UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-K

(Mark One)

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

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

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

oFor ~~ANNUAL~~the ~~REPORT~~transition ~~PURSUANT~~period TOfrom ~~SECTION~~__________ 13to ~~OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934~~__________

For the transition period from to

Commission File Number: 001-38295

~~_________________________________________________________________________________________________________~~_____________________________________________________________________________________

X4 PHARMACEUTICALS, INC.

(Exact name of registrant as specified in its charter)

_____________________________________________________________________________________

Delaware(State or other jurisdiction of incorporation or organization)			27-3181608(I.R.S. Employer Identification No.)
Delaware(State or other jurisdiction ofincorporation or organization)			27-3181608(I.R.S. EmployerIdentification No.)
61 North Beacon Street, 4th FloorBoston, Massachusetts(Address of principal executive offices)			02134(Zip Code)

(857) 529-8300

(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, par value $0.001 per share

XFOR

The Nasdaq Stock Market LLC

Securities registered pursuant to Section 12(g) of the Act: ~~none~~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 (ofor 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 Rule 12b-2 of the Exchange Act.

Large ~~Accelerated~~accelerated ~~Filer~~filer ☐ Accelerated ~~Filer~~filer ☐ Non-accelerated filer ☒ Smaller reporting company ☒ Emerging growth company ☐

~~Indicate~~If an emerging growth company, indicate by check mark ~~whether~~if the registrant has ~~filed~~elected anot ~~report~~to onuse anthe ~~attestation~~extended totransition ~~its~~period ~~management’s~~for ~~assessment~~complying ofwith ~~the~~any ~~effectiveness~~new ofor ~~its~~revised ~~internal~~financial ~~control~~accounting ~~over~~standards ~~financial~~provided ~~reporting~~pursuant ~~under~~to Section ~~404~~ 13(ba) of the ~~Sarbanes-Oxley~~Exchange Act ~~(15 U~~.~~S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. Yes ☐~~ ~~No ☒~~☐

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. Yes ☐ No ☒

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~~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 Exchange Act). Yes ☐ No ☒

On June 30, 2025, the aggregate market value of the registrant’s voting common stock held by non-affiliates of the registrant was approximately $14.9 million based upon the closing sale price on the Nasdaq Capital Market reported on June 30, 2025. In determining the market value of non-affiliate common stock, shares of the registrant’s common stock beneficially owned by officers, directors and affiliates have been excluded. This determination of affiliate status is not necessarily a conclusive determination for other purposes.

Independent Registered Public Accounting Firm PricewaterhouseCoopers LLP Boston, Massachusetts, US Firm ID 238

~~DOCUMENTS~~As ~~INCORPORATED~~of BYMarch 12, ~~REFERENCE~~2026, the registrant had 90,919,696 shares of common stock, $0.001 par value per share, outstanding.

~~Portions~~Documents ofIncorporated the registrant’s definitive proxy statement, (the “2025 Proxy Statement”) for its 2025 Annual Meeting of Stockholders, which the registrant intends to file pursuant to Regulation 14A with the Securities and Exchange Commission not later than 120 days after the registrant’s fiscal year ended December 31, 2024, are incorporated by ~~reference into Part III of this Annual Report on Form 10-K.~~ Reference

Portions of the registrant’s definitive proxy statement, (the “2026 Proxy Statement”) for its 2026 Annual Meeting of Stockholders, which the registrant intends to file pursuant to Regulation 14A with the Securities and Exchange Commission not later than 120 days after the registrant’s fiscal year ended December 31, 2025, are incorporated by reference into Part III of this Annual Report on Form 10-K.

PART I
Item 1.	~~BUSINESS~~Business	5
Item 1A.	~~RISK~~Risk ~~FACTORS~~Factors	2833
Item 1B.	~~UNRESOLVED~~Unresolved ~~STAFF~~Staff ~~COMMENTS~~Comments	6367
Item 1C.	~~CYBERSECURITY~~Cybersecurity	6367
Item 2.	~~PROPERTIES~~Properties	6468
Item 3.	~~LEGAL~~Legal ~~PROCEEDINGS~~Proceedings	6468
Item 4.	~~MINE~~Mine ~~SAFETY~~Safety ~~DISCLOSURES~~Disclosures	6468
PART II		69
Item 5.	~~MARKET~~Market ~~FOR~~For ~~REGISTRANT~~Registrant’Ss ~~COMMON~~Common ~~EQUITY~~Equity, ~~RELATED~~Related ~~STOCKHOLDER~~Stockholder ~~MATTERS~~Matters ~~AND~~and ~~ISSUER~~Issuer ~~PURCHASES~~Purchases OFof ~~EQUITY~~Equity ~~SECURITIES~~Securities	6569
Item 6.	[~~RESERVED~~Reserved]	6569
Item 7.	~~MANAGEMENT~~Management’Ss ~~DISCUSSION~~Discussion ~~AND~~and ~~ANALYSIS~~Analysis OFof ~~FINANCIAL~~Financial ~~CONDITION~~Condition ~~AND~~and ~~RESULTS~~Results OFof ~~OPERATIONS~~Operations	6670
Item 7A.	~~QUANTITATIVE~~Quantitative ~~AND~~and ~~QUALITATIVE~~Qualitative ~~DISCLOSURES~~Disclosures ~~ABOUT~~About ~~MARKET~~Market ~~RISK~~Risk	7678
Item 8.	~~FINANCIAL~~Financial ~~STATEMENTS~~Statements ~~AND~~and ~~SUPPLEMENTARY~~Supplementary ~~DATA~~Data	7678
Item 9.	~~CHANGES~~Changes INin ~~AND~~and ~~DISAGREEMENTS~~Disagreements ~~WITH~~with ~~ACCOUNTANTS~~Accountants ONon ~~ACCOUNTING~~Accounting ~~AND~~and ~~FINANCIAL~~Financial ~~DISCLOSURES~~Disclosures	7678
Item 9A.	~~CONTROLS~~Controls ~~AND~~and ~~PROCEDURES~~Procedures	7678
Item 9B.	~~OTHER~~Other ~~INFORMATION~~Information	7779
Item 9C.	~~DISCLOSURE~~Disclosure ~~REGARDING~~Regarding ~~FOREIGN~~Foreign ~~JURISDICTIONS~~Jurisdictions ~~THAT~~That ~~PREVENT~~Prevent ~~INSPECTIONS~~Inspections	7779
PART III		80
Item 10.	~~DIRECTORS~~Directors, ~~EXECUTIVE~~Executive ~~OFFICERS~~Officers ~~AND~~and ~~CORPORATE~~Corporate ~~GOVERNANCE~~Governance	7880
Item 11.	~~EXECUTIVE~~Executive ~~COMPENSATION~~Compensation	7880
Item 12.	~~SECURITY~~Security ~~OWNERSHIP~~Ownership OFof ~~CERTAIN~~Certain ~~BENEFICIAL~~Beneficial ~~OWNERS~~Owners ~~AND~~and ~~MANAGEMENT~~Management ~~AND~~and ~~RELATED~~Related ~~STOCKHOLDER~~Stockholder ~~MATTERS~~Matters	7880
Item 13.	~~CERTAIN~~Certain ~~RELATIONSHIPS~~Relationships ~~AND~~and ~~RELATED~~Related ~~TRANSACTIONS~~Transactions, ~~AND~~and ~~DIRECTOR~~Director ~~INDEPENDENCE~~Independence	7880
Item 14.	~~PRINCIPAL~~Principal ~~ACCOUNTANT~~Accountant ~~FEES~~Fees ~~AND~~and ~~SERVICES~~Services	7880
PART IV		81
Item 15.	~~EXHIBIT~~Exhibit ~~AND~~and ~~FINANCIAL~~Financial ~~STATEMENT~~Statement ~~SCHEDULES~~Schedules	7981
Item 16.	~~FORM~~Form 10-K ~~SUMMARY~~Summary	8284

EXPLANATORY NOTE

On April 28, 2025, X4 Pharmaceuticals, Inc. (the “Company”), effected a 1-for-30 reverse stock split of its common stock (the “Reverse Stock Split”). Unless otherwise noted, all references to common stock share and per share amounts in this Annual Report on Form 10-K have been retroactively adjusted to reflect the Reverse Stock Split.

See Note 14, “Common Stock and Preferred Stock” of the consolidated financial statements for a description of the Reverse Stock Split.

CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS

This Annual Report on Form 10-K contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). All statements, ~~that~~other ~~relate~~than tostatements ~~future~~of ~~events~~historical orfacts, tocontained in this Annual Report on Form 10-K, including statements regarding our plans, objectives, goals, strategies, future events, future operations, orfuture financial position, future revenues or performance, projected costs, prospects, expectations, plans or intentions relating to clinical development, product candidates, the regulatory approval process, products and markets, and business trends and other information referred to in the sections titled “Business,” “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations,” are forward-looking statements. ~~These~~ In some cases, these statements may be identified by such forward-looking terminology as “may,” “should,” “expects,” “intends,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “continue” or the negative of these terms or other comparable terminology. Our forward-looking statements are based on a series of expectations, assumptions, estimates and projections about our company, are not guarantees of future results or performance and involve substantial risks and uncertainty. We may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements. ~~Actual~~and actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements. These forward-looking statements are subject to a number of known and unknown risks, uncertainties and assumptions, including risks described in the section titled “Risk Factors” and elsewhere in this report, regarding, among other things:

•there can be no assurance that we will be able to regain compliance with Nasdaq’s listing requirements. If we do not regain compliance, our securities may be delisted, which could materially impact the market price and liquidity of our common stock and may adversely affect our ability to raise capital;

•the timing of and our ability to obtain and maintain regulatory approval of our existing product XOLREMDI (mavorixafor), or any product candidates that we may develop in the future, and any related restrictions, limitations, or warnings in the label of any approved product candidates;

•our ability to raise additional capital or achieve sufficient revenue to properly fund our business and operating plan as well as our ability to continue as a going concern;

•our expectations and goals for commercialization of XOLREMDI® (mavorixafor), which has been approved for use as an oral, once-daily therapy to increase the number of circulating mature neutrophils and lymphocytes in patients 12 years of age and older with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome in the U.S., and that XOLREMDI, our one product approved for commercial sale, upon which we depend almost entirely to produce revenue, faces an unknown market size and growth potential, and we have not generated significant revenue from product sales to date, and we may never achieve profitability;

•the initiation, timing, progress and results of our current and future preclinical studies and clinical trials and related preparatory work and the period during which the results of the trials will become available, as well as our research and development programs;

•the potential benefits, including clinical utility, that may be derived from XOLREMDI or any of our product candidates;

•the timing of and our ability to obtain and maintain regulatory approval of our existing product XOLREMDI or any product candidates that we may develop in the future, and any related restrictions, limitations, or warnings in the label of any approved product candidates;

•our plans to research, develop, manufacture and commercialize XOLREMDI or our product candidates;

•the timing of our regulatory filings for our product candidates, along with regulatory developments in the United States and other foreign countries;

•the size and growth potential of the markets for XOLREMDI and our product candidates, if approved, and the rate and degree of market acceptance of XOLREMDI and our product candidates, including reimbursement that may be received from payors;

•the benefits of U.S. Food and Drug Administration (“FDA”) and European Commission (“EC”) designations, including, without limitation, Fast Track, ~~orphan,~~Orphan Drug and Breakthrough Therapy;

•our commercialization, marketing and manufacturing capabilities and strategy;

•our ability to attract and retain qualified employees and key personnel;

•our competitive position and the development of and projections relating to our competitors or our industry;

•our expectations regarding our ability to obtain and maintain intellectual property protection;

•the success of competing therapies that are or may become available;

•our estimates and expectations regarding future operations, financial position, revenues, costs, expenses, uses of cash, capital requirements or our need for additional financing;

•our plans to in-license, acquire, develop and commercialize additional product candidates;

•the impact of laws and regulations;

•our plans to identify additional product candidates with significant commercial potential that are consistent with our commercial objectives;

•our strategies, prospects, plans, expectations or objectives; and

•other risks and uncertainties, including those listed under the section titled “Risk Factors” in this Annual Report.

You should refer to the section titled “Risk Factors” in this Annual Report for a discussion of important factors that may cause our actual results to differ materially from those expressed or implied by our forward-looking statements. As a result of these factors, we cannot assure you that the forward-looking statements in this Annual Report will prove to be accurate. Furthermore, if our forward-looking statements prove to be inaccurate, the inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this Annual Report.

Unless the context requires otherwise, references in this Annual Report to “X4”, “we”, “us” and “our” refer to X4 Pharmaceuticals, Inc. and its subsidiaries.

PART I

~~ITEM~~In 1this Annual Report on Form 10-K, unless context otherwise requires or where otherwise indicated, the terms “X4” “we,” “us,” “our,” and the “Company,” refer to X4 Pharmaceuticals, Inc. ~~BUSINESS~~ and its subsidiaries.

Item 1. Business

Overview

We are a biopharmaceutical company developing and commercializing novel therapeutics for the treatment of rare ~~diseases~~hematology ~~of the immune system~~diseases. WeOur ~~have~~goal ~~successfully developed our first product, mavorixafor, in its first indication. Mavorixafor~~ is ~~an orally available, small-molecule selective antagonist of chemokine receptor CXCR4. Due~~ to ~~its~~build ~~ability~~a toprofitable ~~increase~~company ~~the~~by ~~mobilization~~generating ofincome ~~mature, functional white blood cells~~ from ~~the~~products ~~bone~~we ~~marrow~~develop ~~into~~and ~~the bloodstream~~commercialize, weeither ~~believe~~alone ~~that~~or ~~mavorixafor has the potential to benefit people~~ with ~~a range of immunodeficiencies – a therapeutic market that is principally served by injectable therapies frequently associated with treatment-limiting adverse events~~partners.

InOur ~~April~~primary ~~2024~~asset is mavorixafor, a small molecule delivered in a capsule for oral dosing as a selective antagonist of the ~~U.S.~~chemokine ~~Food~~receptor, ~~and~~CXCR4. ~~Drug~~We ~~Administration~~have ~~(“FDA”)~~one commercially approved product, XOLREMDI® (mavorixafor), which ishas ~~being~~received ~~marketed~~accelerated approval in the ~~U.S.~~United ~~under~~States from the ~~trade~~FDA ~~name XOLREMDI®,~~ for use as an oral, once-daily therapy in patients 12 years of age and older with WHIM ~~syndrome~~ (~~Warts~~warts, ~~Hypogammaglobulinemia~~hypogammaglobulinemia, ~~Infections~~infections, and ~~Myelokathexis~~myelokathexis) syndrome, to increase the number of circulating mature neutrophils and lymphocytes. ~~XOLREMDI~~WHIM syndrome is ~~the~~a ~~first~~rare ~~drug~~combined ~~approved~~primary inimmunodeficiency ~~the~~and ~~U.S.~~chronic toneutropenic ~~treat patients with WHIM syndrome~~disorder. WeMavorixafor ~~launched~~is ~~XOLREMDI in May 2024 and are~~ currently ~~marketing~~being ~~the~~studied ~~drug~~ in ~~the~~a ~~U.S.~~pivotal ~~through~~clinical ~~our~~trial X4in ~~commercial~~chronic ~~team~~neutropenia (“CN”).

We ~~believe~~are ~~that~~focused ~~mavorixafor~~on ~~has~~ the ~~potential~~continued toprogress ~~provide therapeutic benefit across a variety~~ of ~~immune~~our ~~system disorders in addition to WHIM syndrome. As a result~~global, ~~following successful completion of a Phase 2 study evaluating mavorixafor in people with certain chronic neutropenic disorders, we have initiated a~~ pivotal Phase 3 clinical trial ~~of mavorixafor~~ (the “4WARD” ~~study~~trial) to evaluate the efficacy, safety, and tolerability of oral, once-daily mavorixafor (with or without ~~human~~stable doses of granulocyte colony-stimulating factor (“G-CSF”)) in people with congenital, or acquired primary autoimmune, ~~and~~or idiopathic ~~chronic~~CN ~~neutropenia~~ who are experiencing recurrent and/or serious infections. The 52-week trial is a ~~global,~~ randomized, double-blind, placebo-controlled, multicenter study aiming to enroll ~~150~~up ~~participants~~to 176 patients, with full enrollment targeted in the third quarter of 2026. The FDA has granted Fast Track designation to mavorixafor for the treatment of CN.

We are ~~also~~committed ~~seeking~~ to ~~commercialize~~making ~~mavorixafor~~XOLREMDI ~~outside~~available ofto ~~the~~patients ~~U.S. To this end, we announced~~ in ~~January~~need ~~2025 that our Marketing Authorisation Application (“MAA”) for mavorixafor~~ in the ~~treatment of WHIM syndrome was validated for review and is now under evaluation with the European Medicines Agency’s (“EMA”) Committee for Medicinal Products for Human Use~~U. Also in January 2025, we announced that we entered into an exclusive licensing and supply agreement with Norgine Pharma UK Limited (“Norgine”) under which Norgine will commercialize mavorixafor in Europe, Australia, and New Zealand following any regulatory approvals in those territoriesS. Inwhile ~~February~~prioritizing ~~2025,~~our welong-term ~~announced~~strategy ~~that we had entered into an agreement with Taiba Middle East Fz LLC (“taiba rare”)~~ to ~~distribute~~successfully ~~and~~complete ~~commercialize XOLREMDI for~~ the ~~treatment~~4WARD oftrial ~~WHIM syndrome~~ in ~~select~~patients ~~Middle~~with ~~East~~moderate and ~~North~~severe ~~African countries including Saudi Arabia, United Arab Emirates, Qatar, Oman, Kuwait, Bahrain, and Egypt following any regulatory approvals in those countries~~CN.

~~Our~~Management ~~Focus~~and Strategic Changes

~~Since~~In ~~our~~August ~~inception~~2025, wein ~~have~~connection ~~focused~~with ~~our~~the ~~business~~August onPIPE ~~the~~Transaction ~~development~~(as ofdefined ~~small-molecule~~below), ~~oral~~our ~~antagonists~~former ofPresident ~~the~~and ~~chemokine~~Chief ~~receptor~~Executive ~~CXCR4~~Officer, orPaula ~~C-X-C~~Ragan, ~~receptor type 4~~Ph. ~~CXCR4 is a cell receptor that helps regulate the movement of immune cells within the body~~D., ~~CXCR4~~and ~~receptor~~former ~~stimulation~~Chief byFinancial ~~its~~Officer, ~~cognate~~Adam ~~ligand~~Mostafa, ~~CXCL12,~~stepped ~~has~~down ~~been~~from ~~shown~~their torespective ~~play~~roles. aDr. ~~key~~Ragan ~~role~~also inresigned from the ~~maturation~~Company’s ~~and~~Board ~~mobilization~~ of ~~white~~Directors ~~blood cells such as neutrophils, lymphocytes~~ (~~including~~the ~~both B cells and T cells~~“Board”), and ~~monocytes,~~Michael ~~into~~Wyzga ~~the~~transitioned ~~bloodstream.~~from ~~Because~~Board ~~antagonism~~Chair ofto ~~the~~Lead ~~CXCR4~~Independent ~~receptor~~Director. ~~has~~The ~~been~~Board ~~shown~~appointed toAdam ~~increase~~R. ~~the~~Craig, ~~trafficking~~M.D., ~~of white blood cells~~Ph.D, weMBA ~~believe~~as ~~that~~Executive ~~therapeutic~~Chairman, ~~inhibition~~John ofVolpone ~~the~~as ~~CXCR4/CXCL12~~President ~~axis~~and ~~holds~~subsequently ~~the~~as ~~potential~~Chief toOperating ~~benefit people with a wide variety of diseases where there remain significant unmet needs~~Officer, ~~including~~and ~~chronic~~David ~~neutropenic~~Kirske ~~disorders~~as ~~and~~Chief ~~certain~~Financial ~~types of cancer~~Officer.

~~Our~~During ~~Commercial~~2025, ~~Product~~we implemented two strategic restructuring actions designed to sharpen operational focus and align resources with our long‑term strategy to successfully complete the 4WARD trial in patients with moderate and severe CN. These strategic restructuring actions, which resulted in an approximately 65% reduction in head count, together with certain equity financing transactions, as described below under Funding Activity, have provided us with the liquidity to pursue our strategic goals.

~~Our~~Funding deep understanding of the biology of the CXCR4 pathway has enabled us to successfully develop our first product, mavorixafor, in its first indication. In April 2024, we received FDA approval of mavorixafor, which is being marketed in the U.S. under the trade name XOLREMDI, for use as an oral, once-daily therapy in patients 12 years of age and older with WHIM syndrome to increase the number of circulating mature neutrophils and lymphocytes. XOLREMDI is the first drug approved in the U.S. to treat patients with WHIM syndrome. Activity

~~Mavorixafor~~During ~~has~~the ~~received~~year ~~multiple~~ended ~~designations~~December ~~from~~31, ~~global~~2025, ~~regulatory~~we ~~authorities~~completed intwo ~~WHIM~~significant ~~syndrome,~~capital-raising ~~including~~events. ~~Breakthrough~~In ~~Therapy~~the ~~designation,~~third ~~Fast~~quarter ~~Track~~of ~~designation~~2025, we sold shares of our common stock and ~~Rare~~pre-funded ~~Pediatric~~warrants ~~Disease~~to ~~designation~~purchase bycommon ~~the~~stock ~~FDA~~in a private placement that resulted in net proceeds of $81.0 million, after deducting placement agent fees and other expenses (the ~~United~~“August ~~States~~PIPE Transaction”). In the fourth quarter of 2025, we sold shares of common stock and ~~orphan~~pre-funded ~~designation~~warrants to purchase common stock in ~~both~~a ~~the~~public ~~United~~offering ~~States~~that resulted in aggregate net proceeds of $145.6 million. As of December 31, 2025, we had $253.0 million in cash, cash equivalents and ~~European~~marketable ~~Union~~securities.

Our Strategy

Our objective is to become a leader in the development and commercialization of novel targeted therapeutics for the treatment of rare hematology diseases. The key elements of our near-term strategy to achieve these objectives include:

•Fully Enroll our Pivotal 4WARD Trial: Our plan to achieve full enrollment of 176 patients on our pivotal 4WARD trial includes:

•expanding the number of currently active clinical trial sites to over 100, including approximately 20 in the U.S.;

~~Concurrent~~•enhancing ~~with~~our ~~the~~global ~~U.S.~~Medical ~~approval~~Affairs ofactivities ~~XOLREMDI and pursuant~~ to ~~its~~increase ~~Rare~~Medical ~~Pediatric~~Science ~~Disease~~Liaison ~~designation,~~(“MSL”) ~~the~~field ~~FDA~~engagement ~~granted~~and ussite ainteraction ~~Priority~~to ~~Review~~educate ~~Voucher~~physicians ~~(“PRV”)~~on ~~that~~our we4WARD ~~sold~~trial toand ~~another~~mavorixafor’s ~~drug~~potential ~~sponsor shortly thereafter~~ in ~~May~~treating ~~2024.~~ CN;

~~About~~•establishing ~~WHIM~~a ~~Syndrome~~referral pathway for physicians to assist them in finding trial sites for their CN patients;

~~WHIM~~•consolidating ~~syndrome~~our isContract ~~both~~Research aOrganizations rare, combined immunodeficiency and a congenital neutropenic disorder in which the body’s immune system does not function properly and has trouble fighting infections. In many patients, WHIM is caused by (“~~gain of function~~CROs” variations in the single gene that encodes for the CXCR4 receptor. In healthy individuals, the CXCR4 receptor is typically internalized into the cell after CXCL12 binds to it, enabling the receptor to be appropriately recycled and the signaling to be diminished. In most WHIM patients, however, a genetic variation in the receptor gene prevents the post-binding internalization (normal recycling); ~~of the receptor. As a result, the CXCR4 receptor is maintained on the surface of the cell~~ and is exposed to the ligand, which creates a perpetual “on” signal and retention of white blood cells in the bone marrow where they are produced, leading to the chronic peripheral neutropenia and lymphopenia that are the clinical hallmarks of WHIM syndrome.

~~Genetic~~•investing ~~testing~~in isdatabase ~~typically~~mining ~~used~~ to ~~diagnose~~identify ~~WHIM~~potential ~~syndrome to confirm the presence of a genetic variation in the CXCR4 receptor. The diagnosis of WHIM syndrome may occur at any age: about one-half of reported~~ patients ~~are diagnosed as children, primarily before the age of 18 years, with the other half diagnosed as adults, mostly between 18 and 40 years of age~~.

~~WHIM~~We ~~syndrome is named for its four common manifestations, although not all patients experience all symptoms, and not all symptoms~~ are ~~required~~targeting ~~for~~completion aof ~~diagnosis:~~enrollment ~~Warts,~~in ~~related~~4WARD toin ~~infection with~~ the ~~Human~~third ~~Papilloma~~quarter ~~Virus (“HPV”), Hypogammaglobulinemia, a condition~~ of ~~low~~2026 ~~immunoglobulin (“IG”) levels, Infections, including both bacterial~~ and ~~fungal~~expect ~~infections,~~to ~~and~~provide ~~Myelokathexis, a hyper~~top-~~dense~~line ~~population~~data offrom ~~immune~~our ~~cells~~4WARD trial in the ~~bone~~second ~~marrow.~~half ~~These~~of ~~conditions reduce the body’s ability to achieve a healthy immune response~~2027. ~~Left untreated, those with WHIM syndrome may experience debilitating and life-threatening complications, including an increased cancer risk, irreversible end-organ damage, and/or sepsis.~~

~~The~~•Prepare ~~incidence~~for ~~and~~Potential ~~prevalence~~Commercialization of ~~WHIM~~Mavorixafor ~~syndrome~~for ~~are~~the ~~not~~Chronic ~~well~~Neutropenia ~~established.~~Indication: We ~~believe~~plan ~~that~~to ~~this~~independently isadvance ~~due~~mavorixafor toin the ~~relatively~~CN ~~recent~~indication ~~elucidation~~in ofregions ~~the~~that ~~genetics~~we ~~underlying~~believe ~~WHIM~~have ~~syndrome,~~clearly ~~lack~~defined ofregulatory ~~universal~~paths orand ~~accessible~~commercialization ~~genetic~~strategies. ~~testing,~~We ~~and~~intend ~~limited~~to ~~medical~~also ~~education~~opportunistically ~~and~~evaluate ~~awareness~~strategic ofcollaborations to maximize the ~~disease,~~potential ~~which~~commercial isvalue inof ~~part~~our ~~driven~~product bycandidates ~~the~~and ~~previous~~discovery ~~lack~~programs. ofIn ~~available~~order ~~disease-modifying~~to ~~treatments.~~successfully ~~Based~~commercialize onmavorixafor aas ~~preliminary~~an ~~U.S.~~oral ~~market~~therapy ~~research~~for ~~study~~the ~~sponsored~~treatment byof uspatients ~~and~~with ~~conducted~~CN, bywe aintend ~~third-party~~to ~~research~~utilize ~~firm,~~our wemedical ~~believe~~affairs ~~that~~infrastructure ~~the~~to ~~prevalence~~engage ofwith ~~WHIM~~key ~~syndrome~~opinion ~~worldwide~~leaders isand ~~significantly~~physicians ~~higher~~in ~~than~~disease ~~previous~~awareness ~~registries~~and ~~suggest~~education.

•~~The~~Maintain ~~study~~XOLREMDI ~~solicited~~Access: Although ~~input~~we ~~from~~are ~~community-based~~not ~~physicians~~actively ofpromoting ~~different~~XOLREMDI ~~specialties~~in the U.S., ~~including~~our ~~physicians~~strategy ~~focused~~is onto ~~non-malignant~~continue ~~hematology,~~to ~~immunology,~~provide ~~dermatology,~~access ~~pulmonology,~~to ~~and~~XOLREMDI ~~infectious~~to ~~diseases,~~patients ~~who~~through ~~are~~our ~~known~~specialty topharmacy ~~manage~~in the U.S. and~~/or~~ ~~treat~~our global partners internationally for their commercialization efforts. XOLREMDI has received FDA approval in the U.S. for use in patients 12 years of age and older with WHIM syndrome to increase the number of circulating mature neutrophils and lymphocytes. Mavorixafor has also received a positive opinion from the European Medicines Agency’s (the “EMA”) Committee for Medicinal Products for Human Use (“CHMP”) recommending the granting of marketing authorization, under exceptional circumstances, for the treatment of WHIM syndrome in the European Union (“EU”). The positive opinion will now be reviewed by the EC with a final approval decision anticipated in the second quarter of 2026. If approved, mavorixafor is expected to be commercialized in Europe by our partner Norgine Pharma UK Ltd. (“Norgine”), a specialist pharmaceutical company.

~~•The~~Product ~~212~~and ~~physicians~~Development ~~across these specialties identified to participate in this study reported more than 1,700 patients in the United States with genetically confirmed or highly probable WHIM syndrome.~~ Portfolio

WeThe ~~also~~following ~~completed~~table asummarizes ~~study~~our ~~using~~current ~~artificial~~product ~~intelligence, interrogating a database of approximately 300 million American lives that included up to 10 years of insurance claims on diagnoses, drug treatments, procedures,~~ and ~~treatment~~development ~~pathways.~~portfolio ~~This study suggested that there may be~~ as ~~many~~of ~~as 3,700 WHIM patients in~~ the ~~United~~date ~~States~~of ~~based~~this ~~on the WHIM-like phenotypes described.~~report:

While the costs of managing the chronic impact of WHIM syndrome are unknown, the per-patient cost of treating primary immunodeficiencies that are similar to WHIM syndrome, based on drug costs alone, exceeds $100,000 per year in the United States for therapies such as antibiotics, intravenous immunoglobulin (“IVIg”), subcutaneous immunoglobulin (“SCIg”) and/or injectable G-CSF, despite the limited effectiveness of these treatments. Beyond these estimated direct costs, other costs associated with direct and indirect management of the disease, such as repeated immunization, physician visits, or hospitalizations, have not been quantified but are likely to be significant. Mavorixafor

ToMavorixafor ~~address~~is ~~the~~an ~~issue~~orally available, small-molecule selective antagonist of ~~accessible~~chemokine ~~genetic~~receptor ~~testing~~CXCR4. ~~related~~Due to ~~WHIM~~its ~~syndrome,~~ability weto ~~sponsor~~increase athe ~~no-charge~~mobilization ~~genetic~~of ~~testing~~mature, ~~and~~functional ~~counseling~~white ~~program~~blood ~~called~~cells ~~PATH4WARD~~from ~~for~~the ~~individuals~~bone ~~who~~marrow ~~may~~into ~~carry~~the ~~genetic~~bloodstream, ~~variations~~we ~~known~~believe that mavorixafor has the potential to bebenefit ~~associated~~people with ~~chronic~~a ~~neutropenia~~range orof ~~primary~~immunodeficiencies ~~immunodeficiency~~– ~~disorders~~a ~~(“PIDs”),~~therapeutic ~~including~~market ~~WHIM~~that ~~syndrome~~is principally served by injectable therapies frequently associated with treatment-limiting adverse events.

~~Our~~CXCR4 Uis a cell receptor that helps regulate the movement of immune cells within the body.S. ~~Commercial~~CXCR4 ~~Strategy~~receptor stimulation by its cognate ligand, CXCL12, has been shown to play a key role in the maturation and ~~Marketing~~mobilization ~~Efforts~~of white blood cells, such as neutrophils, lymphocytes (including both B cells and T cells), and monocytes, into the bloodstream. Because antagonism of the

We launched XOLREMDI in the U.S. in May 2024 and are currently marketing the drug through our X4 commercial team. We

~~deployed~~CXCR4 areceptor ~~field~~has ~~force~~been ofshown ~~Medical~~to ~~Science~~increase ~~Liaisons~~the ~~(“MSLs”),~~trafficking ~~Rare~~of ~~Disease~~white ~~Specialists~~blood ~~(“RDSs”)~~cells, ~~and~~we abelieve ~~nurse~~that ~~educator~~therapeutic ininhibition of the ~~United~~CXCR4/CXCL12 ~~States~~axis holds the potential to ~~drive~~benefit ~~education~~people ~~and~~with ~~awareness~~a wide variety of ~~WHIM~~diseases ~~syndrome~~where there remain significant unmet needs, including CN disorders and ~~its~~certain ~~diagnosis.~~types of cancer.

WeMavorixafor, ~~are~~approved ~~also~~by ~~hoping~~the toFDA ~~increase~~under ~~awareness~~the trade name XOLREMDI for the treatment of WHIM syndrome, ~~among~~received ~~patients~~Breakthrough Therapy Designation, ~~physicians~~Fast Track Designation, and ~~their~~Rare ~~support~~Pediatric ~~systems~~Designation ~~through~~in ~~our~~the ~~partnerships~~U.S., ~~with~~and ~~key~~Orphan ~~patient~~Drug ~~foundations,~~Designation ~~including~~in both the ~~Jeffrey~~U.S. ~~Modell~~and ~~Foundation,~~EU. ~~the~~The ~~International~~FDA ~~Patient~~has ~~Organisation~~also ~~for~~granted ~~Primary~~Fast ~~Immunodeficiencies~~Track ~~(“IPOPI”),~~designation ~~and~~to ~~the~~mavorixafor ~~Immune~~for ~~Deficiency~~the ~~Foundation~~treatment ~~(“IDF”)~~of CN.

ToChronic ~~further~~Neutropenia ~~our~~Market ~~commitment~~Overview ~~to helping people with WHIM syndrome access XOLREMDI, we created our X4Connect™ program, which offers eligible U.S. patients dedicated support through provision of disease~~ and ~~treatment-related resources, help navigating insurance coverage, and copay assistance.~~ Opportunity

~~XOLREMDI~~CN is ~~commercially~~a ~~available~~primary, inrare ~~the~~blood ~~U.S.~~condition ~~through~~defined ~~our~~as ~~specialty~~periods ~~pharmacy~~lasting ~~partner~~more ~~PANTHERx®~~than ~~Rare,~~three ~~which~~months ~~purchases~~persistently ~~our~~or ~~labelled~~intermittently ~~drug~~where ~~product~~there are abnormally low levels of neutrophils circulating in the blood, and ~~dispenses~~may ~~such~~be ~~drug~~idiopathic ~~product~~(of tounknown ~~patients~~origin), ~~pursuant~~cyclic to(episodes ~~prescriptions~~typically ~~provided~~occurring byevery ~~healthcare~~three ~~providers~~weeks), or congenital (of genetic causation). ~~The~~In ~~specialty~~all ~~pharmacy~~cases, ~~also~~the ~~serves~~CXCL4/CXCR12 aspathway ~~our~~is ~~point~~the key regulator of ~~contact~~neutrophil ~~for~~release ~~inbound~~from ~~health~~the ~~care~~bone ~~provider~~marrow. ~~and~~CN ~~patient~~disorders ~~inquiries,~~are ~~prescription~~characterized ~~processing,~~by ~~insurance~~increased ~~investigation,~~risks of infections and ~~patient~~cancer ~~on-boarding~~due to abnormally low levels of neutrophils in the body.

~~4WHIM~~Patients ~~Phase~~with 3CN ~~Trial~~currently ~~Results~~have few treatment options and may be treated with G-CSF, an injectable therapy approved in the U.S. We believe that there is a broad opportunity for an oral medication, such as mavorixafor, to be used as a monotherapy in CN patients who are either naive, intolerant or unresponsive to G-CSF, with the potential for G-CSF dose reduction or elimination.

~~The~~Our ~~U.S.~~market ~~approval~~research ofwith ~~mavorixafor~~100 inhematologists ~~WHIM~~and ~~syndrome~~oncologists ~~was~~treating ~~based~~patients onwith ~~our~~primary ~~successfully~~CN ~~completed~~indicates ~~Phase~~that 3of ~~clinical~~the ~~trial~~approximately 57,000 ~~referred~~patients towith asprimary ~~the~~CN ~~4WHIM~~(identified ~~trial.~~via ~~4WHIM~~ICD-10 ~~was~~codes aassociated ~~pivotal,~~with ~~global,~~primary ~~randomized,~~CN ~~double~~in database of medical claims from the 1/2023 -~~blind~~ 6/2025 time frame,) ~~placebo-controlled~~an estimated 60%, ~~multicenter~~or ~~Phase~~approximately 334,000, ~~clinical~~of ~~trial~~these ~~designed~~patients tohave ~~evaluate~~moderate ~~the~~or ~~efficacy~~severe ~~and~~disease, ~~safety~~which ofis ~~mavorixafor~~defined inas ~~people~~patients ~~with~~having ~~genetically~~absolute ~~confirmed~~neutrophil ~~WHIM~~counts ~~syndrome~~of <1000 cells/µL. ~~Originally~~Of ~~designed~~these tomoderate ~~enroll~~and ~~18-28~~severe patients, ~~the~~hematologists ~~trial~~and ~~enrolled~~oncologists 31surveyed ~~participants~~estimated ~~aged~~that 12approximately ~~and~~45%, ~~older~~or ~~receiving~~approximately ~~either~~a ~~200~~further orsubset ~~400~~of mg15,000 ~~mavorixafor~~patients, are experiencing serious and/or ~~placebo~~recurring ~~orally~~infections ~~once~~as ~~daily~~result ~~for~~of 52their ~~weeks;~~CN. ~~all~~We ~~participants~~estimate ~~then~~that ~~became~~approximately ~~eligible~~5,000 toof ~~receive~~the 15,000 patients will represent our initial target treatment ~~with~~population. We believe that this patient population represents a significant market opportunity based on mavorixafor’s inunique anvalue ~~open-label~~proposition ~~trial~~for ~~extension~~the ~~(“OLE”)~~treatment of a rare disease that has very limited therapy options. ~~More~~Based ~~than~~on ~~ninety~~our ~~percent~~independent market research, should mavorixafor be approved for the treatment of ~~participants~~CN, ~~opted~~we expect to ~~enroll~~initially inpenetrate the ~~OLE~~market ~~portion~~with ofmavorixafor as both a monotherapy and as a combination therapy, where the ~~trial~~goal is reduction of G-CSF dosing.

~~The~~Clinical ~~primary~~Trial ~~endpoint~~Results ofto ~~the~~Date ~~4WHIM trial was a clinically relevant reduction of duration of severe neutropenia as measured by the increase in time above threshold~~ for ~~absolute~~Mavorixafor ~~neutrophil count (“TAT-ANC”), which was defined as the number of hours during which the absolute neutrophil count was raised above a 500 cells per microliter threshold~~ in ~~peripheral~~Patients ~~blood.~~with ~~Secondary~~Chronic endpoints included time above threshold for absolute lymphocyte count (“TAT-ALC”) of ≥ 1,000 cells per microliter over a 24-hour period, a composite clinical efficacy endpoint for mavorixafor based on total infection score and total wart change score, total wart change score for mavorixafor, total infection score for mavorixafor; and a number of quality-of-life measurements and other exploratory endpoints.Neutropenia

~~Summary~~Phase 1b. In 2022, we conducted a proof-of-concept Phase 1b open-label, multicenter study designed to assess the safety and tolerability of oral mavorixafor, with or without injectable G-CSF, in patients with CN disorders, including idiopathic, cyclic, and congenital neutropenia. Patients received a single dose of 400 mg oral mavorixafor to assess the magnitude of treatment response. In September 2022, we announced positive results from ~~the~~this Phase 31b ~~4WHIM~~clinical trial, ~~were~~which asenrolled ~~follows~~a total of 25 patients:

•~~Primary~~100% ~~Endpoint:~~of ~~4WHIM~~patients ~~met~~responded ~~its~~to ~~primary~~treatment ~~endpoint,~~ with ~~mavorixafor~~a ~~achieving~~single ~~clinical~~dose ~~and statistical superiority over placebo (p<0.0001) when measuring the length~~ of ~~time~~400 ~~that~~mg ~~participants’ ANC remained above a clinically meaningful threshold~~ of ~~500~~mavorixafor, ~~cells~~alone ~~per~~or ~~microliter~~dosed ~~(severe~~concurrently ~~neutropenia)~~with ~~over 24~~G-~~hour periods at 4 time points throughout the 52-week trial.~~CSF:

~~•Key~~▪Patients ~~Secondary~~achieved ~~Endpoint: 4WHIM also met~~ a ~~key~~mean ~~secondary~~absolute ~~endpoint,~~neutrophil ~~with~~count ~~mavorixafor achieving clinical and statistical superiority over placebo~~ (~~p<0.0001~~“ANC”) ~~when~~increase ~~measuring~~at ~~the~~peak ~~length~~ of ~~time that participants’ ALC remained above a clinically meaningful threshold of 1~~>3,000 cells per microliter ~~(lymphopenia), over 24-hour periods at 4 time points throughout the 52-week trial~~.

•Rate of Infections: In the trial, mavorixafor treatment resulted in a statistically significant reduction (~60%) in annualized infection rate versus placebo (p<0.01). In addition, the data showed that the reduction was greater with time on treatment, with participants on mavorixafor experiencing less than one infection per year versus 4.5 for those on placebo; during the second 6 months of the trial, the difference also achieved statistical significance (p<0.005).

•Severity of Infections: During the trial, 29% (5 of 17) of those on placebo experienced Grade 3 or higher infections, whereas only 7% (1 of 14) of those on mavorixafor experienced a Grade 3 or higher infection, equating to a 75% reduction in the number of individuals experiencing severe infections. Importantly, the single Grade 3 infection in the mavorixafor treatment arm occurred during the first 3 months of the trial; after 3 months of treatment, there were no serious infections in the mavorixafor-arm, whereas the frequency of severe infections in those on placebo remained unchanged over the 52-week trial period.

•Duration of Infections: In the trial, mavorixafor treatment reduced the total duration (in days) of infections by more than 70% as compared to placebo, with those on placebo experiencing a mean of 7 weeks (49.1 days) with infections over the 52-week trial period versus a mean of only 2 weeks (14.1 days) with infections for those treated with

mavorixafor.

•Other Infection Metrics: Mavorixafor treatment resulted in a 40% lower total infection score, a metric that combines infection number and severity (LS mean [95% CI]: mavorixafor, 7.41 [1.64–13.19]; placebo, 12.27 [7.24–17.30]). Treatment with mavorixafor also resulted in reductions in upper and lower respiratory tract and skin infections compared with those on placebo; participants on placebo required greater medical intervention, with 10 of the 17 participants on placebo requiring treatment with antibiotics over the course of the study, versus 3 of the 14 receiving mavorixafor; and slight improvements in warts were demonstrated both in the mavorixafor and placebo arms (no difference between arms).

•Safety and Tolerability: Mavorixafor was generally well tolerated in the 4WHIM trial, with no drug-related serious adverse events, no treatment limiting toxicities, and no discontinuations due to safety.

Advancing Mavorixafor for WHIM Syndrome Outside of the U.S.

In January 2025, we announced that our MAA for mavorixafor in the treatment of WHIM syndrome was validated for review and is now under evaluation with the EMA’s Committee for Medicinal Products for Human Use. Following approval in the EU, if received, our partner Norgine, a leading European specialist pharmaceutical company, will be responsible for the commercialization of mavorixafor for the WHIM syndrome indication across the European Union (“EU”).

In addition, in December 2024, we announced that we had entered into an agreement with taiba rare for the distribution and commercialization of XOLREMDI for the treatment of WHIM syndrome in select Middle East countries including Saudi Arabia, United Arab Emirates, Qatar, Oman, Kuwait, Bahrain, and Egypt. taiba will lead the distribution, promotion, marketing, and sales of XOLREMDI within the territory, working jointly with X4 on key strategic decisions. Local regulatory filings for XOLREMDI approval will be based on X4’s registration dossier submitted to the FDA. Pending regulatory approvals in the region, taiba rare is expected to be able to provide XOLREMDI to WHIM patients through a named-patient (compassionate use) program that allows physicians to prescribe medicines approved in other countries to local patients when no other treatment options are available.

Developing Mavorixafor in Chronic Neutropenia

Due to its demonstrated ability to durably elevate levels of circulating white blood cells across multiple clinical trials, we believe that mavorixafor may be useful in the treatment of certain forms of chronic neutropenia.

Chronic neutropenia is defined as periods lasting more than three months persistently or intermittently where there are abnormally low levels of neutrophils circulating in the blood, and may be idiopathic (of unknown origin), cyclic (episodes typically occurring every three weeks), or congenital (of genetic causation). Similar to WHIM syndrome, chronic neutropenia disorders are rare blood conditions similarly characterized by increased risks of infections and cancer due to abnormally low levels of neutrophils in the body. In all cases, the CXCL12/CXCR4 pathway is the key regulator of neutrophil release from the bone marrow.

The incidence and prevalence of chronic neutropenic disorders are not well established. In December 2022, we presented results from what we believe was the first study examining the prevalence of chronic neutropenia disorders (including idiopathic, cyclic, and congenital neutropenia) in the United States; we believe that determining the estimated projected prevalence of chronic neutropenic disorders is a key step to understanding the extent of existing unmet medical needs in this patient population.

•Using a retrospective analysis of a large U.S. claims database, the analysis included people with a diagnosis code for neutropenia during the calendar years 2018, 2019, and 2021 (the year 2020 was excluded from this analysis owing to anticipated reduced claims during the COVID-19 pandemic).

•People with a diagnostic, procedural, or product code for neutropenia resulting from secondary causes including chemotherapy, drug exposure, infection, solid organ transplantation, myelodysplastic syndrome, and end-stage renal disease within 24-month period prior to selection were excluded.

•A 13- to 24-month look back period prior to index date was used to confirm chronic status.

•The analysis used longitudinal prescription data and office-based claims data from an IQVIA claims database that included 93% of retail prescription claims, 77% of mail-in prescription claims, and had more than 1.5 billion office-based claims per year.

•This retrospective analysis projected that in 2021, up to 48,000 people in the United States were living with a diagnosis of chronic neutropenia, with the most common type of chronic neutropenic disorder being idiopathic (~40,000), followed by cyclic (~5,000), and congenital (~3,000), and with the majority of affected people being female adults.

•Our research into the estimated individuals in the U.S. diagnosed with chronic neutropenia confirmed that significant unmet medical needs exist despite the availability and use of G-CSF and, if our analysis is correct, this suggests a potential minimal addressable market for mavorixafor of approximately one third of this population, or approximately 15,000 individuals in the U.S., plus meaningful potential market expansion opportunities.

In 2022, we also completed an electronic medical records study to better understand the risk of serious or severe infection in people with chronic neutropenia in the United States, analyzing the medical records of 44 healthcare organizations treating approximately 66 million patients. The analysis examined patients who had experienced at least two Serious Infections Events (“SIEs”) following documentation of chronic neutropenia in each calendar year compared with those who did not have neutropenia. SIEs are defined as infections requiring hospitalization or intravenous antibiotics or that result in disability or death.

•The results of this analysis indicated that the incidence rate of SIEs per 100,000 person days was increased for all levels of chronic neutropenia: it was two times greater for patients with any chronic neutropenia (ANC less than 1,500 cells per microliter) and four times greater for patients with severe congenital neutropenia (ANC less than 500 cells per microliter).

•The risk of serious infection increased with the worsening of neutropenia.

•Approximately 25% of patients with chronic neutropenia had at least 2 SIEs in the latest calendar year examined, which was 2019.

People living with chronic neutropenia have few treatment options and may be treated with G-CSF, an injectable therapy approved in the United States for the treatment of severe, chronic neutropenia. G-CSF is used to stimulate bone marrow to produce neutrophils. Side effects of G-CSF include disabling bone pain, which can be more severe in certain age groups. Additional, less common, treatment-limiting complications of chronic G-CSF administration include myelofibrosis and leukemia. In chronic neutropenia cases that are unresponsive to G-CSF, or if leukemia has developed, bone marrow transplants have been made with varying degrees of success. Bone marrow transplantation is often applied to severe neutropenia from bone marrow failure. Bone marrow transplants bring additional risks into the management of the disorders.

Clinical Trial Results to Date for Mavorixafor in Chronic Neutropenic Disorders

In 2022, we conducted a proof-of-concept Phase 1b open-label, multicenter study designed to assess the safety and tolerability of oral mavorixafor, with or without injectable G-CSF, in participants with chronic neutropenic disorders, including idiopathic, cyclic, and congenital neutropenia. Participants received a single dose of 400 mg oral mavorixafor to assess the magnitude of treatment response.

In September 2022, we announced positive results from this Phase 1b clinical trial, which enrolled a total of 25 participants:

•100% of study participants responded to treatment with a single dose of 400 mg of mavorixafor, alone or dosed concurrently with G-CSF:

▪Participants achieved a mean ANC increase at peak of >3,000 cells per microliter.

▪Consistent responses were seen across all of the chronic neutropenic disorders studied – idiopathic, cyclic, and congenital neutropenia.

•All neutropenic ~~participants~~patients (n=14) reached normalized ANC levels (>1,500 cells per microliter):

▪When assessed as a monotherapy in ~~participants~~patients with severe ~~chronic~~CN ~~neutropenia~~ who were not being treated with G-CSF (n=6), a single dose of mavorixafor led to normalized ANC levels in all ~~participants~~patients within 2 hours, with a mean ANC increase at peak of ~2,500 cells per microliter.

▪When assessed in ~~participants~~patients with moderate or severe neutropenia, ~~despite~~a ~~being~~single ~~treated~~dose of mavorixafor in combination with G-CSF (n=8), ~~100%~~all patients reached normalized ANC levels~~, suggesting the potential of mavorixafor to both normalize the neutrophil counts in patients with partial response to G-CSF and also to potentially enable the reduction or elimination of G-CSF dosing~~.

•When assessed in ~~participants~~patients with ~~chronic~~CN ~~neutropenia~~ with normalized ANC counts on chronic G-CSF (n=11), all ~~participants~~patients experienced a consistent and sustained increase in ANC~~, suggesting mavorixafor’s potential to reduce or possibly eliminate G-CSF treatment in these patients~~.

•Mavorixafor was well tolerated in the study; all treatment-related adverse events were deemed to be low grade, consistent with previous clinical studies in WHIM syndrome, and no treatment-related serious adverse events were reported.

9Phase 2. An amendment to the Phase 1b clinical trial was initiated as a Phase 2 clinical trial to evaluate the use of daily oral mavorixafor with or without injectable G-CSF for up to six months in patients with CN disorders. For patients being treated with mavorixafor in combination with G-CSF, physicians had the option to reduce the dose of G-CSF starting at Month 3. The completed Phase 2 study of mavorixafor was a six-month, open-label clinical trial that enrolled a total of 23 patients diagnosed

~~consistent with previous clinical studies in WHIM syndrome, and no treatment-related serious adverse events were reported.~~7

~~Following these positive results, an amendment to the Phase 1b clinical trial was initiated aiming to evaluate the use of daily oral mavorixafor~~ with or without injectable G-CSF for up to 6 months in participants with chronic neutropenic disorders as a Phase 2 clinical trial. The completed Phase 2 study of mavorixafor was a six-month, open-label clinical trial that enrolled a total of 23 participants diagnosed with idiopathic, congenital, or cyclic ~~chronic neutropenia~~CN.

The Phase 2 study results below are from the two study treatment groups: mavorixafor monotherapy (n = 10 at baseline) and mavorixafor in combination with injectable G-CSF (n=13 at baseline).

•Mavorixafor monotherapy: Consistent with previously presented analyses, results from ~~participants~~patients receiving mavorixafor monotherapy showed that mavorixafor durably increased mean ANC from baseline, with mean ANC reaching normal levels at Month 3 (n=9) and maintained to the end of study (Month 6 (n=8)).

•~~Further~~Mavorixafor ~~analysis~~in ~~showed~~combination ~~that those~~ with ~~severe~~injectable CNG-CSF: ~~achieved~~In ~~clinically~~the ~~meaningful~~study, ~~increases~~physicians inchose ~~mean~~to ~~ANC~~reduce ~~levels~~G-CSF ~~out~~dosing toin ~~six~~nine ~~months~~of 12 (~~n=4~~75%) eligible patients. Of those nine, ~~reaching~~eight ~~levels~~had ~~typically~~G-CSF ~~targeted~~reduced byat ~~physicians~~the ~~for~~earliest ~~patients~~time-point ~~with~~permitted ~~severe~~and CNthree were taken completely off of G-CSF prior to their Month 6 visit.

•Mavorixafor in combination with injectable G-CSF: In the study, physicians chose to reduce G-CSF dosing in nine of 12 (75%) eligible participants. Of those nine, eight had G-CSF reduced at the earliest timepoint permitted and three were taken completely off of G-CSF prior to their Month 6 visit.

•Mean reductions in G-CSF were 52% at Month 3 (n=8) and 70% at Month 6 (n=9), while mean ANC levels remained in the normal range.

•The three ~~participants~~patients receiving mavorixafor who remained on stable doses of G-CSF maintained mean ANC levels in the normal range at all ~~timepoints~~time-points.

•Safety summary: Mavorixafor was generally well tolerated as a monotherapy and in combination with G-CSF, with no drug-related serious adverse events reported, consistent with previous clinical studies.

In addition, during the Phase 2 clinical trial, ~~we conducted~~ a sub-study was conducted comparing the mean percentage of functional neutrophils in samples from healthy donors (n=5) to ~~participants~~patients in the Phase 2 study (n=9) using two common study methods. These results demonstrated that the mean percentage of functional circulating neutrophils in CN ~~participants~~patients in this sub-study was comparable to that of healthy donors after six months of mavorixafor dosing. ~~This was the first clinical demonstration that the neutrophils mobilized by mavorixafor are fully functional.~~

WePhase ~~are~~3 ~~currently~~(4WARD). The ~~conducting~~4WARD astudy ~~pivotal~~is a Phase 3 clinical trial of mavorixafor in ~~people~~patients with certain ~~chronic~~CN ~~neutropenic~~ disorders ~~(the 4WARD study)~~. The ~~Phase~~4WARD 3 trial is a global, randomized, double-blinded, placebo-controlled trial assessing the safety and efficacy of once-daily oral mavorixafor, ~~with~~as a monotherapy or ~~without~~in combination with stable doses of G-CSF, in ~~people~~patients with idiopathic or congenital, acquired primary autoimmune, or idiopathic ~~chronic~~CN ~~neutropenia~~ who are experiencing recurrent and/or serious infections. The 52-week trial is expected to enroll ~~150~~176 ~~participants~~patients aged 12 years and older. ~~with~~Key ~~both~~study inclusion criteria are an ANC at baseline of less than 1,~~500~~000 cells per microliter and 2 or more infections requiring intervention during the 12 months preceding the trial. The ~~primary~~trial ~~endpoint~~is ofdesigned ~~the~~to ~~trial~~test isfor athe ~~two~~co-~~component~~primary ~~endpoint~~endpoints ~~that~~of ~~includes~~reduction ~~the~~in annualized infection rate and ANC response, defined as an increase in >500 cells per microliter in the mavorixafor-treated group versus the placebo group. Key secondary endpoints ~~are expected to~~ include analysis of the severity and duration of infections, antibiotic use, fatigue, and quality of life parameters. We expect to complete enrollment in the third quarter of 2026 and report top-line data results in the second half of 2027, with the goal of receiving FDA approval in 2028.

~~Other~~XOLREMDI® ~~Pipeline~~(mavorixafor) ~~Candidates~~for WHIM syndrome

We have ~~also~~one ~~developed~~commercially ~~two~~approved ~~pre-clinical~~product, ~~candidates:~~XOLREMDI® ~~X4P-003~~(mavorixafor), awhich ~~second-generation~~has ~~CXCR4~~received ~~antagonist~~accelerated ~~designed~~approval toin ~~have~~the ~~enhanced~~United ~~properties~~States ~~relative~~from tothe ~~mavorixafor,~~FDA ~~potentially~~for ~~enabling~~use ~~broader~~as ~~opportunities~~an inoral, ~~CXCR4~~once-~~dependent~~daily ~~disorders~~therapy ~~and~~in ~~primary~~patients ~~immunodeficiencies;~~12 ~~and~~years ~~X4P-002,~~of aage ~~CXCR4~~and ~~antagonist~~older with aWHIM ~~unique~~syndrome, ~~distribution~~to ~~profile~~increase ~~and~~the anumber ~~demonstrated~~of ~~ability~~circulating tomature ~~cross~~neutrophils ~~the~~and ~~blood-brain barrier~~lymphocytes. InWHIM ~~accordance~~syndrome ~~with~~is ~~our~~an ~~2025~~ultra-rare, ~~Restructuring (as defined below)~~inherited, ~~these~~combined ~~programs~~primary ~~are~~immunodeficiency ~~currently~~and ~~paused~~CN disorder.

~~Competition~~8

~~The~~In ~~pharmaceutical~~January ~~and~~2025, ~~biotechnology~~we ~~industries~~submitted ~~are~~a ~~characterized~~marketing authorisation application (“MAA”) to the EMA seeking regulatory approval to commercialize mavorixafor for WHIM syndrome in the EU. Such MAA was validated for processing by ~~rapidly~~the ~~advancing~~EMA ~~technologies,~~in ~~intense~~January ~~competition~~2025. In February 2026, ~~and~~the EMA’s CHMP adopted a ~~strong~~positive ~~emphasis~~opinion onrecommending ~~proprietary~~the ~~products~~grant of marketing authorization, under exceptional circumstances, for mavorixafor for the treatment of WHIM syndrome in the EU. WeMarketing ~~face~~authorization ~~potential~~“under ~~competition~~exceptional ~~from~~circumstances” ~~many~~is ~~different~~granted ~~sources~~in situations where comprehensive clinical data cannot be obtained, including ~~major~~due to the rarity of the condition, and is subject to specific post-authorization obligations and annual reassessment by the EMA. The positive opinion has been submitted to the EC for review, and we expect the EC to issue a final approval decision in the second quarter of 2026.

10On January 13, 2025, we announced a license and supply agreement (the “Norgine Agreement”) with Norgine, pursuant to which Norgine was granted an exclusive license to distribute, market and sell our drug product for all indications, including WHIM and CN, in the European Economic Area, Switzerland, the United Kingdom, Australia, and New Zealand. In February 2025, we announced that we had entered into an agreement with Taiba Middle East Fz LLC (“taiba rare”) to distribute and commercialize XOLREMDI for the treatment of WHIM syndrome in select Middle East and North African (“MENA”) countries. We also have a license agreement with Abbisko Therapeutics Co. Ltd. (“Abbisko”), which granted Abbisko the exclusive right to perform regulatory activities on, manufacture and distribute mavorixafor in mainland China, Taiwan, Hong Kong and Macau.

pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions, governmental agencies, and public and private research institutions. Any product candidates that we successfully develop and commercialize will compete with existing therapies and new therapies that may become available in the future.

