UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-K

(Mark One)


☒	Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

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


☐	Transition report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

For the transition period from to

Commission File Number: 001-~~39473~~37823

TUHURA BIOSCIENCES, INC.

(Exact name of registrant as specified in its charter)


Nevada	99-0360497
(State or other jurisdiction of incorporation or organization)	(I.R.S. Employer Identification No.)

10500 University Center Dr., Suite 110

Tampa, Florida 33612

(Address of principal executive offices and Zip Code)

(813) 875-6600

(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

     HURA

     The Nasdaq Capital Market LLC

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

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

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

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐

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

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company” and “emerging growth company” in Rule 12b-2 of the Exchange Act.


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

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

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

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

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

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

The aggregate market value of the common equity held by non-affiliates of the registrant, based on the closing price of the shares of common stock on The Nasdaq Stock Market (“Nasdaq”) on June 30, ~~2024~~2025 (the last business day of the registrant’s second fiscal quarter), was $14111,~~932~~000,000, based on the closing price on Nasdaq reported for such date. As of March 3123, ~~2025~~2026, there were 4363,~~680~~578,~~397~~528 shares of the registrant’s common stock outstanding.

DOCUMENTS INCORPORATED BY REFERENCE

Portions of the registrant’s definitive proxy statement for the annual stockholder meeting to be held in 2026 are incorporated by reference into Part III of this Annual Report on Form 10-K as noted herein. The registrant intends to file its proxy statement within 120 days after its fiscal year end.

Table of Contents

Forward-Looking Statements

PART I		43
	Item 1. Business	43
	Item 1A. Risk Factors	4345
	Item 1B. Unresolved Staff Comments	8184
	Item 1C. Cybersecurity	8184
	Item 2. Properties	8285
	Item 3. Legal Proceedings	8285
	Item 4. Mine Safety Disclosures	8285
PART II		8285
	Item 5. Market for Registrant’s Common Equity; Related Stockholder Matters and Issuer Purchases of Equity Securities	8285
	Item 6. [Reserved]	8286
	Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operation	8387
	Item 7A. Quantitative and Qualitative Disclosures About Market Risk	9498
	Item 8. Financial Statements and Supplementary Data	9498
	Item 9. Changes in and Disagreements With Accountants on Accounting and Financial Disclosure	9498
	Item 9A. Controls and Procedures	9498
	Item 9B. Other Information	9599
	Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections	9599
PART III		96100
	Item 10. Directors, Executive Officers and Corporate Governance	96100
	Item 11. Executive Compensation	100
	Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	~~109~~100
	Item 13. Certain Relationships and Related Transactions, and Director Independence	~~113~~100
	Item 14. Principal Accounting Fees and Services	~~114~~100
PART IV		~~115~~101
	Item 15. Exhibits, Financial Statement Schedules	~~115~~101
	Item 16. Form 10-K Summary	~~118~~104
Signatures

EXPLANATORY NOTE

On October 18, 2024, the Nevada corporation formerly known as “Kintara Therapeutics, Inc.” completed its previously announced merger transaction in accordance with the terms of the Agreement and Plan of Merger, dated as of April 2, 2024 (the “Kintara Merger Agreement”), by and among Kintara Therapeutics, Inc. (“Kintara”), TuHURA Biosciences, Inc. (“Legacy TuHURA”), and Kayak Mergeco, Inc., a direct wholly owned subsidiary of Kintara (“Merger Sub”), pursuant to which Merger Sub merged with and into Legacy TuHURA, with Legacy TuHURA surviving as a direct wholly owned subsidiary of Kintara and the surviving corporation of the merger (the “Kintara Merger”). Additionally, as a result of the Kintara Merger, Kintara changed its name from “Kintara Therapeutics, Inc.” to “TuHURA Biosciences, Inc.” Following the completion of the Kintara Merger, the business of Legacy TuHURA became the primary business of the combined company, which is a clinical stage immune-oncology company developing novel personalized cancer vaccine product candidates designed to overcome resistance to immunotherapies like checkpoint inhibitors. Unless the context otherwise requires, “we,” “us,” “our,” and the “Company” refer to TuHURA Biosciences, Inc., a Nevada corporation, and its wholly owned subsidiaries (including Legacy TuHURA).

On October 18, 2023, in connection with the transactions contemplated by the Kintara Merger Agreement, Kintara filed a Certificate of Amendment to its articles of incorporation, as amended, effecting a 1-for-35 reverse stock split of Kintara’s common stock (the “Reverse Stock Split”). As a result of the Reverse Stock Split, the number of issued and outstanding shares of Kintara’s common stock immediately prior to the Reverse Stock Split was reduced such that every 35 shares of Kintara’s common stock held by a stockholder immediately prior to the Reverse Stock Split were combined and reclassified into one share of common stock after the Reverse Stock Split. Unless otherwise noted, all references to shares of common stock and per share amounts in this Annual Report on Form 10-K have been retroactively adjusted to reflect the shares issued to Legacy TuHURA stockholders in the Merger based on an exchange ratio of 0.1789 (the “Exchange Ratio”).

Under the terms of the Kintara Merger Agreement, immediately prior to the effective time of the Kintara Merger, shares of Legacy TuHURA’s preferred stock were converted into shares of Legacy TuHURA’s common stock and all of the convertible notes issued in Legacy TuHURA’s private placement financings were converted into shares of Legacy TuHURA common stock pursuant to the terms therein. At the effective time of the Kintara Merger, Kintara issued an aggregate of approximately 40,411,605 shares of its common stock to Legacy TuHURA stockholders, based on the Exchange Ratio. The issuance of the shares of Kintara’s common stock to the Legacy TuHURA stockholders was registered with the SEC on Kintara’s Registration Statement on Form S-4 (File No. 333-279368), as amended.

This Annual Report contains references to trademarks belonging to other entities, which are the property of their respective holders. We do not intend our use or display of other companies’ trade names or trademarks to imply a relationship with, or endorsement or sponsorship of us by, any other companies.

FORWARD-LOOKING STATEMENTS

This annual report on Form 10-K (the “Annual Report”) contains forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 under Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934 (the “Exchange Act”), as amended. Forward-looking statements include statements with respect to our beliefs, plans, objectives, goals, expectations, anticipations, assumptions, estimates, intentions and future performance, and involve known and unknown risks, uncertainties and other factors, which may be beyond our control, and which may cause our actual results, performance or achievements to be materially different from future results, performance or achievements expressed or implied by such forward-looking statements. All statements other than statements of historical fact are statements that could be forward-looking statements. You can identify these forward-looking statements through our use of words such as “may,” “can,” “anticipate,” “assume,” “should,” “indicate,” “would,” “believe,” “contemplate,” “expect,” “seek,” “estimate,” “continue,” “plan,” “point to,” “project,” “predict,” “could,” “intend,” “target,” “potential” and other similar words and expressions of the future.

There are a number of important factors that could cause the actual results to differ materially from those expressed in any forward-looking statement made by us. These factors include, but are not limited to:

•

our ability to raise funds for general corporate purposes and operations, including our research activities and clinical studies;

•

our ability to ~~recognize~~realize the anticipated benefits of our merger (the ~~Kintara~~“Kineta Merger”) with Kineta, Inc. (“Kineta”);

•

~~our~~the ~~ability~~effects toof ~~complete~~the ~~our~~Kineta ~~previously~~Merger ~~announced~~on ~~merger~~our ~~with~~business ~~Kineta~~relationships, ~~Inc.~~operating ~~(the~~results ~~“Kineta”)~~ and ~~realize~~business ~~the anticipated benefits of such merger~~generally;

•

expectations regarding strategies, prospects, plans, expectations and objectives of our management for future operations of our company following the closing of the Kineta Merger

•

unexpected costs, charges or expenses resulting from the Kineta Merger:

•

our ability to recruit qualified management and technical personnel;

•

the cost, timing, scope and results of our clinical studies;

•

existing regulations and regulatory developments in the United States and other jurisdictions;

•

our ability to attract and retain key scientific, medical, commercial and management personnel;

•

our ability to obtain and maintain required regulatory approvals for our products;

•

our expectations regarding the use of our existing cash;

•

the therapeutic potential of IFx-Hu2.0, ~~IFx~~TBS-~~Hu3.0~~2025 and future product candidates;

•

~~The~~the regulatory approval processes of the U.S. Food and Drug Administration and other comparable foreign regulatory authorities are lengthy, time-consuming and inherently unpredictable. If we are not able to obtain, or if there are delays in obtaining, required regulatory approvals for our product candidates, we will not be able to commercialize, or will be delayed in commercializing, such product candidates, and our ability to generate revenue will be materially impaired;

•

our ability to obtain or maintain patents or other appropriate protection for the intellectual property utilized in our current and planned products;

•

our ability to develop and commercialize products without infringing the intellectual property rights of third parties; and

•

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

Forward-looking statements are based on our management’s beliefs and assumptions and on information currently available to us. Such beliefs and assumptions may or may not prove to be correct. Additionally, such forward-looking statements are subject to a number of known and unknown risks, uncertainties and assumptions, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various factors, including, but not limited to, those identified in Part I, Item 1A. “Risk Factors” and Part II, Item 7. “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in this Annual Report.

Moreover, we operate in an evolving environment. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties.

You should read this Annual Report and the documents that we reference in this Annual Report completely and with the understanding that our actual future results may be materially different from what we expect. We qualify all of our forward-looking statements by these cautionary statements. Except as required by applicable law, we have no obligation to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

3Note Regarding Company References; Trademarks

In this Annual Report, references to the “Company,” “we,” “us,” “our” or similar terms refer to TuHURA Biosciences, Inc., a Nevada corporation, together with its consolidated subsidiaries.

This Annual Report includes trademarks, service marks and trade names owned by us or other companies. All trademarks, service marks and trade names included in this Annual Report are the property of their respective owners. We do not intend our use or display of other companies’ trade names, trademarks or service marks to imply a relationship with, or endorsement or sponsorship of us by, these other companies.

PART I

Item 1. Business

Overview

We are a phase 3 clinical stage immuno-oncology company ~~developing~~with ~~novel~~three distinct technologies ~~designed~~focused toon ~~overcome~~the ~~primary~~development ~~and~~of ~~acquired~~novel ~~resistance~~therapeutics ~~to cancer immunotherapies. Our lead product candidate, IFx2.0, is an innate immune agonist~~ designed to overcome primary resistance to checkpoint inhibitors. We are preparing to initiate a single randomized placebo-controlled Phase 3 registration trial of IFx-2.0 administered as an adjunctive therapy to Keytruda® (pembrolizumab) in first line treatment for patients with advanced or metastatic Merkel cell carcinoma who are checkpoint inhibitor naïve utilizing the FDA’s accelerated approval pathway. In addition to our innate immune agonist candidates, we are leveraging our Delta receptor technology to develop tumor microenvironment modulators in the form of first-in-class bi-specific antibody-peptide conjugates (“APCs”) and antibody-drug conjugates (“ADCs”) targeting Myeloid Derived Suppressor Cells (“MDSCs”). Our APCs and ADCs are being developed to inhibit the immune-suppressing effects of MDSCs on the tumor microenvironment to prevent T cell exhaustion and acquired resistance to ~~checkpoint~~cancer ~~inhibitors and cellular therapies~~immunotherapies.

~~Recent~~Our ~~Developments~~proprietary Immune FxTM technology platform, or IFx, is an innate immune agonist technology designed to “trick” the body’s immune system to attack tumor cells by making tumor cells look like bacteria. Our lead product candidate, IFx2.0, is an innate immune agonist designed to overcome primary resistance to checkpoint inhibitors. In June 2025, we initiated a single randomized placebo-controlled Phase 3 registration trial of administered as an adjunctive therapy to Keytruda® (pembrolizumab) in first line treatment for patients with advanced or metastatic Merkel cell carcinoma who are checkpoint inhibitor naïve utilizing the FDA’s accelerated approval pathway.

WeIn ~~are~~addition ato ~~Nevada~~our ~~corporation~~IFx ~~formed~~technology onplatform, in June ~~24,~~2025 ~~2009~~we ~~under~~acquired the ~~name~~rights ~~Berry~~to ~~Only Inc. On January 25~~TBS-2025, ~~2013,~~a wenovel ~~entered~~VISTA-inhibiting ~~into~~monoclonal ~~and~~antibody ~~closed~~formerly anknown ~~exchange~~as ~~agreement~~KVA1213, ~~with~~through ~~Del~~our ~~Mar~~acquisition ~~Pharmaceuticals~~of ~~(BC)~~Kineta, ~~Ltd~~Inc. (“~~Del Mar (BC)~~Kineta”), ~~0959454~~on ~~B.C.~~June ~~Ltd. (“Callco”)~~30, ~~and 0959456 B~~2025.C. ~~Ltd.~~VISTA (~~“Exchangeco”)~~otherwise ~~and~~referred ~~the~~to ~~security~~as V-domain ~~holders~~Ig suppressor of ~~Del~~T ~~Mar~~cell ~~(BC~~activation). ~~Upon~~is ~~completion~~an ofimmune ~~the~~checkpoint ~~exchange~~highly ~~agreement,~~expressed ~~Del~~on ~~Mar~~myeloid ~~(BC)~~cells ~~became~~that ~~our~~is ~~wholly-owned~~believed ~~subsidiary.~~to Onbe ~~August~~a ~~19,~~strong ~~2020,~~driver weof ~~completed~~immunosuppression ain ~~merger~~the ~~with~~tumor ~~Adgero~~microenvironment ~~Biopharmaceuticals~~and ~~Holdings,~~is ~~Inc.,~~believed ato ~~Delaware~~be ~~corporation~~a ~~(“Adgero”),~~primary inmechanism by which ~~Adgero~~leukemic ~~continued~~blasts ~~its~~escape ~~existence~~immune ~~under~~recognition ~~Delaware~~contributing ~~law~~to ~~and~~low ~~became~~response ~~our~~rates ~~direct,~~and ~~wholly-owned~~high ~~subsidiary.~~rates ~~Following~~of ~~the~~recurrence ~~completion~~in ofacute ~~the~~myeloid ~~merger~~leukemia, weor ~~changed~~AML. Following our ~~name~~acquisition ~~from~~of ~~Del~~Kineta, ~~Mar~~we ~~Pharmaceuticals,~~are ~~Inc.~~currently toplanning ~~Kintara~~on ~~Therapeutics,~~investigating ~~Inc.~~TBS-2025 ~~and~~in ~~began~~a ~~trading~~Phase1b/2 ontrial ~~Nasdaq~~in ~~under~~patients ~~the~~with ~~symbol~~r/r ~~“KTRA~~mutNPM1AML.”

