively allow third parties to commercialize competitive technologies and products. During the course of prosecution, ~~maintenance~~patent examiners may require us or ~~enforcement~~our licensors, licensees or collaborators to narrow the scope of ~~any~~the claims of our or our licensors’, licensees’ or collaborators’ pending and future patent ~~rights~~applications to secure allowance, which may limit the scope of patent protection that may be obtained. Our and our licensors’, licensees’ or collaborators’ patent applications cannot be enforced against third parties practicing the technology claimed in such applications unless and until a patent ~~rights~~issues ~~could~~from such applications, and then only to the extent the issued claims adequately cover our products and only in territories in which patents are issued. Even if patents issue, they may be ~~compromised~~challenged, invalidated, found unenforceable, or construed narrowly, including in post-grant proceedings (such as inter partes review) or other administrative and judicial proceedings.

~~The~~Furthermore, ~~patent~~given ~~position~~the amount of ~~biotechnology~~time ~~and~~required ~~pharmaceutical~~for ~~companies~~the ~~generally~~development, istesting ~~highly~~and ~~uncertain,~~regulatory ~~involves~~review ~~complex~~of ~~legal~~new ~~and~~product ~~factual~~candidates, ~~questions~~patents ~~and~~protecting ~~has~~such incandidates ~~recent~~might ~~years~~expire ~~been~~before ~~the~~or ~~subject~~shortly ofafter ~~much~~such ~~litigation~~candidates are commercialized. As a result, ~~the~~our ~~issuance,~~owned ~~scope,~~and ~~validity,~~licensed ~~enforceability~~patent ~~and~~portfolio ~~commercial~~might ~~value~~not ofprovide ~~our~~us ~~and~~with ~~our~~sufficient ~~current~~rights orto ~~future~~exclude ~~licensors’,~~others ~~licensees’~~from orcommercializing ~~collaborators’~~products ~~patent~~similar ~~rights~~or ~~are~~identical ~~highly~~to ~~uncertain~~our products. Our ~~and~~ability ~~our~~to ~~licensors’,~~protect ~~licensees’~~abdakibart or(AVTX-009) ~~collaborators’ pending~~ and any future ~~patent~~product ~~applications~~candidates ~~might~~may ~~not~~therefore ~~result~~depend inon a combination of patents ~~being~~(including ~~issued~~potential ~~which~~method-of-use, ~~protect~~dosing ~~our~~regimen, ~~technology~~formulation, or ~~products~~manufacturing patents), inregulatory ~~whole~~exclusivities, ortrade insecrets, ~~part~~and other barriers to entry, ornone of which ~~effectively~~can ~~prevent~~be ~~others~~assured. ~~from~~We ~~commercializing~~expect ~~competitive~~to ~~technologies~~seek ~~and~~extensions ~~products~~of patent terms, where available in any countries where we are prosecuting patents. ~~The~~Such patent ~~examination~~term ~~process~~extensions ~~may~~include ~~require~~the usUnited orStates ~~our~~Drug ~~licensors~~Price Competition and Patent Term Restoration Act of 1984, ~~licensees~~which orpermits ~~collaborators~~a patent term extension of up to ~~narrow~~five years beyond the ~~scope~~expiration of the ~~claims~~patent ofto ~~our~~compensate orthe ~~our~~biologics ~~licensors’~~applicant for certain delays caused by the FDA during the drug approval process. However, ~~licensees’~~the orapplicable ~~collaborators’~~authorities, ~~pending~~including the FDA in the United States, and ~~future~~any ~~patent~~equivalent ~~applications~~regulatory authority in other countries, ~~which~~might ~~may~~not ~~limit~~agree ~~the~~with ~~scope~~our assessment of ~~patent~~whether ~~protection~~such ~~that~~extensions are available, and may berefuse ~~obtained.~~to ~~Our~~grant ~~and~~extensions to our ~~licensors’~~patents, ~~licensees’~~ or ~~collaborators’~~may ~~patent~~grant ~~applications~~more ~~cannot~~limited beextensions ~~enforced~~than ~~against~~we ~~third~~request. ~~parties~~Moreover, ~~practicing~~because the ~~technology~~calculation ~~claimed~~of inpatent ~~such~~term ~~applications~~extension ~~unless~~awarded ~~and~~to ~~until~~a biologic applicant are based upon FDA delays, whether we receive a patent ~~issues~~term ~~from~~extension ~~such~~and, ~~applications~~if so, ~~and~~how ~~then~~many ~~only~~years toof ~~the~~PTE ~~extent~~we are eligible for, is a factor that is outside of our control. In addition, patent term extension may be unavailable if the ~~issued~~relevant patent claims, ~~cover~~regulatory ~~the~~pathway, ~~technology~~or timing requirements are not satisfied.

~~Furthermore,~~Our ~~given~~composition ~~the amount~~ of ~~time~~matter ~~required~~patent for ~~the~~abdakibart ~~development,~~(AVTX-009) ~~testing~~expired ~~and~~in ~~regulatory~~February ~~review~~2026. ofIf ~~new~~we ~~product~~are ~~candidates,~~unable ~~patents~~to ~~protecting~~obtain ~~such~~extensions ~~candidates~~to ~~might~~our ~~expire~~patents ~~before~~ or ~~shortly~~other ~~after~~means ~~such~~of ~~candidates~~regulatory ~~are~~exclusivity ~~commercialized.~~for Asour ~~a result~~products, ~~our~~the ~~owned~~expiration ~~and~~of ~~licensed~~patents ~~patent portfolio~~ might ~~not~~create ~~provide~~opportunities usfor ~~with~~competitors ~~sufficient rights~~ to ~~exclude~~enter ~~others~~the ~~from~~market ~~commercializing~~with ~~products~~ similar orproducts ~~identical~~for to our ~~products.~~target Weindications, ~~expect~~which tocould ~~seek~~have ~~extensions~~a ofmaterial ~~patent~~negative ~~terms~~impact ~~where~~on ~~these~~our ~~are~~financial ~~available~~results. inWithout ~~any~~patent ~~countries~~protection, ~~where~~ we are ~~prosecuting~~susceptible ~~patents.~~to ~~This~~competitors ~~includes~~bringing insimilar ~~the~~products ~~United~~to ~~States~~market, ~~under~~obtaining ~~the~~FDA ~~Drug~~approval, ~~Price Competition~~ and ~~Patent~~achieving ~~Term~~regulatory ~~Restoration~~exclusivity ~~Act~~prior ~~of 1984, which permits a patent term extension of up~~ to ~~five~~us. ~~years~~In ~~beyond~~addition, ~~the~~once ~~expiration~~our composition-of-matter ~~the~~ patent. ~~However~~expires, ~~the~~competitors ~~applicable~~may ~~authorities,~~be ~~including~~able ~~the~~to ~~FDA~~develop incompeting ~~the~~antibodies ~~United~~or ~~States,~~biologics ~~and~~that ~~any~~target ~~equivalent~~the ~~regulatory~~same ~~authority in other countries~~pathway, ~~might~~may ~~not~~seek ~~agree~~to ~~with~~rely ~~our~~on ~~assessment~~their ofown ~~whether~~data ~~such~~packages ~~extensions~~for ~~are available~~approval, and may ~~refuse~~be able to ~~grant~~compete ~~extensions~~with tous ~~our~~on ~~patents,~~price or ~~may~~access, ~~grant~~even ~~more~~if ~~limited extensions than~~ we ~~request~~obtain approval.

~~Our~~Abdakibart ~~composition~~(AVTX-009) ofis ~~matter~~classified ~~patent~~as a biologic product, which positions the Company to receive biologics reference product exclusivity, also called regulatory exclusivity, in both the United States (twelve years) and Europe (ten years) if and upon receiving marketing approval for the products. We plan to rely on such exclusivity to protect abdakibart (AVTX-009), ~~expires~~which inhas ~~2026~~its associated risks. IfSee wethe ~~are~~risk ~~unable~~factor tobelow ~~obtain~~titled ~~extensions~~“As toappropriate, ~~our~~we ~~patents~~intend orto ~~other~~seek ~~means~~all available periods of regulatory exclusivity for our ~~products~~product candidates. However, ~~the~~there ~~expiration~~is no guarantee that we will be granted these periods of ~~patents~~regulatory ~~might~~exclusivity ~~create~~or ~~opportunities~~that ~~for~~we ~~competitors~~will tobe ~~enter~~able ~~the~~to ~~market~~maintain ~~for~~these ~~our~~periods ~~target~~of ~~indications,~~exclusivity” ~~which~~for ~~could~~more ~~have~~information aregarding ~~material~~the ~~negative~~risks ~~impact~~of relying on ~~our~~regulatory ~~financial results~~exclusivity. However, ~~Without~~regulatory exclusivity differs from patent protection, weand ~~are~~may ~~susceptible~~not toprevent competitors ~~bringing~~from ~~similar~~developing and obtaining approval for competing products tobased ~~market,~~on ~~obtaining~~their ~~FDA~~own ~~approval~~full data packages, and ~~achieving~~may ~~regulatory~~be ~~exclusivity~~subject ~~prior~~ to ~~us.~~legal, policy, or legislative change.

AVTX-009 is a biologic product, which would allow the Company to receive biologics reference product exclusivity in both the United States (twelve years) and Europe (ten years) if and upon receiving marketing approval for the products. Once our composition of matter patents expire, we plan to rely on such exclusivity to protect our intellectual property, which has its associated risks. See the risk factor below titled “As appropriate, we intend to seek all available periods of regulatory exclusivity for our product candidates. However, there is no guarantee that we will be granted these periods of regulatory exclusivity or that we will be able to maintain these periods of exclusivity” for more information regarding the risks of relying on regulatory exclusivity.

As appropriate, we intend to seek all available periods of regulatory exclusivity for our product candidates. However, there is no guarantee that we will be granted these periods of regulatory exclusivity or that we will be able to maintain these periods of exclusivity.

The Biologics Price Competition and Innovation Act of 2009 (“BPCIA”) created an abbreviated pathway for the approval of biosimilar and interchangeable biological products. ~~The~~This regulatory pathway establishes legal authority for the FDA to review and approve biological products that are biosimilar to or interchangeable with an FDA-licensed reference biologic.

Under the BPCIA, a reference biological product is granted twelve years of exclusivity in the United States from the time of first marketing approval of the product (ten years of data and marketing exclusivity in Europe), and the FDA will not accept an application for a biosimilar or interchangeable product based on the reference biological product until four years after the date of first licensure of the reference product. In addition, the licensure of a biosimilar product may not be made effective by the FDA until twelve years from the date on which the reference product was first licensed. During this 12-year period of exclusivity, another company may still develop and receive approval for a competing version of the reference product if the FDA approves a full biologics license application for the competing product containing the sponsor’s own preclinical data and data from adequate and well-controlled clinical trials to ~~demonstrate the safety, purity and potency of their product.~~

We believe that our current and any future product candidates we develop as biologic products should qualify for the 12-year period of exclusivity in the United States (ten years in Europe). While we intend to apply for all periods of exclusivity that we may be eligible for, there is no guarantee that we will receive all such periods of exclusivity. Additionally, under certain circumstances, the FDA may revoke the period of exclusivity. As a result, there is no guarantee that we will be able to maintain a period of exclusivity, even if granted. Further, there is a risk that any exclusivity we receive is shortened due to Congressional action or otherwise, or that the FDA will not consider subject product candidates to be reference products for competing products, potentially creating the opportunity for biosimilar competition sooner than anticipated. 42

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demonstrate the safety, purity and potency of their product. In addition, the BPCIA includes procedural mechanisms for patent disputes (sometimes referred to as the “patent dance”), and there is substantial uncertainty regarding how these mechanisms may be applied to our products and patents, including the timing and scope of any related litigation.

We believe that our current and any future product candidates we develop as biologic products should qualify for the 12-year period of regulatory exclusivity in the United States (ten years in Europe). While we intend to apply for all periods of exclusivity that we may be eligible for, there is no guarantee that we will receive all such periods of exclusivity. Additionally, under certain circumstances, the FDA may revoke the period of exclusivity. As a result, there is no guarantee that we will be able to maintain a period of regulatory exclusivity for the product, even if such exclusivity is granted. Further, there is a risk that any exclusivity we receive is shortened due to Congressional action or other governmental action, or that the FDA will not consider subject product candidates to be reference products for competing products, potentially creating the opportunity for biosimilar competition sooner than anticipated. Even if exclusivity is granted, competitors may seek to challenge its scope, timing, or applicability, including through administrative or judicial proceedings.

If we breach the license and development agreements related to our product candidates, we could lose the ability to develop and commercialize our product candidates.

Our commercial success depends upon our ability, and the ability of our licensors and collaborators, to develop, manufacture, market and sell our product candidates and use our and our licensors’ or collaborators’ proprietary technologies without infringing the proprietary rights of third parties. If we fail to comply with our obligations in the agreements under which we license intellectual property rights from third parties or otherwise experience disruptions to our business relationships with our licensors, we could lose the ability to continue the development and commercialization of our product candidates or face other penalties under these agreements. In particular, we are party to the following agreements for abdakibart (AVTX-009):

•The Lilly License Agreement; and

•The Leap Agreement.

If we fail to comply with the obligations under either of these agreements, including payment terms, our licensors may have the right to terminate ~~any~~either of these agreements, in which event we might not be able to develop, market or sell the relevant product candidate. Such an occurrence could materially adversely affect the value of the product candidate being developed under any such agreement. Termination of these agreements or reduction or elimination of our rights under these agreements may result in us having to negotiate new or reinstated agreements, which might not be available to us on equally favorable terms, or at all, or cause us to lose our rights under these agreements, including our rights to intellectual property or technology important to our development programs. Any of these occurrences may harm our business, financial condition and prospects significantly. In addition, disputes regarding the scope of rights granted, diligence obligations, sublicensing rights, prosecution and enforcement control, or royalty and milestone interpretations could result in delays, increased costs, or loss of rights.

We may be required to make significant payments in connection with our license and development agreements.

We ~~are party to license and development agreements with various third parties. For example, for our programs we are party to the Lilly License Agreement and the Leap Agreement. We~~ may be required to make significant payments in connection with ~~our~~both of the above listed license and development agreements, including (but not limited to):

•Under the Lilly License Agreement, we will incur development costs for abdakibart (AVTX-009) and are required to make significant payments in connection with the achievement of specified development and regulatory milestones. Additionally, upon commercialization, we are obligated to pay Lilly sales-based milestones and royalties;

•For abdakibart (AVTX-009), we are subject to additional sales-based milestones payable to Leap Therapeutics, Inc.; and

•For abdakibart (AVTX-009), we are subject to additional contingent development milestones in the Leap agreement that are payable to the former AlmataBio stockholders.

If the obligations become due under the terms any of these agreements, we might not have sufficient funds available to meet our obligations and our development efforts may be negatively impacted. Moreover, even if we have sufficient funds, these obligations could materially reduce the economic value of abdakibart (AVTX-009), adversely affect margins, and reduce our ability to fund other programs.

Obtaining and maintaining our patent protection depends on ~~compliance~~our complying with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies worldwide, and our patent protection could be reduced or eliminated for non‑compliance with these requirements.

Periodic maintenance and annuity fees on any issued patent are due to be paid to the U.S. Patent and Trademark Office (“USPTO”), and foreign patent agencies in several stages over the lifetime of the patent. The USPTO and various foreign governmental patent agencies require compliance with procedural, documentary, fee payment and other similar provisions during the patent application process. While an inadvertent lapse in complying with any of these requirements can often be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. Non‑compliance events that could result in abandonment or lapse of a patent or patent application include failure to respond to official actions within prescribed time limits, non‑payment of fees and failure to properly legalize and submit formal documents. If we or our licensors or collaborators fail to maintain the patents and patent applications covering our product candidates, our competitors might be able to enter the market, which would have a material adverse effect on our business.

We may become involved in lawsuits to protect or enforce our intellectual property, which could be expensive, time‑consuming and unsuccessful and have a material adverse effect on the success of our business. 43

Third parties may infringe on our or our licensors’ or collaborators’ patents or misappropriate or otherwise violate our or our licensors’ or collaborators’ intellectual property rights. In the future, we or our licensors or collaborators may initiate legal proceedings to enforce or defend our or our licensors’ or collaborators’ intellectual property rights, to protect our or our licensors’ or collaborators’

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~~trade~~of ~~secrets or to determine~~ the ~~validity~~patent or ~~scope~~patent ~~of intellectual property rights we own or control. Also~~application, ~~third~~resulting ~~parties~~in ~~may~~partial ~~initiate legal proceedings against us~~ or ~~our~~complete ~~licensors~~loss ~~or collaborators to challenge the validity or scope~~ of ~~intellectual~~patent ~~property~~ rights wein ~~own~~the orrelevant ~~control~~jurisdiction. ~~The~~Non‑compliance ~~proceedings~~events ~~can~~that becould ~~expensive~~result ~~and~~in ~~time‑consuming~~abandonment ~~and~~or ~~many~~lapse of ~~our~~a orpatent ~~our licensors’~~ or ~~collaborators’~~patent ~~adversaries~~application ininclude ~~these~~failure ~~proceedings may have the ability~~ to ~~dedicate~~respond ~~substantially greater resources~~ to ~~prosecuting~~official ~~these legal~~ actions ~~than~~within weprescribed ortime ~~our~~limits, ~~licensors~~non‑payment orof ~~collaborators~~fees ~~can.~~and ~~Accordingly,~~failure ~~despite~~to ~~our~~properly orlegalize ~~our~~and ~~licensors’~~submit orformal ~~collaborators’~~documents. ~~efforts,~~If we or our licensors or collaborators ~~might~~fail ~~not~~to ~~prevent~~maintain ~~third~~the ~~parties~~patents ~~from~~and ~~infringing~~patent ~~upon~~applications orcovering ~~misappropriating~~our ~~intellectual~~product ~~property rights we own or control~~candidates, ~~particularly~~our incompetitors ~~countries where the laws~~ might ~~not~~be ~~protect~~able ~~those~~to ~~rights~~enter ~~as fully as in~~ the ~~United~~market, ~~States.~~which ~~Litigation~~would ~~could~~have ~~result~~a inmaterial ~~substantial~~adverse ~~costs~~effect ~~and~~on ~~diversion of management resources, which could harm~~ our business ~~and financial results~~. In addition, inwe anrely ~~infringement~~on ~~proceeding,~~third-party aservice ~~court~~providers ~~may~~and ~~decide~~outside ~~that~~counsel afor certain patent ~~owned by or licensed to us is invalid or unenforceable~~functions, orand ~~may~~failures ~~refuse~~by tosuch ~~stop~~parties the other party from using the technology at issue on the grounds that we or our licensors’ or collaborators’ patents do not cover the technology in question. An adverse result in any litigation proceeding could ~~put~~adversely ~~one~~affect ~~or more of~~ our ~~or our licensors’ or collaborators’ patents at risk of being invalidated, held unenforceable or interpreted narrowly~~rights.

~~Third~~We ~~party~~may ~~pre‑issuance~~become ~~submission~~involved ~~of prior art to the USPTO, or opposition, derivation, reexamination, inter partes review or interference proceedings, or other pre‑issuance or post‑grant proceedings~~ in ~~the~~lawsuits ~~United States or other jurisdictions provoked by third parties or brought by us or our licensors or collaborators may be necessary~~ to ~~determine~~protect ~~the priority of inventions with respect to our~~ or ~~our~~enforce ~~licensors’ or collaborators’ patents or patent applications. An unfavorable outcome could require us or~~ our ~~licensors~~intellectual ~~or collaborators to cease using the related technology and commercializing our product candidates~~property, orwhich ~~to attempt to license rights to it from the prevailing party. Our business~~ could be ~~harmed if the prevailing party does not offer us or our licensors or collaborators a license on commercially reasonable terms or at all. Even if we or our licensors or collaborators obtain a license~~expensive, ~~it may be non~~time‑~~exclusive,~~consuming ~~thereby~~and ~~giving~~unsuccessful ~~our~~and ~~competitors~~have ~~access~~a tomaterial ~~the~~adverse ~~same~~effect ~~technologies~~on ~~licensed to us or our licensors or collaborators. In addition, if~~ the ~~breadth~~success ~~or strength~~ of ~~protection provided by~~ our or our licensors’ or collaborators’ patents and patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize current or future product candidatesbusiness. Even if we successfully defend such litigation or proceeding, we may incur substantial costs and it may distract our management and other employees. We could be found liable for monetary damages, including treble damages and attorneys’ fees if we are found to have willfully infringed a patent.

~~Furthermore,~~Third ~~because~~parties ofmay ~~the~~infringe ~~substantial~~our ~~amount~~or ofour ~~discovery~~licensors’ ~~required~~or incollaborators’ ~~connection~~patents ~~with~~or misappropriate or otherwise violate our or our licensors’ or collaborators’ intellectual property ~~litigation~~rights. In the future, ~~there~~we isor aour ~~risk~~licensors ~~that~~or ~~some~~collaborators ofmay initiate legal proceedings to enforce or defend our ~~confidential~~or ~~information~~our ~~could~~licensors’ beor ~~compromised~~collaborators’ byintellectual ~~disclosure~~property ~~during~~rights, ~~this~~to ~~type~~protect ofour ~~litigation.~~or ~~There~~our ~~could~~licensors’ ~~also~~or becollaborators’ ~~public~~trade ~~announcements~~secrets ofor to determine the ~~results~~validity or scope of ~~hearings~~intellectual property rights that we license, ~~motions~~own or ~~other~~control. ~~interim~~Also, third parties may initiate legal proceedings against us or ~~developments~~our licensors or collaborators to challenge the validity or scope of intellectual property rights we license, own or control. IfThese ~~securities~~proceedings ~~analysts~~can be expensive and time‑consuming and many of our or ~~investors~~our ~~perceive~~licensors’ or collaborators’ adversaries in these ~~results~~proceedings may have the ability to bededicate ~~negative~~substantially greater resources to prosecuting these legal actions than we or our licensors or collaborators can. Accordingly, itdespite our or our licensors’ or collaborators’ efforts, we or our licensors or collaborators might not prevent third parties from infringing or misappropriating intellectual property rights we license, own or control, particularly in countries where the laws might not protect those rights as fully as in the United States. Litigation could ~~have~~result in substantial costs and diversion of management resources, which could harm our business and financial results. In addition, in a ~~material~~patent ~~adverse~~infringement ~~effect~~proceeding, a court may decide that a patent owned by or licensed to us is invalid, unenforceable, or may refuse to stop the other party from using the technology at issue on the ~~price~~grounds that we or our licensors’ or collaborators’ patents do not cover the technology in question. An adverse result in any litigation proceeding could put one or more of our ~~warrants~~or our licensors’ or ~~shares~~collaborators’ patents at risk of being invalidated, held unenforceable or interpreted too narrowly to cover our ~~common~~technology, ~~stock~~which could negatively impact our ability to commercialize our product candidate. Even if we prevail, litigation may be costly and could delay our development or commercialization plans.

Third party pre‑issuance submission of prior art to the USPTO, or opposition, derivation, reexamination, inter partes review or interference proceedings, or other pre‑issuance or post‑grant proceedings in the United States or other jurisdictions provoked by third parties or brought by us or our licensors or collaborators may be necessary to determine the priority of inventions with respect to our or our licensors’ or collaborators’ patents or patent applications. These proceedings can also be used to determine other critical issues, such as the validity of patents based on prior art that was not previously raised or considered during prosecution. An unfavorable outcome in a USPTO proceeding or other similar proceeding in foreign countries could require us or our licensors or collaborators to cease using the related technology and could, therefore, negatively impact our ability to commercialize our product candidates, or to attempt to license rights to it from the prevailing party.

Our business could be harmed if the prevailing party does not offer us or our licensors or collaborators a license on commercially reasonable terms or at all. Even if we or our licensors or collaborators obtain such a license, it may be non‑exclusive, thereby giving our competitors access to the same technologies licensed to us or our licensors or collaborators. In addition, if the breadth or strength of protection provided by our or our licensors’ or collaborators’ patents and patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize current or future product candidates. Even if we successfully defend such litigation or USPTO proceeding, we may incur substantial costs and could result in business disruption that distracts our management and other employees. We could be found liable for monetary damages, including treble damages and attorneys’ fees if a court rules that we are found to have willfully infringed a third party patent.

Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation. There could also be public announcements of the results of hearings, motions or other interim proceedings or developments. If securities analysts or investors perceive these results to be negative, it could have a material adverse effect on the price of our warrants or shares of our common stock. In addition, we could be required to redesign our product candidates, use alternative manufacturing processes, enter into costly licenses, or stop development or commercialization altogether.

Our inability to protect our confidential information and trade secrets would harm our business and competitive position.