Many of our competitors may have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals, and marketing approved products than we do. Other firms also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient enrollment for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Mergers and acquisitions in the pharmaceutical, biotechnology, and diagnostic industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early stage companies may also prove to be significant competitors to us, particularly through collaborative arrangements with large and established companies.

Our commercial opportunities could be reduced or eliminated if our competitors develop and commercialize therapeutics that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we may develop. Our competitors also may obtain marketing approvals for their products more rapidly than we may obtain approval for our products, which could result in our competitors establishing a strong market position before we are able to enter the market. In addition, our ability to compete may be affected because in some cases insurers or other third-party payors, including government programs, seek to encourage the use of generic products. This may have the effect of making branded products less attractive to buyers from a cost perspective.

We are aware of other companies that are developing injectable CXCR4 inhibitors. However, we are not aware of any companies with CXCR4 antagonist programs in development for the indications of WHIM syndrome or chronic neutropenia. With regard to chronic neutropenia, we are not aware of any companies who are developing an oral therapy to elevate neutrophils in the blood. Filgrastim injections (human G-CSF) and two biosimilars (Zarxio and Nivestym) are FDA approved to reduce the incidence and duration of after-effects of severe neutropenia (e.g. fever, infections, oropharyngeal ulcers) in symptomatic patients with severe neutropenia.

Manufacturing

We do not own or operate, and currently have no plans to establish, manufacturing facilities for the production of clinical or commercial quantities of mavorixafor or any of our other product candidates. We currently rely on and expect to continue to rely on, third parties for the manufacture of any of our product or product candidates.

We currently have a master services agreement, as amended from time to time, and a commercial supply agreement with Evotec A.G. (“Evotec,” previously known as Aptuit, Oxford), pursuant to which Evotec manufactures the active pharmaceutical ingredient (“API”) mavorixafor for use in our clinical and commercial supply.

We also have a master services agreement in place with Catalent Inc. (“Catalent”), which is our sole manufacturer for the final capsule drug product formulation of mavorixafor. The term of the master services agreement with Catalent expires on December 31, 2028 and may be terminated by (1) us upon 30 days-notice to Catalent or (2) by either party following a material breach by the other party that remains uncured for 30 days. We have entered into a commercial supply agreement with Catalent to support our global WHIM launch.

We obtain clinical and commercial supplies from Evotec and Catalent pursuant to typical industry-standard commercial and clinical supply agreements. We believe that both manufacturers have the capability and capacity to manufacture currently projected clinical trial supply and commercial volumes of mavorixafor.

License Agreements

License Agreement with Genzyme

In July 2014, we entered into a license agreement (the “Genzyme Agreement”) with Genzyme Corporation (“Genzyme”), a wholly owned subsidiary of Sanofi, pursuant to which we were granted an exclusive license to certain patent applications and other intellectual property owned or controlled by Genzyme related to the CXCR4 receptor to develop and commercialize products containing licensed compounds, including but not limited to, mavorixafor. Genzyme has retained the non-exclusive right to conduct preclinical research involving compounds in any field, including any fields licensed to us, but has not retained rights to conduct any clinical development or commercialization of those compounds identified in the agreement in any of the fields licensed to us. We are primarily responsible for the preparation, filing, prosecution, and maintenance of all patent applications and patents covering the intellectual property licensed to us under the agreement at our sole expense.

compounds in any field, including any fields licensed to us, but has not retained rights to conduct any clinical development or commercialization of those compounds identified in the agreement in any of the fields licensed to us. We are primarily responsible for the preparation, filing, prosecution, and maintenance of all patent applications and patents covering the intellectual property licensed to us under the agreement at our sole expense.

We are obligated to use commercially reasonable efforts to develop and commercialize licensed products for use in the field in the United States and at least one other major market country. We have the right to grant sublicenses of the licensed rights that cover mavorixafor to third parties. If we wish to grant a sublicense to any licensed product other than mavorixafor, we are obligated to first offer the sublicense to Genzyme. If Genzyme expresses written interest for the sublicense, then we will negotiate exclusively with Genzyme for a certain stated period to obtain a license to such rights, after which Genzyme shall have no further rights with respect to such licensed product and we will be free to negotiate a sublicense with respect to such licensed product with any third party.

~~During~~Regulatory ~~2024~~Milestones: The Genzyme Agreement includes certain regulatory milestones that require us to make payments upon achievement. In January 2025, we achieved a regulatory milestone: upon notification of the ~~approval~~acceptance by the ~~FDA~~EMA of our first ~~NDA~~drug application, ~~for~~ which triggered a payment of $73.0 million. ~~has~~Such ~~been~~payment ~~paid.~~was made in March 2025. As of December 31, ~~2024~~2025, we are obligated to pay Genzyme future milestone payments in the aggregate amount of up to $135.0 million, contingent upon our achievement of certain late-stage regulatory ~~and sales~~ milestones with respect to licensed products, and tiered royalties based on net sales of licensed products that we commercialize under the Genzyme ~~agreement~~Agreement. In January 2025, we achieved a regulatory milestone of $3.0 million, which was triggered upon notification of the acceptance by the EMA of our first drug application. Such regulatory milestone was paid in March 2025. The remaining regulatory milestone of $5.0 million is triggered upon the notification by the EMA of regulatory approval of our first drug application. We must also make one-time sales milestone payments of $0.5 million, $1.5 million and $3.0 million upon achieving cumulative net sales of $50 million, $150 million and $300 million, respectively. Upon the first potential sale of our drug candidate in the U.S., we have incurred a royalty on annual net sales at a rate of 6% up to $150 million, and would incur 10% on the portion of annual net sales between $150 million and $300 million, and 12% thereafter. We also incur royalties for certain sublicense fees that we earn from sublicensees of intellectual property (“IP”) that we license from Genzyme. For example, in January 2025 we entered into an exclusive licensing and supply agreement with Norgine whereby we sublicensed intellectual property, including IP that we license from Genzyme. Upon closing of the agreement, Norgine paid us a one-time, nonrefundable fee of €28.5 million for the transfer of such IP. Under our Genzyme agreement we owe a 15% royalty on this upfront payment and certain other regulatory and sales-based milestones that we earn under the Norgine license and supply agreement.

~~Our~~Sales ~~obligation~~Milestones: We tomust ~~pay~~also ~~royalties~~make ~~for each licensed product expires on a country~~one-~~by-country~~time ~~basis~~sales onmilestone ~~the~~payments ~~latest~~ of ~~(i)~~$0.5 ~~the expiration of licensed patent rights that cover that licensed product in that country~~million, ~~(ii)~~$1.5 ~~the~~million ~~expiration of regulatory exclusivity in that country~~ and ~~(iii) ten years after the first commercial sale of such licensed product in that country~~$3.0 ~~Royalty~~million ~~rates~~upon ~~are~~achieving ~~subject~~cumulative tonet reduction under the agreement in specified circumstances, including in any country if we are required to obtain a license from any third party to the extent our patent rights might infringe the third party’s patent rights, if a licensed product is not covered by a valid claim in that country, or if sales of ~~generic~~$50 ~~products reach certain thresholds in that country. Sublicenses that we enter into under the Genzyme agreement obligate us to pay Genzyme a percentage of certain upfront~~million, ~~maintenance~~$150 ~~fees,~~million ~~milestone payments~~ and ~~royalty~~$300 ~~payments~~million, ~~paid to us by the sublicensee~~respectively.

~~The~~Sublicense ~~term~~Fees: We ofalso ~~the~~incur ~~Genzyme~~fees ~~Agreement~~for ~~will~~certain ~~continue~~sublicense ~~until~~revenue ~~the~~that ~~later~~we ofearn ~~the~~from ~~expiration~~sublicensees of ~~the~~intellectual ~~last-to-expire~~property ~~valid~~(“IP”) ~~claim~~that ofwe ~~the~~license ~~patents~~from ~~licensed~~Genzyme. ~~under~~For ~~the~~example, ~~agreement~~in ~~that~~January ~~cover~~2025 ~~any~~we ~~licensed~~entered ~~product,~~into the ~~expiration~~Norgine ofAgreement ~~regulatory~~whereby ~~exclusivity~~we ~~applicable~~sublicensed toIP, ~~any~~including ~~licensed~~IP ~~product,~~that ~~and~~we 10license ~~years~~ from ~~the~~Genzyme. ~~date~~Upon ofclosing ~~first commercial sale~~ of ~~any~~the ~~licensed~~agreement, ~~product.~~Norgine ~~Either~~paid weus ora ~~Genzyme~~one-time, ~~may~~nonrefundable ~~terminate~~fee ~~the~~of ~~Genzyme~~€28.5 million ~~Agreement~~for in the ~~event~~transfer of ~~the~~such ~~bankruptcy or uncured material breach by the other party~~IP. ~~Genzyme~~Under ~~may terminate~~ the Genzyme Agreement if we orpaid ~~our affiliates initiate~~ a ~~patent~~15% ~~challenge~~royalty ofto ~~the~~Genzyme ~~patents~~on ~~licensed~~this ~~under~~upfront ~~the~~payment, ~~agreement.~~and Wewe may ~~terminate~~owe ~~the~~a ~~Genzyme~~15% ~~Agreement~~royalty ~~immediately~~on ~~upon~~certain ~~notice~~other toregulatory ~~Genzyme~~and ifsales-based wemilestones ~~reasonably believe~~ that ~~the~~we ~~development~~earn ~~or commercialization of a licensed compound or product~~ under the ~~Genzyme~~Norgine ~~agreement would result in a material safety issue for patients~~Agreement.

~~License~~Royalties: Upon ~~Agreement~~the ~~with~~first ~~Georgetown~~sale ~~University~~of our drug candidate in the U.S., we incur a royalty on annual net sales at a rate of 6% up to $150 million, and would incur 10% on the portion of annual net sales between $150 million and $300 million, and 12% thereafter on annual net sales of over $300.0 million. Our obligation to pay royalties for each licensed product expires on a

In December 2016, we entered into a license agreement with Georgetown University (“Georgetown”) pursuant to which we obtained an exclusive, worldwide license to practice certain methods, and to make, have made, use, sell, offer for sale or import products, covered by licensed patent rights co-owned by Georgetown. The rights licensed to us are for all therapeutic, prophylactic, and diagnostic uses in all disease indications in humans and animals. We have the right to grant sublicenses of the licensed rights to third parties to the extent consistent with the terms of the Georgetown agreement.9

country-by-country basis on the latest of (i) the expiration of licensed patent rights that cover that licensed product in that country, (ii) the expiration of regulatory exclusivity in that country and (iii) ten years after the first commercial sale of such licensed product in that country. Royalty rates are subject to reduction under the Genzyme Agreement in specified circumstances, including in any country if we are required to obtain a license from any third party to the extent our patent rights might infringe the third party’s patent rights, if a licensed product is not covered by a valid claim in that country, or if sales of generic products reach certain thresholds in that country. Sublicenses that we enter into under the Genzyme Agreement obligate us to pay Genzyme a percentage of certain upfront, maintenance fees, milestone payments and royalty payments paid to us by the sublicensee.

The term of the Genzyme Agreement will continue until the later of (i) the expiration of the last-to-expire valid claim of the patents licensed under the agreement that cover any licensed product, (ii) the expiration of regulatory exclusivity applicable to any licensed product and (iii) 10 years from the date of first commercial sale of any licensed product. Either we or Genzyme may terminate the Genzyme Agreement in the event of a bankruptcy or uncured material breach by the other party. Genzyme may terminate the Genzyme Agreement if we or our affiliates initiate a patent challenge of the patents licensed under the agreement. We may terminate the Genzyme Agreement immediately upon notice to Genzyme if we reasonably believe that the development or commercialization of a licensed compound or product under the Genzyme Agreement would result in a material safety issue for patients.

Norgine Agreement

On January 13, 2025, we entered into a license and supply agreement with Norgine. Under the terms of the Norgine Agreement, we granted Norgine the exclusive right to conduct regulatory activities on, manufacture and commercialize mavorixafor (the “Licensed Product”) in Europe, Australia, and New Zealand (collectively, the “Territory”). The Norgine Agreement grants Norgine an exclusive license to import, export, promote, distribute, conduct medical affairs activities, conduct regulatory activities, have manufactured, market, advertise, offer for sale, have sold and sell the Licensed Product in the Territory and within the field. The Norgine Agreement also grants to Norgine a co-exclusive license under the Licensed IP to manufacture the Licensed Products for the Territory and within the field. We retain all rights to mavorixafor outside the Territory and specific reserved rights within the Territory. Norgine may grant sublicenses to its affiliates and certain third parties subject to the terms of the agreement, except that it may not sublicense the commercial rights granted under the agreement for certain countries without our explicit consent.

Pursuant to the terms of the Norgine Agreement, we are entitled to receive the following payments from Norgine: (i) an upfront payment in the amount of €28.5 million (such payment was received in January 2025), (ii) up to €226.0 million upon the achievement of certain regulatory, commercial and sales milestones, and (iii) escalating double-digit royalties of up to mid-twenties on any future net sales in the Territory. The tiered royalty payments are subject to royalty stacking, and to a material reduction on a country-by-country basis if a generic version of mavorixafor becomes available in the applicable country. We and Norgine will collaborate closely on regulatory filings, while we continue to be responsible for the ongoing 4WARD clinical trial evaluating mavorixafor in CN. Norgine will be responsible for all market access and commercialization activities and will eventually hold all marketing authorizations in the licensed territories. We will manufacture and supply mavorixafor to Norgine. Norgine will be required to pay a supply price for the Licensed Product derived from the contract manufacturing organization costs plus a low double-teen digit percentage of the contract manufacturing costs.

Subject to customary rights of each party to earlier terminate the Norgine Agreement, the term of the agreement continues, on a country-by-country basis, until the later of: (i) the tenth (10th) anniversary of the first commercial sale of mavorixafor, (ii) expiration of regulatory market exclusivity of mavorixafor or (iii) expiration of the last-to-expire licensed patent in such country. The term of the Norgine Agreement will be automatically renewed for additional three-year terms unless either party provides the other party with written notice of its intent not to renew the agreement at least one year prior to the applicable termination date of the agreement. In the event of automatic renewal, the royalty payment rate drops to a single digit royalty.

Patents and Other Intellectual Property Rights

We dedicate significant resources to protecting our intellectual property, which is important to our business. We have filed numerous patent applications in the United States and various other countries seeking protection of inventions originating from our research and development, and we have also obtained rights to various patents and patent applications under licenses with third parties and through acquisitions. We have pending patent applications or issued patents in the United States and foreign countries directed to mavorixafor. Patent coverage for our individual products extends for varying periods according to the date of the patent filing or grant and the legal term of patents in the various countries where we have obtained patent protection.

Patents issued from our co-owned portfolio, if all maintenance fees are paid, are expected to expire in 2036, not including any Patent Term Adjustment (PTA), Patent Term Extension (PTE), or other extensions of term that may be available.

The risks and uncertainties associated with our intellectual property, including our patents, are discussed in more detail in Part I, Item 1A, “Risk Factors.”

Manufacturing, Distribution and Associated Operations

Our manufacturing strategy utilizes third-party contractors for the procurement and manufacture, as applicable, of raw materials, active pharmaceutical ingredients (“API”) and finished drug product, as well as for labeling, packaging, storage and distribution of our compounds and associated supply chain operations. As a result of the April 2024 FDA approval of XOLREMDI and the continued expansion of our clinical development activities to support our 4WARD trial and, following the completion of the 4WARD trial, the potential commercial launch of mavorixafor for patients with CN, we expect that our manufacturing, distribution and related operational requirements will increase correspondingly.

Each third-party contractor undergoes a formal qualification process with our subject matter experts prior to our entry into any service agreement and initiating any manufacturing work. We currently have a master services agreement, as amended from time to time, and a commercial supply agreement with Evotec A.G. (“Evotec,” previously known as Aptuit, Oxford), pursuant to which Evotec manufactures the API mavorixafor for use in our clinical and commercial supply. We also have a master services agreement in place with Catalent Inc. (“Catalent”), which is our sole manufacturer for the final capsule drug product formulation of mavorixafor. The term of the master services agreement with Catalent expires on December 31, 2028 and may be terminated by (i) us upon 30 days-notice to Catalent or (ii) by either party following a material breach by the other party that remains uncured for 30 days.

Integral to our manufacturing strategy is our quality control and quality assurance program, which includes standard operating procedures and specifications with the goal that our compounds are manufactured in accordance with current Good Manufacturing Practices (“cGMPs”) and other applicable global regulations. The cGMP compliance includes strict adherence to regulations for quality control, quality assurance and the maintenance of records and documentation. Manufacturing facilities for products and product candidates must meet cGMP requirements, and commercialized products must have acquired FDA, EMA and any other applicable regulatory approval. In this regard, we expect to continue to rely on contract manufacturers to produce sufficient quantities of our compounds in accordance with cGMPs for use in clinical trials and distribution.

We believe our operational strategy of utilizing qualified outside vendors in the foregoing manner allows us to direct our financial and managerial resources to development and commercialization activities, rather than to the establishment and maintenance of a manufacturing and distribution infrastructure.

Competition

Competition in the pharmaceutical and biotechnology industries is intense. We face competition from a variety of companies focused on developing oncology drugs. We compete with large pharmaceutical companies and with other specialized biotechnology companies. In addition to the specific competitive factors discussed below, new anti-cancer drugs that may be developed and marketed in the future could compete with our various compounds.

Some of our existing or potential competitors have substantially greater financial, technical and human resources than us and may be better equipped to develop, manufacture and market products. Smaller companies may also prove to be significant competitors, particularly through collaborative arrangements with large pharmaceutical and established biotechnology companies. Many of these competitors have products that have been approved or are in development and operate large, well-funded research and development programs.

Companies that complete clinical trials, obtain required regulatory approvals and commence commercial sales of their products before us may achieve a significant competitive advantage if their products work through a similar mechanism as our products and if the approved indications are similar. A number of biotechnology and pharmaceutical companies are developing new products for the treatment of the same diseases being targeted by us. In some instances, such products have already entered late-stage clinical trials or received FDA or EC approval. However, cancer drugs with distinctly different mechanisms of action are often used together in combination for treating cancer, allowing several different products to target the same cancer indication or disease type. Such combination therapy is typically supported by clinical trials that demonstrate the advantage of combination therapy over that of a single-agent treatment.

We believe that our ability to compete successfully will be based on our ability to create and maintain scientifically advanced technology, develop proprietary products, attract and retain scientific personnel, obtain patent or other protection for our products, obtain required regulatory approvals and manufacture and successfully market our products, either alone or through

outside parties. We will continue to seek licenses with respect to technology related to our field of interest and may face competition with respect to such efforts. See the risk factor titled “We face direct and intense competition from our competitors in the biotechnology and pharmaceutical industries, and we may not compete successfully against them.” in Part I, Item 1A, “Risk Factors” of this Annual Report on Form 10-K for additional information regarding the risks and uncertainties we face due to competition in our industry.

Government Regulation

The FDA and other regulatory authorities at federal, state and local levels, as well as in foreign countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring and post-approval reporting of drug products such as those we are developing. We, along with third-party contractors, will be required to navigate the various preclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies or seek approval or licensure of our product candidates.

Failure to comply with the applicable U.S. requirements at any time during the product development process, approval process or post-marketing may subject an applicant to administrative or judicial sanctions. These sanctions could include, among other actions, the FDA’s refusal to approve pending applications from the sponsor, withdrawal of an approval, a clinical hold, untitled or warning letters, product recalls or market withdrawals, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement and civil or criminal penalties. Any agency or judicial enforcement action could have a material adverse effect on our company and our products or product candidates.

U.S. Regulation

In the United States, drugs are subject to regulation under the Federal Food, Drug, and Cosmetic Act (“FDCA”) and other federal, state, local, and foreign statutes and regulations. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, and local statutes and regulations requires the expenditure of substantial time and financial resources. Failure to comply with the applicable U.S. requirements at any time during the product development process, approval process or following approval may subject an applicant to administrative action and judicial sanctions. The process required by the FDA before drug product candidates may be marketed in the United States generally involves the following:

•completion of preclinical laboratory tests and animal studies performed in accordance with the FDA’s current Good Laboratory Practices (“GLP”) regulation;

•submission to the FDA of an Investigational New Drug Application (“IND”), which must become effective before clinical trials may begin and must be updated annually or when significant changes are made;

•approval by an independent institutional review board (“IRB”), or ethics committee at each clinical site before the trial is commenced;

•manufacture of the proposed drug candidate in accordance with cGMPs;

•performance of adequate and well-controlled human clinical trials in accordance with Good Clinical Practice (“GCP”) requirements to establish the safety and efficacy of the proposed drug product candidate for its intended purpose;

•preparation of and submission to the FDA of an NDA, after completion of all pivotal clinical trials;

•satisfactory completion of an FDA Advisory Committee review, if applicable;

•a determination by the FDA within 60 days of its receipt of an NDA to file the application for review;

•satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the proposed product is produced to assess compliance with cGMPs, and to assure that the facilities, methods and controls are adequate to preserve the drug product’s continued safety and efficacy, and of selected clinical investigation sites to assess compliance with GCPs; and

•FDA review and approval of an NDA to permit commercial marketing of the product for particular indications for use in the United States.

Preclinical and Clinical Development

Prior to beginning any clinical trial with a product candidate in the United States, we must submit an IND to the FDA. An IND is a request for authorization from the FDA to administer an investigational new drug product to humans. The central focus of

~~Under~~an IND submission is on the ~~terms~~general investigational plan and the protocol or protocols for preclinical studies and clinical trials. The IND also includes results of animal and in vitro studies assessing the ~~Georgetown~~toxicology, ~~agreement~~pharmacokinetics, wepharmacology ~~paid~~and apharmacodynamic ~~one-time-only~~characteristics of the product, ~~upfront~~chemistry, ~~fee~~manufacturing ofand ~~$50~~controls ~~thousand~~information, and weany ~~may~~available behuman ~~required~~data or literature to ~~pay~~support ~~milestone~~the ~~payments~~use of upthe toinvestigational anproduct. ~~aggregate~~In ofApril ~~$800~~2025, ~~thousand~~the ~~related~~FDA published a roadmap to ~~commercial~~reduce ~~sales~~animal oftesting ain ~~licensed~~preclinical ~~product~~safety studies, including those required in INDs, with scientifically validated new approach methodologies (“NAMs”). WeAn ~~are~~IND ~~responsible~~must ~~for~~become ~~all~~effective ~~patent~~before ~~prosecution~~human ~~costs~~clinical ~~incurred~~trials ~~with~~may ~~respect~~begin. toThe IND automatically becomes effective 30 days after receipt by the ~~licensed~~FDA, ~~patents~~unless the FDA, within the 30-day period, raises safety concerns or questions about the proposed clinical trial. WeIn ~~are~~such ~~obligated~~a ~~under~~case, the ~~agreement~~IND tomay ~~use~~be ~~commercially~~placed ~~reasonable~~on ~~efforts~~clinical tohold ~~develop~~and the IND sponsor and ~~commercialize~~the ~~licensed~~FDA ~~product,~~must toresolve ~~make~~any ~~licensed~~outstanding ~~product~~concerns ~~reasonably~~or ~~available~~questions tobefore the ~~public,~~clinical totrial ~~obtain~~can ~~government~~begin. ~~approvals~~Submission ~~for~~of ~~licensed~~an ~~product~~IND ~~and~~therefore tomay ~~market~~or ~~licensed~~may ~~product~~not result in ~~quantities~~FDA ~~sufficient~~authorization to ~~meet~~begin ~~the~~a ~~market~~clinical ~~demand~~trial.

~~The~~Clinical ~~term~~trials involve the administration of the ~~Georgetown~~investigational ~~agreement~~product ~~will~~to ~~continue~~human ~~until~~subjects under the ~~expiration~~supervision of ~~the~~qualified ~~last~~investigators ~~valid~~in ~~claim~~accordance ~~within~~with GCPs, which include the ~~patent~~requirement ~~rights~~that ~~covering~~all ~~the~~research ~~licensed~~subjects ~~products~~provide their informed consent for their participation in any clinical study. ~~Georgetown~~Clinical ~~may~~trials ~~terminate~~are conducted under protocols detailing, among other things, the ~~Georgetown~~objectives ~~agreement~~of orthe ~~convert~~study, ~~our~~the ~~license~~parameters to ~~non-exclusive~~be used in ~~the~~monitoring ~~event:~~safety ~~(i)~~and wethe ~~fail~~effectiveness criteria to ~~pay~~be ~~any~~evaluated. ~~amount~~A ~~and~~separate ~~fail~~submission to ~~cure~~the ~~such~~existing ~~failure~~IND ~~within~~must 30be ~~days~~made ~~after~~for ~~receipt~~each ofsuccessive ~~notice~~clinical trial conducted during product development and for any subsequent protocol amendments. Furthermore, ~~(ii)~~an weindependent ~~default~~IRB infor ~~our~~each ~~obligation~~site proposing to ~~obtain~~conduct the clinical trial must review and ~~maintain~~approve ~~insurance~~the plan for any clinical trial and ~~fail~~its toinformed ~~remedy~~consent ~~such~~form ~~breach~~before ~~within~~the 45clinical ~~days~~trial ~~after~~begins ~~receipt~~at ofthat ~~notice~~site, ~~(iii)~~and wemust ~~declare~~monitor ~~insolvency~~the orstudy ~~bankruptcy~~until orcompleted. ~~(iv)~~Regulatory weauthorities, ~~materially~~the ~~default~~IRB inor the ~~performance~~sponsor ofmay suspend a clinical trial at any ~~material~~time ~~obligations~~on ~~under~~various grounds, including a finding that the ~~Georgetown~~subjects ~~agreement~~are being exposed to an unacceptable health risk or that the trial is ~~not~~unlikely ~~cured~~to ~~within~~meet its stated objectives. Some studies also include oversight by an independent group of qualified experts organized by the clinical study sponsor, known as a data safety monitoring board, which provides authorization for whether or not a study may move forward at designated check points based on access to certain ~~period~~data from the ~~date~~study ofand ~~written~~may ~~notice~~halt ofthe clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such ~~default~~as no demonstration of efficacy. WeThere ~~may~~are ~~terminate~~also requirements governing the ~~Georgetown~~reporting ~~agreement~~of atongoing ~~any~~preclinical ~~time~~studies ~~upon~~and atclinical ~~least~~trials 60and ~~days’~~clinical ~~written~~study ~~notice~~results to public registries.

~~License~~For ~~Agreement~~purposes ~~with~~of ~~Beth~~NDA ~~Israel~~approval, ~~Deaconess~~human ~~Medical~~clinical ~~Center~~trials are typically conducted in three sequential phases that may overlap.

In•Phase ~~December~~1. ~~2016,~~The weinvestigational ~~entered~~product ~~into~~is ainitially ~~license~~introduced ~~agreement~~into ~~with~~healthy ~~Beth~~human ~~Israel~~subjects ~~Deaconess~~or ~~Medical~~patients ~~Center~~with ~~(“BIDMC”)~~the ~~pursuant~~target todisease ~~which~~or wecondition. ~~obtained~~These anstudies ~~exclusive,~~are ~~worldwide~~designed ~~license~~ to ~~make,~~test ~~have~~the ~~made~~safety, ~~use,~~dosage ~~sell~~tolerance, ~~offer for sale~~absorption, metabolism and ~~import~~distribution of ~~licensed~~the ~~products~~investigational ~~and~~product ~~certain processes covered by licensed patent rights co-owned by BIDMC and a nonexclusive royalty-free right to use certain information pertaining to any invention claimed~~ in humans, the ~~licensed~~side ~~patents~~effects ~~that~~associated iswith ~~owned~~increasing ~~by BIDMC to develop~~doses, ~~make~~and, ~~have~~if ~~made~~possible, ~~use, have used, sell, have sold, and commercialize such licensed products and processes. The rights licensed~~ to usgain ~~are~~early ~~for~~evidence ~~all~~on ~~fields of use~~effectiveness. ~~We have the right to grant sublicenses of the licensed rights to third parties to the extent consistent with the terms of the BIDMC agreement.~~

~~Under~~•Phase ~~the~~2. ~~terms~~The ofinvestigational ~~the~~product ~~BIDMC~~is ~~agreement~~administered weto ~~paid~~a limited patient population with a ~~one-time-only~~specified disease or condition to evaluate the preliminary efficacy, ~~upfront~~optimal ~~fee~~dosages ofand ~~$20~~dosing ~~thousand~~schedule and weto ~~are~~identify ~~responsible~~possible ~~for~~adverse ~~all~~side ~~future~~effects ~~patent~~and ~~prosecution~~safety ~~costs~~risks. Multiple Phase 2 clinical trials may be conducted to obtain information prior to beginning larger and more expensive Phase 3 clinical trials.

~~The~~•Phase ~~term~~3. ofThe ~~the~~investigational ~~BIDMC agreement will continue until the expiration of the last valid claim within the patent rights covering the licensed~~ product. ~~BIDMC~~is ~~may~~administered ~~terminate the agreement in the event: (i) we fail~~ to ~~pay~~an ~~any~~expanded ~~amount~~patient ~~and~~population ~~fail~~ to ~~cure~~further ~~such~~evaluate ~~failure within 15 days after receipt of notice~~dosage, ~~(ii) the insurance coverage that we are obligated~~ to ~~maintain~~provide ~~under~~statistically ~~the~~significant ~~agreement~~evidence isof ~~terminated~~clinical efficacy and ~~we fail~~ to ~~obtain~~further ~~replacement~~test ~~insurance~~for ~~within a certain period of time following notice to BIDMC~~safety, orgenerally ~~(iii)~~at wemultiple ~~declare~~geographically ~~insolvency~~dispersed orclinical ~~bankruptcy~~trial sites. InThese ~~addition,~~clinical iftrials we are inintended ~~material~~to ~~breach~~establish ofthe ~~any~~overall ~~material~~risk/benefit ~~provisions~~ratio of the ~~BIDMC~~investigational ~~agreement~~product and ~~fail~~ to ~~remedy~~provide ~~such~~an ~~breach~~adequate ~~within~~basis 60for ~~days~~product after receipt of notice, BIDMC may terminate the BIDMC agreement or terminate any licenses granted under the BIDMC agreement with respect to the country or countries in which such material breach has occurredapproval. ~~We may terminate the BIDMC agreement at any time upon at least 90 days’ written notice.~~

~~Abbisko~~In ~~Agreement~~some cases, the FDA may require, or companies may voluntarily pursue, additional clinical trials after a product is approved to gain more information about the product. These so-called Phase 4 studies may be made a condition to approval of the NDA. Concurrent with clinical trials, companies may complete additional animal studies and develop additional information about the pharmacological characteristics of the product candidate, and must finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, must develop methods for testing the identity, strength, quality and purity of the final product. Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

InA ~~July~~sponsor ~~2019~~may choose, webut ~~entered~~is ~~into~~not ~~a license agreement with Abbisko Therapeutics Co Ltd. (“Abbisko”). Under the terms of the agreement~~required, ~~we granted Abbisko the exclusive right~~ to ~~develop,~~conduct ~~manufacture~~a ~~and~~foreign ~~commercialize~~clinical ~~mavorixafor~~study inunder ~~mainland~~an ~~China, Taiwan, Hong Kong and Macau~~IND. ~~The~~When ~~agreement~~a ~~provides~~foreign ~~Abbisko~~clinical ~~with~~study ~~the~~is ~~exclusive~~conducted ~~rights~~under inan ~~this territory to develop and commercialize mavorixafor in combination with checkpoint inhibitors or other agents in oncology indications. Pancreatic cancer~~IND, ~~ovarian~~all ~~cancer~~IND ~~and~~requirements ~~triple~~must ~~negative breast cancer are expected to~~ be ~~explored~~met ~~initially~~unless waived. WeWhen ~~retain~~ the ~~full~~foreign ~~rest-of-world~~clinical ~~rights~~study tois ~~develop~~not ~~and~~conducted ~~commercialize~~under ~~mavorixafor~~an ~~outside~~IND, ~~of Greater China for all indications and~~ the ~~ability~~sponsor tomust ~~utilize~~ensure ~~data~~that ~~generated pursuant to~~ the ~~Abbisko~~study ~~collaboration~~complies ~~for~~with ~~rest-of-world~~certain ~~development.~~FDA Inregulatory ~~addition,~~requirements ~~Abbisko~~in ~~has~~order ~~the right of first refusal if we determine~~ to ~~pursue~~use ~~additional products in~~ the ~~Abbisko~~study ~~Territory,~~ as ~~defined~~support infor ~~the~~an ~~agreement.~~IND Weor ~~entered~~application ~~into~~for amarketing ~~separate~~approval ~~agreement~~or ~~in April 2020 whereby we will provide Abbisko with a clinical supply and~~licensure, ifincluding that the ~~product~~study iswas ~~commercialized~~conducted in ~~the territory licensed by Abbisko, we intend to enter into a commercial supply of the licensed compound.~~

Pursuant to the agreement with Abbisko, upon the closing of a qualified financing of Abbisko, as defined in the agreement, which occurred in March 2020, Abbisko made a one-time, non-refundable, non-creditable financial milestone payment of $3 million to us. We are also eligible to receive potential development, regulatory and commercial milestone payments of up to $214.0 million, which will vary based on the ultimate sales, if any, of the approved licensed products. Upon commercialization of mavorixafor in the Abbisko Territory, we are eligible to receive a tiered royalty, with a percentage range in the low double-digits, on net sales of approved licensed products. Abbisko is obligated to use commercially reasonable efforts to develop and commercialize mavorixafor in the Abbisko Territory. Abbisko has responsibility for all activities and costs associated with the further

~~development~~accordance with GCP, ~~manufacture~~including review and ~~commercialization~~approval by an independent ethics committee and use of ~~mavorixafor~~proper inprocedures for obtaining informed consent from subjects, and the ~~Abbisko~~FDA ~~Territory~~is able to validate the data from the study through an onsite inspection if the FDA deems such inspection necessary. The GCP requirements encompass both ethical and data integrity standards for clinical studies.

~~Subject~~NDA toSubmission customary rights of each party to earlier terminate the agreement, the term of the agreement is until the expiration of the royalty term on a region-by-region basis. Upon expiration (but not early termination) of the agreement, on a region-by-region basis, the licenses granted by X4 to Abbisko shall become fully paid-up, royalty free, irrevocable and ~~perpetual. In the event~~ Review

~~for~~Assuming ~~any~~successful ~~reason (a) the parties have not entered into a manufacturing technology transfer agreement, or (b) the~~ completion of ~~the~~all ~~manufacturing~~required ~~technology~~testing ~~transfer contemplated therein is not completed,~~ in ~~each~~accordance ~~case~~with atall ~~least~~applicable ~~six~~regulatory ~~(6)~~requirements, ~~months prior to~~ the ~~expiration~~results of ~~this~~product ~~Agreement in its entirety~~development, ~~then~~nonclinical X4studies ~~shall~~and ~~either~~clinical ~~(i)~~trials ~~itself~~are orsubmitted ~~through~~to ~~its affiliates or contract manufacturing organization for~~ the ~~licensed~~FDA ~~product~~as ~~provide~~part ~~commercial supply~~ of ~~such~~an ~~licensed~~NDA ~~product~~requesting inapproval ~~the Abbisko territory~~ to ~~Abbisko~~market ~~after~~ the ~~Term~~product ~~(including,~~for ~~upon~~one ~~Abbisko’s~~or ~~request,~~more ~~commercial~~indications. ~~supply~~The byNDA amust ~~China~~include ~~contract~~all ~~manufacturing~~relevant ~~organization~~data inavailable ~~mainland~~from ~~China)~~pertinent onpreclinical ~~the~~studies ~~same terms as in the agreement or as otherwise negotiated in good faith~~ and ~~agreed~~clinical ~~upon by the parties~~trials, ~~until~~including ~~the~~negative ~~date that X4~~ or ~~its~~ambiguous ~~affiliate~~results oras ~~contract~~well ~~manufacturing~~as ~~organization~~positive ~~completes~~findings, ~~the~~together ~~manufacturing~~with ~~technology~~detailed ~~transfer~~information ~~under~~relating ~~clause (ii); or (ii)~~ to the ~~extent~~product’s ~~permitted~~chemistry, ~~under the upstream agreement~~manufacturing, ~~provide~~controls, orand ~~use~~proposed ~~commercially~~labeling, ~~reasonable~~among ~~efforts~~other tothings. ~~cause~~Data ~~its~~can ~~affiliate~~come orfrom ~~contract~~company-sponsored ~~manufacturing~~clinical ~~organization~~studies intended to ~~provide,~~test the ~~manufacturing~~safety ~~technology~~and ~~transfer~~effectiveness toof ~~Abbisko~~the product, or from a ~~contract~~number ~~manufacturing~~of ~~organization~~alternative ~~designated by Abbisko at Abbisko’s cost; provided that~~sources, inincluding ~~any~~studies ~~case~~initiated ~~X4’s~~and ~~obligations~~sponsored ~~with~~by ~~respect~~investigators. toThe ~~mainland~~submission ~~China~~of ~~shall~~an ~~survive~~NDA ~~the~~requires ~~expiration~~payment of ~~the~~a ~~agreement~~substantial ~~for~~application souser ~~long~~fee asto ~~X4 is~~ the ~~legal~~FDA, ~~holder~~unless ofa ~~the~~waiver ~~regulatory~~or ~~approval~~exemption ~~for such licensed product in mainland China~~applies.

~~Norgine~~In ~~Agreement~~addition, under the Pediatric Research Equity Act (“PREA”), an NDA or supplement to an NDA must contain data to assess the safety and effectiveness of the biological product candidate 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 Food and Drug Administration Safety and Innovation Act requires that a sponsor who is planning to submit a marketing application for a drug product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial pediatric study plan (“PSP”) within sixty days after an end-of-Phase 2 meeting or as may be agreed between the sponsor and FDA. Unless otherwise required by regulation, PREA does not apply to any drug product for an indication for which orphan designation has been granted, except that the PREA will apply to an original NDA for a new active ingredient that is orphan-designated if the drug is a molecularly targeted cancer product intended for the treatment of an adult cancer and is directed at a molecular target that the FDA determines to be substantially relevant to the growth or progression of a pediatric cancer.

OnWithin ~~January~~60 ~~13,~~days ~~2025~~following submission of the application, wethe ~~entered~~FDA ~~into~~reviews aan ~~license~~NDA ~~and~~submitted ~~supply~~to ~~agreement~~determine ~~with~~if ~~Norgine~~it is substantially complete before the agency accepts it for filing. ~~Under~~The FDA may refuse to file any NDA that it deems incomplete or not properly reviewable at the ~~terms~~time of ~~the~~submission ~~agreement~~and may request additional information. In this event, wethe ~~granted~~NDA ~~Norgine~~must be resubmitted with the ~~exclusive~~additional ~~right~~information. toOnce ~~develop~~an NDA has been accepted for filing, ~~manufacture~~the ~~and~~FDA’s ~~commercialize~~goal ~~mavorixafor~~is into ~~Europe~~review standard applications within ten months after the filing date, ~~Australia~~or, ~~and~~if ~~New~~the ~~Zealand.~~application ~~The~~qualifies ~~agreement~~for ~~grants~~priority ~~Norgine~~review, ansix ~~exclusive~~months ~~license~~after tothe ~~(i)~~FDA ~~distribute,~~accepts ~~market~~the application for filing. In both standard and ~~sell~~priority reviews, the ~~our~~review ~~product~~process ~~mavorixafor~~may also be extended by FDA requests for ~~all~~additional ~~indications~~information inor ~~the~~clarification. ~~European~~The ~~Economic~~FDA ~~Area~~reviews an NDA to determine, ~~Switzerland~~among other things, ~~the~~whether ~~United~~a ~~Kingdom~~product is safe, ~~Australia~~pure and ~~New~~potent ~~Zealand~~and ~~(collectively~~the facility in which it is manufactured, processed, packed or held meets standards designed to assure the ~~“Territory”)~~product’s continued safety, ~~following~~purity ~~regulatory~~and ~~approval~~potency. ~~Additionally,~~The ~~Norgine~~FDA ~~was~~may ~~granted~~convene aan ~~co-exclusive~~advisory ~~license~~committee to ~~manufacture~~provide ~~mavorixafor~~clinical ~~for~~insight on application review questions. The FDA is not bound by the ~~Territory~~recommendations ~~within~~of an advisory committee, but it considers such recommendations carefully when making decisions. Before approving an NDA, the ~~field~~FDA will typically inspect the facility or facilities where the product is manufactured. The ~~Company~~FDA ~~retains~~will ~~all~~not ~~rights~~approve toan ~~mavorixafor~~application ~~outside~~unless it determines that the ~~Territory~~manufacturing processes and ~~specific~~facilities ~~reserved~~are ~~rights~~in ~~within~~compliance with cGMP requirements and adequate to assure consistent production of the ~~Territory~~product within required specifications. ~~Norgine~~Additionally, ~~may~~before ~~grant~~approving ~~sublicenses~~an toNDA, ~~its~~the ~~affiliates~~FDA ~~and~~will ~~certain~~typically ~~third~~inspect ~~parties~~one ~~subject~~or more clinical sites to assure compliance with GCPs. If the ~~terms~~FDA ofdetermines that the ~~agreement~~application, ~~except~~manufacturing ~~that~~process itor ~~may~~manufacturing facilities are not ~~sublicense~~acceptable, it will outline the ~~commercial~~deficiencies ~~rights~~in ~~granted~~the ~~under~~submission and often will request additional testing or information. Notwithstanding the ~~agreement~~submission ~~for~~of ~~certain~~any ~~countries~~requested ~~without~~additional ~~our~~information, ~~explicit~~the ~~consent~~FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

~~Pursuant~~After to the ~~terms~~FDA ofevaluates ~~the~~an ~~Norgine~~NDA ~~Agreement,~~and weconducts ~~shall~~inspections ~~receive~~of ~~the~~manufacturing ~~following~~facilities ~~payments~~where ~~from~~the ~~Norgine:~~investigational ~~(i)~~product anand/or ~~upfront~~its ~~payment~~drug insubstance ~~the~~will ~~amount~~be ofproduced, ~~€28.5 million~~the ~~(such~~FDA ~~payment~~may ~~was~~issue ~~received~~an inapproval ~~January~~letter ~~2025),~~or ~~(ii)~~a upComplete toResponse ~~€226~~letter.~~0 million~~ ~~upon~~An ~~the~~approval ~~achievement~~letter ofauthorizes ~~certain regulatory,~~ commercial ~~and~~marketing ~~sales~~of ~~milestones,~~the ~~and~~product ~~(iii)~~with ~~escalating~~specific ~~double-digit~~prescribing ~~royalties~~information offor upspecific toindications. ~~mid-twenties~~A onComplete ~~any~~Response ~~future~~letter ~~net~~will ~~sales~~describe inall of the ~~Territory.~~deficiencies ~~The~~that ~~tiered~~the ~~royalty~~FDA ~~payments~~has ~~are~~identified ~~subject~~in tothe ~~royalty stacking~~NDA, ~~and~~except tothat awhere ~~material~~the ~~reduction~~FDA ondetermines athat ~~country-by-country~~the ~~basis~~data ifsupporting athe ~~generic~~application ~~version~~are ofinadequate ~~mavorixafor~~to ~~becomes~~support ~~available~~approval, in the ~~applicable~~FDA ~~country.~~may Weissue ~~and~~the ~~Norgine~~Complete ~~will~~Response ~~collaborate~~letter ~~closely~~without onfirst ~~regulatory~~conducting ~~filings~~required inspections, ~~while~~testing wesubmitted ~~continue~~product tolots beand/or ~~responsible~~reviewing ~~for~~proposed ~~the~~labeling. ~~ongoing~~In ~~global,~~issuing ~~pivotal~~the ~~Phase~~Complete 3Response ~~4WARD~~letter, ~~clinical~~the ~~trial~~FDA ~~evaluating~~may ~~mavorixafor~~recommend inactions ~~chronic~~that ~~neuropathy.~~the ~~Norgine~~applicant ~~will~~might betake ~~responsible~~to ~~for~~place ~~all~~the ~~market~~NDA ~~access~~in ~~and~~condition ~~commercialization~~for ~~activities~~approval, ~~and~~including ~~will~~requests ~~eventually~~for ~~hold~~additional ~~all~~information ~~marketing~~or ~~authorizations in the licensed territories~~clarification. WeThe ~~will~~FDA ~~manufacture~~may ~~and~~delay ~~supply~~or ~~mavorixafor~~refuse toapproval ~~Norgine.~~of ~~Norgine~~an ~~shall~~NDA beif ~~required~~applicable toregulatory ~~pay~~criteria aare ~~supply~~not ~~price~~satisfied, ~~for~~require ~~the~~additional ~~licensed~~testing ~~product~~or ~~derived~~information ~~from~~and/or ~~the~~require ~~contract~~post-marketing ~~manufacturing~~testing ~~organization~~and ~~costs~~surveillance ~~plus~~to amonitor ~~low~~safety ~~double-teen~~or ~~digit~~efficacy of ~~the~~a ~~contract manufacturing costs~~product.

Subject to customary rights of each party to earlier terminate the agreement, the term of the agreement continues, on a country-by-country basis, until the later of: (i) the tenth (10th) anniversary of the first commercial sale of mavorixafor, (ii) expiration of regulatory market exclusivity of mavorixafor or (iii) expiration of the last-to-expire licensed patent in such country. The term of the agreement shall be automatically renewed for additional three year terms unless either party provides the other party written notice of its intent not to renew the Agreement at least one year prior to the applicable termination date of the agreement. In the event of automatic renewal, the royalty payment rate drops to a single digit royalty.

Intellectual Property

Our ability to commercialize our product candidates depends in large part on our ability to obtain and maintain intellectual property protection for our product candidates, including mavorixafor, and our preclinical compounds and core technologies. Our policy is to seek to protect our intellectual property position by, among other methods, filing U.S. and foreign patent applications related to the technology, inventions and improvements that are important to the development and implementation of our business strategy. We also rely on trade secrets, know-how and continuing technological innovation to develop and maintain our proprietary position.

WeIf ~~file~~regulatory ~~patent~~approval ~~applications~~of ~~directed~~a ~~to our~~ product ~~candidates~~is granted, ~~preclinical~~such ~~compounds~~approval ~~and~~will ~~related~~be ~~technologies~~granted tofor ~~establish~~particular ~~intellectual~~indications ~~property~~and ~~positions~~may onentail ~~these~~limitations ~~compounds~~on ~~and~~the ~~their~~indicated uses infor ~~disease.~~which Assuch ofproduct ~~December~~may ~~31,~~be ~~2024~~marketed. For example, wethe ~~owned~~FDA ormay ~~exclusively~~approve ~~licensed~~the 18NDA ~~issued~~with ~~U.S.~~a ~~patents,~~REMS 10to ~~pending~~ensure ~~U.S.~~the ~~non-provisional~~benefits ~~patent~~of ~~applications,~~the ~~four~~product ~~pending~~outweigh Uits risks.S. ~~provisional~~A ~~patent~~REMS ~~applications,~~is ~~and~~a ~~approximately~~safety ~~121~~strategy ~~PCT~~to ~~and~~manage ~~foreign~~a ~~patents~~known or potential serious risk associated with a product and ~~patent~~to ~~applications~~enable ~~including~~patients into ~~the~~have ~~following~~continued ~~foreign~~access ~~jurisdictions:~~to ~~Austria,~~such ~~Australia,~~medicines ~~Belgium,~~by ~~Brazil,~~managing ~~Canada,~~their ~~China~~safe use, ~~Czech~~and ~~Republic,~~could ~~Denmark~~include medication guides, ~~Eurasian~~physician ~~Patent~~communication ~~Organization~~plans, ~~European~~or ~~Patent~~elements ~~Office,~~to ~~Finland,~~assure ~~France,~~safe ~~Germany~~use, ~~Greece,~~such ~~Great~~as ~~Britain,~~restricted ~~Hong~~distribution ~~Kong~~methods, ~~Hungry,~~patient ~~India,~~registries ~~Ireland,~~and ~~Israel,~~other ~~Italy,~~risk ~~Japan,~~minimization ~~Kuwait,~~tools. ~~Mexico,~~The ~~Netherlands,~~FDA ~~New~~also ~~Zealand,~~may ~~Norway,~~condition ~~Oman,~~approval ~~Poland~~on, ~~Portugal,~~among ~~Qatar~~other things, ~~Saudi~~changes ~~Arabia,~~to ~~Slovakia,~~proposed ~~Slovenia,~~labeling ~~Singapore,~~or ~~South~~the ~~Africa,~~development ~~South~~of ~~Korea,~~adequate ~~Spain,~~controls ~~Sweden,~~and ~~Switzerland~~specifications. Once approved, ~~Turkey~~the FDA may withdraw the product approval if compliance with pre-and post-marketing requirements is not maintained or if problems occur after the product reaches the marketplace. The FDA may require one or more Phase 4 post-market studies and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization, and ~~United~~may ~~Arab~~limit ~~Emirates~~further marketing of the product based on the results of these post-marketing studies.

~~Patents~~Expedited ~~issued~~Development ~~from the in-licensed portfolio are exclusively licensed to us under the terms of the Genzyme Agreement~~ and ~~are~~Review expected to expire between 2024 and 2027. Additionally, we have exclusively licensed from Genzyme, BIDMC and Georgetown University their interest in certain co-owned patents. Patents issued from our co-owned portfolio, if all maintenance fees are paid, are expected to expire in 2036, not including any Patent Term Adjustment (PTA), Patent Term Extension (PTE), or other extensions of term that may be available.Programs

~~With~~The ~~respect~~FDA tooffers ~~our~~a ~~lead~~number ~~product mavorixafor, as~~ of ~~December~~expedited ~~31,~~development ~~2024,~~and wereview ~~owned~~programs orfor ~~exclusively~~qualifying ~~licensed~~product ~~five~~candidates. ~~issued~~The ~~U.S.~~fast ~~patents~~track ~~and~~program ~~one~~is ~~pending~~intended ~~U.S.~~to ~~non-provisional~~expedite ~~patent~~or ~~application~~facilitate ~~that~~the ~~relate~~process tofor ~~mavorixafor~~reviewing ~~composition~~new ofproducts ~~matter;~~that ~~two~~meet ~~issued~~certain Ucriteria.S. ~~patents~~Specifically, ~~three~~new ~~pending~~products ~~PCT~~are ~~applications,~~eligible ~~one~~for ~~pending~~fast ~~U.S.~~track ~~non-provisional~~designation ~~patent~~if ~~application,~~they ~~and~~are 27intended ~~pending~~to ~~foreign~~treat ~~patent~~a ~~applications~~serious ~~that~~or ~~relate~~life-threatening todisease ~~methods~~or ofcondition ~~manufacturing~~and ~~mavorixafor,~~data ~~including~~demonstrate ~~certain~~the ~~key~~potential ~~intermediate~~to ~~molecules;~~address ~~two~~unmet ~~issued~~medical ~~U.S.~~needs ~~patents~~for ~~and~~the ~~one~~disease ~~pending~~or Ucondition.S. ~~non-provisional~~Fast ~~patent~~track ~~application~~designation ~~that~~applies ~~relate~~ to the ~~use~~combination of ~~mavorixafor~~the ~~for~~product ~~treatment~~and ofthe ~~patients~~specific ~~with~~indication ~~WHIM~~for ~~Syndrome;~~which ~~two~~it ~~pending~~is Ubeing studied.S. ~~non-provisional~~The ~~patent~~sponsor ~~application,~~of ~~one~~a ~~pending~~fast ~~PCT~~track ~~application,~~product ~~and~~has ~~one~~opportunities ~~pending~~for ~~U.S.~~more ~~provisional~~frequent ~~patent~~interactions ~~application~~with ~~that relate to~~ the ~~use~~review ofteam ~~mavorixafor~~during ~~for~~product ~~treatment~~development ofand, ~~patients~~once ~~with~~an ~~conditions~~NDA ~~involving~~is ~~chronic~~submitted, ~~neutropenia;~~the ~~and~~product ~~two~~may ~~U.S.~~be ~~issued~~eligible ~~patents,~~for ~~and~~priority ~~three pending U~~review.S. ~~non-provisional~~A ~~patent~~fast ~~applications,~~track ~~that~~product ~~relate~~may toalso ~~uses~~be ofeligible ~~mavorixafor~~for inrolling ~~other fields~~review, ~~including~~where ~~oncology.~~the ~~The~~FDA ~~issued~~may ~~U.S.~~consider ~~patents~~for ~~covering~~review ~~aspects~~sections of ~~mavorixafor~~the ~~and~~NDA ~~its~~on ~~use,~~a ifrolling ~~all~~basis ~~maintenance~~before ~~fees~~the ~~are~~complete ~~paid,~~application ~~and~~is ~~pending applications~~submitted, if ~~granted~~the ~~and~~sponsor ~~all~~provides ~~maintenance~~a ~~fees~~schedule ~~paid,~~for ~~are~~the ~~expected~~submission toof ~~expire~~the ~~between~~sections ~~2024~~of ~~and~~the ~~2044~~NDA, ~~not~~the ~~including~~FDA ~~any~~agrees ~~(PTA),~~to ~~(PTE)~~accept orsections ~~other extensions~~ of ~~term~~the ~~that~~NDA ~~may~~and bedetermines ~~available.~~that ~~With~~the ~~respect~~schedule tois ~~foreign patent rights to mavorixafor~~acceptable, asand ofthe ~~December~~sponsor ~~31,~~pays ~~2024,~~any werequired ~~had~~user ~~approximately~~fees ~~110~~upon ~~pending~~submission ~~PCT~~of ~~and~~the ~~foreign~~first ~~patents~~section ~~and~~of ~~patent~~the ~~applications~~NDA.

~~With~~Additionally, ~~respect~~products tostudied ~~developmental~~for ~~compounds,~~their ~~including~~safety ~~preclinical~~and ~~candidates~~effectiveness ~~for~~in ~~our~~treating ~~X4P-002~~serious ~~and~~or ~~X4P~~life-~~003~~threatening ~~programs,~~diseases asor ofconditions ~~December~~may ~~31,~~receive ~~2024~~accelerated approval upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, weor ~~had~~on ~~five~~a ~~issued~~clinical ~~U.S.~~endpoint ~~patents~~that can be measured earlier than irreversible morbidity or mortality, ~~four~~that ~~pending~~is ~~U.S.~~reasonably ~~non-provisional~~likely ~~patent~~to ~~applications~~predict an effect on irreversible morbidity or mortality or other clinical benefit, ~~three~~taking ~~pending~~into ~~U.S.~~account ~~provisional~~the ~~patent~~severity, ~~applications~~rarity, or prevalence of the condition and ~~three~~the ~~pending~~availability ~~PCT~~or ~~patent~~lack ~~applications~~of alternative treatments. ~~These~~As ~~issued~~a ~~patents~~condition of accelerated approval, ifthe ~~all~~FDA ~~maintenance~~will ~~fees~~generally ~~are~~require ~~paid,~~the sponsor to perform adequate and ~~pending~~well-controlled ~~applications,~~post-marketing ifclinical ~~granted~~studies to verify and ~~all~~describe ~~maintenance~~the ~~fees~~anticipated ~~paid,~~effect ~~are~~on ~~expected~~irreversible tomorbidity ~~expire~~or ~~between~~mortality ~~2024~~or other clinical benefit. Under the Food and ~~2045~~Drug Omnibus Reform Act of 2022, ~~not~~the ~~including~~FDA ~~any~~may ~~(PTA)~~require, ~~(PTE)~~as appropriate, that such studies be underway prior to approval or ~~other~~within ~~extensions~~a specific time period after the date of ~~term~~approval ~~that~~for a product granted accelerated approval. Products receiving accelerated approval may be ~~available.~~subject ~~With~~to ~~respect~~expedited withdrawal procedures if the sponsor fails to ~~foreign~~conduct ~~patent~~the ~~rights~~required post-marketing studies or if such studies fail to ~~our~~verify ~~developmental~~the ~~compounds~~predicted clinical benefit. In addition, ~~including~~the ~~preclinical~~FDA ~~candidates~~currently requires as a condition for ~~our~~accelerated ~~X4P~~approval pre-~~002~~approval ~~and~~of ~~XP-003~~promotional ~~programs~~materials, wewhich ~~have~~could ~~approximately~~adversely 22impact ~~pending~~the ~~PCT~~timing ~~and~~of ~~foreign~~the ~~patents~~commercial ~~and~~launch ~~patent~~of ~~applications~~the product.

~~The~~A ~~term~~product ofintended ~~individual~~to ~~patents~~treat ~~depends~~a ~~upon~~serious ~~the~~or ~~legal~~life-threatening ~~term~~disease ofor ~~the~~condition ~~patents~~may inalso ~~the~~be ~~countries~~eligible infor ~~which~~breakthrough ~~they~~therapy ~~are~~designation ~~obtained.~~to Inexpedite ~~most~~its ~~countries,~~development ~~including~~and ~~the United States, the patent term is 20 years from the earliest filing date of a non-provisional patent application~~review. InA ~~the~~product ~~United~~can ~~States,~~receive abreakthrough ~~patent’s~~therapy ~~term~~designation ~~may~~if bepreliminary ~~lengthened~~clinical byevidence ~~patent~~indicates ~~term~~that ~~adjustment, which compensates a patentee for administrative delays by~~ the ~~U.S. Patent and Trademark Office~~product, ~~(the~~alone ~~“USPTO”),~~or in ~~examining~~combination ~~and~~with ~~granting~~one ~~a patent,~~ or ~~may~~more beother ~~shortened~~drugs ifor abiologics, ~~patent~~may isdemonstrate ~~terminally~~substantial ~~disclaimed~~improvement over anexisting ~~earlier~~therapies ~~filed~~on ~~patent.~~one ~~The~~or ~~term~~more ofclinically asignificant ~~U.S.~~endpoints, ~~patent~~such ~~that~~as ~~covers~~substantial atreatment ~~drug~~effects orobserved ~~biological~~early ~~product~~in ~~may~~clinical ~~also~~development. beThe ~~eligible~~designation ~~for~~includes ~~patent~~all ~~term~~of ~~extension when approval from~~ the ~~FDA~~fast istrack ~~granted,~~program ~~provided statutory and regulatory requirements are met. In the future~~features, ifas ~~our~~well ~~product~~as ~~candidates~~more ~~receive~~intensive ~~approval from the~~ FDA orinteraction ~~foreign~~and ~~regulatory~~guidance ~~authorities,~~beginning weas ~~expect~~early toas ~~apply~~Phase ~~for~~1 ~~patent~~and ~~term~~an ~~extensions~~organizational oncommitment ~~issued~~to ~~patents~~expedite ~~covering those products, depending upon~~ the ~~length~~development ~~of the clinical trials for each drug~~ and ~~other~~review ~~factors. There can be no assurance that any~~ of ~~our pending patent applications will issue or that we will benefit from any patent term extension or other favorable adjustment to~~ the ~~term~~product, ofincluding ~~any~~involvement of ~~our~~senior ~~patents~~managers.