OnIn ~~October~~addition ~~18, 2024, Kintara completed a reverse merger transaction contemplated by the Kintara Merger Agreement. Pursuant~~ to ~~the~~our ~~Kintara~~IFx ~~Merger Agreement, Merger Sub merged with~~ and ~~into Legacy TuHURA~~TBS-2025, ~~with~~we ~~Legacy~~are ~~TuHURA~~leveraging ~~surviving~~our ~~the~~Delta ~~Kintara~~Opioid ~~Merger~~Receptor ~~and~~(DOR) ~~becoming~~technology ~~our~~to ~~direct~~develop first-in-class bi-functional, ~~wholly~~bi-~~owned~~specific ~~subsidiary.~~antibody-drug Inconjugates ~~connection~~(“ADCs”) ~~with~~targeting the ~~completion~~DOR ~~of the Kintara Merger, effective at 12:01 a.m. Eastern Time~~ on ~~October~~Myeloid ~~18,~~Derived ~~2024,~~Suppressor ~~Kintara~~Cells ~~effected~~(“MDSCs”) to amodulate ~~1-for-35~~their ~~reverse~~immunosuppressive ~~stock~~influence ~~split of its common stock. Effective at 12:03 a.m. Eastern Time~~ on ~~October 18, 2024,~~ the ~~merger~~bone ~~was~~marrow ~~completed,~~ and ~~effective~~tumor atmicroenvironment ~~12:04~~to ~~a.m.~~prevent ~~Eastern~~T ~~Time~~cell onexhaustion ~~October~~and ~~18,~~acquired ~~2024, Kintara~~resistance ~~Therapeutics,~~to ~~Inc.~~checkpoint ~~was~~inhibitors ~~renamed~~and ~~“TuHURA~~cellular ~~Biosciences, Inc~~therapies.”

OnOur ~~December~~History 12, 2024, we announced that we had entered into a definitive merger agreement to acquire Kineta, Inc. (“Kineta”), a Delaware corporation that is developing KVA12123, an anti-VISTA antibody checkpoint inhibitor designed to reverse VISTA immune suppression and remodel the tumor microenvironment to overcome acquired resistance to immunotherapies. The merger agreement (the “Kineta Merger Agreement”) was entered into among our company, Kineta, Hura Merger Sub I, Inc., a Delaware corporation and direct wholly owned subsidiary of ours (“Hura Merger Sub I”), Hura Merger Sub II, LLC, a Delaware limited liability company and direct wholly owned subsidiary of ours (“Hura Merger Sub II”), and Craig Philips, solely in his capacity as the representative, agent and attorney-in-fact of the stockholders of Kineta. The Kineta Merger contemplates the acquisition of Kineta through a merger transaction pursuant to which Hura Merger Sub I will (a) merge with and into Kineta (the “First Merger”), with Kineta being the surviving corporation of the First Merger (also known as the “Surviving Entity”) and (b) immediately following the First Merger and as part of the same overall transaction as the First Merger, the Surviving Entity will merge with and into Hura Merger Sub II (the “Second Merger”, and together with the First Merger, the “Kineta Merger”), with Hura Merger Sub II being the surviving company of the Second Merger. Team

AtWe ~~the~~are ~~effective~~a ~~time~~Nevada ofcorporation ~~the~~originally ~~First~~formed ~~Merger,~~on ~~and~~June ~~subject~~24, to2009 under the ~~terms~~name ~~and~~Berry ~~conditions~~Only ofInc. ~~the~~On ~~Kineta~~January ~~Merger~~25, ~~Agreement~~2013, ~~each~~we ~~share~~entered ofinto ~~Kineta’s~~and ~~common~~closed ~~stock~~an exchange agreement, ~~par~~with ~~value~~Del ~~$0.001~~Mar ~~per~~Pharmaceuticals ~~share~~(BC) Ltd. (“~~Kineta~~Del ~~Common~~Mar ~~Stock~~(BC)”), ~~issued~~0959454 B.C. Ltd., and ~~outstanding~~0959456 ~~immediately~~B.C. ~~prior~~Ltd. toand the ~~effective~~security ~~time~~holders of ~~the~~Del ~~First~~Mar ~~Merger~~(BC). ~~will~~Upon becompletion ~~converted~~of ~~automatically~~the ~~into~~exchange ~~and~~agreement, ~~will~~Del ~~represent~~Mar ~~the~~(BC) ~~right~~became toour ~~receive,~~wholly-owned ~~without~~subsidiary. ~~interest,~~On ~~the~~August ~~number~~19, of2020, ~~shares~~we ofcompleted ~~our~~a ~~common~~merger ~~stock~~with ~~and~~Adgero ~~cash~~Biopharmaceuticals ~~consideration~~Holdings, ~~each~~Inc., ~~calculated~~a ~~according~~Delaware tocorporation ~~the~~(“Adgero”), ~~terms~~in ofwhich ~~the~~Adgero ~~Kineta~~continued ~~Merger~~its ~~Agreement.~~existence ~~The~~under ~~proposed~~Delaware ~~Kineta~~law ~~Merger~~and isbecame ~~expected~~our todirect, bewholly-owned ~~consummated~~subsidiary. inFollowing the ~~second~~completion ~~quarter~~ of ~~2025~~the merger, ~~subject~~we tochanged ~~the~~our ~~satisfaction~~name orfrom ~~waiver~~Del ofMar ~~closing~~Pharmaceuticals, ~~conditions~~Inc. ~~(including~~to aKintara ~~financing~~Therapeutics, ~~condition~~Inc. ("Kintara") and began trading on Nasdaq under the ~~Kineta~~symbol ~~Merger Agreement~~“KTRA. ”

4On October 18, 2024, Kintara completed its reverse merger transaction in accordance with the terms of the Agreement and Plan of Merger, dated as of April 2, 2024 (the “Kintara Merger Agreement”), by and among Kintara, TuHURA Biosciences, Inc. (“Legacy TuHURA”), and Kayak Mergeco, Inc., a direct wholly owned subsidiary of Kintara (“Merger Sub”). Pursuant to the Kintara Merger Agreement, Merger Sub merged with and into Legacy TuHURA, with Legacy TuHURA surviving the merger and becoming our direct, wholly-owned subsidiary (the “Kintara Merger”). Effective at 12:03 a.m. Eastern Time on October 18, 2024, the merger was completed, and effective at 12:04 a.m. Eastern Time on October 18, 2024, Kintara Therapeutics, Inc. was renamed “TuHURA Biosciences, Inc.”

~~IFx~~On ~~Innate~~June ~~Immune~~30, ~~Agonist~~2025, we completed the acquisition via merger of Kineta, Inc. (“Kineta”) pursuant to an Agreement and Plan of Merger, dated December 11, 2024, and as amended by that certain First Amendment to Agreement and Plan of Merger, dated May 5, 2025 (as amended, the “TuHURA-Kineta Merger Agreement”), by and among the Company, Hura Merger Sub I, Inc., a Delaware corporation and a direct wholly-owned subsidiary of the Company, Hura Merger Sub II, LLC, a Delaware limited liability company and direct wholly-owned subsidiary of the Company, Kineta, and Craig Philips, solely in his capacity the representative, agent and attorney-in-fact of the stockholders of Kineta. Pursuant to the terms of the TuHURA-Kineta Merger Agreement, the former stockholders of Kineta received merger consideration in the amount of an aggregate of approximately 4 million shares of Company common stock pursuant to the terms and conditions of the TuHURA-Kineta Merger Agreement, each share of Kineta common stock, par value $0.001 per share (each, a “Kineta Share”), issued and outstanding immediately prior to the First Merger, was converted into the right to receive 0.185298 shares of the Company’s common stock, par value $0.001 per share, for an aggregate of approximately

We have developed Immune FxTM, or IFx, as an innate immune agonist technology designed to “trick” the body’s immune system to attack tumor cells by making tumor cells look like bacteria and to thereby harness the natural power of innate immunity by leveraging natural mechanisms conserved throughout evolution to recognize threats from foreign pathogens like bacteria or viruses. Our innate immune agonist product candidates are delivered either via intratumoral injection (in the case of the Company’s pDNA innate immune agonist) or tumor-targeted via intravenous or autologous whole-cell administration (in the case of our mRNA innate immune agonist).3

~~Our IFx-~~2~~.0 innate immune agonist~~,868,169 ~~our~~shares ~~lead~~of ~~product~~Company ~~candidate,~~common isstock. ~~comparatively~~Also ~~simple~~pursuant to ~~administer~~the terms and ~~involves~~conditions ~~only~~of the ~~injection~~TuHURA-Kineta ~~into~~Merger aAgreement, ~~patient’s~~each ~~tumor,~~Kineta orShare ~~lymph~~received ~~node~~its pro rata portion of approximately 1,129,880 shares of aCompany ~~relatively~~common ~~small~~stock ~~amount~~in December 2025, in accordance with the terms of ~~pDNA~~the ~~that~~TuHURA-Kineta Merger Agreement. In addition, each Kineta share is ~~designed~~entitled to ~~encode~~the ~~for~~right anto ~~immunogenic~~its ~~gram~~pro ~~positive~~rata ~~bacterial~~share ~~protein~~of ~~that~~cash ~~gets~~consideration, ~~expressed~~if onany, received in the ~~surface~~future ofin the ~~patient’s~~form ~~tumor~~of sodisposed ~~that~~asset ~~the~~payments ~~surface~~related ofto ~~the~~legacy ~~tumor~~Kineta ~~looks~~assets ~~like~~transferred aprior ~~bacterium~~to the merger with Kineta.

~~Bacteria,~~Legacy ~~like~~TuHURA's ~~all~~predecessor ~~pathogens,~~company ~~have~~was ~~molecular~~formed ~~patterns~~as orMorphogenesis, ~~motifs~~Inc. ~~that~~in ~~are~~1995 ~~conserved~~by ~~through~~Drs. ~~evolution~~Patricia and ~~that~~Michael ~~are~~Lawman. ~~recognized~~Our byIFx ~~specific~~technology ~~pattern-recognition~~was ~~receptors~~developed onin ~~immune~~the ~~cells~~laboratory of ~~our innate immune system~~Dr. ~~This~~Michael isLawman anat ~~individual’s primary line of defense against pathogens that~~ the ~~individual~~Walt isDisney ~~born~~Memorial ~~with~~Cancer Institute, ~~and~~where ~~the~~Dr. ~~innate~~Michael ~~immune~~Lawman ~~system~~was ~~has~~formerly noa ~~choice~~Director ~~but~~of ~~to recognize~~ the ~~tumor~~Institute, asand itDr. ~~would~~Patricia aLawman ~~gram-positive~~was ~~bacteria~~formerly orDivision ~~any~~Director ~~pathogen.~~of ~~Gram-positive~~Cancer ~~bacterial~~Molecular ~~proteins~~Biology ~~are~~at ~~recognized~~the byInstitute. ~~Toll~~Dr. ~~Like~~Michael ~~Receptor-2~~Lawman ~~(TLR-2)~~is ona ~~antigen~~Fellow ~~presenting~~of ~~cells, which engulf and ingest~~ the ~~entire~~Royal ~~intact~~Society ~~tumor~~of ~~cell~~Biology, ~~packaging~~former ~~all~~Associate ~~the~~Professor ~~foreign~~at ~~tumor~~University ~~neoantigens~~of ~~presenting~~South ~~them~~Florida, to and ~~educating~~former ~~tumor~~Scientific ~~killing~~Research TDirector ~~cells~~of ~~and~~Pediatric BHematology/Oncology ~~cells~~at St. InJoseph’s ~~doing~~Children’s ~~so,~~Hospital. ~~IFx-2~~Dr.0 ~~harnesses~~Patricia ~~the~~Lawman ~~power~~also ofserves ~~the~~as ~~innate~~an ~~immune~~Adjunct ~~response~~Professor toat ~~produce~~University ~~activated~~of ~~tumor-specific~~South TFlorida. ~~cells~~Drs. ~~where~~Patricia ~~they~~and ~~previously~~Michael ~~didn’t~~Lawman ~~exist~~are ~~overcoming~~each ~~primary~~inventors ~~resistance~~on tonumerous ~~checkpoint~~U.S. ~~inhibitor~~and ~~therapy~~foreign patents.