In addition to seeking patents for some of our technology and products, we also rely on trade secrets, including unpatented know‑how, technology and other proprietary information, to maintain our competitive position. Though we seek to protect these trade secrets, in part, by entering into non‑disclosure and confidentiality agreements with parties who have access to them, such as our employees, corporate collaborators, outside scientific collaborators, contract manufacturers, consultants, advisors and other third parties, as well as by entering into confidentiality and invention or patent assignment agreements with our employees and consultants, any of these parties may breach the agreements and disclose our proprietary information, including our trade secrets, and we might not be able to obtain adequate remedies for such breaches. ~~Enforcing~~Also, ~~a claim that a party illegally disclosed or misappropriated a~~ trade secret isprotection ~~difficult,~~only ~~expensive~~lasts ~~and~~as ~~time‑consuming,~~long ~~and~~as the ~~outcome is unpredictable. In addition, some courts both within and outside the United States may be less willing or unwilling to protect~~ trade ~~secrets.~~secret Ifis akept ~~competitor lawfully and without breach of a confidentiality obligation obtained or independently developed any of our trade secrets~~secret, wean ~~would have no right to prevent such competitor from using that technology or information to compete with us, which could harm our competitive position.~~

~~Changes in patent law could diminish the value of patents in general, thereby impairing our ability to protect our product candidates.~~ 44

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~~obtain~~extremely ~~new~~high ~~patents~~burden. orEnforcing toa ~~enforce~~claim ~~existing~~that ~~patents~~a ~~and~~party ~~patents~~illegally wedisclosed ~~and~~or ~~our~~misappropriated ~~licensors~~a ortrade ~~collaborators~~secret ~~may~~is ~~obtain~~difficult into prove, expensive and time‑consuming, and the ~~future.~~outcome ~~Patent~~is ~~reform~~unpredictable. ~~legislation~~In ~~could~~addition, ~~increase~~some ~~the~~courts ~~uncertainties~~both within and ~~costs~~outside ~~surrounding~~ the ~~prosecution~~United ofStates ~~our~~may ~~and~~be ~~our~~less ~~licensors’~~willing or ~~collaborators’~~unwilling ~~patent~~to ~~applications~~enforce ~~and~~trade ~~the~~secret ~~enforcement~~protections. orIf ~~defense~~a ofcompetitor ~~our~~lawfully orand ~~our~~without ~~licensors’~~breach orof ~~collaborators’~~a ~~issued~~confidentiality ~~patents.~~obligation Inobtained ~~addition,~~or ~~the~~independently ~~America~~developed ~~Invents~~any ~~Act~~of ~~includes~~our ~~the~~trade ~~first-to-file provisions~~secrets, ~~which~~we ~~increases~~would ~~the~~have ~~uncertainties~~no ~~and~~right ~~costs~~to ~~surrounding~~prevent ~~the~~such ~~prosecution~~competitor offrom ~~our~~using orthat ~~our~~technology ~~licensors’~~ or ~~collaborators’~~information ~~patent~~to ~~applications~~compete ~~and~~with ~~the~~us, ~~enforcement~~which orcould ~~defense~~harm of our orcompetitive ~~our~~position. Certain ~~licensors’~~aspects orof ~~collaborators’~~biologic ~~issued~~development ~~patents.~~and ~~Future~~manufacturing ~~changes~~may inbe ~~patent~~difficult ~~law~~to ~~could~~maintain ~~have~~as atrade ~~material~~secrets ~~adverse~~once ~~effect~~disclosed onin ~~our~~regulatory ~~business~~submissions, ~~and~~publications, ~~financial~~or ~~condition~~collaborations.

Changes in patent law could diminish the value of patents in general, thereby impairing our ability to protect our product candidates.

As is the case with other biotechnology and pharmaceutical companies, our success is heavily dependent on intellectual property, particularly patents. Obtaining and enforcing patents in the biopharmaceutical industry involves technological and legal complexity, and obtaining and enforcing biopharmaceutical patents is costly, time‑consuming, and inherently uncertain. The United States Supreme Court has ruled on several patent cases in recent years, either narrowing the scope of patent protection available in certain circumstances or weakening the rights of patent owners in certain situations. In addition to increasing uncertainty with regard to our and our licensors’ or collaborators’ ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of U.S. patents, once obtained. Depending on decisions by Congress, the federal courts, and the USPTO, the laws and regulations governing patents could change in unpredictable ways that would weaken our and our licensors’ or collaborators’ ability to obtain new patents or to enforce existing patents and patents that we and our licensors or collaborators may obtain in the future. Patent reform legislation could increase the uncertainties and costs surrounding the prosecution of our and our licensors’ or collaborators’ patent applications and the enforcement or defense of our or our licensors’ or collaborators’ issued patents. In addition, the America Invents Act includes the first-to-file provisions, which increases the uncertainties and costs surrounding the prosecution of our or our licensors’ or collaborators’ patent applications and the enforcement or defense of our or our licensors’ or collaborators’ issued patents. Future changes in patent law could have a material adverse effect on our business and financial condition and could weaken our patent protection. In particular, evolving standards relating to patent eligibility, obviousness, written description, enablement, claim construction, and the availability and use of post-grant proceedings could make it more difficult to obtain or enforce patents covering antibodies, biologics, and methods of treatment.

We might not be able to protect our intellectual property rights throughout the world.

Filing, prosecuting, enforcing and defending patents on product candidates in all countries throughout the world would be prohibitively expensive, and our or our licensors’ or collaborators’ intellectual property rights in some countries outside the United States can be less extensive than those in the United States. Differences in foreign patent laws, examination standards, and enforcement practices may reduce the likelihood of obtaining meaningful claims or effective remedies in certain jurisdictions. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States. Consequently, we and our licensors or collaborators might not be able to prevent third parties from practicing our and our licensors’ or collaborators’ inventions in all countries outside the United States, or from selling or importing products made using our and our licensors’ or collaborators’ inventions in and into the United States or other jurisdictions. Competitors may use our and our licensors’ or collaborators’ technologies in jurisdictions where we or our licensors or collaborators have not obtained patent protection to develop their own products and further, may export otherwise infringing products to territories where we and our licensors or collaborators have patent protection, but in countries where patent enforcement is not as strong as that in the United States. These products may compete with our product candidates and our and our licensors’ or collaborators’ patents or other intellectual property rights might not be effective or sufficient to prevent them from competing.

Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents and other intellectual property protection, particularly those relating to biopharmaceuticals, which could make it difficult for us and our licensors or collaborators to stop the infringement of our and our licensors’ or collaborators’ patents or marketing of competing products in such countries in violation of our and our licensors’ or collaborators’ proprietary rights generally. Proceedings to enforce our and our licensors’ or collaborators’ patent rights in any of these foreign jurisdictions could result in substantial costs and divert our and our licensors’ or collaborators’ efforts and attention from other aspects of our business, could put our and our licensors’ or collaborators’ patents at risk of being invalidated or interpreted narrowly and our and our licensors’ or collaborators’ patent applications at risk of not issuing and could provoke third parties to assert claims against us or our licensors or collaborators. We or our licensors or collaborators might not prevail in any lawsuits in foreign jurisdictions that we or our licensors or collaborators initiate and the damages or other remedies awarded, if any, might not be commercially meaningful.

The requirements for patentability may differ in certain countries, particularly developing countries. For example, unlike other countries, China has a heightened requirement for patentability, and specifically requires a detailed description of medical uses of a claimed drug. Furthermore, generic or biosimilar drug manufacturers or other competitors may challenge the scope, validity or enforceability of our or our licensors’ or collaborators’ patents, requiring us or our licensors or collaborators to engage in complex, lengthy and costly litigation or other proceedings. Generic or biosimilar drug manufacturers may develop, seek approval for, and launch biosimilar versions of our products. Certain countries, including India and China, have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties. In those countries, we and our licensors or collaborators may have limited remedies if patents are infringed or if we or our licensors or collaborators are compelled to grant a license to a third party, which could materially diminish the value of those patents. This could limit our potential revenue opportunities. Accordingly, our and our licensors’ or collaborators’ efforts to enforce intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we own or license.

~~Risks Related to Legal Compliance~~ 45

Ongoing changes to healthcare laws and regulations may increase the difficulty of and costs associated with commercializing our products and may affect the prices we are paid for those products.

The Healthcare sector is heavily regulated in the United States and abroad. New laws, regulations, judicial decisions and/or payment and coverage policies—or new interpretations of such laws, regulations, decisions or policies—could negatively impact our business, operations, and financial condition. The United States federal government, state governments, and foreign governments have shown significant and increasing interest in cost-containment initiatives intended to limit the growth of healthcare costs, including without limitation price controls, restrictions on reimbursement, requirements for substitution of generic products for branded prescription drugs, prior authorization requirements, and increased copays and cost shares for beneficiaries.

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~~The~~launch ~~Patient~~biosimilar ~~Protection~~versions ~~and~~of ~~Affordable~~our ~~Care~~products. ~~Act~~Certain ~~increased~~countries, ~~federal~~including ~~oversight~~India ofand ~~private~~China, ~~health~~have ~~insurance~~compulsory ~~plans~~licensing ~~and~~laws ~~included~~under which a ~~number~~patent ofowner ~~provisions~~may ~~designed~~be compelled to ~~reduce~~grant ~~Medicare~~licenses ~~expenditures~~to third parties. In those countries, we and our licensors or collaborators may have limited remedies if patents are infringed or if we or our licensors or collaborators are compelled to grant a license to a third party, which could materially diminish the ~~cost~~value of ~~health~~those ~~care~~patents ~~generally~~in these foreign countries. Such a scenario could limit our potential revenue opportunities. Geopolitical events, sanctions, trade restrictions, or changes in national policies may further limit our ability to ~~reduce~~obtain, ~~fraud~~maintain, ~~waste~~or enforce intellectual property rights in certain jurisdictions. Accordingly, ~~abuse~~our and our licensors’ or collaborators’ efforts to ~~provide~~enforce ~~access~~intellectual property rights around the world may be inadequate to ~~increased~~obtain ~~health~~a ~~coverage~~significant commercial advantage from the intellectual property that we own or license.

Since its enactment, there have been numerous legal challenges and Congressional actions to repeal and replace provisions of the Affordable Care Act that have resulted in profound changes to the law, and efforts to reform the ACA and healthcare sector are ongoing and are likely to gain momentum during the second Trump administration. Nevertheless, it is likely that any ongoing efforts to reform the financing and delivery of healthcare services in the United States will include the downward pressure on pharmaceutical pricing, especially under the Medicare program. Litigation and legislation related to these reforms are likely to continue, with unpredictable and uncertain results.

Some of these changes could have a material adverse effect on our business and operations. Ongoing and future healthcare reform measures may result, for instance, in more rigorous clinical coverage criteria limiting when our product(s) may be covered and in additional downward pressure on the price that we receive for our product and product candidates, if approved, and could harm our future revenues.

Significant uncertainty exists as to the coverage and reimbursement status of products approved by the FDA and other government authorities. Sales of products approved for marketing in the United States by the FDA will depend, in part, on the extent to which products are covered by third-party payors, including government health programs in the United States such as Medicare and Medicaid, commercial health insurers and managed care organizations. The process for determining whether a payor will provide coverage for a product may be separate from the process for setting the price or reimbursement rate that the payor will pay for the product once coverage is approved. Third-party payors may limit coverage to specific products on an approved list, or formulary, which might not include all of the approved products for a particular indication. Additionally, the containment of healthcare costs has become a priority of federal and state governments, and the prices of drugs have been a focus in this effort. The U.S. government, state legislatures and foreign governments have shown significant interest in implementing cost-containment programs, including price controls, restrictions on reimbursement and requirements for substitution of generic products. Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit our net revenue and results.

In order to secure coverage and reimbursement for any product that might be approved for sale, a company may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of the product, which are separate and apart from the costs required to obtain FDA or other comparable regulatory approvals based on the product’s safety and effectiveness. A payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved. Third-party reimbursement may not be sufficient to maintain price levels high enough to realize an appropriate return on investment in product development.

In Europe and other countries outside of the United States, pricing and reimbursement schemes vary widely from country to country. Some countries provide that drug products may be marketed only after a reimbursement price has been agreed to. Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular product candidate to currently available therapies. In some countries, cross-border imports from low-priced markets exert competitive pressure that may reduce pricing within a country. Any country that has price controls or reimbursement limitations for drug products may not allow favorable reimbursement and pricing arrangements.

As stated above, the prices of prescription drugs have been the subject of considerable debate and regulation in the United States and abroad. Recent years have seen several U.S. congressional inquiries into prescription drug pricing, as well as proposed and enacted state and federal legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the costs of drugs under Medicare, and reform government program reimbursement methodologies for drugs and related products.

Efforts at cost containment in healthcare programs and related reforms are ongoing, with the new Trump administration promising to rollback or rescind many of the reforms and executive orders implemented under the Biden Administration. For example, President Biden signed an Executive Order on July 9, 2021, affirming the administration’s policy to (i) support legislative reforms that would lower the prices of prescription drug and biologics, including by allowing Medicare to negotiate drug prices, by imposing inflation caps, and, by supporting the development and market entry of lower-cost generic drugs and biosimilars; and (ii) support the enactment of a public health insurance option. Among other things, the Executive Order also directs HHS to provide a report on actions to combat excessive pricing of prescription drugs, enhance the domestic drug supply chain, reduce the price that the Federal government pays for drugs, and address price gouging in the industry; and directs the FDA to work with states and Indian Tribes that propose to develop section 804 Importation Programs in accordance with the Medicare Prescription Drug, Improvement, and Modernization Act

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of 2003, and the FDA’s implementing regulations. It is unclear the extent to which any of these policies will continue under the new administration.

On August 16, 2022 the Inflation Reduction Act of 2022 was passed, which among other things, allows CMS to negotiate prices for certain single-source drugs and biologics reimbursed under Medicare Part B and Part D, beginning in 2026 with ten high-cost drugs paid for by Medicare Part D, followed by 15 Part D drugs in 2027, 15 Part B or Part D drugs in 2028, and 20 Part B or Part D drugs in 2029 and beyond. The legislation subjects drug manufacturers to civil monetary penalties and a potential excise tax for failing to comply with the legislation by offering a price that is not equal to or less than the negotiated “maximum fair price” under the law or for taking price increases that exceed inflation. The legislation also caps Medicare beneficiaries’ annual out-of-pocket drug expenses at $2,000. The effect of the Inflation Reduction Act of 2022 on our business and the healthcare industry in general is not yet known. Further, the Trump Administration has frozen funding under the IRA, calling into question the law’s continued viability in the new administration.

Future legislation and regulation is likely to result in further changes in Medicare and other healthcare funding, perhaps significantly, and to otherwise affect the prices we may obtain for any of our product candidates for which we may obtain regulatory approval or the frequency with which any such product candidate is prescribed or used.

Any reduction in reimbursement from Medicare, Medicaid, or other government programs may result in a similar reduction in payments from private payers. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain and maintain profitability of our product and product candidates, if approved.

At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. In addition, regional health care authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug formularies and other health care programs. These measures could reduce the ultimate demand for our product candidates, if approved, and/or may constrain the prices that we are able to charge for such products.

State and federal healthcare program reform measures are ongoing, any of which could limit the amounts that we receive for our product candidates, result in reduced demand for our product candidates, if approved.

Our relationships with commercial and government customers, healthcare providers, third-party payors, and others are subject to applicable anti-kickback, fraud and abuse, transparency and other healthcare related laws, regulations and requirements, which could expose us to criminal and civil liability, exclusion from participation in federal healthcare programs, contractual damages and consequences, reputational harm, administrative burdens, and diminished profits and future earnings.

Federal and state health care fraud and abuse laws and regulations apply to the healthcare providers and third-party payors who play a primary role in the recommendation and prescription of drug products. These laws constrain the business or financial arrangements and relationships through which we would market, sell, and distribute our product candidates and will impact, among other things, any of our future sales, marketing and educational programs. There are also laws, regulations, and requirements applicable to the award and performance of federal grants and contracts.

Our business operations and any current or future arrangements with third-party payors, healthcare providers and physicians may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we develop, market, sell and distribute any drugs for which we obtain marketing approval. In the United States, these laws include, without limitation, state and federal anti-kickback, false claims, physician transparency, and patient data privacy and security laws and regulations, including but not limited to those described below.

Actions resulting in violations of these laws regulations and requirements may result in civil and criminal liability, damages and restitution, as well as exclusion from participation in federal healthcare programs, corporate integrity agreements, deferred prosecution agreements, debarment from government contracts and grants and refusal of future orders under existing contracts or contractual damages, reputational damage, and other consequences. Restrictions under applicable federal and state healthcare related laws and regulations include but are not limited to the following:

•The federal Anti-Kickback Statute, which prohibits any person from, among other things, knowingly and willfully soliciting, offering, receiving or providing anything of value, directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward, or in return for, the referral of an individual for the furnishing or arranging for the furnishing, or the purchase, lease

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or order, or arranging for or recommending purchase, lease or order, of any good or service for which payment may be made under a federal healthcare program;

•The Veterans Health Care Act, which requires manufacturers of covered drugs to offer them for sale on the Federal Supply Schedule and requires compliance with applicable federal procurement laws and regulations;

•The civil monetary penalties statute, which imposes penalties against any person or entity who, among other things, is determined to have presented or caused to be presented a claim to a federal health program that the person knows or should know is for an item or service that was not provided as claimed or is false or fraudulent;

•The false claims act, which imposes liability and significant civil penalties on any person who submits or causes to be submitted a claim to the federal government that he or she knows (or should know) is false;

•Federal transparency laws, including the federal Physician Sunshine Act (PSA), which requires manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to the Centers for Medicare and Medicaid Services, information related to payments or other “transfers of value” made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, and requires applicable manufacturers and applicable group purchasing organizations to report annually to CMS ownership and investment interests held by physicians (as defined above) and their immediate family members; and

•Analogous or similar state, federal, and foreign laws, regulations, and requirements which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third party payors, including private insurers; state and foreign laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the applicable compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers; state and foreign laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; laws, regulations, and requirements applicable to the award and performance of federal contracts and grants and state, federal and foreign laws that govern the privacy and security of health and other information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by federal law, thus complicating compliance efforts.

The laws and regulations applicable to our business are complex, changing and often subject to varying interpretations. As a result, we may not be able to adhere to all applicable laws and regulations. Any violation or alleged violation of any of these laws or regulations by us could have a material adverse effect on our business, financial condition, cash flows and results of operations. We may be a party to various lawsuits, demands, claims, qui tam suits, third-party complaints to the FDA, government investigations and audits, of which any could result in, among other things, substantial financial penalties or awards against us, reputational harm, termination of relationships or contracts related to our business, mandated refunds, substantial payments made by us, required changes to our business practices, exclusion from future participation in Medicare and other healthcare programs and possible criminal penalties.

Compliance with these healthcare laws and regulations involves substantial costs. If a company is found to be in violation of any of these laws or any other laws, regulations or other requirements, it may be subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, restitution exclusion from government funded healthcare programs, corporate integrity agreements, deferred prosecution agreements, debarment from government contracts and grants and refusal of future orders under existing contracts, contractual damages, the curtailment or restructuring of our operations and other consequences.

The availability of any federal grant funds which we may receive or for which we may apply is subject to federal appropriations law. Such grant funding may also be withdrawn or denied due to a violation of the above laws and/or for other reasons or for no reason, as was recently demonstrated when the Trump administration unilaterally halted all payments under federal grants and loans.

Risks Related to Employee Matters and Managing Our Growth

If we fail to attract and keep management and other key personnel, as well as our board members, we may be unable to develop our product candidates or otherwise implement our business plan.

Our success will depend on the retention of our directors and members of our management and leadership team including Dr. ~~Mittie Doyle, Chief Medical Officer, Dr.~~ Garry A. Neil, Chief Executive Officer and ~~Chairman of the Board, Jennifer Riley, Chief Strategy Officer, Christopher Sullivan, Chief Financial Officer, Paul Varki, Chief Legal Officer, Lisa Hegg Ph.D., Senior Vice~~ President ~~of Program Management and Corporate Infrastructure~~, ~~Colleen~~as ~~Matkowski,~~well ~~Senior~~as ~~Vice~~other ~~President~~key ~~of Global Regulatory Affairs and Quality Assurance~~scientific, ~~and Dino Miano~~clinical, ~~Senior~~regulatory ~~Vice President, CMC~~ and ~~Technical~~operational ~~Operations,~~personnel and on our ability to continue to attract and retain highly skilled and qualified personnel. We might face challenges to employee retention and attraction due to our reliance and focus on abdakibart (AVTX-009) and our limited pipeline breadth. In addition, from time to time, there may be changes to our executive management team resulting from the hiring or departure of other executives, which could disrupt our business. The loss of one or more of our executive officers or key associates could have a serious adverse effect on our business prospects, financial condition and results of operations.

37To continue to execute our business strategy, we must be able to attract and retain highly skilled personnel. We might not be able to attract or retain qualified management and other key personnel in the future due to the intense competition for qualified personnel among biotechnology, pharmaceutical and other businesses. Our reliance on abdakibart (AVTX-009) as our lead and only clinical-stage asset might make the attraction of personnel who may be concerned with employment exposure due to one principal product candidate more difficult. Additionally, our lack of experience with indications in dermatology might also make the attraction of personnel more difficult. Our industry has experienced a high rate of turnover of management personnel in recent years. As such, we could have difficulty attracting experienced personnel to our company and may be required to expend significant financial resources in our employee recruitment and retention efforts. In addition, our limited financial resources may hinder our ability to attract and retain competent personnel. Many of the other biotechnology and pharmaceutical companies with whom we compete for qualified personnel have greater financial and other resources, different risk profiles and longer histories in the industry than we have. They also may provide more diverse opportunities and better chances for career advancement. Some of these characteristics may be more appealing to high quality candidates than that which we have to offer. If we are not able to attract and retain the necessary personnel to accomplish our business objectives, we may experience constraints that will impede significantly our ability to implement our business strategy and achieve our business objectives. There can be no assurance that we will retain the services of any of our directors, officers or employees, or attract or retain additional senior managers or skilled employees when and as needed. Furthermore, we do not intend to carry key person insurance with respect to any of such individuals or, if obtained, such insurance may not be sufficient to offset the loss of any such individual.

~~Table~~We ofmay ~~Contents~~encounter difficulties in managing our growth, including the focus on abdakibart (AVTX-009) and the resources necessary for its development, and expanding our operations successfully.

~~hiring~~As we seek to advance our product candidates through clinical trials, we will need to expand our development, regulatory, manufacturing, administrative, marketing and sales capabilities or ~~departure~~contract with third parties to provide these capabilities for us. Considering our near-term focus on the progression of the LOTUS Phase 2 Trial of abdakibart (AVTX-009) in hidradenitis suppurativa, we will need to increase our research and development infrastructure. As our operations expand, we expect that we will need to manage additional relationships with various strategic partners, suppliers and other ~~executives~~third parties. Any future growth will impose significant added responsibilities on members of management including increased demands on our limited internal infrastructure and systems. Our future financial performance and our ability to commercialize our product candidates and to compete effectively will depend, ~~which~~in ~~could~~part, ~~disrupt~~on our ~~business~~ability to manage any future growth efficiently and effectively. ~~For~~To ~~example~~that end, we must be able to manage our ~~executive~~product development efforts and clinical trials effectively and hire, train and integrate additional management, ~~changed~~administrative inand ~~February~~sales ~~2022~~and marketing personnel. The ~~loss~~hiring, training and integration of ~~one~~new oremployees ~~more~~may ofbe ~~our~~more ~~executive~~difficult, ~~officers~~costly and/or ~~key~~time‑consuming ~~associates~~for ~~could~~us because we have fewer resources than a ~~serious~~larger ~~adverse~~organization. ~~effect~~We onmight not be able to accomplish these tasks, and our ~~business~~failure to accomplish any of them could prevent us from successfully developing our product candidates and growing our company or could result in operational inefficiencies, compliance failures or delays.