AsFast ~~with~~track ~~other~~designation ~~biotechnology~~ and ~~pharmaceutical~~breakthrough ~~companies,~~therapy ~~our~~designation ~~ability~~do tonot ~~maintain~~change ~~and~~the ~~solidify~~standards ~~our proprietary and intellectual property position~~ for ~~our~~approval ~~product~~but ~~candidates,~~may ~~including~~expedite ~~mavorixafor,~~the ~~and~~development ~~our~~or ~~preclinical~~approval ~~compounds,~~process. ~~and~~Even ~~our~~if ~~core~~a ~~technologies~~product ~~will~~qualifies ~~depend~~for onone ~~our~~or ~~success~~more inof ~~obtaining~~these ~~effective patent claims and enforcing those claims if granted. However~~programs, ~~patent~~the ~~applications~~FDA ~~that we~~ may ~~file~~later ordecide ~~license~~that ~~from third parties may not result in~~ the ~~issuance~~product ofno ~~patents.~~longer Wemeets ~~also cannot predict~~ the ~~breadth~~conditions offor ~~claims~~qualification ~~that may be allowed~~ or ~~enforced~~decide ~~in our patents. Any issued patents~~ that ~~we may receive in~~ the ~~future~~time ~~may~~period befor ~~challenged,~~FDA ~~invalidated~~review or ~~circumvented.~~approval ~~For~~will ~~example,~~not ~~prior~~be ~~to March 16, 2013, in the United States, patent applications were subject to a “first to invent” rule of law~~shortened. ~~Applications filed after March 16, 2013 (except for certain applications claiming the~~

Orphan Drug Designation and Exclusivity

Under the Orphan Drug Act of 1983, the FDA may grant orphan drug designation to a product candidate intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the United States, or 200,000 or more individuals in the United States for which there is no reasonable expectation that the cost of developing and making available in the United States a drug or biologic for this type of disease or condition will be recovered from sales in the United States for that product candidate. Orphan drug designation must be requested before submitting an NDA. After the FDA grants orphan drug designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the

~~benefit~~FDA. ofThe ~~earlier-filed~~orphan ~~applications)~~drug ~~are~~designation ~~subject~~does tonot aconvey ~~“first~~any toadvantage ~~file”~~in, ~~rule~~or shorten the duration of, ~~law~~the regulatory review or approval process.

~~Discoveries~~If ~~reported~~a inproduct ~~the~~that ~~scientific~~has ~~literature~~orphan ~~often~~drug ~~lag~~designation ~~the~~subsequently ~~actual~~receives ~~discoveries,~~the ~~and~~first ~~patent~~FDA ~~applications~~approval infor the ~~United~~disease ~~States~~or ~~and~~condition ~~other~~for ~~jurisdictions~~which ~~are~~it ~~typically~~has ~~not~~such ~~published until 18 months after filing~~designation, orthe inproduct ~~some~~is ~~cases~~entitled ~~not~~to atorphan ~~all.~~drug Weexclusive ~~cannot~~approval ~~be certain that any existing~~ (or ~~future~~exclusivity), ~~application~~which ~~will~~means bethat ~~subject to~~ the ~~“first~~FDA tomay ~~file”~~not orapprove ~~“first~~any toother ~~invent” rule of law~~applications, ~~that~~including wea ~~were~~full ~~the~~NDA, ~~first~~ to ~~make~~market the ~~inventions~~same ~~claimed~~product infor ~~our~~the ~~existing~~same ~~patents~~approved use or ~~pending~~indication ~~patent~~for ~~applications~~seven ~~subject~~years, toexcept ~~the~~in ~~prior~~limited ~~laws~~circumstances, orsuch ~~that~~as wea ~~were~~showing ~~the first to file for patent protection~~ of ~~such~~clinical ~~inventions~~superiority ~~subject~~ to the ~~new~~product ~~laws.~~with Iforphan ~~third~~drug ~~parties~~exclusivity ~~prepare~~by ~~and~~means ~~file~~of ~~patent~~greater ~~applications~~effectiveness, ingreater ~~the~~safety ~~United~~or ~~States~~providing ~~that~~a ~~also~~major ~~claim~~contribution ~~technology~~to wepatient ~~have~~care ~~claimed~~or inif ~~our~~the ~~patents~~holder orof ~~patent~~the ~~applications,~~orphan wedrug ~~may~~exclusivity ~~have~~cannot toassure ~~participate~~the inavailability ~~interference~~of ~~proceedings~~sufficient inquantities of the ~~USPTO~~orphan drug to ~~determine~~meet ~~priority~~the needs of ~~invention,~~patients ~~which~~with ~~could~~the ~~result~~same inuse ~~substantial~~or ~~costs~~indication tofor ~~us,~~which ~~even~~the ifalready-approved ~~the~~or ~~eventual~~licensed ~~outcome~~product iswas ~~favorable~~approved toor uslicensed. InOrphan ~~addition,~~drug ~~because~~exclusivity ofdoes ~~the~~not ~~extensive~~prevent ~~time~~the ~~required~~FDA ~~for~~from ~~clinical~~approving ~~development~~a ~~and~~different ~~regulatory~~drug ~~review~~or ofbiologic afor ~~product~~the ~~candidate~~same wedisease ~~may~~or ~~develop~~condition, itor isthe ~~possible~~same ~~that,~~drug ~~before~~or ~~any~~biologic offor ~~our~~a ~~product~~different ~~candidates~~disease ~~can~~or becondition. ~~commercialized,~~Among ~~any~~the ~~related~~other ~~patent~~benefits ~~may~~of ~~expire~~orphan ordrug ~~remain~~designation inare ~~force~~tax credits for ~~only~~certain aresearch ~~short~~and ~~period~~a ~~following~~waiver ~~commercialization, thereby reducing any advantage~~ of ~~any~~the ~~such~~NDA ~~patent~~application fee.

InA ~~addition~~designated toorphan ~~patents,~~drug wemay ~~rely~~not ~~upon~~receive ~~unpatented~~orphan ~~trade~~drug ~~secrets,~~exclusivity ~~know-how,~~if ~~and~~it ~~continuing~~is ~~technological~~approved ~~innovation~~for toa ~~develop~~use ~~and~~that ~~maintain~~is ~~our~~broader ~~competitive~~than ~~position.~~the Weindication ~~seek~~for towhich ~~protect~~it ~~our~~received ~~proprietary~~orphan ~~information,~~drug indesignation. ~~part,~~In ~~by using confidentiality agreements with our collaborators~~addition, ~~scientific~~exclusive ~~advisors,~~marketing ~~employees~~rights ~~and~~in ~~consultants,~~the ~~and~~United ~~invention~~States ~~assignment~~may ~~agreements~~be ~~with~~lost ~~our~~if ~~employees.~~the WeFDA ~~also~~later ~~have~~determines ~~agreements~~that ~~requiring~~the ~~assignment~~request offor ~~inventions~~designation ~~with~~was ~~selected~~materially ~~consultants,~~defective ~~scientific~~or ~~advisors,~~if ~~and~~the ~~collaborators.~~manufacturer ~~The~~is ~~confidentiality~~unable ~~agreements are designed~~ to ~~protect~~assure ~~our~~sufficient ~~proprietary~~quantities ~~information~~of ~~and, in~~ the ~~case~~product ~~of agreements or clauses requiring invention assignment,~~ to ~~grant~~meet usthe ~~ownership~~needs of ~~technologies~~patients ~~that~~with ~~are~~the ~~developed~~rare ~~under~~disease ~~those~~or ~~agreements~~condition.

~~Government~~There ~~Regulation~~is ~~and~~some ~~Product~~uncertainty ~~Approval~~with respect to the FDA’s interpretation of the scope of orphan drug exclusivity. Historically, exclusivity was specific to the orphan indication for which the drug was approved. As a result, the scope of exclusivity was interpreted as preventing approval of a competing product. However, in 2021, the federal court in Catalyst Pharmaceuticals, Inc. v. Becerra suggested that orphan drug exclusivity covers the full scope of the orphan-designated “disease or condition” regardless of whether a drug obtained approval for a narrower use.

~~The~~Combination ~~FDA Approval Process~~Therapy

InCombination ~~the~~therapy ~~United~~is ~~States,~~a ~~pharmaceutical~~treatment ~~products~~modality ~~are~~that ~~subject~~involves tothe ~~extensive~~use ~~regulation~~of bytwo ~~the~~or ~~FDA.~~more ~~The~~drugs ~~Federal~~to ~~Food,~~be ~~Drug,~~used ~~and~~in ~~Cosmetic~~combination ~~Act~~to ~~(the~~treat ~~“FDCA”)~~a ~~and~~disease ~~other~~or ~~federal~~condition. ~~and~~If ~~state~~those ~~statutes~~drugs ~~and~~are ~~regulations,~~combined ~~govern,~~in ~~among~~one ~~other~~dosage ~~things~~form, ~~the~~such ~~research,~~as ~~development,~~one ~~testing~~pill, ~~manufacture,~~that ~~storage,~~is ~~recordkeeping,~~known ~~approval,~~as ~~labeling,~~a ~~promotion~~fixed ~~and~~dose ~~marketing,~~combination ~~distribution,~~product ~~post-approval~~and ~~monitoring~~it ~~and~~is ~~reporting,~~reviewed ~~sampling,~~pursuant ~~and~~to ~~import~~the ~~and~~FDA’s ~~export~~Combination ofRule ~~pharmaceutical~~at ~~products.~~21 ~~Failure~~CFR to300.50. ~~comply~~The ~~with~~rule ~~applicable~~provides ~~requirements~~that ~~may~~two ~~subject~~or amore ~~company~~drugs tomay abe ~~variety~~combined ofin ~~administrative~~a orsingle ~~judicial~~dosage ~~sanctions,~~form ~~such~~when aseach ~~imposition~~component ofcontributes ~~clinical~~to ~~holds,~~the ~~refusal~~claimed byeffects and the ~~FDA~~dosage toof ~~approve~~each ~~pending~~component ~~NDAs~~(amount, ~~warning letters~~frequency, ~~product~~duration) ~~recalls,~~is ~~product~~such ~~seizures,~~that ~~total~~the orcombination ~~partial~~is ~~suspension~~safe ofand ~~production~~effective orfor ~~distribution,~~a ~~injunctions,~~significant ~~fines,~~patient ~~refusals~~population ofrequiring ~~government~~such ~~contracts,~~concurrent ~~restitution,~~therapy ~~disgorgement,~~as ~~civil~~defined ~~penalties~~in ~~and~~the ~~criminal~~labeling ~~prosecution~~for the drug.

~~Pharmaceutical~~But ~~product~~not ~~development~~all incombination therapy falls under the ~~United~~category ~~States~~of ~~typically~~a ~~involves~~fixed ~~preclinical~~dose orcombination. ~~other~~For ~~nonclinical~~example, ~~laboratory~~the ~~and~~FDA ~~animal~~recognizes ~~tests~~that two drugs in separate dosage forms and ~~the~~in ~~submission~~separate topackaging, ~~the~~that ~~FDA~~otherwise ofmight anbe ~~Investigational~~administered ~~New~~as ~~Drug~~monotherapy ~~(“IND”)~~for ~~application~~an indication, ~~which~~also ~~must~~may ~~become~~be ~~effective~~used ~~before~~in ~~clinical~~combination ~~testing~~for ~~may~~the ~~commence~~same indication. ~~For~~In ~~commercial approval~~2013, the ~~sponsor~~FDA ~~must~~issued ~~submit~~guidance ~~adequate~~to ~~and~~assist ~~well-controlled~~sponsors ~~investigations~~that ~~demonstrating~~were developing the range of combination therapies that fall outside the ~~drug~~category isof ~~safe~~fixed ~~for~~dose ~~use~~combinations. ~~under~~That guidance provides recommendations and advice on such topics as: (1) assessment at the ~~conditions~~outset ~~prescribed,~~whether ~~recommended~~two or ~~suggested~~more therapies are appropriate for use in ~~the~~combination; ~~proposed~~(2) ~~labeling~~guiding principles for nonclinical and ~~providing~~clinical ~~substantial~~development ~~evidence,~~of ~~generally~~the ~~consisting~~combination; (3) options for regulatory pathways to seek marketing approval of ~~adequate,~~the ~~well~~combination; and (4) post-~~controlled~~marketing ~~clinical~~safety ~~trials~~monitoring toand ~~establish~~reporting ~~that~~obligations. Given the ~~drug~~wide ~~will~~range ~~have~~of potential combination therapy variations, the ~~effect~~FDA indicated it ~~purports~~intends orto isassess ~~represented~~each topotential ~~have~~combination ~~under~~on ~~the~~a ~~conditions~~case-by ofcase ~~use~~basis ~~prescribed,~~and ~~recommended~~encouraged orsponsors ~~suggested~~to engage in early and regular consultation with the relevant review division at the agency throughout the development process for its proposed ~~labeling~~combination.

Nonclinical tests include laboratory evaluation of product chemistry, formulation, and toxicity, as well as animal studies to assess the characteristics and potential safety and efficacy of the product. The conduct of certain nonclinical tests must comply with federal requirements, including, as applicable, the FDA’s good laboratory practices regulations and the U.S. Department of Agriculture’s regulations implementing the Animal Welfare Act. The results of nonclinical testing are submitted to the FDA as part of an IND along with other information, including information about product chemistry, manufacturing and controls, and a proposed clinical trial protocol. LongPost-~~term~~Approval ~~nonclinical tests, such as animal studies of reproductive toxicity and carcinogenicity, may continue after the IND is submitted.~~Requirements

AAny ~~30-day~~products ~~waiting~~manufactured ~~period~~or ~~after~~distributed by us pursuant to FDA approvals are subject to pervasive and continuing regulation by the ~~submission~~FDA, including, among other things, requirements relating to record-keeping, reporting of ~~each~~adverse ~~IND~~experiences, isperiodic ~~required~~reporting, ~~prior~~product sampling and distribution, and advertising and promotion of the product. After approval, most changes to the ~~commencement~~approved ofproduct, ~~clinical~~such ~~testing~~as adding new indications or other labeling claims, are subject to prior FDA review and approval. There also are continuing user fee requirements, under which the FDA assesses an annual program fee for each product identified in ~~humans~~an approved NDA. IfDrug manufacturers and their subcontractors are required to register their establishments with the FDA ~~has~~and ~~not~~certain ~~imposed~~state aagencies, ~~clinical~~and ~~hold~~are onsubject to periodic unannounced inspections by the ~~IND~~FDA ~~within~~and ~~this~~certain ~~30-day~~state ~~period~~agencies for compliance with cGMPs, which impose certain procedural and documentation requirements upon us and our third-party manufacturers. Changes to the ~~clinical~~manufacturing ~~trial~~process ~~proposed~~are instrictly regulated, and, depending on the ~~IND~~significance of the change, may ~~begin~~require prior FDA approval before being implemented.

Clinical trials involve the administration of the investigational new drug to healthy volunteers or patients under the supervision of a qualified investigator. Clinical trials must be conducted in compliance with applicable federal regulations, including good clinical practices, which are meant to protect the rights and safety of study subjects and ensure the integrity of the data generated in the clinical trials and under protocols detailing the objectives of the trial, the parameters to be used in monitoring safety and the

~~effectiveness~~FDA ~~criteria~~regulations toalso berequire ~~evaluated.~~investigation ~~Each~~and ~~protocol~~correction of any deviations from cGMPs and ~~subsequent~~impose ~~protocol~~reporting ~~amendments~~requirements ~~must~~upon beus ~~submitted~~and any third-party manufacturers that we may decide to use. Accordingly, manufacturers must continue to expend time, money and effort in the ~~FDA~~area asof ~~part~~production and quality control to maintain compliance with cGMPs and other aspects of ~~the~~regulatory ~~IND~~compliance.

The FDA may ~~order~~withdraw ~~the~~approval ~~temporary,~~if orcompliance ~~permanent,~~with ~~discontinuation~~regulatory ofrequirements aand ~~clinical~~standards ~~trial~~is atnot ~~any~~maintained ~~time~~ or ~~impose other sanctions~~ if itproblems ~~believes~~occur ~~that~~after the ~~clinical~~product ~~trial~~reaches ~~either~~the ismarket. ~~not~~Later ~~being~~discovery ~~conducted~~of inpreviously ~~accordance~~unknown problems with ~~applicable~~a ~~requirements~~product, orincluding ~~presents~~adverse anevents ~~unacceptable~~of ~~risk~~unanticipated toseverity ~~the~~or ~~clinical~~frequency, ~~trial~~or ~~patients.~~with ~~The~~manufacturing ~~trial~~processes, ~~protocol~~or ~~and~~failure ~~informed~~to ~~consent~~comply ~~information~~with ~~for~~regulatory ~~patients~~requirements, ~~must~~may ~~also~~result bein ~~submitted~~revisions to anthe ~~institutional~~approved ~~review~~labeling ~~board~~to ~~(“IRB”)~~add atnew ~~each~~safety ~~site~~information; ~~where~~imposition aof ~~trial~~post-market ~~will~~studies beor ~~conducted.~~clinical Anstudies ~~IRB~~to ~~may~~assess ~~also~~new ~~require~~safety ~~the~~risks; ~~clinical~~or ~~trial~~imposition atof ~~the~~distribution ~~site~~restrictions ~~to be halted, either temporarily~~ or ~~permanently,~~other ~~for~~restrictions ~~failure~~under toa ~~comply~~REMS ~~with~~program. ~~the~~Other ~~IRB’s~~potential ~~requirements~~consequences orinclude, ~~may~~among ~~impose~~ other ~~conditions.~~things:

~~Clinical~~•restrictions ~~trials~~on ~~are typically conducted in three sequential phases, but~~ the ~~phases~~marketing ~~may overlap. In general, in Phase 1, the initial introduction of the drug into healthy human volunteers~~ or, inmanufacturing ~~some cases, patients, the drug is tested to assess metabolism, pharmacokinetics, pharmacological actions, side effects associated with increasing doses and, if possible, early evidence~~ of ~~effectiveness. Phase 2 usually involves trials in~~ a ~~limited patient population to determine the effectiveness of the drug for a particular indication~~product, ~~dosage~~complete ~~tolerance~~withdrawal ~~and optimum dosage, and to identify common adverse effects and safety risks. If a drug demonstrates evidence~~ of effectiveness and an acceptable safety profile in Phase 2 evaluations, Phase 3 trials are undertaken to obtain additional information about clinical efficacy and safety in a larger number of patients, typically at geographically dispersed clinical trial sites, to permit the ~~FDA~~product tofrom ~~evaluate~~ the overall benefit-risk relationship of the drug and to provide adequate information for the labeling of the drug. In most cases, the FDA requires two adequate and well-controlled Phase 3 clinical trials to demonstrate the safety and efficacy of the drug. The FDA may, however, determine that a drug is safe and effective based on one clinical trial plus confirmatory evidence. In some cases, the FDA may require post-market ~~studies,~~or ~~known~~product as Phase 4 studies, to be conducted as a condition of approval to gather additional information on the drug’s effect in various populations and any side effects associated with long-term use. Depending on the risks posed by the drugs, other post-market requirements may be imposed.recalls;

~~After completion of the required clinical testing~~•fines, anwarning ~~NDA~~letters isor ~~prepared~~holds ~~and~~on ~~submitted to the FDA. FDA~~ post-approval ~~of the NDA is required before marketing of the product may begin in the United States. The NDA must include the results of all relevant preclinical,~~ clinical, and other testing and data and information relating to the product’s pharmacology, chemistry, manufacture, and controls. In addition, the submission of NDAs is generally subject to a substantial application fee, although there are certain exceptions and waivers, such as for orphan-designated drugs.studies;

~~The~~•refusal ~~FDA has 60 days from its receipt~~ of ~~an NDA to determine whether~~ the ~~application will be accepted for filing based on the agency’s threshold determination that it is sufficiently complete to permit substantive review. Once the submission is accepted for filing, the~~ FDA ~~begins an in-depth review. Under the performance goals established pursuant~~ to ~~the~~approve ~~Prescription~~pending ~~Drug~~applications ~~User~~or ~~Fee~~supplements ~~Act the FDA aims~~ to ~~complete~~approved ~~review~~applications, ofor ~~90%~~suspension ofor ~~standard~~revocation ~~(non-priority) NDAs within 10 months~~ of ~~filing~~existing ~~and~~product ~~within six months of filing for priority NDAs.~~ approvals;

~~The~~•product ~~FDA~~seizure ~~may~~or ~~also refer applications for novel drug products~~detention, or ~~drug~~refusal ~~products that present difficult questions~~ of ~~safety or efficacy, to an advisory committee, which is typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation on questions presented by~~ the FDA, ~~which may include questions related~~ to ~~whether~~permit the ~~application~~import ~~should~~or beexport ~~approved. The FDA is not bound by the recommendation~~ of an advisory committee, but it generally follows such recommendations. Before approving an NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP. Additionally, the FDA will inspect the facility or the facilities at which the drug is manufactured to assess compliance with cGMP.products;

~~After~~•consent ~~the FDA evaluates the NDA and has conducted applicable inspections~~decrees, itcorporate ~~issues~~integrity ~~either an approval letter or a complete response letter. A complete response letter generally outlines the deficiencies in the submission and actions the sponsor may take~~agreements, ~~such~~debarment ~~as additional testing,~~ or ~~information,~~exclusion infrom ~~order~~federal ~~for~~healthcare ~~the FDA to reconsider the application. If, and when, those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA, the FDA will issue an approval letter.~~ programs;

An•mandated ~~approval~~modification ~~letter authorizes commercial marketing~~ of ~~the~~promotional ~~drug~~materials ~~with specific prescribing information for specific indications. An approval letter may also include post-marketing requirements~~ and ~~commitments,~~labeling ~~such as the conduct of additional clinical trials or CMC studies. As a condition of NDA approval, the FDA may require a risk evaluation~~ and ~~mitigation strategy (“REMS”) to ensure that~~ the ~~benefits~~issuance of ~~the~~corrective drug outweigh the potential risks. REMS can include medication guides, communication plans for health care professionals, and elements to assure safe use (“ETASU”). ETASU can include, but are not limited to, special training 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.

The FDA closely regulates the marketing, labeling, advertising and promotion of drugs. A company can make only those claims relating to safety and efficacy that are approved by the FDA and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses. Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties. Physicians may prescribe legally available products for uses that are not described in the product’s labeling and that differ from those tested by us and approved by the FDA. Such off-label uses are common across medical specialties. Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances. The FDA does not regulate the behavior of physicians in their choice of treatments. The FDA does, however, restrict manufacturer’s communications on the subject of off-label use of their products.

Abbreviated New Drug Applications for Generic Drugs

In 1984, with passage of the Drug Price Competition and Patent Term Restoration Act of 1984 (commonly referred to as the “Hatch-Waxman Amendments”) amending the Federal Food, Drug, and Cosmetic Act (“FDCA”), Congress authorized the FDA to approve generic drugs that are the same as drugs previously approved by the FDA under the NDA provisions of the statute. To obtain approval of a generic drug, an applicant must submit an abbreviated new drug application (“ANDA”) to the agency. Upon approval of an ANDA, the FDA indicates that the generic product is “therapeutically equivalent” to the drug product previously approved under an NDA, known as the reference listed drug (“RLD”), and it assigns a therapeutic equivalence rating to the approved generic drug in its publication “Approved Drug Products with Therapeutic Equivalence Evaluations,” also referred to as the “Orange Book.” Physicians and pharmacists consider the therapeutic equivalence rating to mean that a generic drug is fully substitutable for the RLD. In addition, by operation of certain state laws and numerous health insurance programs, the FDA’s designation of a therapeutic equivalence rating often results in substitution of the generic drug without the knowledge or consent of either the prescribing physician or patient.

Under the Hatch-Waxman Amendments, the FDA may not approve an ANDA until any applicable period of nonpatent exclusivity for the RLD has expired. The FDCA provides a period of five years of data exclusivity for NDAs containing a new chemical entity. In cases where such exclusivity has been granted, an ANDA may not be filed with the FDA until the expiration of five years unless the submission is accompanied by a Paragraph IV certification (discussed further below), in which case the applicant may submit its application four years following the original product approval. The FDCA also provides for a period of three years of exclusivity if the NDA includes reports of one or more new clinical investigations, other than bioavailability or bioequivalence studies, that were conducted by or for the applicant and are essential to the approval of the application. This three-year exclusivity period often protects changes to a previously approved drug product, such as a new dosage form, route of administration, combination or indication.

orHatch-Waxman ~~certification~~Patent ~~for~~Certification ~~prescribing or dispensing, dispensing only under certain circumstances, special monitoring,~~ and the ~~use~~30 ofMonth ~~patient registries. The requirement for a REMS can materially affect the potential market and profitability of the drug.~~ Stay

~~The~~Upon ~~Hatch-Waxman~~approval ~~Act~~of an NDA or a supplement thereto, NDA sponsors are required to list with the FDA each patent with claims that cover the applicant’s product or a method of using the product. When an ANDA applicant files its application with the FDA, the applicant is required to certify to the FDA concerning any patents listed for the reference product in the Orange Book, except for patents covering methods of use for which the ANDA applicant is not seeking approval.

~~Orange~~A ~~Book~~certification ~~Listing~~that the new product will not infringe the already approved product’s listed patents or that such patents are invalid or unenforceable is called a Paragraph IV certification. If the applicant does not challenge the listed patents or indicate that it is not seeking approval of a patented method of use, the ANDA application will not be approved until all the listed patents claiming the referenced product have expired. If the ANDA applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA and patent holders once the ANDA has been accepted for filing by the FDA. The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV certification. The filing of a patent infringement lawsuit within 45 days after the receipt of a Paragraph IV certification automatically prevents the FDA from approving the ANDA until the earlier of 30 months, expiration of the patent, settlement of the lawsuit or a decision in the infringement case that is favorable to the ANDA applicant.

When seeking NDA approval, applicants are required to list with the FDA each patent whose claims cover the applicant’s product. Upon approval of a drug, 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 (“Orange Book”). Drugs listed in the Orange Book can, in turn, be referenced by potential competitors in support of approval of an abbreviated new drug application (“ANDA”) or an NDA submitted under section 505(b)(2) ofNew ~~the~~Drug FD&C Act (“505(b)(2) NDA”). An ANDA provides for marketing of a drug product that has the same active ingredients in the same strengths and dosage form as the listed drug and has been shown to be bioequivalent to the listed drug. Other than bioequivalence testing, ANDA applicants are not required to conduct, or submit results of, pre-clinical or clinical tests to demonstrates the safety or effectiveness of their drug product. Drugs approved in this way generally are considered to be therapeutically equivalent to the listed drug, are commonly referred to as “generic equivalents” to the listed drug and can often be substituted by pharmacists under prescriptions written for the original listed drug in accordance with state law. A 505(b)(2) NDA provides for the marketing of a drug for which one or more investigations supporting its approval were not conducted by or for the applicant or for which the applicant had not obtained a right of reference. In some instances, a 505(b)(2) NDA applicant may rely on the FDA’s findings of safety and effectiveness for a previously approved drug. Applications

AnAs ~~ANDA~~an ~~applicant,~~alternative path to FDA approval for modifications to formulations or auses of products previously approved by the FDA pursuant to an NDA, an applicant may submit an NDA under Section 505(b)(2) ~~NDA~~of ~~applicant~~the ~~that~~FDCA. isSection ~~relying~~505(b)(2) onwas ~~FDA’s~~enacted ~~finding~~as part of ~~safety~~the Hatch-Waxman Amendments and ~~effectiveness~~permits ~~for~~the afiling ~~previously~~of ~~approved~~an ~~drug,~~NDA iswhere ~~required~~at toleast ~~certify~~some toof the ~~FDA~~information ~~concerning~~required ~~any patents listed~~ for ~~the~~approval ~~approved~~comes ~~product~~from instudies ~~the~~not ~~FDA’s~~conducted ~~Orange~~by, ~~Book.~~or ~~Specifically~~for, the applicant, ~~must~~and ~~certify~~for ~~that:~~which ~~(i)~~ the ~~required~~applicant ~~patent information~~ has not ~~been~~obtained ~~filed;~~a ~~(ii)~~right ~~the~~of ~~listed~~reference. ~~patent~~If ~~has~~the ~~expired;~~ 505(~~iii~~b)(2) ~~the~~applicant ~~listed~~can ~~patent~~establish ~~has~~that ~~not~~reliance ~~expired~~on ~~but~~the ~~will~~FDA’s ~~expire~~previous onfindings aof ~~particular~~safety ~~date~~ and ~~approval~~effectiveness is ~~sought~~scientifically ~~after~~and ~~patent~~legally ~~expiration;~~appropriate, orit ~~(iv)~~may eliminate the ~~listed~~need ~~patent~~to isconduct ~~invalid~~certain orpreclinical ~~will~~studies ~~not~~or beclinical ~~infringed~~trials byof the new product. The ~~applicant~~FDA may also ~~elect~~require companies to ~~submit~~perform aadditional ~~section~~bridging ~~viii~~studies ~~statement~~or measurements, ~~certifying~~including ~~that~~clinical trials, to support the ~~proposed~~change ~~product~~from ~~labeling~~the ~~does~~previously ~~not~~approved ~~contain~~reference (drug. The FDA may then approve the new drug candidate for all, or ~~carves~~some, ~~out)~~of ~~any~~the ~~language~~label ~~related~~indications tofor which the ~~listed~~reference drug has been approved, as well as for any new indication sought by the ~~patent~~505(b)(2) applicant.

IfTo the extent that a Section 505(b)(2) applicant ~~does~~is ~~not~~relying ~~challenge~~on studies conducted for an already approved product, the ~~listed~~applicant is required to certify to the FDA concerning any patents, listed for the approved product in the Orange Book to the same extent that an ANDA ~~application~~applicant ~~will~~would. ~~not~~As a result, approval of a 505(b)(2) NDA can be ~~approved~~stalled until all the listed patents claiming the referenced product have expired, until any non-patent exclusivity, such as exclusivity for obtaining approval of a new chemical entity, listed in the Orange Book for the referenced product has expired, and, in the case of a Paragraph IV certification and subsequent patent infringement suit, until the earlier of 30 months, settlement of the lawsuit or a decision in the infringement case that is favorable to the Section 505(b)(2) applicant.

A certification that an ANDA or 505(b)(2) NDA will not infringe the already approved product’s listed patents, or that such patents are invalid, is called a Paragraph IV certification. If the applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA and patent holders once the application has been accepted for filing by the FDA. The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV certification. The filing of a patent infringement lawsuit within 45 days of the receipt of a Paragraph IV notice automatically prevents the FDA from approving the ANDA or 505(b)(2) NDA until the earlier of 30 months, expiration of the patent, settlement of the lawsuit, or a decision in the infringement case that is favorable to the applicant.

The ANDA or 505(b)(2) NDA application also will not be approved until any applicable non-patent exclusivity listed in the Orange Book for the referenced product has expired.

Exclusivity

Upon NDA approval of a new chemical entity (“NCE”), which is a drug that contains no active moiety that has been approved by the FDA in any other NDA, that drug receives five years of marketing exclusivity during which time the FDA cannot receive any ANDA or 505(b)(2) NDA application seeking approval of a drug that references the NCE drug. Certain changes to an approved drug that are supported by clinical studies that are essential to the approval of such changes, such as the addition of a new indication, are associated with a three-year period of exclusivity during which the FDA cannot approve an ANDA or 505(b)(2) NDA application that includes the change.

An ANDA or 505(b)(2) NDA application may be submitted one year before NCE exclusivity expires if a Paragraph IV certification is filed. If there is no listed patent in the Orange Book, there may not be a Paragraph IV certification and thus no ANDA or 505(b)(2) application may be filed before the expiration of the exclusivity period.

Five-year and three-year exclusivities do not preclude FDA approval of another 505(b)(1) NDA application for the drug during the period of exclusivity, provided that the 505(b)(1) applicant conducts or obtains a right of reference to all of the preclinical studies and adequate and well controlled clinical trials necessary to demonstrate safety and effectiveness.

Patent Term Extension

~~After~~In the United States, after an NDA ~~approval~~is approved, owners of relevant drug patents may apply for up to a five-year patent extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory process. The allowable patent term extension ~~generally~~ is typically calculated ~~based~~as on one-half ofthe time between, the ~~drug’s~~latter ~~testing~~of ~~phase—~~the ~~time~~effective ~~between~~date of an IND ~~clearance~~and issue date of the patent for which extension is sought, and ~~NDA~~the submission~~—and~~ ~~all~~date of ~~the~~an ~~review~~NDA, ~~phase—~~plus the time between NDA submission date and the NDA approval date up to a maximum of five years. The ~~extension~~time ~~period~~ can be shortened if the FDA determines that the applicant did not pursue ~~approval~~licensure with due diligence. The total patent term after the extension may not exceed 14 years from the date of product approval. Only one patent applicable to an approved drug product is eligible for extension and only those claims covering the product, a method for using it, or a method for manufacturing it may be extended and the application for the extension must be submitted prior to the expiration of the patent in question. However, we may not be granted an extension because of, for example, failing to exercise due diligence during the testing phase or regulatory review process, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements. Some, but not all, foreign jurisdictions possess patent term extension or other additional patent exclusivity mechanisms that may be more or less stringent and comprehensive than those of the U.S.

~~For~~Other ~~patents~~Healthcare ~~that~~Laws ~~might expire during the application phase, the patent owner may request an interim patent extension. An interim patent extension increases the patent term by one year~~ and ~~may~~Compliance be renewed up to four times. For each interim patent extension granted, the post-approval patent extension is reduced by one year. The director of the USPTO must determine that approval of the drug covered by the patent for which a patent extension is being sought is likely. Interim patent extensions are not available for a drug for which an NDA has not been submitted.Requirements

~~Postmarket~~Pharmaceutical ~~Requirements~~companies are subject to additional healthcare regulation and enforcement by the federal government and by authorities in the states and foreign jurisdictions in which they conduct their business. Such laws include, without limitation: the federal Anti-Kickback Statute (“AKS”); the federal False Claims Act (“FCA”); the Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) and similar foreign, federal and state fraud, abuse and transparency laws.

Once an NDA is approved, the manufacturer and the product will be subject to continuing regulation by the FDA, including, among other things, monitoring and recordkeeping activities, annual report requirements, reporting of adverse experiences, and complying with promotion and advertising requirements. The FDA closely regulates the post-approval marketing and promotion of drugs.18

~~Drugs~~The AKS prohibits, among other things, persons and entities from knowingly and willfully soliciting, receiving, offering or paying remuneration, to induce, or in return for, either the referral of an individual, or the purchase or recommendation of an item or service for which payment may be ~~marketed~~made under any federal healthcare program. The term remuneration has been interpreted broadly to include anything of value. The AKS has been interpreted to apply to arrangements between pharmaceutical manufacturers on one hand, and prescribers and purchasers on the other. The government often takes the position that to violate the AKS, only one purpose of the remuneration need be to induce referrals, even if there are other legitimate purposes for the ~~approved~~remuneration. ~~indications~~There are a number of statutory exceptions and inregulatory asafe ~~manner~~harbors protecting some common commercial activities from AKS prosecution, but they are drawn narrowly and practices that isinvolve ~~consistent~~remuneration, ~~with~~such ~~their~~as ~~approved~~consulting ~~labeling.~~agreements, ~~Although~~for ~~physicians~~persons in a position to refer or recommend federally reimbursable healthcare business may ~~prescribe~~be ~~legally~~alleged ~~available~~to ~~products~~be ~~for~~intended ~~off-label~~to ~~uses~~induce prescribing, ~~manufacturers~~purchasing or recommending, and may be subject to scrutiny if they do not ~~market~~qualify for an exception or ~~promote~~regulatory ~~such~~safe ~~uses~~harbor. ~~Prescription~~Qualifying ~~drug~~for ~~promotional~~a ~~materials~~statutory ~~must~~exception beor ~~submitted~~regulatory safe harbor requires satisfying all of the criteria for the exception or safe harbor. Our practices may not in all cases meet all of the criteria for protection under a statutory exception or regulatory safe harbor. Failure to meet all of the ~~FDA~~requirements atof a particular applicable statutory exception or regulatory safe harbor does not make the ~~time~~conduct per se illegal under the AKS, but it does increase the risk of ~~their~~regulatory ~~first~~scrutiny. ~~use~~Ultimately, the legality of the arrangement will be evaluated on a case-by-case basis based on a cumulative review of all of its facts and circumstances. A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.

~~Changes~~The toFCA, ~~certain~~which ~~conditions~~can ~~established~~be inenforced anthrough ~~approved~~civil ~~application,~~whistleblower ~~including~~or ~~changes~~qui intam ~~indications~~actions, ~~labeling~~prohibits, oramong ~~manufacturing~~other ~~processes~~things, individuals or ~~facilities~~entities from knowingly presenting, ~~require~~or ~~submission~~causing ~~and~~to ~~FDA~~be ~~approval~~presented, claims for payment of afederal ~~new~~government ~~NDA~~funds, orincluding ~~NDA~~in ~~supplement~~federal ~~before~~healthcare ~~the~~programs, ~~change~~that ~~can~~are befalse ~~implemented~~or fraudulent. AnPharmaceutical ~~NDA~~and ~~supplement~~other healthcare companies have been prosecuted under these laws for engaging in a ~~new~~variety ~~indication~~of ~~typically~~different ~~requires~~types ~~clinical~~of ~~data~~conduct ~~similar~~that caused the submission of false claims to ~~that~~federal inhealthcare programs. Under the ~~original~~AKS, ~~application~~for example, ~~and~~a ~~the~~claim ~~FDA~~resulting ~~uses~~from ~~similar~~a ~~procedures~~violation inof ~~reviewing~~the ~~and~~AKS ~~approving~~is ~~NDA~~deemed ~~supplements~~to asbe ita ~~does~~false or fraudulent claim for ~~original~~purposes ~~NDAs~~of the FCA.

~~Adverse~~HIPAA ~~event~~created ~~reporting~~additional ~~and~~federal ~~submission~~criminal ofstatutes ~~annual~~that ~~safety~~prohibit, ~~reports~~among isother ~~also~~things, ~~required~~executing ~~following~~a ~~FDA~~scheme ~~approval~~to ofdefraud anany ~~NDA.~~healthcare ~~New~~benefit ~~safety~~program, ~~information~~including ~~that~~private ~~emerges~~third-party ~~after~~payors, ~~NDA~~and ~~approval~~making ~~may~~false ~~require~~statements ~~changes~~relating to ahealthcare ~~drug’s~~matters. ~~approved~~A ~~labeling,~~person ~~including~~or ~~the~~entity ~~addition~~does ofnot ~~new~~need ~~warnings~~to ~~and~~have ~~precautions~~actual orknowledge ~~contraindications,~~of ~~and could require~~ the ~~implementation~~healthcare offraud ~~other~~statute ~~risk~~implemented ~~management~~under ~~measures,~~HIPAA ~~including a REMS~~ or ~~the~~specific ~~conduct~~intent ~~of post-marketing studies~~ to ~~assess~~violate the ~~newly~~statute ~~discovered~~in ~~safety~~order ~~issue.~~to ~~Product~~have ~~approvals~~committed ~~also~~a ~~may be withdrawn if problems occur following initial marketing~~violation.

InThe ~~addition~~FDCA addresses, ~~quality~~among ~~control~~other things, ~~drug~~the ~~manufacture~~design, ~~packaging~~production, ~~and~~ labeling, ~~procedures~~promotion, ~~must~~manufacturing, ~~continue to conform to cGMP after approval. Drug manufacturers~~ and ~~certain~~testing of ~~their~~drugs, ~~subcontractors~~biologics ~~are~~and ~~required~~medical todevices, ~~register their establishments with the FDA~~ and ~~certain~~prohibits ~~state~~such ~~agencies.~~acts ~~Registration~~as ~~with~~ the ~~FDA~~introduction ~~subjects~~into ~~entities~~interstate tocommerce ~~periodic~~of ~~unannounced~~adulterated ~~inspections~~or bymisbranded ~~the~~drugs ~~FDA,~~or ~~during which the agency inspects manufacturing facilities to assess compliance with cGMP~~devices. ~~Manufacturers~~The ~~are~~PHSA also ~~subject~~prohibits tothe ~~tracking~~introduction ~~and~~into ~~tracing~~interstate ~~requirements.~~commerce ~~Accordingly, manufacturers must continue to expend time, money and effort in the areas~~ of ~~production~~unlicensed ~~and quality control to maintain compliance with cGMP. Regulatory authorities may withdraw product approvals~~ or ~~request~~mislabeled ~~product~~biological ~~recalls if a company fails to comply with regulatory standards, if it encounters problems following initial marketing or if previously unrecognized problems are subsequently discovered~~products.

~~From~~The ~~time~~U.S. tofederal ~~time,~~Physician ~~legislation~~Payments isSunshine ~~drafted,~~Act ~~introduced,~~requires ~~passed~~certain inmanufacturers ~~Congress~~of drugs, devices, biologics and ~~signed~~medical ~~into~~supplies ~~law~~for ~~that~~which ~~could~~payment ~~significantly~~is ~~change~~available ~~the~~under ~~statutory~~Medicare, ~~provisions~~Medicaid ~~governing~~or the ~~approval,~~Children’s ~~manufacturing~~Health Insurance Program, ~~and~~with ~~marketing~~specific ofexceptions, ~~products~~to ~~regulated~~annually byreport to the ~~FDA.~~Centers Infor ~~addition~~Medicaid & Medicare Services (“CMS”) information related to ~~new~~payments ~~legislation~~or other transfers of value to various healthcare professionals including physicians, ~~FDA~~physician ~~regulations~~assistants, ~~guidance~~nurse practitioners, clinical nurse specialists, certified nurse anesthetists, certified nurse-midwives, and ~~policies~~teaching ~~are~~hospitals, ~~often~~as ~~revised~~well oras ~~reinterpreted~~ownership and investment interests held by ~~the~~physicians ~~agency~~and intheir ~~ways~~immediate ~~that~~family ~~may~~members. ~~significantly~~Beginning ~~affect~~on ~~the~~January ~~manner~~1, in2023, ~~which~~California ~~pharmaceutical~~Assembly ~~products~~Bill ~~are~~1278 ~~regulated~~requires California physicians and ~~marketed~~surgeons to notify patients of the Open Payments database established under the federal Physician Payments Sunshine Act.

We are also subject to federal price reporting laws and federal consumer protection and unfair competition laws. Federal price reporting laws require manufacturers to calculate and report complex pricing metrics to government programs, where such reported prices may be used in the calculation of reimbursement and/ or discounts on approved products. Federal consumer protection and unfair competition laws broadly regulate marketplace activities and activities that potentially harm consumers.

We are also subject to additional similar U.S. state and foreign law equivalents of each of the above federal laws, which, in some cases, differ from each other in significant ways, and may not have the same effect, thus complicating compliance efforts. If our operations are found to be in violation of any of such laws or any other governmental regulations that apply, we may be subject to penalties, including, without limitation, civil, criminal and administrative penalties, damages, fines, exclusion from government-funded healthcare programs, such as Medicare and Medicaid or similar programs in other countries or jurisdictions, integrity oversight and reporting obligations to resolve allegations of non-compliance, disgorgement, individual imprisonment, contractual damages, reputational harm, diminished profits and the curtailment or restructuring of our operations.

~~Pediatric~~Data ~~Exclusivity~~Privacy and ~~Pediatric Information~~Security

~~The~~Numerous ~~Best~~state, ~~Pharmaceuticals~~federal, ~~for~~and ~~Children~~foreign ~~Act~~laws ~~(“BPCA”)~~govern ~~provides~~the ~~NDA~~collection, ~~holders~~dissemination, ause, ~~six-month~~access ~~period~~to, ofconfidentiality, ~~exclusivity~~and ~~attached~~security toof ~~any~~personal ~~patent~~information, orincluding ~~regulatory~~health-related ~~exclusivity~~information. ~~listed~~In in the ~~Orange~~United ~~Book~~States, ifnumerous ~~certain~~federal ~~conditions~~and ~~are~~state ~~met.~~laws ~~Conditions~~and ~~for~~regulations, ~~pediatric~~including ~~exclusivity~~state ~~include~~data abreach ~~determination~~notification bylaws, ~~the~~state ~~FDA~~health ~~that~~ information ~~relating~~privacy tolaws, ~~the~~and ~~use~~federal ofand astate ~~new~~consumer ~~drug~~protection inlaws ~~the~~and ~~pediatric~~regulations, ~~population~~govern ~~may produce health benefits in that population; a written request by~~ the ~~FDA~~collection, ~~for~~use, ~~pediatric studies~~disclosure, ~~completion~~and protection of ~~the~~health-related ~~studies~~and inother ~~accordance~~personal ~~with~~information ~~the~~and ~~written~~could ~~request~~apply ~~and~~to ~~submission~~our ofoperations ~~reports~~or ~~from~~ the ~~requested~~operations ~~studies~~of toour ~~the FDA~~partners.

InFor ~~addition~~example, ~~under~~HIPAA, as amended by the ~~Pediatric~~Health ~~Research~~Information ~~Equity~~Technology for Economic and Clinical Health Act (“~~PREA~~HITECH”), ~~certain~~and ~~NDAs~~their orrespective ~~NDA~~implementing ~~supplements~~regulations ~~must~~impose ~~contain~~ data toprivacy, ~~assess~~security, ~~the~~and ~~safety~~breach ~~and~~notification ~~effectiveness~~obligations ofon ~~the~~certain ~~drug~~health ~~for~~care ~~the~~providers, ~~claimed~~health ~~indications~~plans, inand ~~all~~health ~~relevant~~care ~~pediatric~~clearinghouses, ~~subpopulations~~known ~~and~~as tocovered ~~support~~entities, ~~dosing~~as well as their business associates and ~~administration~~their ~~for~~covered ~~each~~subcontractors ~~pediatric~~that ~~subpopulation~~perform ~~for~~certain ~~which~~services ~~the~~that ~~drug~~involve isusing, ~~safe~~disclosing, ~~and~~creating, ~~effective~~receiving, ~~unless~~maintaining, ~~the~~or ~~sponsor~~transmitting ~~has~~individually ~~received~~identifiable aprotected ~~deferral~~health information (PHI) for or ~~waiver~~on ~~from~~behalf ~~the~~of ~~FDA~~such covered entities. ~~Unless~~These ~~otherwise~~requirements ~~required~~imposed by ~~regulation,~~HIPAA ~~PREA~~and ~~does~~HITECH ~~not~~on ~~apply~~covered toentities ~~any~~and ~~drug~~business ~~for~~associates aninclude ~~indication~~entering ~~for~~into ~~which~~agreements ~~orphan~~that ~~designation~~require ~~has~~business ~~been~~associates ~~granted.~~protect ~~The~~PHI ~~sponsor~~provided ~~may~~by ~~request~~the acovered ~~deferral~~entity against improper use or ~~waiver~~disclosure, ofamong ~~pediatric~~other ~~studies~~things; following certain standards for ~~some~~the privacy of PHI, which limit the disclosure of a patient’s past, present, or ~~all~~future physical or mental health or condition or information about a patient’s receipt of health care if the ~~pediatric~~information ~~subpopulations.~~identifies, Aor ~~deferral~~could ~~may~~reasonably be ~~granted~~used ~~for~~to ~~several reasons~~identify, ~~including~~the aindividual; ~~finding~~ensuring ~~that~~ the ~~drug~~confidentiality, isintegrity, ~~ready~~and ~~for~~availability ~~approval~~of ~~for~~all ~~use~~PHI created, received, maintained, or transmitted in ~~adults~~electronic ~~before~~form, ~~pediatric~~to ~~studies~~identify ~~are~~and ~~complete~~protect oragainst ~~that~~reasonably ~~additional~~anticipated ~~safety~~threats or ~~effectiveness~~impermissible ~~data~~uses ~~need~~or disclosures to bethe ~~collected~~security ~~before~~and ~~the~~integrity ~~pediatric~~of ~~studies~~such ~~begin.~~PHI; and reporting of breaches of PHI to individuals and regulators.

~~Orphan~~Entities ~~Drug~~that are found to be in violation of HIPAA may be subject to significant civil, criminal, and ~~Rare~~administrative ~~Pediatric~~fines ~~Disease~~and ~~Designation~~penalties and/or additional reporting and oversight obligations if required to enter into a resolution agreement and corrective action plan with HHS to settle allegations of HIPAA non-compliance. A covered entity or business associate is also liable for civil money penalties for a violation that is based on an act or omission of any of its agents, which may include a downstream business associate, as determined according to the federal common law of agency. HITECH also increased the civil and criminal penalties applicable to covered entities and business associates and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce HIPAA and seek attorneys’ fees and costs associated with pursuing federal civil actions. To the extent that we submit electronic healthcare claims and payment transactions that do not comply with the electronic data transmission standards established under HIPAA and HITECH, payments to us may be delayed or denied.

~~Under~~In ~~the Orphan Drug Act~~addition, ~~the~~state ~~FDA~~health ~~may~~information ~~grant~~privacy ~~orphan drug designation to drugs intended to treat a rare disease or condition—generally a disease or condition that affects fewer than 200~~laws,~~000~~ individuals in the United States (or affects more than 200,000 in the United States and for which there is no reasonable expectation that the cost of developing and making available in the United States a drug for such ~~disease~~as orCalifornia’s ~~condition~~Confidentiality ~~will be recovered from sales~~ of ~~such~~Medical ~~drug~~Information inAct ~~the~~and ~~United~~Washington’s ~~States).~~My ~~Orphan~~Health ~~drug~~My ~~designation~~Data ~~must be requested before submitting an NDA. After the FDA grants orphan drug designation~~Act, ~~the~~that ~~generic~~govern ~~identity of~~ the ~~drug~~privacy and ~~its~~security ~~designated orphan use are disclosed publicly by the FDA. Orphan drug designation does not convey any advantage in, or shorten the duration~~ of, ~~the regulatory review and approval process. The first NDA applicant to receive FDA approval for a particular drug to treat a particular disease with FDA orphan drug designation is entitled to a seven~~health-~~year~~related ~~exclusive marketing period in the United States for that drug~~information, ~~for that disease. During the seven-year exclusivity period~~specifically, ~~the FDA~~ may ~~not~~apply ~~approve~~even ~~any~~when ~~other~~HIPAA ~~applications~~does tonot market the same drug for the same disease, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity. If the FDA designates an orphan drug based on a finding of clinical superiority, the FDA must provide a written notification to the sponsor that states the basis for orphan designation. The FDA must also publish a summary of its clinical superiority findings upon granting approval and ~~orphan~~impose ~~drug~~additional ~~exclusivity to a subsequent product based on clinical superiority~~requirements.

~~Orphan~~Even ~~drug~~when ~~exclusivity~~HIPAA ~~does~~and ~~not~~state ~~prevent~~health ~~the~~information ~~FDA~~privacy ~~from~~laws ~~approving~~do anot ~~different~~apply, ~~drug~~according ~~for~~to the ~~same~~FTC ~~disease~~and orstate ~~condition~~attorneys general, violating consumers’ privacy rights or ~~the~~failing ~~same~~to ~~drug~~take ~~for~~appropriate asteps ~~different~~to ~~disease~~keep orconsumers’ ~~condition.~~personal ~~Among~~information ~~the~~secure ~~other~~may ~~benefits~~constitute ofunfair ~~orphan~~acts ~~drug~~or ~~designation~~practices ~~are~~in ~~tax~~or ~~credits~~affecting ~~for~~commerce ~~certain~~in ~~research~~violation ~~and~~of Section 5(a) ~~waiver~~ of the ~~NDA~~Federal ~~application~~Trade ~~fee~~Commission Act and state consumer protection laws.

~~The~~In ~~FDA~~addition, ~~grants~~certain ~~Rare~~state ~~Pediatric~~laws, ~~Disease~~such ~~designation~~as ~~for~~the ~~serious~~California ~~and~~Consumer ~~life-threatening~~Privacy ~~diseases~~Act ~~that~~of ~~primarily~~2018 ~~affect~~(“CCPA”), ~~children~~as ~~ages~~amended 18by ~~years~~the orCalifornia ~~younger~~Privacy Rights Act of 2020, govern the privacy and ~~fewer~~security ~~than~~of ~~200~~personal information,~~000~~ ~~individuals~~including health-related information in ~~the~~certain ~~United~~circumstances, ~~States~~some of which are more stringent than HIPAA in various ways. ANumerous ~~priority~~other ~~review~~states ~~voucher~~have passed similar laws, but many differ from each other in significant ways and may benot ~~issued~~have ~~upon~~the ~~approval~~same effect, thus complicating compliance efforts. The CCPA applies to personal data of anconsumers, ~~NDA~~business ~~for~~representatives, ~~therapies~~and ~~developed~~employees, and imposes obligations on certain businesses that do business in California, including to ~~treat~~provide ~~such~~specific ~~rare~~disclosures ~~pediatric~~in ~~diseases~~privacy notices, and affords rights to California residents in relation to their personal information. ~~Priority~~Health ~~review~~information ~~vouchers~~falls ~~may~~under bethe ~~redeemed~~CCPA’s definition of personal information where it identifies, relates to, ~~obtain~~describes, ~~priority~~or ~~review~~is ~~for~~reasonably ~~any~~capable ~~subsequent~~of ~~marketing~~being ~~application~~associated with or could reasonably be ~~sold~~linked, directly or ~~transferred.~~indirectly, ~~Under~~with ~~amended~~a ~~statutory~~particular ~~sunset~~consumer ~~provisions,~~or ~~after~~household ~~December~~and 20is included under a new category of personal information, ~~2024~~“sensitive personal information,” ~~the~~which ~~FDA~~is ~~may~~offered ~~award~~greater aprotection. ~~priority~~The ~~review~~CCPA ~~voucher~~and ~~for~~numerous another ~~approved~~comprehensive ~~rare~~privacy ~~pediatric~~laws ~~disease~~that ~~product~~have ~~application~~passed ~~only~~or ifare ~~rare~~being ~~pediatric~~considered ~~disease~~in ~~designation~~other ~~was~~states, ~~granted~~as bywell ~~December~~as ~~20,~~at ~~2024.~~the ~~After~~federal ~~September~~and ~~30,~~local ~~2026~~levels, ~~the~~exempt ~~FDA~~PHI ~~may~~that ~~not~~is ~~award~~subject ~~any~~to ~~rare~~HIPAA; ~~pediatric~~and ~~disease~~others ~~priority~~exempt ~~review~~covered ~~vouchers.~~entities ~~Congress~~and ~~may~~business ~~vote~~associates subject to ~~reauthorize~~HIPAA ~~this~~altogether, ~~program~~further complicating compliance efforts, ~~but~~and ~~its~~increasing ~~future~~legal ~~remains~~risk ~~unknown~~and atcompliance ~~this~~costs ~~time~~for us and the third parties upon whom we rely.

Expedited Development and Review Programs

The FDA has a Fast Track program that is intended to expedite or facilitate the process for development and review of new drugs that meet certain criteria. Specifically, new drugs are eligible for Fast Track designation if they are intended to treat a serious or life-threatening condition and preclinical or clinical data demonstrate the potential to address unmet medical needs for the condition. Fast Track designation applies to both the product and the specific indication for which it is being studied. Products that receive Fast Track designation may also be eligible for other types of FDA programs intended to expedite development and review, such as priority review and accelerated approval.

Any product is eligible for priority review if it treats a serious or life-threatening condition and, if approved, would provide a significant improvement in safety and effectiveness compared to available therapies. The FDA will attempt to direct additional

~~resources~~Failure to comply with these laws, where applicable, can result in the ~~evaluation~~imposition of ansignificant ~~application~~civil ~~for~~and/or acriminal ~~new~~penalties ~~drug~~and ~~designated~~private ~~for~~litigation. ~~priority~~Privacy ~~review~~and security laws, regulations, and other obligations are constantly evolving, may conflict with each other to ~~facilitate~~complicate ~~the~~compliance ~~review~~efforts, and can result in investigations, proceedings, or actions that lead to significant civil and/or criminal penalties and restrictions on data processing.

ACoverage ~~product can be designated as a Breakthrough Therapy by FDA if it is intended to treat a serious or life-threatening condition~~ and preliminary clinical evidence indicates that it may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. A sponsor may request that a product candidate be designated as a breakthrough therapy concurrently with the submission of an IND or any time afterward, but ideally before an end-of-Phase-2 meeting. The FDA must determine if the product candidate qualifies for Breakthrough Therapy designation within 60 days of receipt of the sponsor’s request. If so designated, the FDA shall act to expedite the development and review of the product’s marketing application, including by meeting with the sponsor throughout the product’s development, providing timely advice to the sponsor to ensure that the development program to gather pre-clinical and clinical data is as efficient as practicable, involving senior managers and experienced review staff in a cross-disciplinary review, assigning a cross-disciplinary project lead for the FDA review team to facilitate an efficient review of the development program and to serve as a scientific liaison between the review team and the sponsor, and taking steps to ensure that the design of the clinical trials is as efficient as practicable.Reimbursement

~~Rest~~In the United States and markets in other countries, patients generally rely on third-party payors to reimburse all or part of ~~World~~the costs associated with their treatment. Adequate coverage and reimbursement from governmental healthcare programs, such as Medicare and Medicaid, and commercial payors is critical to new product acceptance. Our ability to successfully commercialize our product candidates will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations. Even if coverage is provided, the approved reimbursement amount may not be high enough to allow it to establish or maintain pricing sufficient to realize a sufficient return on its investment. Government ~~Regulation~~authorities and third-party payors, such as private health insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels.