WeOur ~~have~~Delta ~~entered~~Opioid ~~into~~Receptor aADC ~~Special~~technology ~~Protocol~~was ~~Assessment~~developed ~~agreement with the FDA for a single Phase 3 randomized placebo and injection -ontrolled trial for IFx-2.0, our lead innate immune agonist, as an adjunctive therapy to pembrolizumab (Keytruda®)~~ in the ~~first~~laboratory ~~line treatment~~ of ~~patients with advanced or metastatic Merkel cell carcinoma who are checkpoint inhibitor-naïve utilizing the FDA’s accelerated approval pathway~~Dr. ~~The~~Mark ~~Company~~McLaughlin ~~worked~~at ~~with~~ the ~~deputy~~Moffitt ~~director~~Cancer ~~of the FDA’s Oncology~~ Center ofand ~~Excellence~~at ~~(OCE) on a unique trial design. Consistent with~~ the ~~FDA’s~~West ~~Project~~Virginia ~~Front~~University ~~Runner~~Research ~~initiative, the FDA recommended investigating IFx-2~~Corporation.0 ~~in the front-line treatment setting rather than in patients who are progressing on checkpoint inhibitor therapy~~Dr. InMcLaughlin ~~doing~~was ~~so,~~previously ~~data from~~ a ~~primary~~Senior ~~endpoint~~Member of ~~objective~~the ~~response~~Drug ~~rate,~~Discovery orDepartment ~~ORR,~~at ~~that~~the isMoffitt ofCancer ~~sufficient~~Center ~~magnitude~~ and ~~duration~~previously ~~and~~Professor ~~with a favorable risk/benefit profile could be sufficient to support accelerated approval. Furthermore, OCE requested that we consider incorporating a key secondary endpoint that is~~ of ~~clinical~~Medicinal ~~benefit,~~Chemistry ~~such~~and ~~that~~Member ~~results~~WVU ~~from~~Cancer ~~a key secondary endpoint of progression-free survival~~Institute, orwhere ~~PFS,~~his ~~that~~research isfocused ~~adequately powered with statistical assumptions in the statistical analysis plan provided to the FDA, if achieved without a detrimental effect~~ on ~~overall~~protein-protein ~~survival,~~interaction orinhibitor ~~OS,~~design ~~could~~and bemolecular ~~adequate~~targeted ~~to support conversion to regular approval satisfying the requirement for a confirmatory trial~~immunotherapy. ~~Notwithstanding~~The ~~the~~discovery ~~foregoing,~~that the ~~results~~Delta ofreceptor ~~clinical~~is ~~trials~~highly ~~are~~expressed ~~inherently~~on ~~uncertain,~~MDSCs ~~and~~was ~~the~~jointly ~~results~~discovered ofby ~~our~~scientists ~~planned~~at ~~Phase~~Moffitt 3Cancer ~~clinical~~Center ~~trial may fail to satisfy the ORR, PFS,~~ and~~/or~~ OSTuHURA ~~endpoints~~Biopharma, ~~and~~a ~~none~~separate ofcompany ~~our~~whose ~~prior~~intellectual ~~clinical~~property ~~trials~~assets ~~with~~we ~~respect~~acquired toin ~~IFx-2.0~~January ~~were powered to determine statistical significance over a control~~2023.

AsOur ~~set~~CEO, ~~forth~~Dr. inJames Bianco, is a ~~January~~33-year ~~2024~~veteran ~~partial~~of ~~clinical~~the ~~trial~~biopharmaceutical ~~hold~~industry. ~~letter~~Dr. ~~from~~Bianco is the ~~FDA~~principal ~~regarding~~founder ~~the~~of ~~chemistry,~~CTI ~~manufacturing~~Biopharma, ~~and~~where ~~controls~~he ~~(CMC)~~served ~~requirements~~as ~~for~~its ~~our~~CEO ~~planned~~from ~~Phase~~1992 3to ~~trial~~October ~~for~~2016. ~~IFx-2~~Dr.0 toBianco’s beexperience ~~conducted~~spans ~~under~~all ~~the~~aspects ~~Special~~of ~~Protocol~~drug ~~Assessment~~development ~~agreement,~~from ~~the~~phase ~~FDA~~I-IV isclinical ~~requiring that~~trials, ~~prior~~regulatory ~~to initiating the trial~~approval, weand ~~must~~pricing ~~qualify~~reimbursement ~~potency~~to ~~assay~~sales and ~~the~~marketing. ~~mixing~~He ~~process~~has ~~for~~extensive ~~IFx-2.0.~~experience Wein ~~have~~financing, ~~reached~~negotiating ~~agreement~~and ~~with~~execution ~~FDA~~of onpharmaceutical ~~the~~development ~~requirements~~and ~~for~~commercial ~~lifting~~license ~~the~~agreements. ~~partial~~During ~~clinical~~his ~~hold~~tenure ~~and~~at ~~believe~~CTI weBiopharma, ~~will~~Dr. ~~meet~~Bianco ~~the~~was ~~requirements~~responsible ~~and~~for ~~consequently~~strategic ~~expect~~portfolio todevelopment ~~receive~~and aidentifying, ~~complete~~acquiring, ~~response~~licensing, ~~letter~~purchasing, or ~~CRL,~~acquiring ~~lifting~~through ~~the~~international ~~partial~~merger ~~clinical~~and ~~hold~~acquisition, infive ~~the~~drug ~~second~~candidates, ~~quarter~~four of ~~2025.~~which Wehave ~~may~~since bebeen inapproved ~~position~~by ~~to initiate~~ the ~~Phase~~FDA 3and ~~study~~with inthree ~~the~~receiving ~~second~~accelerated ~~quarter~~or ofconditional ~~2025~~regulatory ifapproval ~~the~~in ~~results of~~ the ~~mixing~~U.S. ~~studies~~ and/or ~~potency~~E.U. ~~assay~~In ~~qualifications are acceptable to the FDA~~2013, ~~but~~Dr. ~~there~~Bianco isled noCTI ~~assurance~~Biopharma ~~that~~in ~~we will be able to satisfy~~ the ~~requirements~~identification ~~set~~and ~~forth~~negotiation inof the ~~partial~~asset ~~clinical~~purchase ~~trial~~for ~~hold~~VONJO® ~~letter~~(pacritinib), on a ~~timely~~novel ~~basis~~JAK2 orselective attyrosine ~~all~~kinase inhibitor. WeHe ~~anticipate~~also ~~that~~led ~~enrollment~~CTI ~~for~~Biopharma in the ~~Phase~~negotiation 3of ~~would~~the ~~take~~development ~~approximately~~and 12commercial ~~months,~~license agreement with ~~top-line data potentially being available 6 to 7 months following the last patient enrolled~~Baxalta. IfAs ~~successful,~~CEO ~~this Phase 3 trial would form the basis~~ of aCTI ~~Biologics License Application~~Biopharma, ~~or BLA~~Dr. ABianco ~~Special~~was ~~Protocol~~also ~~Assessment~~responsible ~~agreement~~for ~~is a binding written agreement between~~ the ~~U.S.~~PERSIST-2 ~~Food~~Phase ~~and~~3 ~~Drug Administration (FDA) and a~~ trial ~~sponsor that indicates the study’s~~ design and ~~analysis~~conduct, ~~are~~the ~~adequate~~successful toresults ~~support~~of anwhich ~~application~~served ~~submission.~~as Athe ~~Special~~basis ~~Protocol~~for ~~Assessment agreement does not increase~~ the ~~likelihood~~2022 ofFDA ~~marketing~~accelerated approval ~~for~~of ~~the~~Vonjo® ~~product~~(pacritinib) and ~~may~~the ~~not~~subsequent ~~lead~~acquisition toof aCTI ~~faster~~Biopharma orby ~~less~~SOBI ~~costly~~for ~~development,~~$1.75 ~~review, or approval process~~billion.

~~We are also developing our~~ IFx~~-3.0~~ ~~product~~Innate ~~candidate,~~Immune anAgonist ~~mRNA~~Development innate immune agonist candidate for intravenous or autologous whole cell administration for blood-related cancers, to expand the utility of our IFx™ technology to tumor types not accessible by intra-tumoral injection. We are designing our mRNA innate immune agonist to be carried by a targeted lipid nanoparticle (“LNP”) coupled to an antibody which is intended to recognize and target CD22, a receptor overexpressed on B cell cancers like lymphoma. We believe that our novel LNP-anti CD22 construct may be the first intravenously administered, tumor-targeted mRNA innate immune agonist in preclinical development. Subject to further testing and development, we believe that systemically targeting a tumor with our mRNA innate immune agonist should induce a more widespread innate immune response Program

5We have developed Immune FxTM, or IFx, as an innate immune agonist technology designed to “trick” the body’s immune system to attack tumor cells by making tumor cells look like bacteria and to thereby harness the natural power of innate immunity by leveraging natural mechanisms conserved throughout evolution to recognize threats from foreign pathogens like bacteria or viruses. Our innate immune agonist product candidates are delivered either via intratumoral injection (in the case of the Company’s pDNA innate immune agonist) or tumor-targeted via intravenous or autologous whole-cell administration (in the case of our mRNA innate immune agonist).

~~given~~Our ~~the~~IFx-2.0 ~~larger~~innate ~~tumor~~immune ~~burden~~agonist, ~~associated~~our ~~with~~lead ~~blood-related~~product ~~malignancies~~candidate, ~~than~~is ~~with~~comparatively ~~localized~~simple to administer and involves only the injection into ~~small~~a ~~cutaneous~~patient’s tumor, or ~~other~~lymph ~~accessible~~node, ~~lesions~~of a relatively small amount of pDNA that is designed to encode for an immunogenic gram positive bacterial protein that gets expressed on the surface of the patient’s tumor so that the surface of the tumor looks like a bacterium.

~~Tumor~~Bacteria, ~~Microenvironment~~like ~~Modulators:~~all Bipathogens, have molecular patterns or motifs that are conserved through evolution and that are recognized by specific pattern-~~Specific/Bi~~recognition receptors on immune cells of our innate immune system. This is an individual’s primary line of defense against pathogens that the individual is born with, and the innate immune system has no choice but to recognize the tumor as it would a gram-~~Functional~~positive ~~Antibody~~bacteria ~~Peptide~~or ~~Conjugates~~any pathogen. Gram-positive bacterial proteins are mostly recognized by Toll Like Receptor-2 (~~APCs~~TLR-2) on antigen presenting cells, which engulf and ~~Antibody~~ingest ~~Drug~~the ~~Conjugates~~entire ~~(ADCs)~~intact ~~using~~tumor ~~Delta~~cell ~~Opioid~~packaging ~~Receptor~~all ~~Technology~~the foreign tumor neoantigens presenting them to and educating tumor killing T cells and B cells. In doing so, IFx-2.0 harnesses the power of the innate immune response to produce activated tumor-specific T cells where they previously didn’t exist overcoming primary resistance to checkpoint inhibitor therapy.

In addition to our innate immune agonist product candidates, we are using proprietary Delta Opioid Receptor technology to develop small molecule or bi-specific/bi-functional immune modulating APCs and ADCs designed to inhibit the immune suppressing effects of tumor associated MDSCs on the tumor microenvironment, TME, to prevent T cell exhaustion and acquired resistance to checkpoint inhibitors. Our Delta Opioid Receptor technology was developed by scientists at Moffitt Cancer Center and TuHURA Biopharma, Inc., a separate company whose intellectual property assets we acquired in January 2023 (“TuHURA Biopharma”). We believe the Delta Opioid Receptor represents a novel target to inhibit the immunosuppressive capacity of MDSCs through its control of the production of multiple immunosuppressive soluble factors.4

~~The~~We ~~tumor~~have ~~microenvironment~~entered isinto ~~the~~a ~~tissue~~Special ~~surrounding~~Protocol aAssessment ~~tumor,~~agreement ~~including~~with the ~~normal~~FDA ~~cells,~~for ~~blood~~a ~~vessels,~~single ~~and~~Phase ~~molecules~~3 ~~that~~randomized ~~surround~~placebo and ~~feed~~injection-controlled atrial ~~tumor~~for ~~cell~~IFx-2.0, ~~and~~our ~~shield~~lead itinnate ~~from~~ immune ~~attack~~agonist, ~~and~~as ~~eradication.~~an ~~MDSCs~~adjunctive ~~are~~therapy ato ~~heterogeneous~~pembrolizumab ~~group~~(Keytruda®) in the first line treatment of ~~immature~~patients ~~myeloid~~with ~~cells~~advanced or metastatic Merkel cell carcinoma, ~~which~~who ~~when~~are ~~recruited~~checkpoint ~~from~~inhibitor-naïve utilizing the ~~bone~~FDA’s ~~marrow~~accelerated toapproval ~~the~~pathway. ~~tumor~~A ~~microenvironment,~~Special ~~they~~Protocol ~~transform~~Assessment toagreement ~~tumor-associated~~is ~~MDSCs~~a ~~which~~binding ~~are~~written ~~characterized~~agreement bybetween ~~their~~the ~~ability~~U.S. toFood ~~suppress~~and ~~both~~Drug ~~innate~~Administration (FDA) and ~~adaptive~~a ~~immune~~trial ~~responses.~~sponsor ~~Tumor~~that ~~associated~~indicates ~~MDSCs~~the ~~are~~FDA ~~generally~~has ~~believed~~agreed to bethe astudy’s ~~major~~design, ~~contributor~~charters, toand Tstatistical ~~cell~~analysis ~~exhaustion~~plan, ~~(which~~and isif the ~~loss~~study ofendpoints ~~ability~~are ofmet Twithin ~~cells~~the tocontext ~~proliferate~~of ~~and~~the toSPA ~~kill~~Agreement, ~~cancer~~such ~~cells)~~results ~~and~~would ~~for~~be ~~acquired~~adequate ~~resistance~~ to ~~checkpoint~~support ~~inhibitors~~accelerated and ~~cellular~~regular ~~therapies~~approval. ~~like~~A TSpecial ~~cell~~Protocol ~~therapies.~~Assessment ~~The~~agreement ~~presence~~does ofnot ~~tumor~~increase ~~associated~~the ~~MDSCs~~likelihood inof ~~the~~marketing ~~tumor~~approval ~~microenvironment~~for orthe ~~circulating~~product inand ~~the~~may ~~bloodstream~~not islead ~~highly~~to ~~correlated~~a ~~with~~faster ~~poor~~or ~~prognosis~~less ~~and~~costly ~~outcome~~development, inreview, aor ~~wide~~approval ~~variety~~process. ofWe ~~solid~~initiated ~~tumors~~the ~~and~~Phase ~~blood~~3 ~~related~~trial ~~cancers~~in June 2025.