To continue to execute our business strategy, we must be able to attract and retain highly skilled personnel. We might not be able to attract or retain qualified management and other key personnel in the future due to the intense competition for qualified personnel among biotechnology, pharmaceutical and other businesses. Our reliance on AVTX-009 might make the attraction of personnel who may be concerned with employment exposure due to one principal product candidate more difficult. Additionally, our lack of experience with indications in dermatology might also make the attraction of personnel more difficult. Our industry has experienced a high rate of turnover of management personnel in recent years. As such, we could have difficulty attracting experienced personnel to our company and may be required to expend significant financial resources in our employee recruitment and retention efforts. In addition, our limited financial resources may hinder our ability to attract and retain competent personnel. Many of the other biotechnology and pharmaceutical companies with whom we compete for qualified personnel have greater financial and other resources, different risk profiles and longer histories in the industry than we have. They also may provide more diverse opportunities and better chances for career advancement. Some of these characteristics may be more appealing to high quality candidates than that which we have to offer. If we are not able to attract and retain the necessary personnel to accomplish our business objectives, we may experience constraints that will impede significantly our ability to implement our business strategy and achieve our business objectives. There can be no assurance that we will retain the services of any of our directors, officers or employees, or attract or retain additional senior managers or skilled employees when and as needed. Furthermore, we do not intend to carry key man insurance with respect to any of such individuals.

We may encounter difficulties in managing our growth, including the focus on AVTX-009 and the resources necessary for its development, and expanding our operations successfully.

In March 2024, we acquired AVTX-009 and AVTX-009 is currently the primary focus of our business. While we have experience with anti-inflammatory product candidates and AVTX-009 is an anti-inflammatory product candidate, we only have recently begun incorporating it into our operations. This could pose challenges to us in developing AVTX-009.

As we seek to advance our product candidates through clinical trials, we will need to expand our development, regulatory, manufacturing, administrative, marketing and sales capabilities or contract with third parties to provide these capabilities for us. Considering our near-term focus on the progression of the LOTUS Phase 2 Trial of AVTX-009 in hidradenitis suppurativa, we will need to increase our research and development infrastructure. As our operations expand, we expect that we will need to manage additional relationships with various strategic partners, suppliers and other third parties. Any future growth will impose significant added responsibilities on members of management. Our future financial performance and our ability to commercialize our product candidates and to compete effectively will depend, in part, on our ability to manage any future growth efficiently and effectively. To that end, we must be able to manage our product development efforts and clinical trials effectively and hire, train and integrate additional management, administrative and sales and marketing personnel. The hiring, training and integration of new employees may be more difficult, costly and/or time‑consuming for us because we have fewer resources than a larger organization. We might not be able to accomplish these tasks, and our failure to accomplish any of them could prevent us from successfully developing our product candidates and growing our company.

Our Chief Executive Officer has interests in the development of AVTX-006 pursuant to a royalty agreement that may conflict with interests of stockholders.

Entities affiliated with Dr. Garry Neil, our Chief Executive Officer, are parties to a Royalty Agreement with us relating to AVTX-006, a program we are no longer developing. The Royalty Agreement was entered into in July 2019 and we assumed the agreement in the Aevi Merger. The Investors will be entitled to an aggregate amount equal to a low-single digit percentage of the aggregate net sales of AVTX-006 products. At any time beginning three years after the date of the first public launch of AVTX-006 product, we may exercise, at our sole discretion, a buyout option that terminates any further obligations under the Royalty Agreement in exchange for a payment to the Investors of an aggregate of 75% of the net present value of the royalty payments. As a result of this arrangement, the interests of Dr. Neil with respect to our development programs may conflict with the interests of our stockholders. Dr. Neil could make substantial profits as a result of opportunities related to AVTX-006, which may result in him having more interest in advancing programs related to AVTX-006 as opposed to our other pipeline programs. In addition, there would be a conflict of interest if the Company determines to exercise its buyout rights under the Royalty Agreement, the exercise of which would be subject to certain approvals including by our Audit Committee and a majority of our independent directors.

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Aevi Merger. The Investors will be entitled to an aggregate amount equal to a low-single digit percentage of the aggregate net sales of AVTX-006 products. At any time beginning three years after the date of the first public launch of AVTX-006 product, we may exercise, at our sole discretion, a buyout option that terminates any further obligations under the Royalty Agreement in exchange for a payment to the Investors of an aggregate of 75% of the net present value of the royalty payments. As a result of this arrangement, the interests of Dr. Neil with respect to our development programs may conflict with the interests of our stockholders. Dr. Neil could make substantial profits as a result of opportunities related to AVTX-006, which may result in him having more interest in advancing programs related to AVTX-006 as opposed to our other pipeline programs. In addition, there would be a conflict of interest if the Company determines to exercise its buyout rights under the Royalty Agreement, the exercise of which would be subject to certain approvals including by our Audit Committee and a majority of our independent directors in accordance with applicable corporate governance requirements.

We may be subject to claims by third parties asserting that our employees or we have misappropriated their intellectual property, or claiming ownership of what we regard as our own intellectual property.

Many of our employees, including our senior management, were previously employed at universities or at other biotechnology or pharmaceutical companies, including our competitors or potential competitors. Some of these employees executed proprietary rights, non‑disclosure and non‑competition agreements in connection with such previous employment. We may be subject to claims that we or these employees have used or disclosed confidential information or intellectual property, including trade secrets or other proprietary information, of any such employee’s former employer. In addition, we may be subject to claims that former employees, collaborators, or other third parties of ours have an ownership interest in our patents or other intellectual property. While it is our policy to require our employees and contractors who may be involved in the development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in obtaining or enforcing such an agreement with each party who in fact develops intellectual property that we regard as our own. We could be subject to ownership disputes arising, for example, from conflicting obligations of consultants or others who are involved in developing our product candidates. Litigation may be necessary to defend against these claims.

38If we fail in prosecuting or defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel or sustain damages. Such intellectual property rights could be awarded to a third party, and we could be required to obtain a license from such third party to commercialize our technology or products. Such a license might not be available on commercially reasonable terms or at all. Even if we successfully prosecute or defend against such claims, litigation could result in substantial costs and distract management and key personnel from their core responsibilities.

We or the third parties upon whom we depend may be adversely affected by unforeseen global events, natural disasters, and our business continuity and disaster recovery plans may not adequately protect us from a serious disaster.

Unforeseen global events, such as macroeconomic conditions, outbreaks of violence, or geopolitical instability could adversely impact our business. Such conflicts could lead to sanctions, embargoes, supply shortages, regional instability, geopolitical shifts, cyberattacks, other retaliatory actions, and adverse effects on macroeconomic conditions, currency exchange rates, and financial markets, which could adversely impact our operations and financial results, as well as those of third parties with whom we conduct business.

Additionally, any unplanned event, such as flood, fire, explosion, earthquake, extreme weather condition, medical epidemics or pandemics, power shortage, telecommunication failure or other natural or man-made accidents or incidents that result in us being unable to fully utilize our facilities, or the manufacturing facilities of our third-party contract manufacturers, may have a material and adverse effect on our ability to operate our business and have significant negative consequences on our financial and operating conditions. Loss of access to these facilities may result in increased costs, delays in the development of our product candidates or interruption of our business operations. Natural disasters or pandemics could further disrupt our operations, and have a material and adverse effect on our business, financial condition, results of operations and prospects. If a natural disaster, power outage or other event occurred that prevented us from using all or a significant portion of our headquarters, that damaged critical infrastructure, such as our research facilities or the manufacturing facilities of our third-party contract manufacturers, or that otherwise disrupted operations, it may be difficult or, in certain cases, impossible, for us to continue our business for a substantial period of time. The disaster recovery and business continuity plans we have in place may prove inadequate in the event of a serious disaster or similar event. We may incur substantial expenses as a result of the limited nature of our disaster recovery and business continuity plans, which could have a material adverse effect on our business. As part of our risk management policy, we maintain insurance coverage at levels that we believe are appropriate for our business. However, in the event of an accident or incident at these facilities, we cannot assure our investors that the amounts of insurance will be sufficient to satisfy any damages and losses. If our facilities or the manufacturing facilities of our third-party contract manufacturers are unable to operate because of an accident or incident or for any other reason, even for a short period of time, any or all of our research and development programs may be harmed. Any business interruption may have a material and adverse effect on our business, financial condition, results of operations and prospects.

Our employees, independent contractors, consultants, commercial partners and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements.

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~~non‑disclosure~~We ~~and~~are ~~non‑competition~~exposed ~~agreements~~to inthe ~~connection~~risk ~~with~~of ~~such~~employee ~~previous~~fraud ~~employment.~~or Weother ~~may~~illegal beactivity ~~subject~~by toour ~~claims~~employees, ~~that~~independent wecontractors, orconsultants, ~~these~~commercial ~~employees~~partners ~~have~~and ~~used~~vendors. orMisconduct ~~disclosed~~by ~~confidential~~these ~~information~~parties orcould ~~intellectual~~include ~~property~~intentional, ~~including~~reckless ~~trade~~and/or ~~secrets~~negligent orconduct ~~other~~that ~~proprietary~~fails ~~information,~~to comply with the laws of ~~any~~the ~~such~~FDA ~~employee’s~~and ~~former~~other ~~employer.~~similar Inforeign ~~addition~~regulatory authorities, weprovide ~~may~~true, becomplete ~~subject~~and accurate information to ~~claims~~the ~~that~~FDA ~~former~~and ~~employees,~~other ~~collaborators,~~similar orforeign ~~other~~regulatory ~~third~~authorities, ~~parties~~comply ofwith ~~ours~~manufacturing standards we have anestablished, ~~ownership~~comply ~~interest~~with healthcare fraud and abuse laws in ~~our~~the ~~patents~~U.S. and similar foreign fraudulent misconduct laws or ~~other~~report ~~intellectual~~financial ~~property.~~information ~~While~~or itdata isaccurately ~~our~~or ~~policy~~to disclose unauthorized activities to ~~require~~us. If we obtain FDA approval of any of our ~~employees~~product candidates and ~~contractors~~begin ~~who~~commercializing ~~may~~those beproducts ~~involved~~ in the ~~development~~U.S., ofour ~~intellectual~~potential ~~property~~exposure tounder ~~execute~~such ~~agreements~~laws ~~assigning~~will increase significantly, and our costs associated with compliance with such ~~intellectual~~laws ~~property~~are also likely to ~~us,~~increase. weThese laws may beimpact, ~~unsuccessful~~among inother ~~obtaining~~things, orour ~~enforcing~~current ~~such~~activities anwith ~~agreement~~principal ~~with~~investigators ~~each~~and ~~party~~research ~~who~~patients, inas ~~fact~~well ~~develops~~as ~~intellectual~~proposed ~~property~~and future sales, marketing and education programs. It is possible that wegovernmental ~~regard~~and asenforcement authorities will conclude that our ~~own.~~business Wepractices ~~could~~may benot ~~subject~~comply towith ~~ownership~~current ~~disputes~~or ~~arising~~future statutes, ~~for~~regulations ~~example,~~or ~~from~~case ~~conflicting~~law ~~obligations~~interpreting ofapplicable ~~consultants~~fraud and abuse or ~~others~~other ~~who~~healthcare laws and regulations. If any such actions are ~~involved~~instituted against us, and we are not successful in ~~developing~~defending ourselves or asserting our ~~product~~rights, ~~candidates.~~those ~~Litigation~~actions ~~may~~could behave ~~necessary~~a tosignificant ~~defend~~impact ~~against~~on ~~these~~our ~~claims~~business.

IfRisks weRelated ~~fail in prosecuting or defending any such claims, in addition~~ to paying monetary damages, we may lose valuable intellectual property rights or personnel or sustain damages. Such intellectual property rights could be awarded to a third party, and we could be required to obtain a license from such third party to commercialize our ~~technology or products. Such a license might not be available on commercially reasonable terms or at all. Even if we successfully prosecute or defend against such claims~~Stock, ~~litigation~~Charter ~~could result in substantial costs~~ and ~~distract management.~~Bylaws

~~Risks~~The ~~Related~~price of our common stock could be subject to rapid and substantial volatility. Such volatility, including any stock run-ups, may be unrelated to our ~~Stock~~actual or expected operating performance and financial condition or prospects, making it difficult for prospective investors to assess the rapidly changing value of our common stock. Volatility in our common stock price may subject us to securities litigation or regulatory scrutiny.

The market for our common stock may have, when compared to seasoned issuers, significant price volatility and we expect that the price of our shares of common stock ~~could~~may continue to be ~~subject~~more tovolatile ~~rapid~~than ~~and~~that ~~substantial~~of ~~volatility~~a seasoned issuer for the indefinite future. ~~Such~~As ~~volatility~~a relatively small-capitalization company with a relatively small public float, ~~including~~we ~~any~~may ~~stock~~experience greater share price volatility, extreme price run-ups, ~~may~~lower betrading ~~unrelated~~volume, toand less liquidity than large-capitalization companies. In particular, our ~~actual~~common orstock ~~expected~~may ~~operating~~be ~~performance~~subject ~~and~~to ~~financial~~rapid ~~condition~~and orsubstantial ~~prospects~~price volatility, ~~making~~low itvolumes ~~difficult~~of ~~for~~trades, ~~prospective~~heightened ~~investors~~price sensitivity to ~~assess~~individual ~~the~~transactions, ~~rapidly~~and ~~changing~~large ~~value~~spreads ofin ~~our~~bid ~~common~~and ~~stock~~ask prices. ~~Volatility~~The inmarket price for our common stock ~~price~~ may ~~subject~~be usinfluenced toby ~~securities~~many ~~litigation.~~factors, including:

~~The~~•Results ~~market for our common stock may have, when compared to seasoned issuers, significant price volatility and we expect that the price~~ of our ~~shares~~clinical ~~of common stock may continue to be more volatile than that of a seasoned issuer for the indefinite future~~trials. AsIncluding atopline ~~relatively~~or ~~small-capitalization~~preliminary ~~company~~data ~~with a relatively small public float, we may experience greater share price volatility, extreme price run-ups, lower trading volume,~~ and ~~less~~preclinical ~~liquidity than large-capitalization companies. In particular~~studies, ~~our common stock may be subject to rapid~~ and ~~substantial~~the ~~price~~results ~~volatility,~~of ~~low~~trials ~~volumes~~ of ~~trades, and large spreads in bid and ask prices. Such volatility, including any stock run-ups, may be unrelated to~~ our ~~actual~~competitors or ~~expected~~those ~~operating~~of ~~performance~~other ~~and~~companies ~~financial~~in ~~condition or prospects, making it difficult for prospective investors to assess the rapidly changing value of~~ our ~~common~~market ~~stock.~~sector;

In•Our ~~addition,~~ability if the trading volumes of our common stock are low, persons buying or selling in relatively small quantities may easily influence the price of our common stock. This low volume of trades could also cause the price of our common stock to ~~fluctuate~~enroll ~~greatly,~~patients ~~with large percentage changes~~ in ~~price occurring in any trading day session. Holders of~~ our ~~common~~future ~~stock~~clinical ~~may~~trials; also not be able to readily liquidate their investment or may be forced to sell at depressed prices due to low volume trading. Broad market fluctuations and general economic and political conditions may also adversely affect the market price of our common stock. As a result of this volatility, investors may experience losses on their investment in our common stock. A decline in the market price of our common stock also could adversely affect our ability to issue additional common stock or other securities and our ability to obtain additional financing in the future.

To•Our ~~the~~ability ~~extent~~to ~~that~~obtain aand ~~secondary~~maintain ~~market~~regulatory ~~for~~approval ~~the~~of ~~Series~~any Cof ~~non-voting~~our ~~convertible~~current ~~preferred stock~~ or ~~the~~future ~~warrants~~product ~~develops,~~candidates weor ~~believe~~additional ~~that~~indications ~~the~~thereof, ~~market~~including ~~price of~~ the ~~Series~~timing, Cscope ~~non-voting convertible preferred stock~~ and ~~the~~conditions ~~warrants would be significantly affected by the market price~~ of ~~our~~such ~~common~~approvals ~~stock.~~or Nolimitations ~~assurance~~to ~~can~~specific belabel ~~given~~indications ~~that an active market in our Series C non-voting convertible preferred stock~~ or ~~the~~patient ~~warrants~~populations ~~will~~for ~~develop~~its ~~or be sustained. If an active market does not develop~~use, ~~holders~~or ofchanges ~~our Series C non-voting convertible preferred stock~~ or ~~the~~delays ~~warrants~~in ~~may be unable to readily sell~~ the ~~securities~~regulatory ~~they~~review ~~hold~~process; ~~or may not be able to sell their securities at all.~~

In•Regulatory ~~addition,~~or inlegal ~~the~~developments ~~past, plaintiffs have often initiated securities class action litigation against a company following periods of volatility~~ in the ~~market~~United ~~price~~States ~~of its securities. We may, in the future, be the target of similar litigation. Securities litigation could result in substantial costs~~ and ~~liabilities~~foreign tocountries; ~~the Company and could divert our management’s attention and resources.~~

~~Conversion~~•Changes ofin the ~~outstanding~~structure ~~shares~~ of ~~our~~healthcare ~~preferred~~payment ~~stock~~systems; ~~will dilute the percentage ownership of the holders of our common stock.~~

•The ~~non-voting~~success ~~convertible~~or ~~preferred~~failure ~~stock outstanding at December 31, 2024 is convertible into an aggregate~~ of ~~approximately 24.9 million shares of~~ our ~~common~~efforts ~~stock, subject~~ to ~~certain~~develop, ~~beneficial~~acquire, ~~ownership~~or ~~limitations.~~license ~~The~~any ~~conversion~~ of ~~those shares will cause the percentage of voting ownership of~~ our ~~existing~~current ~~stockholders~~or tofuture beproduct ~~significantly~~candidates; ~~diluted, although the economic interest will not change because the value of shares issuable upon conversion was reflected in the purchase price of the preferred stock.~~

39•Innovations, clinical trial results, product approvals and other developments regarding our competitors;

•Announcements by us or our competitors of significant acquisitions, strategic partnerships, joint ventures, or capital commitments;

•Manufacturing, supply, or distribution delays or shortages;

•Any changes to our relationship with any manufacturers, suppliers, collaborators or other strategic partners;

•Achievement of expected product sales and profitability or failure to achieve anticipated milestones;

•Variations in our financial results or development timelines or those of companies that are perceived to be similar to us, including variations from expectations of securities analysts or investors;

•Market conditions in the biopharmaceutical sector and issuance of securities analysts’ reports or recommendations;

•Trading volume of our common stock;

•An inability to obtain additional funding on acceptable terms, or at all;

•Sales of our stock by us, our insiders or our stockholders, as well as the anticipation of lock-up releases or expiration of market stand-off or lock-up agreements;

•General economic, industry, geopolitical and market conditions, such as military conflict or war, inflation and financial institution instability, or pandemic or epidemic disease outbreaks, many of which are beyond our control;

•Additions or departures of senior management, directors or key personnel;

•Intellectual property, product liability or other litigation against us or our inability to enforce our intellectual property;

•Changes in our capital structure, such as future issuances of securities and the incurrence of additional debt; and

•Changes in accounting standards, policies, guidelines, interpretations or principles or their application to our business.

The realization of any of the above risks or any of a broad range of other risks, including those described in this “Risk Factors” section, could have a dramatic and adverse impact on the market price of our common stock. Such volatility, including any stock run-ups, may be unrelated to our actual or expected operating performance and financial condition or prospects, making it difficult for prospective investors to assess the rapidly changing value of our common stock. As a result of this volatility, investors may experience losses on their investment in our common stock. A decline in the market price of our common stock also could adversely affect our

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ability to issue additional common stock or other securities and our ability to obtain additional financing in the future on favorable terms.

In addition, if the trading volumes of our common stock are low, persons buying or selling in relatively small quantities may easily influence the price of our common stock over short or extended periods of time. This low volume of trades could also cause the price of our common stock to fluctuate greatly, with large percentage changes in price occurring in any trading day session. Holders of our common stock may also not be able to readily liquidate their investment or may be forced to sell at depressed prices due to low volume trading. No assurance can be given that a higher volume active market in our common stock will develop or be sustained. If a higher volume active market does not develop, holders of our common stock may be unable to readily sell the shares they hold or may not be able to sell their shares at all.

To the extent that a secondary market for the Series C non-voting convertible preferred stock or the warrants develops, we believe that the market price of the Series C non-voting convertible preferred stock and the warrants would be significantly affected by the market price of our common stock and overall market conditions. No assurance can be given that an active market in our Series C non-voting convertible preferred stock or the warrants will develop or be sustained. If an active market does not develop, holders of our Series C non-voting convertible preferred stock or the warrants may be unable to readily sell the securities they hold or may not be able to sell their securities at all at prices they consider acceptable.

In addition, in the past, plaintiffs have often initiated securities class action litigation against a company following periods of volatility in the market price of its securities. We may, in the future, be the target of similar litigation regardless of the merits of such claims. Securities litigation could result in substantial costs and liabilities to the Company and could divert our management’s attention and resources.

Conversion of the outstanding shares of our preferred stock will dilute the percentage ownership of the holders of our common stock.

The non-voting convertible preferred stock outstanding at December 31, 2025 is convertible into an aggregate of approximately 18.8 million shares of our common stock, subject to certain beneficial ownership limitations. The conversion of those shares will cause the percentage of voting ownership of our existing stockholders to be significantly diluted, even though the economic interest will not change because the value of shares issuable upon conversion was reflected in the purchase price of the preferred stock and such dilution may adversely affect the market price of our common stock.

Future sales and issuances of shares of our common stock or rights to purchase common stock, including pursuant to our equity incentive plans, could result in additional dilution of the percentage ownership of our stockholders and could cause our stock price to fall.

We expect to need to raise additional capital in the future to continue our planned operations, including conducting clinical trials, commercialization efforts, and expanded research and development activities. To raise capital, we expect to sell common stock, convertible securities or other equity securities in one or more transactions at prices and in a manner we determine from time to time. If we sell common stock, convertible securities or other equity securities, investors may be materially diluted by such sales and new investors could gain rights, preferences and privileges senior to our existing stockholders.

We are authorized to grant equity awards, including stock grants and stock options, to our employees, directors and consultants. As of December 31, ~~2024~~2025, there were 1327,~~301,050~~806 shares available for future issuance under the Fourth Amended and Restated 2016 Equity Incentive Plan (the “2016 Fourth Amended Plan”). During the term of the 2016 Fourth Amended Plan, the share reserve will automatically increase on the first trading day in January of each calendar year, by an amount equal to 5% of the total number of outstanding shares of our common stock and Series C Preferred Stock (determined on an as-converted stock basis) plus all outstanding prefunded warrants to acquire shares of common stock (if any) as of December 31st of the preceding calendar year. On January 1, ~~2025~~2026, under these terms, an additional 1,~~768~~865,~~393~~256 shares were made available for issuance. In addition, as of December 31, ~~2024~~2025, there were ~~226~~533,~~577~~159 shares available for future issuance under the 2016 Employee Stock Purchase Plan (the “ESPP”). On January 1 of each calendar year, the aggregate number of shares that may be issued under the ESPP automatically increases by a number equal to 1% of the Company’s outstanding shares of our common stock and Series C Preferred Stock (determined on an as-converted basis) plus all outstanding prefunded warrants to acquire shares of common stock (if any), as of December 31st of the preceding calendar year. On January 1, ~~2025~~2026, under these terms, the number of shares available for issuance under the ESPP increased by ~~353~~373,~~679~~051 shares. Future issuances, as well as the possibility of future issuances, under the 2016 Fourth Amended Plan or the ESPP or other equity incentive plans could cause the market price of our common stock to decrease.

If we are not able to comply with the applicable continued listing requirements or standards of The Nasdaq Stock Market, Nasdaq could delist our common stock.

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Our common stock is currently listed on The Nasdaq Stock Market. In order to maintain that listing, we must satisfy minimum financial and other continued listing requirements and standards, including those regarding director independence and independent committee requirements, minimum stockholders’ equity, a minimum closing bid price of $1.00 per share, and certain corporate governance requirements. There can be no assurances that we will be able to comply with the applicable listing standards.

In the event that our common stock is delisted from The Nasdaq Stock Market and is not eligible for quotation or listing on another market or exchange, trading of our common stock could be conducted only in the over‑the‑counter market or on an electronic bulletin board established for unlisted securities such as the Pink Sheets or the OTC Bulletin Board. In such event, it could become more difficult to dispose of, or obtain accurate price quotations for, our common stock, and there would likely also be a reduction in our coverage by securities analysts and the news media, which could cause the price of our common stock to decline further. Also, it may be difficult for us to raise additional capital if we are not listed on an exchange on a timely basis or at all.

A delisting would also likely have a negative effect on the price of our common stock and would impair your ability to sell or purchase our common stock when you wish to do so. In the event of a delisting, we may take actions to restore our compliance with The Nasdaq Stock Market’s listing requirements, but we can provide no assurance that any such action taken by us would allow our common stock to become listed again, stabilize the market price or improve the liquidity of our common stock, prevent our common stock from dropping below The Nasdaq Stock Market minimum bid price requirement or prevent non‑compliance with The Nasdaq Stock Market’s listing requirements.

Low trading volume of our common stock on the Nasdaq Capital Market may increase price volatility.