InSignificant ~~addition~~uncertainty exists as to ~~laws~~the coverage and ~~regulations~~reimbursement status of any pharmaceutical or biological product for which we obtain regulatory approval. Sales of any product, if approved, depend, in part, on the ~~United~~extent ~~States,~~to wewhich ~~are~~such ~~and~~product will be ~~subject~~covered by third-party payors, ~~either~~such ~~directly~~as orfederal, ~~through~~state, and foreign government healthcare programs, commercial insurance and managed healthcare organizations, and the level of reimbursement, if any, for such product by third-party payors. Decisions regarding whether to cover any of our ~~distribution~~product ~~partners~~candidates, if approved, the extent of coverage and amount of reimbursement to be provided are made on a ~~variety~~plan-by-plan ofbasis. ~~regulations~~Further, no uniform policy for coverage and reimbursement exists in ~~other~~the ~~jurisdictions~~United ~~governing~~States, ~~among~~and ~~other~~coverage ~~things~~and reimbursement can differ significantly from payor to payor. Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement rates, ~~clinical~~but ~~trials~~also have their own methods and approval process apart from Medicare determinations. As a result, ~~manufacturing~~the coverage determination process is often a time-consuming and ~~any~~costly ~~commercial~~process ~~sales~~that will require us to provide scientific and ~~distribution~~clinical support for the use of our ~~products~~product candidates to each payor separately, ifwith ~~approved~~no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance. Factors payors consider in determining reimbursement are based on whether the product is:

As•a incovered ~~the~~benefit ~~United~~under ~~States,~~its wehealth must obtain the requisite authorization or approvals from regulatory authorities in non-U.S. countries prior to the commencement of clinical trials or marketing of the product in those countries. The requirements of regulatory authorities outside the United States are in many respects similar to those we are subject to in the United States, but in some instances the legal and regulatory requirements outside the United States may differ from or be more stringent than what we must comply with in the United States.plan;

~~Brexit~~•safe, effective and ~~the~~medically ~~Regulatory Framework in the United Kingdom~~ necessary;

The UK formally left the EU on January 31, 2020. As a result of the Northern Ireland Protocol, following Brexit, the EMA remained responsible for approving novel medicines for supply in Northern Ireland under the EU centralized procedure, and a separate authorization was required to supply the same medicine in Great Britain (England, Wales and Scotland). A new framework named the Windsor Framework was approved by the EU•cost-UKeffective; ~~Joint Committee on March 24, 2023,~~ and the medicines aspects of the Windsor Framework have applied since January 1, 2025. This new framework fundamentally changes the previous system under the Northern Ireland Protocol, including with respect to the regulation of medicinal products in the UK. The MHRA is now responsible for approving all medicinal products destined for the UK market (i.e., Great Britain and Northern Ireland) and the EMA no longer has any role in approving medicinal products destined for Northern Ireland under the EU centralized procedure. A single UK-wide MA will be granted by the MHRA for all novel medicinal products to be sold in the UK, enabling products to be sold in a single pack and under a single authorization throughout the UK. However, although a separate authorization is now required to market medicinal products in the UK, under an international recognition procedure which was put in place by the MHRA on January 1, 2024, the MHRA may take into account decisions on the approval of a marketing authorization from the EMA (and certain other regulators) when considering an application for a UK MA. There is now no pre-marketing authorization orphan designation in the UK. Instead, the MHRA reviews applications for orphan designation in parallel to the corresponding MA application. The criteria are essentially the same, but have been tailored for the UK market, i.e., the prevalence of the condition in UK (rather than the EU) must not be more than five in 10,000. Should an orphan designation be granted, the period of market exclusivity will be set from the date of first approval of the product in the UK.

~~European~~•neither ~~Union~~experimental ~~Drug~~nor ~~Development~~investigational.

InThird-party payors are increasingly challenging the EUprices charged for medical products and services, ~~our~~examining ~~future~~the medical necessity and reviewing the cost effectiveness of pharmaceutical or biological products, ~~may~~medical ~~also~~devices beand ~~subject~~medical services, in addition to ~~extensive~~questioning ~~regulatory~~safety ~~requirements~~and efficacy. AsAdoption of price controls and cost-containment measures, and adoption of more restrictive policies in ~~the~~jurisdictions ~~United~~with ~~States~~existing controls and measures, ~~medicinal~~could ~~products~~further ~~can~~limit besales ~~marketed~~of ~~only~~any ifproduct that receives approval. Decreases in third-party reimbursement for any product or a ~~marketing~~decision ~~authorization~~by ~~from~~a ~~the~~third-party ~~competent~~not ~~regulatory~~to ~~agencies~~cover ~~has~~a ~~been~~product ~~obtained.~~could reduce physician usage and patient demand for the product.

~~Similar~~For toproducts administered under the ~~United~~supervision ~~States~~of a physician, ~~the~~obtaining ~~various~~coverage ~~phases~~and ofadequate ~~preclinical~~reimbursement ~~and~~may ~~clinical~~be ~~research~~particularly indifficult because of the EUhigher ~~are~~prices ~~subject~~often toassociated ~~significant~~with ~~regulatory~~such ~~controls~~drugs. InAdditionally, ~~April~~separate ~~2014,~~reimbursement for the EUproduct ~~adopted~~itself or the ~~Clinical~~treatment ~~Trials~~or ~~Regulation~~procedure ~~(EU)~~in Nowhich ~~536/2014~~the product is used may not be available, which ~~replaced~~may ~~the~~impact ~~Clinical~~physician ~~Trials~~utilization. ~~Directive~~In ~~2001/20/EC~~addition, oncompanion ~~January~~diagnostic ~~31,~~tests ~~2022.~~require ~~The~~coverage ~~transitory~~and ~~provisions~~reimbursement ofseparate and apart from the ~~Regulation~~coverage ~~provide~~and ~~that,~~reimbursement byfor ~~January~~their ~~31,~~companion ~~2025~~pharmaceutical or biological products. Similar challenges to obtaining coverage and reimbursement, ~~all~~applicable ~~ongoing~~to ~~clinical~~pharmaceutical ~~trials~~or ~~must~~biological ~~have~~products, ~~transitioned~~will apply to ~~the~~companion ~~Regulation~~diagnostics.

~~The~~In ~~Regulation~~addition, ~~overhauled~~ the ~~system~~U.S. ofgovernment, ~~approvals~~state legislatures and foreign governments have continued implementing cost-containment programs, including price controls, restrictions on coverage and reimbursement and requirements for ~~clinical~~substitution ~~trials~~of ingeneric ~~the~~products. EUThe IRA provides CMS with significant new authorities intended to curb drug costs and to encourage market competition. ~~Specifically~~For the first time, itCMS iswill be able to directly ~~applicable~~negotiate inprescription ~~all~~drug EUprices ~~Member~~and ~~States~~to ~~(meaning~~cap out-of-pocket costs. Each year, CMS will select and negotiate a preset number of high-spend drugs and biologics that noare ~~national~~covered ~~implementing~~under ~~legislation~~Medicare inPart ~~each~~B EUand ~~Member~~Part ~~State~~D isthat ~~required)~~do not have generic or biosimilar competition. On August 29, ~~and~~2023, ~~aims~~HHS atannounced ~~simplifying~~the list of the first

~~and~~ten ~~streamlining~~drugs ~~the~~subject ~~approval~~to ofprice ~~clinical~~negotiations. ~~trials~~These inprice ~~the~~negotiations EUoccurred in 2024. ~~The~~In ~~main~~January ~~characteristics~~2025, CMS announced a list of ~~the~~15 ~~Regulation~~additional ~~include:~~Medicare aPart ~~streamlined~~D ~~application~~drugs ~~procedure~~that ~~via~~will abe ~~single-entry~~subject ~~point~~to ~~through~~price ~~the~~negotiations. ~~Clinical~~The ~~Trials~~IRA ~~Information~~also ~~System~~provides (a new “~~CTIS~~inflation rebate”); acovering ~~single~~Medicare ~~set~~patients ofthat ~~documents~~took toeffect bein ~~prepared~~2023 and ~~submitted~~is ~~for~~intended ~~the~~to ~~application~~counter ascertain ~~well~~price asincreases ~~simplified~~in ~~reporting~~prescriptions ~~procedures~~drugs. ~~for~~The ~~clinical~~inflation ~~trial~~rebate ~~sponsors;~~provision ~~and~~requires adrug ~~harmonized~~manufacturers ~~procedure~~to ~~for~~pay a rebate to the ~~assessment~~federal ofgovernment ~~applications~~if ~~for~~the ~~clinical~~price ~~trials,~~for ~~which~~a isdrug ~~divided~~or inbiologic ~~two~~under ~~parts~~Medicare (Part IB ~~contains~~and ~~scientific~~Part ~~and~~D ~~medicinal~~increases ~~product~~faster ~~documentation~~than ~~and~~the ~~Part~~rate IIof ~~contains~~inflation. ~~the~~To ~~national~~support ~~and~~biosimilar ~~patient-level~~competition, ~~documentation).~~beginning ~~Part~~in IOctober is2022, ~~assessed~~qualifying bybiosimilars amay ~~coordinated~~receive ~~review~~a byMedicare ~~the~~Part ~~competent~~B ~~authorities~~payment ofincrease ~~all~~for EUa ~~Member~~period ~~States~~of infive ~~which~~years. anSeparately, ~~application~~if ~~for~~a ~~authorization~~biologic ofdrug afor ~~clinical~~which ~~trial~~no ~~has~~biosimilar ~~been~~exists ~~submitted~~delays ~~(Member~~a ~~States~~biosimilar’s ~~concerned)~~market ofentry abeyond ~~draft~~two ~~report~~years, ~~prepared~~CMS bywill abe ~~Reference~~authorized ~~Member~~to ~~State.~~subject ~~Part~~the IIbiologics ismanufacturer ~~assessed~~to ~~separately~~price bynegotiations ~~each~~intended ~~Member~~to ~~State~~ensure ~~concerned~~fair competition. ~~Strict~~Notwithstanding ~~deadlines~~these ~~have~~provisions, ~~also~~the ~~been~~IRA’s ~~established~~impact ~~for~~on ~~the~~commercialization ~~assessment~~and ofcompetition ~~clinical~~remains ~~trial~~largely ~~applications~~uncertain.

~~European~~In ~~Union~~addition, ~~Drug~~net ~~Review~~prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and ~~Approval~~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 U.S. 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 may 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 government healthcare programs.

InFinally, in some foreign countries, the EUproposed pricing for a drug must be approved before it may be lawfully marketed. The requirements governing drug pricing vary widely from country to country. For example, the EU provides options for its member states to restrict the range of medicinal products ~~can~~for ~~only~~which betheir ~~commercialized~~national ~~after~~health ~~obtaining~~insurance systems provide reimbursement and to control the prices of medicinal products for human use. To obtain reimbursement or pricing approval, some of these countries may require the completion of clinical trials that compare the cost effectiveness of a ~~marketing~~particular ~~authorization~~product ~~(“MA”)~~candidate to currently available therapies. A member state may approve a specific price for the medicinal product or it may instead adopt a system of direct or indirect controls 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 pricing arrangements for any of our product candidates. Historically, products launched in the EU do not follow price structures of the U.S. and generally prices tend to be significantly lower.

~~The~~Healthcare centralized MA is issued by the European Commission through the centralized procedure, based on the opinion of the Committee for Medicinal Products for Human Use (“CHMP”), of the EMA, and is valid throughout the entire territory of the EU and the additional countries of the European Economic Area (Iceland, Liechtenstein and Norway) (“EEA”). The centralized procedure is mandatory for certain types of products, including products produced by biotechnological processes, products designated as orphan medicinal products, advanced-therapy medicinal products (gene-therapy, somatic cell-therapy, or tissue-engineered medicines) and medicinal products containing a new active substance indicated for the treatment of HIV, AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and other immune dysfunctions or viral diseases. The centralized procedure is optional for products containing a new active substance not yet authorized in the EU, or for products that constitute a significant therapeutic, scientific, or technical innovation or which are in the interest of public health in the EU. Reform

~~Under~~The ~~the~~United ~~centralized~~States ~~procedure,~~and ~~the~~some ~~EMA’s~~foreign ~~CHMP~~jurisdictions isare ~~responsible~~considering ~~for~~or ~~conducting~~have ~~the~~enacted ~~initial assessment of~~ a ~~product~~number ~~and for several post-authorization and maintenance activities, such as the assessment~~ of ~~modifications~~reform orproposals ~~extensions~~ to anchange ~~existing MA. The maximum timeframe for~~ the ~~evaluation~~healthcare ofsystem. anThere ~~MA application by the EMA~~ is ~~210~~significant ~~days,~~interest ~~excluding~~in ~~clock~~promoting ~~stops~~changes ~~when additional written or oral information is to be provided by the applicant~~ in ~~response~~healthcare tosystems ~~questions~~with ~~asked by~~ the ~~CHMP.~~stated ~~Clock~~goals ~~stops may extend the timeframe~~ of ~~evaluation~~containing ofhealthcare ancosts, MAimproving ~~application~~quality ~~considerably~~or ~~beyond~~expanding ~~210 days~~access. ~~Where~~In the ~~CHMP~~United ~~gives a positive opinion~~States, ~~it provides~~ the ~~opinion~~pharmaceutical ~~together~~industry ~~with~~has ~~supporting~~been ~~documentation~~a toparticular ~~the~~focus ~~European Commission, who makes the final decision to grant an MA, which is issued within 67 days~~ of ~~receipt~~these ofefforts ~~the~~and ~~EMA’s~~has ~~recommendation.~~been ~~Accelerated~~significantly ~~assessment~~affected ~~might be granted~~ by ~~the~~federal ~~CHMP~~and instate ~~exceptional cases~~initiatives, ~~when~~including athose ~~medicinal~~designed ~~product is expected~~ to belimit ofthe ~~major~~pricing, ~~public health interest~~coverage, ~~particularly~~and ~~from~~reimbursement ~~the point~~ of ~~view~~pharmaceutical ofand ~~therapeutic~~biopharmaceutical ~~innovation. If the CHMP accepts such request~~products, ~~the~~especially ~~time~~under ~~limit~~government-funded ofhealth ~~210~~care ~~days will be reduced to 150 days~~programs, ~~excluding~~and ~~clock~~increased ~~stops,~~governmental ~~but~~control itof isdrug ~~possible that the CHMP may revert to the standard time limit for the centralized procedure if it determines that the application is no longer appropriate to conduct an accelerated assessment~~pricing.

~~European~~The ~~Union~~ACA, ~~New~~which ~~Chemical~~was ~~Entity~~enacted ~~Exclusivity~~in March 2010, substantially changed the way healthcare is financed by both governmental and private insurers in the United States, and significantly affected the pharmaceutical industry. The ACA contains a number of provisions of particular import to the pharmaceutical and biotechnology industries, including, but not limited to, those governing enrollment in federal healthcare programs, a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, and annual fees based on pharmaceutical companies’ share of sales to federal health care programs. Since its enactment, there have been judicial and Congressional challenges to certain aspects of the ACA, and we expect there will be additional challenges and amendments to the ACA in the future. For example, the IRA, among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025. The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program.

InOther ~~the~~legislative ~~EU,~~changes ~~innovative~~have ~~medicinal~~been ~~products~~proposed ~~approved on the basis of a complete~~ and ~~independent~~adopted ~~data~~since ~~package~~the ~~qualify~~ACA ~~for~~was ~~eight~~enacted, ~~years~~including ofautomatic ~~data~~aggregate ~~exclusivity~~reductions ~~upon the grant~~ of anMedicare MApayments ~~and~~to anproviders ~~additional two years~~ of ~~market~~on ~~exclusivity.~~average ~~The~~2% ~~data~~per ~~exclusivity,~~fiscal ifyear ~~granted,~~as ~~prevents~~part ~~generic or biosimilar applicants from referencing the innovator’s preclinical and clinical trial data contained in the dossier~~ of the ~~reference~~federal ~~product~~budget ~~when~~sequestration ~~applying~~under ~~for a generic or biosimilar MA in~~ the ~~EU,~~Budget ~~during~~Control aAct ~~period~~ of ~~eight~~2011. ~~years~~These ~~from~~reductions ~~the~~went ~~date~~into oneffect ~~which the reference product was first authorized~~ in ~~the~~April ~~EU.~~2013 ~~During the additional two-year period of market exclusivity, a generic or biosimilar MA application can be submitted~~ and ~~authorized~~, ~~and~~due ~~the~~to ~~innovator’s~~subsequent ~~data~~legislative ~~may be referenced~~amendments, ~~but~~will noremain ~~generic~~in oreffect ~~biosimilar~~until ~~product~~2032 ~~can~~unless beadditional ~~placed~~action onis ~~the~~taken EUby ~~market until the expiration of the market exclusivity~~Congress. ~~The~~In ~~overall ten-year period will be extended to a maximum of eleven years if~~addition, ~~during~~ the ~~first~~Bipartisan ~~eight~~Budget ~~years~~Act of ~~those ten years~~2018, ~~the~~among MAother ~~holder obtains an MA for one or more new therapeutic indications which~~things, ~~during~~amended the ~~scientific~~Medicare ~~evaluation~~Act ~~prior~~(as toamended ~~their authorization, are determined to bring a significant clinical benefit in comparison with currently approved therapies. There is no guarantee that a product will be considered~~ by the ~~EMA~~ACA) to beincrease ~~an innovative medicinal product, and products may not qualify for data exclusivity. Even if a product is considered to be an innovative medicinal product so that~~ the ~~innovator gains the prescribed period~~ point-of-sale ~~data~~discounts ~~exclusivity,~~that ~~another~~manufacturers ~~company~~must ~~could~~agree ~~nevertheless~~to ~~also~~offer ~~market~~under ~~another version of~~ the ~~product~~Medicare ifPart ~~such~~D ~~company~~coverage ~~obtained~~discount anprogram MAfrom ~~based~~50% onto an70% MAoff ~~application~~negotiated ~~with a complete and independent data package of pharmaceutical tests, preclinical tests and clinical trials.~~

European Union Orphan Designation and Exclusivity

In the EU, the European Commission grants orphan designation in respect of a product, after receiving the opinion of the EMA’s Committee for Orphan Medicinal Products, if its sponsor can establish that: (1) the product is intended for the diagnosis,

~~prevention~~prices ~~or treatment~~ of aapplicable ~~life-threatening~~brand ordrugs chronically debilitating condition; (2) either (i) such condition affects no more than five in 10,000 persons in the EU when the application is made, or (ii) it is unlikely that the product, without the benefits derived from orphan status, would generate sufficient return in the EU to ~~justify~~eligible ~~the~~beneficiaries ~~necessary~~during ~~investment~~their incoverage ~~its~~gap ~~development; and (3) there exists no satisfactory method of diagnosis~~period, ~~prevention~~as ora ~~treatment of such~~ condition ~~authorized~~ for ~~marketing in~~ the ~~EU,~~manufacturer’s ~~or,~~outpatient ifdrugs ~~such~~being acovered ~~method~~under ~~exists,~~Medicare ~~the~~Part ~~product would be a significant benefit to those affected by that condition~~D.

InMoreover, there has recently been heightened governmental scrutiny over the ~~EU,~~manner ~~orphan~~in ~~designation~~which ~~entitles~~manufacturers aset ~~party~~prices tofor ~~financial~~their ~~incentives~~marketed ~~such~~products, aswhich ~~reduction~~has ofresulted ~~fees~~in orseveral ~~fee~~Congressional ~~waivers~~inquiries and ~~ten~~proposed ~~years~~and ofenacted ~~market~~federal ~~exclusivity~~and isstate ~~granted~~measures ~~following~~designed to, among other things, reduce the ~~grant~~cost of anprescription ~~MA.~~drugs, ~~During~~bring ~~this~~more ~~market~~transparency ~~exclusivity~~to ~~period~~product pricing, ~~neither~~review the ~~EMA~~relationship ~~nor~~between ~~the~~pricing ~~European~~and ~~Commission~~manufacturer ~~nor~~patient ~~any~~programs, ofand ~~the~~reform ~~competent~~government ~~authorities~~program inreimbursement ~~the~~methodologies EUfor ~~Members~~drug ~~States~~products. ~~can~~For ~~accept~~example, anin ~~application~~May or2019, ~~grant~~CMS anadopted MAa ~~for~~final arule ~~“similar~~allowing ~~medicinal~~Medicare ~~product”~~Advantage ~~for~~Plans the ~~authorized~~option ~~orphan~~to ~~indication.~~use Astep ~~“similar~~therapy ~~medicinal~~for ~~product”~~Part isB ~~defined~~drugs, aspermitting aMedicare ~~medicinal~~Part ~~product~~D ~~containing~~plans ato ~~similar~~apply ~~active~~certain ~~substance~~utilization orcontrols ~~substances~~to asnew ~~contained~~starts inof anfive ~~authorized~~of ~~orphan~~the ~~medicinal~~six ~~product~~protected class drugs, and ~~which~~requiring isthe ~~intended~~Explanation of Benefits for ~~the~~Part ~~same~~D beneficiaries to disclose drug price increases and lower cost therapeutic ~~indication.~~alternatives, ~~This~~which ~~period~~went ~~may~~into beeffect ~~reduced~~on toJanuary ~~six~~1, ~~years~~2021. In ifMay 2025, atthe Trump Administration renewed the ~~end~~idea of ~~the~~international ~~fifth~~reference ~~year,~~pricing itthrough isan ~~established~~executive ~~that~~order ~~the~~entitled ~~orphan~~“Delivering ~~designation~~Most-Favored-Nation ~~criteria~~Prescription ~~are~~Drug noPricing ~~longer~~to ~~met~~American Patients,” ~~including~~which, ~~where~~among itother isthings, ~~shown~~directs ~~that~~ the ~~product~~HHS isand ~~sufficiently~~other ~~profitable~~agencies ~~not~~to communicate most-favored-nation price targets to ~~justify~~pharmaceutical ~~maintenance~~manufacturers ofto ~~market~~bring ~~exclusivity~~prices for U.S. Anpatients MAin ~~may~~line bewith ~~granted~~comparably todeveloped anations ~~similar~~and ~~medicinal~~to ~~product~~facilitate direct-to-consumer anpurchasing ~~authorized~~programs. ~~orphan~~The ~~product~~HHS insubsequently ~~very~~issued ~~select~~guidance ~~cases,~~indicating ~~such~~the asMFN ~~if:~~target ~~(i)~~price itwill isbe ~~established~~the ~~that~~lowest aprice ~~similar~~paid ~~medicinal~~in ~~product~~an isOrganisation ~~safer,~~for ~~more~~Economic ~~effective~~Co-operation orand ~~otherwise~~Development ~~clinically~~country ~~superior~~with toa ~~the~~gross ~~authorized~~domestic product; (iiGDP) ~~the~~per MAcapita ~~holder~~of ~~for~~at least 60% of the ~~authorized~~U.S. ~~orphan~~GDP ~~product~~per ~~consents~~capital. toIn ~~the~~addition, ~~authorization~~in ofDecember ~~the~~2025, ~~similar~~CMS ~~medicinal~~proposed ~~product;~~new ordrug ~~(iii)~~payment ~~the~~models MAto ~~holder~~lower drug prices for ~~the~~Medicare ~~authorized~~beneficiaries; ~~orphan~~under ~~product~~the ~~cannot~~models, ~~supply~~CMS ~~enough~~would ~~orphan~~explore ~~medicinal~~potential ~~product.~~adjustments ~~Orphan~~to ~~designation~~Medicare ~~must~~drug beinflation ~~requested~~rebate ~~before~~calculations ~~submitting~~by ancomparison ~~application~~to ~~for~~international andrug MApricing information. ~~Orphan~~It ~~designation~~is ~~does~~currently ~~not~~unclear ~~convey~~whether ~~any~~and ~~advantage~~to ~~in,~~what orextent ~~shorten~~these ~~the~~measures ~~duration~~will ~~of,~~be ~~the~~implemented ~~regulatory~~and ~~review~~what ~~and~~impact ~~approval~~any ~~process.~~such implementation would have on our business.

~~European~~Notwithstanding ~~Union~~the ~~Regulatory~~IRA, ~~Requirements~~continued ~~After~~legislative aand ~~Marketing~~enforcement ~~Authorization~~interest ~~has~~exists ~~been~~in ~~Obtained~~the United States with respect to specialty drug pricing practices. Specifically, we expect government authorities to continue pushing for transparency to drug pricing, reducing the cost of prescription drugs under Medicare, reviewing the relationship between pricing and manufacturer patient programs, and reforming government program reimbursement methodologies for drugs.

IfIndividual ~~authorization~~states ~~for~~in athe ~~medicinal~~U.S. ~~product~~have also become increasingly active in ~~the~~passing EUlegislation isand ~~obtained~~implementing regulations designed to control pharmaceutical and biological product pricing, ~~the~~including ~~holder~~price ofor ~~the~~patient MAreimbursement isconstraints, ~~required~~discounts, torestrictions ~~comply~~on ~~with~~certain adrug ~~range~~access ofand ~~requirements~~marketing ~~applicable~~cost disclosure and transparency measures, and designed to ~~the~~encourage ~~manufacturing~~importation from other countries and bulk purchasing. Legally mandated price controls on payment amounts by third-party payors or other restrictions could harm our business, ~~marketing~~financial condition, ~~promotion~~results of operations and prospects. In addition, regional healthcare authorities and ~~sale~~individual ofhospitals ~~medicinal~~are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs. ~~These~~This ~~include:~~could reduce the ultimate demand for its drugs or put pressure on its drug pricing, which could negatively affect our business, financial condition, results of operations and prospects.

~~•Compliance~~Other ~~with~~Government ~~the~~Regulation ~~EU’s~~Outside ~~stringent~~of ~~pharmacovigilance~~the orUnited ~~safety reporting rules must be ensured. These rules can impose post-authorization studies and additional monitoring obligations.~~ States

~~•The~~In ~~manufacturing~~addition ofto ~~authorized~~regulations ~~medicinal~~in ~~products,~~the ~~for~~United ~~which~~States, awe ~~separate~~are ~~manufacturer’s~~subject ~~license~~to isa ~~mandatory,~~variety ~~must~~of ~~also~~regulations ~~be conducted~~ in ~~strict~~other ~~compliance~~jurisdictions ~~with~~governing, ~~the~~among ~~applicable~~other ~~EU laws~~things, ~~regulations~~research and ~~guidance~~development, ~~including~~clinical ~~Directive~~trials, ~~2001/83/EC~~testing, ~~Directive~~manufacturing, ~~2017/1572~~safety, ~~Regulation~~efficacy, ~~(EC)~~quality Nocontrol, ~~726/2004~~labeling, ~~and~~packaging, ~~the~~storage, ~~European~~record ~~Commission~~keeping, ~~Guidelines~~distribution, ~~for~~reporting, ~~Good~~export ~~Manufacturing~~and ~~Practice~~import, ~~(“EU~~advertising, ~~cGMP”).~~marketing ~~These~~and ~~requirements~~other ~~include~~promotional ~~compliance~~practices ~~with~~involving EUbiological ~~cGMP~~products ~~standards~~as ~~when~~well ~~manufacturing~~as ~~medicinal~~authorization, ~~products~~approval ~~and~~as ~~active~~well ~~pharmaceutical~~as ~~ingredients,~~post-approval ~~including~~monitoring ~~the~~and ~~manufacture~~reporting of ~~active~~our ~~pharmaceutical~~products. ~~ingredients~~Because ~~outside~~biologically ofsourced ~~the~~raw EUmaterials ~~with~~are ~~the~~subject ~~intention~~ to ~~import~~unique ~~the~~contamination ~~active~~risks, ~~pharmaceutical~~their ~~ingredients~~use ~~into~~may ~~the~~be ~~EU.~~restricted in some countries.

~~•Much~~Whether ~~like~~or ~~the~~not ~~Anti-Kickback~~we ~~Statute~~obtain ~~prohibition~~FDA inapproval ~~the~~for ~~United~~a ~~States~~product, ~~the~~we ~~provision~~must ofobtain ~~benefits or advantages to physicians to induce or encourage~~ the ~~prescription,~~requisite ~~recommendation,~~approvals ~~endorsement,~~from ~~purchase,~~regulatory ~~supply,~~authorities ~~order, or use of medicinal products is also prohibited~~ in ~~the~~foreign ~~EU.~~countries ~~The~~prior ~~provision of benefits or advantages~~ to ~~reward improper performance generally may be governed by~~ the ~~national~~commencement ~~anti-bribery laws~~ of EUclinical ~~Member~~trials ~~States,~~or ~~and~~marketing ~~the~~of ~~Bribery Act 2010 in~~ the ~~UK.~~product ~~Infringement of these laws could result~~ in ~~substantial~~those ~~fines and imprisonment~~countries. EUCertain ~~Directive~~countries ~~2001/83/EC,~~outside ~~which~~of is the EUUnited ~~Directive~~States ~~governing~~have ~~medicinal~~a ~~products~~similar ~~for~~process ~~human use, further provides~~ that, ~~where~~requires medicinal products are being promoted to persons qualified to prescribe or supply them, no gifts, pecuniary advantages, or benefits in kind may be supplied, offered or promised to such persons unless they are inexpensive and relevant to the ~~practice~~submission of ~~medicine~~a orclinical ~~pharmacy.~~trial ~~This~~application ~~provision~~much ~~has~~like ~~been transposed into~~ the ~~Human~~IND ~~Medicines~~prior ~~Regulations~~to ~~2012 and so remains applicable in~~ the UKcommencement ~~despite~~of ~~its~~human ~~departure~~clinical ~~from the EU~~trials.

~~Payments~~The ~~made~~requirements toand ~~physicians~~process ingoverning ~~certain~~the EUconduct ~~Member~~of ~~States~~clinical ~~must~~trials, beincluding ~~publicly~~requirements ~~disclosed.~~to ~~Moreover~~conduct additional clinical trials, ~~agreements~~product ~~with~~licensing, ~~physicians~~safety ~~often~~reporting, ~~must~~post-authorization berequirements, ~~the~~marketing ~~subject~~and ofpromotion, ~~prior~~interactions ~~notification~~with healthcare professionals, pricing and ~~approval~~reimbursement bymay ~~the~~vary ~~physician’s~~widely ~~employer,~~from ~~his~~country orto ~~her~~country. ~~competent~~No ~~professional~~action ~~organization~~can asbe ~~well~~taken asto ~~the~~market ~~regulatory~~any ~~authorities~~product ofin ~~the~~a ~~individual~~country EUuntil ~~Member~~an ~~States.~~appropriate ~~These~~approval ~~requirements~~application ~~are~~has ~~provided~~been inapproved by the ~~national~~regulatory ~~laws,~~authorities ~~industry~~in ~~codes~~that orcountry. ~~professional~~The ~~codes~~current ofapproval ~~conduct,~~process ~~applicable~~varies infrom country to country, and the EUtime ~~Member~~spent ~~States.~~in ~~Failure~~gaining toapproval ~~comply~~varies ~~with~~from ~~these~~that ~~requirements~~required ~~could~~for ~~result~~FDA inapproval. ~~reputational~~In ~~risk~~certain countries, ~~public~~the ~~reprimands,~~sales ~~administrative~~price ~~penalties,~~of ~~fines~~a orproduct ~~imprisonment~~must also be approved. The pricing review

All of the aforementioned EU rules are generally applicable in the EEA.

~~Reform~~period often begins after market approval is granted. Even if a product is approved by a regulatory authority, satisfactory prices may not be approved for such product, which would make launch of ~~the~~such ~~Regulatory~~products ~~Framework~~commercially unfeasible in ~~the~~such ~~European Union~~countries.

~~The~~Regulation ~~European Commission introduced legislative proposals~~ in ~~April 2023 that, if implemented, will replace~~ the ~~current regulatory framework in the EU for all medicines (including those for rare diseases and for children). The~~ European Commission has provided the legislative proposals to the European Parliament and the European Council for their review and approval, and, in April 2024, the European Parliament proposed amendments to the legislative proposals. Once the European Commission’s legislative proposals are approved (with or without amendment), they will be adopted into EU law.Union

~~Pharmaceutical~~European ~~Coverage,~~Data ~~Pricing and Reimbursement~~Laws

~~Sales~~The processing of ~~pharmaceutical~~personal ~~products~~data, including health-related personal data in the ~~United~~European ~~States~~Economic ~~will~~Area ~~depend~~(“EEA”) is mainly governed by the provisions of the European General Data Protection Regulation (EU) 2016/679 (“GDPR”), and related data protection laws in ~~part~~individual EEA countries. In the United Kingdom, onthe processing of personal data is mainly governed by the ~~extent~~GDPR as incorporated into UK law pursuant to ~~which~~the European Union (Withdrawal) Act 2018 (the ~~costs~~“UK GDPR”). The GDPR and UK GDPR impose a number of strict obligations and requirements for the ~~products~~processing, ~~will~~including becollecting, ~~covered~~analyzing byand ~~third-party~~transferring, ~~payors~~of personal data of individuals in the EEA or in the UK, in particular with respect to health data from clinical trials and adverse event reporting. The GDPR and UK GDPR include requirements relating to the legal basis of the processing (such as ~~government~~consent ~~health~~of ~~programs~~the individuals to whom the personal data relates), the information provided to the individuals prior to processing their personal data, the personal data breaches which may have to be notified to the national data protection authorities and ~~commercial~~data ~~insurance~~subjects, the measures to be taken when engaging processors, and ~~managed~~obligations ~~health~~relating ~~care~~to ~~organizations~~the security and confidentiality of the personal data. ~~These~~EEA ~~third-party~~countries ~~payors~~may ~~are~~also ~~increasingly~~impose ~~challenging~~additional ~~the~~requirements ~~prices~~in ~~charged~~relation ~~for~~to ~~medical~~the ~~products~~processing of health, genetic and ~~services~~biometric data through their national legislation.

~~Significant~~In ~~uncertainty~~addition, ~~exists~~the asGDPR toimposes ~~the~~specific ~~coverage~~restrictions ~~and~~on ~~reimbursement~~the ~~status~~transfer of ~~any~~personal ~~drug~~data ~~products~~to ~~for~~countries ~~which~~outside weof ~~obtain~~the ~~regulatory~~EEA ~~approval.~~that Inare ~~the~~not ~~United~~considered ~~States,~~by ~~sales~~the ofEC ~~any~~to ~~products~~provide ~~for~~an ~~which~~adequate welevel ~~receive~~of ~~regulatory~~data ~~approval~~protection. ~~for~~Appropriate ~~commercial~~safeguards ~~sale~~are ~~will~~required ~~depend~~to inenable ~~part~~such ontransfers. Among the ~~availability~~appropriate ofsafeguards ~~coverage~~that ~~and~~can ~~reimbursement~~be ~~from~~used, ~~third-party~~the ~~payors.~~data ~~Third-party~~exporter ~~payors~~may ~~include~~use ~~government~~the ~~authorities,~~standard ~~managed~~contractual ~~care~~clauses ~~providers,~~(“SCCs”). ~~private~~When ~~health~~relying ~~insurers~~on ~~and~~the ~~other~~appropriate ~~organizations.~~safeguards, ~~Coverage~~data ~~and~~exporters, ~~reimbursement~~with ~~policies~~the ~~for~~assistance ~~drug~~of ~~products~~the ~~can~~data ~~differ~~importers, ~~significantly~~are ~~from~~also ~~payor~~required to ~~payor~~conduct asa ~~there~~transfer isrisk noassessment ~~uniform~~to ~~policy~~verify ofif ~~coverage~~anything ~~and~~in ~~reimbursement~~the ~~for~~law ~~drug~~and/or ~~products~~practices ~~among~~of the third ~~party~~country ~~payors~~may inimpinge on the ~~United~~effectiveness ~~States.~~of ~~Third-party~~the ~~payors~~safeguards ~~often~~in ~~rely~~the ~~upon~~context ~~Medicare~~of ~~coverage~~the ~~policy~~transfer ~~and~~at ~~payment~~stake ~~limitations~~and, inif ~~setting their own reimbursement rates~~so, ~~but~~to ~~also~~identify ~~have~~and ~~their~~adopt ~~own~~supplementary ~~methods~~measures ~~and~~that ~~approval~~are ~~process~~necessary ~~apart~~to ~~from~~bring ~~Medicare~~the ~~determinations.~~level ~~The~~of ~~process~~protection ~~for~~of ~~determining~~the ~~whether~~data atransferred ~~payor~~to ~~will~~the ~~provide~~EU ~~coverage~~standard ~~for~~of aessential ~~drug~~equivalence. ~~product~~Where ~~may~~no besupplementary ~~separate~~measure ~~from~~is suitable, the ~~process~~data ~~for~~exporter ~~setting~~should ~~the~~avoid, ~~reimbursement~~suspend ~~rate~~or ~~that~~terminate the ~~payor~~transfer. ~~will~~With ~~pay~~regard ~~for~~to the ~~drug~~transfer ~~product.~~of ~~Third-party~~data ~~payors~~from ~~may~~the ~~limit~~EEA ~~coverage~~ to ~~specific~~the ~~drug~~United ~~products~~States, on anJuly ~~approved list~~10, ~~or formulary~~2023, ~~which might not include all of~~ the ~~FDA-approved~~EC ~~drugs~~adopted ~~for~~its aadequacy ~~particular indication. Moreover, a payor’s~~ decision ~~to provide coverage~~ for athe ~~drug~~EU-US ~~product~~Data ~~does~~Privacy ~~not imply that an adequate reimbursement rate will be approved~~Framework. ~~Adequate~~On ~~third-party~~the ~~reimbursement~~basis ~~may~~of ~~not~~the benew ~~available~~adequacy todecision, ~~enable~~personal usdata tocan ~~maintain~~flow ~~price~~from ~~levels~~the ~~sufficient~~EEA to ~~realize~~U.S. ancompanies ~~appropriate~~participating ~~return on our investment~~ in ~~product~~the ~~development~~framework.

~~Additionally,~~With ~~the~~regard ~~containment~~to ofthe ~~health~~transfer ~~care costs has become a priority~~ of ~~federal~~data ~~and~~from ~~state~~the ~~governments,~~EEA ~~and~~to the ~~prices of drugs have been a focus in this effort. The U.S. government~~UK, ~~state~~based ~~legislatures~~on ~~and~~the ~~foreign~~EC’s ~~governments~~adequacy ~~have~~decision ~~shown~~of ~~significant~~June ~~interest in implementing cost-containment programs~~28, ~~including~~2021 ~~price controls, utilization management~~ and ~~requirements~~subsequent ~~for substitution of generic products. Adoption of price controls and cost-containment measures~~renewals, ~~and~~personal ~~adoption~~data ofmay ~~more~~continue ~~restrictive~~to ~~policies~~flow infreely ~~jurisdictions~~from ~~with~~the ~~existing~~EEA ~~controls~~to ~~and~~the ~~measures,~~UK ~~could~~on ~~further~~the ~~limit~~basis ~~our~~that ~~net~~the ~~revenue~~UK ~~and~~is ~~results.~~deemed ~~If these third-party payors do not consider our products~~ to beprovide ~~cost-effective~~an ~~compared~~adequate ~~to other available therapies, they may not cover our products after approval as a benefit under their plans or, if they do, the~~ level of ~~payment~~data ~~may~~protection ~~not~~until beDecember ~~sufficient~~27, to2031. ~~allow~~The usadequacy todecisions ~~sell~~will ~~our~~automatically ~~products~~expire onunless ~~a profitable basis~~renewed.

~~The~~With ~~Medicare~~respect ~~Prescription~~to ~~Drug,~~transfers ~~Improvement,~~from ~~and Modernization Act of 2003 (“MMA”), imposed requirements for~~ the ~~distribution~~UK and pricing of prescription drugs for Medicare beneficiaries and included a major expansion of the prescription drug benefit under Medicare Part D (“Part D”). Under Part D, Medicare beneficiaries may enroll in prescription drug plans offered by private entities that provide coverage of outpatient prescription drugs. Part D is available through both stand-alone prescription drug benefit plans and prescription drug coverage as a supplement to ~~Medicare~~other ~~Advantage plans. Unlike Medicare Parts A and B~~countries, ~~Part~~these Dtransfers ~~coverage is not standardized. Part D prescription drug plan sponsors~~ are ~~not~~also ~~required~~subject to ~~pay~~specific ~~for~~transfer ~~all~~rules ~~covered~~under ~~Part~~the DUK ~~drugs, and each drug plan can develop its own drug formulary that identifies which drugs it will cover and at what tier or level~~regime. ~~However,~~These ~~Part~~UK Dinternational ~~prescription~~transfer ~~drug~~rules ~~formularies~~broadly ~~must~~mirror ~~include drugs within each therapeutic category and class of covered Part D drugs, though not necessarily all~~ the ~~drugs~~EU inGDPR ~~each category or class~~rules. ~~Any formulary used by a Part D prescription drug plan must be developed and reviewed by a pharmacy and therapeutic committee.~~

~~Government~~On ~~payment~~February ~~for~~2, ~~some~~2022, the UK Secretary of State laid before the ~~costs~~UK ofParliament ~~prescription~~the ~~drugs~~international ~~may~~data ~~increase~~transfer ~~demand~~agreement ~~for~~(“IDTA”) ~~products~~and the international data transfer addendum to the EC’s standard contractual clauses for ~~which~~international wedata ~~receive~~transfers ~~marketing~~(UK ~~approval~~Addendum) and a document setting out transitional provisions. ~~However~~The IDTA and UK Addendum came into force on March 21, ~~any~~2022 ~~negotiated~~and ~~prices~~are the primary UK-approved mechanisms for ~~our~~putting ~~products~~in ~~covered~~place byappropriate asafeguards ~~Part~~for DUK ~~prescription~~restricted ~~drug~~transfers, ~~plan~~subject ~~will~~to ~~likely~~transitional bearrangements ~~lower~~for ~~than~~legacy SCCs. Regarding transfers from the ~~prices~~UK weto ~~might~~the ~~otherwise~~EEA, ~~obtain~~the UK Information Commissioner’s Office (“ICO”) guidance indicates that organizations do not need new arrangements. ~~Moreover,~~With ~~while~~regard to the ~~MMA~~transfer ~~applies~~of ~~only~~personal data from the UK to ~~drug~~the ~~benefits~~United States, the UK government has adopted an adequacy decision for ~~Medicare~~the ~~beneficiaries,~~UK ~~private~~Extension ~~payors~~to ~~often~~the ~~follow~~EU-US ~~Medicare~~Data ~~coverage~~Privacy ~~policy~~Framework, ~~and~~the ~~payment~~UK-US ~~limitations~~Data inBridge, ~~setting~~which ~~their~~came ~~own~~into ~~payment~~force ~~rates.~~on ~~Any~~October ~~reduction~~12, in2023. ~~payment~~The ~~that~~UK-US ~~results~~Data ~~from~~Bridge recognizes the ~~MMA~~United ~~may~~States ~~result~~as inoffering an adequate level of data protection where the recipient is a ~~similar~~U.S. ~~reduction~~organization certified to the EU-US Data Privacy Framework and participating in ~~payments~~the ~~from~~UK ~~non~~Extension to the EU-~~governmental~~US ~~payors~~Data Privacy Framework.

~~Third-party~~Failure ~~payors~~to ~~are~~comply ~~increasingly~~with ~~challenging~~the requirements of the ~~price~~GDPR ~~and~~or ~~examining~~UK GDPR and the ~~medical~~related ~~necessity~~national ~~and~~data ~~cost-effectiveness~~protection laws of ~~medical~~the ~~products~~EEA ~~and~~countries ~~services,~~may result in ~~addition~~significant monetary fines for noncompliance of up to ~~their~~€20 ~~safety~~million or £17.5 million (as applicable), 4% of the total worldwide annual turnover (for higher-tier infringements). This is enforced by ICO and ~~efficacy~~is entirely separate from fines under EU GDPR. In ~~order~~addition, toviolations ~~obtain~~of ~~coverage~~national laws can trigger additional, administrative penalties, investigations, corrective orders, temporary or definitive bans, and, ~~reimbursement~~in ~~for~~some ~~any~~jurisdictions, ~~product~~and ~~that~~a number of criminal offenses for organizations

~~might be approved for sale, we may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity~~ and ~~cost-effectiveness of our products~~, in ~~addition~~certain to the costs required to obtain regulatory approvals. Our product candidates may not be considered medically necessary or cost-effective. If third-party payors do not consider a product to be cost-effective compared to other available therapiescases, ~~they may not cover the product after approval as a benefit under~~ their ~~plans~~directors ~~or,~~and ~~if they do~~officers, ~~the~~as ~~level~~well ofas ~~payment~~civil ~~may~~liability ~~not~~claims befrom ~~sufficient~~individuals towhose ~~allow~~personal adata ~~company~~was ~~to sell its products at a profit~~processed.

~~Healthcare~~Data ~~Reform~~protection authorities from the different EEA countries may still implement certain variations, enforce the GDPR and national data protection laws differently, and introduce additional national regulations and guidelines, which adds to the complexity of processing personal data in the EEA.

~~Payors~~Furthermore, ~~whether~~there ~~domestic, foreign, governmental or private,~~ are ~~developing~~specific ~~increasingly~~requirements ~~sophisticated~~relating ~~methods~~to ofprocessing ~~controlling~~health ~~healthcare~~data ~~costs.~~from Inclinical ~~both the U.S. and certain foreign jurisdictions~~trials, ~~there~~including ~~have~~public ~~been~~disclosure aobligations ~~number~~provided ofin ~~legislative and regulatory changes to~~ the ~~health~~EU ~~care~~Clinical ~~system~~Trials ~~that~~Regulation ~~could impact our ability to sell our products profitably~~No. ~~For~~536/2014 ~~example~~(“CTR”), ~~the~~EMA ~~Patient~~disclosure ~~Protection~~initiatives and ~~Affordable~~voluntary ~~Care~~commitments ~~Act, as amended~~ by ~~the~~industry. ~~Health~~Failure ~~Care~~to ~~and~~comply ~~Education Reconciliation Act of 2010, collectively, the ACA, was enacted~~ with ~~the~~these ~~goal~~obligations ofcould ~~expanding~~lead ~~coverage~~to ~~for~~government ~~the~~enforcement ~~uninsured~~actions ~~while~~and atsignificant ~~the~~penalties ~~same~~against ~~time~~us, ~~containing~~harm ~~overall health care costs. With regard~~ to ~~pharmaceutical~~our ~~products~~reputation, ~~among other things, the ACA expanded~~ and ~~increased~~adversely ~~industry~~impact ~~rebates~~our ~~for~~business ~~drugs covered under Medicaid programs~~ and ~~made~~operating ~~changes to the coverage requirements under the Medicare D program~~results.

~~Since~~Drug ~~its enactment, there have been a number of judicial, administrative, executive,~~ and ~~legislative~~Biologic ~~challenges~~Development to certain aspects of the ACA. On June 17, 2021, for example, the U.S. Supreme Court dismissed a judicial challenge on procedural grounds that argued the ACA is unconstitutional in its entirety because the “individual mandate” was repealed by Congress. In addition, the Inflation Reduction Act of 2022 (“IRA”), among other things, extended enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025. The IRA also eliminated the “donut hole” under the Medicare Part D program (effective January 1, 2025) by capping the beneficiary maximum out-of-pocket cost at $2,000 per year and creating a new manufacturer discount program. The ACA continues to be subject to judicial or challenges and may be subject to legislative healthcare reform measures in the future. It is unclear how any such challenges and or healthcare reform measures will impact the ACA. Process

~~There~~Regardless ~~has~~of ~~been~~where ~~heightened~~they ~~governmental~~are ~~scrutiny~~conducted, ~~recently~~all ~~over~~clinical ~~pharmaceutical~~trials ~~pricing~~included ~~practices~~ in ~~light~~applications offor ~~the~~marketing ~~rising~~authorization ~~cost~~(“MA”) offor ~~prescription~~human ~~drugs~~medicines ~~and biologics. Such scrutiny has resulted~~ in ~~several Presidential executive orders, Congressional hearings and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review~~ the ~~relationship~~EU/EEA ~~between~~must ~~pricing~~have ~~and~~been ~~manufacturer~~carried ~~patient~~out ~~programs,~~in ~~and~~accordance ~~reform~~with ~~government~~EU ~~program reimbursement methodologies for products~~regulations. ~~Congress~~This ~~has~~means ~~also~~that ~~passed~~clinical ~~additional~~trials ~~reform~~conducted ~~measures.~~in ~~This includes~~ the ~~IRA,~~EU/EEA ~~which,~~have ~~(i) directs HHS~~ to ~~negotiate~~comply ~~the~~with ~~price~~EU ofclinical ~~certain~~trial ~~high-expenditure,~~legislation ~~single-source~~but ~~drugs~~also ~~and~~that ~~biologics~~clinical ~~covered~~trials ~~under~~conducted ~~Medicare,~~outside ~~and~~the ~~subject~~EU/EEA ~~drug~~have ~~manufacturers~~ to ~~civil~~comply ~~monetary~~with ~~penalties~~ethical ~~and~~principles aequivalent ~~potential excise tax by offering a price that is not equal~~ to orthose ~~less~~set ~~than~~out ~~the~~in ~~negotiated “maximum fair price” for such drugs and biologics under~~ the ~~law~~EEA, ~~and~~including ~~(ii)~~adhering ~~requires drug manufacturers~~ to ~~pay~~international ~~drug~~good ~~rebates~~clinical ~~with~~practice ~~respect to certain drugs~~ and ~~biologics covered under Medicare Part B or Medicare Part D to~~ the ~~extent~~Declaration ~~that~~of ~~drug~~Helsinki. ~~prices~~The ~~increase~~conduct ~~faster~~of ~~than~~clinical ~~inflation.~~trials ~~Under~~in the ~~IRA,~~EU ~~orphan~~is ~~drugs~~governed ~~are~~by ~~exempted from~~ the ~~Medicare drug price negotiation program~~CTR, ~~but only if they have one orphan designation and for~~ which ~~the~~entered ~~only~~into ~~approved~~force ~~indication(s)~~on isJanuary ~~for~~31, ~~that disease or condition~~2022. The ~~IRA~~CTR ~~permits~~replaced ~~HHS~~the toClinical ~~implement~~Trials ~~many~~Directive ~~of these provisions through guidance~~2001/20/EC, as(“Clinical ~~opposed~~Trials toDirective”) ~~regulation,~~and ~~for~~introduced ~~the~~a ~~initial~~complete ~~years.~~overhaul ~~These provisions have taken effect progressively starting in fiscal year 2023, although the implementation~~ of the ~~IRA~~existing isregulation ~~currently subject to ongoing litigation that challenges the constitutionality~~ of ~~the~~clinical ~~IRA’s~~trials ~~Medicare~~for ~~drug~~medicinal ~~price~~products ~~negotiation~~in ~~program. It is currently unclear how~~ the ~~IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry~~EU.

InUnder ~~addition,~~ the ~~Trump~~CTR, ~~Administration~~a sponsor is ~~likely~~able to ~~propose~~submit ~~new~~a ~~regulations~~single ~~that~~application ~~reform~~for ~~healthcare~~approval ~~delivery~~of a clinical trial through a centralized EU clinical trials portal (the “Clinical Trials Information System” or “CTIS”). One national regulatory authority (the reporting EU member state proposed by the applicant) will take the lead in validating and evaluating the ~~United~~application consult and coordinate with the other concerned EU Member States. If an application is rejected, ~~including~~it ~~related~~may tobe ~~healthcare~~amended and ~~drug~~resubmitted ~~costs~~through ~~and~~the ~~pharmacy~~EU ~~benefit~~clinical ~~manager~~trials ~~reform~~portal. If an approval is issued, ~~among~~the ~~other~~sponsor ~~areas~~may start the clinical trial in all concerned EU Member States. However, a concerned EU member state may in limited circumstances declare an “opt-out” from an approval and prevent the ~~effect~~clinical oftrial ~~which~~from being conducted in such member state. The CTR also aims to streamline and simplify the rules on ~~our~~safety ~~business~~reporting, and introduces enhanced transparency requirements such as mandatory submission of a summary of the ~~pharmaceutical~~clinical ~~industry~~trial inresults ~~general~~to the EU database, including a layperson’s summary. Since January 31, 2023, submission of initial clinical trial applications via CTIS is ~~not~~mandatory ~~yet~~and ~~known~~CTIS serves as the single entry point for submission of clinical trial-related information and data. As of January 31, 2025, all ongoing trials approved under the former Clinical Trials Directive need to comply with the CTR and have to be transitioned to CTIS.

InUnder ~~addition~~the CTR, innational ~~some foreign countries~~laws, ~~the proposed pricing for a drug must be approved before it may be lawfully marketed. The requirements governing drug pricing vary widely from country to country. For example~~regulations, ~~some~~and ~~E.U.~~the ~~jurisdictions~~applicable ~~operate~~GCP ~~positive~~ and ~~negative~~GLP ~~list~~standards ~~systems~~must ~~under~~also ~~which products may only~~ be ~~marketed~~respected ~~once~~during athe ~~reimbursement~~conduct ~~price has been agreed. To obtain reimbursement or pricing approval, some~~ of ~~these countries may require~~ the ~~completion of clinical~~ trials, ~~that~~including ~~compare~~ the ~~cost-effectiveness~~International ofCouncil afor ~~particular~~Harmonization ~~product~~of ~~candidate~~Technical toRequirements ~~currently~~for ~~available~~Pharmaceuticals ~~therapies.~~for ~~Other~~Human ~~member~~Use ~~states~~(ICH) ~~allow~~guidelines ~~companies~~on toGood ~~fix~~Clinical ~~their~~Practice ~~own~~and ~~prices~~the ~~for~~ethical ~~medicines~~principles ~~but~~that ~~monitor~~have ~~and~~their ~~control~~origin ~~company profits. Such differences~~ in ~~national~~the ~~pricing~~Declaration ~~regimes~~of ~~may~~Helsinki. ~~create~~Under ~~price~~the ~~differentials~~current ~~between~~regime ~~E.U.~~all ~~member~~suspected ~~states.~~unexpected ~~There~~serious ~~can~~adverse bereactions noto ~~assurance~~the ~~that~~investigated ~~any~~drug ~~country~~ that ~~has~~occur ~~price~~during ~~controls~~the orclinical ~~reimbursement~~trial ~~limitations~~must ~~for~~be ~~pharmaceutical~~reported ~~products~~to ~~will~~the ~~allow~~National ~~favorable~~Competent ~~reimbursement~~Authority and ~~pricing~~to ~~arrangements for any of our products. Historically, products launched in~~ the ~~European~~Ethics ~~Union~~Committees ~~do not follow price structures~~ of the ~~United~~EU ~~States.~~member Instate ~~the~~where ~~European~~they ~~Union,~~ occur.

During the development of a medicinal product, the EMA and national regulators within the EU provide the opportunity for dialogue and guidance on the development program. At the EMA level, this is usually done in the form of scientific advice, which is given by the CHMP on the recommendation of the Scientific Advice Working Party (“SAWP”). A fee is incurred with each scientific advice procedure, but is significantly reduced for designated orphan medicines. Advice from the EMA is typically provided based on questions concerning, for example, quality (chemistry, manufacturing and controls testing), nonclinical testing and clinical studies, and pharmacovigilance plans and risk-management programs. Advice is not legally binding with regard to any future Marketing Authorization Application (“MAA”) of the product concerned.

Drug Marketing Authorization

In the EEA, after completion of all required clinical testing, pharmaceutical products may only be placed on the market after obtaining a MA. To obtain an MA of a drug under EU regulatory systems, an applicant can submit an MAA through, amongst others, a centralized or decentralized procedure.

To be used or sold in the UK, a drug must have an effective MA granted by the Medicines and Healthcare Products Regulatory Agency (“MHRA”) under the Human Medicines Regulations 2012 (SI 2012/1916), as amended. MA applications are submitted electronically via the MHRA Submissions Portal. Under the MHRA’s national assessment procedure, the MHRA generally

~~the~~aims ~~downward~~to ~~pressure~~reach ona ~~healthcare~~decision ~~costs~~within in210 ~~general,~~“clock-on” ~~particularly prescription medicines~~days, ~~has~~excluding ~~become~~any ~~intense.~~“clock-stops” Aswhile athe ~~result,~~applicant ~~barriers~~prepares toresponses ~~entry of new products are becoming increasingly high and patients are unlikely~~ to ~~use~~MHRA ~~a drug product that is not reimbursed by their government~~questions.

~~Other~~On ~~Healthcare~~August ~~Laws~~30, 2023, the MHRA published detailed guidance on its recently announced new International Recognition Procedure (“IRP”) for MAAs. The IRP applies since January 1, 2024 and ~~Compliance~~replaces ~~Requirements~~existing EU reliance procedures to apply for authorizations from seven international regulators (e.g. Health Canada, Swiss Medic, FDA, EMA, among others). The IRP allows medicinal products approved in other jurisdictions that meet certain criteria to undergo a fast-tracked MHRA review to obtain and/or update a MA in the UK. Applicants can submit initial MAAs to the IRP but the procedure can also be used throughout the lifecycle of a product for post-authorization procedures including line extensions, variations and renewals.