WeIn ~~believe~~designing ~~we are~~ the ~~first~~Phase ~~company~~3 ~~developing~~trial ~~immune~~for ~~modulating APC/ADCs targeting the Delta Opioid Receptor on MDSCs. We are developing peptidomimetic or small molecule DOR~~IFx-~~selective inhibitors to incorporate into our bi-specific/bi-functional APCs and ADCs~~2.0, ~~which~~ we ~~believe~~worked represents a paradigm shift from conventional APCs or ADCs that are currently in development or being marketed. Traditional ADCs are a class of drugs in which a monoclonal antibody is chemically linked to a cancer-fighting substance. The antibody carries the cancer fighting payload to the tumor cell improving the selectivity of the resulting anti-cancer activity. Next generation ADCs incorporate non-chemotherapeutic technologies to interfere with ~~tumor cell cycle growth or to carry with~~ the ~~antibody~~deputy adirector checkpoint inhibitor (so called “checkpoint ADCs”). In contrast, our APCs or ADCs do not target tumor associated receptor targets but rather target the Delta Opioid Receptor on MDSCs while carrying with them an immune effector to target a second receptor target like VISTA with a VISTA inhibiting antibody or other checkpoint inhibitor(s) producing novel bi-specific conjugates. These[CC1] two functions are intended to work together with the goal of ~~overcoming acquired resistance, preventing T cell exhaustion and allowing checkpoint inhibitors and cellular therapies to be safer and more effective while interfering with~~ the ~~tumor~~FDA’s ~~ability to invade and spread throughout the body.~~Oncology

~~These~~Center ~~two~~of ~~functions~~Excellence ~~are~~(OCE) ~~intended~~on towhat ~~work~~we ~~together~~believe is a unique trial design. Consistent with the ~~goal~~FDA’s ofProject ~~overcoming~~Front ~~acquired~~Runner ~~resistance~~initiative, ~~preventing~~the TFDA ~~cell~~recommended ~~exhaustion~~investigating ~~and~~IFx-2.0 ~~allowing~~in the front-line treatment setting rather than in patients who are progressing on checkpoint ~~inhibitors~~inhibitor therapy. In doing so, data from a primary endpoint of objective response rate, or ORR, that is of sufficient magnitude and ~~cellular~~duration ~~therapies~~and towith a favorable risk/benefit profile could be ~~safer~~sufficient ~~and~~to ~~more~~support ~~effective~~accelerated ~~while~~approval. ~~interfering~~Furthermore, OCE requested that the Company consider incorporating a key secondary endpoint that is of clinical benefit such that results from a key secondary endpoint of progression-free survival, or PFS, that is adequately powered with statistical assumptions in the ~~tumor’s~~statistical ~~ability~~analysis plan provided to ~~invade~~the ~~and~~FDA, ~~spread~~if ~~throughout~~achieved without a detrimental effect on overall survival, or OS, could be adequate to support conversion to regular approval satisfying the ~~body~~requirement for a confirmatory trial.

~~Our~~We ~~Pipeline~~anticipate that enrollment for the Phase 3 will take approximately 18 – 24 months from the initiation of the trial, with top-line data potentially being available 6 to 7 months following the last patient enrolled. If successful, this Phase 3 trial would form the basis of a Biologics License Application, or BLA.

~~Our~~We ~~pipeline~~previously ~~focuses~~announced onthat ~~acquiring~~we ~~and~~were ~~developing~~pursuing ~~technologies~~development ~~designed~~of a product candidate referred to ~~overcome~~as ~~tumor~~IFx-~~intrinsic~~3.0, ~~mechanisms~~an ~~underlying~~mRNA ~~primary~~innate ~~resistance~~immune toagonist ~~checkpoint~~candidate ~~inhibitors.~~for Weintravenous ~~also~~or ~~focus~~autologous onwhole ~~technologies~~cell toadministration ~~overcome~~for ~~acquired~~blood- ~~resistance~~related tocancers. ~~cancer~~However, ~~immunotherapies~~with ~~related~~the acquisition of Kineta, we have determined not to advance the ~~immune~~development ~~suppressing~~of ~~characteristics~~IFx-3.0 ofuntil the ~~tumor~~results ~~microenvironment~~of the IFx-2.0 WePhase ~~are~~3 ~~leveraging~~trial ~~our~~in ~~technology~~Merkel ~~platforms~~cell tocarcinoma ~~advance~~are ~~several~~known ~~diversified~~and ~~product~~have ~~candidates,~~reallocated ~~including~~resources ~~principally~~to the ~~following:~~below-described planned trial for TBS-2025.

6TBS-2025 Development Program

~~Fx-2.0~~As ~~Innate~~a ~~Immune~~result ~~Agonist.~~of ~~IFx~~our acquisition of Kineta in June 2025, we acquired the rights to TBS-22025, a novel VISTA- inhibiting monoclonal antibody formerly known as KVA1213.0 Unlike other checkpoints, which are mostly present on activated T cells, VISTA is ~~our~~predominately ~~lead~~expressed ~~product~~on ~~candidate~~myeloid cells, notably MDSCs, and on quiescent T cells. WeResearch ~~received~~has ~~guidance~~demonstrated ~~from~~that when mutated, NPM1 and ~~worked~~DNM3TA, ~~with~~two of the ~~FDA’s~~most ~~Office~~common ofmutations ~~Tissues~~in AML and ~~Advanced~~typically ~~Therapies~~co-mutated ~~and~~in ~~Oncology~~myelodysplasia ~~Center~~(MDS), result in high expression of ~~Excellence~~VISTA inon ~~developing~~the surface of leukemic blasts. The presence of VISTA on these cells is believed to be the ~~Phase~~primary 3mechanism ~~trial~~by ~~for~~which ~~IFx-2~~leukemic cells escape immune recognition and attack, resulting in a low treatment response rate and a short duration of response in AML.0.

~~IFx~~TBS-~~2.0~~2025 ~~Phase~~was ~~1b/2a~~previously ~~Basket~~investigated ~~Trial.~~in Wea ~~are~~dose ~~planning~~escalation a Phase 1b1/2a2 trial, ~~referred~~both to as a ~~“basket”~~monotherapy ~~trial~~and in combination with pembrolizumab, ~~which~~in ispatients awith ~~type~~relapsed ofand/or ~~clinical~~treatment-refractory ~~trial~~advanced ~~that~~solid ~~tests~~tumors. aTBS-2025 ~~new~~was ~~product~~well ~~candidate~~tolerated when administered every 2 weeks at doses up to 1,000mg both in ~~patients~~the ~~who~~monotherapy ~~have~~arm ~~different~~(n=24) ~~types~~or ofin ~~cancer~~the ~~but~~pembrolizumab ~~common~~combination ~~biologic~~therapy ~~reason~~arm ~~for~~(n=16). ~~resistance~~Pharmacokinetic toand ~~checkpoint~~pharmacodynamic ~~inhibitors~~data demonstrated greater than 90% receptor occupancy across the every two- week dosing interval. Immunocytokine analysis was consistent with the mechanism of action for VISTA inhibition on immune cells.

~~Approximately~~Applying ~~30%~~the toFDA’s ~~35%~~guidelines offor ~~patients~~development ~~with~~of ~~advanced~~drugs ~~Merkel~~in ~~cell~~AML, ~~carcinoma~~the dopharmacokinetic ~~not present with cutaneous or nodal lesions~~ and ~~are~~safety ~~therefore~~data ~~not~~from ~~eligible~~VISTA ~~for~~101, ~~participation~~the ~~in our~~ Phase 31 study. Inin ~~the~~solid ~~first stage of this basket study~~tumors, ~~IFx-2.0~~can ~~will~~ be ~~administered~~used ~~via~~to ~~interventional~~determine ~~radiology~~a ~~into~~starting ~~lesions~~dose in ~~the~~a ~~liver,~~Phase ~~retroperitoneum~~1b ~~or lungs of patients who have advanced and metastatic Merkel cell carcinoma who are checkpoint inhibitor naïve who accessible cutaneous or lymph nodes. This~~ trial ~~will has the potential to extend the application of IFx-2~~.0.

~~The~~We ~~Phase~~anticipate 2aconducting ~~stage~~an abbreviated Phase1b dose escalation study in mutNPM1 r/r AML, which is a subtype of acute myeloid leukemia characterized by the ~~trial~~presence ~~will~~of ~~include~~mutations ~~patients~~in ~~with~~the ~~checkpoint~~NPM1 ~~inhibitor~~gene. ~~resistant~~This ~~cancers~~mutation ~~such~~is aspresent ~~triple~~in ~~negative~~approximately ~~breast~~30% ~~cancer~~to or35% ~~other~~of ~~cancers~~cases ~~known~~of ~~not~~AML. toPatients ~~respond~~who tofail ~~checkpoint~~or relapse following treatment with a menin inhibitor ~~therapy~~have no approved effective therapies and represent an unmet medical need population. We ~~currently~~believe ~~anticipate~~this ~~initiating~~population of patients with this ~~study~~genetic inmutation ~~second~~may ~~half~~qualify offor ~~2025.~~investigation Ifunder ~~successful~~the FDA’s Plausible Mechanism Pathway, ~~this~~which ~~trial~~is ~~could~~a ~~expand~~regulatory ~~the~~framework ~~utility~~allowing ofapproval based ~~IFx-2.0~~on ~~beyond~~biological ~~advanced~~rationale ~~Merkel~~and ~~cell~~target ~~carcinoma~~engagement rather than traditional, large randomized trials.

IFx-3.0. IFx-3.0 is our mRNA innate immune agonist for intravenous or autologous whole cell administration. We believe that advancing an mRNA innate immune agonist candidate for systemic or autologous whole cell administration may allow our company to expand the utility of our innate immune agonist technology to blood-related cancers, which are not amenable to intratumoral administration. The first planned application of IFx-3.0, is to target the CD22 receptor, which is over expressed on a number of B cell cancers like aggressive lymphomas. We plan to test various constructs in vitro before advancing to humanized immune competent murine models of aggressive lymphoma planned for 2026. 5

~~Antibody~~In ~~drug~~addition ~~or Peptide conjugates. We are also developing novel immune modulating bi-functional ADCs and APCs~~ to ~~modulate~~examining the ~~tumor~~potential ~~microenvironment by reprograming MDSCs’ immune suppressing capabilities through inhibition~~ of ~~the~~TBS-2025 ~~Delta~~monotherapy ~~Opioid Receptor on MDSCs while localizing checkpoint inhibitors to checkpoint release activated T cells~~ in ~~the~~this ~~tissue~~patient ~~where~~population, the ~~tumor~~Phase ~~resides.~~1b Westudy ~~are~~will ~~working~~also onbe ~~developing~~used ~~and~~to ~~expanding~~establish a ~~portfolio~~recommended ofdose ~~novel~~to ~~Delta~~be ~~Opioid~~investigated ~~Receptor~~in a ~~specific~~Phase ~~small~~2 ~~molecule~~trial ~~or peptidomimetic inhibitors~~ of ~~MDSC~~TBS-2025 ~~immunosuppressive~~in ~~functions~~combination aswith ~~potential~~a ~~modulators~~menin ofinhibitor ~~the~~in ~~tumor~~mutNPM1 ~~microenvironment~~r/rAML ~~alone~~in orpatients ~~conjugated~~previously tountreated anwith ~~immune~~a ~~effector~~menin ~~to construct its bi-functional ADCs~~inhibitor. The Company’s ~~prototype~~currently ~~APC~~plans ~~consists~~on ofdiscussing aits ~~proprietary~~development ~~peptidomimetic~~plans ~~inhibitor~~with of the ~~Delta~~FDA ~~Opioid~~late ~~Receptor~~in the ~~conjugated~~first tohalf anof ~~antiPD-1~~2026 ~~checkpoint~~and ~~inhibitor.~~initiating ~~Preclinical~~the ~~studies~~planned ~~demonstrated~~Phase1b/2 ~~that~~trial ~~our~~in ~~APC~~as ~~significantly~~early ~~prolonged~~as ~~survival~~the ~~compared~~second tohalf ~~antiPD-1 checkpoint inhibitor alone in a murine model~~ of ~~PD-1 resistant lung cancer~~2026.

~~Our~~DOR ~~History~~Technology ~~and~~Development ~~Team~~Program

~~Our~~In ~~predecessor~~addition ~~company~~to ~~was~~its ~~formed~~innate asimmune ~~Morphogenesis,~~agonist ~~Inc.~~and inVISTA-inhibiting ~~1995~~product bycandidates, ~~Drs.~~we ~~Patricia~~are ~~and~~using ~~Michael~~proprietary ~~Lawman.~~Delta ~~Our~~Opioid ~~IFx~~Receptor (DOR) technology ~~was~~to ~~developed~~develop insmall ~~the~~molecule ~~laboratory~~bi-specific/bi-functional ofimmune ~~Dr.~~modulating ~~Michael~~ADCs ~~Lawman~~designed atto inhibit the ~~Walt~~immune ~~Disney~~suppressing ~~Memorial~~effects ~~Cancer~~of ~~Institute,~~tumor ~~where~~associated ~~Dr.~~MDSCs ~~Michael~~on ~~Lawman~~the ~~was~~bone ~~formerly~~marrow aand ~~Director~~tumor ofmicroenvironment ~~the~~to ~~Institute,~~prevent T cell exhaustion and Dracquired resistance to checkpoint inhibitors. ~~Patricia~~The ~~Lawman~~Company’s DOR technology was ~~formerly~~developed ~~Division~~by ~~Director~~scientists ofat Moffitt Cancer ~~Molecular~~Center ~~Biology~~and atTuHURA ~~the~~Biopharma, ~~Institute~~Inc., ~~Dr.~~a ~~Michael~~separate ~~Lawman~~company iswhose aintellectual ~~Fellow~~property ofassets we acquired in January 2023 (“TuHURA Biopharma”) We believe the ~~Royal~~DOR ~~Society~~represents ofa ~~Biology,~~novel ~~former~~target ~~Associate~~to ~~Professor~~inhibit atthe ~~University~~immunosuppressive capacity of ~~South~~MDSCs ~~Florida,~~through ~~and~~its ~~former~~control ~~Scientific~~of ~~Research~~the ~~Director~~production of ~~Pediatric~~multiple ~~Hematology/Oncology~~immunosuppressive atsoluble ~~St.~~factors, ~~Joseph’s~~chemokines ~~Children’s~~and ~~Hospital.~~direct ~~Dr.~~cell-cell interactions.