Our common stock may be subject to price volatility, low trading volume and large spreads in bid and ask prices quoted by market makers. Low trading means that trading in relatively small quantities may easily influence prices of our common stock. Low trading volume could also cause the price of our stock to fluctuate greatly, with large percentage changes in price occurring in any trading day session. Holders of our common stock may also not be able to readily liquidate their investment or may be forced to sell at depressed prices due to low trading volume. If large spreads between the bid and ask prices of our common stock exist at the time of a purchase, the stock would have to appreciate substantially on a relative percentage basis for an investor to recoup their investment. No assurance can be given that a higher volume active market in our common stock will develop or be sustained. If a higher volume active market does not develop, holders of our common stock may be unable to readily sell the shares they hold or may not be able to sell their shares at all.

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Sales of a significant number of shares of our common stock in the public markets, or the perception that such sales could occur, could depress the market price of our common stock.

We expect to need to raise capital to fund our operations in the future and may do so through the sale of common stock or securities convertible into shares of common stock in registered offerings, at-the-market (“ATM”) programs, private placements, or other financings. Sales of a substantial number of shares of our common stock in the public markets could depress the market price of our common stock and impair our ability to raise capital through the sale of additional equity securities on favorable terms, or at all. Sales of shares of common stock or common stock equivalents also may be offered in private placements, and these sales also may have a depressive effect on the market for our shares of common stock due to the delayed issuance of these shares into the public market. Further, as additional shares of our common stock become available for resale in the public market resale registration and subsequent selling, and otherwise, the supply of our common stock will increase, which could decrease its price. We cannot predict the effect that future sales of our common stock or common stock ~~or common stock~~ equivalents would have on the market price of our common stock.

The non-voting convertible preferred stock outstanding at December 31, ~~2024~~2025 is convertible into an aggregate of approximately 2418.98 million shares of our common stock, subject to certain beneficial ownership limitations and other terms and conditions. The sale of a substantial number of shares of our securities in the public market, or the perception that such sales may occur, could adversely affect the price of our common stock on the Nasdaq Capital Market and could increase volatility and reduce liquidity. We cannot predict the effect, if any, that market sales of those shares of common stock or the availability of those shares of common stock for sale will have on the market price of our common stock or on investor perception regarding dilution.

In addition, in the future, we may also issue shares of our common stock in connection with investments or acquisitions or pursuant to strategic collaborations, licensing transactions, or other business development activities. The amount of shares of our common stock issued in connection with an investment or acquisition could substantially increase our shares of common stock outstanding, which could adversely affect the price of our common stock on the Nasdaq Capital Market.

Unstable global economic and geopolitical conditions may have serious adverse consequences on our business, financial condition, stock price and results of operations.

As widely reported, global credit and financial markets have experienced extreme volatility and disruptions in the past several years, including severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, increases in unemployment rates and uncertainty about economic stability. The financial markets and the global economy may also be adversely affected by the potential for significant changes in U.S. policies or regulatory environment given the new administration, military conflict, including the ongoing conflicts between Russia and Ukraine, and in the Middle East, terrorism, or other geopolitical events. Sanctions imposed by the United States and other countries in response to such conflicts, including in Ukraine, may also continue to adversely impact the financial markets and the global economy, and any economic countermeasures by the affected countries or others could exacerbate market and economic instability. There can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur. Our general business strategy may be adversely affected by any such economic downturn, volatile business environment or continued unpredictable and unstable market conditions. If the current equity and credit markets deteriorate, or do not improve, it may make any necessary debt or equity financing more difficult, more costly, and more dilutive. Furthermore, our stock price may decline due in part to the volatility of the stock market and the general economic downturn and sector-specific rotations away from small-cap biotechnology companies. Failure to secure any necessary financing in a timely manner and on favorable terms could have a material adverse effect on our growth strategy, financial performance and stock price and could require us to delay, scale back or discontinue the development and commercialization of one or

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more of our product candidates or delay our pursuit of potential in-licenses or acquisitions. In addition, there is a risk that one or more of our current service providers, manufacturers and other partners may not survive these difficult economic times, may reduce capacity, prioritize other customers, or increase prices which could directly affect our ability to attain our operating goals on schedule and on budget.

Separately, changes in U.S. federal policy that affect the geopolitical landscape could give rise to circumstances outside our control that could have negative impacts on our business operations. In 2025, the United States imposed significant tariffs on imports from other countries, including a baseline tariff of 10% on imports into the United States and higher tariffs on multiple designated countries (including the EU Member States, China, Canada, and Mexico), such as “reciprocal” tariffs at varying rates. Such tariffs have prompted retaliatory measures from several countries, which may further escalate. On April 9, 2025, the U.S. announced a temporary pause on its tariffs applicable to many countries, while increasing the tariffs applicable to imports from China. In addition, the current U.S. administration has expressed an intent to impose tariffs on pharmaceutical imports, with the stated policy objective of reshoring pharmaceutical manufacturing to the United States. Among other means, such tariffs may be imposed by the United States under Section 232 of the Trade Expansion Act of 1962, as amended, pursuant to which the U.S. Department of Commerce recently initiated an investigation to determine the effects of importing pharmaceuticals and pharmaceutical ingredients on national security. The new U.S. administration has threatened to continue to broadly impose tariffs, which could lead to corresponding punitive actions by the countries with which the U.S. trades. Historically, tariffs have led to increased trade and political tensions, between not only the U.S. and China, but also between the U.S. and other countries in the international community. In response to tariffs, other countries have implemented retaliatory tariffs on U.S. goods. Political tensions as a result of trade policies could reduce trade volume, investment, technological exchange and other economic activities between major international economies, resulting in a material adverse effect on global economic conditions and the stability of global financial markets. Any changes in political, trade, regulatory, and economic conditions, including U.S. trade policies, could have a material adverse effect on our financial condition or results of operations including through higher input costs, delays in logistics, or reduced availability of materials and services used by our third-party manufacturers and clinical trial vendors. We are continuing to monitor global capital markets and assessing the potential impact of these factors on our business.

Our business is subject to risks arising from pandemics and epidemic diseases.

Public health crises such as pandemics or similar outbreaks could adversely impact our business and the operations of the third parties on which we rely. Infectious diseases may also affect research activities and employees of third-party CROs located in affected geographies that we rely upon to carry out our clinical trials. In addition, the patient populations that our lead and other core product candidates target may be particularly susceptible to infectious diseases or its variants, which may make it more difficult for us to identify patients able to enroll in our clinical trials and may impact the ability of enrolled patients to complete any such trials. Any negative impact that any future infectious disease spread has to patient enrollment or treatment, or the execution of our product candidates could cause costly delays to clinical trial activities, which could adversely affect our ability to obtain regulatory approval for and to commercialize our product candidates, increase our operating expenses, and have a material adverse effect on our financial results and liquidity.

Additionally, timely enrollment in clinical trials is dependent upon clinical trial sites which will be adversely affected by global health matters, such as pandemics. Some factors from any public health crisis that may delay or otherwise adversely affect enrollment in the clinical trials of our product candidates, as well as our business generally, include:

•The potential diversion of healthcare resources away from the conduct of clinical trials to focus on pandemic concerns;

•Limitations on travel that could interrupt key trial and business activities;

•The potential negative effect on the operations of our third-party manufacturers and the supply chain for our product candidates;

•Interruptions in global shipping affecting the transport of clinical trial materials; and

•Business disruptions caused by potential workplace, laboratory and office closures or workforce unavailability.

Any future pandemic or epidemic disease outbreak could also potentially further affect the business of the FDA or other foreign regulatory authorities, which could result in delays in meetings related to our planned clinical trials, as well as have an adverse impact on global economic conditions which could have an adverse effect on our business and financial condition, including impairing our ability to raise capital when needed or causing capital to be less available to small-cap biotechnology companies.

If securities or industry analysts do not publish research or publish inaccurate or unfavorable research about our business, our securities prices and trading volume could decline.

The trading market for our securities depends in part on the research and reports that securities or industry analysts publish about us or our business. We currently have limited, and might not sustain, research coverage by securities and industry analysts. If we do not sustain coverage of ourselves, the trading price for our securities would be negatively impacted and volatility could increase. If the securities and industry analysts are unable to predict accurately the cost of advancing our pipeline, that could result in our reported costs being different than expectations, which could negatively affect our stock price. If one or more of the analysts who covers us downgrades our securities or publishes inaccurate or unfavorable research about our business, our securities prices would likely decline. If one or more of these analysts ceases coverage of us or fails to publish reports on us regularly, demand for our securities could decrease, which could cause our securities prices and trading volume to decline.

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downgrades our securities or publishes inaccurate or unfavorable research about our business, our securities prices would likely decline. If one or more of these analysts ceases coverage of us or fails to publish reports on us regularly, demand for our securities could decrease, which could cause our securities prices and trading volume to decline and impair our ability to access the capital markets.

Because we do not intend to declare cash dividends on our shares of common stock in the foreseeable future, stockholders must rely on appreciation of the value of our common stock for any return on their investment.

We have never declared or paid cash dividends on our common stock. The continued operation and expansion of our business will require substantial funding. We currently intend to retain all of our future earnings, if any, to finance the growth and development of our business. Accordingly, we do not anticipate that we will pay any cash dividends on shares of our common stock for the foreseeable future. Consequently, stockholders must rely on sales of their common stock after price appreciation, which may never occur, as the only way to realize any gains on their investment. Any determination to pay dividends in the future will be at the discretion of our board of directors and will depend upon results of operations, financial condition, contractual restrictions, restrictions imposed by applicable law and other factors our board of directors deems relevant.

Changes in tax law may adversely affect us or our investors.

The rules dealing with U.S. federal, state and local and non-U.S. taxation are constantly under review by persons involved in the legislative process and by the Internal Revenue Service (the “IRS”), the U.S. Treasury Department and other taxing authorities. For example, the One Big Beautiful Bill Act (the “OBBBA”), was signed into law on July 4, 2025 and made significant changes to the U.S. federal tax law. Changes to tax laws (which changes may have retroactive application) could adversely affect us or holders of our common stock. These changes could subject us to additional income-based taxes and non-income taxes (such as payroll, sales, use, value-added, net worth, property, and goods and services taxes), which in turn could materially affect our financial position and results of operations. For example, under Section 174 of the Internal Revenue Code of 1986, as amended (the “IRC”), in taxable years beginning after December 31, 2021, expenses that are incurred for research and development performed outside the U.S. will be capitalized and amortized, which may have an adverse effect on our cash flow. The OBBBA provides that for taxable years beginning after December 31, 2024, expenses that are incurred for research and development performed in the U.S. may, at the taxpayer’s election, be immediately deducted or capitalized and amortized. In addition, the OBBBA provides that for taxable years beginning after December 31, 2021 and before January 1, 2025, certain eligible taxpayers generally may elect to retroactively deduct expenses for research and development performed in the U.S. in such taxable years by filing amended tax returns for such taxable years, and all other taxpayers that are not eligible to make such an election and that amortized expenses for research and development performed in the U.S. in such taxable years generally may elect to accelerate and deduct the remaining unamortized amounts of such research and development expenses (i) in the first taxable year beginning after December 31, 2024, or (ii) ratably over the two-taxable year period beginning with the first taxable year beginning after December 31, 2024. Additionally, new, changed, modified, or newly interpreted or applied tax laws could increase our customers’ and our compliance, operating and other costs, as well as the costs of our products. In recent years, many such changes have been made and changes are likely to continue to occur in the future. It cannot be predicted whether, when, in what form, or with what effective dates, new tax laws may be enacted, or regulations and rulings may be promulgated or issued under existing or new tax laws, which could result in an increase in our or our stockholders’ tax liability or require changes in the manner in which we operate in order to minimize or mitigate any adverse effects of changes in tax law or in the interpretation thereof and could adversely affect the market price of our common stock.

As we expand the scale of our business activities, any changes in the U.S. and non-U.S. taxation of such activities may increase our effective tax rate and harm our business, financial condition and results of operations. You are urged to consult your tax advisor regarding the implications of potential changes in tax laws on an investment in our common stock.

We incur increased costs and obligations as a result of being a public company.

As a public company, we are required to comply with certain additional corporate governance and financial reporting practices and policies and are subject to heightened public-company scrutiny, including by regulators, stock exchanges, investors, and proxy advisory firm. As a result, due to compliance requirements of the Exchange Act, the Sarbanes-Oxley Act, the Dodd-Frank Wall Street Reform and Protection Act, the listing requirements of the Nasdaq, and other applicable securities rules and regulations, we have and will continue to incur significant legal, accounting, and other expenses. and may be required to implement additional policies, procedures, and internal controls. The Exchange Act requires, among other things, that we file annual, quarterly, and current reports with respect to our business and operating results with the SEC. We are also required to ensure that we have the ability to prepare financial statements and other disclosures that are fully compliant with all SEC reporting requirements on a timely basis and to maintain effective disclosure controls and procedures and internal control over financial reporting. Compliance with these rules and regulations has increased and may continue to increase our legal and financial compliance costs, make some activities more difficult, time-consuming, or costly, and increase demand on our systems and resources.

~~Our~~In ~~amended~~addition, ~~and restated certificate of incorporation provides that unless~~ we ~~consent~~may inbe ~~writing~~required to ~~the~~incur ~~selection~~significant ofexpenses anand ~~alternative~~devote ~~forum,~~substantial ~~the~~management ~~Court~~effort ofto ~~Chancery~~maintain ofappropriate ~~the~~public ~~State~~company ofgovernance ~~Delaware~~practices, ~~will~~including beboard ~~the sole~~ and ~~exclusive~~committee ~~forum for substantially all disputes between us and our stockholders~~composition, ~~which~~executive ~~could~~compensation ~~limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors~~practices, ~~officers~~stockholder ~~or employees.~~

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engagement, and compliance with evolving SEC and Nasdaq rules. If we fail to maintain adequate processes and resources to satisfy our reporting obligations, or if our reporting is delayed, incomplete, or inaccurate, we could be subject to regulatory investigations or enforcement actions, securities litigation, reputational harm, and a decline in the trading price of our common stock.

Our amended and restated certificate of incorporation provides that unless we consent in writing to the selection of an alternative forum, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for substantially all disputes between us and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees.

Our amended and restated certificate of incorporation provides that, unless we consent in writing to the selection of an alternative forum, the Court of Chancery of the State of Delaware will be the exclusive forum for any derivative action or proceeding brought on our behalf; any action asserting a breach of fiduciary duty; any action asserting a claim against us arising pursuant to the DGCL, our amended and restated certificate of incorporation or our bylaws; or any action asserting a claim against us that is governed by the internal affairs doctrine.

Any person or entity purchasing or otherwise acquiring any interest in any of our securities will be deemed to have notice of and consented to these provisions. These exclusive‑forum provisions may limit a stockholder’s ability to bring a claim in a judicial forum of its choosing for disputes with us or our directors, officers or other employees, which may discourage lawsuits against us and our directors, officers and other employees and may result in increased costs to a stockholder to bring a claim.

If a court were to find the choice of forum provision contained in our amended and restated certificate of incorporation to be inapplicable or unenforceable in an action, we may incur additional costs associated with resolving such action in other jurisdictions, which could harm our business, results of operations, and financial condition. Even if we are successful in defending against these claims, litigation could result in substantial costs and be a distraction to management and other employees.

This choice of forum provision does not preclude or contract the scope of exclusive federal or concurrent jurisdiction for any actions brought under the Securities Act or the Exchange Act. Accordingly, our exclusive forum provision will not relieve us of our duties to comply with the federal securities laws and the rules and regulations thereunder, and our stockholders will not be deemed to have waived our compliance with these laws, rules and regulations.

Some provisions of our charter documents and Delaware law may have anti‑takeover effects that could discourage an acquisition of us by others, even if an acquisition would benefit our stockholders and may prevent attempts by our stockholders to replace or remove our current management.

Provisions in our amended and restated certificate of incorporation and third amended and restated bylaws, as well as provisions of Delaware law, could make it more difficult for a third party to acquire us or increase the cost of acquiring us, even if doing so would benefit our stockholders, or remove our current management. These provisions include:

•Authorizing the issuance of “blank check” preferred stock, the terms of which we may establish and shares of which we may issue without stockholder approval;

•Prohibiting cumulative voting in the election of directors, which would otherwise allow for less than a majority of stockholders to elect director candidates;

•Prohibiting stockholder action by written consent, thereby requiring all stockholder actions to be taken at a meeting of our stockholders;

•Eliminating the ability of stockholders to call a special meeting of stockholders; and

•Establishing advance notice requirements for nominations for election to the board of directors or for proposing matters that can be acted upon at stockholder meetings.

These provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders to replace members of our board of directors, who are responsible for appointing the members of our management. Because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the DGCL which may discourage, delay or prevent someone from acquiring us or merging with us whether or not it is desired by or beneficial to our stockholders. Under the DGCL, a corporation may not, in general, engage in a business combination with any holder of 15% or more of its capital stock unless the holder has held the stock for three years or, among other things, the board of directors has approved the transaction or the transaction otherwise satisfies statutory exceptions. Any provision of our amended and restated certificate of incorporation or third amended and restated bylaws or Delaware law that has the effect of delaying or deterring a change of control could limit the opportunity for our stockholders to receive a premium for their shares of our common stock, and could also affect the price that some investors are willing to pay for our securities and the marketability of our common stock.

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The rights associated with our outstanding Series D and Series E preferred stock may concentrate control of our Board of Directors and could adversely affect the interests of holders of our common stock.

We have issued one share of Series D Preferred Stock and one share of Series E Preferred Stock to two institutional investors that each carry the right to designate one member of our Board of Directors. For so long as the Series D and Series E preferred stock remains outstanding, the Series D holder and the Series E holder shall also have the right to appoint one non-voting observer to the Board of Directors. This preferred stock was issued solely for governance purposes and does not represent a material economic interest in our Company. As a result, the holder of this preferred stock is able to exercise significant influence over the composition of our Board of Directors that is disproportionate to its economic ownership of our equity and, in turn, may influence our strategic direction and governance practices.

The directors designated by the holders of this preferred stock may have interests that differ from, or conflict with, our interests or our common stockholders generally. The presence of a director appointed by a particular investor could affect deliberations of the Board of Directors and decision-making, including with respect to strategic transactions, financings, executive compensation, or other matters requiring Board of Directors approval. In addition, this governance structure could discourage or delay a change of control of our Company or other transactions that our common stockholders may otherwise view as favorable by affecting third-party perceptions of governance, decision-making dynamics, or deal certainty.

The existence of this preferred stock and its associated director designation rights may also be viewed negatively by investors or proxy advisory firms, could reduce the perceived independence of our Board of Directors, and may adversely affect the market price of our common stock. The rights associated with our outstanding Series D and Series E preferred stock to designate a director may impair Nasdaq board independence and discourage or delay a change of control, which could adversely affect holders of our common stock. If the preferred stockholders continues to hold these rights for an extended period, holders of our common stock may have limited ability to influence Board of Directors composition through traditional stockholder voting mechanisms.

General Risk Factors

Our business and operations could suffer in the event of ~~computer~~information ~~system~~technology systems and infrastructure failures, cyber-attacks or deficiencies in our cyber-security.

In the ordinary course of our business, we collect and store sensitive data, including intellectual property, research data, our proprietary business information and that of our suppliers, technical information about our product candidates, clinical trial plans and employee records. Similarly, our third-party providers (including CROs, CMOs, cloud service providers, collaboration and productivity platforms, payroll and HR providers, and other vendors)possess certain of our sensitive data and confidential information. The secure maintenance of this information is critical to our operations and business strategy. Despite the implementation of security measures, our internal information technology systems and infrastructure, and those of third parties on which we rely, are vulnerable to damage from computer viruses, malware, ransomware, cyber fraud, natural disasters, terrorism, war, telecommunication and electrical failures, cyber-attacks or cyber-intrusions over the Internet, including, denial-of-service attacks, business email compromises, social engineering (including phishing attacks), theft, fraud and subsequent misuse of employee credentials, as well as wrongful conduct by persons inside our organization, insiders at third-party service providers, or persons with access to systems inside our organization. The risk of a cybersecurity incident, data breach or other disruption, including by computer hackers, foreign governments, and cyber terrorists, has generally increased as the number, intensity and sophistication of attempted attacks and intrusions from around the world have increased and as remote work, cloud-based services, and vendor-connected systems expand our potential attack surface. These attacks and activity are also being facilitated or enhanced by evolving technologies, including artificial intelligence.

42Although we have data security measures in place designed to protect personal data, sensitive data and our systems, techniques used to obtain unauthorized access or to sabotage systems and data change frequently and often are not recognized until launched against a target. It is also possible that, due to the surreptitious nature of certain data breaches and other cybersecurity incidents, such incidents may remain undetected for an extended period, which may exacerbate harm to the company. We cannot ensure that our privacy and security measures will not be breached or otherwise fail to protect sensitive information or prevent disruption of our operations, including as a result of inadvertent disclosures through technological or human error (including employee or service provider error), or malfeasance. Unauthorized individuals may acquire or obtain unauthorized access to sensitive information. Data breaches, failures of our privacy or security measures, inadvertent disclosures, disruptions of our services, and other cybersecurity incidents could result in serious harm to our reputation, our business might suffer, and we could incur serious liability and other expenses related to litigation (such as damages associated with breach-of-contract claims), penalties for violation of applicable laws or regulations, costly litigation or government investigations, and significant costs for remediation and remediation efforts to prevent future occurrences (including forensic investigations, notification costs, credit monitoring, business interruption, increased cybersecurity controls, and vendor replacement costs). The harm associated with these negative results is likely to be exacerbated if the affected information is personally identifiable or includes sensitive health, genetic, or clinical trial-related data.

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~~maintenance~~Like ofothers ~~this~~in ~~information is critical to~~ our ~~operations and business strategy. Despite the implementation of security measures~~industry, ~~our~~we ~~internal computer systems,~~ and ~~those~~our ofvendors ~~third~~have ~~parties~~experienced onthreats ~~which~~and wecybersecurity ~~rely,~~incidents ~~are~~relating ~~vulnerable~~ to ~~damage~~our ~~from~~information ~~computer~~technology ~~viruses,~~systems ~~malware, ransomware, cyber fraud, natural disasters, terrorism, war, telecommunication~~ and ~~electrical~~infrastructure. ~~failures,~~Attempts ~~cyber-attacks or cyber-intrusions over the Internet, attachments~~ to ~~emails,~~disrupt ~~persons inside our organization,~~ or ~~persons~~gain ~~with~~unauthorized access to ~~systems~~our ~~inside~~and our ~~organization.~~third-party ~~The~~vendors’ ~~risk~~information ofsystems afrom ~~security~~malicious ~~breach~~third orparties ~~disruption, particularly through cyber-attacks~~ or ~~cyber-intrusion,~~insider ~~including~~threats bymay ~~computer~~incorporate ~~hackers,~~widely ~~foreign~~varying ~~governments,~~ and ~~cyber~~frequently ~~terrorists,~~changing ~~has generally increased as the number~~tactics, ~~intensity~~which ~~and~~may ~~sophistication~~be ofenhanced ~~attempted~~or ~~attacks~~facilitated ~~and~~by ~~intrusions~~artificial ~~from~~intelligence. ~~around~~Any ~~the~~such ~~world~~cybersecurity ~~have~~incident ~~increased.~~or ~~Any~~data ~~such~~ breach could compromise our networks and the information stored there could be accessed, publicly disclosed, encrypted, lost, or stolen. Any such access, inappropriate disclosure of confidential or proprietary information or other loss of information, including ~~our~~a ~~data~~cybersecurity ~~being~~incident ~~breached~~or data breach at third-party providers, could result in legal claims or proceedings, liability or financial loss under laws that protect the privacy of personal information, disruption of our operations or the development of our pipeline assets and damage to our reputation, which could adversely affect our business. For example, the loss of clinical trial data from completed or ongoing or planned clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data and could jeopardize the integrity of our trial results or require us to repeat certain trial activities. Furthermore, as a result of cyber-attacks we may inadvertently misappropriate assets that we may not be able to fully recover or may be accused of misappropriation or unauthorized access based on compromised credentials or systems. Our contracts may not contain limitations of liability, and even where they do, there can be no assurance that limitations of liability in our contracts are sufficient to protect us from liabilities, damages, or claims related to our privacy and data security obligations. Further, although we maintain cyber liability insurance, this insurance may not provide adequate coverage against potential liabilities related to any experienced cybersecurity incident or data breach and may be subject to exclusions, sublimits, deductibles, coverage disputes, or premium increases.

Any cybersecurity incident or disruption, including those affecting third parties on which we rely, could also impair our ability to comply with applicable reporting obligations and could expose us to regulatory scrutiny, enforcement actions, and securities litigation.