~~Our~~Centralized ~~current~~Authorization and future operations may subject us to various federal and state laws targeting fraud and abuse in the healthcare industry. These laws may impact, among other things, our research and proposed sales, marketing and education programs. In addition, we may be subject to patient privacy regulation by both the federal government and the states and foreign jurisdictions in which we conduct our business. The laws that may affect our ability to operate include:Procedure

•The centralized procedure provides for the ~~federal~~grant ~~Anti-Kickback~~of ~~Statute~~a single MA that is issued by the EC following the scientific assessment of the application by the EMA that is valid for all EU Member States as well as in the three additional EEA Member States (Norway, ~~which~~Iceland ~~prohibits~~and Liechtenstein). The centralized procedure is compulsory for specific medicinal products, ~~among~~including ~~other~~for ~~things~~medicines developed by means of certain biotechnological processes, ~~persons~~products ~~from~~designated ~~knowingly~~as ~~and~~orphan ~~willfully~~medicinal ~~soliciting~~products, ~~receiving~~advanced therapy medicinal products (gene therapy, ~~offering~~somatic cell therapy, or ~~paying~~tissue ~~remuneration~~engineered medicines) and medicinal products with a new active substance indicated for the treatment of certain diseases (HIV/AIDS, ~~directly~~cancer, orneurodegenerative ~~indirectly~~disorders, todiabetes, ~~induce~~auto-immune diseases and other immune dysfunctions, orand viral diseases). For medicinal products containing a new active substance not yet authorized in ~~return~~the ~~for~~EEA before May 20, ~~the~~2004 ~~purchase~~and orindicated ~~recommendation~~for the treatment of another ~~item~~diseases, medicinal products that constitute significant therapeutic, scientific or ~~service~~technical ~~reimbursable~~innovations ~~under~~or for which the grant of a ~~federal~~MA ~~healthcare~~through ~~program,~~the ~~such~~centralized asprocedure would be in the ~~Medicare~~interest ~~and~~of ~~Medicaid~~public ~~programs;~~health at EU level, an applicant may voluntarily submit an application for a MA through the centralized procedure.

~~•federal~~Under ~~civil~~the ~~and~~centralized ~~criminal~~procedure, ~~false~~the ~~claims~~CHMP ~~laws~~is ~~and~~responsible ~~civil~~for ~~monetary~~conducting ~~penalty~~the ~~laws~~initial assessment of a drug. The CHMP is also responsible for several post-authorization and maintenance activities, ~~which~~such ~~prohibit~~as the assessment of modifications or extensions to an existing MA. Under the centralized procedure, ~~among~~the ~~other~~timeframe ~~things~~for the evaluation of an MAA by the EMA’s CHMP is, ~~individuals~~in orprinciple, ~~entities~~210 days from ~~knowingly~~receipt ~~presenting~~of a valid MAA. However, this timeline excludes clock stops, when additional written or ~~causing~~oral information is to be ~~presented~~provided by the applicant in response to questions asked by the CHMP, ~~claims~~so the overall process typically takes a year or more, unless the application is eligible for ~~payment~~an accelerated assessment. Accelerated evaluation might be granted by the CHMP in exceptional cases, when a medicinal product is expected to be of a major public health interest, particularly from ~~Medicare~~the point of view of therapeutic innovation. Upon request, ~~Medicaid~~the CHMP can reduce the time frame to 150 days if the applicant provides sufficient justification for an accelerated assessment. The CHMP will provide a positive opinion regarding the application only if it meets certain quality, orsafety ~~other~~and ~~third-party~~efficacy ~~payors~~requirements. ~~that~~This ~~are~~opinion ~~false~~is orthen ~~fraudulent;~~transmitted to the EC, which has the ultimate authority for granting MA within 67 days after receipt of the CHMP opinion.

~~•the~~Decentralized ~~federal~~Authorization Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which created additional federal criminal statutes that prohibit, among other things, executing a scheme to defraud any healthcare benefit program and making false statements relating to healthcare matters;Procedure

~~•the~~Medicines ~~federal~~that ~~transparency~~fall ~~laws,~~outside ~~including~~ the ~~federal~~mandatory ~~Physician~~scope ~~Payments~~of ~~Sunshine~~the ~~Act,~~centralized ~~that~~procedure ~~require~~have ~~drug~~three ~~manufacturers~~routes to ~~disclose~~authorization: ~~payments~~(i) ~~and~~they ~~other~~can ~~transfers~~be ofauthorized ~~value~~under ~~provided~~the tocentralized ~~physicians,~~procedure ~~(currently~~if ~~defined~~they toconcern ~~include~~a ~~doctors,~~significant ~~dentists~~therapeutic, ~~optometrists,~~scientific ~~podiatrists~~or ~~and~~technical ~~chiropractors)~~innovation, ~~certain~~or ~~other~~if ~~healthcare~~their ~~professionals~~authorization would be in the interest of public health; (~~such~~ii) asthey ~~physician~~can ~~assistants~~be ~~and~~authorized ~~nurse~~under ~~practitioners~~a decentralized procedure where an applicant applies for simultaneous authorization in more than one EU member state; or (iii) ~~and~~they ~~teaching~~can ~~hospitals,~~be asauthorized ~~well~~in asan ~~ownership~~EU member state in accordance with that state’s national procedures and ~~investment~~then ~~interests~~be ~~held~~authorized in other EU countries by ~~physicians~~a ~~and~~procedure ~~their~~whereby ~~immediate~~the ~~family~~countries ~~members;~~concerned agree to recognize the validity of the original, national MA (mutual recognition procedure).

~~•HIPAA,~~The asdecentralized ~~amended~~procedure bypermits companies to file identical MA applications for a medicinal product to the ~~Health~~competent ~~Information~~authorities ~~Technology~~in ~~and~~various ~~Clinical~~EU ~~Health~~Member ~~Act~~States ~~(“HITECH”),~~simultaneously ~~and~~if ~~its~~such ~~implementing~~medicinal ~~regulations,~~product ~~which~~has ~~imposes~~not ~~certain~~received ~~requirements~~marketing onapproval ~~“covered~~in ~~entities,”~~any ~~including~~EU ~~certain~~Member ~~healthcare~~State ~~providers~~before. This procedure is available for pharmaceutical products not falling within the mandatory scope of the centralized procedure. The competent authority of a single EU Member State, ~~health~~the ~~plans~~reference member state, is appointed to review the application and ~~healthcare~~provide ~~clearinghouses,~~an asassessment ~~well~~report. asThe ~~their~~competent ~~respective~~authorities ~~“business~~of ~~associates”~~the ~~that~~other ~~create~~EU Member States, ~~receive~~the concerned member states, ~~maintain~~are orsubsequently ~~transmit~~required ~~individually~~to ~~identifiable~~grant ~~health~~a ~~information~~MA for ortheir territories on ~~behalf~~the basis of athis ~~covered~~assessment. ~~entity,~~The ~~and~~only ~~their~~exception ~~covered~~to ~~subcontractors~~this is where the competent authority of an EU Member State considers that there are concerns of potential serious risk to public health, ~~with~~the ~~respect~~disputed points are subject to ~~safeguarding~~a dispute resolution mechanism and may eventually be referred to the ~~privacy~~EC, ~~security~~whose ~~and~~decision ~~transmission~~is ofbinding ~~individually~~for ~~identifiable~~all ~~health~~EU ~~information;~~Member States.

~~•Federal~~Risk ~~drug~~Management price reporting laws, which require manufacturers to calculate and report complex pricing metrics to government programs, where such reported prices may be used in the calculation of reimbursement and/or discounts on approved products; andPlan

~~•Foreign~~All ~~and~~new ~~state~~MAAs ~~law~~must ~~equivalents~~include ofa ~~each~~Risk ofManagement ~~the~~Plan ~~above~~(“RMP”) ~~federal~~describing ~~laws, such as anti-kickback and false claims laws which may apply to items or services reimbursed by any third-party payor, including commercial insurers, state and local laws governing~~ the ~~disclosure~~risk ofmanagement ~~payments~~system ~~to health care professionals, state laws~~ that ~~require pharmaceutical companies to comply with~~ the ~~pharmaceutical~~company ~~industry’s~~will ~~voluntary~~put ~~compliance~~in ~~guidelines~~place and ~~the~~documenting ~~relevant~~measures ~~compliance~~to ~~guidance~~prevent ~~promulgated~~or byminimize the ~~federal~~risks ~~government,~~associated ~~state~~with ~~laws that require~~ the ~~reporting~~product. ofRMPs ~~information~~are ~~related~~continually tomodified ~~drug pricing, state~~ and ~~local~~updated ~~laws~~throughout ~~requiring~~ the ~~registration~~lifetime of ~~pharmaceutical sales representatives and state laws governing~~ the ~~privacy~~medicine ~~and~~as ~~security~~new ~~of health~~ information inbecomes ~~certain~~available. ~~circumstances,~~An ~~many~~updated ofRMP ~~which~~must ~~differ~~be ~~from each other in significant ways and may not have the same effect, thus complicating compliance efforts.~~

Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs. 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 it, we may be subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, exclusion from government funded healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations. If any of the physicians or other healthcare providers or entities with whom we expect to do business is found to be

~~not~~submitted: in(i) ~~compliance~~at ~~with~~the ~~applicable~~request ~~laws~~of EMA or a national competent authority, ~~they~~or ~~may~~(ii) bewhenever ~~subject~~the risk-management system is modified, especially as the result of new information being received that may lead to a significant ~~criminal,~~change ~~civil~~to the benefit-risk profile or ~~administrative~~as ~~sanctions~~a result of an important pharmacovigilance or risk-minimization milestone being reached. The regulatory authorities may also impose specific obligations as a condition of the MA. Since October 20, ~~including~~2023, ~~exclusions~~all ~~from~~RMPs ~~government~~for ~~funded~~centrally ~~healthcare~~authorized ~~programs~~products are published by the EMA, subject only to limited redactions.

MA Validity Period

MAs have an initial duration of five years. After these five years, the authorization may subsequently be renewed on the basis of a reevaluation of the risk-benefit balance. Once renewed, the MA is valid for an unlimited period unless the EC or the national competent authority decides, on justified grounds relating to pharmacovigilance, to proceed with only one additional five-year renewal. Applications for renewal must be made to the EMA at least nine months before the five-year period expires.

Any authorization which is not followed by the actual placing of the drug on the EU market (in case of centralized procedure) or on the market of the authorizing member state within three years after authorization ceases to be valid.

For the UK, the period of three years during which the drug has not been marketed in Great Britain will be restarted from the date of conversion to a Great Britain MA. Following Windsor Framework changes, which became effective January 1, 2025, EC authorizations are no longer valid in Northern Ireland and centrally authorized products are instead authorized by the MHRA under UK-wide marketing authorizations; existing licenses for product licensed by the MHRA that covers Great Britain only become geographically valid UK-wide while retaining their license number/prefix.

On the other hand, for the EU, in the case the drug has been marketed in the UK, the placing on the UK market before the end of the period starting when the UK left the EU on January 31, 2020 and ending on December 31, 2020 (the Brexit Transition Period) will be taken into account. If, after the end of the Brexit Transition Period, the drug is not placed on any other market of the remaining member states of the EU, the three-year period will start running from the last date the drug was placed on the UK market before the end of the Brexit Transition Period.

Advanced Therapy Medicinal Products

In the EU, medicinal products, including advanced therapy medicinal products (“ATMPs”) are subject to extensive pre-and post-market regulation by regulatory authorities at both the EU and national levels. ATMPs comprise gene therapy products, somatic cell therapy products and tissue engineered products, which are genes, cells or tissues that have undergone substantial manipulation and that are administered to human beings in order to cure, diagnose or prevent diseases or regenerate, repair or replace a human tissue. Pursuant to Regulation (EC) No 1394/2007, the Committee for Advanced Therapies (“CAT”) is responsible in conjunction with the CHMP for the evaluation of ATMPs. The CHMP and CAT are also responsible for providing guidelines on ATMPs. These guidelines provide additional guidance on the factors that the EMA will consider in relation to the development and evaluation of ATMPs and include, among other things, the preclinical studies required to characterize ATMPs. Although such guidelines are not legally binding, compliance with them is often necessary to gain and maintain approval for product candidates.

In addition to the mandatory RMP, the holder of a MA for an ATMP must put in place and maintain a system to ensure that each individual product and its starting and raw materials, including all substances coming into contact with the cells or tissues it may contain, can be traced through the sourcing, manufacturing, packaging, storage, transport and delivery to the relevant healthcare institution where the product is used.

Exceptional Circumstances/Conditional Approval

Similar to accelerated approval regulations in the United States, conditional MAs can be granted in the EU in exceptional circumstances. A conditional MA can be granted for medicinal products where, although comprehensive clinical data referring to the safety and efficacy of the medicinal product have not been supplied, a number of criteria are fulfilled: (i) the benefit/risk balance of the product is positive, (ii) it is likely that the applicant will be in a position to provide the comprehensive clinical data, (iii) unmet medical needs will be fulfilled by the grant of the MA and (iv) the benefit to public health of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are still required. Once a conditional MA has been granted, the MA holder must fulfil specific obligations within defined timelines. A conditional MA is valid for one year and must be renewed annually, but it can be converted into a standard MA once the MA holder fulfils the obligations imposed and the complete data confirm that the medicine’s benefits continue to outweigh its risks.

Data and Market Exclusivity

As in the United States, it may be possible to obtain a period of market and / or data exclusivity in the EU that would have the effect of postponing the entry into the marketplace of a competitor’s generic, hybrid or biosimilar product (even if the

pharmaceutical product has already received a MA) and prohibiting another applicant from relying on the MA holder’s pharmacological, toxicological and clinical data in support of another MA for the purposes of submitting an application, obtaining MA or placing the product on the market. Innovative medicinal products, referred to as New Chemical Entities (“NCE”), approved in the EU qualify for eight years of data exclusivity and 10 years of marketing exclusivity.

An additional non-cumulative one-year period of marketing exclusivity is possible if during the data exclusivity period (the first eight years of the 10-year marketing exclusivity period), the MA holder obtains an authorization for one or more new therapeutic indications that are deemed to bring a significant clinical benefit compared to existing therapies.

The data exclusivity period begins on the date of the product’s first MA in the EU. After eight years, a generic product application may be submitted, and generic companies may rely on the MA holder’s data. However, a generic product cannot launch until two years later (or a total of 10 years after the first MA in the EU of the innovator product), or three years later (or a total of 11 years after the first MA in the EU of the innovator product) if the MA holder obtains MA for a new indication with significant clinical benefit within the eight-year data exclusivity period. Additionally, another noncumulative one-year period of data exclusivity can be added to the eight years of data exclusivity where an application is made for a new indication for a well-established substance, provided that significant pre-clinical or clinical studies were carried out in relation to the new indication. Another year of data exclusivity may be added to the eight years, where a change of classification of a pharmaceutical product has been authorized on the basis of significant pre-trial tests or clinical trials (when examining an application by another applicant for or holder of market authorization for a change of classification of the same substance the competent authority will not refer to the results of those tests or trials for one year after the initial change was authorized).

Products may not be granted data exclusivity since there is no guarantee that a product will be considered by the EU’s regulatory authorities to include a NCE. Even if a compound is considered to be a NCE and the MA applicant is able to gain the prescribed period of data exclusivity, another company nevertheless could also market another version of the medicinal product if such company can complete a full MAA with their own complete database of pharmaceutical tests, preclinical studies and clinical trials and obtain MA of its product.

On April 26, 2023, the EC submitted a proposal for the reform of the European pharmaceutical legislation and negotiations are still ongoing. The timing for finalization of these negotiations and entry into force are unclear. The current drafts envisage (i) a shortening of the periods of data exclusivity from eight to six years (with transferrable vouchers for an additional year of market protection as an incentive for the development of new antibiotics), (ii) earlier regulatory guidance and extension of market exclusivity for orphan medicines (depending on certain conditions), (iii) four-year data exclusivity for additional indications of existing products, and (iv) rules governing the availability of products (including shortage prevention plans and some supply obligations for manufacturers).

Orphan Designation and Exclusivity

The criteria for designating an orphan medicinal product in the EU are similar in principle to those in the United States. The EMA grants orphan drug designation if the medicinal product is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting no more than five in 10,000 persons in the EU (prevalence criterion). In addition, Orphan Drug Designation can be granted if, for economic reasons, the medicinal product would be unlikely to be developed without incentives and if there is no other satisfactory method approved in the EU of diagnosing, preventing, or treating the condition, or if such a method exists, the proposed medicinal product is a significant benefit to patients affected by the condition. An application for orphan drug designation (which is not a MA, as not all orphan-designated medicines reach the authorization application stage) must be submitted first before an application for MA of the medicinal product is submitted. The applicant will receive a fee reduction for the MAA if the orphan drug designation has been granted, but not if the designation is still pending at the time the MA is submitted, and sponsors must submit an annual report to EMA summarizing the status of development of the medicine. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process. Designated orphan medicines are eligible for conditional MA.

The EMA’s Committee for Orphan Medicinal Products (“COMP”) reassesses the orphan drug designation of a product in parallel with the review for a MA; for a product to benefit from market exclusivity it must maintain its orphan drug designation at the time of MA review by the EMA and approval by the EC. Additionally, any MA granted for an orphan medicinal product must only cover the therapeutic indication(s) that are covered by the orphan drug designation. Upon the grant of a MA, orphan drug designation provides up to ten years of market exclusivity in the orphan indication.

During the 10-year period of market exclusivity, with a limited number of exceptions, the regulatory authorities of the EU Member States and the EMA may not accept applications for MA, accept an application to extend an existing MA or grant a

MA for other similar medicinal products for the same therapeutic indication. A similar medicinal product is defined as a medicinal product containing a similar active substance or substances as contained in a currently authorized orphan medicinal product, and which is intended for the same therapeutic indication. An orphan medicinal product can also obtain an additional two years of market exclusivity for an orphan-designated condition when the results of specific studies are reflected in the Summary of Product Characteristics (“SmPC”) addressing the pediatric population and completed in accordance with a fully compliant Pediatric Investigation Plan (“PIP”). No extension to any supplementary protection certificate can be granted on the basis of pediatric studies for orphan indications.

The 10-year market exclusivity may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan designation, i.e. the condition prevalence or financial returns criteria under Article 3 of Regulation (EC) No. 141/2000 on orphan medicinal products. When the period of orphan market exclusivity for an indication ends, the orphan drug designation for that indication expires as well. Orphan exclusivity runs in parallel with normal rules on data exclusivity and market protection. Additionally, a MA may be granted to a similar medicinal product (orphan or not) for the same or overlapping indication subject to certain requirements.

In the UK, following the post-Brexit transition period, a system for incentivizing the development of orphan medicines was introduced. Overall, the requirements for orphan designation largely replicate the requirements in the EU and the benefit of market exclusivity has been retained. Products with an orphan designation in the EU can be considered for an orphan MA in Great Britain and, marketing authorizations granted for products that fulfil UK orphan criteria are valid UK-wide regardless of whether there is an EU orphan designation. The MHRA will review applications for orphan designation at the time of a MA, and will offer incentives, such as market exclusivity and full or partial refunds for MA fees to encourage the development of medicines in rare diseases. Separately, the MHRA has stated that it is considering updating its licensing framework for orphan medicines, with a draft framework expected by spring 2026.

Pediatric Development

In the EU, companies developing a new medicinal product are obligated to study their product in children and must therefore submit a PIP together with a request for agreement to the EMA. The EMA issues a decision on the PIP based on an opinion of the EMA’s Pediatric Committee (“PDCO”). Companies must conduct pediatric clinical trials in accordance with the PIP approved by the EMA, unless a deferral (e.g. until enough information to demonstrate its effectiveness and safety in adults is available) or waiver (e.g. because the relevant disease or condition occurs only in adults) has been granted by the EMA. The MAA for the medicinal product must include the results of all pediatric clinical trials performed and details of all information collected in compliance with the approved PIP, unless a waiver or a deferral has been granted, in which case the pediatric clinical trials may be completed at a later date. Medicinal products that are granted a MA on the basis of the pediatric clinical trials conducted in accordance with the approved PIP are eligible for a six month extension of the protection under a supplementary protection certificate (if any is in effect at the time of approval) or, in the case of orphan medicinal products, a two year extension of the orphan market exclusivity. This pediatric reward is subject to specific conditions and is not automatically available when data in compliance with the approved PIP are developed and submitted. An approved PIP is also required when a MA holder wants to add a new indication, medicinal form or route of administration for a medicine that is already authorized and covered by intellectual property rights.

In the UK, the MHRA has published guidance on the procedures for UK Paediatric Investigation Plans (“PIPs”) which, where possible, mirror the submission format and requirements of the EU system. From January 1, 2025, EU pediatric requirements are addressed via Windsor Framework categorization: for Category 2 products, both UK and EU pediatric requirements apply, and an EU-agreed PIP must also be in place (unless waived).

PRIME Designation

In March 2016, the EMA launched an initiative to facilitate development of product candidates in indications, often rare, for which few or no therapies currently exist. The Priority Medicines (“PRIME”) scheme is intended to encourage drug development in areas of unmet medical need and provides accelerated assessment of products representing substantial innovation reviewed under the centralized procedure. Products from small-and medium-sized enterprises may qualify for earlier entry into the PRIME scheme than larger companies on the basis of compelling non-clinical data and tolerability data from initial clinical trials. Many benefits accrue to sponsors of product candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements, and potentially accelerated MAA assessment once a dossier has been submitted. Importantly, once a candidate medicine has been selected for the PRIME scheme, a dedicated contact point and rapporteur from the CHMP or from CAT are appointed facilitating increased understanding of the product at EMA’s Committee level. A kick-off meeting with the CHMP/CAT rapporteur initiates these relationships and includes a team of multidisciplinary experts to provide guidance on the

overall development plan and regulatory strategy. PRIME eligibility does not change the standards for product approval, and there is no assurance that any such designation or eligibility will result in expedited review or approval.

Post-Approval Regulation

Similar to the United States, both MA holders and manufacturers of medicinal products are subject to comprehensive regulatory oversight by the EMA, the EC and/or the competent regulatory authorities of the EU Member States. This oversight applies both before and after grant of manufacturing licenses and MAs. It includes control of compliance with EU good manufacturing practices rules, manufacturing authorizations, pharmacovigilance rules and requirements governing advertising, promotion, sale, and distribution, recordkeeping, importing and exporting of medicinal products.

Failure by us or by any of our third-party partners, including suppliers, manufacturers and distributors to comply with EU laws and the related national laws of individual EU Member States governing the conduct of clinical trials, manufacturing approval, MA of medicinal products and marketing of such products, both before and after grant of MA, statutory health insurance, bribery and anti-corruption or other applicable regulatory requirements may result in administrative, civil or criminal penalties. These penalties could include delays or refusal to authorize the conduct of clinical trials or to grant MA, product withdrawals and recalls, product seizures, suspension, withdrawal or variation of the MA, total or partial suspension of production, distribution, manufacturing or clinical trials, operating restrictions, injunctions, suspension of licenses, fines and criminal penalties.

The holder of a MA for a medicinal product must also comply with EU pharmacovigilance legislation and its related regulations and guidelines, which entail many requirements for conducting pharmacovigilance, or the assessment and monitoring of the safety of medicinal products.

These pharmacovigilance rules can impose on holders of MAs the obligation to conduct a labor intensive collection of data regarding the risks and benefits of marketed medicinal products and to engage in ongoing assessments of those risks and benefits, including the possible requirement to conduct additional clinical studies or post-authorization safety studies to obtain further information on a medicine’s safety, or to measure the effectiveness of risk-management measures, which may be time consuming and expensive and could impact our profitability. MA holders must establish and maintain a pharmacovigilance system and appoint an individual qualified person for pharmacovigilance, who is responsible for oversight of that system. Key obligations include expedited reporting of suspected serious adverse reactions and submission of Periodic Safety Update Reports (“PSURs”) in relation to medicinal products for which they hold MAs. The EMA reviews PSURs for medicinal products authorized through the centralized procedure. If the EMA has concerns that the risk benefit profile of a product has varied, it can adopt an opinion advising that the existing MA for the product be suspended, withdrawn or varied. The agency can advise that the MA holder be obliged to conduct post-authorization Phase IV safety studies. If the EC agrees with the opinion, it can adopt a decision varying the existing MA. Failure by the MA holder to fulfill the obligations for which the EC’s decision provides can undermine the ongoing validity of the MA.

More generally, non-compliance with pharmacovigilance obligations can lead to the variation, suspension or withdrawal of the MA for the product or imposition of financial penalties or other enforcement measures.

The manufacturing process for pharmaceutical products in the EU is highly regulated and regulators may shut down manufacturing facilities that they believe do not comply with regulations.

Manufacturing requires a manufacturing authorization, and the manufacturing authorization holder must comply with various requirements set out in the applicable EU laws, regulations and guidance, including Directive 2001/83/EC, Directive 2003/94/EC (repealed by Directive 2017/1572 on January 31, 2022), Regulation (EC) No 726/2004 and the European Commission Guidelines for Good Manufacturing Practice. These requirements include compliance with EU GMP standards when manufacturing pharmaceutical products and active pharmaceutical ingredients, including the manufacture of active pharmaceutical ingredients outside of the EU with the intention to import the active pharmaceutical ingredients into the EU. Amendments or replacements of at least Directive 2001/83/EC and Regulation (EC) No 726/2004 are part of the reform proposal for European pharmaceutical legislation. Similarly, the distribution of pharmaceutical products into and within the EU is subject to compliance with the applicable EU laws, regulations and guidelines, including the requirement to hold appropriate authorizations for distribution granted by the competent authorities of the EU Member States. The manufacturer or importer must have a qualified person who is responsible for certifying that each batch of product has been manufactured in accordance with GMP, before releasing the product for commercial distribution in the EU or for use in a clinical trial. Manufacturing facilities are subject to periodic inspections by the competent authorities for compliance with GMP.

On October 27, 2025, the Council of the EU approved a framework for compulsory licensing of crisis-relevant products (including medicinal products) in crisis situations. While the proposal focuses on voluntary agreements with intellectual property rights holders, it includes rules on compulsory licensing as a measure of last resort upon activation / declaration of a crisis or emergency mode. The European Parliament has not yet voted on the proposal.

Sales and Marketing Regulations

The advertising and promotion of our products is also subject to EU laws concerning promotion of medicinal products, interactions with physicians, misleading and comparative advertising and unfair commercial practices. In addition, other national legislation of individual EU Member States may apply to the advertising and promotion of medicinal products and may differ from one country to another. These laws require that promotional materials and advertising in relation to medicinal products comply with the product’s SmPC as approved by the competent regulatory authorities. The SmPC is the document that provides information to physicians concerning the safe and effective use of the medicinal product. It forms an intrinsic and integral part of the MA granted for the medicinal product. Promotion of a medicinal product that does not comply with the SmPC is considered to constitute off-label promotion. All advertising and promotional activities for the product must be consistent with the approved SmPC and therefore all off-label promotion is prohibited. Direct-to-consumer advertising of prescription-only medicines is also prohibited in the EU. Violations of the rules governing the promotion of medicinal products in the EU could be penalized by administrative measures, fines and imprisonment. These laws may further limit or restrict the advertising and promotion of our products to the general public and may also impose limitations on its promotional activities with healthcare professionals. EU regulation with regards to dispensing, sale and purchase of medicines has generally been preserved in the UK following Brexit, through the Human Medicines Regulations. However, organizations wishing to sell medicines online need to register with the MHRA. Following Brexit, the requirements to display the common logo no longer apply to UK-based online sellers, except for those established in Northern Ireland.

Anti-Corruption Legislation

In the EU, interactions between pharmaceutical companies and physicians are also governed by strict laws, regulations, industry self-regulation codes of conduct and physicians’ codes of professional conduct both at EU level and in the individual EU Member States. 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 EU. The provision of benefits or advantages to physicians is also governed by the national anti-bribery laws of the EU Member States. Violation of these laws could result in substantial fines and imprisonment.

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

In the UK, the pharmaceutical sector is recognized as being particularly vulnerable to corrupt practices, some of which fall within the scope of the Bribery Act 2010. Due to the Bribery Act 2010’s far-reaching territorial application, the potential penalized act does not have to occur in the UK to become within its scope. If the act or omission does not take place in the UK, but the person’s act or omission would constitute an offense if carried out there and the person has a close connection with the UK, an offense will still have been committed.

The Bribery Act 2010 is comprised of four offenses that cover (i) individuals, companies and partnerships that give, promise or offer bribes, (ii) individuals, companies and partnerships that request, agree to receive or accept bribes, (iii) individuals, companies and partnerships that bribe foreign public officials and (iv) companies and partnerships that fail to prevent persons acting on their behalf from paying bribes. The penalties imposed under the Bribery Act 2010 depend on the offence committed, harm and culpability and penalties range from unlimited fines to imprisonment for a maximum term of ten years and in some cases both.

Regulations in the UK and Other Markets

The UK formally left the EU on January 31, 2020 and EU laws now only apply to the UK in respect of Northern Ireland as laid out in the protocol on Ireland and Northern Ireland and as amended by the Windsor Framework sets out a long-term set of arrangements for the supply of medicines into Northern Ireland. The EU and the UK agreed on a trade and cooperation agreement, which includes provisions affecting the life sciences sector (including on customs and tariffs). There are some specific provisions concerning pharmaceuticals, including the mutual recognition of GMP, inspections of manufacturing

facilities for medicinal products and GMP issued documents. The TCA does not, however, contain wholesale mutual recognition of UK and EU pharmaceutical regulations and product standards.

The UK government has adopted the Medicines and Medical Devices Act 2021 (the “MMDA”) to enable the UK’s regulatory frameworks to be updated following the UK’s departure from the EU. The MMDA introduces regulation-making, delegated powers covering the fields of human medicines, clinical trials of human medicines, veterinary medicines and medical devices. The MHRA has since been consulting on future regulations for medicines and medical devices in the UK.

For other countries outside of the EU, such as countries in Eastern Europe, Latin America or Asia, the requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country. In all cases, again, the clinical trials must be conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension of clinical trials, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.

Additional Regulation

In addition to the foregoing, local, state and federal laws regarding such matters as safe working conditions, manufacturing practices, environmental protection, fire hazard control and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservancy and Recovery Act and the Toxic Substances Control Act, affect our business. These and other laws govern our use, handling and disposal of various biological, chemical and radioactive substances used in, and wastes generated by, our operations. If our operations result in contamination of the environment or expose individuals to hazardous or biohazardous substances, we could be liable for damages, environmental remediation, and/or governmental fines. We believe that we are in material compliance with applicable environmental laws and occupational health and safety laws that continued compliance therewith will not have a material adverse effect on our business. We cannot predict, however, how changes in these laws may affect our future operations. We may incur significant costs to comply with such laws and regulations now or in the future.

Human Capital Policies and Procedures

As of December 31, ~~2024~~2025, we had ~~143~~45 full-time employees. Of these employees, 8429 were engaged in research and development and 5916 were engaged in ~~selling,~~ general and administrative functions. In February 2025, as part of the 2025 Restructuring, we implemented a net reduction of our employee headcount by 43 employees. All of our employees, for fiscal year 2024 were located in the United States or Vienna, Austria. We have no collective bargaining agreements with our employees and have not experienced any work stoppages. We consider our relationship with our employees to be good. ~~As of March 1, 2025, we had approximately 100 employees in the United States.~~

Human capital is critical to our success. Our overarching human capital resource strategy is to recruit, hire, incentivize and retain employees consistent with our stage of operations and strategic objectives. We believe we offer our employees compensation that is competitive and consistent with the markets in which we operate, namely the Greater Boston metropolitan area. We supplement base cash employee compensation with awards of stock options and/or restricted stock units under our equity incentive plans. We review employee performance annually and our Compensation Committee approves associated merit increases and annual incentive bonus payments during the first quarter of the year annually. When needed, we augment our employee base with outside consultants who specialize in various fields.

Corporate Information ~~and Trademarks~~

WeOur ~~were~~website ~~incorporated~~address ~~under~~is ~~the~~located ~~laws~~at ofwww.x4pharma.com; however, the ~~State~~information ofin, ~~Delaware~~or inthat ~~2010~~can ~~under~~be ~~the~~accessed ~~name~~through, ~~Arsanis~~our ~~Inc.~~website ~~Following~~is ~~the~~not ~~merger~~part ~~with~~of X4or ~~Therapeutics~~incorporated ~~Inc.~~by ~~(formerly~~reference X4into ~~Pharmaceuticals~~this ~~Inc.)~~Annual Report on ~~March~~Form 1310-K, ~~2019,~~and weany ~~changed~~references to our ~~name~~website are intended to X4be ~~Pharmaceuticals,~~inactive ~~Inc~~textual references only provided for convenience. ~~Our~~We ~~principal~~make ~~executive~~available ~~offices~~free ~~are~~of ~~located~~charge aton 61our ~~North~~website ~~Beacon~~our ~~Street~~Annual Reports on Form 10-K, ~~4th~~Quarterly ~~Floor~~Reports on Form 10-Q, ~~Boston~~Current Reports on Form 8-K, ~~Massachusetts~~and ~~02134~~amendments to those reports, and ~~our~~other ~~telephone~~filings ~~number~~pursuant isto Section 13(~~857~~a) ~~529-8300~~or 15(d) of the Exchange Act, as soon as reasonably practicable after each is electronically filed with, or furnished to, the SEC. The SEC maintains an Internet site that contains reports, proxy and information statements, and other information regarding reports that we file or furnish electronically with them at www.sec.gov.

WeThis ~~view~~Annual ~~our~~Report ~~operations~~on ~~and~~Form ~~measure~~10-K includes our ~~business~~trademarks asand ~~one~~registered ~~reportable segment. All of the Company’s tangible assets are held in the United States. Refer to Note 2~~trademarks, ~~Summary~~including of“XOLREMDI” ~~Significant~~Each ~~Accounting~~other ~~Policies~~trademark, totrade ~~our~~name ~~financial~~or ~~statements~~service mark appearing ~~elsewhere~~ in this Annual Report on Form 10-K ~~for~~belongs ~~additional~~to ~~information~~their respective holders.

We own or have rights to various trademarks, service marks and trade names that we use in connection with the operation of our business. This Annual Report on Form 10-K may also contain trademarks, service marks and trade names of third parties, which are the property of their respective owners. Our use or display of third parties’ trademarks, service marks, trade names or products in this Annual Report on Form 10-K is not intended to, and does not imply a relationship with, or endorsement or sponsorship by us. Solely for convenience, the trademarks, service marks and trade names referred to in this Annual Report on Form 10-K may appear without the ®, ™ or SM symbols, but the omission of such references is not intended to indicate, in any way, that we will not assert, to the fullest extent under applicable law, our rights or the right of the applicable owner of these trademarks, service marks and trade names.32

~~Available~~Item 1A. Risk ~~Information~~ Factors

WeAn ~~maintain~~investment in our securities involves a ~~website~~high atdegree ~~http://www~~of risk.~~x4pharma.com.~~ ~~Our~~You ~~annual~~should ~~reports~~carefully onconsider ~~Form~~the ~~10-K~~following information about these risks, ~~quarterly~~together ~~reports~~with onthe ~~Form~~other ~~10-Q,~~information ~~proxy~~appearing ~~statements~~elsewhere in this Annual Report, ~~current~~including ~~reports~~our onaudited ~~Form~~consolidated ~~8-K~~financial statements and ~~amendments~~related tonotes ~~those~~hereto, ~~reports~~before ~~filed~~deciding orto ~~furnished~~invest ~~pursuant~~in toour ~~Section~~common ~~13(a)~~stock. orThe ~~15(d)~~occurrence of any of the ~~Exchange~~following ~~Act~~risks ~~are~~could ~~available~~have ~~free~~a ofmaterial ~~charge~~adverse effect on our ~~website~~business, asfinancial ~~soon~~condition, asresults ~~reasonably~~of ~~practicable~~operations ~~after~~and ~~electronically~~future ~~filing~~growth ~~such~~prospects, ~~reports~~or ~~with~~cause ~~the~~our ~~SEC.~~actual ~~Such~~results ~~reports~~to differ materially from those contained in forward-looking statements we have made in this report and ~~other~~those ~~information~~we may bemake ~~accessed~~from ~~through~~time to time. The risks and uncertainties described below are not the ~~SEC’s~~only ~~website~~ones atfacing ~~www~~us.~~sec.gov.~~ WeAdditional dorisks and uncertainties not ~~incorporate~~presently ~~the~~known ~~information~~to onus, or ~~accessible~~that ~~through~~we currently see as immaterial, may also adversely affect our ~~website~~business. ~~into~~In ~~this~~these ~~Annual~~circumstances, ~~Report~~the onmarket ~~Form~~price ~~10-K~~of our common stock could decline, and you ~~should~~may ~~not~~lose ~~consider~~all ~~any~~or ~~information~~part ~~on,~~of oryour investment. We cannot assure you that ~~can~~any beof ~~accessed~~the ~~through,~~events discussed below will not occur. The disclosures in this section reflect our ~~website~~beliefs and opinions as to befactors ~~part~~that ofcould ~~this~~materially ~~Annual~~and ~~Report~~adversely onaffect ~~Form~~us ~~10-K~~in the future. WeReferences to past events are provided by way of example only and are not intended to be a complete listing or a representation as to whether or not such factors have ~~included~~occurred ~~our~~in ~~website~~the ~~address~~past. The information discussed below should be considered carefully with the other information contained in this Annual Report on Form 10-K ~~solely~~and the other documents and materials we file with the SEC, as anwell ~~inactive~~as ~~textual~~news ~~reference~~releases and other information we publicly disseminate from time to time.

ITEM 1A. RISK FACTORS

An investment in our securities involves a high degree of risk. You should carefully consider the following information about these risks, together with the other information appearing elsewhere in this Annual Report, including our audited consolidated financial statements and related notes hereto, before deciding to invest in our common stock. The occurrence of any of the following risks could have a material adverse effect on our business, financial condition, results of operations and future growth prospects, or cause our actual results to differ materially from those contained in forward-looking statements we have made in this report and those we may make from time to time. In these circumstances, the market price of our common stock could decline, and you may lose all or part of your investment. We cannot assure you that any of the events discussed below will not occur.

Summary of Selected Risks Associated with Our Business

Our business faces significant risks and uncertainties. If any of the following risks are realized, our business, financial condition and results of operations could be materially and adversely affected. You should carefully review and consider the full discussion of our risk factors in the section titled “Risk Factors” in Part I, Item 1A of this Annual Report. Some of the more significant risks include the following:

•WeUntil ~~have~~we ~~incurred~~achieve ~~significant~~profitability, ~~losses and have not generated significant revenue from product sales since~~ our ~~inception~~operations ~~and we cannot predict whether or when and if we~~ will berequire ~~able~~substantial toadditional ~~generate~~funding. ~~meaningful~~Our ~~revenues~~history ~~from sales~~ of ~~XOLREMDI~~recurring atlosses ~~levels or on timing necessary to support our operational costs~~ and ~~commercial~~anticipated ~~goals.~~future ~~Our~~expenditures ~~ability~~could toraise ~~generate~~substantial ~~revenue~~doubts ~~and~~about ~~become profitable depends upon~~ our ability to ~~successfully~~continue ~~commercialize~~as ~~XOLREMDI~~a ~~and~~going ~~to obtain marketing approval and commercialize of our product candidates, including mavorixafor, or other product candidates that we may develop, in-license or acquire in the future~~concern. ~~Even~~If if we are ~~able~~unable to ~~successfully~~raise ~~achieve~~capital ~~regulatory~~when ~~approval for these potential product candidates~~needed, we ~~are~~could ~~unable~~be forced to ~~predict~~delay, ~~the~~reduce ~~extent~~or ofeliminate any ~~future losses and do not know when any of these potential~~ product ~~candidates~~development ~~will~~programs ~~generate revenue for us, if at all. We expect to continue to incur losses for the foreseeable future, and we may never achieve~~ or ~~maintain~~commercialization ~~profitability~~efforts.

•~~Our~~We ~~liquidity~~have ~~position~~incurred ~~raises~~significant ~~substantial~~losses ~~doubt~~and ~~about~~have ~~our~~not ~~ability~~generated tosignificant ~~continue~~revenue asfrom aproduct ~~going~~sales ~~concern~~since ~~and~~our ~~we will require substantial additional funding~~inception. IfWe weexpect ~~are~~to ~~unable~~continue to ~~raise~~incur ~~capital~~losses ~~when~~for ~~needed,~~the weforeseeable ~~could~~future beand ~~forced~~we tomay ~~delay,~~never ~~reduce~~achieve or ~~eliminate~~maintain ~~any product development programs or commercialization efforts~~profitability.

•Raising additional capital may cause dilution to our investors, restrict our operations or require us to relinquish rights to our technologies or product candidates. Future debt obligations may expose us to risks that could adversely affect our business, operating results and financial condition and may result in further dilution to our stockholders.

•WeChanges ~~depend~~in ~~almost~~estimates ~~entirely~~regarding onfair ~~the~~value ~~success~~ of ~~our~~intangible ~~commercial~~assets ~~product,~~may ~~XOLREMDI~~result ~~and~~in onan ~~our~~adverse ~~development~~impact ~~product~~on ~~candidate,~~our ~~mavorixafor,~~results ~~which we are advancing for the potential treatment~~ of ~~other chronic neutropenic disorders~~operations. We cannot be certain that we will be able to obtain regulatory approval for or successfully commercialize, mavorixafor for other chronic neutropenic disorders or any other product candidate for other indications.

•~~The~~We ~~regulatory~~have ~~review~~not ~~and~~generated ~~approval~~significant ~~processes~~revenues offrom ~~the~~product ~~FDA~~sales ~~and~~since ~~comparable~~inception ~~foreign~~and ~~regulatory~~may ~~authorities~~never ~~are~~become ~~lengthy,~~profitable. ~~time-consuming~~We ~~and~~may ~~inherently~~never ~~unpredictable,~~be ~~and~~able ifto wegenerate ~~are~~meaningful ~~ultimately~~revenues ~~unable~~from tosales ~~obtain~~of ~~regulatory approval for~~ our ~~commercial~~ product, ~~XOLREMDI~~candidates and ~~product~~approved ~~candidates,~~commercial ~~including~~products ~~additional~~at ~~indications~~levels ~~for~~or ~~mavorixafor,~~on ~~our~~timing ~~business~~necessary ~~will~~to besupport ~~substantially~~our ~~harmed~~investment and goals.

•WeIf ~~depend~~the oncommercial ~~license~~opportunity ~~agreements,~~for ~~including~~mavorixafor ain ~~license~~chronic ~~agreement~~neutropenic ~~with~~(“CN”) ~~Genzyme,~~disorders tois ~~permit~~smaller usthan towe ~~use~~anticipate, ~~patents~~our ~~and~~potential ~~patent~~future ~~applications.~~revenue ~~Termination~~from ofmavorixafor ~~these~~for ~~rights or~~ the ~~failure~~treatment toof ~~comply~~any ~~with~~of ~~obligations under~~ these ~~agreements~~diseases ~~could~~may ~~materially~~be ~~harm~~adversely ~~our~~affected ~~business~~ and ~~prevent us from developing or commercializing~~ our ~~product~~business ~~candidates~~may suffer.

•IfWe depend almost entirely on the ~~commercial~~success ~~opportunity~~of ~~for~~our future product candidate, mavorixafor. inWe ~~WHIM~~cannot ~~syndrome~~be ~~and~~certain ~~other~~that ~~chronic~~we ~~neutropenic~~will ~~disorders~~be isable ~~smaller~~to ~~than~~obtain weregulatory ~~anticipate~~approval for, ~~our~~or ~~potential~~successfully ~~future~~commercialize, ~~revenue~~mavorixafor ~~from~~for ~~mavorixafor~~disorders ~~may~~other bethan ~~adversely~~WHIM, ~~affected~~including ~~and~~CN, ~~our~~or ~~business~~any ~~may~~other ~~suffer~~product candidate.

•~~Interim~~We ~~top-line and preliminary data from our clinical trials that we announce or publish from time to time~~ may ~~change~~develop asmavorixafor, ~~more patient data become available~~ and ~~are~~future ~~subject~~product tocandidates, ~~audit~~in ~~and~~combination ~~verification~~with ~~procedures~~other ~~that~~therapies, which could ~~result~~expose inus ~~material~~to ~~changes~~additional ~~in the final data~~risks.

2833

•Our product candidates that have received regulatory approval may still face future development and regulatory difficulties and any approved products will be subject to extensive post-approval regulatory requirements. Additionally, ~~any~~our approved product, ~~candidate~~XOLREMDI, ~~for~~and ~~which~~future weapproved ~~obtain~~products, ~~marketing~~if ~~approval~~any, could be subject to marketing restrictions or withdrawal from the market, and we may be subject to penalties if we fail to comply with regulatory requirements or if we experience unanticipated problems with our products.

•The ~~FDA~~Food and ~~other~~Drug ~~domestic~~Administration (“FDA”) and ~~foreign~~other regulatory agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses. If we are found or alleged to have improperly promoted off-label uses, we may become subject to significant liability.

•Our commercial ~~products~~success ~~may~~depends ~~become~~upon ~~subject~~attaining tosignificant ~~unfavorable~~market ~~pricing~~acceptance ~~regulations,~~of ~~third-party~~our ~~reimbursement~~approved ~~practices~~product or ~~healthcare~~product ~~reform~~candidates, ~~initiatives~~if approved, ~~which~~among ~~would~~hospitals, ~~harm~~physicians, ~~our~~patients ~~business~~and healthcare payors.

•WeIf ~~have~~we ~~limited~~are ~~experience~~unable ~~manufacturing~~to ~~our~~maintain ~~product~~effective ~~candidates~~sales onand amarketing ~~large~~capabilities ~~clinical~~ or ~~commercial~~to ~~scale~~selectively ~~and~~enter ~~have~~into noagreements ~~manufacturing~~with ~~facility. We are currently dependent on a single~~ third~~-party~~ ~~manufacturer~~parties ~~for~~to ~~the~~sell ~~manufacture of mavorixafor, the active pharmaceutical ingredient (“API”)~~ and amarket ~~single~~our ~~manufacturer~~product ofor ~~mavorixafor finished drug~~ product ~~capsules.~~candidates, If we ~~experience~~may ~~problems~~not ~~with~~be ~~these~~successful ~~third~~in ~~parties,~~commercializing ~~the~~our ~~manufacturing~~product ofcandidates ~~mavorixafor~~that ~~could~~have bebeen ~~delayed, which could harm our results of operations~~approved.

•WeOur ~~rely~~relationships onwith customers and third-party ~~contract~~payors ~~research~~are ~~organizations~~subject ~~(“CROs”)~~ to ~~conduct~~applicable ~~our~~anti-kickback, ~~preclinical~~fraud ~~studies~~ and ~~clinical~~abuse ~~trials.~~and Ifother ~~these~~healthcare ~~CROs~~laws doand ~~not~~regulations, ~~successfully~~which ~~carry~~could ~~out~~expose ~~their~~us ~~contractual~~to ~~duties~~significant orpenalties, ~~meet~~including ~~expected deadlines~~administrative, wecivil ~~may~~and ~~not~~criminal bepenalties, ~~able~~contractual todamages, ~~obtain~~reputational ~~regulatory~~harm ~~approval~~and ~~for~~diminished orprofits ~~commercialize our product candidates~~ and ~~our~~future ~~business could be substantially harmed~~earnings.

•Current and future legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product or product candidates and affect the prices we may obtain.

•We are subject to anti-corruption laws, as well as export control laws, customs laws, sanctions laws and other laws governing our operations. If we fail to comply with these laws, we could be subject to civil or criminal penalties, other remedial measures and legal expenses, which could adversely affect its business, results of operations and financial condition.

•We have limited experience manufacturing our product or product candidates on a large clinical or commercial scale and have no manufacturing facility. We are currently dependent on a single third-party manufacturer for the manufacture of the active pharmaceutical ingredient (“API”) for mavorixafor, and a single manufacturer of mavorixafor finished drug product capsules. If we experience problems with these third parties, the manufacturing of mavorixafor could be delayed, which could harm our results of operations.

•We rely on third-party clinical research organizations (“CROs”) to conduct our preclinical studies and clinical trials. If these CROs do not successfully carry out their contractual duties or meet expected deadlines, we may not be able to obtain regulatory approval for or commercialize our product candidates and our business could be substantially harmed.

•Disruptions in our supply chain could delay the commercial sale of our product.

•Our employees, principal investigators, CROs, CMOs and consultants may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could have a material adverse effect on our business.

•Recent laws and rulings by U.S. courts make it difficult to predict how patents will be issued or enforced in our industry.

•If we are unable to protect our intellectual property rights, our competitive position could be harmed.

•~~Third~~We ~~parties~~could ~~may~~be ~~initiate~~required ~~legal~~to ~~proceedings~~incur ~~alleging~~significant ~~that~~expenses weto ~~are~~obtain ~~infringing~~our ~~their~~ intellectual property rights, ~~the outcome of which would be uncertain~~ and ~~could~~we ~~have~~cannot aensure ~~material~~that ~~adverse~~we ~~effect~~will onobtain ~~the~~meaningful ~~success~~patent ofprotection for our ~~business~~product candidates.

•~~Our~~Obtaining ~~term~~and ~~loan~~maintaining ~~contains~~our ~~restrictions~~patent ~~that~~protection ~~limit~~depends ~~our~~on ~~flexibility~~compliance inwith ~~operating~~various procedural, documentary, fee payment and other requirements imposed by governmental patent agencies, and our ~~business~~patent protection could be reduced or eliminated for non-compliance with these requirements.

•Our future success depends on our ability to retain executives and to attract, retain and motivate key personnel in a competitive environment for skilled biotechnology personnel.

•We may experience difficulties in managing the reduction in size of our organization due to our restructuring activities, and we may not achieve the expected benefits of such activities.

•The pharmaceutical industry is highly competitive and is subject to rapid and significant technological change, which could render our technologies and products obsolete or uncompetitive.

•Our internal information technology systems and infrastructure, or those of our contractors, consultants, or other third parties, may be subject to cyber attacks, or data breaches, compromises, or other security incidents, which could result in additional costs, loss of revenue, significant liabilities, harm to our reputation, and disruption of our development programs and operations.

•Although we are currently in compliance with the Nasdaq continued listing requirements, if we are unable to maintain compliance with Nasdaq’s listing requirements, our securities could be delisted, which could affect our common stock’s market price and liquidity and reduce our ability to raise capital.

•Our stock price has been and is likely to continue to be volatile and fluctuate substantially.

•“Penny stock” rules may make buying or selling our securities difficult which may make our stock less liquid and make it harder for investors to buy and sell our securities.

•If securities analysts do not publish research or reports about our business or if they publish negative evaluations of our stock, the price of our stock could decline.

Risks Related to Our Financial Position and Need for Additional Capital

Until we achieve profitability, our operations will require substantial additional funding. Our history of recurring losses and anticipated future expenditures could raise substantial doubts about our ability to continue as a going concern. If we are unable to raise capital when needed, we could be forced to delay, reduce or eliminate any product development programs or commercialization efforts.

Our operations have consumed a large amount of cash since inception. To date, we have funded our operations primarily with proceeds from sales of common stock, warrants, prefunded warrants, and preferred stock, proceeds from the issuance of convertible debt and borrowings under loan and security agreements. We expect to continue to incur research and development expenses as we continue to advance the clinical development of our product candidates and prepare for the launch and commercialization of any product candidates for which we receive regulatory approval. We expect to incur significant commercialization expenses related to product sales, marketing, distribution and manufacturing. Furthermore, we expect to continue to incur costs associated with operating as a public company.

As of December 31, 2025, we have cash and cash equivalents of $217.0 million and short-term marketable securities of $35.9 million, which provides funding for our operations into 2028. Until we become profitable, our operations will require us to obtain additional funding in the future. If we are unable to obtain sufficient funding when needed in the future, our business, prospects, financial condition and results of operations will be materially and adversely affected, and we may be unable to continue as a going concern. Such additional funding may include raising funds through public or private equity or debt financings, third-party funding, marketing and distribution arrangements, as well as other collaborations, strategic alliances and licensing arrangements, or any combination of these approaches. If we are unable to raise capital when needed or on acceptable terms, we would be forced to delay, limit, reduce, restructure or terminate our product development or future commercialization efforts of one or more of our product candidates, or may be forced to reduce, restructure or terminate our operations. If we are unable to continue as a going concern, we may have to liquidate our assets and may receive less than the value at which those assets are carried on our audited financial statements, and it is likely that investors will lose all or a part of their investment. In our own future required quarterly assessments, we may again conclude that there is substantial doubt about our ability to continue as a going concern, and future reports from our independent registered public accounting firm may also contain statements expressing substantial doubt about our ability to continue as a going concern. If we seek additional financing to fund our business activities in the future and there exists substantial doubt about our ability to continue as a going concern, investors or other financing sources may be unwilling to provide additional funding to us on commercially reasonable terms, if at all.

Although we believe our current cash, cash equivalents and short-term marketable securities, together with our expected decrease in annual spending under our previously announced February 2025 Restructuring and September 2025 Restructuring, respectively, will be sufficient to support our operations into 2028, subject to our continued compliance with our Hercules Loan Agreement covenants, there can be no assurance that these initiatives will be successful or that any anticipated spending reductions will be adequate, which could materially affect our future operations.

While we have successfully raised capital in the past, our ability to raise capital in future periods is not assured. We may be required to raise additional capital to satisfy the cash covenant under our existing debt facility with Hercules that requires that we maintain a minimum level of cash at a level greater than 20% of our outstanding borrowings under the Hercules Loan Agreement and subject to certain operational covenants. Based on our current cash flow projections, excluding additional sources of external financing, we anticipate that we will be able to maintain the minimum cash required to satisfy this covenant for at least the next 12 month period following the issuance of these consolidated financial statements. See also the risk factor titled “Our term loan contains restrictions that limit our flexibility in operating our business” below.

We have incurred significant losses and have not generated significant revenue from product sales since our inception. We expect to continue to incur losses for the foreseeable future and we may never achieve or maintain profitability.

We are a commercial-stage biopharmaceutical company. Investment 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 adequate effect or an acceptable safety profile, gain regulatory approval, become commercially viable, or maintain commercial viability. Since inception, ~~other than during the three and nine months ended September 30, 2024,~~ we have incurred significant operating losses. Our net losses were $3779.52 million, $~~101~~37.25 million, and $93101.92 million for the years ended December 31, ~~2024~~2025, ~~2023~~2024, and ~~2022,~~2023. ~~respectively,~~We ~~and we~~ generated negative operating cash flows in each of these periods. As of December 31, 2024, we had an accumulated deficit of $515.4 million. To date, we have funded our operations to date primarily with proceeds from sales of common stock, warrants, and prefunded warrants for the purchase of our preferred stock and our common stock, sales of preferred stock, proceeds from the issuance of convertible debt, and borrowings under loan and security agreements. We have one product approved for commercial sale, XOLREMDI, upon which we depend almost entirely on to produce revenue. XOLREMDI, which has been approved for WHIM syndrome in the U.S., faces an unknown market size and growth potential and we have not generated significant revenue from product sales to date, and we may never achieve profitability.

We expect to continue to incur significant expenses and operating losses for at least the next several years as we conduct ~~additional clinical trials for~~ our ~~product~~global, ~~candidates;~~pivotal ~~continue~~Phase to3 ~~discover~~clinical ~~and~~trial ~~develop~~for ~~additional~~mavorixafor ~~product~~for ~~candidates;~~the ~~acquire~~treatment orof ~~in-license~~CN ~~other~~(the ~~product~~“4WARD” ~~candidates and technologies~~trial); ~~maintain, expand and protect our intellectual property portfolio; hire additional clinical, scientific and commercial personnel;~~ establish a commercial manufacturing source and secure supply chain capacity sufficient to provide commercial quantities of any product candidates for which we may obtain regulatory approval; seek regulatory approvals for any product candidates that successfully complete clinical trials; further grow a sales, marketing and distribution infrastructure to commercialize ~~XOLREMDI~~product ~~and~~candidates ~~any other products~~ for which we may obtain regulatory approval; and add operational, financial and management information systems and personnel, including personnel to support our product development and planned future commercialization efforts. We may encounter unforeseen expenses, difficulties, complications, delays, and/or other unknown factors that may adversely affect our business. The size of our future net losses will depend, in part, on the rate of future growth of our expenses and our ability to generate revenues.

development and planned future commercialization efforts. We may encounter unforeseen expenses, difficulties, complications, delays, and/or other unknown factors that may adversely affect our business. The size of our future net losses will depend, in part, on the rate of future growth of our expenses and our ability to generate revenues.

Our ability to generate profits from operations and thereafter to remain profitable depends heavily on:

•our ability to generate revenue from ~~XOLREMDI~~mavorixafor;

•outcomes and timing of regulatory reviews, approvals and other actions;

•our ability to manufacture any approved products on commercially reasonable terms;

•our ability to maintain an effective sales and marketing organization or suitable third-party alternatives for any approved products;

•the scope, number, progress, duration, endpoints, cost, results and timing of clinical trials and nonclinical studies of our current or potential future product candidates, including in particular the scope, progress, duration, endpoints, cost, results and timing for completion of our Phase 3 clinical trial of mavorixafor for the treatment of chronic neutropenic disorders;36

•the scope, number, progress, duration, endpoints, cost, results and timing of clinical trials and nonclinical studies of our current or potential future product candidates, including in particular the scope, progress, duration, endpoints, cost, results and timing for completion of our 4WARD Phase 3 clinical trial of mavorixafor for the treatment of chronic neutropenic disorders;

•our ability to raise sufficient funds to support the development and potential commercialization of our product candidates;

•our ability to market our approved product and obtain marketing approval for our product candidates;

•our ability to manage our cash expenditures in line with our budget as approved by our Board of Directors, which reflects the cost savings we anticipate from our restructuring activities executed in 2025;

•our ability to establish and maintain licensing, collaboration or similar arrangements on favorable terms and whether and to what extent we retain development or commercialization responsibilities under any new licensing, collaboration or similar arrangement;

•the success of any other business, product or technology that we acquire or in which we invest;

•our ability to maintain, expand and defend the scope of our intellectual property portfolio;

•the number and characteristics of product candidates and programs that we pursue;

•our ability to hire additional clinical, regulatory and scientific personnel; and

•~~incur~~the ~~additional~~extent of legal, accounting and other expenses ~~associated~~that ~~with~~we ~~operating~~incur to continue to operate as a public company.

Although we have obtained marketing approval for, and have begun to commercialize one of our product candidates, we may never generate revenues that are significant enough to generate profits from operations. Even if we do generate profits from operations, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our failure to generate profits from operations and remain profitable would decrease our value and could impair our ability to raise capital, expand our business, maintain our research and development efforts, diversify our product offerings or continue our operations. A decline in our value could also cause you to lose all or part of your investment.

We may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown factors that may alter or delay our plans. As we have completed the development of and obtained marketing approval in the U.S. for mavorixafor, we will need to transition from a company with a research and development focus to a company capable of supporting commercial activities. We may encounter unforeseen expenses, difficulties, complications and delays, and may not be successful in such a transition.