7The tumor microenvironment is the tissue surrounding a tumor, including the normal cells, blood vessels, and molecules that surround and feed a tumor cell and shield it from immune attack and eradication. MDSCs are a heterogeneous group of immature myeloid cells, which when recruited from the bone marrow to the tumor microenvironment, they transform to tumor-associated MDSCs which are characterized by their ability to suppress both innate and adaptive immune responses. Tumor associated MDSCs are generally believed to be a major contributor to T cell exhaustion (which is the loss of ability of T cells to proliferate and to kill cancer cells) and for acquired resistance to checkpoint inhibitors and cellular therapies like T cell therapies. The presence of tumor associated MDSCs in the tumor microenvironment or circulating in the bloodstream is highly correlated with poor prognosis and outcome in a wide variety of solid tumors and blood related cancers. MDSCs play a similar role in blood related cancers such as AML or Myelodysplasia (pre-leukemic syndrome) where their immune suppressing effects in the bone marrow create a permissive environment to allow leukemic cells to grow and escape immune recognition.

~~Patricia~~We ~~Lawman~~believe ~~also~~we ~~serves~~are asthe anfirst ~~Adjunct~~company ~~Professor~~developing immune modulating ADCs targeting the Delta Opioid Receptor on MDSCs. We have developed a series of small molecule inhibitors of the DOR representing new molecular entities These inhibitors are highly selective (>1,000 fold) for the DOR over other opioid receptors and highly potent with IC50 (ability to inhibit 50% of DOR activity) at ~~University~~low nanomolar concentrations. We plan on selecting a lead compound to incorporate into our bi-specific, bi-functional ADCs, which we believe represents a paradigm shift from conventional ADCs that are currently in development or being marketed. Traditional ADCs are a class of ~~South~~drugs ~~Florida~~in which a monoclonal antibody is chemically linked to a “payload” such as cancer-fighting substance. ~~Drs~~The antibody carries the payload to the tumor cell, improving the selectivity of the resulting anti-cancer activity. ~~Patricia~~Next ~~and~~generation ~~Michael~~ADCs ~~Lawman~~incorporate non-chemotherapeutic technologies to interfere with tumor cell cycle growth or to carry with the antibody a checkpoint inhibitor (so called “checkpoint ADCs”). In contrast, our ADCs do not target tumor associated receptor targets, are ~~each~~not ~~inventors~~internalized, and do not carry a cancer fighting substances, but rather they target the Delta Opioid Receptor on ~~numerous~~MDSCs Uwhile carrying with them an immune effector to target a second receptor target like VISTA with a VISTA inhibiting antibody.S These constructs result in novel bi-specific, bi-functional conjugates. They are bi-specific by targeting 2 distinct receptors (DOR and ~~foreign~~VISTA) ~~patents~~and bi-functional by inhibiting DOR related immune suppression and checkpoint releasing resting T cells to become activated. These two functions are intended to work together with the goal of overcoming acquired resistance, preventing T cell exhaustion and allowing checkpoint inhibitors and cellular therapies to be safer and more effective while interfering with the tumor’s ability to invade and spread throughout the body.

With respect to our bi-functional ADC technology, our Delta receptor APC and ADC technology was developed in the laboratory of Dr. Mark McLaughlin at the Moffitt Cancer Center and at the West Virginia University Research Corporation. Dr. McLaughlin was previously a Senior Member of the Drug Discovery Department at the Moffitt Cancer Center and previously Professor of Medicinal Chemistry and Member WVU Cancer Institute, where his research focused on protein-protein interaction inhibitor design and molecular targeted immunotherapy. The discovery that the Delta receptor is highly expressed on MDSCs was jointly discovered by scientists at Moffitt Cancer Center and TuHURA Biopharma, a separate company whose intellectual property assets we acquired in January 2023.6

Our CEO, Dr. James Bianco, is a 30-year veteran of the biopharmaceutical industry. Dr. Bianco is the principal founder of CTI Biopharma, where he served as its CEO from 1992 to October 2016. Dr. Bianco’s experience spans all aspects of drug development from phase I-IV clinical trials, regulatory approval, and pricing reimbursement to sales and marketing. He has extensive experience in financing, negotiating and execution of pharmaceutical development and commercial license agreements. During his tenure at CTI Biopharma, Dr. Bianco was responsible for strategic portfolio development and identifying, acquiring, licensing, purchasing, or acquiring through international merger and acquisition, five drug candidates, four of which have since been approved by the FDA and with three receiving accelerated or conditional regulatory approval in the U.S. and/or E.U. In 2013, Dr. Bianco led CTI Biopharma in the identification and negotiation of the asset purchase for VONJO® (pacritinib), a novel JAK2 selective tyrosine kinase inhibitor. He also led CTI Biopharma in the negotiation of the development and commercial license agreement with Baxalta. As CEO of CTI Biopharma, Dr. Bianco was also responsible for the PERSIST-2 Phase 3 trial design and conduct, the results of which served as the basis for the 2022 FDA accelerated approval of pacritinib and the subsequent acquisition of CTI Biopharma by SOBI for $1.75 billionPipeline

Our ~~Strategy~~pipeline focuses on acquiring and developing technologies designed to overcome tumor-intrinsic mechanisms underlying primary resistance to checkpoint inhibitors. We also focus on technologies to overcome acquired resistance to cancer immunotherapies related to the immune suppressing characteristics of the tumor microenvironment. We are leveraging our technology platforms to advance several diversified product candidates, including principally the following, each of which is described in more detail below.

Our goal is to become a leading immuno-oncology company by developing innate immune agonist candidates designed to harness the power of the innate immune system to overcome primary resistance to cancer immunotherapies, broadening the impact of therapies such as checkpoint inhibitors. We are also developing novel bi-functional ADCs and APCs to modulate the tumor microenvironment by reprograming MDSCs’ immune suppressing capabilities through inhibition of Delta Opioid Receptor on MDSCs to overcome acquired resistance to cancer immunotherapies.Strategy

Our ~~strategy~~goal ~~leverages~~is ~~our~~to ~~technologies~~become ~~and~~a leading immuno-oncology company by developing novel ~~product~~therapeutics ~~candidates~~designed to overcome primary and acquired resistance to ~~checkpoint~~cancer ~~inhibitors~~immunotherapies, ~~molecularly~~thereby ~~modified~~broadening ~~immune~~the impact of therapies such as checkpoint inhibitors. Our strategy is focused on leveraging our current technologies and ~~cellular~~novel ~~therapies~~product candidates and development programs in order to advance our current product candidates and expand our portfolio of products and technologies. The key elements of this strategy include:

•

Shortening the time and cost to product registration. We are working to shorten the time and cost to product registration by focusing on patient populations that qualify for accelerated approval, such as patients with advanced and metastatic Merkel cell carcinoma in our ~~planned~~ Phase 3 trial for IFx-2.0. We believe this trial could significantly reduce the time and cost to potential approval and the cost associated with precluding the need for a postmarketing confirmatory trial.

•

~~Expanding~~Acquire ~~the~~and ~~application~~develop ofnovel ~~the~~immunomodulatory ~~IFx-2.0~~technologies ~~innate~~or ~~immune~~product ~~agonist.~~candidates Weblood ~~plan~~related tocancers. ~~pursue~~Currently ~~the~~there ~~potential~~are ~~expansion~~no ofcancer ~~IFx-2.0~~immunotherapies toapproved ~~the~~in ~~30%~~ blood-related ~~35%~~cancers oflike ~~patients~~AML ~~with advanced~~ or ~~metastatic~~MDS, ~~Merkel~~which ~~cell~~presents ~~carcinoma~~an ~~who~~opportunity doto ~~not~~develop ~~present~~novel ~~with~~agents ~~cutaneous~~to oraddress ~~lymph~~such ~~nodal~~unmet ~~lesions~~medical ~~by examining the safety and efficacy of IFx-2~~needs.0 inWe ~~first~~believe ~~line~~we ~~treatment~~are asuniquely ~~adjunctive~~positioned ~~therapy~~ to ~~Keytruda® when administered via interventional radiology to lesion in the liver~~identify, ~~lung~~evaluate orand ~~retroperitoneal.~~potentially ~~Once~~acquire wenovel ~~determine~~drug ~~feasibility~~candidates ~~and~~that ~~safety~~focus ~~when~~on ~~IFx~~blood-~~2.0~~related iscancers ~~administered~~that ~~this~~provide ~~way, we plan on~~ a ~~second~~strategic ~~stage~~fit ofwithin ~~this~~our ~~study~~product ~~open~~pipeline toand ~~other~~or ~~cancers~~with ~~beyond~~our ~~Merkel~~DOR ~~cell~~technology ~~carcinoma by conducting the planned basket trial described above~~platforms. WeOur ~~plan~~acquisition onof ~~examining IFx~~TBS-~~2.0~~2025 inis ~~patients~~consistent with ~~any~~this ~~type~~acquisition ofstrategy ~~advanced cancer where their tumor exhibits primary resistance to~~ and ~~who~~also ~~fail~~provides ~~checkpoint~~synergy ~~inhibitor~~with ~~therapy.~~our IfDOR ~~successful,~~technology ~~this~~providing ~~basket trial is intended to potentially expand~~ the ~~use~~antibody ~~of IFx-2.0 to many types of cancer~~ for ~~which~~our ~~there~~ADC ~~are no effective or approved therapies for patients who fail to respond to checkpoint inhibitors or whose cancers are known not to respond to checkpoint inhibitors~~program.

•

~~Leverage~~Parallel ~~the~~development ~~IFx~~of ~~technology~~differentiated ~~platform~~drug toproduct ~~develop~~candidates ~~next~~within ~~generation~~a ~~candidates~~therapeutic tostrategic ~~expand~~focus ~~into~~on ~~hematologic~~diseases ~~cancer~~with ~~indications~~unmet medical needs like blood related cancers. We ~~are~~believe ~~also~~a ~~developing~~development ~~IFx-3.0,~~program ~~our~~leveraging ~~mRNA~~distinct ~~based~~technologies ~~innate~~across ~~immune~~a ~~agonist~~pipeline ~~candidate,~~of ~~for~~differentiated ~~systemic~~drug ~~(intravenous)~~candidates oroffers ~~autologous~~an ~~whole~~efficient ~~cell~~model ~~administration~~of ~~targeting~~how ~~the~~small ~~CD22~~biotech ~~receptor~~companies oncan ~~malignant~~align Bcapital ~~cells~~and asclinical adevelopment ~~potential~~execution ~~treatment~~while ~~for~~managing ~~blood~~technology ~~related~~and ~~cancers~~regulatory ~~like~~risks. ~~aggressive~~We ~~lymphoma,~~will ~~with~~continue ~~the~~to ~~intention~~be ofopportunistic ~~expanding~~in ~~the~~acquiring ~~application~~drug candidates that are within our therapeutic strategic focus, like our recent acquisition of ~~IFx~~TBS-2025. ~~technology~~In addition to ~~blood~~providing ~~related~~a ~~cancers~~Phase ~~not~~2 ~~amenable~~ready candidate to ~~intratumoral~~advance ~~administration.~~to ~~The~~clinical ~~Company~~studies ~~believes~~in ~~this~~mutNPM1 ~~would~~AML, bewe ~~the~~are ~~first~~investigating ~~systemically~~TBS-2025 ~~targeted~~when ~~mRNA~~conjugated ~~innate~~to ~~immune~~a ~~agonist~~DOR ~~known~~inhibitor toas beour lead ADC candidate in preclinical development.

•

Establish a leadership position in developing immune modulating bi-functional, ~~ADCs~~bi-specific ~~and APCs~~ADCs. We believe that we may be the first company to identify athat ~~novel~~the Delta Opioid Receptor is highly expressed on tumor-associated MDSCs and that it controls the regulation of multiple immune suppressive functions of MDSCs, the primary contributor to immune suppression of the bone marrow in the tumor microenvironment ~~immunosuppression~~. We believe that inhibiting MDSC functionality may represent a novel way to overcome acquired resistance to immunotherapies. ~~The~~Our ~~Company believes that its~~ immune modulating bi-specific, ~~and~~ bi-functional ADCs ~~and APCs~~ represent a paradigm shift in this important class of therapeutics and ~~has~~have the potential to position ~~the~~TuHURA ~~Company~~ to take the lead on advancing these novel immunomodulatory bi- specific, bi-functional ADCs ~~and APCs~~ to clinical trials.

•

Establish Development and Commercial License Collaborations. Leveraging our CEO’s track record of successfully establishing development and commercial partnerships, we intend to seek and establish partnerships with large pharmaceutical or biotech companies as a source of non-dilutive capital and funding to advance the global development of our product candidates.