We may be subject to future litigation against us, which could be costly and time‑consuming to defend.

We may become subject, from time to time, to legal proceedings and claims that arise in the ordinary course of business such as claims brought by our collaborators in connection with commercial disputes, or employment claims made by our current or former employees as well as claims relating to intellectual property, privacy and data security, contracts, securities laws, product development activities, or other matters. Litigation might result in substantial costs and may divert management’s attention and resources, which might seriously harm our business, overall financial condition, and operating results. Insurance might not cover such claims, might not provide sufficient payments to cover all the costs to resolve one or more such claims, and might not continue to be available on terms acceptable to us. A claim brought against us that is uninsured or underinsured could result in unanticipated costs, thereby reducing our operating results and leading analysts or potential investors to reduce their expectations of our performance, which could reduce the trading price of our stock.

We may be subject to numerous and varying privacy and security laws, and our failure to comply could result in penalties and reputational damage.

We ~~maintain~~collect aand ~~large~~process ~~quantity of~~ sensitive information, including confidential business information and information associated with clinical trials. ~~Because~~including ofin ~~the~~some ~~sensitivity~~limited ~~of this information~~cases, ~~our~~personal ~~privacy and security measures related to such~~ information ~~are very important. Although we have privacy~~ and ~~security measures in place designed to protect~~ sensitive ~~data~~health-related ~~and our systems, techniques used to obtain unauthorized access or to sabotage systems and~~ data ~~change frequently and often are not recognized until launched against a target~~. It is also possible that, due to the surreptitious nature of certain data breaches and other incidents, they may remain undetected for an extended period, which may exacerbate harm to the company. We cannot ensure that our privacy and security measures will not be breached or otherwise fail to protect sensitive information or prevent disruption of our operations, including as a result of inadvertent disclosures through technological or human error (including employee or service provider error), malfeasance, hacking, ransomware, social engineering (including phishing schemes), computer viruses, malware, or otherwise. Unauthorized individuals may acquire or obtain unauthorized access to sensitive information. Data breaches, failures of our privacy or security measures, inadvertent disclosures, disruptions of our services, and other incidents could result in serious harm to our reputation, our business might suffer, and we could incur serious liability and other expenses related to litigation (such as damages associated with breach-of-contract claims), penalties for violation of applicable laws or regulations, costly litigation or government investigations, and significant costs for remediation and remediation efforts to prevent future occurrences. The harm associated with these negative results is likely to be exacerbated if the affected information is personally identifiable.

~~Like~~As ~~others~~such, inwe ~~our~~might ~~industry,~~be wesubject ~~experience~~to ~~cyber-attacks~~certain laws and ~~other~~regulations ~~attempts~~governing tothe ~~disrupt~~privacy orand ~~gain~~security ~~unauthorized~~of ~~access~~personal toinformation, ~~our~~including ~~systems~~regulations onpertaining ato ~~regular~~health ~~basis~~information. ~~When~~The welegislative ~~become~~and ~~aware~~regulatory oflandscape for privacy orand data security ~~incidents~~continues to evolve, weand ~~work~~there ~~diligently~~has tobeen ~~address~~an ~~them~~increasing focus on privacy and data security issues that may affect our business. In the United States, ~~including~~numerous byfederal ~~working~~and tostate ~~terminate~~privacy ~~unauthorized~~and ordata ~~inappropriate~~security ~~access~~laws and ~~implementing~~regulations ~~additional~~that ~~measures~~govern the collection, ~~training~~use, disclosure, and ~~providing~~protection ~~guidance~~of topersonal ~~end~~information, ~~users~~including infederal ~~order~~and tostate ~~avoid~~health ~~the~~information ~~reoccurrence~~privacy laws, federal and ~~future~~state ~~incidents.~~security ~~Although~~breach tonotification ~~date~~laws, ~~privacy~~and federal and state data security ~~incidents~~laws. ~~have~~Each ~~not~~of ~~been~~these ~~material~~laws, ~~they~~, ~~could~~such ~~expose~~as usthe toHealth ~~significant~~Insurance ~~expense,~~Portability ~~legal~~and ~~liability~~Accountability Act (“HIPAA”), is subject to extensive interpretations by courts and ~~harm~~government agencies, creating complex compliance issues for us. If we fail to ~~our~~comply ~~reputation~~with applicable laws and regulations, ~~which~~we ~~might~~could ~~result~~be insubject anto ~~adverse~~lawsuits, ~~impact~~penalties, ~~our~~or ~~operating~~sanctions, ~~results~~consent decrees, audits, and reputational harm.

WeAt ~~might~~the befederal ~~subject~~level, failing to ~~certain~~take ~~laws~~appropriate ~~and~~steps ~~regulations~~to ~~governing~~keep ~~the~~consumers’ ~~privacy~~personal ~~and~~information ~~security~~secure ofmay ~~personal~~constitute ~~information,~~unfair ~~including~~acts ~~regulations~~or ~~pertaining~~practices toin ~~health~~or ~~information.~~affecting ~~The~~commerce ~~legislative~~in ~~and~~violation ~~regulatory~~of ~~landscape~~Section ~~for~~5(a) ~~privacy~~of ~~and~~the ~~data~~Federal ~~security~~Trade ~~continues~~Commission ~~to evolve~~Act, ~~and~~15 ~~there~~U.S.C ~~has~~§ ~~been~~45(a). anThe ~~increasing~~FTC ~~focus~~expects ona ~~privacy~~company’s ~~and~~ data security ~~issues~~measures ~~that~~to ~~may~~be ~~affect~~reasonable ~~our~~and ~~business.~~appropriate Inin light of the ~~United~~sensitivity ~~States,~~and ~~there~~volume ~~are~~of ~~numerous~~consumer ~~federal~~information ~~and~~it ~~state~~holds, ~~privacy~~the size and ~~data~~complexity ~~security~~of ~~laws~~its business and ~~regulations~~the ~~that~~cost ~~govern~~of ~~the~~available ~~collection,~~tools ~~use,~~to ~~disclosure,~~improve security and ~~protection~~reduce ofvulnerabilities. ~~personal~~The ~~information,~~HHS ~~including~~Office ~~federal~~for ~~and~~Civil ~~state~~Rights, ~~health~~which ~~information~~enforces ~~privacy laws~~HIPAA, ~~federal~~also ~~and~~remains ~~state~~active ~~security~~in ~~breach~~its ~~notification~~enforcement ~~laws,~~of ~~and~~the ~~federal~~law. ~~and~~Additionally, state ~~data~~attorneys ~~security~~general ~~laws.~~may ~~Each~~bring ofcivil ~~these~~actions ~~laws~~seeking iseither ~~subject~~injunctions toor ~~varying~~damages ~~interpretations~~in byresponse ~~courts~~to ~~and~~violations ~~government~~of ~~agencies,~~HIPAA ~~creating~~that ~~complex~~threaten ~~compliance~~the ~~issues~~privacy ~~for~~of ~~us.~~state Ifresidents weand ~~fail~~private tolitigants ~~comply~~may ~~with~~assert ~~applicable~~state-law ~~laws~~claims ~~and~~based ~~regulations,~~on wethe ~~could~~same beunderlying ~~subject~~conduct. ~~to lawsuits,~~

43Privacy and data security have become an area of emphasis for some state legislatures, many of which have passed comprehensive state privacy laws. For example, California enacted the California Consumer Privacy Act(“CCPA”), which creates individual privacy rights for California consumers (as the term “consumers” is defined by the law) and increases the privacy and security obligations of entities handling certain personal data. The CCPA requires covered companies to provide certain disclosures to consumers about their data collection, use and sharing practices, and to provide affected California residents with ways to opt-out of certain sales or transfers

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~~penalties,~~of orpersonal ~~sanctions~~information. ~~The~~While ~~HHS~~there ~~Office~~is currently an exception for ~~Civil~~protected ~~Rights,~~health ~~which~~information ~~enforces~~that is subject to HIPAA, ~~remains~~as ~~active~~well as for data collected in ~~its~~the ~~enforcement~~context of clinical trials, the ~~law.~~CCPA ~~Additionally,~~may ~~state~~impact ~~attorneys~~our ~~general~~business ~~may~~activities. ~~bring~~Following ~~civil~~California’s ~~actions~~lead, ~~seeking~~more ~~either~~than ~~injunctions~~19 oradditional ~~damages~~states, inincluding ~~response~~Virginia, toColorado, ~~violations~~Connecticut, ofNew ~~HIPAA~~Jersey, ~~that~~and ~~threaten~~New ~~the~~Hampshire, ~~privacy~~have ofadopted ~~state~~comprehensive ~~residents~~privacy laws. ~~Privacy~~While ~~and~~these ~~data~~laws ~~security~~incorporate ~~has~~many ~~become~~similar anconcepts ~~area~~to ofthose ~~emphasis~~in ~~for~~the ~~some~~CCPA, ~~state~~there ~~legislatures,~~are ~~which~~also ~~have~~several ~~passed~~key ~~comprehensive~~differences ~~state~~in ~~privacy~~the ~~laws~~scope, ~~such~~application, asand enforcement of the ~~California~~laws ~~Consumer~~that ~~Privacy~~will ~~Act,~~change the ~~Colorado~~operational ~~Privacy~~practices ~~Act,~~of ~~and~~regulated ~~the~~businesses. ~~Virginia~~These ~~Consumer~~laws ~~Data~~will, ~~Protection~~among ~~Act.~~other ~~State~~things, ~~legislatures~~impact ~~continue~~how toregulated ~~pass~~businesses ~~comprehensive~~collect and ~~industry-specific~~process ~~privacy~~personal ~~and~~sensitive data, ~~security~~conduct ~~laws~~data ~~that~~protection ~~may~~assessments, ~~present~~transfer ~~compliance~~personal ~~challenges~~data to affiliates, ~~including~~and ~~privacy~~respond ~~laws~~to consumer rights requests. There are also states that are specifically regulating health~~-related~~ information. InFor ~~addition~~example, toWashington’s My Health My Data Act regulates the ~~risk~~collection ~~associated~~and ~~with~~sharing ~~enforcement~~of health information and has a private right of action, which further increases the relevant compliance ~~with~~risk. Connecticut and ~~implementation~~Nevada ofhave ~~these~~also ~~evolving~~passed similar laws, ~~rules~~regulating consumer health data. In addition, other states have proposed and/or ~~regulations~~passed ~~regarding~~legislation that regulates the privacy, ~~security~~ and/or ~~protection~~security of ~~personal~~certain ~~information~~specific ~~could~~types ~~result~~of ininformation. ~~higher~~For ~~compliance~~example, ~~and~~a ~~technology~~small ~~costs~~number ~~for~~of usstates, including Illinois and ~~present~~Texas, ~~challenges~~have ~~for~~passed ~~our~~laws ~~business~~that ~~model~~regulate biometric data specifically.

~~There~~State ~~are~~legislatures ~~numerous~~continue ~~federal and state laws that generally require notice~~ to ~~affected~~pass ~~individuals,~~comprehensive ~~regulators,~~ and ~~sometimes~~industry-specific ~~the~~privacy ~~media~~and ordata ~~credit~~security ~~reporting~~laws ~~agencies~~that inmay ~~the~~present ~~event~~compliance ofchallenges, aincluding ~~data~~privacy ~~breach~~laws ~~impacting~~regulating ~~personal~~health-related information. ~~For~~The ~~example,~~existence atof ~~the~~a ~~federal~~patchwork ~~level,~~of ~~HIPAA~~privacy ~~Breach~~laws ~~Notification~~in ~~Rule~~different ~~mandates~~states ~~notification~~make ofour ~~breaches~~compliance ~~affecting~~obligations ~~protected~~add ~~health~~complexity, ~~information~~variation toin ~~affected~~requirements, ~~individuals~~restrictions and ~~regulators~~potential ~~under~~legal ~~conditions~~risk ~~set~~that ~~forth~~requires inadditional ~~the~~investment ~~Rule. Covered entities must report breaches~~ of ~~unsecured~~resources ~~protected~~in ~~health~~compliance ~~information~~programs. ~~to affected individuals without unreasonable delay~~Further, ~~but~~these ~~not~~privacy tolaws ~~exceed~~may 60increase ~~days of discovery of~~ the ~~breach~~likelihood bythat awe ~~covered~~may ~~entity or its agents. Notification must also~~ be ~~made~~subject to ~~HHS~~enforcement ~~and,~~actions inor ~~certain~~otherwise ~~circumstances~~incur ~~involving~~liability ~~large~~for ~~breaches, to the media~~noncompliance. ~~Business~~In ~~Associates~~addition ~~must report breaches of unsecured protected health information~~ to ~~covered entities. All states,~~ the ~~District~~risk ofassociated ~~Columbia,~~with ~~Guam~~enforcement, ~~Puerto~~compliance ~~Rico,~~with and ~~the~~implementation ~~Virgin~~of ~~Islands~~these ~~have~~evolving ~~enacted data breach notification~~ laws., ~~These laws may impose notification obligations in addition to~~rules, orand ~~inconsistent~~regulations ~~with,~~regarding the ~~HIPAA~~privacy, ~~Breach~~security ~~Notification~~and ~~Rule~~protection ~~when~~of apersonal ~~data breach implicates protected health~~ information. Incould ~~that~~result ~~event~~in ~~that~~higher wecompliance ~~fail~~and totechnology ~~detect~~costs orfor ~~timely~~us, ~~report~~present achallenges ~~data~~for ~~breach~~our itbusiness ~~may~~model beand ~~subject~~could torequire significant ~~penalties~~changes ~~under~~to ~~federal~~our ~~and state law. In the event that we report a data breach as required by federal or state law~~policies, ~~federal or state regulators may initiate an investigation into~~procedures, and~~/or~~ ~~litigation related to, our privacy or~~ data-processing ~~security~~ practices. ~~Private plaintiffs may also initiate costly class action litigation following a data breach.~~

~~Numerous~~There ~~other~~are ~~countries~~numerous ~~have,~~federal orand ~~are~~state ~~developing,~~ laws ~~governing~~that ~~the~~generally ~~collection,~~require ~~use,~~notice ~~and~~to ~~transmission~~affected ofindividuals, ~~personal~~regulators, ~~information.~~and ~~These~~sometimes ~~laws~~the ~~often~~media ~~impose~~or ~~significant~~credit ~~compliance~~reporting ~~obligations.~~agencies ~~For~~in ~~example,~~ the ~~General~~event ~~Data~~of ~~Protection~~a ~~Regulation~~data ~~(“GDPR”)~~breach ~~has~~impacting ~~imposed~~personal ~~stringent~~information. ~~obligations~~For ~~and~~example, ~~restrictions~~at on the ~~ability~~federal tolevel, ~~process~~HIPAA ~~and~~Breach ~~transfer~~Notification ~~personal~~Rule ~~information,~~mandates ~~including~~notification ~~health~~of ~~data~~breaches ~~from~~affecting ~~clinical~~protected ~~trials~~health ~~and~~information ~~substantial~~to ~~fines~~affected ~~for~~individuals ~~breaches~~and ofregulators ~~the~~under ~~data~~conditions ~~protection~~set ~~rules~~forth in the ~~European~~Rule. ~~Economic~~Covered ~~Area~~entities ~~(“EEA”).~~must Toreport ~~the~~breaches ~~extent~~of ~~that~~unsecured ~~our~~protected ~~activities~~health ~~are~~information orto ~~become~~affected ~~subject~~individuals towithout ~~the~~unreasonable ~~GDPR~~delay, webut ~~may~~not ~~need~~ to ~~devote~~exceed ~~significant~~60 ~~effort~~days ~~and~~of ~~resources~~discovery toof ~~complying~~the ~~with~~breach ~~those~~by ~~legal~~a ~~regimes.~~covered ~~Any~~entity ~~failure~~or toits ~~comply~~agents. ~~with~~Notification ~~the~~must ~~rules~~also ~~arising~~be ~~from~~made ~~the GDPR could lead~~ to ~~government~~HHS ~~enforcement actions~~ and, ~~significant~~in ~~penalties~~certain ~~against~~circumstances usinvolving ~~and~~large ~~adversely~~breaches, ~~impact~~to ~~our~~the ~~operating results~~media. If ~~our~~Business ~~operations~~Associates ~~are~~must ~~found~~report tobreaches ~~violate~~of ~~GDPR~~unsecured ~~requirements,~~protected wehealth ~~may~~information ~~incur~~to ~~substantial~~covered ~~fines,~~entities. ~~have~~All tostates, ~~change~~the ~~our~~District ~~business~~of ~~practices~~Columbia, ~~and~~Guam, ~~face~~Puerto ~~reputational harm~~Rico, ~~any~~and ofthe ~~which~~Virgin ~~could~~Islands have anenacted ~~adverse~~data ~~effect~~breach onnotification ~~our business~~laws. InThese ~~particular,~~laws ~~serious~~may ~~breaches~~impose ofnotification ~~the~~obligations ~~GDPR can result~~ in ~~administrative~~addition ~~fines of up~~ to, 4%or ofinconsistent ~~annual~~with, ~~worldwide~~the ~~revenues.~~HIPAA ~~Fines~~Breach ofNotification upRule towhen 2%a ofdata ~~annual~~breach ~~worldwide~~implicates ~~revenues~~protected ~~can~~health ~~be levied for other specified violations~~information. ~~The~~In ~~validity~~the ofevent ~~data~~that ~~transfer~~we ~~mechanisms~~fail ~~remains subject~~ to ~~legal,~~detect ~~regulatory,~~or ~~and~~timely ~~political~~report ~~developments~~a indata ~~both~~breach ~~Europe~~it ~~and~~may ~~the~~be ~~United~~subject ~~States,~~to ~~such~~significant aspenalties ~~recent~~under ~~recommendations~~federal ~~from~~and ~~the~~state ~~European~~law. ~~Data~~In ~~Protection Board,~~ the ~~invalidation~~event ofthat ~~the~~we ~~EU-U.S.~~report ~~Privacy~~a ~~Shield,~~data ~~and~~breach ~~potential~~as ~~invalidation~~required ofby ~~other~~federal ~~data~~or ~~transfer~~state ~~mechanisms~~law, ~~which~~federal ~~could~~or ~~have~~state aregulators ~~significant~~may ~~adverse~~initiate ~~impact~~an oninvestigation ~~our ability to process and transfer personal data outside of the EEA. These developments create some uncertainty~~into, and/or ~~compliance~~litigation ~~obligations~~related ~~could cause us~~ to, ~~incur~~our ~~costs~~privacy or ~~harm~~data ~~the~~security ~~operations~~practices. ofPrivate ~~our~~plaintiffs ~~products~~may ~~and~~also ~~services~~initiate incostly ~~ways~~class ~~that~~action ~~harm~~litigation ~~our~~following ~~business~~a data breach.

Numerous other countries have, or are developing, laws governing the collection, use, and transmission of personal information. These laws often impose significant compliance obligations. For example, our operations involving clinical trials in the European Economic Area (“EEA”) bring us within the scope of the EU General Data Protection Regulation (“EU GDPR”), as well as other national data protection legislation in force in relevant EEA Member States, which govern the collection, use, storage, disclosure, transfer, or other processing of personal data (including health data processed in the context of clinical trials) regarding individuals in the EEA. The GDPR is wide-ranging in scope and imposes additional obligations on companies that process personal information. These, include specific requirements regarding the processing of health and other sensitive data; obtaining valid consent from individuals in certain circumstances; providing expanded disclosures about data processing; implementing safeguards to ensure the security and confidentiality of personal data; limiting retention periods; and strengthening obligations around pseudonymized (i.e., key-coded) data. The GDPR also introduces mandatory breach notification obligations and requires that contractual and other measures be in place when engaging third-party service providers. In addition, the GDPR imposes strict rules on transfers of personal data out of the EEA to third countries, such as the U.S., unless a valid transfer mechanism (e.g., the European Commission’s Standard Contractual Clauses, or SCCs) is in place or a derogation applies. Where we rely on the SCCs, we may also be required to carry out transfer impact assessments to evaluate whether recipients are subject to local laws that could permit government access to personal data. If we are unable to lawfully transfer personal data from the EEA to the U.S., our operations, business continuity, and financial position could be adversely affected.

We are taking steps to comply with the GDPR as appropriate and as applicable to our operations, but compliance is an ongoing and evolving process. Meeting GDPR requirements is rigorous and time-intensive, and may increase our operational costs or require changes to our business practices. Any failure to comply with the EU GDPR could lead to government enforcement actions and significant penalties against us and adversely impact our operating results. If our operations are found to violate EU GDPR requirements, we may incur substantial fines, have to change our business practices, and face reputational harm, any of which could have an adverse effect on our business. In particular, serious breaches of the GDPR can result in regulatory sanctions and administrative fines of up to €20 million or 4% of annual worldwide revenues for the preceding financial year. The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies and obtain compensation for damages resulting from violations of the GDPR.

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In addition, EEA Member States have adopted national laws to implement the GDPR that may deviate in part from the EU regulation. The GDPR also allows each Member State to introduce its own legal requirements for processing genetic, biometric, or health data. Competent authorities across Member States may also interpret and enforce GDPR obligations differently. As a result, we do not expect to operate under a uniform legal framework within the EEA. These variations may increase the complexity and cost of compliance, limit our ability to use and share personal data across jurisdictions, and affect our operational efficiency. Further, the UK data protection regime is currently independent from the EU GDPR but remains broadly aligned with it. To the extent our activities become subject to the UK GDPR in the future, we would be required to comply with obligations similar to those under the EU GDPR in relation to the processing of UK personal data. Any future divergence between the UK and EU data protection regimes could create legal uncertainty, increase compliance complexity and cost, and require us to adjust how we handle personal data in these regions.

All of these evolving compliance and operational requirements impose costs, such as costs related to organizational changes, implementing additional protection technologies, training employees and engaging consultants and legal advisors, which are likely to increase over time. In addition, such requirements may require us to modify our data processing practices and policies, utilize management’s time and/or divert resources from other initiatives and projects. Any failure or perceived failure by us to comply with any applicable federal, state or foreign laws and regulations relating to data privacy and security could result in damage to our reputation, as well as proceedings or litigation by governmental agencies or other third parties, including class action privacy litigation in certain jurisdictions, which would subject us to significant fines, sanctions, awards, injunctions, penalties or judgments. Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations and prospects.

The U.S. Congress or the current administration may make substantial changes to fiscal, tax, and other federal policies that may adversely affect our business.

Since the start of the current administration in 2025, there have been significant changes to U.S. trade, healthcare, immigration and government regulatory policy and additional changes are likely. For example, the U.S. government has imposed substantial tariffs on most countries throughout the world and has further threatened to continue to broadly impose tariffs, which could lead to corresponding punitive actions by the countries with which the U.S. trades. Changes to U.S. policy implemented by the U.S. Congress, the current administration or any new future administration have impacted and may in the future impact, among other things, the U.S. and global economy, international trade relations, unemployment, immigration, healthcare, taxation, the U.S. regulatory environment, inflation and other areas. Although we cannot predict the impact, if any, of these changes to our business, they could adversely affect our business, including by increasing our costs, restricting access to suppliers, vendors, or clinical trial sites, or creating delays in procurement, logistics, or regulatory interactions. Until we know what policy changes are made, whether those policy changes are challenged and subsequently upheld by the court system and how those changes impact our business and the business of our competitors over the long term, we will not know if, overall, we will benefit from them or be negatively affected by them.

Our use of new and evolving technologies, such as artificial intelligence, may present risks and challenges that can impact our business, including by posing cybersecurity and other risks to our confidential and/or proprietary information, including personal information, and as a result we may be exposed to reputational harm and liability.

We may use, and our vendors may incorporate, artificial intelligence (“AI”) both in our own development and implementation of AI and through the adoption of commercially available tools. The use of AI presents risks and challenges that could adversely affect our business, including cybersecurity, data privacy, IT, confidentiality, regulatory, legal, operational, competitive, reputational and intellectual property risks. Specifically, risks related to accuracy, bias, artificial intelligence hallucinations, discrimination, harmful content, misinformation, fraud, scams, targeted attacks (including model poisoning or data poisoning), surveillance, data leakage, environmental and other harms may flow from our development, use, or deployment of AI technologies. For example, use of certain AI tools may increase the risk of unauthorized disclosure of confidential information, compromise of proprietary intellectual property, or inadvertent inclusion of third-party intellectual property or other protected material, which could result in disputes or claims of infringement.