Our operating plan and liquidity position will require substantial additional funding. Our history of recurring losses and

anticipated expenditures could raise substantial doubts about our ability to continue as a going concern. If we are unable to raise capital when needed, we could be forced to delay, reduce or eliminate any product development programs or commercialization efforts.

We may be forced to delay or reduce the scope of our development programs and/or limit or cease our operations if we are unable to obtain additional funding to support our current operating plan.

Our operations have consumed a large amount of cash since inception. To date, we have funded our operations primarily with proceeds from sales of common stock, warrants and prefunded warrants for the purchase of our preferred stock and our common stock, sales of preferred stock, proceeds from the issuance of convertible debt and borrowings under loan and security agreements. We expect to continue to incur research and development expenses as we continue to advance the clinical development of our product candidates and prepare for the launch and commercialization of any product candidates for which we receive regulatory approval. We expect to incur significant commercialization expenses related to product sales, marketing, distribution and manufacturing. Furthermore, we expect to incur additional costs associated with operating as a public company.

As of December 31, 2024, we have cash and cash equivalents of $55.7 million and short-term marketable securities of $46.4 million. Although we have an approved drug product, sales of our drug product over the next 12 months will not be sufficient to fund our operating expenses. Our ability to continue as a going concern will require us to obtain additional funding. If we are unable to obtain sufficient funding, our business, prospects, financial condition and results of operations will be materially and adversely affected, and we may be unable to continue as a going concern. We will require additional capital to sustain our operations, and to carry out our business plans thereafter, which may include raising funds through public or private equity or debt financings, third-party funding, marketing and distribution arrangements, as well as other collaborations, strategic alliances and licensing arrangements, or any combination of these approaches. If we are unable to raise capital when needed or on acceptable terms, we would be forced to delay, limit, reduce, restructure or terminate our product development or future commercialization efforts of one or more of our product candidates, or may be forced to reduce, restructure or terminate our operations. If we are unable to continue as a going concern, we may have to liquidate our assets and may receive less than the value at which those assets are carried on our audited financial statements, and it is likely that investors will lose all or a part of their investment. In our own future required quarterly assessments, we may again conclude that there is substantial doubt about our ability to continue as a going concern, and future reports from our independent registered public accounting firm may also contain statements expressing substantial doubt about our ability to continue as a going concern. If we seek additional financing to fund our business activities in the future and there exists substantial doubt about our ability to continue as a going concern, investors or other financing sources may be unwilling to provide additional funding to us on commercially reasonable terms, if at all.

Although we announced in February 2025 that, as part of our 2025 Restructuring, we expect to decrease annual spending by approximately $30–35 million and believe this will provide sufficient funds to support operations into the first half of 2026, there can be no assurance that these initiatives will be successful or that the anticipated funding will be adequate, which could materially affect our future operations.

While we have successfully raised capital in the past, our ability to raise capital in future periods is not assured. We will also require additional capital to satisfy the covenant under our existing debt facility with Hercules Capital, Inc. and certain affiliated entities (“Hercules”) that requires that we maintain a minimum level of cash at a level greater than 20% of our outstanding borrowings under the Loan and Security Agreement, as most recently amended in August 2023 with Hercules Capital, Inc. (the “Hercules Loan Agreement”) and subject to certain operational covenants. Based on our current cash flow projections, excluding additional sources of external financing, we anticipate that we will not be able to maintain the minimum cash required to satisfy this covenant for at least the next 12 month period following the issuance of these consolidated financial statement. See also the risk factor titled “Our term loan contains restrictions that limit our flexibility in operating our business” below.

To finance our future operations, we will need to raise additional capital, which cannot be assured. We cannot be certain that additional funding will be available on acceptable terms, or at all. If we are unable to raise additional capital when needed or in sufficient amounts or on terms acceptable to us, we could be forced to delay, reduce or eliminate our research and development programs or any future commercialization efforts of one or more of our product candidates or one or more of our other research and development initiatives. In addition, when we need to secure additional financing, such 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. Any of these events could significantly harm our business, financial condition and prospects, and our stockholders could lose all or part of their investment in our company.

We also could be required to:

•seek new or additional collaborators for one or more of our current or future product candidates at an earlier stage than otherwise would be desirable or on terms that are less favorable than might otherwise be available; or

•relinquish or license on unfavorable terms our rights to technologies or product candidates that we otherwise would seek to develop or commercialize ourselves.

Our future funding requirements, both near and long-term, will depend on many factors, including, but not limited to:

•the outcome, timing and cost of regulatory reviews, approvals or other actions to meet regulatory requirements established by the FDA and comparable foreign regulatory authorities, including the potential for the FDA or comparable foreign regulatory authorities to require that we perform more studies for our product candidates than those that we currently expect;

•our ability to obtain marketing approval for our product candidates, including for additional indications;

•the success of our exclusive licensing and supply agreement which Norgine and any potential regulatory and commercial milestone payments that we may receive under that agreement;

•the scope, number, initiation, progress, timing, costs, design, duration, any potential delays, and results of clinical trials and nonclinical studies for our current or future product candidates;

•the number and characteristics of product candidates and programs that we develop or may in-license;

•the cost of filing, prosecuting, defending and enforcing our patent claims and other intellectual property rights covering our product candidates, including any such patent claims and intellectual property rights that we have licensed from Genzyme pursuant to the terms of our license agreement with Genzyme or from other third parties;

•our ability to maintain, expand and defend the scope of our intellectual property portfolio, including the cost of defending intellectual property disputes, including patent infringement actions brought by third parties against us or our product candidates;

•the cost and timing of completion of commercial-scale manufacturing activities with respect to our product candidates;

•the cost of establishing sales, marketing and distribution capabilities for any product candidates for which we may receive regulatory approval in regions where we choose to commercialize our products on our own;

•the success of any other business, product or technology that we acquire or in which we invest;

•the costs of acquiring, licensing or investing in businesses, product candidates and technologies;

•our need and ability to hire additional management and scientific and medical personnel;

•market acceptance of our product candidates, to the extent any are approved for commercial sale;

•the effect of competing technological and market developments;

•the costs to operate as a public company; and

•business interruptions resulting from pandemics and public health emergencies, geopolitical actions, including war and terrorism or natural disasters including earthquakes, typhoons, floods and fires.

Raising additional capital may cause dilution to our investors, restrict our operations or require us to relinquish rights to our technologies or product candidates. Future debt obligations may expose us to risks that could adversely affect our business, operating results and financial condition and may result in further dilution to our stockholders.

Until such time, if ever, as we can generate ~~substantial~~ product and licensing revenues that are in excess of our operating expense, we expect to finance our cash needs through public or private equity or debt financings, third-party funding, marketing and distribution arrangements, as well as other collaborations, strategic alliances and licensing arrangements, or any combination of these approaches. ~~Other~~We ~~than~~do ~~our~~not ~~common~~have ~~stock~~any ~~purchase~~committed ~~agreement~~external ~~with~~sources ~~Lincoln~~of ~~Park~~funds ~~Capital~~and ~~Fund~~may ~~LLC~~seek ~~(“Lincoln~~to ~~Park”),~~raise ~~pursuant~~additional tocapital ~~which~~at ~~Lincoln~~any ~~Park~~time. isTo ~~obligated,~~the ~~subject~~extent tothat ~~certain~~we ~~limitations~~raise ~~and~~additional ~~conditions,~~capital tothrough ~~purchase~~the upsale toof aequity ~~remaining~~or ~~$47.0~~convertible ~~million~~debt insecurities, your ownership interest will be diluted, and the ~~aggregate~~terms of ~~shares~~these securities may include liquidation or other preferences that adversely affect your rights as a holder of our common stock. Debt financing, weif doavailable, ~~not~~may ~~have~~involve ~~any~~agreements ~~committed~~that ~~external~~include ~~sources~~covenants oflimiting ~~funds~~or ~~and~~restricting ~~may~~our ~~seek~~ability to ~~raise~~take specific actions, such as incurring additional debt, making capital atexpenditures, ~~any~~declaring ~~time.~~dividends Toor ~~the~~other ~~extent~~distributions, acquiring or licensing intellectual property rights and other operating restrictions that wecould ~~raise~~adversely impact our ability to conduct our business and may result in liens being placed on additional ~~capital~~assets ~~through~~such ~~the~~as ~~sale~~intellectual ofproperty. ~~equity~~For orexample, ~~convertible~~our debt ~~securities~~facility with Hercules contains a minimum cash financial covenant. If we default on such indebtedness, ~~your~~with ~~ownership~~Hercules ~~interest~~or ~~will~~a future lender, we could be ~~diluted~~required to pledge additional assets, ~~and~~or the ~~terms~~lenders ofcould enforce remedies on the current collateral.

32If we raise additional funds through licensing, collaboration or similar arrangements with third parties, we may be required to relinquish valuable rights to our technologies, future revenue streams, research and development programs or product candidates or grant licenses on terms that are not favorable to us. If we are unable to raise additional funds through equity or debt financings or through licensing, collaboration or similar arrangements when needed, we may be required to delay, limit, reduce, restructure or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

these securities may include liquidation or other preferences that adversely affect your rights as a holder of our common stock. Debt financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures, declaring dividends or other distributions, acquiring or licensing intellectual property rights and other operating restrictions that could adversely impact our ability to conduct our business and may result in liens being placed on additional assets such as intellectual property. For example, our

debt facility with Hercules contains a minimum cash financial covenant. If we default on such indebtedness, with Hercules or a future lender, we could be required to pledge additional assets, or the lenders could enforce remedies on the current collateral.

If we raise additional funds through licensing, collaboration or similar arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research and development programs or product candidates or grant licenses on terms that are not favorable to us. If we are unable to raise additional funds through equity or debt financings or through licensing, collaboration or similar arrangements when needed, we may be required to delay, limit, reduce, restructure or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

Changes in estimates regarding fair value of intangible assets may result in an adverse impact on our results of operations.

We test our goodwill for impairment annually or more frequently if changes in circumstances or the occurrence of events suggest impairment exists. Any significant change in market conditions, including a sustained decline in our stock price, that indicate a reduction in carrying value may give rise to a significant impairment charge in the period that the change becomes known. For example, as of December 31, 2021, our market capitalization, measured as the price of our common stock multiplied by shares of common stock outstanding, declined to below the value of our net assets, including goodwill. As a result of the sustained decline in the market price of our common stock, the fair value of our single reporting unit, measured based on our market capitalization as of December 31, 2021, was lower than its carrying value and we concluded that goodwill was impaired. Accordingly, we recorded an impairment charge of $9.8 million to reduce the carrying amount of goodwill to $17.4 million as of December 31, 2021. While we determined that goodwill was not impaired based on our quantitative test as of December 31, 2024, future declines in the market value of our common stock and additional funding may result in additional impairment charges being recorded.

Risks Related to Development of Our Product Candidates

We have not generated significant revenues from product sales since inception and may never become profitable. We may never be able to generate meaningful revenues from sales of ~~XOLREMDI~~our product candidates and approved commercial products at levels or on timing necessary to support our investment and goals.

To date, we have not generated significant revenues from product sales and cannot predict whether or when we will be able to generate meaningful revenues from sales of XOLREMDI at levels or on timing necessary to support our investment and38

~~goals.~~To ~~Our~~date, ~~ability~~we tohave ~~generate~~not ~~revenue~~generated ~~and~~significant ~~become~~revenues ~~profitable~~from ~~depends~~product ~~upon~~sales ~~our~~and ~~ability~~cannot topredict ~~successfully~~whether ~~commercialize~~or ~~XOLREMDI~~when ~~and~~we will be able to ~~obtain~~generate ~~marketing~~meaningful ~~approval~~revenues ~~and~~from ~~commercialize~~sales of our product candidates, ~~including~~and ~~mavorixafor,~~our approved commercial products at levels or ~~other~~on ~~product~~timing ~~candidates~~necessary ~~that~~to wesupport ~~may~~our ~~develop,~~investment ~~in-license~~and orgoals. ~~acquire~~Our inability ~~the~~to ~~future~~generate revenue and become profitable depends upon our ability to successfully commercialize mavorixafor. Even if we are able to successfully achieve regulatory approval for ~~these~~our product candidates, we are unable to predict the extent of any future losses and do not know when any of these product candidates will generate revenue for us, if at all. Our ability to generate revenue from ~~XOLREMDI,~~ mavorixafor or any of our ~~current or~~ future product candidates also depends on a number of additional factors, including but not limited to our ability to:

•successfully complete development activities, including all necessary nonclinical studies and clinical trials;

•complete and submit ~~New~~NDAs ~~Drug Applications~~ to the FDA and obtain regulatory approval for indications for which there is a commercial market;

•complete and submit marketing applications to, and obtain regulatory approval from, foreign regulatory authorities;

•set and obtain a commercially viable price for our products;

•obtain commercial quantities of our products at acceptable cost levels;

•further develop a commercial organization capable of sales, marketing and distribution for the products we intend to sell ourselves in the markets in which we have retained commercialization rights;

•find suitable collaborators to help us market, sell and distribute our approved products in other markets; and

•obtain coverage and adequate reimbursement from third-party, including government, payors.

In addition, because of the numerous risks and uncertainties associated with product development, including the possibility that our product candidates may not advance through development or demonstrate safety and efficacy for their intended uses, the FDA or any other regulatory agency may require additional clinical trials or nonclinical studies. We are unable to predict the timing or amount of increased expenses, or when or if we will be able to achieve or maintain profitability, and such expense could increase beyond our expectations if the FDA or any other regulatory agency requires such additional clinical trials or nonclinical studies as part of the application and approval process or post-approval process if we are successful at achieving regulatory approval. Even if we are able to successfully complete the development and regulatory reviews described above, we anticipate incurring significant costs associated with commercializing these products, if they are approved.

Even if we are able to generate meaningful revenues from the sale of our product, we may not become profitable and may need to obtain additional funding to continue operations. If we fail to become profitable or are unable to sustain profitability on a continuing basis, then we may be unable to continue our operations at planned levels and be forced to reduce our operations. 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 would decrease the value of the company and could impair our ability to raise capital, maintain our discovery and preclinical development efforts, expand our business or continue our operations and may require us to raise additional capital that may dilute your ownership interest. A decline in our value could also cause you to lose all or part of your investment.

If the commercial opportunity for mavorixafor in ~~WHIM syndrome and other~~ chronic neutropenic disorders is smaller than we anticipate, our potential future revenue from mavorixafor for the treatment of any of these diseases may be adversely affected and our business may suffer.

If the size of the commercial opportunities in any of our target indications is smaller than we anticipate, we may not be able to achieve profitability and growth. ~~Our~~We ~~lead~~continue ~~clinical~~to ~~candidate~~progress our 4WARD trial to evaluate the efficacy, safety, and tolerability of oral, once-daily mavorixafor (with or without stable doses of G-CSF) in people with congenital, ~~has~~acquired ~~been~~primary ~~approved~~autoimmune, byor idiopathic CN who are experiencing recurrent and/or serious infections. We estimate that there are approximately 15,000 patients in the ~~FDA~~U.S. ~~for~~with ~~use~~CN aswho anexperience ~~oral~~serious and/or recurring infections. We plan to initially focus on one third of these patients, representing our initial target market penetration. If the commercial opportunity is smaller than we anticipate, whether because our estimates of the addressable patient population prove to be incorrect or for other reasons, our potential future revenue from mavorixafor may be adversely affected and our business may suffer.

~~once-daily~~It ~~therapy~~is critical to ~~increase~~our ~~the~~ability ~~number~~to ofgrow ~~circulating mature neutrophils~~ and ~~lymphocytes~~become ofprofitable ~~patients~~that ~~aged~~we 12successfully ~~years~~identify ~~and~~patients ~~older~~ with ~~WHIM~~CN ~~and~~disorders. isOur ~~being~~projections ~~developed~~of ~~as an oral, once-daily therapy for~~ the ~~potential~~number ~~treatment~~ of ~~other~~people ~~chronic~~who ~~neutropenic~~have CN disorders. We are ~~currently~~based ~~aware~~on ~~of only~~ a ~~few~~variety ~~small~~of ~~available patient registries for WHIM syndrome~~sources, ~~and~~including wethird-party ~~rely on various~~ estimates and ~~assumptions~~analyses toin ~~estimate~~ the ~~addressable~~scientific ~~WHIM~~literature, ~~syndrome~~and ~~population.~~may ~~Based~~prove ~~on a broad online survey of physicians~~ to ~~validate~~be ~~current~~incorrect. ~~prevalence~~Further, ~~estimates~~new ~~and~~information ~~additional~~may ~~research~~emerge ~~using~~that ~~artificial~~changes ~~intelligence,~~our ~~which~~estimate ~~interrogated~~of athe ~~database~~prevalence of ~~more~~these ~~than~~diseases ~~300~~or ~~million~~the ~~anonymized~~number of patient ~~records~~candidates ~~that~~for ~~spanned~~each 10disease. ~~years~~The ofeffort ~~insurance~~to ~~claims,~~identify wepatients ~~estimate~~for ~~there~~treatment ~~are~~is upat toan 3early stage,~~700~~ ~~diagnosed~~ and ~~undiagnosed~~we ~~WHIM~~cannot ~~patients~~accurately inpredict the ~~United~~number ~~States,~~of ~~many~~patients offor whom ~~were~~treatment ~~previously~~might ~~undiagnosed~~be possible. IfAdditionally, the ~~commercial~~addressable ~~opportunity~~patient inpopulation ~~any~~for of our ~~target~~ indications, ~~including~~may ~~WHIM~~be ~~syndrome~~limited isor ~~smaller~~may ~~than~~not webe ~~anticipate,~~amenable ~~whether~~to ~~because~~treatment ~~our~~with ~~estimates~~mavorixafor, ofand ~~the~~new ~~addressable~~patients ~~patient~~may ~~population~~become ~~prove~~increasingly difficult to beidentify ~~incorrect~~ or ~~for~~gain ~~other~~access ~~reasons~~to, ~~our~~which ~~potential~~would ~~future~~adversely ~~revenue~~affect ~~from~~our ~~mavorixafor~~results ~~may~~of beoperations ~~adversely affected~~ and our business ~~may suffer~~.

It is critical to our ability to grow and become profitable that we successfully identify patients with WHIM syndrome and other chronic neutropenic disorders. Our projections of the number of people who have WHIM syndrome (or its other potential primary immunodeficiencies) and chronic neutropenic disorders are based on a variety of sources, including third-party estimates and analyses in the scientific literature, and may prove to be incorrect. Further, new information may emerge that changes our estimate of the prevalence of these diseases or the number of patient candidates for each disease. The effort to identify patients for treatment is at an early stage, and we cannot accurately predict the number of patients for whom treatment might be possible. Additionally, the addressable patient population for our indications may be limited or may not be amenable to treatment with mavorixafor, and new patients may become increasingly difficult to identify or gain access to, which would adversely affect our results of operations and our business.39

We depend almost entirely on the success of our ~~commercial~~future product, ~~XOLREMDI, which has been approved for use in patients 12 years of age and older with WHIM syndrome in the U.S., and on our lead product~~ candidate, mavorixafor~~, which we are developing for the potential treatment of other chronic neutropenic disorders~~. We cannot be certain that we will be able to obtain regulatory approval for, or successfully commercialize, mavorixafor for ~~chronic neutropenic~~ disorders other than WHIM, including CN, or any other product candidate.

Our business depends almost entirely on the successful clinical development, regulatory approval and commercialization of mavorixafor. We currently have only one product for sale, XOLREMDI, and may never be able to develop additional marketable drug products. The clinical trials of our product candidates are, and the manufacturing and marketing of our product candidates will be, subject to extensive and rigorous review and regulation by government authorities in the United States and in other countries where we intend to test and, if approved, market any product candidate. Before obtaining regulatory approvals for the commercial sale of any product candidate, we must successfully meet a number of critical developmental milestones, including:

•developing dosages that will be well-tolerated, safe and effective;

•completing the development and scale-up to permit manufacture of our product candidates in commercial quantities and at acceptable costs;

•demonstrating through pivotal clinical trials that each product candidate is safe and effective in patients for the intended indication;

•establishing commercial manufacturing capabilities or making arrangements with third-party manufacturers; and

•obtaining and maintaining patent and trade secret protection and non-patent exclusivity for our product candidates.

The time necessary to achieve these developmental milestones for any individual product candidate is long and uncertain, and we may not successfully complete these milestones for additional indications for mavorixafor or any other product candidates that we may develop. We also may not be able to finalize the design or formulation for our other programs. We may not be able to complete development of any additional product candidates that demonstrate safety and efficacy and that will have a commercially reasonable treatment and storage period. If we are unable to complete development for additional indications for mavorixafor or any other product candidates that we may develop, we will not be able to commercialize and earn revenue from them.

We may develop mavorixafor, and ~~potentially~~ future product candidates, in combination with other therapies, which could expose us to additional risks.

We may develop mavorixafor, and may develop future product candidates, in combination with one or more currently approved therapies. Even though XOLREMDI received marketing approval, we would continue to be subject to the risks that the FDA or similar regulatory authorities outside of the United States could revoke approval of the therapy used in combination with our product candidate or that safety, efficacy, manufacturing or supply issues could arise with these existing therapies. Combination therapies are commonly used for the treatment of diseases, and we would be subject to similar risks if we develop any of our product candidates for use in combination with other drugs. This could result in our own products being removed from the market or being less successful commercially.

We may also evaluate mavorixafor or any other future product candidates in combination with one or more other cancer therapies that have not yet been approved for marketing by the FDA or similar regulatory authorities outside of the United States. We will not be able to market and sell mavorixafor or any product candidate we develop in combination with any such unapproved therapies that do not ultimately obtain marketing approval.

If the FDA or similar regulatory authorities outside of the United States do not approve these other drugs or revoke their approval of, or if safety, efficacy, manufacturing or supply issues arise with, the drugs that we choose to evaluate in combination with mavorixafor or any product candidate we develop, we may be unable to obtain approval of or market mavorixafor or any product candidate we develop.

Disruptions at the FDA, the SEC and other government agencies caused by funding shortages or global health concerns, in addition to substantial uncertainty regarding the Trump administration’s initiatives and staffing cuts and how these might impact the FDA, its implementation of laws, regulations, policies and guidance, and its personnel, could hinder their 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 and approve new products 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. As a result of some of these factors, average review times at the FDA have fluctuated in recent years. In addition, government funding of the SEC and other government 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. Without appropriation of additional funding to federal agencies, our business operations related to our product development activities for the U.S. market could be impacted.

Disruptions at the FDA and other agencies, including substantial leadership departures, personnel cuts, and policy changes, may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business. Changes and cuts in FDA staffing could result in delays in the FDA’s responsiveness or in its ability to review IND submissions or applications, issue regulations or guidance, or implement or enforce regulatory requirements in a timely fashion or at all. For example, over the last several years the U.S. government has shut down several times, including as recently as October 2025, and certain regulatory agencies, such as the FDA and the SEC, have had to furlough critical government employees and stop critical activities. In 2025, the FDA has been subject to reductions in force and reorganization. A prolonged government shutdown or significant leadership, personnel and/or policy changes, or substantial modification in agency activities could significantly impact the ability of the FDA or other regulatory authorities to conduct their regular inspections, reviews, or other regulatory activities. Additionally, a prolonged shutdown 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, including INDs placed on clinical holds or delayed new drug approvals. Further, in our operations as a public company, 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.

With the changes being implemented by the Trump administration in 2025, there is substantial uncertainty as to whether and how the Trump administration will 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. This uncertainty could present new challenges and/or opportunities as we navigate development and approval of our product candidates. Some of these efforts have manifested to date in the form of personnel cuts and measures that could impact the FDA’s ability to hire and retain key personnel, which could result in delays or limitations on our ability to obtain guidance from the FDA on our product candidates in development and obtain the requisite regulatory approvals in the future. There remains general uncertainty regarding future activities. The Trump 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 products. Alternatively, state governments may attempt to address or react to changes at the federal level with changes to their own regulatory frameworks in a manner that is adverse to our operations. If we become negatively impacted by future governmental orders, regulations, policies or guidance as a result of the Trump administration, there could be a material adverse effect on us and our business.

The regulatory review and approval processes of the FDA and comparable foreign regulatory authorities are lengthy, time-consuming and inherently unpredictable, and if we are ultimately unable to obtain regulatory approval for our product candidates, including additional indications for mavorixafor, our business will be substantially harmed.

We are not permitted to market mavorixafor or any other product candidate in the United States until we receive approval of an NDA from the FDA, or in any foreign countries until we receive the requisite approval from such countries or jurisdictions, such as approval of the marketing authorization application in the European Union from the European Commission. Our future NDA submissions may receive a refusal to file response from the FDA, and even if filed by the FDA, we may receive a Complete Response Letter rather than approval for commercial marketing. In addition, we may be required by the FDA to conduct additional clinical trials and/or nonclinical studies to support potential approval. Successfully completing clinical trials and obtaining approval of an NDA is a complex, lengthy, expensive and uncertain process, and the FDA, or a comparable foreign regulatory authority, may delay, limit or deny approval of mavorixafor for the treatment of other indications for many reasons, including, among others:

•disagreement with the design or implementation and sufficiency of our clinical trials;

•failure to demonstrate the safety and efficacy of mavorixafor or any other product candidate for its proposed indications and that;

•any clinical and other benefits of mavorixafor or any other product candidate outweigh its safety risks;

•deficiencies in the manufacturing or control processes or failure of third-party manufacturing facilities with which we contract for clinical and commercial supplies to comply with current cGMPs;

•insufficient data collected from clinical trials of mavorixafor or any other product candidate, or changes in the approval requirements that render its nonclinical and clinical data insufficient to support the filing of an NDA or to obtain regulatory approval; or

•changes in clinical practice in or approved products available for the treatment of the target patient population that could have an impact on the indications that we are pursuing for mavorixafor or our other product candidates.

The FDA or a comparable foreign regulatory authority may also require more information, including additional nonclinical or clinical data to support approval, which may delay or prevent approval of our commercialization plans, or cause us to abandon the development program. If our current or future product candidates receive regulatory approval, these product candidates may be approved for fewer or more limited indications than we request, such approval may be contingent on the performance of costly post-marketing clinical trials, or we may not be allowed to include the labeling claims necessary or desirable for the successful commercialization of such product candidate.

We depend on license agreements with Genzyme, ~~Beth Israel Deaconess Medical Center, Georgetown University~~ and ~~Dana-Farber~~others ~~Cancer Institute~~ to permit us to use patents and patent applications. Termination of these rights or the failure to comply with obligations under these agreements could materially harm our business and prevent us from developing or commercializing our product candidates.

We are party to license agreements with Genzyme, ~~Beth Israel Deaconess Medical Center, Georgetown University~~ and ~~Dana-Farber~~other ~~Cancer~~entities ~~Institute~~ under which we were granted rights to patents and patent applications that are important to our business. We rely on these license agreements in order to be able to use various proprietary technologies that are material to our business, including certain patents and patent applications that cover our product candidates, including mavorixafor. Our rights to use these patents and patent applications and employ the inventions claimed in these licensed patents are subject to the continuation of and our compliance with the terms of our license agreements.

Our license agreement with Genzyme imposes upon us various diligence, payment and other obligations, including the obligation to pay Genzyme (i) future milestone payments in the aggregate amount of up to $1310.0 million as of December 31, ~~2024~~2025, contingent upon our achievement of certain late-stage regulatory and sales milestones with respect to licensed products, ~~of which we achieved a regulatory milestone of $3.0 million in January 2025 and paid in March 2025,~~ (ii) our obligation to pay Genzyme tiered royalties based on net sales of licensed products that we commercialize under the agreement; and (iii) our obligation to pay Genzyme a certain percentage of cash payments received by us or our affiliates in consideration for the grant of a sublicense under the license granted to us by Genzyme. If we fail to comply with any of our obligations under the Genzyme license agreement, or we are subject to bankruptcy, Genzyme may have the right to terminate the license agreement, in which event we would not be able to market any product candidates covered by the license.

If we fail to comply with any of our obligations under the Genzyme license agreement, or we are subject to a bankruptcy, Genzyme may have the right to terminate the license agreement, in which event we would not be able to market any product candidates covered by the license.

Prior to July 2014, we did not control the prosecution, maintenance, or filing of the patents and patent applications that are licensed to us under the Genzyme license agreement, or the enforcement of these patents and patent applications against infringement by third parties. Thus, these patents and patent applications were not drafted by us or our attorneys, and we did not control or have any input into the prosecution of these patents and patent applications prior to our execution of the Genzyme license agreement in July 2014. Under the terms of the license agreement with Genzyme, since July 2014, we have controlled the right to control the prosecution, maintenance, and filing of the patents and patent applications that are licensed to us, and the enforcement of these patents and patent applications against infringement by third parties. However, we cannot be certain that the same level of attention was given to the drafting and prosecution of these patents and patent applications as we may have used if we had control over the drafting and prosecution of such patents and patent applications. We also cannot be certain that drafting or prosecution of the patents and patent applications licensed to us has been conducted in compliance with applicable laws and regulations or will result in valid and enforceable patents.

Pursuant to our license agreement with Beth Israel Deaconess Medical Center, we paid an upfront, one-time fee for the rights granted by the license agreement. This license agreement imposes upon us various obligations, including the requirement to provide Beth Israel Deaconess Medical Center with progress reports at regular intervals and to maintain specified levels of insurance. Beth Israel Deaconess Medical Center may terminate the agreement for our non-payment, insolvency or default of material obligations. We have the right to terminate the agreement for any reason upon 90 days’ advance written notice.

Our license agreement with Georgetown imposes upon us various diligence, payment and other obligations, including our obligations to pay Georgetown milestone payments in the aggregate amount of up to $0.8 million, contingent upon our achievement of certain sales milestones with respect to licensed products, to deliver reports upon certain events and at regular intervals and to maintain customary levels of insurance. Georgetown may terminate the agreement for our non-payment, insolvency, failure to maintain insurance or default of material obligations. We have the right to terminate the agreement for any reason upon 60 days advance written notice.

Our license agreement with the Dana-Farber Cancer Institute (“DFCI”) imposes upon us various diligence, payment and other obligations, including our obligations to pay DFCI milestone payments in the aggregate amount of up to approximately $32 million, contingent upon our achievement of certain regulatory and sales milestones with respect to licensed products, to deliver reports at regular intervals and to maintain certain minimum levels of insurance. DFCI may terminate the agreement if (i) we cease to carry on our business with respect to the licensed products, (ii) we default on diligence, insurance, payment or any other material obligations, (iii) one of our officers or that of a sublicensee is convicted of a felony relating to the manufacture, use, sale or importation of one or more licensed product, (iv) we become insolvent, (v) we grant a sublicense without notifying DFCI or on terms inconsistent with the terms required of sublicenses under the agreement or (vi) we bring a patent challenge against the licensed products. We have the right to terminate the agreement for any reason upon 90 days advance written notice.

Disputes may arise under any of our license agreements with Genzyme, Beth Israel Deaconess Medical Center, Georgetown University and/or Dana-Farber Cancer Institute regarding the intellectual property that is subject to such license agreement, including:

•the scope of rights granted under the applicable license agreement and other interpretation-related issues;

•whether and the extent to which our technology and processes infringe on intellectual property that is not subject to the applicable license agreement;

•our diligence obligations with respect to the use of the licensed technology under the applicable license agreement to develop and commercialize products and technologies, including the level of effort and specific activities that will satisfy those diligence obligations; and

•the ownership of inventions and know-how resulting from the joint creation or use of intellectual property by us and our collaborators.

If disputes over intellectual property that we have licensed prevent or impair our ability to maintain any of our license agreements on acceptable terms, we may be unable to successfully develop and commercialize the affected product or product candidates and technologies.

The results of clinical trials may not support our product candidate claims.

Even if our clinical trials are completed as planned, we cannot be certain that their results will support the safety and/or efficacy of our product candidates, that the FDA or foreign government authorities will agree with our conclusions regarding such results, or that the FDA or foreign governmental authorities will not require additional clinical trials. Success in preclinical testing and early clinical trials does not ensure that later clinical trials will be successful and the results of later clinical trials often do not replicate the results of prior clinical trials and preclinical testing. The clinical trial results may fail to demonstrate that our product candidates are safe for humans and effective for the intended indications. This failure could cause us to abandon a product candidate and may delay development of other product candidates. Any delay in, or termination of, our clinical trials will delay or prevent the submission of our marketing applications (NDA and/or MAA) and, ultimately, our ability to obtain approval and commercialize our product candidates and generate product revenues. Information about certain clinical trials, including results (positive or negative) will be made public according to each country’s clinical trial registration policies. Competitors may use this publicly available information to gain knowledge regarding the progress of development programs.

Product development involves a lengthy and expensive process, with uncertain outcomes. Delays in or failure to complete any of our clinical trials may lead to a delay in the submission of our marketing approval application and jeopardize our ability to potentially receive approvals and generate revenues from the sale of our products.

To receive the required approval to commercialize any product candidates, we must demonstrate through extensive clinical trials that our product candidates are safe and effective in humans. Clinical testing is expensive and can take many years to complete, and its outcome is inherently uncertain. We may be unable to establish clinical endpoints that applicable regulatory authorities would consider clinically meaningful, and a clinical trial can fail at any stage of testing. Clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in clinical trials have nonetheless failed to receive marketing approval of their product candidates.

In addition, we may experience delays in our current or future clinical trials, including our Phase 3 clinical trial of mavorixafor for the treatment of chronic neutropenic disorders. For example, as a result of the COVID-19 pandemic, we experienced delays in clinical trial site activation and slower patient enrollment in our clinical trials of mavorixafor for WHIM syndrome. Clinical trials may be delayed, suspended or terminated for a variety of reasons, including the following:

•delay or failure in reaching agreement with the FDA or a comparable foreign regulatory authority on a trial design that we are able to execute;

•delay or failure in obtaining authorization to commence a trial or inability to comply with conditions imposed by a regulatory authority regarding the scope or design of a clinical trial;

•inability, delay or failure in identifying and maintaining a sufficient number of trial sites, many of which may already be engaged in competing clinical trial programs;

•delay or failure in recruiting and enrolling suitable subjects to participate in a trial;

•delay or failure in having subjects complete a trial or return for post-treatment follow-up;

•clinical sites and investigators deviating from trial protocol, failing to conduct the trial in accordance with regulatory requirements, or dropping out of a trial;

•delay or failure in reaching agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites;

•delay or failure in obtaining institutional review board (“IRB”) approval to conduct a clinical trial at each site;

•delays resulting from negative or equivocal findings of the Data Safety Monitoring Board (“DSMB”), if any;

•ambiguous or negative results;

•decision by the FDA, a comparable foreign regulatory authority, or recommendation by a DSMB to suspend or terminate clinical trials at any time for safety issues or for any other reason;

•inadequate supply of drug product for use in nonclinical studies or clinical trials;

•lack of adequate funding to continue the product development program;

•external business disruptions affecting the initiation, patient enrollment, development and operation of our clinical trials, including public health emergencies and geopolitical conflicts such as the war in Ukraine or in Gaza; or

•changes in governmental regulations or requirements.

Any delays in completing or failures to complete our clinical trials will increase our costs, slow down our product candidate development and approval process and jeopardize our ability to commence product sales and generate revenues. Any of these occurrences may significantly harm our business, financial condition and prospects. In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our product candidates.

Product candidates may cause undesirable side effects that could delay or prevent their marketing approval, limit the commercial profile of an approved label, or result in significant negative consequences following marketing approval, if any, including marketing withdrawal.

Undesirable side effects caused by any of our product candidates that we may develop or acquire could cause us or the FDA or other regulatory authorities to interrupt, delay or halt our clinical trials and could result in more restrictive labels or the delay or denial of marketing approval by the FDA or other regulatory authorities of such product candidates. Results of our clinical trials could reveal a high and unacceptable severity and prevalence of these or other side effects. In such an event, our trials could be suspended or terminated and the FDA or comparable foreign regulatory authorities could order us to cease further development of or deny approval of our product candidates for any or all targeted indications. In addition, any drug-related side effects could affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. Any of these occurrences may harm our business, financial condition and prospects significantly.

Further, clinical trials by their nature utilize a sample of the potential patient population. With a limited number of patients, rare and severe side effects of our product candidates may only be uncovered with a significantly larger number of patients exposed to the product candidate. For XOLREMDI and any other product candidates that receive marketing approval in the future, if we or others identify undesirable side effects caused by such product candidates (or any other similar drugs) after such approval, a number of potentially significant negative consequences could result, including:

or others identify undesirable side effects caused by such product candidates (or any other similar drugs) after such approval, a number of potentially significant negative consequences could result, including:

•regulatory authorities may withdraw or limit their approval of such product candidates;

•regulatory authorities may require the addition of labeling statements, such as a “boxed” warning or a contraindication;

•we may be required to create a medication guide outlining the risks of such side effects for distribution to patients;

•we may be required to change the way such product candidates are distributed or administered, conduct additional clinical trials or change the labeling of the product candidates;

•regulatory authorities may require a Risk Evaluation and Mitigation Strategy to mitigate risks, which 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;

•we may be subject to regulatory investigations and government enforcement actions;

•we may decide to remove such product candidates from the marketplace after they are approved;

•we could be sued and held liable for injury caused to individuals exposed to or taking our product candidates; and

•our reputation may suffer.

We believe that any of these events could prevent us from achieving or maintaining market acceptance of the affected product or product candidates and could substantially increase the costs of commercializing our products or product candidates, and significantly impact our ability to successfully commercialize our products or product candidates and generate revenues.

We may fail to enroll a sufficient number of patients in our clinical trials in a timely manner, which could delay or prevent clinical trials of our product candidates.

Identifying and qualifying patients to participate in clinical trials of our product candidates is critical to our success. The timing of our clinical trials depends on the rate at which we can recruit, enroll and retain patients in testing our product candidates, and we have made certain assumptions about the rate at which we can enroll patients in our clinical trials. The timing of our clinical trials depends in part on the speed at which we can recruit patients to participate in testing mavorixafor and any other current or future product candidates that we may develop as well as completion of required follow-up periods. ~~For example, as a result of the COVID-19 pandemic, we previously have experienced a slower enrollment pace in some of our clinical trials.~~

If we cannot identify patients to participate in our clinical trials or if patients are unwilling to participate in our clinical trials for any reason, including if patients choose to enroll in competitive clinical trials for similar patient populations, the timeline for recruiting patients, conducting studies and obtaining regulatory approval of mavorixafor and any other current or future product candidates that we may develop may be delayed. These delays could result in increased costs, delays in advancing our current or future product candidates, delays in testing the effectiveness of our product candidates or termination of the clinical trials altogether.

We may not be able to identify, recruit and enroll a sufficient number of patients, or those with required or desired characteristics to achieve diversity in a trial, to complete our current and future clinical trials in a timely manner. In particular, we are currently evaluating mavorixafor for the treatment of chronic neutropenic disorders, which are rare diseases with limited patient pools from which to draw for clinical trials. The eligibility criteria of our clinical trials will further limit the pool of available trial ~~participants~~patients. If we experience difficulty enrolling a sufficient number of patients to conduct our clinical trials as planned, we may be forced to delay, limit or terminate ongoing or planned clinical trials of our product candidates, which would delay our ability to obtain approvals and generate product revenues from any of these product candidates.

Results of earlier clinical trials may not be predictive of the results of later-stage clinical trials.

The results of pre-clinical studies and early clinical trials of our product candidates may not be predictive of the results of later-stage clinical trials. Interpretation of results from early, usually smaller, trials that suggest positive trends in some subjects, require caution. Results from later stage clinical trials enrolling more subjects may fail to show the desired safety and efficacy results or otherwise fail to be consistent with the results of earlier trials of the same product candidate. Inconsistencies may occur for a variety of reasons, including differences in trial design, trial endpoints (or lack of trial endpoints in exploratory studies), subject population, number of subjects, subject selection criteria, trial duration, drug dosage and formulation or lack of statistical power in the earlier trials.

Data obtained from preclinical and clinical activities are subject to varying interpretations, which may delay, limit, or prevent regulatory approval. In addition, we may experience regulatory delays or rejections as a result of many factors, including due to changes in regulatory policy during the period of our product candidate development. Any such delays could negatively impact our business, financial condition, results of operations and prospects.

Interim top-line 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.

From time to time, we may publish interim top-line or preliminary data from our clinical trials. Interim data from 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. Preliminary or top-line data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. Preliminary or top-line data may include, for example, data regarding a small percentage of the patients enrolled in a clinical trial, and such preliminary data should not be viewed as an indication, belief or guarantee that other patients enrolled in such clinical trial will achieve similar results or that the preliminary results from such patients will be maintained. As a result, interim and preliminary data should be viewed with caution until the final data are available. Differences between preliminary or interim data and final data could significantly harm our business prospects and may cause the trading price of our common stock to fluctuate significantly.

Risks Related to the Marketing and Commercialization of Our Product Candidates

Our ~~approved~~ product ~~and~~candidates ~~any~~that ~~future~~have ~~approved~~received ~~products~~regulatory approval may still face future development and regulatory difficulties and any approved products will be subject to extensive post-approval regulatory requirements. Additionally, our approved product, XOLREMDI, and ~~any~~ future approved products, if any, could be subject to marketing restrictions or withdrawal from the market, and we may be subject to penalties if we fail to comply with regulatory requirements or if we experience unanticipated problems with our products.

~~Our~~Any ~~approved~~ product ~~and~~candidate ~~product candidates~~ that ~~receive~~receives regulatory approval will be subject to extensive ongoing requirements by the FDA and comparable foreign regulatory authorities governing the manufacture, quality control, further development, labeling, packaging, storage, distribution, safety surveillance, import, export, advertising, promotion, recordkeeping and reporting of safety and other post-market information. The safety profile and efficacy of any product will continue to be closely monitored by the FDA and comparable foreign regulatory authorities after approval. If the FDA or comparable foreign regulatory authorities become aware of new safety information after approval of any of our product candidates, these regulatory authorities may require labeling changes or the FDA may require establishment of a Risk Evaluation Mitigation Strategy (“REMS”), impose significant restrictions on our product’s indicated uses or marketing, or impose ongoing requirements for potentially costly post-approval studies or post-market surveillance. Progress reports are required at quarterly intervals, every six months and at annual intervals depending upon the country, and more frequently if serious adverse events occur.

40Our approved product, XOLREMDI, and future product candidates that receive marketing approval, if any, will be subject to continual requirements of and review by the FDA and other regulatory authorities. These requirements include submissions of safety and other post-marketing information and reports, registration and listing requirements, cGMP requirements, quality assurance and corresponding maintenance of records and documents and requirements regarding the distribution of samples to physicians and recordkeeping. The marketing approval of our product candidate may be subject to limitations on the indicated uses for which the product may be marketed or to other conditions of approval, or contain requirements for costly post-marketing testing and surveillance to monitor the safety or efficacy of the drug. The FDA closely regulates the post-approval marketing and promotion of drugs to ensure that they are marketed only for the approved indications and in accordance with the provisions of the approved labeling.

studies or post-market surveillance. Progress reports are required at quarterly intervals, every six months and at annual intervals depending upon the country, and more frequently if serious adverse events occur.

Our approved product and our product candidates that receive marketing approval will be subject to continual requirements of and review by the FDA and other regulatory authorities. These requirements include submissions of safety and other post-marketing information and reports, registration and listing requirements, cGMP requirements, quality assurance and corresponding maintenance of records and documents and requirements regarding the distribution of samples to physicians and recordkeeping. The marketing approval of our product candidate may be subject to limitations on the indicated uses for which the product may be marketed or to other conditions of approval, or contain requirements for costly post-marketing testing and surveillance to monitor the safety or efficacy of the drug. The FDA closely regulates the post-approval marketing and promotion of drugs to ensure that they are marketed only for the approved indications and in accordance with the provisions of the approved labeling.

In addition, manufacturers of drugs and their facilities are subject to continual review and periodic inspections by the FDA and other regulatory authorities for compliance with cGMP regulations. If a regulatory agency discovers previously unknown problems with our product, such as adverse events of unanticipated severity or frequency, or problems with the facility where the product is manufactured, a regulatory agency may impose restrictions on that product, the manufacturing facility or us, including requiring recall or withdrawal of the product from the market or suspension of manufacturing. If we, our product or product candidates or the manufacturing facilities for our product or product candidates fail to comply with cGMPs and other applicable regulatory requirements, the FDA may, among other things:

•issue warning letters;

•request modifications to promotional materials 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;

•suspend or withdraw regulatory approval;

•suspend any ongoing clinical trials;

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

•suspend or impose restrictions on operations, including costly new manufacturing requirements; or

•seize or detain products, refuse to permit the import or export of products, or require us to initiate a product recall.

The occurrence of any event or penalty described above, or any other sanction by a regulatory authority or other governmental entity, may inhibit our ability to commercialize our products and generate revenue.

The FDA and other regulatory agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses. If we are found or alleged to have improperly promoted off-label uses, we may become subject to significant liability.

The FDA and other regulatory agencies strictly regulate the promotional claims that may be made about drug products. These regulations include standards and restrictions for direct-to-consumer advertising, industry-sponsored scientific and educational activities, promotional activities involving the internet and off-label promotion. Any regulatory approval that the FDA grants is limited to those indications and patient populations for which a drug is deemed to be safe and effective by the FDA.

While physicians in the United States may choose, and are generally permitted, to prescribe products for uses that are not described in the product’s labeling and for uses that differ from those tested in clinical trials and approved by the regulatory authorities, our ability to promote any of our products will be limited to those indications and populations that are specifically approved by the FDA or such other regulatory agencies, and if we are found to have promoted such off-label uses, we may become subject to significant liability. For example, the federal government has levied large civil and criminal fines against companies for alleged improper promotion and in some instances has also required companies to enter into corporate integrity agreements or imposed permanent injunctions under which specified promotional conduct is changed or curtailed. If we cannot successfully manage the promotion of our products, we could become subject to significant liability, which would materially adversely affect our business and financial condition.

Our commercial success depends upon attaining significant market acceptance of our approved product or product candidates, if approved, among hospitals, physicians, patients and healthcare payors.

Our approved product may not gain market acceptance among hospitals, physicians, health care payors, patients and the medical community. Market acceptance of any of our approved product or product candidates for which we receive approval in the future, if any, depends on a number of factors, including:

•the efficacy and safety of such product candidates as demonstrated in clinical trials;

•the clinical indications for which the product candidate is approved;

•acceptance by hospitals, physicians and patients of the product candidate as a safe and effective treatment, particularly the ability of mavorixafor and our other product candidates to establish themselves as a new standard of care for the indications that we are pursuing;

•the potential and perceived advantages of our products and product candidates over alternative treatments as compared to their relative costs;

•the prevalence and severity of any side effects with respect to our products or product candidates, including mavorixafor;

•our ability to offer any approved products for sale at competitive prices;

•the timing of market introduction of our products as well as competitive products;

•our pricing, and the availability of coverage and adequate reimbursement by third party payors and government authorities;

•relative convenience and ease of administration; and

•the effectiveness of our sales and marketing efforts and those of our potential future collaborators.

There may be delays in getting our products or product candidates on hospital or insurance formularies or limitations on coverages that may be available in the early stages of commercialization for newly approved drugs. If our product or any product candidate that is approved fails to achieve market acceptance among hospitals, physicians, patients or health care payors, we will not be able to generate significant revenues, which would have a material adverse effect on our business, prospects, financial condition and results of operations.

If we are unable to maintain effective sales and marketing capabilities or to selectively enter into agreements with third parties to sell and market our product or product candidates, we may not be successful in commercializing our product candidates that have been approved.

~~Although we have built a sales or marketing infrastructure, as an organization we have no experience in the sales, marketing or distribution of pharmaceutical products.~~ To achieve commercial success for our approved product for which we retain sales and marketing responsibilities, we ~~are~~must ~~continuing~~either to build or outsource a focused sales and marketing infrastructure to sell ~~XOLREMDI in the U.S. Although~~ our ~~management~~approved ~~team has previous experience with such efforts, there can be no assurance that we will be successful in building these operations~~product. If we are unable to establish and maintain adequate sales, marketing and distribution capabilities, we may not be able to generate product revenue and may not become profitable. We will also be competing with many companies that currently have extensive and well-funded sales and marketing operations. If any of our product candidates are approved, we may be unable to compete successfully against these more established companies.

and maintain adequate sales, marketing and distribution capabilities, we may not be able to generate product revenue and may not become profitable. We will also be competing with many companies that currently have extensive and well-funded sales and marketing operations. If any of our product candidates are approved, we may be unable to compete successfully against these more established companies.

There are risks involved both with establishing our own sales and marketing capabilities and with entering into arrangements with third parties to perform these services, such as the exclusive licensing and supply agreement we entered into with Norgine in January 2025. For example, recruiting and training a sales force is expensive and time consuming and could delay any product 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.

Factors that may inhibit our efforts to commercialize our product candidates on our own include:

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

•the inability of sales personnel to obtain access to physicians or educate adequate numbers of physicians on the benefits of prescribing any future products; and

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

If we enter into arrangements with third parties to perform sales, marketing and distribution services, our product revenue or the profitability of these product ~~revenue~~revenues to us may be lower than if we were to market and sell any products that we develop ourselves. In addition, we may not be successful in entering into arrangements with third parties to sell and market our product or product candidates or may be unable to do so on terms that are favorable to us. We may have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our products effectively. If we do not establish sales and marketing capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing our product or product candidates.

establish sales and marketing capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing our product or product candidates.

We face substantial competition that may result in others discovering, developing or commercializing products before or more successfully than we do.

The development and commercialization of new drug products is highly competitive. We face competition with respect to our current product candidates, and will face competition with respect to any product candidates that we may seek to develop or commercialize in the future, from major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies worldwide. Some of these competitive products and therapies are based on scientific approaches that are the same as or similar to our approach and others are based on entirely different approaches. Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for research, development, manufacturing and commercialization.

We have obtained FDA approval for mavorixafor for use as an oral, once-daily therapy to increase the number of circulating mature neutrophils and lymphocytes in patients aged 12 years and older with WHIM syndrome, and are developing mavorixafor for potential use in other chronic neutropenic disorders. We are aware of other companies that are developing CXCR4 inhibitors that are in a similar stage of development as mavorixafor, including BioLineRx, Noxxon, Upsher-Smith, Polyphor and Glycomimetics. To our knowledge, there do not appear to be any competitors with programs in development for WHIM syndrome or chronic neutropenia disorders. With respect to chronic neutropenia, filgrastim injections (G-CSF) and two biosimilars (Zarxio and Nivestym) are FDA-approved to reduce the incidence and duration of after effects of severe neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia or idiopathic neutropenia.

In many diseases, these drugs are administered in combination to enhance efficacy. Some of the currently approved drug therapies are branded and subject to patent protection, and others are available on a generic basis. Many of these approved drugs are well-established therapies and are widely accepted by physicians, patients and third-party payors. Insurers and other third-party payors may also encourage the use of generic products. We expect that if any of our product candidates are approved, they will be priced at a significant premium over competitive generic products. This may make it difficult for us to achieve our business strategy of using our product candidates in combination with existing therapies or replacing existing therapies with our product candidates.

Our competitors may develop products that are more effective, have a better safety profile, are more convenient or less costly than any that we are developing or that would render our product candidates obsolete or non-competitive. Our competitors may also obtain marketing approval from the FDA or other regulatory authorities for their products sooner than we may obtain approval for our product candidates, which could result in our competitors establishing a strong market position before we are able to enter the market.

Many of our competitors have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller and other early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These third parties may compete with us in recruiting and retaining qualified scientific and management personnel, establishing clinical trial ~~sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.~~

Even though we have obtained approval for one of our product candidates from the FDA, we may never obtain approval for our product candidates outside of the United States, which would limit our market opportunities and could harm our business.47

~~Approval~~sites ~~of a product candidate in the United States by the FDA does not ensure approval of such product candidate by regulatory authorities in other countries or jurisdictions,~~ and ~~approval~~patient byregistration a foreign regulatory authority does not ensure approval by regulatory authorities in other foreign countries or by the FDA. Clinical trials conducted in one country may not be accepted by regulatory authorities in other countries. Even if the FDA grants marketing approval for a product candidate, comparable foreign regulatory authorities also must approve the manufacturing and marketing of the product candidate in those countries. Approval procedures vary among jurisdictions and can involve requirements and administrative review periods different from, and more onerous than, those in the United States, including additional preclinical studies or clinical trials~~. In many countries outside the United States~~, aas ~~product~~well ~~candidate~~as ~~must be approved for reimbursement before it can be approved for sale~~ in ~~that~~acquiring ~~country.~~technologies Incomplementary ~~some cases~~to, ~~the~~or ~~price~~necessary ~~that we intend to charge~~ for ~~any product candidates~~, isour ~~also subject to approval~~programs. ~~Obtaining approval for any future product candidates in the European Union from the European Commission following the opinion of the~~

43Even though we have obtained FDA approval for one of our product candidates, we may never obtain approval for our product candidates outside of the United States, which would limit our market opportunities and could harm our business.

Approval of a product candidate in the United States by the FDA does not ensure approval of such product candidate by regulatory authorities in other countries or jurisdictions, and approval by a foreign regulatory authority does not ensure approval by regulatory authorities in other foreign countries or by the FDA. Clinical trials conducted in one country may not be accepted by regulatory authorities in other countries. Even if the FDA grants marketing approval for a product candidate, comparable foreign regulatory authorities also must approve the manufacturing and marketing of the product candidate in those countries. Approval procedures vary among jurisdictions and can involve requirements and administrative review periods different from, and more onerous than, those in the United States, including additional preclinical studies or clinical trials. In many countries outside the United States, a product candidate must be approved for reimbursement before it can be approved for sale in that country. In some cases, the price that we intend to charge for any product candidate is also subject to approval. Obtaining approval for any future product candidates in the European Union from the European Commission following the opinion of the European Medicines Agency (“EMA”) ~~would~~could be a lengthy and expensive process. Even if a product candidate is approved, the FDA or the European Commission, as the case may be, may limit the indications for which the drug may be marketed, require extensive warnings on the drug labeling or require expensive and time-consuming additional clinical trials or reporting as conditions of approval. If marketing authorization for mavorixafor in the European Union is granted under exceptional circumstances, such authorization would be subject to specific post-authorization obligations and annual review, and failure to comply with such obligations or adverse findings in required follow-up studies could result in modification, suspension or withdrawal of the authorization. Obtaining foreign regulatory approvals and compliance with foreign regulatory requirements could result in significant delays, difficulties and costs for us and could delay or prevent the introduction of any future product candidates in certain countries.

Significant political, trade, regulatory developments, economic downturns, inflation, increases in interest rates, natural disasters, public health crises, geopolitical events, such as the war in Ukraine and in Gaza and other circumstances beyond our control, could have a material adverse effect on our business, financial condition or results of operations.

Significant political, trade, or regulatory developments, such as those stemming from the change in U.S. federal administration, are difficult to predict and may have a material adverse effect on us. Similarly, 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 2017, the U.S. Congress and the Trump administration made substantial changes to U.S. policies, which included comprehensive corporate and individual tax reform. In addition, the Trump administration called for significant changes to U.S. trade, healthcare, immigration and government regulatory policy. With the transition to the Biden administration in early 2021, changes to U.S. policy occurred and since the start of the Trump administration in 2025, U.S. policy changes have been implemented at a rapid pace and additional changes are likely. Changes to U.S. policy implemented by the U.S. Congress, the Trump administration or any new 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. For example, in early 2025, the United States imposed blanket 10% tariffs on virtually all imports to the U.S. and significantly higher so-called reciprocal tariffs applicable to imports from many countries. In September 2025, President Trump announced 100% tariffs on imported branded or patented pharmaceuticals, effective October 1, 2025, unless the importing company is building U.S. manufacturing capacity. It is not yet clear whether these tariffs would apply to the importation of active pharmaceutical ingredients and possibly bulk drug products that are intended for use in clinical trials and not for commercial sale, which could increase the costs of materials for our clinical trials. The Trump 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. While certain tariffs have been suspended, modified or temporarily reduced, we cannot predict the results of the U.S. government’s trade negotiations or the outcome of ongoing legal challenges to specific tariff policies. Historically, tariffs have led to increased trade and political tensions. 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. 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.

Further, the global economy, including credit and financial markets, outside of recent tariffs, has experienced extreme volatility and disruptions, including, among other things, severely diminished liquidity and credit availability, declines in consumer

confidence, declines in economic growth, supply chain shortages, increases in inflation rates, higher interest rates and uncertainty about economic stability. For example, the COVID-19 pandemic resulted in widespread unemployment, economic slowdown and extreme volatility in the capital markets. The U.S. Federal Reserve recently raised interest rates multiple times in response to concerns about inflation and it may raise them again. Higher interest rates, coupled with reduced government spending and volatility in financial markets may increase economic uncertainty. If the equity and credit markets deteriorate, including as a result of political unrest or war, such as the war in Ukraine or in Gaza, it may make any necessary debt or equity financing more difficult to obtain in a timely manner or on favorable terms, more costly or more dilutive. Increased inflation rates can adversely affect us by increasing our costs, including labor and employee benefit costs.

If we seek approval to commercialize our product candidates outside of the United States, a variety of risks associated with international operations could harm our business.

If we seek approval of our product candidates outside of the United States, we expect that we will be subject to additional risks in commercialization including:

•different regulatory requirements for approval of therapies in foreign countries;

•reduced protection for intellectual property rights;

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

•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, which could result in increased operating expenses and reduced revenues, and other obligations incident to doing business in another country;

•foreign reimbursement, pricing and insurance regimes;

•workforce uncertainty in countries where labor unrest is more common than in the United States;

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

•business interruptions resulting from geopolitical actions, including war and terrorism, or natural disasters and public health epidemics.