Cancer Immunotherapies and IFx Technology

The Cancer-Immunity Cycle

For an anti-cancer immune response to lead to effective killing of cancer cells, a series of stepwise events must be initiated and allowed to proceed and expand iteratively. These steps, ~~which~~ are ~~illustrated in the graphic below, are~~ referred to as the “cancer-immunity cycle”. The human immune system is comprised of the innate immune system and adaptive immune system. The innate immune response, through evolution, has developed to protect us from our surrounding environment. It is the defense system with which we are born and serves as the body’s first defense mechanism against pathogens like bacteria or viruses and alerts the immune system to those threats. It works together with its complementary arm, the adaptive immune system, to address threats in the body, including cancer.

In the first step of the cycle, foreign proteins called “neoantigens” are created by cancer-related genes and are released and captured by dendritic cells (“DCs”) for processing. In order for this step to lead to a tumor killing T cell response, it must be accompanied by signals that specify immunity, or otherwise tolerance to the tumor antigens will be induced. Such immunogenic signals might include proinflammatory cytokines and factors released by dying tumor cells. During the next step, DCs present the captured neoantigens on MHCI and MHCII molecules to T cells, resulting in the priming and activation of tumor cell killing, or cytotoxic, T cell responses against these cancer-specific neoantigens, which are viewed as foreign. Finally, the activated cytotoxic T cells traffic to and infiltrate the tumor bed, specifically recognizing and binding to cancer cells through the interaction between its T cell receptor ~~(“TCR”)~~ and its cognate antigen bound to MHCI and kill their target cancer cell. Killing of the cancer cell releases additional tumor-associated neoantigens repeating the first step of the cancer- immunity cycle, to increase the breadth and depth of the response in subsequent revolutions of the cycle.

In cancer patients, the cancer-immunity cycle does not perform optimally. In order for an innate response to be activated against a tumor, the tumor must appear foreign to the immune system. Tumor neoantigens may not be detected due to low neoantigen load or mutational burden, DCs and T cells may treat antigens as self rather than foreign thereby creating T regulatory cell responses rather than cytotoxic responses, T cells may not properly home to tumors, may be inhibited from infiltrating the tumor, or, importantly, factors in the tumor microenvironment might suppress those effector T cells that are produced. The goal of cancer immunotherapy is to initiate and reinitiate a self-sustaining cycle of cancer immunity, enabling it to amplify and propagate.

9IFx Technology

~~Source:~~The ~~Oncology~~goal ~~Meets~~of ~~Immunology:~~cancer ~~The~~immunotherapies ~~Cancer-Immunity~~generally ~~Cycle,~~is ~~Immunity,~~to ~~Volume~~initiate 39an immune response to tumor neoantigens, ~~July~~which ~~2013~~are the abnormal proteins that tumor-associated genetic mutations cause the cells to produce. There are a number of approaches that attempt to make a tumor look foreign to the immune system. The optimal cancer immunotherapy would make a patient’s entire tumor appear foreign and activate an innate immune response through the comprehensive and efficient packaging of tumor neoantigens which are

~~IFx Technology~~8

The goal of cancer immunotherapies generally is to initiate an immune response to tumor neoantigens, which are the abnormal proteins that tumor-associated genetic mutations cause the cells to produce. There are a number of approaches that attempt to make a tumor look foreign to the immune system. The optimal cancer immunotherapy would make a patient’s entire tumor appear foreign and activate an innate immune response through the comprehensive and efficient packaging of tumor neoantigens which are presented to cytotoxic T cells, leading to their priming, activation, and proliferation of an immune attack against the tumor. Our IFx ~~Technology~~technology is designed to accomplish this goal.

~~Our~~TuHURA's IFx platform technology utilizes a proprietary plasmid DNA (“pDNA”) or messenger RNA (“mRNA”) which, when introduced into a tumor cell, results in the expression of a highly immunogenic gram positive bacterial protein (Emm55) from a rare variant of Streptococcus pyogenes on the surface of the tumor cell. This is graphically demonstrated above. By mimicking a bacterium, our technology makes a tumor cell look like bacteria. By making a tumor look like a bacterium, the molecular pattern of the bacterial protein is recognized by specific receptors on immune cells called pattern recognition receptors, also referred to as toll-like receptors or TLRs. These receptors are pre-programmed over evolution to recognize specific molecular patterns or motifs on pathogens like bacteria and activate and harness the power of the body’s innate immune response.

10IFx is designed to harness the body’s natural innate immune response making the patients entire tumor appear foreign. This causes antigen presenting cells (APCs) like DCs to phagocytize (which is the process of “eating” and “digesting”) the tumor cell, thinking they are bacteria. DCs present the captured neoantigens on MHCI and MHCII molecules to T cells, resulting in the priming and activation of cytotoxic T cell responses against these cancer-specific neoantigens, which are viewed as foreign. This is referred to as “primary epitope spreading.” Epitopes are the region/part of tumor antigens that are recognized by the immune system, specifically by antibodies, B cells and T cells. In doing so the first step of the cancer-immunity cycle is activated and restored.

~~bacterium~~Plasmid DNA, ~~our~~or ~~technology~~plasmids, ~~makes~~are asmall, ~~tumor~~circular, double-stranded DNA molecules that are separate from a cell’s ~~look~~chromosomal ~~like~~DNA and can replicate independently. Plasmids are most commonly found in bacteria, but can also be found in archaea and eukaryotic organisms. ByThey ~~making~~can arange ~~tumor~~in ~~look~~length ~~like~~from aabout ~~bacterium~~1,000 ~~the~~to ~~molecular~~hundreds ~~pattern~~of thousands of ~~the~~DNA ~~bacterial~~base ~~protein~~pairs. isPlasmids ~~recognized~~often bycarry ~~specific~~genes ~~receptors~~that oncan ~~immune~~benefit ~~cells~~the ~~called~~survival ~~pattern~~of ~~recognition~~an ~~receptors~~organism, ~~also~~such ~~referred~~as toantibiotic asresistance. ~~toll-like~~When ~~receptors~~a orbacterium ~~TLRs.~~divides, ~~These~~all ~~receptors~~of the plasmids in the call are ~~pre-programmed~~copied, ~~over~~so ~~evolution~~each todaughter ~~recognize~~cell ~~specific~~receives ~~molecular~~a ~~patterns~~copy orof ~~motifs~~each onplasmid. ~~pathogens~~Plasmids ~~like~~can also be transmitted horizontally to other bacteria ~~and~~in ~~activate~~some ~~and~~cases. ~~harness~~Scientists ~~the~~have ~~power~~taken advantage of ~~the~~plasmids ~~body’s~~to ~~innate~~use ~~immune~~them ~~response~~as tools to clone, transfer, and manipulate genes.

~~IFx~~Other isTypes ~~designed to harness the body’s natural innate immune response making the patients entire tumor appear foreign. This causes antigen presenting cells like DCs to phagocytize (which is the process~~ of ~~“eating”~~Cancer and “digesting”) the tumor cell, thinking they are bacteria. DCs present the captured neoantigens on MHCI and MHCII molecules to T cells, resulting in the priming and activation of cytotoxic T cell responses against these cancer-specific neoantigens, which are viewed as foreign. This is referred to as “primary epitope spreading.” Epitopes are the region/part of tumor antigens that are recognized by the immune system, specifically by antibodies, B cells and T cells. In doing so the first step of the cancer-immunity cycle is activated and restored. Immunotherapies

~~Plasmid~~To ~~DNA~~date, ~~or plasmids, are small, circular, double-stranded DNA molecules that are separate from a cell’s chromosomal DNA and can replicate independently. Plasmids are~~ most ~~commonly~~cancer ~~found in bacteria~~immunotherapies, but can also be found in archaea and eukaryotic organisms. They can range in length from about 1,000 to hundreds of thousands of DNA base pairs. Plasmids often carry genes that can benefit the survival of an organism, such as ~~antibiotic~~those ~~resistance.~~described ~~When a bacterium divides~~below, ~~all~~have ofutilized ~~the plasmids in the call are copied, so each daughter cell receives~~ a ~~copy~~number of ~~each~~different ~~plasmid.~~approaches ~~Plasmids can also be transmitted horizontally~~ to ~~other~~initiate ~~bacteria~~an ininnate ~~some~~immune ~~cases.~~response ~~Scientists have taken advantage of plasmids~~ to ~~use~~generate ~~them~~tumor asspecific ~~tools~~activated toT ~~clone, transfer, and manipulate genes~~cells.

~~Other~~Oncolytic ~~Types~~Virus Vaccines. Oncolytic virus vaccines are designed to preferentially induce viral replication-dependent oncolysis (viral induced killing) in tumors in an effort to stimulate antitumor immune responses. Intratumoral injection is thought to trigger both local and systemic immunological responses leading to tumor cell lysis, the release of ~~Cancer~~tumor-associated ~~Immunotherapies~~antigens into the

~~To date, most cancer immunotherapies, such as those described below, have utilized a number of different approaches to initiate an innate immune response to generate tumor specific activated T cells.~~9

Oncolytic Virus Vaccines. Oncolytic virus vaccines are designed to preferentially induce viral replication-dependent oncolysis (viral induced killing) in tumors in an effort to stimulate antitumor immune responses. Intratumoral injection is thought to trigger both local and systemic immunological responses leading to tumor ~~cell lysis, the release of tumor-associated antigens into the tumor~~ microenvironment where they need to be recognized by antigen presenting cells leading to subsequent activation of innate and adaptive immune systems to induce tumor antigen-specific effector T-cell antitumor immunity.

Tumor-associated antigen vaccines. Another approach is to utilize Tumor-Associated Antigens (“TAAs”), some of which may also be similar to self-antigens, although preferentially overexpressed on tumor cells. However, these TAAs may also be displayed by normal healthy cells or cancer testis antigens that are only expressed by tumor cells and adult reproductive tissues. T and B cells with high affinity toward these TAAs also target self-antigens leading to the removal of these T and B cells from the immune repertoire by central and peripheral tolerance. Thus, a potent vaccine must break tolerance for them to work. To date, this approach has had limited success.

Individual Neoantigen Therapy. Tumor-Specific Antigens (“TSAs”) differ from tumor-associated antigens since they are not shared with similar self-antigens. They are typically de novo epitopes expressed by cancer-causing viruses (or oncoviruses) or private neoantigens encoded by somatic mutations. TSAs are truly tumor specific with no central tolerance. Deciding which TSAs to select and how to configure such multivalent vaccines is itself a daunting challenge. It may be insufficient to rely entirely on sequencing the expressed tumor genome looking for point mutations, translocation fusions, or CT antigens. Not only might this vary from patient to patient or even from cell to cell within a single patient’s tumor, expression at the messenger RNA or protein level does not assure that predicted antigenic peptides will be generated and expressed as peptide-MHCI complexes, especially in the face of the allelic complexity in the MHC. Several groups are actively approaching this problem by using a combination of informatics and mass spectroscopy of peptides eluted from MHCI molecules. Early clinical trials used as neo-adjuvant therapy in combination with checkpoint inhibitors among patients with potentially surgically curable disease at risk for relapse has yielded encouraging results, although how best to deliver them to patients remains a critical unknown.

Potential Advantages of IFx Innate Immune Agonist Technology

IFx’s approach is designed to naturally harness the power of the innate immune response leveraging Pathogen Associated Molecular Patterns (PAMP), or motifs present on pathogens, like bacteria and conserved through evolution. These patterns are recognized by pattern recognition receptors on antigen presenting and other immune cells of our innate immune system. By expressing a bacterial protein on the surface of a tumor cell the intact tumor cell is digested and the full complement of foreign tumor neoantigens are packaged and presented to newly produced T and B cells producing activated tumor specific T cells, the primary target allowing checkpoint inhibitors to work where they previously failed.

11We believe that our IFx technology avoids problems associated with trying to predict which tumor- specific antigens are important and avoids the challenges associated with selection, analysis, production and delivery that accompanies individual neoantigen therapy approaches. Unlike oncolytic viral therapies which lyse the tumor cell disseminating tumor neoantigens throughout the tissue surrounding the tumor relying on antigen presenting cells in the vicinity to recognize, digest and present neoantigens to naïve T and B cells, IFx technology presents the full complement of tumor neoantigens from the intact tumor cell providing more optimal neoantigen presentation and inter-antigenic epitope spreading more effectively than oncolytic viral therapy or individual neoantigen therapy approaches.

WeImportantly, ~~believe that our~~ IFx ~~technology~~is ~~avoids~~not ~~problems~~an ~~associated~~oncolytic ~~with~~viral ~~trying~~technology. toOncolytic ~~predict~~viral technologies which ~~tumor-~~work ~~specific~~by ~~antigens~~“exploding” ~~are important and avoids~~ the ~~challenges~~tumor ~~associated~~cell ~~with~~resulting ~~selection,~~in ~~analysis, production and delivery that accompanies individual neoantigen therapy approaches. Unlike oncolytic viral therapies which lyse~~ the ~~tumor~~random ~~cell~~dissemination ~~disseminating~~of tumor neoantigens ~~throughout~~into the ~~tissue surrounding the~~ tumor ~~relying~~microenvironment onwhere ~~antigen~~immune ~~presenting~~ cells incan ~~the~~potentially ~~vicinity~~see toand ~~recognize,~~ digest ~~and~~them. ~~present~~In ~~neoantigens to naïve T and B cells~~contrast, IFx ~~technology~~ presents the full complement of tumor neoantigens ~~from~~packaged inside the intact tumor cell providing much more optimal neoantigen presentation and more efficient inter-antigenic epitope spreading ~~more effectively than oncolytic viral therapy or individual neoantigen therapy approaches~~.