Additionally, government and supranational regulation related to AI is evolving and could increase the burden and cost of compliance, including through requirements related to transparency, accountability, risk management, human oversight, and data governance . For example, the EU’s Artificial Intelligence Act (“AI Act”) began its implementation on August 1, 2024, with a larger portion of the law scheduled to come into effect in August 2026. As currently enacted, the AI Act, which may be amended as part of the EU’s Digital Omnibus, imposes significant obligations on providers and deployers of high-risk artificial intelligence systems, and encourages providers and deployers of artificial intelligence systems to account for EU ethical principles in their development and use of these systems. The scope of requirements depends on legal and risk determinations that rely on novel legal provisions that have not yet been interpreted by courts or regulators, and non-compliance can lead to significant fines.

In the U.S., the regulatory environment is complex and uncertain. Over the past year, states have advanced, and in some cases passed, dozens of laws focusing on AI governance and regulation, including on deployment of AI in healthcare settings. At the federal level, the Trump Administration has endorsed a federal moratorium on the enforcement of state AI laws, including through a December 11, 2025, executive order on “Ensuring a National Policy Framework for Artificial Intelligence.” So far, these efforts have not been

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successful at curtailing state action on AI regulation, contributing to a complicated legislative patchwork, which may be litigated in state and federal courts. In addition, there continues to be uncertainty regarding the application of existing federal and state legal frameworks to uses and development of AI, and legal norms and market standards regarding AI continue to evolve. For example, various federal and state regulators have issued guidance and focused enforcement efforts on the use of AI in regulated sectors. The U.S. Food and Drug Administration, for example, issued guidance on the use of artificial intelligence in medical devices, requiring detailed risk management and review processes to obtain approvals. If we develop or use AI systems that are governed by the these laws or regulations, we will need to meet higher standards of data quality, transparency, and human oversight, and we would need to adhere to specific and potentially burdensome and costly ethical, accountability, and administrative requirements. We may also be subject to significant enforcement or litigation in the event of any perceived non-compliance.

The rapid evolution of artificial intelligence will require the application of significant resources to design, develop, test and maintain our products and services to help ensure that artificial intelligence is implemented in accordance with applicable law and regulation and in a socially responsible manner and to minimize any real or perceived unintended harmful impacts. The use of certain AI technologies can also give rise to intellectual property risks, including by disclosing or otherwise compromising our confidential or proprietary intellectual property, or by undermining our ability to assert or defend ownership rights in intellectual property created with the assistance of artificial intelligence tools.

Our vendors may in turn incorporate artificial intelligence tools into their offerings, and the providers of these artificial intelligence tools may not meet existing or rapidly evolving regulatory or industry standards, including with respect to privacy and data security. Further, bad actors around the world use increasingly sophisticated methods, including the use of artificial intelligence, to engage in illegal activities involving the theft and misuse of personal information, confidential information and intellectual property. In addition, the use of generative AI models in our internal or third-party systems may create new attack surfaces or methods for adversaries, which could impact us and our vendors. Any of these effects could damage our reputation, result in the loss of valuable property and information, cause us to breach applicable laws and regulations, and adversely impact our business.

Item 1B. Unresolved Staff Comments.

None.

Item 1C. Cybersecurity.

~~Avalo’s~~As ~~management~~part ~~and Board~~ of ~~Directors~~our ~~recognize~~overall ~~the~~risk ~~importance~~management ofprocess, ~~information~~we ~~security and managing cybersecurity risks across the enterprise. We~~ have ~~strategically~~established ~~designed~~an ~~our robust~~ Information Security Program (the “Program”) designed to assess, identify, and manage ~~these~~ cybersecurity risks, ~~protect~~as ~~the~~well ~~Company~~as ~~from~~support ~~such~~efforts ~~risks,~~in ~~and~~responding ~~respond~~ to, and ~~recover~~recovering from, cybersecurity threats and incidents.

The Company’s Information Security Working Group (“ISWG”) is actively engaged in managing cybersecurity risks and overseeing the design, implementation, and evaluation of the Program. The purpose of the ISWG is to define cybersecurity risk tolerance, guide implementation of the Program, monitor Program development and effectiveness, and validate investments in cybersecurity measures and infrastructure. Members of the ISWG include: the Chief Financial Officer, the Chief Legal Officer, the head of the Company’s Human Resource department, the Senior Vice President of Program Management and Corporate Infrastructure, the Senior Vice President of Regulatory and Quality Assurance, and the Company’s head of Information Technology. The group meets semi-annually to review the effectiveness of the Program, discuss any new developments and potential improvements to the Program, and evaluate internal and external security-related events to determine how Avalo can take appropriate steps to mitigate such risks.Governance

44Our Board of Directors has delegated Program oversight to the Audit Committee (the “Committee”). The Committee is composed of directors with expertise in technology, audit, finance, and compliance. The Company’s Information Security Working Group (“ISWG”) manages cybersecurity risks and oversees the design, implementation, and evaluation of the Program. The responsibilities of the ISWG include defining cybersecurity risk tolerance, guiding implementation of the Program, monitoring Program development and effectiveness, and validating investments in cybersecurity measures and infrastructure. Members of the ISWG include: the Chief Financial Officer, the Chief Legal Officer, the Senior Vice President of Human Resources, the Senior Vice President of Regulatory and Quality Assurance, and the Vice President of Information Technology. The ISWG meets semi-annually to review the effectiveness of the Program, discuss any new developments and potential improvements to the Program, and evaluate internal and external security-related events to determine how Avalo can take appropriate steps to mitigate such risks.

Our Vice President of Information Technology (“VP of IT”), is responsible for Avalo’s enterprise-wide cybersecurity strategy, architecture, policies, processes, and controls, and is directly responsible for the day-to-day management of the Program. The individual serving in this role has over 20 years of experience with information technology and over 8 years of experience managing cybersecurity risk management programs. Our VP of IT reports to the Senior Vice President of Human Resources (“SVP of HR”). The VP of IT regularly informs the SVP of HR, and other members of the leadership team, about the Program, best practices, current cybersecurity threats, the cyber-risk landscape, and mitigation strategies. These reports include the following on an as-needed basis: updates on the Program; assessment of the Program; emerging risks or concerns; policies, procedures, and training; and risk mitigation strategies. The SVP of HR provides information technology and cybersecurity reports as necessary at meetings of management’s Disclosure Committee. These reports are also communicated to the Audit Committee, as necessary.

Risk Management and Strategy

The underlying controls of our Program incorporate elements of recognized industry standards for cybersecurity and information technology, including the National Institute of Standards and Technology (“NIST”) Cybersecurity Framework.

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~~The~~We ~~Audit~~use ~~Committee~~various ~~(the~~tools ~~“Committee”) is primarily responsible for oversight of the Program. The Committee is composed of directors with expertise in technology, audit, finance,~~ and ~~compliance,~~methodologies ~~equipping~~designed ~~them~~ to ~~effectively~~identify, ~~oversee the program. Yingping Zhang serves as our Vice President of Information Technology~~manage, and ~~she~~test ~~also~~for ~~helps~~cybersecurity ~~oversee~~risk ~~the~~on ~~implementation and effectiveness of the Program as~~ a ~~member~~regular ofcadence ~~the~~both ~~ISWG.~~at ~~Ms. Zhang graduated from~~ the ~~University~~enterprise oflevel ~~Pittsburgh with a Master of Science in Electrical Engineering~~ and ~~has~~through ~~over~~our ~~thirty~~use ~~years~~ of ~~experience~~third-party asservice ~~an information technology professional~~providers. ~~Prior~~These tothird ~~Avalo,~~parties ~~Ms.~~include ~~Zhang~~cybersecurity ~~worked~~managed assecurity anservice ~~Executive~~providers ~~Consultant~~(“MSSPs”), ~~for Insightful Group~~consultants, ~~the Vice President of Information Technology at Horizon~~advisors, and ~~the~~auditors, ~~Vice~~who ~~President~~we ofengage ~~Informational~~to ~~Technology~~evaluate ~~and~~our ~~Information~~controls, ~~Services~~whether atthrough ~~Viela~~penetration ~~Bio~~testing, ~~among~~independent ~~other~~audits, ~~positions~~or ~~within~~consulting ~~biopharma~~on ~~companies.~~best ~~Ms.~~practices ~~Zhang reports~~ to ~~Lisa~~address ~~Hegg,~~new ~~Senior~~threats ~~Vice~~or ~~President~~challenges. ofWe ~~Program~~also ~~Management~~engage ~~and~~internal ~~Corporate~~auditors ~~Infrastructure.~~to ~~Ms.~~audit ~~Hegg~~our ~~provides~~ information technology ~~and~~control ~~cybersecurity~~environment, ~~reports~~test asour ~~necessary~~information attechnology ~~meetings of management’s Disclosure Committee~~controls, ~~which~~and isreport ~~communicated quarterly~~ to ~~the~~us ~~Audit~~any ~~Committee,~~findings. ~~with~~External ~~greater~~security ~~frequency~~service asfirms ~~necessary.~~monitor ~~Ms.~~Avalo’s ~~Zhang~~networks ~~regularly~~at ~~informs~~all ~~Ms. Hegg~~times, ~~our~~and ~~Chief~~Avalo ~~Executive~~laptops ~~Officer~~are ~~(CEO)~~patched ~~and~~frequently ~~other~~with ~~members~~up-to-date ofantivirus ~~the~~and ~~leadership~~real ~~team,~~time ~~about~~threat-monitoring ~~the~~protection. ~~Program~~Further, ~~best~~we ~~practices,~~actively ~~current~~engage ~~cybersecurity~~with ~~threats~~key vendors, ~~the~~industry ~~risk landscape~~participants, and ~~mitigation~~law ~~strategies.~~enforcement ~~These~~officials ~~reports include the following on an~~ as~~-needed~~ ~~basis:~~part ~~updates on the Program; assessment~~ of ~~the~~our ~~Program;~~continuing ~~emerging~~efforts ~~risks~~to orevaluate ~~concerns; policies, procedures,~~ and ~~training;~~improve ~~and~~our ~~risk mitigation strategies~~Program.

~~The~~As ~~underlying~~part ~~controls~~ of ~~our~~the Program, ~~are~~we ~~based~~maintain onprocesses ~~recognized~~related ~~best~~to ~~practices~~third-party vendor cybersecurity risk management. We review and ~~standards~~confirm controls for ~~cybersecurity~~vendors providing critical business services and ~~information~~employ ~~technology,~~quality ~~including~~agreements ~~the~~and ~~National~~vendor ~~Institute~~audits ofdesigned ~~Standards~~to ~~and~~ensure ~~Technology~~vendor ~~(NIST)~~compliance ~~Cybersecurity~~with ~~Framework~~our ~~(CSF).~~Program Msand applicable regulatory requirements. ~~Zhang~~Further, iswe ~~responsible~~conduct information security assessments before onboarding new vendors and upon detection of an increase in risk profile for ~~developing~~existing ~~enterprise~~vendors. We also require our third-~~wide~~party ~~cybersecurity~~service ~~strategy,~~providers ~~architecture,~~to ~~policies,~~meet ~~processes~~appropriate security requirements, controls and ~~controls,~~responsibilities via additional security and isprivacy ~~directly~~addenda ~~responsible~~which ~~for~~we include in our ~~cybersecurity~~contracts ~~program.~~where applicable.

WeAs ~~use~~part ~~various~~of tools and methodologies to identify, manage, and test for cybersecurity risk on a regular cadence both at the enterprise level and using third-party service providers. These third parties include cybersecurity managed security service providers (MSSPs), consultants, advisors, and auditors, who we engage to evaluate our ~~controls~~Program, ~~whether through penetration testing, independent audits, or consulting on best practices to address new threats or challenges. To ensure~~ we ~~use~~maintain ~~reputable~~written ~~vendors for our~~ information ~~systems~~security policies, weincluding ~~review~~an ~~and~~incident ~~confirm~~response ~~SOC 1 reports for vendors providing critical business services~~plan. ~~For~~All ~~vendors handling~~ Avalo’s ~~clinical~~employees and ~~manufacturing~~contractors ~~information,~~are werequired ~~employ quality agreements and vendor audits~~ to ~~ensure~~participate ~~vendor~~in ~~compliance~~annual ~~with~~security ~~our~~awareness ~~Program~~training, ~~and~~which ~~all~~includes ~~applicable~~phishing ~~regulatory requirements~~simulations. WeAvalo ~~also~~employees ~~engaged~~are ~~internal~~also ~~auditors~~trained toon ~~conduct a walkthrough of~~ our ~~information~~written ~~technology control environment, test our~~ information ~~technology~~security ~~controls,~~policies and ~~report to us any findings. External security service firms monitor~~ the ~~Company’s~~acceptable ~~networks~~usage atof ~~all times~~systems, ~~and~~as ~~Company~~well ~~laptops are patched weekly with up-to-date antivirus and real time threat-monitoring protection. Further, we actively engage with key vendors, industry participants, and law enforcement officials~~ as ~~part~~procedures ofrelated ~~our continuing efforts~~ to ~~evaluate~~electronic ~~and~~record ~~improve our Program~~management.

~~Our~~Although ~~regular~~risks ~~interactions~~from ~~with~~cybersecurity ~~third-party~~threats ~~vendors~~have not materially affected, and ~~suppliers~~are ~~pose~~not areasonably ~~cybersecurity~~likely ~~risk~~to ~~that~~materially ~~could~~affect ~~adversely~~our ~~impact~~company, including our business strategy, results of operations, or ~~employees.~~financial Wecondition, ~~conduct~~to ~~information~~date, ~~security~~we ~~assessments~~may, ~~before~~from ~~onboarding~~time ~~and~~to ~~upon~~time, ~~detection~~experience ofthreats anto ~~increase~~and insecurity ~~risk~~incidents ~~profile.~~related Into ~~addition,~~our weand ~~require~~our ~~providers~~third-party tovendors’ ~~meet~~information ~~appropriate~~systems. ~~security~~For ~~requirements~~further information, ~~controls~~refer ~~and~~to ~~responsibilities~~Section ~~and~~1A, ~~include~~Risk ~~additional~~Factors, ~~security~~for ~~and~~a ~~privacy~~discussion ~~addenda~~of torisks ~~our~~related ~~contracts~~to ~~where~~cybersecurity ~~applicable~~and technology.

Internally, our employees are a key part of our Program. All Avalo employees and contractors are required to participate in annual security awareness training, which includes phishing simulations. Company Employees are also trained on policies of information security and acceptable usage of systems, as well as procedures related to electronic record management, and Avalo regularly reviews and updates user accounts and permissions and ensures that only approved applications are installed on Company devices. The Company manages endpoints centrally and content can be deleted remotely in the event of stolen devices or terminated users.

To date, Avalo has not identified any cyber event or risks from cybersecurity threats that could be considered material, individually or in the aggregate. Notwithstanding our vigilance and our Program, we may not be successful in preventing or mitigating a cybersecurity incident that could have a material adverse effect on us. For further information, refer to Section 1A, Risk Factors, for a discussion of risks related to cybersecurity and technology.

Item 2. Properties.

Our headquarters are located in ~~Rockville~~Wayne (Chesterbrook), ~~Maryland~~Pennsylvania, where we occupy approximately 511,000 square feet of administrative office space. The lease expires on ~~January 31~~February 28, ~~2026~~2027.

The Company also occupies approximately 11,000 square feet of administrative office space in Chesterbrook, Pennsylvania. The lease expires on February 28, 2027.

We believe that our existing facilities are adequate to meet our current needs, and that suitable spaces will be available in the future on commercially reasonable terms.

Item 3. Legal Proceedings.

None.

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Item 4. Mine Safety Disclosures.

Not applicable.

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PART II

Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities.

Market Information

Our common stock is listed and publicly traded on The Nasdaq Capital Market under the symbol “AVTX.”

Holders

As of March 1718, ~~2025~~2026, there were approximately ~~149~~145 holders of record of our common stock. This number does not include beneficial owners whose shares are held by nominees in street name.

Dividends

We have never declared or paid cash dividends on our capital stock. We intend to retain all of our available funds and future earnings, if any, to finance the growth and development of our business. We do not intend to pay cash dividends to our stockholders in the foreseeable future. Any future determination related to our dividend policy will be made at the discretion of our board of directors and will depend upon, among other factors, our results of operations, financial condition, capital requirements, contractual restrictions, business prospects and other factors our board of directors may deem relevant.

Recent Sales of Unregistered Securities

Except for sales of unregistered securities that have been previously reported by the Company in either its quarterly reports on Form 10-Q or current reports on Form 8-K, there were no sales of unregistered securities of the Company during the period covered by this report.

Equity Compensation Plans

Information regarding securities authorized for issuance under equity compensation plans is set forth in Item 12 of this report is under the section captioned “Equity Compensation Plan Information”.

Issuer Purchases of Equity Securities

None.

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Item 6. Reserved.

4861

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Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations.

The following discussion and analysis of our financial condition and results of operations should be read in conjunction with our consolidated financial statements and related notes included elsewhere in this Annual Report on Form 10-K. Some of the information contained in this discussion and analysis or set forth elsewhere in this Annual Report on Form 10-K, including information with respect to our plans and strategy for our business, includes forward-looking statements that involve risks and uncertainties. You should review the “Risk Factors” section in this Annual Report on Form 10-K for a discussion of important factors that could cause actual results to differ materially from the results described in or implied by the forward-looking statements contained in the following discussion and analysis.

Overview

~~Avalo~~We ~~Therapeutics,~~are ~~Inc. (the “Company,” “Avalo” or “we”) is~~ a clinical stage biotechnology company ~~focused~~fully ondedicated ~~the~~to ~~treatment~~developing ofIL-1β-based treatments for immune-mediated ~~dysregulation~~inflammatory diseases. ~~Avalo’s~~Our lead ~~asset~~product iscandidate, abdakibart (AVTX-009), an anti-IL-1β monoclonal antibody (“mAb”), ~~targeting~~is ~~inflammatory~~in ~~diseases~~a Phase 2 clinical trial for hidradenitis suppurativa (“HS”). We are also exploring additional opportunities to make an impact in prevalent indications that have significant remaining unmet needs.

~~Our initial focus in 2024 was augmenting our immunology pipeline and securing financing to develop our pipeline.~~ In ~~March 2024~~2025, we ~~acquired~~were ~~our~~focused ~~lead~~on ~~asset,~~executing ~~AVTX-009,~~operationally ~~through~~on ~~our~~the ~~acquisition~~development of ~~AlmataBio,~~abdakibart ~~Inc.~~ (~~“AlmataBio”~~AVTX-009). ~~Concurrently,~~in weHS ~~executed~~including aprogressing ~~private~~the ~~placement~~Phase of2 ~~$185~~clinical ~~million~~trial, ~~including~~which ~~initial~~we ~~upfront~~refer ~~investment~~to ofthe ~~$115.6~~Phase ~~million~~2 ~~received~~LOTUS ~~in March 2024~~trial. WeThe ~~received~~global ~~the~~study ~~remaining~~which ~~$69.4~~includes ~~million~~approximately of250 ~~gross~~adults ~~proceeds~~with inmoderate ~~the~~to ~~fourth~~severe ~~quarter~~hidradenitis ofsuppurativa ~~2024~~is ~~upon~~designed ~~the~~to ~~full~~evaluate ~~exercise of~~ the ~~warrants~~efficacy ~~issued~~and assafety ~~part~~ of ~~the~~subcutaneous ~~transaction.~~bi-weekly ~~Immediately~~and ~~following~~monthly ~~the~~dosing ~~acquisition~~regimens ofcompared ~~AVTX-009, our focus shifted~~ to ~~executing operationally on the development of AVTX-009 for the treatment of hidradenitis suppurativa (“HS”)~~placebo. ~~This~~Our ~~included~~current ~~activation~~focus ofis ~~the~~completing ~~Investigational New Drug (“IND”) application in July 2024 and enrolling~~ the ~~first patient in our~~ Phase 2 LOTUS trial, inpreparing ~~October~~for ~~2024 (~~the ~~“LOTUS~~anticipated ~~Trial”).~~topline ~~The~~data ~~LOTUS~~readout ~~Trial~~in ~~is a global study designed to enroll 180 adults with HS to assess~~ the ~~efficacy~~second ~~and~~quarter ~~safety~~ of ~~convenient~~2026, ~~subcutaneous bi-weekly~~ and ~~monthly~~planning ~~dosing~~for ~~regimens~~our ofPhase ~~AVTX-009,~~3 ~~compared to placebo, with topline data expected in 2026~~trial(s).

~~Our~~Management’s ~~focus~~primary inevaluation ~~2025~~of isour ~~continuing~~success tois ~~execute~~the ~~operationally~~ability onto ~~the~~progress ~~development~~its ofprograms ~~AVTX-009,~~towards ~~most~~commercialization ~~notably~~or ~~the~~opportunistically ~~progression~~out-licensing ofrights ~~the~~to ~~LOTUS~~indications ~~Trial~~or geographies. We ~~are~~believe ~~committed~~the ability to ~~executing~~achieve the ~~LOTUS~~next ~~Trial~~anticipated ~~effectively~~milestone ~~and~~as ~~efficiently,~~presented asin ~~well~~the assection ~~exploring~~entitled ~~AVTX-009’s~~“Business” ~~potential~~in ~~broad~~Item ~~applications~~1 ~~for~~of ~~other~~this ~~immune~~Annual Report on Form 10-~~mediated~~K ~~diseases~~represents asour wemost ~~work~~immediate ~~toward~~evaluation point as to the ~~announcement~~progression of our ~~second indication~~pipeline.

~~Management’s~~2025 ~~primary~~Financial ~~evaluation~~Operations of Avalo’s success is the ability to progress its programs towards commercialization or opportunistically out-licensing rights to indications or geographies. We believe the ability to achieve the next anticipated milestone as presented in the section entitled “Business” in Item 1 of this Annual Report on Form 10-K represents our most immediate evaluation point as to the progression of our pipeline.Overview

~~2024~~As ~~Financial~~of ~~Operations~~December 31, ~~Overview~~2025, we had $98.3 million in cash and cash equivalents and short-term investments. Net cash used in operating activities was $51.5 million for the year ended December 31, 2025. Our current cash, cash equivalents and short-term investments are expected to fund operations into 2028.

AsNet ofloss for the year ended December 31, ~~2024,~~2025 ~~Avalo~~was ~~had~~ $~~134~~78.53 million ~~in cash and cash equivalents~~, representing a $~~127~~43.1 million increase ~~compared~~in tonet ~~December~~loss ~~31,~~as ~~2023.~~compared ~~During~~to the prior year,. weResearch ~~raised~~and ~~approximately~~development expenses increased $~~175~~25.86 million offrom ~~net~~the ~~proceeds~~prior ~~from~~year adriven ~~private~~by ~~placement~~costs related to and supporting the ~~subsequent~~Phase ~~exercise~~2 ofLOTUS ~~warrants~~trial. ~~issued~~General inand administrative expenses increased $5.7 million from the ~~private~~prior ~~placement~~year mainly due to increased stock-based compensation. ~~Net~~These ~~cash~~increases ~~used~~were offset by a $27.6 million acquired in-process ~~operating~~research ~~activities~~and ~~were~~development charge in 2024 that did not repeat. Further, we recognized $495.12 million of other expense for the year ended December 31, ~~2024,~~2025 ~~which~~as ~~includes~~compared to $1233.5 million of ~~milestone~~other ~~payments~~income toin ~~AlmataBio~~the ~~pursuant~~prior toyear, ~~the~~which ~~terms~~contributed ofto the ~~acquisition~~increase in ~~the~~net ~~first quarter~~loss. The ~~Company’s~~other ~~current~~income ~~cash~~recognized onin ~~hand~~the isprior ~~expected~~period primarily related to ~~fund~~the ~~operations~~accounting ~~into~~impact atof ~~least~~the ~~2027~~warrants that were issued and exercised in 2024.

~~Net~~We ~~loss~~expect ~~for the year ended December 31, 2024 was $35.1 million, representing a $3.6 million increase in net loss as compared to the prior year. Total~~ operating expenses ~~increased~~to bybe ~~$39.7 million,~~largely ~~which~~consistent ~~was~~with ~~driven~~2025 bythrough the ~~recognition~~Phase of2 ~~$27.6 million~~LOTUS oftrial ~~acquired~~topline ~~in-process~~data ~~research~~readout ~~and~~expected ~~development from the acquisition of AlmataBio~~ in the ~~first~~second quarter of ~~2024~~2026, ashowever, ~~well as a $10.7 million increase in research and development~~ expenses ~~and~~beyond athe ~~$6.9 million~~data ~~increase~~readout inare ~~general~~difficult ~~and~~to ~~administrative~~predict ~~expenses.~~given ~~Increased~~they ~~research~~will ~~and~~be ~~development~~highly ~~expenses~~dependent ~~were driven by AVTX-009 development costs, including trial initiation and progression, as well as manufacturing, partially offset by limited development costs incurred in 2024~~ on other legacy programs. Increased general and administrative costs were driven by employee compensation costs, including stock-based compensation expense, as well as increased consulting, legal and other professional expenses following acquisition and financing that took place in the ~~first~~outcome ~~quarter~~ of ~~2024. Operating expense increases were partially offset by a $37.7 million increase to other income, primarily related to~~ the ~~warrants that were issued in 2024~~trial.