We or our collaborators may not seek, or may seek but never receive, regulatory approval to market our products, including XOLREMDI, or product candidates outside of the U.S. or in any particular country or region. In order to market any product outside of the U.S., we or our collaborators must establish and comply with the numerous and varying safety, efficacy and other regulatory requirements of other countries. Approval procedures vary among countries and can involve additional non-clinical studies or clinical trials, additional work related to manufacturing and analytical testing on controls, and additional administrative review periods. The time required to obtain approvals in other countries might differ from that required to obtain FDA approval. Marketing approval in one country does not ensure marketing approval in another, but a failure or delay in obtaining marketing approval in one country may have a negative effect on the regulatory process in other countries. The marketing approval processes in other countries may implicate all of the risks detailed above regarding FDA approval in the U.S. as well as other risks. In particular, in many countries outside of the U.S., products must receive pricing and reimbursement approval before the product can be commercialized. Obtaining this approval may require additional studies and data, and can result in substantial delays in bringing products to market in such countries and such investment may not be justified from a business standpoint given the market opportunity or level of required investment. Even if we or our collaborators generate the data and information which we or our collaborators believe may be sufficient to file an application for regulatory approval of any of our products or product candidates in a region or country outside the U.S., the relevant regulatory agency may find that we or our collaborators did not meet the requirements for approval, or even if our application is approved, we may have significant post-approval obligations.

We have no prior experience in these areas. In addition, there are complex regulatory, tax, labor and other legal requirements imposed by many of the individual countries in and outside of Europe with which we will need to comply. Many biopharmaceutical companies have found the process of marketing their own products in foreign countries to be very challenging. Any setback or delay in obtaining regulatory approval or commencing marketing, if approved, for our product candidates in a country or region outside the U.S. where we or our collaborators have decided it makes business sense to proceed may have a material adverse effect on our business and prospects.

product candidates in a country or region outside the U.S. where we or our collaborators have decided it makes

business sense to proceed may have a material adverse effect on our business and prospects.

Any products that we commercialize may become subject to unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, which would harm our business.

The laws and regulations that govern marketing approvals, pricing, coverage and reimbursement for new drug products vary widely from country to country. Current and future legislation may significantly change the approval requirements in ways that could involve additional costs and cause delays in obtaining approvals. Some countries require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins after marketing or product licensing approval is granted and, in some markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted. As a result, we might be subject to price regulations that delay our commercial launch of a product, possibly for lengthy time periods, and negatively impact the revenues we are able to generate from the sale of the product in that

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widely from country to country. Current and future legislation may significantly change the approval requirements in ways that could involve additional costs and cause delays in obtaining approvals. Some countries require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins after marketing or product licensing approval is granted and, in some markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted. As a result, we might be subject to price regulations that delay our commercial launch of a product, possibly for lengthy time periods, and negatively impact the revenues we are able to generate from the sale of the product in that country. Adverse pricing limitations may hinder our ability to recoup our investment in ~~XOLREMDI~~mavorixafor or future product candidates, even if those candidates obtain marketing approval.

Our ability to commercialize ~~XOLREMDI~~mavorixafor or future product candidates successfully depends in part on the extent to which coverage and adequate reimbursement for these products and related treatments are available from government health administration authorities, private health insurers and other organizations. Government authorities and other third-party payors, such as private health insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels. A primary trend in the U.S. and E.U. healthcare industries and elsewhere is cost containment.

Government authorities and other third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications. 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 coverage and reimbursement will be available for ~~XOLREMDI~~mavorixafor or any other product that we commercialize and, if coverage and reimbursement is available, the level of reimbursement. Reimbursement may impact the demand for, or the price of, any product candidate for which we obtain marketing approval. Obtaining and maintaining adequate reimbursement for ~~XOLREMDI~~mavorixafor may be particularly difficult because of the higher prices typically associated with drugs directed at smaller populations of patients. In addition, third-party payors are likely to impose strict requirements for reimbursement of a higher priced drug, and any launch of a competitive product is likely to create downward pressure on the price initially charged. If reimbursement is not available or is available only to a limited degree, we may not be able to successfully commercialize ~~XOLREMDI~~mavorixafor or any future product candidate for which we obtain marketing approval. Even if favorable coverage and reimbursement status is attained, less favorable coverage policies and reimbursement rates may be implemented in the future.

There may be significant delays in obtaining coverage and reimbursement for newly approved drugs, and coverage may be more limited than the purposes for which the drug is approved by the applicable regulatory authority. Moreover, eligibility for coverage and reimbursement does not imply that any drug will be paid for in all cases or at a rate that covers our costs, including research, development, intellectual property, manufacturing, sale and distribution expenses. Interim reimbursement levels for new drugs, if applicable, may also not be sufficient to cover our costs and may not be made permanent.

Reimbursement rates may vary according to the use of the drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost drugs, and may be incorporated into existing payments for other services. 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. In the United States, third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement policies. In the European Union, reference pricing systems and other measures may lead to cost containment and reduced prices. Our inability to promptly obtain coverage and adequate reimbursement rates from both government-funded and private payors for XOLREMDI ~~(mavorixafor)~~ or for any future approved product candidates could have a material adverse effect on our operating results, our ability to raise capital needed to develop additional product candidates and commercialize products and our overall financial condition.

Governments outside the United States tend to impose strict price controls, which may adversely affect our revenues, if any.

In some countries, particularly the countries of the European Union, 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 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. If reimbursement of our products is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our business could be harmed, possibly materially.

Product liability lawsuits against us could cause us to incur substantial liabilities and could limit the commercialization of any product candidates 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 will face an even greater risk with respect to commercial sales of any products that we may develop. 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:~~

Regardless of merit or eventual outcome, liability claims may result in:

•reduced resources of our management to pursue our business strategy;

•decreased demand for any products that we may develop;

•injury to our reputation and significant negative media attention;

45•withdrawal of clinical trial patients;

•withdrawal of clinical trial participants;

•significant costs to defend any related litigation;

•substantial monetary awards to trial ~~participants~~patients or patients;

•loss of revenue;

•increased insurance costs; and

•the inability to commercialize any products that we may develop.

Although we maintain clinical trial insurance coverage, it may not be adequate to cover all liabilities that we may incur. We anticipate that we will need to increase our insurance coverage as we continue clinical trials or begin commercialization of any products. Insurance coverage is increasingly expensive. We may not be able to obtain or maintain insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise.

Risks Related to Government Regulation

Our relationships with customers and third-party payors are subject to applicable anti-kickback, fraud and abuse and other healthcare laws and regulations, which could expose us to significant penalties, including administrative, civil and criminal penalties, contractual damages, reputational harm and diminished profits and future earnings.

We have an approved, commercialized product, and we are subject to additional healthcare statutory and regulatory requirements and enforcement by the federal government and the states and foreign governments in the jurisdictions in which we conduct our business. Healthcare providers and third-party payors will play a primary role in the recommendation and prescription of any product candidates for which we obtain marketing approval. Our current and future arrangements with third-party payors and customers 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 research, market, sell and distribute XOLREMDI or any products candidates for which we obtain marketing approval in the future. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, structuring and commission(s), certain customer incentive programs and other business arrangements generally. Activities subject to these laws also involve the improper use of information received in the course of patient recruitment for clinical trials. See the section in this Annual Report on Form 10-K for the fiscal year ended December 31, ~~2024~~2025 ~~entitled~~titled “Business – Government Regulation – Other Healthcare Laws and Compliance Requirements.”

Efforts to ensure that our business arrangements with third parties comply with applicable healthcare laws and regulations involve substantial costs. 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 it, we may be subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, exclusion from government funded healthcare programs, such as Medicare and Medicaid, additional reporting requirements and/or 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. If any of the physicians or other healthcare providers or entities with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to significant criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.

Current and future legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product or product candidates and affect the prices we may obtain.

In the United States 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 product candidates, restrict post-approval activities and affect our ability to sell profitably any approved product or product candidates for which we obtain marketing approval in the future.

We cannot predict what healthcare reform initiatives may be adopted in the future. However, we expect that the ACA, 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 may receive for any approved product. These laws may result in additional reductions in Medicare and other healthcare funding. Any reduction in payments from Medicare or other government programs may result in a similar reduction in payments from private payors. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize our products.

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may result in a similar reduction in payments from private payors. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize our products.

Multiple recent executive actions have signaled the federal government’s increasing focus on lowering prescription drug prices, adding to the uncertainty surrounding future drug pricing and reimbursement frameworks, including the executive orders titled “Delivering Most-Favored-Nation Prescription Drug Pricing,” which directed the Secretary of Health and Human Services (HHS) to identify and communicate most-favored-nation price targets for prescription drugs and to propose a rulemaking plan to impose such pricing if “significant progress” is not made, and “Lowering Drug Prices by Once Again Putting Americans First,” which contained a broad set of directives aimed at reducing drug costs. Separately, prior to the enactment of “An Act to provide for reconciliation pursuant to title II of H. Con. Res. 14” (the “Act”), orphan drugs were exempt from Medicare price negotiation only if they had received a single orphan designation and were approved solely for the corresponding rare disease or condition. The Act amended this exemption to apply more broadly: now, any orphan-designated drug is exempt from price negotiation, regardless of the number of orphan designations it has received, provided the drug’s approved indications are exclusively for those rare diseases.

Legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical products. We cannot be sure whether additional legislative changes will be enacted, or whether FDA regulations, guidance or interpretations will be changed, or what the impact of such changes on our operations may be. In addition, increased scrutiny by the U.S. Congress of the FDA’s approval process may significantly delay or prevent marketing approval for our future product candidates, as well as subject us to more stringent product labeling and post-marketing conditions and other requirements. Moreover, the U.S. Supreme Court’s June 2024 decision to overturn established case law giving deference to regulatory agencies’ interpretations of ambiguous statutory language has introduced uncertainty regarding the extent to which the U.S. government regulations, policies and decisions may become subject to increasing legal challenges, delays, and/or changes.

See the sections of this Annual Report on Form 10-K for the fiscal year ended December 31, ~~2024~~2025 ~~entitled~~titled, “Business – Government Regulation – ~~Pharmaceutical~~ Coverage, ~~Pricing~~ and Reimbursement” and “Business – Government Regulation – Healthcare Reform.”

We are subject to anti-corruption laws, as well as export control laws, customs laws, sanctions laws and other laws governing our operations. If we fail to comply with these laws, we could be subject to civil or criminal penalties, other remedial measures and legal expenses, which could adversely affect its business, results of operations and financial condition.

Our operations are subject to anti-corruption laws, including the Foreign Corrupt Practices Act (“FCPA”) and other anti-corruption laws that apply in countries where we do business and may do business in the future. The FCPA and these other laws generally prohibit us, our officers and employees and intermediaries from bribing, being bribed or making other prohibited payments to government officials or other persons to obtain or retain business or gain some other business advantage. We may in the future operate in jurisdictions that pose a high risk of potential FCPA violations, and may participate in collaborations and relationships with third parties whose actions could potentially subject us to liability under the FCPA or local anti-corruption laws. In addition, we cannot predict the nature, scope or effect of future regulatory requirements to which its international operations might be subject or the manner in which existing laws might be administered or interpreted.

We are also subject to other laws and regulations governing our international operations, including regulations administered by the U.S. government and authorities in the European Union or the United Kingdom, including applicable export control regulations, economic sanctions on countries and persons, customs requirements and currency exchange regulations, which we collectively refer to as Trade Control Laws.

There is no assurance that we will be completely effective in ensuring our compliance with all applicable anti-corruption laws, including the FCPA or other legal requirements, including Trade Control Laws. If we are not in compliance with the FCPA and other anti-corruption laws or Trade Control Laws, we may be subject to criminal and civil penalties, disgorgement and other sanctions and remedial measures, and legal expenses, which could have an adverse impact on our business, financial condition, results of operations and liquidity. Likewise, any investigation of any potential violations of the FCPA, other anti-corruption laws or Trade Control Laws by U.S. or other authorities could also have an adverse impact on our reputation, business, results of operations and financial condition.

Inadequate funding for the FDA, the SEC and other government agencies could hinder their ability to hire and retain key personnel, and substantial leadership, personnel, and policy changes could 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 and approve new products can be affected by a variety of factors, including government budget and funding levels, the 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 government 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, including substantial leadership, personnel, and policy changes, may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business. For example, over the last several years the U.S. government has shut down several times and certain regulatory agencies, such as the FDA and the SEC, have had to furlough critical FDA, SEC and other government employees and stop critical activities. 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, in our operations as a public company, 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.

Risks Related to Our Dependence on Third Parties

We have limited experience manufacturing our product or product candidates on a large clinical or commercial scale and have no manufacturing facility. We are currently dependent on a single third party manufacturer for the manufacture of the active pharmaceutical ingredient (“API”) for mavorixafor, and a single manufacturer of mavorixafor finished drug product capsules. If we experience problems with these third parties, the manufacturing of mavorixafor could be delayed, which could harm our results of operations.

have no manufacturing facility. We are currently dependent on a single third-party manufacturer for the manufacture of the API for mavorixafor, and a single manufacturer of mavorixafor finished drug product capsules. If we experience problems with these third parties, the manufacturing of mavorixafor could be delayed, which could harm our results of operations.

To meet our projected needs for clinical supplies to support our development activities through regulatory approval and commercial manufacturing, the manufacturers with whom we currently work will need to increase its frequency and/or scale of production or we will need to find additional or alternative manufacturers. We have not yet secured alternate suppliers in the event the current manufacturer we utilize is unable to meet demand, or if otherwise we experience any problems with them. If such problems arise and we are unable to arrange for alternative third-party manufacturing sources, we are unable to find an alternative third party capable of reproducing the existing manufacturing method or we are unable to do so on commercially reasonable terms or in a timely manner, we may not be able to complete development of our product candidates, or market or distribute them.

Reliance on third-party manufacturers entails risks to which we would not be subject if we manufactured our product or product candidates ourselves, including reliance on the third party for regulatory compliance and quality assurance, the possibility of breach of the manufacturing agreement by the third party because of factors beyond our control (including a failure to synthesize and manufacture our product candidates or any products that we may eventually commercialize in accordance with our specifications), and the possibility of termination or nonrenewal of the agreement by the third party, based on its own business priorities, at a time that is costly or damaging to us. In addition, the FDA and other regulatory authorities require that our product or product candidates that we may eventually commercialize be manufactured according to cGMP and similar foreign standards. Drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and some state agencies, and are subject to periodic unannounced inspections for compliance with cGMP requirements. Manufacturers and other parties in the supply chain also must meet chain of distribution requirements and build electronic, interoperable systems for product tracking and tracing and for notifying the FDA of counterfeit, diverted, stolen and intentionally adulterated products or other products that are otherwise unfit for distribution in the United States. Changes to the manufacturing process are strictly regulated and often require prior FDA or other regulatory authority approval before being implemented. FDA requirements also require investigation and correction of any deviations from cGMP and impose reporting and documentation requirements upon us and any third-party manufacturers that we may decide to use. Accordingly, the manufacturers must continue to expend time, money and effort in the areas of production and quality control to maintain cGMP compliance. Any failure by our third-party manufacturers to comply with cGMP or failure to scale up manufacturing processes, including any failure to deliver sufficient quantities of product candidates or products if they are approved in a timely manner, could lead to a delay in, or failure to obtain, regulatory approval of any of our product candidates. In addition, such failure could be the basis for the FDA to issue a warning letter, withdraw approvals for product candidates previously granted to us, or take other regulatory or legal action, including recall or seizure, total or partial suspension of production, suspension of ongoing clinical trials, refusal to approve pending applications or supplemental applications, detention of product, refusal to permit the import or export of products, injunction, or imposing civil and criminal penalties.

Our current manufacturers and any future manufacturers may not be able to manufacture our product or product candidates at a cost or in quantities or in a timely manner necessary to make commercially successful products. If we successfully commercialize any of our product candidates, we may be required to establish large-scale commercial manufacturing capabilities. In addition, as our drug development pipeline increases and matures, we will have a greater need for clinical study and commercial manufacturing capacity. We have limited experience manufacturing pharmaceutical products on a commercial scale and some of these manufacturers will need to increase their scale of production to meet our projected needs for commercial manufacturing, the satisfaction of which may not be met on a timely basis.

We rely on third-party CROs to conduct our preclinical studies and clinical trials. If these CROs do not successfully carry out their contractual duties or meet expected deadlines, we may not be able to obtain regulatory approval for or commercialize our product candidates and our business could be substantially harmed.

We have relied upon and plan to continue to rely upon third-party contract research organizations, or CROs, and clinical data management organizations to monitor and manage data for our ongoing preclinical and clinical programs. Although we control only certain aspects of their activities, we are responsible for ensuring that each of our studies is conducted in accordance with the applicable protocol and legal, regulatory and scientific standards, and our reliance on the CROs does not relieve us of our regulatory responsibilities. We also rely on third parties to conduct our preclinical studies in accordance with Good Laboratory Practice, or GLP, requirements and the Laboratory Animal Welfare Act of 1966 requirements, where applicable. We, our CROs and our clinical trial sites are required to comply with regulations and current Good Clinical Practices, or GCP, and comparable foreign requirements to ensure that the health, safety and rights of patients are protected in clinical trials, and that data integrity is assured. Regulatory authorities ensure compliance with GCP requirements through periodic inspections of trial sponsors and trial sites. If we, any of our CROs or our clinical trial sites fail to comply with applicable GCP requirements, the clinical data generated in our clinical trials or a specific site may be deemed unreliable and the FDA or comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications.

generated in our clinical trials or a specific site may be deemed unreliable and the FDA or comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications.

Our CROs are not our employees, and except for remedies available to us under our agreements with such CROs, we cannot control whether or not they devote sufficient time and resources to our ongoing clinical and preclinical programs. If CROs do not successfully carry out their contractual obligations or meet expected timelines 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 may not be able to obtain regulatory approval for or successfully commercialize our product candidates. 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.

Disruptions in our supply chain could delay the commercial sale of our product.

Any significant disruption in our supplier relationships could harm our business. We currently rely on a single source supplier of mavorixafor, as well a single supplier for the finished product capsules for mavorixafor. If either of these single source suppliers suffers a major natural or man-made disaster at its manufacturing facility, we would not be able to manufacture mavorixafor on a commercial scale until a qualified alternative supplier is identified. Although alternative sources of supply exist, the number of third party suppliers with the necessary manufacturing and regulatory expertise and facilities is limited, and it could be expensive and take a significant amount of time to arrange for alternative suppliers. Any significant delay in the supply of a product or product candidate or its key materials for an ongoing clinical study could considerably delay completion of our clinical studies, product testing and potential regulatory approval of our product candidates. If we or our manufacturers are unable to purchase these key materials after regulatory approval of our product candidates, the commercial launch of our product candidates would be delayed, which would impair our ability to generate revenues from the sale of our product candidates.

Our employees, principal investigators, CROs, CMOs and consultants may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could have a material adverse effect on our business.

We are exposed to the risk that our employees, principal investigators, CROs, CMOs and consultants may engage in fraudulent conduct or other illegal activity. Misconduct by these parties could include intentional failures to comply with FDA regulations or similar regulations of comparable foreign regulatory authorities, to provide accurate information to the FDA or comparable foreign regulatory authorities, to comply with manufacturing standards we have established, to comply with federal and state healthcare fraud and abuse laws and regulations and similar laws and regulations established and enforced by comparable foreign regulatory authorities, to report financial information or data accurately or to disclose unauthorized activities to us. In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, 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. Employee or third party misconduct could also involve the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation. It is not always possible to identify and deter employee misconduct and the precautions we take to detect and prevent this activity, such as employee training, 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 be in compliance with such laws or regulations. 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 and results of operations, including the imposition of significant fines or other sanctions.

We have established, and may seek to selectively establish in the future, collaborations, and, if we are unable to establish them on commercially reasonable terms, we may have to alter our development and commercialization plans.

Our drug development programs and the potential commercialization of our product candidates will require substantial additional cash to fund expenses. For some of our product candidates, we may decide to collaborate with pharmaceutical and biotechnology companies for the development and potential commercialization of those product candidates.

We face significant competition in seeking appropriate collaborators. Whether we reach a definitive agreement for a collaboration will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors. Those factors may include the design or results of clinical trials, the likelihood of approval by the FDA or similar regulatory authorities outside the United States, the potential market for the subject product candidate, the costs and complexities of manufacturing and delivering such product candidate to patients, the potential of competing products, the existence of uncertainty with respect to our ownership of technology, which can exist if there is a challenge to such ownership without regard to the merits of the challenge and industry and market conditions generally. The collaborator may also consider alternative product candidates for similar indications that may be available to collaborate on and whether such a collaboration could be more attractive than the one with us for our product candidates.

challenge and industry and market conditions generally. The collaborator may also consider alternative product candidates for similar indications that may be available to collaborate on and whether such a collaboration could be more attractive than the one with us for our product candidates.

We may depend on such collaborations for the development and commercialization of our product candidates. If those collaborations are not successful, we may not be able to capitalize on the market potential of our product candidates.

We have, and may selectively seek in the future, third-party collaborators for the development and commercialization of our product candidates. Our likely collaborators for any collaboration arrangements include large and mid-size pharmaceutical companies, regional and national pharmaceutical companies and biotechnology companies. If we enter into any such arrangements with any third parties, we will likely have limited control over the amount and timing of resources that our collaborators dedicate to the development or commercialization of our product candidates. Our ability to generate revenue from these arrangements will depend on our collaborators’ abilities to successfully perform the functions assigned to them in these arrangements, for example the Norgine Agreement and our agreement with Taiba Middle East Fz LLC.

Collaborations involving our product candidates pose many risks to us, including that:

•collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations;

•collaborators may not pursue development and commercialization of our product candidates or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborator’s strategic focus or available funding or external factors such as an acquisition that diverts resources or creates competing priorities;

•collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing;

•collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates or products 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;

•collaborators with marketing and distribution rights to one or more product candidates or products may not commit sufficient resources to the marketing and distribution of such drugs;

•collaborators may 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 proprietary information or expose us to potential litigation;

•disputes may arise between the collaborators and us that result in the delay or termination of the research, development or commercialization of our product candidates or products or that result in costly litigation or arbitration that diverts management attention and resources;

•we may lose certain valuable rights under circumstances identified in our collaborations if we undergo a change of control;

•collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates; and

•collaboration agreements may not lead to development or commercialization of products or product candidates in the most efficient manner or at all. In addition, if a future collaborator of ours were to be involved in a business combination, the continued pursuit and emphasis on our product development or commercialization program under such collaboration could be delayed, diminished or terminated.

Risks Related to Our Intellectual Property

Recent laws and rulings by U.S. courts make it difficult to predict how patents will be issued or enforced in our industry.

Changes in either the patent laws or interpretation of the patent laws in the United States and other countries may have a significant impact on our ability to protect our technology and enforce our intellectual property rights.

There have been numerous changes over the past ten years to the patent laws and to the rules of the United States Patent and Trademark Office (“USPTO”), which may have a significant impact on our ability to protect our technology and enforce our intellectual property rights. For example, the Leahy-Smith America Invents Act (“AIA”), which was signed into law in 2011, includes a transition from a “first-to-invent” system to a “first-to-file” system, and changes the way issued patents are challenged. Certain changes, such as the institution of inter partes review proceedings, that allow third parties to challenge newly issued patents, came into effect on September 16, 2012. The burden of proof required for challenging a patent in these proceedings is lower than in district court litigation, and patents in the biologics and pharmaceuticals industry have been successfully challenged using these new post-grant challenges. In addition, the U.S. Supreme Court has ruled on several patent cases in recent years, either narrowing the scope of patent protection available in specified circumstances or weakening the rights of patent owners in specified situations. Depending on decisions by the U.S. Congress, the federal courts, and the USPTO, these substantive changes to patent law associated with the AIA may further weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future, all of which could harm our business.

intellectual property rights. For example, the Leahy-Smith America Invents Act (“AIA”), which was signed into law in 2011, includes a transition from a “first-to-invent” system to a “first-to-file” system, and changes the way issued patents are challenged. Certain changes, such as the institution of inter partes review proceedings, that allow third parties to challenge newly issued patents, came into effect on September 16, 2012. The burden of proof required for challenging a patent in these proceedings is lower than in district court litigation, and patents in the biologics and pharmaceuticals industry have been successfully challenged using these new post-grant challenges. In addition, the U.S. Supreme Court has ruled on several patent cases in recent years, either narrowing the scope of patent protection available in specified circumstances or weakening the rights of patent owners in specified situations. Depending on decisions by the U.S. Congress, the federal courts, and the USPTO, these substantive changes to patent law associated with the AIA may further weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future, all of which could harm our business.

Furthermore, the patent positions of companies engaged in the development and commercialization of biologics and pharmaceuticals are particularly uncertain. We cannot assure you that our efforts to seek patent protection for our technology and products will not be negatively impacted by the changes described above, future rulings in district court cases or changes in guidance or procedures issued by the USPTO. We cannot fully predict what impact the Supreme Court’s decisions may have on the ability of life science companies to obtain or enforce patents relating to their products and technologies in the future.

Moreover, although the Supreme Court has held in Myriad that isolated segments of naturally occurring DNA are not patent-eligible subject matter, certain third parties could allege that activities that we may undertake infringe other gene-related patent claims, and we may deem it necessary to defend ourselves against these claims by asserting non-infringement and/or invalidity positions, or pay to obtain a license to these claims. In any of the foregoing or in other situations involving third-party intellectual property rights, if we are unsuccessful in defending against claims of patent infringement, we could be forced to pay damages or be subjected to an injunction that would prevent us from utilizing the patented subject matter. Such outcomes could harm our business.

If we are unable to protect our intellectual property rights, our competitive position could be harmed.

We depend on our ability to protect our proprietary technology. We rely on trade secret, patent, copyright and trademark laws, and confidentiality, licensing and other agreements with employees and third parties, all of which offer only limited protection. Our success depends in large part on our ability to obtain and maintain patent protection in the United States and other countries with respect to our proprietary technology and products. Where we have the right to do so under our license agreements, we seek to protect our proprietary position by filing patent applications in the United States and abroad related to our novel technologies and products that are important to our business.

Our success depends in large part on our ability to obtain and maintain patent protection in the United States and other countries with respect to our proprietary technology and products. Where we have the right to do so under our license agreements, we seek to protect our proprietary position by filing patent applications in the United States and abroad related to our novel technologies and products that are important to our business.

The patent positions of biotechnology and pharmaceutical companies generally are highly uncertain, involve complex legal and factual questions and have in recent years been the subject of much litigation. As a result, the issuance, scope, validity, enforceability and commercial value of our patents, including those patent rights licensed to us by third parties, are highly uncertain.

The steps we have taken to police and protect our proprietary rights may not be adequate to preclude misappropriation of our proprietary information or infringement of our intellectual property rights, both inside and outside the United States. The rights already granted under any of our currently issued patents and those that may be granted under future issued patents may not provide us with the proprietary protection or competitive advantages that we are seeking. If we are unable to obtain and maintain patent protection for our technology and products, or if the scope of the patent protection obtained is not sufficient, our competitors could develop and commercialize technology and products similar or superior to ours, and our ability to successfully commercialize our technology and products may be adversely affected.

With respect to patent rights, we do not know whether any of the pending patent applications for any of our products or product candidates will result in the issuance of patents that protect our technology or products, or which will effectively prevent others from commercializing competitive technologies and products. Our pending applications cannot be enforced against third parties practicing the technology claimed in such applications unless and until a patent issues from such applications. Further, the examination process may require us or our licensors to narrow the claims, which may limit the scope of patent protection that may be obtained. Although our license agreement with Genzyme includes a number of issued patents that are exclusively licensed to us, the issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, issued patents that we own or have licensed from third parties may be challenged in the courts or patent offices in the United States and abroad. Such challenges may result in the loss of patent protection, the narrowing of claims in such patents, or the invalidity or unenforceability of such patents, which could limit our ability to stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection for our technology and products. Protecting against the unauthorized use of our patented technology, trademarks and other intellectual property rights is expensive, difficult and may,

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~~from commercializing competitive technologies and products. Our pending applications cannot be enforced against third parties practicing the technology claimed~~ in such applications unless and until a patent issues from such applications. Further, the examination process may require us or our licensors to narrow the claims, which may limit the scope of patent protection that may be obtained. Although our license agreement with Genzyme includes a number of issued patents that are exclusively licensed to us, the issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, issued patents that we own or have licensed from third parties may be challenged in the courts or patent offices in the United States and abroad. Such challenges may result in the loss of patent protection, the narrowing of claims in such patents, or the invalidity or unenforceability of such patents, which could limit our ability to stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection for our technology and products. Protecting against the unauthorized use of our patented technology, trademarks and other intellectual property rights is expensive, difficult and may, in some cases, not be possible. In some cases, it may be difficult or impossible to detect third party infringement or misappropriation of our intellectual property rights, even in relation to issued patent claims, and proving any such infringement may be even more difficult.

We could be required to incur significant expenses to obtain our intellectual property rights, and we cannot ensure that we will obtain meaningful patent protection for our product candidates.

The patent prosecution process is expensive and time-consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. In addition, it is also possible that we will fail to identify patentable aspects of further inventions made in the course of our development and commercialization activities before they are publicly disclosed, making it too late to obtain patent protection on them. Further, given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. We expect to seek extensions of patent terms where these are available in any countries where we are prosecuting patents. This includes in the United States under the Drug Price Competition and Patent Term Restoration Act of 1984, which permits a patent term extension of up to five years beyond the expiration of a patent that covers an approved product where the permission for the commercial marketing or use of the product is the first permitted commercial marketing or use, and as long as the remaining term of the patent does not exceed 14 years. However, the applicable authorities, including the FDA in the United States, and any equivalent regulatory authority in other countries, may not agree with our assessment of whether such extensions are available, and may refuse to grant extensions to our patents, or may grant more limited extensions than we request. If this occurs, our competitors may be able to take advantage of our investment in development and clinical trials by referencing our clinical and preclinical data and launch their product earlier than might otherwise be the case. Changes in either the patent laws or interpretation of the patent laws in the United States and other countries may diminish the value of our patents or narrow the scope of our patent protection. The laws of foreign countries may not protect our rights to the same extent as the laws of the United States, and these foreign laws may also be subject to change. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing or in some cases not at all. Therefore, we cannot be certain that we or our licensors were the first to make the inventions claimed in our owned or licensed patents or pending patent applications, or that we or our licensors were the first to file for patent protection of such inventions.

Obtaining and maintaining our patent protection depends on compliance with various procedural, documentary, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements.

Periodic maintenance fees on any issued patent are due to be paid to the 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 a number of procedural, documentary, fee payment and other requirements during the patent application process. While an inadvertent lapse can in many cases 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, but are not limited to, 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 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.

Patent terms may be inadequate to protect our competitive position on our product candidates for an adequate amount of time.

Patents have a limited lifespan. In the United States, if all maintenance fees are timely paid, the natural expiration of a patent is generally 20 years from its earliest U.S. non-provisional filing date. Various extensions may be available, but the life of a patent, and the protection it affords, is limited. Even if patents covering our product candidates are obtained, once the patent life has expired, we may be open to competition from competitive products, including generics or biosimilars. Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.

required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.

We may become involved in lawsuits to protect or enforce our intellectual property, which could be expensive, time consuming and unsuccessful.

In addition to the possibility of litigation relating to infringement claims asserted against it, we may become a party to other patent litigation and other proceedings, including inter partes review proceedings, post-grant review proceedings, derivation proceedings declared by the USPTO and similar proceedings in foreign countries, regarding intellectual property rights with respect to our current or future technologies or product candidates or products. The cost to us of any patent litigation or other proceeding, even if resolved in our favor, could be substantial. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their substantially greater financial resources. Patent litigation and other proceedings may also absorb significant management time. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could impair our ability to compete in the marketplace.

respect to our current or future technologies or product candidates or products. The cost to us of any patent litigation or other proceeding, even if resolved in our favor, could be substantial. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their substantially greater financial resources. Patent litigation and other proceedings may also absorb significant management time. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could impair our ability to compete in the marketplace.

Competitors may infringe or otherwise violate our intellectual property, including patents that may issue to or be licensed by us. As a result, we may be required to file claims in an effort to stop third-party infringement or unauthorized use. Any such claims could provoke these parties to assert counterclaims against us, including claims alleging that we infringe their patents or other intellectual property rights. This can be prohibitively expensive, particularly for a company of our size, and time-consuming, and even if we are successful, any award of monetary damages or other remedy we may receive may not be commercially valuable. In addition, in an infringement proceeding, a court may decide that our asserted intellectual property is not valid or is unenforceable, or may refuse to stop the other party from using the technology at issue on the grounds that our intellectual property does not cover its technology. An adverse determination in any litigation or defense proceedings could put our intellectual property at risk of being invalidated or interpreted narrowly and could put our patent applications at risk of not issuing.

If the breadth or strength of our patent or other intellectual property rights is compromised or threatened, it could allow third parties to commercialize our technology or products or result in our inability to commercialize our technology and products without infringing third-party intellectual property rights. Further, third parties may be dissuaded from collaborating with us.

Interference or derivation proceedings brought by the USPTO or its foreign counterparts may be necessary to determine the priority of inventions with respect to our patent applications, and we may also become involved in other proceedings, such as re-examination proceedings, before the USPTO or its foreign counterparts. Due to the substantial competition in the pharmaceutical space, the number of such proceedings may increase. This could delay the prosecution of our pending patent applications or impact the validity and enforceability of any future patents that we may obtain. In addition, any such litigation, submission or proceeding may be resolved adversely to us and, even if successful, may result in substantial costs and distraction to our management.

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. Moreover, intellectual property law relating to the fields in which we operate is still evolving and, consequently, patent and other intellectual property positions in our industry are subject to change and are often uncertain. We may not prevail in any of these suits or other efforts to protect our technology, and the damages or other remedies awarded, if any, may not be commercially valuable. During the course of this type of litigation, there could 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, the market price for our common stock could be significantly harmed.

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 intellectual property rights that are important to our business.

We are a party to several license agreements and may need to obtain additional licenses from others to advance our research and development activities or allow the commercialization of our current product candidates and any that we may identify and pursue in the future. Our currently license agreements impose, and we expect that future license agreements will impose, various development, diligence, commercialization, and other obligations on us. In spite of our efforts, our licensors might conclude that we have materially breached our obligations under such license agreements and might therefore terminate the license agreements, thereby removing or limiting our ability to develop and commercialize products and technology covered by these license agreements. If these in-licenses are terminated, or if the underlying patents fail to provide the intended exclusivity, competitors or other third parties may gain the freedom to seek regulatory approval of, and to market, products identical to ours and we may be required to cease our development and commercialization of our product candidates. Any of the foregoing could have a material adverse effect on our competitive position, business, financial conditions, results of operations, and prospects.

required to cease our development and commercialization of our product candidates. Any of the foregoing could have a material adverse effect on our competitive position, business, financial conditions, results of operations, and prospects.

Moreover, disputes may arise regarding intellectual property subject to a licensing agreement, including:

•the scope of rights granted under the license agreement and other interpretation-related issues;

•the extent to which our product candidates, technology and processes infringe on intellectual property of the licensor that is not subject to the licensing agreement;

•the sublicensing of patent and other rights under our collaborative development relationships;

•our diligence obligations under the license agreement and what activities satisfy those diligence obligations;

•the inventorship and ownership of inventions and know-how resulting from the joint creation or use of intellectual ~~property by our licensors and us and our partners; and~~

property by our licensors and us and our partners; and

•the priority of invention of patented technology.

In addition, the agreements under which we currently license intellectual property or technology from third parties are complex, and certain provisions in such agreements may be susceptible to multiple interpretations. The resolution of any contract interpretation disagreement that may arise could narrow what we believe to be the scope of our rights to the relevant intellectual property or technology, or increase what we believe to be our financial or other obligations under the relevant agreement, either of which could have a material adverse effect on our business, financial condition, results of operations, and prospects. Moreover, if disputes over intellectual property that we have licensed prevent or impair our ability to maintain our current licensing arrangements on commercially acceptable terms, we may be unable to successfully develop and commercialize the affected product candidates, which could have a material adverse effect on our business, financial conditions, results of operations, and prospects.

From time to time, we may need to rely on licenses to proprietary technologies, which may be difficult or expensive to obtain or we may lose certain licenses which may be difficult to replace.

We may need to obtain licenses to patents and other proprietary rights held by third parties to develop, manufacture and market our product candidates. If we are unable to timely obtain these licenses on commercially reasonable terms and maintain these licenses, our ability to commercially market our product candidates may be inhibited or prevented, which could have a material adverse effect on our business, results of operations, financial condition and cash flows.

Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could have a material adverse effect on the success of our business.

Our commercial success depends upon our ability to develop, manufacture, market and sell our product candidates, and to use our proprietary technologies without infringing the proprietary rights of third parties. We may become party to, or threatened with, future adversarial proceedings or litigation regarding intellectual property rights with respect to our products and technology, including interference and various post grant proceedings before the USPTO, non-U.S. opposition proceedings, and German nullity proceedings. Third parties may assert infringement claims against us based on existing patents or patents that may be granted in the future.

As a result of any such infringement claims, or to avoid potential claims, we may choose or be compelled to seek intellectual property licenses from third parties. These licenses may not be available on acceptable terms, or at all. Even if we are able to obtain a license, the license would likely obligate us to pay license fees or royalties or both, and the rights granted to us likely would be nonexclusive, which would mean that our competitors also could obtain licenses to the same intellectual property. Ultimately, we could be prevented from commercializing a product candidate or technology or be forced to cease some aspect of our business operations if, as a result of actual or threatened infringement claims, we are unable to enter into licenses of the relevant intellectual property on acceptable terms. Further, if we attempt to modify a product candidate or technology or to develop alternative methods or products in response to infringement claims or to avoid potential claims, we could incur substantial costs, encounter delays in product introductions or interruptions in sales. Ultimately, such efforts could be unsuccessful.

Parties making claims against us may obtain injunctive or other equitable relief, which could effectively block our ability to further develop and commercialize our product candidates that we may identify. Defense of these claims, regardless of their merit, would involve substantial litigation expense and would be a substantial diversion of employee resources from our business. In the event of a successful claim of infringement against us, we may have to pay substantial damages, including treble damages and attorneys’ fees for willful infringement, pay royalties, redesign our infringing products or obtain one or more licenses from third parties, which may be impossible or require substantial time and monetary expenditure.

Parties making claims against us may be able to sustain the costs of complex patent litigation more effectively than we can because they have substantially greater resources. Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation or administrative proceedings, there is a risk that some of our confidential information could be compromised by disclosure. In addition, any uncertainties resulting from the initiation and continuation of any litigation could have material adverse effect on our ability to raise additional funds or otherwise have a material adverse effect on our business, results of operations, financial condition and prospects.

Intellectual property litigation could cause us to spend substantial resources and distract our personnel from their normal responsibilities.

Litigation or other legal proceedings relating to intellectual property claims, with or without merit, is unpredictable and generally expensive and time consuming and is likely to divert significant resources from our core business, including distracting our technical and management personnel from their normal responsibilities. 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. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock and negatively impact our ability to raise additional funds. Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities.

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. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock and negatively impact our ability to raise additional funds. Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities.

We may not have sufficient financial or other resources to adequately conduct such litigation or proceedings. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources and more mature and developed intellectual property portfolios. Accordingly, despite our efforts, we may not be able to prevent third parties from infringing upon or misappropriating or from successfully challenging our intellectual property rights. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could have a material adverse effect on our ability to compete in the marketplace.

Our trade secrets are difficult to protect and if we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed.

In addition to seeking patents for some of our technologies and product candidates, we also rely on trade secrets, including unpatented know-how, technology and other proprietary information, to maintain our competitive position. 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. We also enter into confidentiality, non-competition, non-solicitation, and invention assignment agreements with our employees and consultants that obligate them to assign to us any inventions developed in the course of their work for us. However, we cannot guarantee that we have executed these agreements with each party that may have or have had access to our trade secrets or that the agreements we have executed will provide adequate protection. Despite these efforts, any of these parties may breach the agreements and disclose our proprietary information, including our trade secrets, and we may not be able to obtain adequate remedies for such breaches. As a result, we may be forced to bring claims against third parties, or defend claims that they bring against us, to determine ownership of what we regard as our intellectual property. Monitoring unauthorized disclosure is difficult and we do not know whether the procedures that we have followed to prevent such disclosure are or will be adequate. Enforcing a claim that a party illegally disclosed or misappropriated a trade secret is difficult, expensive and time-consuming, and the outcome is unpredictable. In addition, some courts inside and outside the United States may be less willing or unwilling to protect trade secrets. If any of the technology or information that we protect as trade secrets were to be lawfully obtained or independently developed by a competitor, we would have no right to prevent them from using that technology or information to compete with us. If any of our trade secrets were to be disclosed to, or independently developed by, a competitor, our competitive position would be harmed.

We may be subject to claims that our employees have wrongfully used or disclosed alleged trade secrets of their former employers.

Our employees, including members of our senior management, were previously employed at other biotechnology or pharmaceutical companies, including our competitors or potential competitors. All such individuals, including each member of our senior management, executed proprietary rights, non-disclosure and non-competition agreements in connection with such previous employment. Although we try to ensure that our employees do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or these employees have used or disclosed intellectual property, including trade secrets or other proprietary information, of any such employee’s former employer. We are not aware of any threatened or pending claims related to these matters or concerning the agreements with our senior management, but in the future litigation may be necessary to defend against such claims. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management.

litigation may be necessary to defend against such claims. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management.

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

Filing, prosecuting and defending patents on all of our product candidates throughout the world would be prohibitively expensive. In general, we have sought patent protection of our intellectual property in the following jurisdictions: US, Canada, China, Japan and in countries within Europe via the European Patent Office. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products and further, may export otherwise infringing products to territories where we have patent protection, but where enforcement is not as strong as that in the United States. These products may compete with our products in jurisdictions where we do not have any issued patents and our patent claims or other intellectual property rights may not be effective or sufficient to prevent them from so 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 to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally. Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial cost and divert our efforts and attention from other aspects of our business.

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 to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally. Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial cost and divert our efforts and attention from other aspects of our business.

As another example, the complexity and uncertainty of European patent laws have increased in recent years. In Europe, a new unitary patent system will likely be introduced by the end of 2023, which would significantly impact European patents, including those granted before the introduction of such a system. Under the unitary patent system, European applications will soon have the option, upon grant of a patent, of becoming a Unitary Patent which will be subject to the jurisdiction of the Unitary Patent Court (“UPC”). As the UPC is a new court system, there is no precedent for the court, increasing the uncertainty of any litigation. Patents granted before the implementation of the UPC will have the option of opting out of the jurisdiction of the UPC and remaining as national patents in the UPC countries. Patents that remain under the jurisdiction of the UPC will be potentially vulnerable to a single UPC-based revocation challenge that, if successful, could invalidate the patent in all countries who are signatories to the UPC. We cannot predict with certainty the long-term effects of any potential changes.

Risks Related to Our Business Operations, Employee Matters and Managing Growth

Our future success depends on our ability to retain executives and to attract, retain and motivate key personnel in a competitive environment for skilled biotechnology personnel.

Because of the specialized scientific and managerial nature of our business, we rely heavily on our ability to attract and retain qualified scientific, technical and managerial personnel. We are also highly dependent upon members of our ~~current~~ management team~~, including Paula Ragan, Ph~~.~~D.,~~ ~~our Chief Executive Officer.~~ The loss of the services provided by these individuals will adversely impact the achievement of our objectives. These individuals could leave our employment at any time, as they are “at will” employees. Effective succession planning is also important to our long-term success. Failure to ensure effective transfer of knowledge and smooth transitions involving key employees could hinder our strategic planning and execution. While we expect to engage in an orderly transition process if and when we integrate newly appointed officers and managers, we face a variety of risks and uncertainties relating to management transition, including diversion of management attention from business concerns, failure to retain other key personnel, or loss of institutional knowledge. In addition, the loss of the services of any of our executive officers, other key employees, and other scientific and medical advisors, and an inability to find suitable replacements could result in delays in product development, and harm our business.

Our success will depend on our ability to retain our management team and other key employees, and to attract and retain qualified personnel in the future. The loss of the services of certain members of our senior management or key employees could prevent or delay the implementation and completion of our strategic objectives, or divert management’s attention to seeking qualified replacements. The competition for qualified personnel in the pharmaceutical field is intense and we cannot guarantee that we will be able to retain our current personnel or attract and retain new qualified personnel necessary for the development of our business or to recruit suitable replacement personnel.

The recent restructuring changes in our business may make it more difficult to attract and retain qualified personnel. We cannot guarantee we will achieve our goals or that our actions will result in expected benefits to our business.

56We may experience difficulties in managing the reduction in size of our organization due to our restructuring activities, and we may not achieve the expected benefits of such activities.

WeIn ~~will~~September ~~need~~2025, towe ~~scale~~announced ~~the~~a ~~size~~strategic restructuring of our ~~organization~~business operations, workforce and capital spending (the “September 2025 Restructuring”) to sharpen operational focus and align resources with the Company’s long‑term strategy to successfully complete the 4WARD Phase 3 trial in patients with moderate and severe CN. As part of the September 2025 Restructuring, we ~~may~~implemented ~~experience~~a ~~difficulties~~net reduction of our employee headcount by approximately 50%. The workforce reduction was substantially completed in ~~managing~~the ~~this~~third quarter of 2025. In addition, as part of a prior strategic restructuring plan announced in February 2025 (the “February 2025 Restructuring”), we previously implemented a net reduction of our employee headcount by 43 employees, or approximately 30% of our total workforce as of February 2025. The strategic restructuring activities included (i) discontinuing of certain research efforts, (ii) closing the Company’s facility in ~~size~~Vienna, Austria, (iii) pausing certain pre-clinical drug candidate programs, (iv) scaling back the U.S. commercial field team and supporting roles across the Company and (v) streamlining other spending to support the ongoing clinical development of mavorixafor for the larger population of those with CN.

AsWe ofmay ~~December~~not 31realize, ~~2024,~~in ~~we had 143~~ full~~-time~~ ~~employees.~~or Inin February 2025, we implemented a strategic restructuring of our business operations, workforce and capital spending to focus efforts on advancing mavorixafor to treat those with chronic neutropenia, while also optimizing its U.S. promotion of XOLREMDI (the “2025 Restructuring”). As part ~~of the 2025 Restructuring~~, we implemented a net reduction of our employee headcount by 43 employees, or approximately 30% of our total workforce. The strategic restructuring activities include (i) discontinuing of research efforts, (ii) closing the ~~Company’s~~anticipated ~~facility in Vienna~~benefits, ~~Austria,~~savings ~~(iii) pausing pre-clinical drug candidate programs, (iv) scaling the U.S. commercial field team~~ and ~~supporting~~improvements ~~roles~~from ~~across~~ the ~~Company~~September and (v) streamlining other spending to support the ongoing clinical development of mavorixafor for the larger population of those with chronic neutropenia. The Company estimates that the workforce reduction will be substantially completed in the first quarter of 2025. As we pause our development and scale our commercialization plans and strategies back, we may lack adequate managerial, operational, development, sales, marketing, financial and other resources. Our management, personnel and systems currently in place, after the 2025 Restructuring, may not be adequate to support future operations.

Restructuring and February 2025 Restructuring to the extent or as quickly as anticipated due to unforeseen difficulties, delays or unexpected costs. If we are unable to realize the expected operational efficiencies and cost savings from the restructuring, our operating results and financial condition could be adversely affected. As we pause our development and scale our commercialization plans and strategies back, we may lack adequate managerial, operational, development, sales, marketing, financial and other resources. Our management, personnel and systems currently in place may not be adequate to support future operations.

The pharmaceutical industry is highly competitive and is subject to rapid and significant technological change, which could render our technologies and products obsolete or uncompetitive.

The pharmaceutical industry is highly competitive and is subject to rapid and significant technological change, which could render certain of our products obsolete or uncompetitive. This is particularly true in the development of therapeutics for oncology indications where new products and combinations of products are rapidly being developed that change the treatment paradigm for patients. There is no assurance that our product candidates will be the best, have the best safety profile, be the first to market, or be the most economical to make or use. The introduction of competitive therapies as alternatives to our product candidates could dramatically reduce the value of those development projects or chances of successfully commercializing those product candidates, which could have a material adverse effect on our long-term financial success.

We will compete with companies in the United States and internationally, including major pharmaceutical and chemical companies, specialized CROs, research and development firms, universities and other research institutions. Many of our competitors have greater financial resources and selling and marketing capabilities, greater experience in clinical testing and human clinical trials of pharmaceutical products and greater experience in obtaining FDA and other regulatory approvals than we do. In addition, some of our competitors may have lower development and manufacturing costs.

Our internal information technology systems and infrastructure, or those of our contractors, consultants, or other third parties, may be subject to cyber attacks, or data breaches, compromises, or other security incidents, which could result in additional costs, loss of revenue, significant liabilities, harm to our reputation, and disruption of our development programs and operations.

We rely significantly on information technology and any failure, inadequacy, interruption or security lapse of that technology or loss of data, including any cyber security incidents, could compromise sensitive information related to our business, prevent us from accessing critical information or expose us to liability which could harm our ability to operate our business effectively and adversely affect our business and reputation.

In the ordinary course of our business, we, our contract research organizations and other third parties on which we rely collect and store sensitive data, including legally protected patient health information, personally identifiable information about our employees, intellectual property, and proprietary business information. We manage and maintain our applications and data utilizing on-site systems. These applications and data encompass a wide variety of business-critical information including research and development information and business and financial information. The secure processing, storage, maintenance and transmission of this critical information is vital to our operations and business strategy.

Additionally, despite the implementation of security measures, our internal computer systems and those of third parties with which we contract are vulnerable to damage from cyber-attacks, computer viruses, breaches, unauthorized access, interruptions due to employee error or malfeasance or other disruptions, or damage from natural disasters, terrorism, war and telecommunication and electrical failures. Like other companies in our industry, we, and our third -party vendors, have experienced, and will continue to experience, cybersecurity threats and incidents relating to our information technology systems and infrastructure.

In addition, we have implemented a work model that has enabled substantially all of our employees to periodically work remotely, which may make us more vulnerable to cyberattacks. Any such event could compromise our networks and the information stored there could be accessed by unauthorized parties, publicly disclosed, lost or stolen. We have measures in place that are designed to detect and respond to such security incidents and breaches of privacy and security mandates. Any such access, disclosure or other loss of information could result in legal claims or proceedings, liability under laws that protect the privacy of personal information, government enforcement actions and regulatory penalties. Unauthorized access, loss or dissemination could also disrupt our operations, including our ability to conduct research, development and commercialization activities, process and prepare company financial information, manage various selling, general and administrative aspects of our business and damage our reputation, in addition to possibly requiring substantial expenditures of resources to remedy, any of which could adversely affect our business. The loss of clinical trial data could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. In addition, there can be no assurance that we will promptly detect any such disruption or security breach, if at all. To the extent that any disruption or security breach were to

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~~loss of information could~~ result in legal claims or proceedings, liability under laws that protect the privacy of personal information, government enforcement actions and regulatory penalties. Unauthorized access, loss or dissemination could also disrupt our operations, including our ability to conduct research, development and commercialization activities, process and prepare company financial information, manage various selling, general and administrative aspects of our business and damage our reputation, in addition to possibly requiring substantial expenditures of resources to remedy, any of which could adversely affect our business. The loss of clinical trial data could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. In addition, there can be no assurance that we will promptly detect any such disruption or security breach, if at all. To the extent that any disruption or security breach were to result in a loss of, or damage to, our data or applications, or inappropriate disclosure of confidential or proprietary information our development and commercialization efforts could be delayed and we could be required to notify impacted stakeholders (including affected individuals, regulators and investors) what could lead to significant liability through litigation and regulatory investigations and enforcement actions, including under state (e.g., state breach notification and consumer protection laws), federal (e.g., HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”)), and international law (e.g., the GDPR).

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.

Our ability to use our net operating losses to offset future taxable income may be subject to certain limitations.

Our net operating loss (“NOL”) carryforwards could expire unused and be unavailable to offset future tax liabilities because of their limited duration or because of restrictions under U.S. tax law. As of December 31, ~~2024~~2025, we had U.S. federal and state NOLs of $~~372~~432.90 million and $~~374~~383.29 million, respectively. Our NOLs generated in tax years ending on or prior to December 31, 2017 are only permitted to be carried forward for 20 years under applicable U.S. tax law. Under the Tax Act, as modified by the CARES Act, our federal NOLs generated in tax years ending after December 31, 2017 may be carried forward indefinitely, but the deductibility of federal NOLs, particularly for tax years beginning after December 31, 2020, may be limited. It is uncertain if and to what extent various states will conform to the Tax Act and the CARES Act.

Section 382 of the Internal Revenue Code of 1986, as amended (“Section 382”) contains rules that limit the ability of a company that undergoes an ownership change to utilize its net operating losses (“NOLs”) and tax credits existing as of the date of such ownership change. Under the rules, such an ownership change is generally any change in ownership of more than 50% of a company’s stock within a rolling three-year period. The rules generally operate by focusing on changes in ownership among stockholders considered by the rules as owning, directly or indirectly, 5% or more of the stock of a company and any change in ownership arising from new issuances of stock by the company. We have completed a Section 382 study that has identified ownership changes that will limit the future use of our NOL carryforwards. See Note ~~16,~~17 ~~Income~~of ~~Taxes,~~our Annual Report on Form 10-K for a further discussion of these limitations. Future ownership changes as defined by Section 382 may further limit the amount of NOL carryforwards that could be utilized annually to offset future taxable income.

We may be subject to adverse legislative or regulatory changes in tax laws that could negatively impact our financial condition.

The rules dealing with U.S. federal, state and local income taxation are constantly under review by persons involved in the legislative process and by the U.S. Internal Revenue Service and the U.S. Treasury Department. For example, the One Big Beautiful Bill Act (“OBBBA”) was signed into law on July 4, 2025 and made significant changes to U.S. federal tax law. Changes to tax laws (which changes may have retroactive application) could adversely affect our stockholders or us. In recent years, many changes to tax laws have been made and changes are likely to occur in the future. We cannot predict whether, when, in what form, or with what effective dates, tax laws, regulations and rulings may be enacted, promulgated or decided, 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 increases in our tax liability.

Our term loan contains restrictions that limit our flexibility in operating our business.

Our Hercules Loan Agreement is secured by a lien on substantially all of our assets, excluding intellectual property. This loan contains various covenants that limit our ability to engage in specified types of transactions. These covenants limit our ability to, among other things:

•sell, transfer, lease or dispose of certain assets;

•incur indebtedness;

•encumber or permit liens on certain assets;

•make certain investments;

•make certain restricted payments, including paying dividends on, or repurchasing or making distributions with respect to, our common stock; and

•enter into certain transactions with affiliates.

As noted above, the Hercules Loan Agreement also requires that we maintain a minimum level of cash of greater than 20% of our outstanding borrowings under the Hercules Loan Agreement and subject to certain operational covenants.

Our business could be adversely affected by economic downturns, inflation, increases in interest rates, natural disasters, public health crises, political crises, geopolitical events, such as the war in Ukraine and in Gaza, or other macroeconomic conditions, which have in the past and may in the future negatively impact our business and financial performance.63

The global economy, including credit and financial markets, has experienced extreme volatility and disruptions, including, among other things, severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, supply chain shortages, increases in inflation rates, higher interest rates and uncertainty about economic stability. For example, the COVID-19 pandemic resulted in widespread unemployment, economic slowdown and extreme volatility in the capital markets. The U.S. Federal Reserve recently raised interest rates multiple times in response to concerns about inflation and it may raise them again. Higher interest rates, coupled with reduced government spending and volatility in financial markets may increase economic uncertainty. If the equity and credit markets deteriorate, including as a result of political unrest or war, such as the war in Ukraine or in Gaza, it may make any necessary debt or equity financing more difficult to obtain in a timely manner or on favorable terms, more costly or more dilutive. Increased inflation rates can adversely affect us by increasing our costs, including labor and employee benefit costs.

Risks Related to Ownership of Our Common Stock

WeAlthough we are currently ~~not~~ in compliance with the Nasdaq continued listing requirements., Ifif we are unable to ~~regain~~maintain compliance with Nasdaq’s listing requirements, our securities could be delisted, which could affect our common stock’s market price and liquidity and reduce our ability to raise capital.

OnOur ~~August~~common ~~13,~~stock ~~2024,~~is welisted ~~received~~on aThe ~~letter~~Nasdaq ~~from~~Capital ~~the~~Market ~~Listing~~(“Nasdaq”). ~~Qualifications~~There ~~Staff~~are a number of ~~The~~continued listing requirements that we must satisfy in order to maintain our listing on Nasdaq, ~~Stock~~including ~~Market~~the ~~LLC~~requirement to maintain a minimum bid price of at least $1.00 (the “~~Nasdaq~~Bid Price Rule”). ~~indicating~~If ~~that~~a deficiency with respect to this requirement continues for a period of 30 consecutive business days, ~~based~~Nasdaq ~~upon~~may ~~the~~require ~~closing~~us to satisfy a minimum bid price per share of our common stock of at least $1.00 for ~~the~~a ~~last~~period 30in excess of ten consecutive business days, webut generally no ~~longer~~more ~~meet~~than ~~Nasdaq~~20 ~~Listing~~consecutive ~~Rule~~business ~~5550(a)(2)~~days, ~~which~~before ~~requires~~determining ~~listed~~that ~~companies~~we have demonstrated an ability to maintain long-term compliance with the Bid Price Rule. We have been unable to comply with the Bid Price Rule in the past, such as in 2025, and our continued listing on Nasdaq required the grant of a ~~minimum~~grace ~~bid~~period ~~price~~from Nasdaq and the implementation of ata ~~least~~reverse $1stock split.00 ~~per~~If ~~share~~we fail to comply with the Bid Price Rule in the future, there can be no assurance that we will be granted such grace periods or that we will be able to receive the necessary shareholder approval to implement an additional reverse stock split. In particular, we may encounter difficulties obtaining such shareholder approval due to our heavily retail investor shareholder base, which may also affect our ability to obtain shareholder approval of other significant corporate actions.