~~Importantly,~~Clinical ~~IFx~~Rationale isfor not an oncolytic viral technology. Oncolytic viral technologies which work by “exploding” the tumor cell resulting in the random dissemination of tumor neoantigens into the tumor microenvironment where immune cells can potentially see and digest them. In contrast, IFx presents the full complement of tumor neoantigens packaged inside the intact tumor cell providing much more optimal neoantigen presentation and more efficient interTBS-~~antigenic epitope spreading.~~2025

BiTBS-~~specific~~2025 (f/Bik/a KVA-~~functional~~12123), ~~APCs~~a VISTA inhibiting antibody, was initially investigated by Kineta in a Phase 1 trial either as monotherapy (n=24) or in combination with pembrolizumab (n=16) among patients with advanced, therapy refractory cancers, including, breast, lung, colorectal and ~~ADCs:~~ovarian ~~Inhibiting~~cancer. ~~MDSC~~The ~~immune~~drug ~~suppressing~~demonstrated ~~functions~~a favorable safety profile at the highest dose level of 1,000mg administered every two weeks. No significant anti-tumor activity was observed among the 40 patients treated in the trial.

VISTA is a novel negative checkpoint expressed on quiescent (resting) T cells and highly expressed on myeloid cells like MDSCs. While VISTA is expressed on a wide variety of solid tumor cancers, its role in resistance or failure of cancer- immunotherapy is not well established. In contrast scientific evidence demonstrates that mutNPM1 a mutation present in approximately 30% to 35% of cases of AML, drives the expression of VISTA on leukemic blasts in AML and is reported to be the primary mechanism by which AML has a poor response to and high relapse rates following current therapies. VISTA expression is linked to high relapse rate in AML due to its ability to allow leukemic blasts to evade immune recognition and attack by the patient’s

MDSCs are among the most common cells present in the tumor microenvironment, which is the tissue surrounding the tumor, where they are a major regulator of suppression of the immune system. MDSCs are normally produced during pregnancy where they migrate to and populate the placenta, creating an immunologic sanctuary for the fetus. Since half of the genetic make-up of the fetus comes from the father, this is necessary to prevent the mother’s immune system from attacking the fetus. They are also produced in settings of chronic inflammation or autoimmune disease as a mechanism to decrease inflammation or autoimmunity. Under normal conditions, MDSCs represent less than 2% of circulating peripheral blood mononuclear cells (PBMCs) and lack potent immune suppressing characteristics10

Inimmune ~~cancer, MDSCs are hijacked by tumors to create an immunosuppressive environment in the tissues in which the tumor lives~~system. ~~MDSCs~~When ~~are~~VSIR, the ~~primary~~gene ~~driver~~that ofencodes ~~the~~for ~~immunosuppressive~~VISTA ~~tumor~~is ~~microenvironment.~~edited Multiple effector molecules and signaling pathways are used by MDSCs to regulate immune suppression. One main mechanism involves depletion of necessary amino acids like arginine through production of arginase (“Arg-1”), or ~~“destruction”~~when ofVISTA ~~inflammatory~~is ~~cytokines~~inhibited ~~via~~with ~~production~~a ofVISTA ~~inducible~~inhibiting ~~nitric oxide (“iNOS”)~~antibody, inan ~~addition to anti-inflammatory prostaglandins (“COX2”),~~ immune ~~suppressing~~response ~~cytokines~~is ~~like~~observed ~~transforming growth factor beta (“TGF-®”) or Interleukin 10 (“IL-10”)~~ and ~~recruitment~~survival ~~and~~is ~~induction~~enhanced of immune inhibitory cells such as regulatory T cells (T regs) and M2 polarized tumor associated macrophages (“TAMs”). Accumulating evidence demonstrates that the enrichment and activation of MDSCs correlates with tumor progression, metastasis and recurrence. In addition, MDSCs circulating in ~~the~~murine ~~blood~~models of ~~patients~~mutNPM1 ~~with cancer is highly correlated to poor clinical outcome~~AML.

12Recently, several new drugs called menin inhibitors have received approval in patients with relapsed and refractory (r/r) mutNPM1 AML. Menin is the “carrier” protein that exerts the proliferative effect on leukemic blasts. While the response rates of 22% to 25% that are seen following therapy with menin inhibitors are encouraging, they are of short duration followed by leukemia recurrence. For the >75% of patients who fail to respond to or relapse following a menin inhibitor, there are no approved or effective therapies. Translational scientific data supports the potential for TBS-2025 as monotherapy to improve potential response rates in this patient population.

WeApplying ~~believe~~the ~~that~~FDA’s ~~inhibiting~~guidelines ~~and~~for ~~reprograming~~development ~~MDSC~~of ~~function~~drugs ~~represents~~in aAML ~~promising~~to ~~novel~~the ~~approach~~pharmacokinetic toand ~~overcome~~safety ~~MDSC-induced~~data ~~tumor~~from ~~microenvironment~~VISTA ~~immunosuppression~~101, ~~and~~ the ~~resulting~~Phase ~~acquired~~1 ~~resistance~~study in solid tumors can potentially be used to ~~cancer~~determine ~~immunotherapies~~a starting dose in a Phase 1b trial. We ~~Various~~anticipate ~~companies~~conducting ~~are~~an ~~focusing~~abbreviated onPhase1b ~~several~~dose ~~strategies,~~escalation ~~including~~study ~~blocking~~in ~~MDSC~~mutNPM1 ~~recruitment~~r/r AML in patients who failed to ~~the~~respond ~~microenvironment~~to or ~~inhibiting~~relapsed ~~their~~following ~~production~~therapy with a menin inhibitor in mutNPM1 ~~the~~r/r ~~bone~~AML. ~~marrow~~This patient population represents an unmet medical need. ~~Another~~We ~~potential~~believe ~~strategy~~this ispopulation ~~inhibiting~~of ~~MDSC-mediated~~patients ~~immunosuppression~~with bythis ~~developing~~genetic ~~inhibitors~~mutation tomay ~~individual~~qualify ~~MDSC-~~for ~~related~~investigation ~~immune~~under ~~suppressing~~the ~~compounds~~FDA’s ~~such~~Plausible asMechanism ~~IDO~~Pathway, ~~iNOS~~which oris ~~COX2~~a ~~inhibitors~~regulatory framework allowing approval based on biological rationale and target engagement rather than traditional, large randomized trials.

~~Our~~In ~~Delta~~addition ~~Opioid~~to ~~Receptor~~examining ~~(DOR)~~the ~~inhibitors:~~potential biof TBS-~~specific~~2025 monotherapy in this patient population, bithe Phase 1b study will also be used to establish a recommended dose to be investigated in a Phase 2 trial of TBS-~~functional~~2025 ~~antibody~~in ~~peptide~~combination orwith ~~drug~~a ~~conjugates~~menin ~~(APC,~~inhibitor ~~ADCs)~~in mutNPM1 r/rAML in patients previously untreated with a menin inhibitor. The Phase 2 study would explore whether TBS-2025 when used in patients with mutNPM1 r/rAML who are receiving a menin inhibitor may improve both response rate and duration of response by allowing immune recognition and attack against leukemic cells. The Company plans on discussing its development plans with the FDA late in the first half of 2026 and initiating the planned Phase1b/2 trial in as early as the second half 2026.

~~The Delta Opioid Receptor, or~~ DOR, isTechnology the first cloned G protein-coupled receptor. Many recent studies on Delta Opioid Receptor functions have determined that the Delta Opioid Receptor is involved in the regulation of malignant transformation and ~~tumor progression in multiple cancers. In hepatocellular carcinoma (HCC)~~Bi-functional, ~~higher~~Bi-specific ~~expression~~ADCs: ofInhibiting ~~Delta~~MDSC ~~Opioid~~immune ~~Receptor~~suppressing was observed in liver tumor tissue cells compared to normal liver tissue/cells. When Delta Opioid Receptorgene expression was silenced or inhibited, the proliferation of HCC ells was inhibited, and tumor cells underwent apoptosis, the cell cycle was arrested and tumor cell invasion and migration.functions

While Delta Opioid Receptor overexpression and its role in tumor biology is well established in the literature, we believe that the Company, along with scientists at Moffitt Cancer Center, are the first to describe the high differential expression of the Delta Opioid Receptor on tumor associated MDSCs ~~compared to bone marrow (BM) or spleen derived MDSCs either in tumor free or tumor bearing models. (See Figures 1 and 2 below, courtesy of P Rodriguez, Moffitt Cancer Center ).~~

AsMDSCs aare ~~previously~~among ~~unrecognized~~the ~~target~~most tocommon ~~reprogram~~immunosuppressive ~~tumor~~cells ~~associated~~present ~~MDSCs~~in ~~immunosuppressive~~the ~~functions~~bone onmarrow of patients with hematologic cancer and in the tumor microenvironment, ~~developing~~which ~~small~~is ~~molecule~~the ortissue ~~peptide~~surrounding ~~antagonists~~the tumor, where they are a major regulator of suppression of the ~~Delta~~immune ~~Opioid~~system. ~~Receptor~~MDSCs ~~represents~~are anormally ~~novel~~produced ~~approach~~during pregnancy where they migrate to ~~reprograming~~and ~~MDSC~~populate ~~functionality~~the placenta, creating an immunologic sanctuary for the fetus. Since half of the genetic make-up of the fetus comes from the father, this is necessary to ~~overcome~~prevent ~~acquired~~the ~~resistance~~mother’s immune system from attacking the fetus. They are also produced in settings of chronic inflammation or autoimmune disease as a mechanism to ~~checkpoint~~decrease ~~inhibitors~~inflammation or autoimmunity. Under normal conditions, MDSCs represent less than 2% of circulating peripheral blood mononuclear cells (PBMCs) and ~~other~~lack ~~cancer~~potent ~~immunotherapies.~~immune suppressing characteristics

13In cancer, MDSCs are hijacked by tumors to create an immunosuppressive environment in the tissues in which the tumor lives. In solid tumors, MDSCs are the primary driver of the immunosuppressive tumor microenvironment and function similarly in the bone marrow of patients with hematologic cancers like leukemia and MDS. Multiple effector molecules and signaling pathways are used by MDSCs to regulate immune suppression. One main mechanism involves depletion of necessary amino acids like arginine through production of arginase (“Arg-1”), or “destruction” of inflammatory cytokines via production of inducible nitric oxide (“iNOS”), in addition to anti-inflammatory prostaglandins (“COX2”), immune suppressing cytokines like transforming growth factor beta (“TGF-®”) or Interleukin 10 (“IL-10”) and recruitment and induction of immune inhibitory cells such as regulatory T cells (T regs) and M2 polarized tumor associated macrophages (“TAMs”). Accumulating evidence demonstrates that the enrichment and activation of MDSCs correlates with tumor progression, metastasis and recurrence. In addition, MDSCs circulating in the blood of patients with leukemia is highly correlated to poor clinical outcome.

Inhibition of the Delta Opioid Receptor on tumor associated MDSCs is designed to block MDSC production of multiple immunosuppressing factors through a single point of intervention. Our bi-specific APCs consist of a patented peptidomimetic Delta Opioid Receptor specific inhibitor conjugated to a checkpoint inhibitor like anti-PD-1 antibody. Moffitt Cancer Center scientists demonstrated that in Delta Opioid Receptor expressing, PD-1 resistant murine lung cancer models, treatment with its APC, accumulated in the tumor microenvironment and resulted in a significant and dramatic improvement in survival when compared to treatment with anti-PD-1 antibody alone. We have established multiple functional assay screens to investigate the effects of both novel peptidomimetic or small molecule Delta Opioid Receptor specific inhibitors of tumor associated MDSC functionality to guide its selection of both APCs and ADCs for further in vitro and in vivo characterization and development.11

We believe that ~~our~~inhibiting ~~tumor~~and ~~associated~~reprograming MDSC~~-targeting~~ ~~APCs~~function ~~and~~represents ~~ADCs~~a ~~have~~promising anovel ~~number~~approach ofto ~~potential~~overcome ~~benefits~~MDSC-induced ~~over~~tumor ~~current~~microenvironment ~~approaches~~immunosuppression toand ~~overcoming~~the resulting acquired resistance to cancer immunotherapies. Various companies are focusing on several strategies, including blocking MDSC recruitment to the ~~following:~~microenvironment or inhibiting their production in the bone marrow. Another potential strategy is inhibiting MDSC-mediated immunosuppression by developing inhibitors to individual MDSC- related immune suppressing compounds such as IDO, iNOS or COX2 inhibitors.

~~Inhibiting~~Our ~~tumor associated MDSC production of multiple immune suppressing factors. The~~ Delta Opioid Receptor on(DOR) ~~tumor~~inhibitors: ~~associated MDSCs functions like a “master switch” controlling the regulation of multiple immune suppressing factors such as~~bi-specific, ~~iNOS, Arg~~bi-1functional ~~and~~antibody ~~COX2.~~drug ~~Inhibiting~~conjugates ~~the receptor results in “shutting off” production of these and other immune suppressing factors as compared to the industry focus of developing inhibitors targeting a single factor.~~(ADCs)

~~Blocking~~The ~~tumor~~Delta ~~associated~~Opioid ~~MDSC~~Receptor, ~~recruitment~~or toDOR, is the ~~microenvironment~~first cloned G protein-coupled receptor. ToWhile ~~exhibit~~Delta ~~their~~Opioid ~~immunosuppressive~~Receptor ~~phenotype,~~overexpression ~~MDSCs~~and ~~have~~its torole bein ~~recruited~~tumor tobiology is well established in the ~~tumor~~literature, ~~site~~we believe that the Company, ~~transitioning~~along with scientists at Moffitt Cancer Center, are the first to describe the high differential expression of the Delta Opioid Receptor on tumor associated MDSCs ~~which~~compared ~~display~~to ~~maximum~~bone ~~immunosupressive~~marrow ~~properties.~~(BM) ~~This~~or ~~process~~spleen isderived ~~mediated~~MDSCs, ~~mainly~~either byin ~~chemokines~~tumor ~~secreted~~free inor ~~the~~ tumor ~~microenvironment~~bearing models. (See figures below, source: TuHURA research files).