We expect future research and development expenses and cash used in operations, excluding the milestone payments made to the former AlmataBio stockholders, to increase in 2025 as a result of our development plans for AVTX-009, including the continued execution of the LOTUS Trial which commenced in October 2024.

Results of Operations

49Comparison of the Years Ended December 31, 2025 and 2024

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Comparison of the Years Ended December 31, 2024 and 2023

Product Revenue, net

~~The~~We ~~Company’s~~recognized ~~license~~minimal ~~and~~net ~~supply~~product ~~agreement~~revenue for ~~Millipred®~~the ~~expired,~~year asended ~~planned~~December 31, on2025 ~~September~~compared ~~30,~~to ~~2023~~$0.4 ~~The~~million for ~~Company~~the year ~~continues~~ended December 31, 2024, which related to ~~monitor~~a ~~estimates~~change ~~for~~in estimate of commercial liabilities, ~~such~~mainly as sales returns., Asfor ~~additional~~the ~~information~~Millipred® ~~becomes~~product. ~~available,~~Our ~~the~~license ~~Company~~and ~~could~~supply ~~recognize~~agreement ~~expense~~for ~~(or~~Millipred® ~~benefit)~~expired ~~for~~on ~~differences~~September ~~between~~30, ~~actuals~~2023 oras ~~updated~~planned ~~estimates~~and toas ~~the~~such ~~reserves~~there ~~previously~~was no gross revenue recognized. Asfrom ~~such,~~sales for the ~~Company~~years ~~recognized~~ended ~~$0.4~~December 31, ~~million~~2025 inand ~~product~~December ~~revenue~~31, ~~net~~2024. ~~for~~We ~~the~~do ~~year~~not ~~ended~~expect ~~December~~significant 31movement in estimates of commercial liabilities, ~~2024~~however, ~~compared~~if toadditional ~~$1.4~~information ~~million~~becomes ~~related~~available, towe ~~product~~could ~~sales~~recognize expense (or a benefit) for ~~the~~differences ~~year~~between ~~ended~~actuals ~~December~~or ~~31,~~updated ~~2023.~~estimates Weto dothe ~~not~~reserves ~~expect~~previously ~~future~~recognized, ~~gross~~which ~~product~~could ~~revenue~~be ~~for~~recognized ~~Millipred®~~in net product revenue.

~~License and Other Revenue~~62

~~Avalo~~Table ~~recognized no license and other revenue for the year ended December 31, 2024. The Company recognized $0.5 million for the year ended December 31, 2023 as a result~~ of ~~the sale of its rights, title and interest in assets relating to the 800 Series (as defined in Note 4 to the consolidated financial statements) to AUG Therapeutics, LLC (“AUG”).~~ Contents

Cost of Product Sales

We recognized ano ~~benefit of $0.4 million to~~ cost of product sales for the year ended December 31, ~~2024,~~2025 compared to ~~cost~~a ofbenefit ~~product sales~~ of $10.34 million for the same period in ~~2023.~~2024, ~~The~~which ~~benefit~~related ~~recognized~~to in the ~~current~~change ~~period~~in ~~was~~an ~~mainly~~estimate ~~driven by the reversal~~ of acommercial ~~$1.0 million~~liabilities ~~reserve~~for ~~against~~ the ~~receivable~~Millipred® ~~due~~product. ~~from~~The ~~Aytu~~Company ~~BioScience,~~ceased ~~Inc.~~selling ~~(“Aytu”)~~Millipred® in ~~December~~September ~~2024~~2023. ~~given~~We ~~that~~do ~~Avalo~~not ~~expected~~expect ~~the~~significant ~~receivable~~movement toin beestimates ~~collectible as~~ of ~~December~~commercial 31liabilities, ~~2024~~however, ~~partially~~if ~~offset by~~ additional ~~royalty~~information onbecomes ~~the~~available, ~~profit~~we ~~share~~could asrecognize aexpense ~~result~~(or of a ~~change~~benefit) infor ~~estimate~~differences ~~for~~between ~~commercial~~actuals ~~liabilities.~~or ~~Avalo~~updated ~~collected~~estimates to the ~~receivable~~reserves ~~from~~previously ~~Aytu~~recognized, inwhich ~~January~~could ~~2025.~~be ~~The~~recognized in cost of product sales ~~incurred in the prior period was driven by units sold~~.

The Company will continue to monitor estimates for commercial liabilities, such as sales returns and profit share with the supplier pursuant to the reconciliation process. As additional information becomes available, the Company could recognize expense (or a benefit) for differences between actuals or updated estimates to the reserves previously recognized, which could be recognized in cost of product sales.

Research and Development Expenses

The following table summarizes our research and development expenses for the years ended December 31, ~~2024~~2025 and ~~2023~~2024:

Year Ended December 31,

2024

2023

2025

2024

(in thousands)

Nonclinical expenses

~~570~~824

~~1,029~~570

Clinical expenses

924,~~966~~865

59,~~780~~966

CMC expenses

59,~~106~~657

15,~~855~~106

Internal expenses:

Salaries, benefits and related costs

68,~~164~~502

36,~~576~~164

Stock-based compensation expense

25,~~402~~992

12,~~318~~402

Other

~~229~~244

~~226~~229

2450,~~437~~084

1324,~~784~~437

Research and development expenses increased $1025.76 million for the year ended December 31, ~~2024,~~2025 compared to the ~~year~~prior ~~ended~~period. ~~December~~The ~~31,~~increase ~~2023.~~was ~~Notably,~~driven by increases in clinical and CMC expenses ~~increased~~of $14.9 million and $4.26 million, inrespectively. ~~the~~Clinical ~~current~~expenses ~~period~~increased due to ~~LOTUS~~progress ~~Trial~~in ~~activities~~the ~~including~~current ~~expenses~~year ~~incurred~~for ~~to activate~~ the ~~IND~~Phase ~~and~~2 LOTUS trial ~~initiation~~in ~~and~~HS, ~~execution~~including ~~expenses.~~site ~~Additionally~~activations, ~~chemistry,~~patient ~~manufacturing,~~trial costs and ~~control~~clinical ~~(“CMC”)~~trial ~~expenses~~work ~~increased~~performed ~~$3.3 million~~by asour acontract ~~result~~research oforganization, ~~AVTX-009~~as ~~raw~~compared ~~material~~to ~~purchases~~trial ~~and~~enabling ~~manufacturing. Clinical~~ and ~~CMC~~activation ~~expense~~activities ~~increases~~incurred ~~were partially offset by clinical development and manufacturing activity ongoing~~ in the prior year ~~for~~period. ~~quisovalimab~~CMC ~~that~~expenses ~~did~~increased ~~not~~due ~~repeat~~to inraw ~~the~~material ~~current~~purchases ~~year~~and ~~given~~drug ~~the~~manufacturing ~~conclusion~~activities ofto support the ~~Phase 2~~ trial ofduring ~~quisovalimab~~the incurrent ~~June 2023~~year.

50Additionally, stock-based compensation increased $3.6 million compared to the year ended December 31, 2024 due to option and restricted stock unit grants made during the second half of 2024 and in 2025, including the annual employee grants in August 2024 and January 2025, as well as headcount additions. Salaries, benefits and related costs increased $2.3 million compared to the year ended December 31, 2024 primarily due to headcount additions.

~~Table~~We expect research and development expenses to be largely consistent with 2025 through the Phase 2 LOTUS trial topline data readout expected in the second quarter of ~~Contents~~2026, however, expenses beyond the data readout are difficult to predict given they will be highly dependent on the outcome of the trial.

~~Salaries,~~Acquired ~~benefits and related costs increased $2.6 million in the current period primarily due to increased non~~In-~~equity~~Process ~~incentive~~Research ~~plan compensation expense incurred. Stock-based compensation expense increased $1.1 million due to option~~ and ~~restricted stock unit grants during the period, including the annual grant in August 2024.~~ Development

WeIn ~~expect~~the ~~future~~first ~~research~~quarter ~~and~~of ~~development~~2024, ~~expenses~~we toacquired ~~increase~~abdakibart (AVTX-009) through the AlmataBio Transaction (as adefined ~~result~~in ofNote ~~our~~3 ~~development~~to ~~plans~~the ~~for~~consolidated ~~AVTX~~financial statements included in this Annual Report on Form 10-~~009~~K), ~~including~~resulting ~~the~~in ~~continued~~us ~~execution~~acquiring $27.6 million of ~~the~~in-process ~~LOTUS~~research ~~Trial~~and ~~which~~development ~~commenced~~(“IPR&D”) infor ~~October~~the year ended December 31, 2024. There was no acquired IPR&D for the year ended December 31, 2025.

Acquired in-process research and development

In the first quarter of 2024, we acquired AVTX-009 pursuant to the AlmataBio Transaction (as defined in Note 3 to the consolidated financial statements), resulting in us recording $27.6 million of acquired in-process research and development (“IPR&D”). We recognized the fair value of the IPR&D, substantially all of which is related to AVTX-009, for the year ended December 31, 2024 as there is no alternative future use. There was no acquired IPR&D for the year ended December 31, 2023.

General and Administrative Expenses

The following table summarizes our general and administrative expenses for the years ended December 31, ~~2024~~2025 and ~~2023~~2024:

	Year Ended December 31,
	2024		2023
	(in thousands)
Salaries, benefits and related costs	$	4,634	$	2,340
Legal, consulting and other professional expenses	7,096		4,959
Stock-based compensation expense	3,450		2,157
Commercial planning and marketing expenses	789		33
Other	1,272		811
	$	17,241	$	10,300

General and administrative expenses increased $6.9 million for the year ended December 31, 2024, compared to the year ended December 31, 2023. The increase was driven by a $2.3 million increase in salaries, benefits and related costs due to increased non-equity incentive plan compensation expense, as well as a $1.3 million increase to stock-based compensation expense due to option and restricted stock unit grants during the period, including the annual grant in August 2024. In addition, legal, consulting and other professional expenses increased $2.1 million for accounting and reporting work incurred as well as increased consulting services following and largely related to the AlmataBio acquisition and March 2024 private placement. Commercial planning and marketing expenses increased $0.8 million due to work performed for HS and indication expansion, such as market opportunity assessments and competitive intelligence.

Although we expect the majority of our future operating expense increases will be focused on research and development activities to progress AVTX-009, we also expect moderate increases to general and administrative expenses to support the AVTX-009 program.

Goodwill Impairment

There was no goodwill impairment loss recognized for the year ended December 31, 2024. The Company recognized $3.9 million of goodwill impairment loss for its sole reporting unit for the year ended December 31, 2023 as part of its annual goodwill impairment test performed on the last day of the fiscal year. The impairment loss recognized represented the difference between the reporting unit’s carrying value and its fair value as of December 31, 2023.

Other Income (Expense), net

The following table summarizes our other income (expense), net for the years ended December 31, 2024 and 2023:

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	Year Ended December 31,
	2024		2023
	2025		2024
	(in thousands)
Excess of initial warrant fair value over private placement proceeds	$	(79,276)	$	—
Salaries, benefits and related costs	$	6,558	$	4,634
Change of fair value of warrant liability	121,611		—
Legal, consulting and other professional expenses	6,786		7,096
Private placement transaction costs	(9,220)		—
Stock-based compensation expense	7,629		3,450
Change in fair value of derivative liability	(2,930)		(720)
Commercial planning and marketing expenses	470		789
Interest income (expense), net	3,317		(3,417)
Other	1,457		1,272
Other expense, net	(5)		(42)
	$	22,900	$	17,241
	$	33,497	$	(4,179)

~~Other~~General ~~income,~~and ~~net~~administrative expenses increased $375.7 million for the year ended December 31, ~~2024~~2025 as compared to the prior year period. inThe ~~2023,~~increase ~~primarily~~was driven primarily by ~~the~~a ~~accounting~~$4.2 million ~~impact~~increase ofin ~~the~~stock-based ~~warrant~~compensation ~~liability~~expense ~~associated~~due ~~with~~to ~~the~~option ~~warrants~~and ~~issued~~restricted instock ~~the~~unit ~~March~~grants ~~2024~~made ~~financing~~during ~~that were subsequently exercised in~~ the ~~fourth~~second ~~quarter~~half of 2024. ~~For~~and ~~the~~in ~~year ended December 31~~2025, ~~2024,~~including ~~we recognized a $79.3 million loss at issuance on~~ the ~~excess~~annual ofgrants ~~initial~~in ~~warrant~~August ~~liability~~2024 ~~fair~~and ~~value~~January ~~($194.9 million)~~2025 ~~over~~as ~~the~~well ~~private~~as ~~placement~~new ~~proceeds~~hire ~~($115~~grants.~~6 million).~~ ~~The~~Salaries, ~~loss~~benefits ~~was~~and ~~more~~related ~~than~~costs ~~offset~~increased ~~by a~~ $~~121~~1.~~6 million gain recognized on the change in fair value of the warrant liability from its initial valuation ($194.~~9 million) compared to the ~~settlement~~year ofended ~~the~~December ~~warrant~~31, ~~liability in the fourth quarter of~~ 2024 ~~($73.3~~due ~~million)~~to ~~upon~~headcount ~~the full exercise of the warrants~~additions. This ~~gain~~increase was ~~mainly~~partially ~~driven~~offset by a ~~decrease in the stock price from the initial valuation (~~$210.753 million ~~per~~decrease ~~share)~~ to ~~the~~commercial ~~stock~~planning ~~prices~~and onmarketing ~~each warrant exercise date (weighted average of approximately $12.00 per share). Given the full exercise of the warrants in the fourth quarter of 2024, there was no warrant liability~~ as ~~of December 31, 2024, and~~ we ~~therefore~~transitioned docertain ~~not~~third-party ~~expect~~consulting ~~related~~engagements ~~future~~for ~~activity~~market inopportunity ~~other~~assessments ~~income~~and ~~(expense),~~competitive ~~net.~~intelligence ~~Refer~~ to ~~Note~~salaried ~~6 - Fair Value Measurements of the consolidated financial statements for more information~~headcount.

~~Additionally,~~These ~~interest~~increases ~~income~~were ~~increased~~partially offset by a $60.73 million ~~contributing~~decrease toin ~~the~~legal, ~~overall~~consulting ~~increase~~and to other ~~income,~~professional ~~net.~~expenses ~~The~~compared ~~increase~~to ~~was~~the aprior ~~result~~year ofperiod ~~the~~related ~~Company’s~~to increased ~~cash~~expenses ~~position,~~incurred ~~paired~~in ~~with~~the noprior ~~interest~~period ~~expense~~for inaccounting, ~~2024~~reporting ~~given~~and consulting services incurred following the ~~Company’s~~AlmataBio ~~full~~Transaction ~~payoff~~and ofconcurrent ~~its~~private ~~loan~~placement financing in ~~2023~~March 2024.

~~The~~We ~~increase~~expect ingeneral other income, net was partially offset by a $2.9 million loss recognized on the increase in fair value of the derivative liability driven by changes in assumptions utilized in the valuation of both the AVTX-501 Milestone and ~~the~~administrative ~~AVTX-007~~expenses ~~Milestones and Royalties (as defined in Note 6 - Fair Value Measurements of the consolidated financial statements) due~~ to ~~updated~~be ~~publicly~~largely ~~available~~consistent ~~information~~with of2025 ~~the~~through ~~development plans for~~ the ~~assets~~Phase by2 ~~J&J~~LOTUS ~~and~~trial ~~Apollo,~~topline ~~respectively~~data ~~(as~~readout ~~defined~~expected in ~~Note 6 to~~ the ~~consolidated~~second ~~financial~~quarter ~~statements). Refer to Note 6 - Fair Value Measurements~~ of ~~the consolidated financial statements for more information. The overall increase to other income~~2026, ~~net was also partially offset by $9.2 million of private placement transaction costs~~however, ~~largely~~expenses ~~consisting~~beyond of the ~~private~~data ~~placement~~readout ~~agent~~are ~~fee~~difficult ofto ~~$7.0 million~~predict ~~due~~given inthey ~~March~~will ~~2024~~be ~~and~~highly ~~$1.7 million~~dependent ~~due~~ on the ~~exercise~~outcome of the ~~warrants~~trial.

Other (Expense) Income, net

The following table summarizes our other (expense) income, net for the years ended December 31, 2025 and 2024:



	Year Ended December 31,
	2025		2024

	(in thousands)
Change in fair value of derivative liability	(9,520)		(2,930)
Interest income, net	4,351		3,312
Excess of initial warrant fair value over private placement proceeds	$	—	$	(79,276)
Change of fair value of warrant liability	—		121,611
Private placement transaction costs	—		(9,220)

	$	(5,169)	$	33,497

Other expense, net was $5.2 million for the year ended December 31, 2025 compared to other income, net of $33.5 million for the prior year period ended December 31, 2024. The $38.7 million change was primarily driven by (i) the accounting impact in the prior period of the warrant liability associated with the warrants issued in the March 2024 financing that were subsequently exercised in the fourth quarter of 2024, and (ii) the change in the fair value of the derivative liability in the current period driven by changes in assumptions related to the AVTX-007 Milestones and Royalties (as defined in Note 6 to the consolidated financial statements included in this Annual Report on Form 10-K). Further, we incurred $9.2 million of private placement transaction costs in the prior year period that did not repeat in the current period, largely consisting of the placement agent fee of $7.0 million and $1.7 million fee payable upon exercise of the warrants issued in the private placement investment.

Income Tax Expense

The following table summarizes our income tax expense for the years ended December 31, ~~2024~~2025 and ~~2023~~2024:

	Year Ended December 31,
	2024		2023
	(in thousands)
Income tax expense	$	114	$	14

The Company recognized minimal income tax expense for the years ended December 31, 2024 and 2023.

Liquidity and Capital Resources, including Capital Expenditure and Cash Requirements

Since inception, we have incurred significant operating and cash losses from operations. We have primarily funded our operations to date through sales of equity securities, out-licensing transactions and sales of assets.

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For the year ended December 31, 2024, Avalo generated a net loss of $35.1 million and negative cash flows from operations of $49.1 million. As of December 31, 2024, Avalo had $134.5 million in cash and cash equivalents. For the year ended December 31, 2024, the Company raised approximately $175.8 million of net proceeds from a private placement and the subsequent exercise of warrants issued in the private placement.



	Year Ended December 31,
	2025		2024

	(in thousands)
Income tax expense	$	165	$	114

Based on our current operating plans, we expect that our existing cash and cash equivalents are sufficient to fund operations into at least 2027. The Company closely monitors its cash and cash equivalents and seeks to balance the level of cash and cash equivalents with our projected needs to allow us to withstand periods of uncertainty relative to the availability of funding on favorable terms. We ~~may~~recognized ~~satisfy~~minimal ~~any~~income ~~future~~tax ~~cash~~expense ~~needs~~for ~~through sales of equity securities under~~ the ~~Company’s~~years ~~at-the-market~~ended ~~program or other equity financings~~December 31, ~~out-licensing~~2025 ~~transactions, strategic alliances/collaborations, sale of programs,~~ and~~/or~~ ~~mergers and acquisitions~~2024. There can be no assurance that any financing or business development initiatives can be realized by the Company, or if realized, what the terms may be. To the extent that we raise capital through the sale of equity, the ownership interest of our existing stockholders will be diluted, and the terms may include liquidation or other preferences that adversely affect the rights of our stockholders. Further, if the Company raises additional funds through collaborations, strategic alliances or licensing arrangements with third parties, the Company might have to relinquish valuable rights to its technologies, future revenue streams, research programs or product candidates.

Liquidity and Capital Resources, including Capital Expenditure and Cash Requirements

Since inception, we have incurred significant operating losses and negative cash flows from our operations. We have primarily funded our operations to date through sales of equity securities, out-licensing transactions and sales of assets.

For the year ended December 31, 2025, we generated a net loss of $78.3 million and negative cash flows from operations of $51.5 million. As of December 31, 2025, we had $98.3 million in cash and cash equivalents and short-term investments.

Based on our current operating plans, we expect that our existing cash, cash equivalents and short-term investments are sufficient to fund operations into 2028. We closely monitor our cash and cash equivalents and seek to balance the level of cash and cash equivalents with our projected needs to allow us to withstand periods of uncertainty relative to the availability of funding on favorable terms. We may satisfy any future cash needs through sales of equity securities under the our at-the-market program or other equity financings, out-licensing transactions, strategic alliances/collaborations, sale of programs, and/or mergers and acquisitions. There can be no assurance that any financing or business development initiatives can be realized by us, or if realized, what the terms may be. To the extent that we raise capital through the sale of equity, the ownership interest of our existing stockholders will be diluted, and the terms may include liquidation or other preferences that adversely affect the rights of our stockholders. Further, if we raise additional funds through collaborations, strategic alliances or licensing arrangements with third parties, we might have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates.

Uses of Liquidity

~~The~~We ~~Company~~ primarily ~~uses~~use cash to fund the ongoing development of ~~our~~abdakibart ~~research~~(AVTX-009) and ~~development pipeline assets and~~ costs associated with its organizational infrastructure. As of December 31, ~~2024~~2025, ~~Avalo~~we had $~~134~~98.5 3 million in cash and cash equivalents, ~~representing~~and ashort-term ~~$127~~investments.~~1 million~~ ~~increase compared to December 31, 2023.~~ We expect cash used in ~~operating~~operations ~~activities,~~to ~~excluding~~be ~~the~~largely ~~milestone~~consistent ~~payments~~with ~~made~~2025 tothrough the ~~former~~Phase ~~AlmataBio~~2 ~~stockholders,~~LOTUS totrial ~~increase~~topline indata ~~future~~readout ~~periods~~expected asin athe ~~result~~second quarter of ~~our~~2026, ~~development~~however, ~~plans~~cash ~~for~~used ~~AVTX-009,~~in ~~including~~operations beyond the ~~execution~~data ofreadout ~~the~~are ~~LOTUS~~difficult ~~Trial~~to ~~which~~predict ~~commenced~~given inthey ~~October~~will ~~2024~~be highly dependent on the outcome of the trial.

Cash Flows

The following table summarizes our cash flows for the years ended December 31, ~~2024~~2025 and ~~2023~~2024:

	Year Ended December 31,
	2024		2023
	2025		2024
	(in thousands)
Net cash provided (used in) by:
Net cash (used in) provided by:
Operating activities	$	(4951,~~056~~458)	$	(3049,~~680~~056)
Investing activities	~~356~~(81,720)		~~(133)~~356
Financing activities	~~175~~14,~~849~~587		25175,~~042~~849
Net increase (decrease) in cash and cash equivalents	$	127,149	$	(5,771)
Net (decrease) increase in cash and cash equivalents	$	(118,591)	$	127,149

Net cash used in operating activities

Net cash used in operating activities inwas ~~2024~~$51.5 ~~consisted~~million ~~primarily~~for ofthe ayear ~~net~~ended ~~loss~~December of31, ~~$35.1~~2025 ~~million~~ and ~~non-cash~~consisted ~~adjustments~~primarily toof ~~reconcile~~ net loss toof ~~net~~$78.3 ~~cash~~million, ~~used~~partially inoffset ~~operating~~by ~~activities~~net ~~including~~non-cash ~~the~~charges ~~change in fair value~~ of ~~the warrant liability of~~ $~~121~~23.6 0 million, ~~excess~~and ofchanges ~~initial~~in ~~warrant~~our ~~fair~~operating ~~value~~assets ~~over~~and ~~private~~liabilities ~~placement proceeds~~ of $~~79.~~3 .8 million,. ~~acquired~~The ~~IPR&D~~non-cash charges consisted primarily of $2713.6 million, ~~$12.5~~in ~~million~~stock-based ~~milestone~~compensation ~~payments~~and ~~made~~a ~~to the former AlmataBio stockholders, the~~ change in the fair value of the derivative liability of $2.9.5 million,. ~~and~~Changes ~~stock-based~~in ~~compensation~~our ofoperating ~~$5.9~~assets ~~million.~~and ~~Prepaid~~liabilities ~~expenses~~consisted ~~increased~~primarily of a $2.96 million ~~from~~increase ~~December~~in ~~31, 2023 due to the increased research and development activity for AVTX-009.~~

Net cash used in operating activities in 2023 consisted primarily of a net loss of $31.5 million and non-cash adjustments to reconcile net loss to net cash used in operating activities, including goodwill impairment of $3.9 million, stock-based compensation of $3.5 million, accretion of debt discount of $1.8 million, and increase in fair value of the derivative liability of $0.7 million. Accrued expenses and accounts payable decreased an aggregate of $11.5 million from December 31, 2022.65

We expect cash used in operating activities, excluding the milestone payments made to the former AlmataBio stockholders, to increase in future periods as a result of our development plans for AVTX-009, including the continued execution of the LOTUS Trial which commenced in October 2024.