InAny ~~accordance~~delisting ~~with the listing rules~~ of ~~Nasdaq,~~our ~~the~~common ~~Company~~stock ~~was~~would ~~given~~likely ~~180~~adversely ~~calendar~~affect ~~days,~~the ormarket ~~until~~liquidity ~~February~~and ~~10,~~market ~~2025, to regain compliance with the minimum bid~~ price ~~requirement.~~of Onour ~~February~~common 2,stock ~~2025,~~and weour ~~submitted~~ability ~~a letter~~ to ~~Nasdaq~~obtain ~~requesting~~financing anfor ~~additional~~the ~~180~~continuation ~~day~~of ~~compliance~~our ~~period~~operations and/or result in ~~this~~the ~~letter,~~loss ~~per~~of ~~Nasdaq’s~~confidence ~~rules,~~by weinvestors. ~~noted~~If ~~our~~we ~~intention~~fail to ~~cure~~meet the ~~deficiency~~continued ~~during~~listing ~~such~~requirements ~~additional~~of ~~compliance period~~Nasdaq, bywe ~~effecting~~could aface ~~reverse~~significant ~~stock~~material ~~split~~adverse consequences, ifincluding: ~~necessary.~~(1) Wea ~~were~~limited ~~granted~~availability anof ~~additional~~market ~~180~~quotations ~~days~~for toour ~~regain~~securities; ~~compliance~~ (~~the “Compliance Date”~~2). Ifreduced atliquidity ~~any~~with ~~time~~respect ~~before~~to ~~the~~our ~~Compliance~~securities; ~~Date,~~(3) ~~the~~a ~~closing~~determination ~~bid~~that ~~price~~our ofshares ~~the~~are ~~Company’s Common Stock is at least $1.00 per share for~~ a ~~minimum~~“penny ofstock” ~~ten~~if ~~consecutive~~they ~~business~~are ~~days,~~not ~~Nasdaq~~already ~~will~~determined ~~provide written notification~~ to ~~the~~be ~~Company~~a ~~that~~“penny itstock” ~~complies~~at ~~with~~ the ~~minimum~~time ~~bid~~of ~~price~~such ~~requirement.~~failure ~~If the Company is unable~~ to ~~regain~~meet ~~compliance~~such ~~before the Compliance Date~~requirements, ~~Nasdaq~~which will ~~provide~~require ~~written~~brokers ~~notification~~trading toin ~~the~~our ~~Company~~securities ~~that~~to ~~its~~adhere ~~Common Stock is subject~~ to ~~delisting.~~more Atstringent ~~that time~~rules, ~~the~~possibly ~~Company~~resulting ~~may~~in ~~appeal~~a ~~the~~reduced ~~delisting~~level ~~determination~~of totrading aactivity ~~hearings~~in ~~panel pursuant to~~ the ~~procedures~~secondary ~~set~~trading ~~forth~~market infor ~~the~~our ~~applicable~~securities; ~~Nasdaq~~(4) ~~Listing~~a ~~Rules.~~limited ~~However,~~amount ~~there~~of ~~can~~news beand noanalyst ~~assurance~~coverage ~~that,~~for ifus; ~~the~~and ~~Company~~(5) ~~does~~a ~~appeal~~decreased ~~the~~ability ~~delisting~~to ~~determination~~issue byadditional ~~Nasdaq~~securities toor ~~the~~obtain ~~panel,~~additional ~~such~~financing ~~appeal~~in ~~would~~the ~~be successful~~future.

If we fail to regain compliance with the Nasdaq continued listing standards, Nasdaq will provide notice that our common stock will be subject to delisting. We would then be entitled to appeal that determination to a Nasdaq hearings panel.

The notification has no immediate effect on the listing of our common stock on Nasdaq.

On March 14, 2025, we filed a preliminary proxy indicating our intent to seek shareholder approval to effect a reverse stock split of the outstanding shares of our Common Stock at any time by a ratio of not less than one-for-fifteen and not more than one-for thirty, with the specific ratio to be fixed within this range by the Board in its sole discretion without further stockholder approval (the “Proposal”). We intend to hold the special meeting of stockholders to vote on the Proposal on April 17, 2025. There is no guarantee that the stockholders of the Company will approve the reverse stock split or that the Board will effect the reverse stock split if it is approved by the stockholders. The exact timing of effecting the reverse stock split, if it is approved by the stockholders, will be determined by the Board in its sole discretion. Furthermore, the Company can provide no assurance that the reverse stock split, if effected, will result in a permanent increase in the trading price of our common stock.

If the Company does not regain compliance within the allotted compliance period, Nasdaq will provide notice that the Company’s common stock will be subject to delisting. The Company would then be entitled to appeal Nasdaq’s delisting determination. However, there can be no assurance that, if we do appeal the delisting determination by Nasdaq, that such appeal would be successful.

There can be no assurance that the Company will be successful in maintaining the listing of our common stock on the Nasdaq Global Market. If we fail to meet the continued listing requirements of Nasdaq, we could face significant material adverse consequences, including: (1) a limited availability of market quotations for our securities; (2) reduced liquidity with respect to our securities; (3) a determination that our shares are a “penny stock” if they are not already determined to be a “penny stock” at the time of such failure to meet such requirements, which will require brokers trading in our securities to adhere to more stringent rules, possibly resulting in a reduced level of trading activity in the secondary trading market for our securities; (4) a limited amount of news and analyst coverage for us; and (5) a decreased ability to issue additional securities or obtain additional financing in the future.

Our stock price has been and is likely to continue to be volatile and fluctuate substantially.

The market price of our common stock has been and could continue to be subject to significant fluctuations. Market prices for securities of pharmaceutical, biotechnology and other life sciences companies have historically been particularly volatile. Some of the factors that may cause the market price of our common stock to fluctuate include:

•our ability or the ability of our collaborators to develop product candidates and conduct clinical trials that demonstrate such product candidates are safe and effective;

•our ability or the ability of our collaborators to obtain regulatory approvals for product candidates, and delays or failures to obtain such approvals;

•failure of any our product candidates to demonstrate safety and efficacy, receive regulatory approval and achieve commercial success;

•failure to maintain our existing third-party license, manufacturing and supply agreements;

•failure by us or our licensors to prosecute, maintain or enforce our intellectual property rights;

•changes in laws or regulations applicable to our current or future product candidates;

•any inability to obtain adequate supply of product candidates or the inability to do so at acceptable prices;

•adverse decisions by regulatory authorities;

•introduction of new or competing products by our competitors;

•failure to meet or exceed financial and development projections that we may provide to the public;

•the perception of the pharmaceutical industry by the public, legislatures, regulators and the investment community;

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

•disputes or other developments relating to proprietary rights, including patents, litigation matters and our ability to obtain intellectual property protection for our technologies;

•additions or departures of key personnel;

•significant lawsuits, including intellectual property or stockholder litigation;

•announcements by us of material developments in our business, financial condition and/or operations;

•if securities or industry analysts do not publish research or reports about us, or if they issue an adverse or misleading ~~opinions regarding our business and stock;~~

opinions regarding our business and stock;

•changes in the market valuations of similar companies;

•general macroeconomic, political and market conditions and overall fluctuations in the financial markets in the United States and abroad;

•sales of our common stock or our stockholders in the future;

•trading volume of our common stock;

•adverse publicity relating to our markets generally, including with respect to other products and potential products in such markets;

•changes in the structure of health care payment systems;

•period-to-period fluctuations in our financial results; and

•the other factors described in this “Risk Factors” section and elsewhere in this Annual Report.

In addition, companies trading in the stock market in general have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies, which has resulted in decreased stock prices for many companies notwithstanding the lack of a fundamental change in their underlying business models or prospects. Broad market and industry factors, including potentially worsening economic conditions and other adverse effects, may negatively affect the market price of our common stock, regardless of our actual operating performance. In the past, following periods of volatility in the market price of a company’s securities, stockholders have often instituted class action securities litigation against those companies. Such litigation, if instituted, could result in substantial costs and diversion of management attention and resources, which could significantly harm our business, financial condition, results of operations and reputation.

“Penny stock” rules may make buying or selling our securities difficult which may make our stock less liquid and make it harder for investors to buy and sell our securities.

Trading in our securities is subject to the SEC’s “penny stock” rules and it is anticipated that trading in our securities will continue to be subject to the penny stock rules for the foreseeable future. The SEC has adopted regulations that generally define a penny stock to be any equity security that has a market price of less than $5.00 per share, subject to certain exceptions. These rules require that any broker-dealer who recommends our securities to persons other than prior customers and accredited investors must, prior to the sale, make a special written suitability determination for the purchaser and receive the purchaser’s written agreement to execute the transaction. Unless an exception is available, the regulations require the delivery, prior to any transaction involving a penny stock, of a disclosure schedule explaining the penny stock market and the risks associated with trading in the penny stock market. In addition, broker-dealers must disclose commissions payable to both the broker-dealer and the registered representative and current quotations for the securities they offer. The additional burdens imposed upon broker-dealers by these requirements may discourage broker-dealers from recommending transactions in our securities, which could severely limit the liquidity of our securities and consequently adversely affect the market price for our securities.

If securities analysts do not publish research or reports about our business or if they publish negative evaluations of our stock, the price of our stock could decline.

The trading market for our common stock will be influenced, in part, on the research and reports that industry or financial analysts publish about us or our business. Equity research analysts may elect not to provide research coverage of our common stock, and such lack of research coverage may adversely affect the market price of our common stock. In the event we do have equity research analyst coverage, we will not have any control over the analysts or the content and opinions included in their reports. The price of our common stock could decline if one or more equity research analysts downgrade our stock or issue other unfavorable commentary or research. If one or more equity research analysts ceases coverage of us or fails to publish reports on us regularly, demand for our common stock could decrease, which in turn could cause our stock price or trading volume to decline.

We do not anticipate that we will pay any cash dividends in the foreseeable future.

The current expectation is that we will retain our future earnings to fund the development and growth of our business. ~~In addition, the terms of our debt agreements preclude us from paying dividends.~~ As a result, capital appreciation, if any, of our common stock will be your sole source of gain, if any, for the foreseeable future. We are prohibited from declaring or paying any cash dividends under our existing loan and security agreement with Hercules.

Sales of a substantial number of shares of our common stock in the public market could cause our stock price to decline.

Sales of a substantial number of shares of our common stock in the public market, or the perception that these sales might occur, could depress the market price of our common stock and could impair our ability to raise capital through the sale of additional equity securities. We are unable to predict the effect that sales, particularly sales by our directors, executive officers, and significant stockholders, may have on the prevailing market price of our common stock.

In addition, we have filed registration statements on Form S-8 registering the issuance of shares of common stock subject to options or other equity awards issued or reserved for future issuance under our equity incentive plans. Shares registered under these registration statements are available for sale in the public market subject to vesting arrangements and exercise of options, as well as Rule 144 in the case of our affiliates.

If we fail to maintain an effective system of internal control over financial reporting, we may not be able to accurately report our financial results or prevent fraud. As a result, stockholders could lose confidence in our financial and other public reporting, which would harm our business and the trading price of our common stock.

We are subject to the reporting requirements of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), the Sarbanes-Oxley Act of 2002 and the rules and regulations of The Nasdaq Stock Market (“Nasdaq”). Pursuant to Section 404 of the Sarbanes-Oxley Act of 2002 (“Section 404”), we are required to perform system and process evaluation and testing of our internal control over financial reporting to allow our management to report on the effectiveness of our internal control over financial reporting in this Annual Report.

Effective internal control over financial reporting is necessary for us to provide reliable financial reports and, together with adequate disclosure controls and procedures, is designed to prevent fraud. Any failure to implement required new or improved controls, or difficulties encountered in their implementation, could cause us to fail to meet our reporting obligations. In addition, any testing by us, as and when required, conducted in connection with Section 404, or any subsequent testing by our independent registered public accounting firm, as and when required, may reveal deficiencies in our internal control over financial reporting that are deemed to be significant deficiencies or material weaknesses or that may require prospective or retroactive changes to our

consolidated financial statements or identify other areas for further attention or improvement. Inferior internal controls could also cause investors to lose confidence in our reported financial information, which could have a negative effect on the trading price of our common stock.

Pursuant to Section 404, we are required to furnish a report by our management on our internal control over financial reporting beginning with this Annual Report. However, while we remain a non-accelerated filer, we will not be required to include an attestation report on internal control over financial reporting issued by our independent registered public accounting firm. When we cease to be a smaller reporting company and no longer qualify as a non-accelerated filer, we will be required to incur substantial additional professional fees and internal costs to expand our accounting and finance functions in order to include such attestation report.

We may in the future discover weaknesses in our system of internal financial and accounting controls and procedures that could result in a material misstatement of our consolidated financial statements. Our internal control over financial reporting will not prevent or detect all error and all fraud. A control system, no matter how well designed and operated, can provide only reasonable, not absolute, assurance that the control system’s objectives will be met. Because of the inherent limitations in all control systems, no evaluation of controls can provide absolute assurance that misstatements due to error or fraud will not occur or that all control issues and instances of fraud will be detected. If we identify one or more material weaknesses in our internal controls, investors could lose confidence in the reliability of our consolidated financial statements, the market price of our stock could decline and we could be subject to sanctions or investigations by Nasdaq, the SEC or other regulatory authorities.

We are a “smaller reporting company” and cannot predict if the reduced reporting requirements applicable to smaller reporting companies will make our securities less attractive to investors.

We are a “smaller reporting company” under the Exchange Act as of June 30, ~~2024~~2025. We may continue to be a smaller reporting company if either (i) the market value of our common stock held by non-affiliates is less than $250 million or (ii) our annual revenue was less than $100.0 million during the most recently completed fiscal year and the market value of our common stock held by non-affiliates is less than $700.0 million. As a smaller reporting company, we may rely on exemptions from certain disclosure requirements that are available to smaller reporting companies, including not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act and reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements. For so long as we remain a smaller reporting company, we are permitted and intend to rely on such exemptions from certain disclosure and other requirements that are applicable to other public companies that are not smaller reporting companies.

We cannot predict if investors will find our securities less attractive because we may rely on the exemptions and reduced disclosure obligations applicable to smaller reporting companies. If some investors find our securities less attractive as a result, there may be a less active trading market for our common stock and our stock price may be more volatile.

We may become involved in securities class action litigation or shareholder derivative litigation that could divert management’s attention and harm our business and insurance coverage may not be sufficient to cover all costs and damages.

In the past, securities class action or shareholder derivative litigation has often followed certain significant business transactions, such as the sale of a business division or announcement of a merger. This risk is especially relevant for us because biopharmaceutical companies have experienced significant stock price volatility in recent years. We may become involved in this type of litigation in the future. The outcome of litigation is necessarily uncertain, and we could be forced to expend significant resources in the defense of such suits, and we may not prevail. Monitoring and defending against legal actions is time-consuming for our management and detracts from management’s ability to fully focus our internal resources on our business activities. In addition, we may incur substantial legal fees and costs in connection with any such litigation. We have not established any reserves for any potential liability relating to any such potential lawsuits. It is possible that we could, in the future, incur judgments or enter into settlements of claims for monetary damages. We currently maintain insurance coverage for some of these potential liabilities. Other potential liabilities may not be covered by insurance, insurers may dispute coverage or the amount of insurance may not be enough to cover damages awarded. In addition, certain types of damages may not be covered by insurance, and insurance coverage for all or certain forms of liability may become unavailable or prohibitively expensive in the future. A decision adverse to our interests on one or more legal matters or litigation could result in the payment of substantial damages, or possibly fines, and could have a material adverse effect on our reputation, financial condition and results of operations.

Provisions in our corporate charter documents and under Delaware law could make an acquisition of our company, which may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or remove our current management.

Provisions in our corporate charter and by-laws may discourage, delay or prevent a merger, acquisition or other change in control of our Company that stockholders may consider favorable, including transactions in which you might otherwise receive a premium for your shares. These provisions also could limit the price that investors might be willing to pay in the future for shares of our common stock, thereby depressing the market price of our common stock. In addition, because our board of directors is responsible for appointing the members of our management team, 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. Among other things, these provisions:

•establish a classified board of directors such that not all members of the board are elected at one time;

•allow the authorized number of our directors to be changed only by resolution of the board of directors;

•limit the manner in which stockholders can remove directors from the board;

•establish advance notice requirements for stockholder proposals that can be acted on at stockholder meetings and nominations to the board of directors;

•require that stockholder actions must be effected at a duly called stockholder meeting and prohibit actions by our stockholders by written consent;

•limit who may call stockholder meetings;

•authorize the board of directors to issue preferred stock without stockholder approval, which could be used to institute a shareholder rights plan, or so-called “poison pill,” that would work to dilute the stock ownership of a potential hostile acquirer, effectively preventing acquisitions that have not been approved by the board of directors; and

•require the approval of the holders of at least 75% of the votes that all our stockholders would be entitled to cast to amend or repeal certain provisions of our charter or by-laws.

Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which prohibits a person who owns in excess of 15% of our outstanding voting stock from merging or combining with the Company for a period of three years after the date of the transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in a prescribed manner.

Our certificate of incorporation provides that the Court of Chancery of the State of Delaware will be the exclusive forum for substantially all disputes between the Company and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with the Company or our directors, officers, employees or stockholders.

Our certificate of incorporation provides that the Court of Chancery of the State of Delaware is the exclusive forum for any derivative action or proceeding brought on the Company’s behalf, any action asserting a breach of fiduciary duty owed by our directors, officers, other employees or stockholders to the Company or our stockholders, any action asserting a claim against the Company arising pursuant to the Delaware General Corporation Law or as to which the Delaware General Corporation Law confers jurisdiction on the Court of Chancery of the State of Delaware, or any action asserting a claim arising pursuant to our certificate of incorporation or by-laws or governed by the internal affairs doctrine. This provision may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with the Company or our directors, officers, employees or stockholders, which may discourage such lawsuits against the Company and our directors, officers, employees or stockholders.

Company arising pursuant to the Delaware General Corporation Law or as to which the Delaware General Corporation Law confers jurisdiction on the Court of Chancery of the State of Delaware, or any action asserting a claim arising pursuant to our certificate of incorporation or by-laws or governed by the internal affairs doctrine. This provision may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with the Company or our directors, officers, employees or stockholders, which may discourage such lawsuits against the Company and our directors, officers, employees or stockholders.

Alternatively, if a court were to find this provision in our 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 adversely affect our business and financial condition.

~~ITEM~~Item 1B. ~~UNRESOLVED~~ Unresolved ~~STAFF~~Staff ~~COMMENTS~~Comments

None.

~~ITEM~~Item 1C. ~~CYBERSECURITY~~ Cybersecurity

Cybersecurity Risk Management and Strategy

Our management recognizes the impact that cybersecurity threats could have on our business operations, our compliance with regulations, and our reputation. We have identified cybersecurity as a critical business risk as part of our overall risk management strategy, which our ~~board~~Board of ~~directors~~Directors (the “Board”) oversees.

We have implemented a cybersecurity program in accordance with our risk profile and business that includes, among other things, written policies, monitoring and filtering procedures, and employee training. We have also developed an incident response policy and procedure designed to facilitate the timely reporting and assessment of cybersecurity incidents.

63Our cybersecurity risk management program, which is part of our enterprise risk management program, aims to identify risks related to the Company, including risks from cybersecurity threats. We engage third party advisors, including assessors and cybersecurity consultants, to assess, validate and enhance our cybersecurity program. Our cybersecurity risk management program includes a number of components, including informal self-assessments and audits, penetration testing, and vulnerability assessments, that are conducted periodically by both internal and external resources. The Company also analyzes current and emerging cyber threats that pose a risk to the organization using various threat intelligence tools and services.

Our cybersecurity risk management program, which is part of our enterprise risk management program, aims to identify risks related to the Company, including risks from cybersecurity threats. Our cybersecurity risk management program includes a number of components, including informal self-assessments and audits, penetration testing, and vulnerability assessments, that are conducted periodically by both internal and external resources. The Company also analyzes current and emerging cyber threats that pose a risk to the organization using various threat intelligence tools and services.

As part of our cybersecurity risk management program, we take a risk-based approach to the evaluation of third-party vendors, and apply mitigations and processes based on our evaluation of the sensitivity of the data accessed by the vendor and the maturity of the vendor’s programs. Our vendor evaluation procedures include, as appropriate, the review of vendors’ SOC 2 Type 2 reports and a vendor security questionnaire.

Governance Related to Cybersecurity Risks

Our Director of Infrastructure, Operations and Cybersecurity (“IT Director”), who reports to our Chief Financial Officer, has over ten years of experience managing organizational operations, security and infrastructure,. The IT Director manages the Company’s cybersecurity program. Weand ~~have~~is aresponsible ~~cyber~~for ~~subcommittee (~~the ~~“Subcommittee”),~~day-to-day ~~which~~monitoring ~~includes~~and ~~members~~remediation of ~~our~~cybersecurity ~~finance,~~risks. ~~legal,~~The ~~and~~ IT ~~departments,~~Director ~~that~~ meets periodically towith ~~discuss~~members ~~the~~of ~~Company’s~~our ~~ongoing~~finance ~~cybersecurity~~and ~~efforts.~~legal ~~The~~departments ~~Subcommittee reports~~ to ~~the~~discuss ~~Chief Operating Officer (“COO”) and Chief Financial Officer (“CFO”), who report outputs from~~ the ~~Subcommittee regarding potential cybersecurity risks to the~~ Company’s ~~executive~~ongoing ~~team and the board. The Director of Infrastructure, Operations & Cybersecurity is responsible for the day-to-day monitoring and remediation of~~ cybersecurity ~~risks~~efforts.

The ~~board~~Board is responsible for informed oversight of our risk management process. The ~~board~~Board administers this oversight function through various board standing committees that address risks inherent in their respective areas of oversight. The ~~board~~Board has delegated oversight for cybersecurity risk management to the Audit Committee. The Audit Committee reviews the Company’s policies and procedures with respect to cybersecurity risk management.

Since the beginning of fiscal year 2025, we have not identified risks from known cybersecurity threats or incidents that have materially affected us or are reasonably likely to materially affect us. Although risks from cybersecurity threats have to date not materially affected us, our business strategy, results of operations or financial condition this fiscal year, we have, from time to time, experienced threats to and breaches of our and our third-party vendors’ data and systems. For more information, see Item 1A. Risk Factors.

~~ITEM 2. PROPERTIES~~67

WeItem ~~lease approximately 28,000 square feet of office space at 61 North Beacon Street, 4th Floor, Boston, Massachusetts, which serves as our corporate headquarters~~2. The lease expires on November 30, 2026. The base monthly payment on the lease is approximately $91 thousand as of December 31, 2024, subject to specified annual increases of approximately 3% during the term of the lease and not including operating expenses, certain utilities, taxes and insurance for which we are responsible. We have the right to sublease the premises, subject to landlord consent and we have the right to renew the lease for an additional five years at the then-prevailing effective market rental rate. Properties

We lease approximately 128,~~200~~000 square ~~meters~~feet of ~~laboratory and~~ office space inat ~~Vienna~~61 North Beacon Street, ~~Austria~~4th ~~under~~Floor, aBoston, ~~lease~~Massachusetts, ~~that~~which ~~will~~serves ~~expire~~as inour ~~March~~corporate ~~2028~~headquarters. The lease expires on November 30, ~~with~~2026. aThe base monthly payment ofon the lease is approximately $2496 thousand as of December 31, 2025, not including operating expenses, certain utilities, taxes and insurance for which we are responsible. We have the right to sublease the premises, subject to landlord consent.

~~ITEM~~ Item 3. ~~LEGAL~~ Legal ~~PROCEEDINGS~~ Proceedings

From time to time, we may bebecome involved in ~~lawsuits,~~legal proceedings or be subject to claims, ~~investigations~~arising ~~and~~in ~~proceedings,~~the ~~consisting~~ordinary course of ~~intellectual~~our ~~property,~~business. ~~commercial,~~We ~~employment~~are ~~and~~not ~~other~~currently ~~matters~~a ~~which~~party ~~arise~~to inany ~~the~~material ~~ordinary~~legal ~~course~~proceedings ofand ~~business.~~we ~~While~~are ~~the~~not ~~outcome~~aware of any ~~such~~pending or threatened legal proceedings ~~cannot~~against beus ~~predicted~~that ~~with~~we ~~certainty,~~believe ascould ofhave ~~December~~a ~~31,~~material ~~2024,~~adverse weeffect ~~were~~on ~~not~~our ~~party~~business, tooperating ~~any~~results ~~legal~~or ~~proceedings~~financial condition.

~~ITEM~~Item 4. ~~MINE~~ Mine ~~SAFETY~~Safety ~~DISCLOSURES~~Disclosures

Not applicable.

6468

PART II

~~ITEM~~ Item 5. ~~MARKET~~ Market ~~FOR~~for ~~REGISTRANT~~Registrant’Ss ~~COMMON~~Common ~~EQUITY~~Equity, ~~RELATED~~Related ~~STOCKHOLDER~~Stockholder ~~MATTERS~~Matters ~~AND~~and ~~ISSUER~~Issuer ~~PURCHASES~~Purchases OFof ~~EQUITY~~Equity ~~SECURITIES~~Securities

Market Information

Our common stock ~~commenced~~is ~~trading~~traded on the Nasdaq Global Market under the symbol “ASNS” on November 16, 2017. Prior to that date, there was no public trading market for our common stock. On March 13, 2019, we completed a business combination in accordance with the terms of the Merger Agreement, by and among us, X4 Therapeutics, Inc. (formerly X4 Pharmaceuticals, Inc.) and the Merger Sub, pursuant to which, among other matters, Merger Sub merged with and into X4 Therapeutics, Inc., with X4 Therapeutics, Inc. continuing as our wholly-owned subsidiary and the surviving corporation of the merger. Following the Merger, on March 14, 2019, we effected a 1-for-6 reverse stock split of our common stock and changed our name to “X4 Pharmaceuticals, Inc.” On March 13, 2019, following the completion of the Merger, our common stock began trading on the Nasdaq Capital Market under the symbol “XFOR”.

Holders of Our Common Stock

As of March 1312, ~~2025~~2026, based on information from our transfer agent, there were 4838 holders of record of our common stock, one of which is Cede & Co., a nominee for Depository Trust Company (“DTC”). All of the shares of common stock held by brokerage firms, banks and other financial institutions as nominees for beneficial owners are deposited into participant accounts at DTC, and are considered to be held of record by Cede & Co. as one stockholder. The actual number of stockholders is greater than this number of record holders, and includes stockholders who are beneficial owners, but whose shares are held in street name by brokers and other nominees. This number of holders of record also does not include stockholders whose shares may be held in trust by other entities.

Dividend Policy

We have never declared or paid cash dividends on our common stock. We currently intend to retain all available funds and any future earnings to fund the development and expansion of our business, and we do not anticipate paying any cash dividends in the foreseeable future. Any future determination to declare and pay dividends will be made at the discretion of our board of directors and will depend on then-existing conditions, including our results of operations, financial condition, contractual restrictions, capital requirements, business prospects and other factors our board of directors may deem relevant.

Equity Compensation Plan

The information required by Item 5 of Form 10-K regarding equity compensation plans is incorporated herein by reference to Item 12 of Part III of this Annual Report on Form 10-K.

Recent Sales of Unregistered Securities

None.

Purchase of Equity Securities by the Issuer and Affiliated Purchasers

None.

~~ITEM~~ Item 6. [~~RESERVED~~Reserved]

6569

~~ITEM~~ Item 7. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

~~You~~The ~~should read the~~ following discussion and analysis ofis ~~our~~intended ~~financial~~to ~~condition~~provide ~~and~~material ~~results~~information ofaround ~~operations~~events ~~together~~and ~~with~~uncertainties ~~our~~known ~~consolidated~~to ~~financial~~management ~~statements~~that ~~and~~are ~~the~~relevant ~~related~~to ~~notes~~an ~~and~~assessment of the ~~other~~ financial ~~information~~condition ~~included~~and ~~elsewhere~~results inof ~~this~~operations ~~Annual Report. Some~~ of ~~the~~X4 ~~information~~Pharmaceuticals ~~contained in this discussion~~ and ~~analysis~~should ortherefore ~~set~~be ~~forth~~read ~~elsewhere~~ in ~~this~~conjunction ~~Annual Report, including information~~ with ~~respect to~~ our ~~plans~~audited ~~and~~Consolidated ~~strategy~~Financial ~~for~~Statements ~~our business~~ and the related ~~financing,~~notes ~~includes~~thereto ~~forward-looking statements that involve risks~~ and ~~uncertainties.~~other Asdisclosures aincluded ~~result~~as ofpart ~~many factors, including those factors set forth in the “Risk Factors” section~~ of this Annual Report, ~~our~~on ~~actual~~Form ~~results~~10-K, ~~could~~including ~~differ materially from~~ the ~~results~~disclosures ~~described~~under inPart orI, ~~implied~~Item by1A. ~~these~~Risk ~~forward-looking statements~~Factors.

For the discussion of the financial condition and results of operations for the year ended December 31, 2023 compared to the year ended December 31, 2022, refer to “Management’s Discussion and Analysis of Financial Condition and Results of Operations” to our Annual Report on Form 10-K filed with the SEC on March 21, 2024.

Overview

We are a biopharmaceutical company ~~discovering,~~ developing, and commercializing novel therapeutics for the treatment of rare hematology diseases. ~~and~~We ~~those~~continue ~~with~~to ~~limited~~progress ~~treatment~~our ~~options~~global, ~~with~~pivotal aPhase ~~focus~~3 onclinical ~~conditions~~trial, ~~resulting~~(the ~~from~~“4WARD” ~~dysfunction~~trial) ofto evaluate the ~~immune~~efficacy, ~~system.~~safety, Onand ~~April~~tolerability 29of oral, ~~2024~~once-daily mavorixafor (with or without stable doses of granulocyte colony-stimulating factor (“G-CSF”) in people with congenital, weacquired ~~announced~~primary ~~that~~autoimmune, ~~the~~or Uidiopathic chronic neutropenia (“CN”) who are experiencing recurrent and/or serious infections.S. ~~FDA~~The ~~approved~~52-week ~~our~~trial ~~NDA~~is ~~for~~a ~~mavorixafor~~randomized, ~~which~~double-blind, isplacebo-controlled, ~~being~~multicenter ~~marketed~~study aiming to enroll up to 176 patients, with full enrollment expected in the third quarter of 2026. The U.S. ~~under~~Food ~~the~~and ~~trade~~Drug ~~name~~Administration ~~XOLREMDI,~~(“FDA”) ~~for~~has ~~use~~granted asFast anTrack ~~oral,~~designation ~~once-daily~~to ~~therapy~~mavorixafor infor ~~patients~~the ~~aged~~treatment 12of ~~years~~CN, ofwhich ~~age~~is ~~and~~defined ~~older~~as ~~with~~periods ~~WHIM~~lasting ~~(warts,~~more ~~hypogammaglobulinemia,~~than ~~infections,~~three ~~and~~months ~~myelokathexis)~~persistently ~~syndrome,~~or tointermittently ~~increase~~where ~~the~~there ~~number~~are abnormally low levels of neutrophils circulating ~~mature~~in ~~neutrophils~~the blood, and ~~lymphocytes.~~may ~~WHIM~~be ~~syndrome~~idiopathic (~~Warts,~~of ~~Hypogammaglobulinemia,~~unknown ~~Infections~~origin), ~~and~~cyclic ~~Myelokathexis)~~(episodes istypically aoccurring ~~rare~~every ~~combined~~three ~~primary~~weeks), ~~immunodeficiency~~or ~~and~~congenital ~~chronic~~(of ~~neutropenic~~genetic ~~disorder~~causation). ~~Concurrent~~CN ~~with~~disorders ~~the~~are ~~U.S.~~rare ~~approval~~blood conditions similarly characterized by increased risks of ~~XOLREMDI~~infections and ~~pursuant~~cancer due to ~~its~~abnormally ~~Rare~~low ~~Pediatric~~levels ~~Disease~~of ~~designation,~~neutrophils in the ~~FDA~~body. ~~granted~~In usall acases, ~~PRV~~the ~~that~~CXCL12/CXCR4 wepathway ~~sold~~is tothe ~~another~~key ~~drug~~regulator ~~sponsor~~of ~~shortly~~neutrophil ~~thereafter.~~release from the bone marrow.

We have one commercially approved product, XOLREMDI ~~Commercial~~® ~~Launch~~(mavorixafor), which has received accelerated approval in the United States from the FDA for use as an oral, once-daily therapy in patients 12 years of age and older with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, to increase the number of circulating mature neutrophils and lymphocytes. WHIM syndrome is a rare combined primary immunodeficiency and CN disorder. In connection with our long term strategy to successfully complete the 4WARD Phase 3 trial in patients with moderate and severe CN, we are no longer prioritizing investment in the WHIM indication.

WePrivate ~~are~~Placement ~~currently~~Financing ~~engaged in our U.S. launch of XOLREMDI in WHIM syndrome, continuing our engagements with physicians~~ and ~~rare~~Management disease patient advocacy organizations and our disease-awareness campaign to further the understanding of WHIM syndrome and educate patients and physicians on the importance and benefits of early diagnosis. We have entered into agreements with a third-party logistics organization and a specialty pharmacy to support the distribution of XOLREMDI in the U.S., to mitigate barriers to product access, and to provide a suite of patient support services to help patients through their treatment journey. We submitted a Marketing Authorisation Application (“MAA”) to the European Medicines Agency (“EMA”) in early 2025 seeking regulatory approval to commercialize mavorixafor for WHIM syndrome outside of the U.S. Such MAA was accepted for processing by the EMA in January 2025. As discussed further below, on January 13, 2025, we entered into a License and Supply Agreement (the “Norgine Agreement”) with Norgine Pharma UK Limited (“Norgine”), pursuant to which Norgine is granted an exclusive license to distribute, market and sell our drug product for all indications in the European Economic Area, Switzerland, the United Kingdom, Australia and New Zealand. In February 2025, we announced that we had entered into an agreement with taiba rare to distribute and commercialize XOLREMDI for the treatment of WHIM syndrome in select Middle East and North African countries. We continue to explore additional potential commercial and distribution opportunities in geographies where we may be able to efficiently leverage any of our regulatory approvals. Changes

~~The~~During ~~U.S.~~the ~~approval~~third quarter of ~~XOLREMDI~~2025, inwe ~~the~~sold ~~WHIM~~shares ~~syndrome~~of ~~indication~~common isstock ~~the~~and ~~first~~pre-funded ~~for~~warrants ~~mavorixafor,~~to ~~which~~purchase isshares anof ~~orally~~common ~~active,~~stock ~~selective~~in ~~antagonist~~a ofprivate ~~chemokine~~placement ~~receptor~~that ~~CXCR4,~~resulted ain ~~key~~net ~~regulator~~proceeds of ~~the~~approximately ~~movement~~$81.0 ofmillion, ~~immune~~after ~~cells~~deducting ~~throughout~~placement ~~the~~agent ~~body.~~fees ~~Due~~and toother ~~its~~expenses. ~~ability~~Pursuant to ~~increase~~registration ~~the~~rights ~~mobilization~~agreements, ofwe ~~white~~registered ~~blood cells from~~ the ~~bone~~shares ~~marrow~~of ~~into~~common ~~the~~stock ~~bloodstream,~~issued weand ~~believe~~issuable ~~that~~under ~~mavorixafor~~pre-funded ~~has~~warrants ~~the~~under ~~potential~~a toregistration ~~provide~~statement ~~therapeutic~~on ~~benefit~~Form ~~across~~S-3 athat ~~variety~~was ofdeclared ~~immune~~effective ~~system~~by ~~disorders~~the inSEC ~~addition~~on toSeptember ~~WHIM~~17, ~~syndrome~~2025.

~~Phase~~Concurrent 2with ~~Clinical~~the ~~Study~~financing inand ~~Chronic~~effective ~~Neutropenia~~August 12, 2025, our former President and Chief Executive Officer, Paula Ragan, PhD, and Chief Financial Officer, Adam Mostafa, stepped down from their respective roles and their employment was terminated. Dr. Ragan also resigned from the Company’s Board of Directors (the “Board”), and Michael Wyzga transitioned from Board Chair to Lead Independent Director. The Board appointed Adam R. Craig, M.D., Ph.D, MBA as Executive Chairman, John Volpone as President and subsequently as Chief Operating Officer, and David Kirske as Chief Financial Officer.

~~Following~~Q4 ~~positive~~2025 ~~results~~Equity from a Phase 1b clinical study of a single dose of mavorixafor in people with idiopathic, cyclic, and congenital chronic neutropenia (“CN”), we recently completed and announced positive results from a Phase 2 clinical study evaluating the durability of effect, safety, and tolerability of chronic dosing of once-daily oral mavorixafor with or without concurrent treatment with injectable granulocyte colony-stimulating factor (“G-CSF”) in the same patient population.Financing

66In October 2025, we closed an underwritten public offering of our common stock and, in lieu of common stock to certain investors, pre-funded warrants to purchase shares of common stock, raising net proceeds of $145.6 million, net of underwriting discounts and estimated offering expenses.

~~The~~Strategic results from the completed six-month study showed that once-daily oral mavorixafor was generally well tolerated and durably increased participants’ absolute neutrophil counts (“ANC”) both as a monotherapy and in combination with G-CSF, the only therapy approved in the U.S. for severe chronic neutropenia. In addition, when tested in combination with G-CSF, mavorixafor treatment enabled physicians to substantially reduce G-CSF dosing while maintaining normal mean ANC levels.Restructurings

~~Phase~~•In 3the ~~Clinical~~first ~~Trial~~quarter of 2025, we implemented a strategic restructuring of our business operations, workforce and capital spending to focus efforts on advancing mavorixafor to treat patients with CN. As part of this restructuring, we (i) implemented a net reduction of our employee headcount by 43 employees, representing approximately 30% of our total workforce, including our U.S. commercial field team, (ii) commenced the closure of our research and development facility in ~~Chronic~~Vienna, ~~Neutropenia~~Austria, (iii) paused our pre-clinical drug candidate programs and (iv) streamlined other spending to support the ongoing clinical development of mavorixafor for the larger population of those with chronic neutropenia. We incurred charges of approximately $2.1 million for severance and other employee termination-related costs related to this strategic restructuring.

We continue to progress our global, pivotal Phase 3 clinical trial, (the “4WARD” study) to evaluate the efficacy, safety, and tolerability of oral, once-daily mavorixafor (with or without stable doses of G-CSF) in people with congenital, acquired primary autoimmune, or idiopathic CN who are experiencing recurrent and/or serious infections. The 52-week trial is a randomized, double-blind, placebo-controlled, multicenter study aiming to enroll 150 participants. We believe we are on track to complete enrollment in the 4WARD study in the third or fourth quarter of 2025.70

We•In ~~believe~~the ~~that~~third ~~successfully~~quarter ~~developing~~2025, ~~and~~we ~~commercializing~~announced ~~mavorixafor~~an toadditional ~~provide~~strategic arestructuring ~~new~~designed ~~therapeutic~~to ~~option~~further tosharpen ~~individuals~~operational ~~diagnosed~~focus ~~with~~and ~~certain~~align ~~immunodeficiencies~~resources ~~has~~with ~~the~~our ~~potential~~long‑term strategy to ~~revolutionize~~successfully complete the ~~current~~4WARD ~~treatment~~Phase ~~landscape~~3 trial in patients with moderate and severe CN. As part of this initiative, ~~which~~we isfurther ~~principally~~reduced ~~served~~our workforce by ~~injectable~~approximately 50%. We incurred expenses of approximately $4.9 million during the third quarter for severance and ~~infused~~other ~~therapies~~employee termination-related costs related to this strategic restructuring. This workforce reduction was substantially completed in the third quarter of 2025.

These strategic restructuring actions have allowed us to decrease our operating expenses, including research and development and general and administrative expenses, from $143.2 million in 2024 to $116.2 million in 2025. ~~Restructuring~~The estimate of costs that we expect to incur related to these workforce reduction as well as the decrease in spending, and the timing thereof are subject to a number of assumptions and actual results may differ. We may also incur additional costs not currently contemplated due to events that may occur as a result of, or that are associated with, the actions described above.

InRegulatory ~~February~~Update ~~2025, we implemented a strategic restructuring of our business operations, workforce~~ and capital spending to focus efforts on advancing mavorixafor to treat those with chronic neutropenia, while also optimizing its U.S. promotion of XOLREMDI (the “2025 Restructuring”). As part of the 2025 Restructuring, we implemented a net reduction of our employee headcount by 43 employees, or approximately 30% of our total workforce. The strategic restructuring activities include (i) discontinuing of research efforts, (ii) closing of our facility in Vienna, Austria, (iii) pausing preOut-~~clinical~~License drug candidate programs, (iv) scaling the U.S. commercial field team and supporting roles across our business and (v) streamlining other spending to support the ongoing clinical development of mavorixafor for the larger population of those with chronic neutropenia. We estimate that the workforce reduction will be substantially completed in the first quarter of 2025. We estimate that it will incur charges of approximately $3.0 million for severance and other employee termination-related costs, primarily in the first quarter of 2025. We expect the 2025 Restructuring will decrease annual spending by $30 to 35 million and believe it will have sufficient funds to support operations into the first half of 2026. The estimate of costs that we expect to incur related to the 2025 Restructuring as well as the decrease in annual spending, and the timing thereof are subject to a number of assumptions and actual results may differ. Agreements

WeIn ~~may~~early ~~also~~2025, ~~incur~~we ~~additional~~submitted ~~costs~~a ~~not~~Marketing ~~currently~~Authorization ~~contemplated~~Application ~~due~~(“MAA”) to ~~events~~the ~~that~~EMA ~~may~~seeking ~~occur~~regulatory asapproval to commercialize mavorixafor for WHIM syndrome in the European Union. Such MAA was validated for processing by the EMA in January 2025. In February 2026, the EMA’s Committee for Medicinal Products for Human Use adopted a ~~result~~positive opinion recommending the grant of, ormarketing ~~that~~authorization, ~~are~~under ~~associated~~exceptional ~~with~~circumstances, for mavorixafor for the ~~actions~~treatment ~~described~~of WHIM syndrome in the European Union. The positive opinion has been submitted to the European Commission for review, and we expect the European Commission to issue a final approval decision in the second quarter of 2026. On January 13, 2025, ~~Restructuring~~we ~~above~~announced a License and Supply Agreement (the “Norgine Agreement”) with Norgine Pharma UK (“Norgine”), pursuant to which Norgine was granted an exclusive license to distribute, market and sell our drug product for all indications in the European Economic Area, Switzerland, the United Kingdom, Australia, and New Zealand.

Norgine Agreement

On January 13, 2025, we entered into the Norgine Agreement, pursuant to which Norgine is granted an exclusive license to distribute, market and sell our product mavorixafor for all indications in the European Economic Area, Switzerland, the United Kingdom, Australia and New Zealand following regulatory approval. Pursuant to the terms of the Norgine Agreement, we received an upfront payment of €28.5 million upon signing of the agreement and could receive up to €226.0 million upon the achievement of certain regulatory, commercial and sales milestones. We will also receive escalating, double-digit royalties of up to mid-twenties on any future net sales of our drug product by Norgine. Norgine will be responsible for all market access and commercialization activities and will eventually hold all marketing authorizations in the licensed territories. We will manufacture and supply drug product to Norgine for a supply price derived from our product manufacturing cost plus a low double-teen digit margin.

Results of Operations

The following table summarizes the results of our operations for the years ended December 31, 2025 and 2024:

Comparison of the Years Ended December 31, 2024 and 2023


	Year Ended December 31,
(in millions)		2025		2024		Change

Revenue		$	35.1	$	2.6	$	32.5
Cost and operating expenses:
Cost of revenue		5.8		0.8		5.0
Research and development		72.7		81.6		(8.9)
General and administrative		43.5		61.6		(18.1)
Gain on sale of non-financial asset		—		(105.0)		105.0
Total operating expenses		122.0		39.0		83.0
Loss from operations		(86.9)		(36.4)		(50.5)
Total other income (expense), net		7.7		(0.7)		8.4
Loss before income taxes		(79.2)		(37.1)		(42.1)
Provision for income taxes		—		(0.4)		0.4
Net loss		$	(79.2)	$	(37.5)	$	(41.7)

	Year Ended December 31,
	2024		2023		Change
	(in thousands)
Product revenue, net	$	2,557	$	—	$	2,557
Costs and operating expenses:
Cost of revenue	797		—		797
Research and development	81,643		72,017		9,626
Selling, general and administrative	61,518		35,505		26,013
Gain on sale of non-financial asset	(105,000)		—		(105,000)
Total operating expenses	38,958		107,522		(68,564)
Loss from operations	(36,401)		(107,522)		71,121
Total other (expense) income, net	(739)		6,433		(7,172)
Loss before provision for income taxes	(37,140)		(101,089)		63,949
Provision for income taxes	310		78		232
Net loss	$	(37,450)	$	(101,167)	$	63,717

Revenue

License and Other

In January 2025, we granted an exclusive license to Norgine to distribute, market and sell our product for all indications in the European Economic Area, Switzerland, the United Kingdom, Australia and New Zealand following regulatory approval. For the year ended December 31, 2025, we recognized $27.6 million for the delivery of the license and $1.0 million for the provision of research and development services to Norgine. We had no license or other revenue during the year ended December 31, 2024.

Product Revenue, Net

~~Net~~We ~~revenue~~began ~~from~~recognizing ~~the~~product ~~sale~~sales ofin ~~our~~June ~~drug~~2024 ~~product~~following ~~was~~FDA ~~$2.6~~approval ~~million~~of ~~for~~XOLREMDI ~~the~~on ~~year~~April ~~ended December 31~~29, 2024. ~~There~~and ~~was~~its nosubsequent ~~product~~commercial ~~revenue~~launch in the ~~prior~~United ~~periods~~States. WeNet ~~sell our approved drug~~ product insales the U.S. to a specialty pharmacy that dispenses the product to patients who have been prescribed our drug product by their health-care providers. We also sell our drug product through international distributors. There were noas ~~sales~~follows ~~to international distributors~~ for ~~the~~years ~~year~~ ended December 31, ~~2024.~~2025 ~~Net~~and ~~revenue includes reserves for distributor discounts~~2024, ~~estimated rebates that we may owe to U.S. government payors, future co-pay assistance payments that we may owe for patients who enroll in our patient assistance program,~~ and for ~~potential~~each ~~product~~of ~~returns. As we have just recently launched our first drug product in~~ the ~~U.S. in 2024, we have limited history of returns or downstream rebates or co-pay assistance payments. Therefore, we expect to adjust these estimates~~ quarterly asperiods ~~new information becomes available~~therein.


(in thousands)	2025		2024
First quarter	$	942	$	—
Second quarter	1,744		563
Third quarter	1,566		560
Fourth quarter	2,271		1,434
Year ended December 31,	$	6,523	$	2,557

Co-pay assistance payments and rebates to U.S. government payors have comprised the majority of our gross-to-net revenue adjustments. Gross-to-net adjustments were approximately 10% and 9% for the years ended December 31, 2025 and 2024, respectively.

Operating Cost and Expenses:

Cost of Revenue

~~For~~Cost of revenue primarily consists of amortization of an intangible asset related to accrued and paid milestone payments associated with our license agreement (the ~~year~~“Genzyme ~~ended~~Agreement”) ~~December~~with 31Genzyme Corporation (“Genzyme”), ~~2024~~a wholly owned subsidiary of Sanofi, ~~cost~~and sales and sublicense-based royalty payments due thereunder. Cost of revenue ~~was~~increased $05.80 million. ~~There~~in ~~was~~the noyear ~~cost~~ended ofDecember ~~revenue~~31, in2025, as compared to the prior ~~periods.~~year, primarily due to additional royalties in the current year associated with sublicense income from our Norgine Agreement.

Cost of revenue primarily consists of $0.5 million of amortization of an intangible asset related to accrued and paid milestone payments associated with our Genzyme license agreement, $0.2 million of sales-based royalty payments accrued and paid under our Genzyme license agreement, and $0.1 million of drug product costs.

Research and Development Expenses

Research and development expenses consist primarily of costs incurred in connection with the development of our product candidates, including employee salaries and related expenses ~~for personnel in our clinical operations~~, ~~biostatistics, medical affairs, manufacturing and technical, quality and regulatory affairs departments; external expenses incurred in connection with the~~ clinical development ~~of our product candidates~~expenses, ~~including~~internal ~~under~~and ~~agreements with~~ third-party ~~parties,~~costs ~~such as consultants and contract research organizations (“CROs”); the cost~~ of manufacturing our drug products for use in our clinical trials,. ~~including~~Research ~~under~~and ~~agreements~~development ~~with~~expenses ~~third~~also ~~parties,~~include ~~such~~costs asrelated ~~consultants~~to ~~and~~compliance ~~contract~~with ~~manufacturing~~regulatory ~~organizations (“CMOs”)~~requirements; ~~facilities,~~and ~~depreciation~~prior ~~and~~to ~~other~~the ~~expenses,~~FDA’s ~~which~~approval ~~include~~of ~~direct~~XOLREMDI orin ~~allocated~~the ~~expenses~~U.S. ~~for~~in ~~rent~~the ~~and~~second ~~maintenance~~quarter of ~~facilities~~2024, ~~and~~payments ~~insurance;~~made ~~and~~under ~~costs~~third-party ~~related~~licensing toagreements ~~compliance~~were ~~with~~charged ~~regulatory~~to ~~requirements. We expense~~ research and development ~~costs as incurred~~expense. ~~We capitalized as intangible assets certain milestone payments due under our key in-license agreement.~~

68Following our strategic restructuring announced during the first quarter of 2025, substantially all of our research and development has been focused on our one product candidate, mavorixafor. The following table shows external costs incurred by product candidate (primarily external contract research organization costs) and unallocated research and development costs, primarily consisting of employee salaries and related expense for our research and development organization.

	Year EndedDecember 31,
			Year Ended December 31,
	2024		2023		Change
(in millions)							2025		2024		Change
	(in thousands)
Direct research and development expenses by product candidate:
Mavorixafor (X4P-001)	$	41,483	$	41,163	$	320
Mavorixafor							$	41.4	$	41.5	$	(0.1)
X4P-002	~~159~~		~~(34)~~		~~193~~		—		0.2		(0.2)
X4P-003	~~150~~		75		75		—		0.2		(0.2)
Unallocated expense	~~39,851~~		~~30,813~~		~~9,038~~		31.3		39.7		(8.4)
Total research and development expenses	$	~~81,643~~	$	~~72,017~~	$	~~9,626~~	$	72.7	$	81.6	$	(8.9)

Research and development expenses ~~increased~~decreased by $98.69 million ~~for~~in the year ended December 31, ~~2024,~~2025 as compared to the prior year primarily due to andecreases ~~increase~~ in ~~unallocated~~spending ~~expense~~associated with our 2025 strategic restructurings, including lower spending on non-clinical programs, lower consulting fees, lower drug substance manufacturing costs, and lower regulatory costs. ~~Unallocated~~For ~~expense~~the ~~increased~~year ~~primarily~~ended ~~due~~December to31, an2025, ~~increase~~unallocated expense includes $2.0 million in ~~personnel~~severance ~~within~~charges ~~our~~for terminated employees. The overall decrease in research and development ~~functions,~~expenses ~~primarily~~ in ~~our~~the ~~clinical~~current ~~operations,~~year ~~biostatistics,~~was ~~medical~~partially ~~affairs,~~offset ~~manufacturing~~by ~~and~~higher ~~technical,~~clinical ~~and~~costs ~~quality~~associated ~~organizations.~~with our 4WARD trial.

We expect that our research and development expenses, particularly for our mavorixafor programs, will be relatively consistent over the next several years as we continue to conduct our clinical trials of mavorixafor in chronic neutropenic disorders. Research and development expenses related to our X4P-002 and X4P-003 programs was not significant in 2024 or 2023 relative to our overall research and development expenses.72

~~Selling,~~ General and Administrative Expenses

~~Selling,~~General ~~general~~ and administrative expenses consist primarily of salaries and related costs, including stock-based compensation, for personnel in ~~sales and marketing,~~ executive, finance, and administrative functions. ~~Selling,~~General ~~general~~ and administrative expenses also include direct and allocated facility-related costs, as well as professional fees for legal, patent, consulting, investor and public relations, accounting, and audit services.

~~Selling,~~General ~~general~~ and administrative expenses ~~increased~~decreased by ~~$26.0~~approximately ~~million to~~ $6118.51 million ~~for~~in the year ended December 31, ~~2024~~2025 as compared to ~~$35~~the prior year. General and administrative expenses include $5.0 million in ~~the~~severance ~~prior~~charges ~~year.~~for ~~The~~terminated ~~increase~~employees in ~~selling~~the year ended December 31, 2025. The decrease to general and administrative ~~expense~~expenses was primarily due to an ~~increase of~~ $158.20 million decrease in ~~selling~~compensation ~~and~~expense ~~marketing~~due ~~expenses,~~to ~~including~~lower ~~increases~~head count in our sales, general and ~~marketing~~administrative ~~personnel~~functions, and ~~external~~a ~~marketing~~decrease ~~costs~~of to$9.0 ~~support~~million ~~the~~in ~~ongoing~~sales ~~launch~~and ~~activities~~marketing ofexpenses ~~our~~in ~~approved~~the ~~product,~~current ~~XOLREMDI~~year inas compared to the ~~U.S.~~prior ~~Selling,~~year ~~general~~during ~~and~~which ~~administrative~~we ~~expenses~~incurred ~~also~~commercialization ~~increased~~sales ~~due~~and tomarketing anlaunch ~~increase~~costs ofrelated ~~$10~~to XOLREMDI.8 ~~million~~These decreases in general and administrative expenses, ~~primarily~~were ~~due~~partially tooffset by higher ~~legal,~~severance ~~corporate~~costs ~~communications,~~associated ~~accounting,~~with ~~information~~our ~~technology,~~2025 strategic restructurings and ~~professional~~higher ~~service~~legal costs ~~associated~~in ~~with~~ the ~~ongoing~~current ~~commercialization of our drug product~~year.

~~Gain~~Other onIncome ~~Sale~~(Expense), ~~of Non-Financial Asset~~Net

During the year ended December 31, 2024, we entered into contractual arrangement with a third party that transferred the rights to a Priority Review Voucher (“PRV”) awarded to the Company as a result of the FDA’s approval of XOLREMDI. The PRV was accounted for as an intangible asset with no accounting cost basis. The third party purchased the PRV for $105.0 million. As a result of the transfer of control of the PRV to the third party, the Company derecognized the associated intangible asset and recorded a gain through “gain on transfer of nonfinancial assets.” There was no such transaction in year ended December 31, 2023 and we do not expect similar PRV sales in the future.


	Year Ended December 31,
		2025		2024		change
(in millions)
Interest income		$	4.6	$	5.8	$	(1.2)
Interest expense		(8.9)		(8.8)		(0.1)
Change in fair value of Class C warrant liability		12.8		1.9		10.9
Other (expense) income, net		(0.8)		0.4		(1.2)
Total other income (expense), net		$	7.7	$	(0.7)	$	8.4

~~Operating~~Other ~~Expenses~~income (expense), net, increased approximately $8.4 million in the year ended December 31, 2025 as compared to the prior year primarily due to higher gains in the current year on fair value adjustments related to our Class C warrants, partially offset by lower interest income earned on our marketable security investment portfolio.

~~Our~~Provision ~~operating expenses decreased by $68.6 million~~ for ~~the~~Income year ended December 31, 2024 as compared to the prior year. Excluding the impact of the PRV sale, operating expenses increased $36.4 million in the current year as compared to the prior year, primarily due to an increase in head count to support our U.S. launch of XOLREMDI and to support our 4WARD clinical trial. As a result of the strategic restructuring of our workforce and capital spending to focus efforts on advancing mavorixafor to treat those with chronic neutropenia, while also optimizing its U.S. promotion of XOLREMDI, we expect that our operating expenses will decrease by approximately $30.0 million to $35.0 million in 2025. Taxes

69Our income tax provision of $41.0 thousand for the year ended December 31, 2025, which was primarily related to our Austrian subsidiary, was lower than our income tax provision in the prior year. Our income tax provision for the year ended December 31, 2024 of $0.3 million reflected U.S. federal and state taxable income that included the sale of a priority review voucher, generating $105.0 million of taxable income, partially offset by available deductions, net operating loss carryforwards, which were limited under IRC 382 due to several qualifying ownership changes, and available research and development credits. We will continue to maintain a full valuation allowance against net deferred tax assets, including net operating loss carryforwards, until we are able to consistently generate sufficient taxable income to realize the benefit of our net deferred tax assets.

	Year EndedDecember 31,
	2024		2023		Change
	(in thousands)
Interest income	$	5,769	$	4,582	$	1,187
Interest expense	(8,768)		(5,777)		(2,991)
Change in fair value of warrant and derivative liabilities	1,928		7,074		(5,146)
Research and development incentive program	659		553		106
Foreign currency (losses) gains	(327)		1		(328)
Total other (expense) income, net	$	(739)	$	6,433	$	(7,172)

The increase in other (expense) income, net, of $7.2 million for the year ended December 31, 2024 as compared to 2023 was primarily due (i) lower income resulting from the decrease in the fair value of outstanding Class C warrants, which are accounted for as a liability and are remeasured to fair value each period, as compared to the prior year and, (ii) an increase in interest expense associated with the Hercules Loan agreement due to more borrowings outstanding during the current period. These increases were partially offset by higher interest income earned in the current year on our marketable security portfolio as compared to the prior year.

Income Taxes

For the year ended December 31, 2024, we recorded an income tax provision of $0.3 million related to our U.S. operations and related to our Austrian subsidiary. Our tax provision in the year ended December 31, 2023 was related to our U.S. security corporation, which holds our investment portfolio, and our Austrian subsidiary. During the current year, our U.S. entity generated taxable income due to the sale of a PRV voucher, which generated $105.0 million of taxable income, and product revenue, partially offset by available deductions, net operating loss carryforwards and available research and development credits. Our net operating loss carryforwards were limited under IRC 382 due to several qualifying changes in ownership resulting from certain of our equity financings and therefore we were not able to fully offset our taxable income in the current year. We do not expect to record a significant income tax benefit or expense for several years until such time as we begin to generate meaningful and sustained taxable income in our U.S. jurisdiction.

Liquidity and Capital Resources

Sources of Liquidity

To date, we have funded our operations primarily with proceeds from sales of common stock, warrants, prefunded warrants and ~~prefunded~~preferred stock, proceeds from the issuance of convertible debt and borrowings under loan and security agreements.

~~warrants~~Public ~~for~~and Private Equity Offerings. Over the ~~purchase~~past ofseveral ~~our~~years ~~preferred~~we ~~stock~~have ~~and~~funded our ~~common~~operations ~~stock,~~primarily from sales of ~~preferred~~common stock, ~~proceeds~~warrants ~~from~~and ~~the~~prefunded ~~issuance~~warrants

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