Net cash provided by (used in) investing activities

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~~Net~~prepaid ~~cash~~expenses ~~provided~~and byother ~~investing~~current ~~activities~~assets ~~for~~due ~~the~~to ~~year~~our ~~ended~~ongoing ~~December~~clinical ~~31,~~work ~~2024~~and ~~consisted~~a of$6.7 ~~the~~million ~~cash~~increase ~~acquired~~in asaccrued ~~part~~expenses ofand ~~the~~other ~~AlmataBio~~liabilities ~~Transaction.~~primarily ~~Net~~due ~~cash~~to ~~used~~increased indrug ~~investing~~manufacturing activities ~~was~~as ~~minimal~~well ~~for~~as ~~the~~compensation ~~year~~and ~~ended~~benefits ~~December 31, 2023~~accruals.

Net cash used in operating activities in 2024 consisted primarily of a net loss of $35.1 million and non-cash adjustments to reconcile net loss to net cash used in operating activities including the change in fair value of the warrant liability of $121.6 million, excess of initial warrant fair value over private placement proceeds of $79.3 million, acquired IPR&D of $27.6 million, $12.5 million milestone payments made to the former AlmataBio stockholders, the change in fair value of the derivative liability of $2.9 million, and stock-based compensation of $5.9 million. Prepaid expenses increased $2.9 million from December 31, 2023 due to the increased research and development activity for abdakibart (AVTX-009).

We expect cash used in operations to be largely consistent with 2025 through the Phase 2 LOTUS trial topline data readout expected in the second quarter of 2026, however, cash used in operations beyond the data readout are difficult to predict given they will be highly dependent on the outcome of the trial.

Net cash (used in) provided by investing activities

Net cash used in investing activities for the year ended December 31, 2025 consisted of $113.7 million of purchases of available-for-sale investments, partially offset by $32.0 million of proceeds from maturities of available-for-sale investments.

Net cash provided by investing activities for the year ended December 31, 2024 consisted of the cash acquired as part of the AlmataBio Transaction.

Net cash provided by financing activities

Net cash provided by financing activities for the year ended December 31, 2025 consisted of proceeds of $14.8 million from the sales of shares made pursuant to our “at-the-market” sales agreement and proceeds of $0.8 million from stock option exercises, partially offset by $0.5 million in cash paid to tax authorities related to withholding shares to satisfy RSU vesting withholding obligations on behalf of employees.

Net cash provided by financing activities for the year ended December 31, 2024 consisted of gross proceeds of $115.6 million from the private placement that closed on March 28, 2024 and $69.4 million of gross proceeds from the exercise of warrants in the fourth quarter of 2024. The increase was partially offset by $7.5 million of transaction costs paid related to the private placement and $1.7 million of transaction costs paid related to the warrant exercises.

Net cash provided by financing activities for the year ended December 31, 2023 consisted of net proceeds of $46.2 million from equity financings, partially offset by debt principal payments of $21.2 million, inclusive of the full payoff of the loan in September of 2023. Avalo fully retired its debt in 2023.

Critical Accounting Estimates and Assumptions

In preparing the financial statements, ~~the~~we ~~Company~~make ~~makes~~ estimates and assumptions that have an impact on assets, liabilities, revenue and expenses reported. These estimates can also affect supplemental information disclosed by us, including information about contingencies, risk and financial condition. ~~The~~We ~~Company believes~~believe, given current facts and circumstances, our estimates and assumptions are reasonable, adhere to U.S. generally accepted accounting principles (“GAAP”) and are consistently applied. Inherent in the nature of an estimate or assumption is the fact that actual results may differ from estimates, and estimates may vary as new facts and circumstances arise.

While our significant accounting policies are more fully described in Note 2 to the consolidated financial statements appearing at the end of this Annual Report on Form 10-K, we believe the following accounting policies are critical to the understanding of our financial condition and results.

Stock-Based Compensation

~~The~~We ~~Company~~apply ~~applies~~ the provisions of ASC 718, Compensation—Stock Compensation, which requires the measurement and recognition of compensation expense for all stock‑based awards made to employees, including employee stock options, in the statements of operations and comprehensive loss.

For stock options issued to employees and members of the board of directors for their services, ~~the~~we ~~Company~~estimate ~~estimates~~ the grant date fair value of each option using the Black‑Scholes option pricing model. The use of the Black‑Scholes option pricing model requires management to make assumptions with respect to the expected term of the option, the expected volatility of the common stock consistent with the expected ~~life~~term of the option, risk‑free interest rates and expected dividend yields of the common stock. Additionally, the stock price on the date of grant is utilized in the Black-Scholes option pricing model. For awards subject to service‑based vesting conditions, including those with a graded vesting schedule, the Company recognizes stock‑based compensation expense equal to the grant date fair value of stock options on a straight‑line basis over the requisite service period, which is generally the vesting term. Forfeitures are recorded as they are incurred as opposed to being estimated at the time of grant and revised.

~~The assumptions we used to determine the fair value of stock options granted to employees and members of the board of directors are as follows:~~66

	Year Ended December 31,
Service-based options	2024			2023
Expected term of options (in years)	5.81	—	6.25	5.00	—	6.25
Expected stock price volatility	113.1%	—	116.9%	89.8%	—	146.0%
Risk-free interest rate	3.70%	—	4.26%	3.43%	—	4.13%
Expected annual dividend yield	0%			0%

The estimates involved in the valuations include inherent uncertainties and the application of our judgment. As a result, if factors change and we use significantly different assumptions or estimates when valuing our stock options, our stock‑based compensation expense could be materially different. We recognize compensation expense for only the portion of awards that are expected to vest.

Warrant Liability

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Onincluding ~~March~~those ~~28,~~with ~~2024, the Company closed~~ a ~~private~~graded ~~placement~~vesting ~~in which the investors received (i) 19~~schedule,~~946~~ ~~shares~~we ofrecognize ~~Series~~stock‑based Ccompensation ~~Preferred~~expense ~~Stock~~equal ~~and (ii) warrants~~ to ~~purchase~~the upgrant todate anfair ~~aggregate~~value of ~~11,967,526 shares of Avalo’s common~~ stock ~~(or~~options on a ~~number~~straight‑line ofbasis ~~shares~~over ~~of Series C Preferred Stock convertible into~~ the ~~number~~requisite ofservice ~~shares~~period, ofwhich ~~common~~is ~~stock~~generally the ~~warrant~~vesting ~~is then exercisable into) with an exercise price of $5~~term.~~796933.~~ ~~Refer~~Forfeitures toare ~~Note~~recorded 11as -they ~~Capital~~are ~~Structure and sub-header “March 2024 Financing” of the consolidated financial statements for more information~~incurred.

The ~~Company~~assumptions ~~determined~~we ~~that~~used ~~the~~to ~~warrants~~determine ~~did not satisfy~~ the ~~conditions~~fair tovalue beof ~~accounted~~stock ~~for~~options asgranted ~~equity~~to ~~instruments.~~employees Asand ~~the~~members ~~warrants~~of ~~did not meet~~ the ~~equity~~board ~~contract~~of ~~scope~~directors ~~exception,~~are ~~the Company classified the warrants~~ as ~~a derivative liability upon issuance.~~ follows:

The Company’s warrant liability was measured at fair value on the issuance date and was measured at fair value each reporting period thereafter until the warrants were fully exercised in the fourth quarter of 2024. As of December 31, 2024, there were no warrants associated with the private placement outstanding and thus no corresponding warrant liability.


	Year Ended December 31,
Service-based options	2025			2024
Expected term of options (in years)	5.00	—	6.10	5.81	—	6.25
Expected stock price volatility	99.9%	—	113.1%	113.1%	—	116.9%
Risk-free interest rate	3.73%	—	4.45%	3.70%	—	4.26%
Expected annual dividend yield	0%			0%

~~For~~Each ~~the~~Restricted ~~initial~~Stock ~~warrant~~Unit ~~valuation~~(“RSU”) inrepresents ~~the~~one ~~first~~equivalent ~~quarter~~share of ~~2024~~our ~~and~~common ~~subsequent~~stock ~~fair~~to ~~value~~be ~~measurement~~issued atafter ~~each~~satisfying ~~reporting period prior to exercises,~~ the ~~Company~~applicable ~~utilized~~continued ~~the Black~~service-~~Scholes~~based ~~option~~vesting ~~pricing~~criteria ~~model~~over toa ~~measure~~specified period. The fair value of ~~the~~these ~~warrants,~~RSUs ~~which~~is ~~required~~based ~~assumptions~~on ~~including~~ the ~~value~~closing price of ~~the~~our common stock on the ~~measurement~~ date, ~~exercise~~of ~~price, expected term, expected volatility, and~~ the ~~risk-free interest rate~~grant. ~~Certain assumptions, including the expected term and expected volatility, were subjective and required judgment.~~ The ~~warrant~~compensation ~~liability~~for ~~was~~RSUs ~~classified~~is asrecognized on a ~~Level~~straight-line 3basis ~~instrument~~over asthe ~~its~~vesting ~~value was based on unobservable market inputs~~period.

~~The~~Each ~~initial~~Performance ~~fair~~Stock ~~value~~Unit ~~measurement~~(“PSU”) ofrepresents ~~the~~one ~~warrant~~equivalent ~~liability~~share ~~was~~of ~~$194.9~~our ~~million~~common ~~and~~stock ~~exceeded~~to ~~the~~be ~~initial~~issued ~~gross~~after ~~proceeds~~achievement ~~received~~of ~~from~~ the ~~private~~performance ~~placement~~goals ofspecified ~~$115.6 million, resulting~~ in athe ~~$79~~grant.~~3 million~~ ~~loss~~We atestimate ~~issuance of~~ the ~~excess of initial liability~~ fair value. ~~Upon exercise~~ of ~~the~~our ~~warrants~~PSUs inas ~~the fourth quarter~~ of ~~2024,~~ the ~~final~~grant ~~fair~~date ~~value~~based ofupon the ~~warrant~~expected ~~liability~~likelihood ~~was~~of ~~$73.3~~achievement ~~million. Given the full exercise~~ of the ~~warrants,~~performance ~~there~~goals ~~was~~specified ~~no warrant liability as of December 31, 2024, resulting~~ in the ~~$121.6~~grant ~~million~~and ~~gain on~~ the ~~change~~closing inmarket ~~fair~~price ~~value~~of ~~recognized~~our incommon ~~other~~stock ~~income~~on ~~(expense), net in~~ the ~~accompanying~~date ~~consolidated financial statements~~ of ~~operations and comprehensive loss for the year ended December 31, 2024~~grant. ~~Refer~~We torecognize ~~Note 11~~ stock-based ~~Capital~~compensation ~~Structure~~expense ofover the ~~consolidated~~requisite ~~financial~~service ~~statements~~period, ~~for~~if ~~additional~~it ~~discussion~~is ~~regarding~~probable ~~the~~that ~~issuance of~~ the ~~Series~~performance Cgoal ~~Preferred~~will ~~Stock~~be ~~and common stock pursuant to the warrant exercises~~achieved.

Derivative Liability

In the fourth quarter of 2022, ~~Avalo~~we sold ~~its~~our economic rights to future milestone and royalty payments for previously out-licensed assets AVTX-501, AVTX-007, and AVTX-611 to ES Therapeutics, LLC (“ES”), an affiliate of Armistice Capital ~~Master Fund Ltd. (an affiliate of Armistice Capital,~~ LLC, ~~and collectively~~ (“Armistice”), in exchange for $5.0 million (the “ES Transaction”). At the time of the transaction, Armistice was a significant stockholder of ~~the~~ours ~~Company~~ whose chief investment officer, Steven Boyd, and managing director, Keith Maher, served on ~~Avalo’s~~our Board until August 8, 2022. The ES Transaction was approved in accordance with ~~Avalo’s~~our related party transaction policy.

The economic rights sold include (a) rights to a milestone payment of $20.0 million upon the filing and acceptance of an NDA for AVTX-501 pursuant to an agreement with Janssen ~~Pharmaceuticals~~Pharmaceutics, Inc., now Johnson & Johnson Innovative Medicine (“J&J”) (the “AVTX-501 Milestone”) and (b) rights to any future milestone payments and royalties relating to AVTX-007 under a license agreement with Apollo AP43 Limited (“Apollo”), including up to $6.25 million of development milestones, up to $67.5 million in sales-based milestones, and royalty payments over a ten year period of a low single digit percentage of annual net sales (which percentage increases to another low single digit percentage if annual net sales exceed a specified threshold) (the “AVTX-007 Milestones and Royalties”). In addition, ~~Avalo~~we waived all ~~its~~of our rights to AVTX-611 sales-based payments of up to $20.0 million that were payable by ES.

The exchange of the economic rights of the AVTX-501 Milestone and AVTX-007 Milestones and Royalties for cash met the definition of a derivative instrument. The fair value of the derivative liability is determined using a combination of a scenario-based method and an option pricing method (implemented using a Monte Carlo simulation). The significant inputs ~~include~~including probabilities of success, expected timing, and forecasted sales as well as market-based inputs for volatility, risk-adjusted discount rates and allowance for counterparty credit risk, ~~all of which~~ are unobservable and based on the best information available to ~~Avalo~~us. Certain information used in the valuation is inherently limited in nature and could differ from J&J’s and Apollo’s internal estimates.

The fair value of the derivative liability as of the transaction date was approximately $4.8 million, of which $3.5 million was attributable to the AVTX-501 Milestone and $1.3 million was attributable to the ~~AVX~~AVTX-007 Milestones and Royalties. Subsequent to the transaction date, at each reporting period, the derivative liability is remeasured at fair value. As of December 31, ~~2024~~2025, the fair value of the derivative liability was $818.5 0 million, all of which was attributable to the AVTX-007 ~~Milestones~~Milestone and Royalties and ~~$0.4 million~~ ~~of which~~ was classified as a current liability with the remainder classified as a non-current liability as of December 31, 2024. For the year ended December 31, 2024, the $2.9 million loss on the change in fair value was recognized in other income (expense), net in the accompanying consolidated statements of operations and comprehensive loss.

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~~The~~classified ~~fair~~as ~~value~~a ~~of the AVTX~~non-~~501~~current ~~Milestone~~liability. ~~was~~For ~~deemed~~the toyear beended ~~$0.0~~December ~~million~~31, driven by less than 1% probability of success based on Avalo’s interpretation of a recent announcement from J&J noting the discontinuation of the aticaprant depression program (previously referred to as AVTX-501 by Avalo)2025, ~~which was~~ the only indication that we are aware they were pursuing, paired with a lack of commitment to an alternative indication. The fair value of AVTX-007 Milestones and Royalties was primarily driven by sales forecasts with peak annual net sales reaching $19.~~8 billion~~5 inmillion ~~atopic~~change ~~dermatitis, which is a much larger market opportunity than adult-onset Still’s disease (the previous indication being pursued that was contemplated~~ in valuations through the first quarter of 2024), an approximate 17% probability of success, and an estimated time to commercialization of approximately 6.0 years. We estimated these unobservable inputs based on limited publicly available information and therefore could differ from J&J’s and Apollo’s respective internal development plans, assessments of probability of success and other inputs of our fair value ~~calculation.~~was ~~Any~~recognized ~~changes to these inputs may result~~ in ~~significant~~other ~~changes to the fair value measurement. Notably~~expense, ~~the peak annual~~ net ~~sales~~in ~~forecast (for~~ the ~~AVTX-007~~accompanying consolidated ~~Milestones~~statements ~~and Royalties) and the probability~~ of ~~success~~operations ~~(for both the AVTX-501 Milestone~~ and ~~the~~comprehensive ~~AVTX-007 Milestone and Royalties) are the largest drivers of the fair value, so changes to either would likely result in significant changes to the fair value~~loss.

InThe ~~the~~fair ~~event~~value ~~that~~of ~~J&J~~the ~~and/or~~AVTX-501 ~~Apollo~~Milestone ~~are~~was ~~required~~deemed to ~~make~~be ~~payment(s)~~de tominimis, ESdriven ~~Therapeutics~~by ~~pursuant~~less tothan ~~the~~1% ~~underlying~~probability ~~agreements~~of success based on our interpretation of an announcement from J&J in March 2025, ~~Avalo~~noting ~~will~~the ~~recognize~~discontinuation ~~revenue~~of ~~under~~the ~~its~~aticaprant ~~existing~~depression ~~contracts~~program ~~with~~(previously ~~those~~referred ~~customers~~to ~~for~~as ~~that~~AVTX-501 ~~amount~~by ~~when~~us), itwhich iswas nothe ~~longer~~only ~~probable~~indication ~~there~~publicly ~~would~~disclosed, bepaired with a ~~significant~~lack ~~revenue~~of ~~reversal~~commitment ~~with~~to ~~any~~an ~~differences~~alternative ~~between~~indication. ~~the~~The fair value of ~~the~~AVTX-007 ~~derivative~~Milestones ~~liability~~and ~~related~~Royalties towas ~~that~~primarily ~~payment~~driven ~~immediately~~by ~~prior~~sales toforecasts ~~the~~with ~~revenue~~peak ~~recognition~~annual ~~and~~net ~~revenue~~sales ~~recognized~~reaching to$1.7 billion bein ~~recorded~~atopic asdermatitis, ~~other~~an ~~expense.~~approximate ~~However,~~41% ~~given~~probability ~~Avalo~~of issuccess, noand ~~longer~~an ~~entitled~~estimated time to ~~collect~~commercialization ~~these~~of ~~payments~~approximately 6.5 years, ~~the~~based ~~potential~~on ~~ultimate~~our ~~settlement~~interpretation of Apollo’s September 2025 announcement that the ~~payments~~drug inmet the ~~future~~primary endpoint in its Phase 2a clinical trial in atopic dermatitis. We estimated these unobservable inputs based on limited publicly available information and therefore could differ from J&J’s and~~/or~~ Apollo’s respective internal development plans, assessments of probability of success and other inputs of our fair value calculation. Any changes to ESthese ~~Therapeutics~~inputs may result in significant changes to the fair value measurement. Notably, the peak annual net sales forecast (for the AVTX-007 Milestones and Royalties) and the ~~future~~probability ~~mark~~of success (for both the AVTX-~~to-market~~501 ~~activity~~Milestone ~~each~~and ~~reporting~~the ~~period~~AVTX-007 Milestone and Royalties) ~~will~~are ~~not~~the ~~impact~~largest ~~Avalo’s~~drivers ~~future~~of ~~cash~~the ~~flows~~fair value, so changes to either would likely result in significant changes to their respective fair values.

~~Asset~~In ~~Acquisition~~the event that J&J and/or Apollo are required to make payment(s) to ES Therapeutics pursuant to the underlying agreements, we will recognize revenue under our existing contracts with those customers for that amount when it is no longer probable there would be a significant revenue reversal with any differences between the fair value of the derivative liability related to that payment immediately prior to the revenue recognition and revenue recognized to be recorded as other expense. However, given we are no longer entitled to collect these payments, the potential ultimate settlement of the payments in the future from J&J and/or Apollo to ES Therapeutics (and the future mark-to-market activity each reporting period) will not impact our future cash flows.

To evaluate a transaction to assess whether or not the transaction should be accounted for as a business combination or asset acquisition, the Company first applies a screen test to determine if substantially all of the fair value of the gross assets acquired is concentrated in a single identifiable asset or group of similar identifiable assets. If the screen is met, the transaction is accounted for as an asset acquisition. If the screen is not met, further determination is required as to whether the Company has acquired inputs and processes that have the ability to create outputs which would meet the definition of a business. Significant judgment is required in the application of the screen test to determine whether an acquisition is a business combination or an acquisition of assets.

In the first quarter of 2024, we acquired AVTX-009, through a merger with AlmataBio and its wholly owned subsidiary, resulting in us acquiring $27.6 million of IPR&D. The fair value of the IPR&D, substantially all of which is related to AVTX-009, was immediately recognized as acquired IPR&D expense as there is no alternative future use.

Research and Development Costs

Research and development costs are expensed as incurred. These costs include, but are not limited to, expenses incurred under agreements with contract research organizations and investigative sites that conduct clinical trials and preclinical studies; the cost of acquiring, developing and manufacturing clinical trial materials; costs associated with preclinical activities and regulatory operations, pharmacovigilance and quality; costs and milestones associated with certain licensing agreements, and employee‑related expenses, including salaries, benefits and stock‑based compensation of research and development personnel.

Costs for certain development activities, such as clinical trials, are recognized based on an evaluation of the progress to completion of specific tasks using data such as patient enrollment, clinical site activations, or information provided to ~~the~~us ~~Company~~ by ~~its~~our vendors, such as clinical research organizations, with respect to their actual costs incurred. Payments for these activities are based on the terms of the individual arrangements, which may differ from the pattern of costs incurred, and are reflected in the financial statements as prepaid or accrued research and development expense, as the case may be.

~~The~~We ~~Company~~are ~~is a~~ party to license and development agreements for in-licensed research and development assets with third parties. Such agreements often contain future payment obligations such as royalties and milestone payments. ~~The~~We ~~Company~~recognize ~~recognizes~~ a liability (and related research and development expense) for each milestone if and when such milestone is probable and can be reasonably estimated. As typical in the biotechnology industry, each milestone has its own unique risks that ~~the~~we ~~Company~~evaluate ~~evaluates~~ when determining the probability of achieving each milestone and the probability of success evolves over time as the programs progress and additional information is obtained. ~~The~~We ~~Company~~consider ~~considers~~ numerous factors when evaluating whether a given milestone is probable including (but not limited to) the regulatory pathway, development plan, ability to dedicate sufficient funding to reach a given milestone and the probability of success.

Clinical Trial Expense Accruals

56We estimate our expenses resulting from our obligations under contracts with vendors, clinical research organizations and consultants and under clinical site agreements in connection with conducting clinical trials. The financial terms of these contracts are subject to negotiations, which vary from contract to contract and may result in payment flows that do not match the periods over which materials or services are provided under such contracts. Our objective is to reflect the appropriate trial expenses in our financial statements by matching those expenses with the period in which services are performed and efforts are expended. We account for these expenses according to the progress of the trial as measured by subject progression and the timing of various aspects of the trial. We determine accrual estimates by taking into account discussions with applicable personnel and outside service providers as to the progress or state of consummation of trials, or the services completed. During the course of a clinical trial, we adjust our clinical expense recognition if actual results differ from its estimates. We make estimates of our accrued expenses as of each balance sheet date based on the facts and circumstances known at that time. Our clinical trial accruals are dependent upon the timely and accurate reporting of contract research organizations and other third‑party vendors. Although we do not expect our estimates to be materially different from amounts

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The Company estimates its expenses resulting from its obligations under contracts with vendors, clinical research organizations and consultants and under clinical site agreements in connection with conducting clinical trials. The financial terms of these contracts are subject to negotiations, which vary from contract to contract and may result in payment flows that do not match the periods over which materials or services are provided under such contracts. The Company’s objective is to reflect the appropriate trial expenses in its financial statements by matching those expenses with the period in which services are performed and efforts are expended. The Company accounts for these expenses according to the progress of the trial as measured by subject progression and the timing of various aspects of the trial. The Company determines accrual estimates by taking into account discussions with applicable personnel and outside service providers as to the progress or state of consummation of trials, or the services completed. During the course of a clinical trial, the Company adjusts its clinical expense recognition if actual results differ from its estimates. The Company makes estimates of its accrued expenses as of each balance sheet date based on the facts and circumstances known to it at that time. The Company’s clinical trial accruals are dependent upon the timely and accurate reporting of contract research organizations and other third‑party vendors. Although the Company does not expect its estimates to be materially different from amounts actually incurred, ~~its~~our understanding of the status and timing of services performed relative to the actual status and timing of services performed might vary and might result in it reporting amounts that are too high or too low for any particular period.

Off‑Balance Sheet Arrangements

~~The~~We ~~Company~~do ~~does~~ not have any off‑balance sheet arrangements, as defined by applicable SEC rules and regulations.

Recently Adopted Accounting Pronouncements

For a discussion of new accounting standards, see Note 2 to consolidated financial statements contained in this Annual Report on Form 10-K.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk.

As a smaller reporting company, we are not required to provide the information required by this Item.

Item 8. Financial Statements and Supplementary Data.

The consolidated financial statements required to be filed pursuant to this Item 8 are appended to this report. An index of those consolidat

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