1412

~~and~~MDSC: ~~chemokine~~MDSC ~~receptors~~isolated ~~expressed~~from ~~on MDSCs. There are a number of strategies to prevent the recruitment of MDSCs to the microenvironment through the development of inhibitors of chemokines such as CCL2/CCR2 blockade. However brain~~BM, ~~heart, kidney, liver, lung, ovary, pancreas, spinal cord,~~ spleen, and ~~thymus also express CCR2, introducing the potential for off-target side effects with this approach~~Tumor. ~~Inhibiting~~* ~~the~~p ~~Delta~~α ~~Opioid Receptor prevents the proliferation and production of tumor associated MDSC-monocyte subpopulations (M-MDSC)~~0.05, ~~promotes~~** ~~repolarizing~~p M2α ~~to M1 phenotype decreasing Th-2 cytokines while increasing Th-1 (g-IFN, IL-2) cytokines~~0. ~~Thus changing the immunosuppressive phenotype of the tumor microenviroment to an immunogenic phenotype more favorable to cancer immunotherapies.~~01

~~Immune~~As ~~modulation~~a ofpreviously ~~tumor~~unrecognized ~~microenviroment/potentiating~~target ~~the~~to ~~effects~~reprogram ~~of checkpoint inhibitors. To date the prior and future development of ADC,s ADC-checkpoint inhibitors or bi-specific all have one thing ion common, they target~~ tumor associated receptors with the antibody and carry with it either a payload toxin, or other tumor cell cycle disruptors or checkpoint inhibitor. To our knowledge we are the only company developing APCs or ADCs targeting MDSCs ~~where~~ ~~our~~immunosuppressive ~~APCs, and ADCs are designed to be bi-specific/ bi-functional, i.e., affecting two targets and having two~~ functions: ~~inhibiting~~on ~~tumor~~the ~~associated MDSC-related immune suppression and thereby making~~ tumor ~~susceptible to attack~~microenvironment, ~~while~~developing ~~localizing~~small ~~checkpoint~~molecule antagonists ~~inhibitors~~of ~~where~~ the ~~tumor~~Delta ~~resides.~~Opioid ~~These~~Receptor ~~two~~represents ~~functions~~a ~~are~~novel ~~intended~~approach to ~~work~~reprograming ~~together~~MDSC ~~with~~functionality ~~the~~to ~~goal~~overcome ~~of overcoming~~ acquired resistance, ~~preventing~~to ~~T cell exhaustion and allowing~~ checkpoint inhibitors and ~~cellular~~other ~~therapies~~cancer ~~to be safer and more effective while interfering with the tumor’s ability to invade and spread throughout the body~~immunotherapies.

~~Our~~The ~~Clinical~~Company ~~Development~~has ~~Program~~established multiple functional assay screens to investigate the effects of small molecule Delta Opioid Receptor specific inhibitors of tumor-associated MDSC functionality to guide its selection of ADCs for further invitro and in vivo characterization and development. The Company anticipates utilizing TBS-2025, its VISTA inhibiting antibody, as the first ADC to enter preclinical development.

~~For~~The ~~purposes~~Company ofbelieves ~~the~~that ~~below descriptions of~~ our ~~Phase~~tumor 1associated ~~and 1b clinical trials, the response rates for IFx~~MDSC-~~2.0~~targeting ~~are~~ADCs ~~determined~~have under best clinical practice by the principal investigators, evaluating and confirming clinical progression prior to or during therapy utilizing conventional and appropriate radiographic or metabolic (Positron Emission Tomography – PET) methodologies. Response determination utilizes conventional terminologies under standardized response evaluation criteria. A “complete response”, or CR, is deemed to be disappearance of all lesions. A “partial response”, or PR, is at least a ~~30%~~number ~~decrease in the sum~~ of ~~the~~potential ~~size~~benefits ofover ~~the~~current ~~target~~approaches lesions. “Progressive disease”, or PD, is at least a 20% increase in the sum of the longest diameter or the appearance of new lesions. “Stable disease”, or SD, means that the patient has neither sufficient shrinkage in the lesions to ~~qualify~~overcoming ~~for~~acquired PRresistance ~~nor sufficient increase~~ to qualify for PD. The term “objective response rate” is defined as the proportion of patients who have a partial or complete response to therapy. Furthermore, the term “pCR” refers to a pathological complete response, which is the absence of signs of cancer ~~in tissue samples removed during surgery or biopsy after treatment. “Progression-free survival”~~immunotherapies, orincluding ~~PFS, means~~ the ~~length of time after the treatment that a patient lives without disease progression.~~following:

•

~~Planned~~Inhibiting ~~Phase~~tumor 3associated ~~Trial~~MDSC ~~for~~production ~~IFx-2~~of multiple immune suppressing factors.0 The Delta Opioid Receptor on tumor associated MDSCs functions like a “master switch” controlling the regulation of multiple immune suppressing factors such as, iNOS, S100A9 among others. Inhibiting the receptor results in “shutting off” production of these and other immune suppressing factors as compared to the industry focus of developing inhibitors targeting a single factor.

•

WeBlocking ~~have~~tumor ~~entered~~associated ~~into~~MDSC arecruitment ~~Special~~to ~~Protocol Assessment agreement with~~ the ~~FDA for a single Phase 3 randomized placebo and injection controlled trial for IFx-2~~microenvironment.0, ~~our~~To ~~lead~~exhibit ~~innate~~their ~~immune~~immunosuppressive ~~agonist~~phenotype, asMDSCs ~~adjunctive~~have ~~therapy~~ to ~~pembrolizumab~~be ~~(Keytruda®)~~recruited into the ~~first~~tumor ~~line~~site, ~~treatment~~transitioning ofto ~~patients~~tumor ~~with~~associated ~~advanced~~MDSCs orwhich ~~metastatic~~display ~~Merkel~~maximum ~~cell~~immunosupressive ~~carcinoma~~properties. ~~who~~This ~~are~~process ~~checkpoint~~is ~~inhibitor-naïve~~mediated ~~utilizing~~mainly ~~the~~by ~~FDA’s~~chemokines ~~accelerated~~secreted ~~approval~~in ~~pathway. The Company has worked~~ the ~~deputy~~tumor ~~director~~microenvironment ofand ~~the~~chemokine ~~FDA’s~~receptors ~~Oncology~~expressed ~~Center of Excellence (OCE)~~ on ~~a unique trial design~~MDSCs. ~~Consistent~~There ~~with~~are ~~the~~a ~~FDA’s~~number ~~Project~~of ~~Front~~strategies ~~Runner~~to ~~initiative,~~prevent the ~~FDA~~recruitment ~~recommended~~of ~~investigating~~MDSCs ~~IFx-2.0~~to in the ~~front~~microenvironment ~~line~~through ~~treatment setting rather than in patients who are progressing on checkpoint inhibitor therapy,~~ the ~~latter~~development of ~~which~~inhibitors ~~was~~of ~~the~~chemokines ~~conduct~~such inas ~~the~~CCL2/CCR2 ~~phase 1b trial~~blockade. InHowever ~~doing~~brain, soheart, ~~data~~kidney, ~~from~~liver, alung, ~~primary~~ovary, ~~endpoint~~pancreas, ofspinal ~~objective response rate~~cord, ~~or ORR~~spleen, ~~that is of sufficient magnitude~~ and ~~duration~~thymus ~~and~~also ~~with~~express ~~a favorable risk/benefit profile could be sufficient to support accelerated approval. Furthermore~~CCR2, ~~OCE~~introducing ~~requested~~the ~~that~~potential wefor ~~consider incorporating a key secondary endpoint that is of clinical benefit such that results from a key secondary endpoint of progression~~off-~~free~~target ~~survival,~~side oreffects ~~PFS, that is adequately powered~~ with ~~statistical~~this ~~assumptions~~approach. inInhibiting the ~~statistical~~Delta ~~analysis~~Opioid ~~plan~~Receptor ~~provided~~prevents to the ~~FDA,~~proliferation ifand ~~achieved~~production ~~without~~of atumor ~~detrimental~~associated ~~effect~~MDSC-monocyte onsubpopulations ~~overall survival~~(M-MDSC), orpromotes ~~OS,~~repolarizing ~~could~~M2 ~~be adequate~~ to ~~support~~M1 ~~conversion~~phenotype todecreasing ~~regular~~Th-2 ~~approval~~cytokines ~~satisfying~~while ~~the~~increasing ~~requirement~~Th-1 ~~for~~(g-IFN, aIL-2) ~~confirmatory trial~~cytokines. ~~Notwithstanding~~Thus ~~the~~changing ~~foregoing,~~ the ~~results~~immunosuppressive phenotype of ~~clinical trials are inherently uncertain, and~~ the ~~results~~tumor ofmicroenviroment ~~our planned Phase 3 clinical trial may fail~~ to ~~satisfy~~an ~~the~~immunogenic ~~ORR,~~phenotype ~~PFS,~~more ~~and/or~~favorable ~~OS endpoints, and none of our prior clinical trials with respect~~ to ~~IFx-2.0~~cancer ~~were powered to determine statistical significance over a control~~immunotherapies.

•

AsImmune ~~set~~modulation ~~forth~~of intumor amicroenviroment/potentiating ~~January~~the ~~2024~~effects ~~partial~~of ~~clinical~~checkpoint ~~trial~~inhibitors. ~~hold~~To ~~letter~~date ~~from~~ the ~~FDA~~prior ~~regarding~~and ~~the~~future ~~chemistry,~~development ~~manufacturing~~of ADC,s ~~and~~ADC-checkpoint ~~controls~~inhibitors ~~(CMC)~~or ~~requirements~~bi-specific ~~for~~all ~~our~~have ~~planned~~one ~~Phase~~thing 3in ~~trial~~common, ~~for~~which ~~IFx-2.0~~is tothat bethey ~~conducted~~target ~~under~~tumor ~~the~~associated ~~Special~~receptors ~~Protocol~~with ~~Assessment agreement,~~ the ~~FDA~~antibody isand ~~requiring~~carry ~~that,~~with ~~prior~~it toeither ~~initiating~~a ~~the~~payload ~~trial~~toxin, weor ~~must~~other ~~qualify~~tumor ~~potency~~cell ~~assay~~cycle ~~and~~disruptors ~~the~~or ~~mixing~~checkpoint ~~process for IFx-2~~inhibitor.0 toTo beour ~~used~~knowledge atwe are the ~~clinical~~only ~~site. We~~company ~~have~~developing ~~reached~~ADCs ~~agreement~~targeting ~~with~~MDSCs where ~~FDA~~our onADCs ~~the~~are ~~requirements~~designed ~~for~~to ~~lifting~~be ~~the~~bi-specific/ ~~partial~~bi-functional, ~~clinical~~i.e., ~~hold~~affecting ~~and~~two ~~believe~~targets weand ~~will~~having ~~meet~~two ~~the~~functions: ~~requirements~~inhibiting ~~and~~tumor ~~consequently~~associated ~~expect~~MDSC-related toimmune ~~receive~~suppression aand ~~complete~~thereby ~~response~~making ~~letter,~~tumor orsusceptible ~~CRL~~to attack, ~~lifting~~while ~~the~~localizing ~~partial~~checkpoint ~~clinical~~inhibitors ~~hold~~where in the ~~second~~tumor ~~quarter of 2025~~resides. ~~The~~These ~~Company~~two ~~currently~~functions ~~believes~~are itintended ~~may~~to bework intogether ~~position~~with tothe ~~initiate~~goal ~~the~~of ~~Phase~~overcoming 3acquired ~~study~~resistance, inpreventing ~~the~~T ~~second~~cell ~~quarter~~exhaustion ofand ~~2025~~allowing ifcheckpoint ~~the~~inhibitors ~~results~~and ofcellular ~~the~~therapies ~~mixing~~to ~~studies~~be safer and ~~potency~~more ~~assay~~effective ~~qualifications~~while ~~are~~interfering ~~acceptable~~with to the ~~FDA,~~tumor’s ~~but~~ability ~~there~~to isinvade noand ~~assurance~~spread ~~that~~throughout the body.

15TuHURA's IFx Clinical Development Program

weFor ~~will~~purposes beof ~~able~~the tobelow ~~satisfy~~descriptions ~~the~~of ~~requirements~~our ~~set~~Phase ~~forth~~1 inand ~~the~~1b ~~partial~~ clinical ~~trial~~trials, ~~hold~~the ~~letter~~response onrates afor ~~timely~~IFx-2.0 ~~basis~~are ordetermined atunder ~~all.~~best Weclinical ~~anticipate~~practice ~~that~~by ~~enrollment for~~ the ~~Phase~~principal ~~3 would take approximately 12 months~~investigators, ~~with~~evaluating ~~topline~~and ~~data~~confirming ~~potentially~~clinical ~~being~~progression ~~available~~prior 6 to 7or ~~months~~during ~~following~~therapy ~~the~~utilizing ~~last~~conventional ~~patient~~and ~~enrolled.~~appropriate Ifradiographic ~~successful,~~or ~~this~~metabolic ~~Phase~~(Positron 3Emission ~~trial~~Tomography ~~would~~– ~~form~~PET) ~~the~~methodologies. ~~basis~~Response ofdetermination autilizes ~~Biologics~~conventional ~~License~~terminologies ~~Application,~~under orstandardized ~~BLA~~response evaluation criteria. A ~~Special~~“complete ~~Protocol~~response”, ~~Assessment~~or ~~agreement~~CR, is adeemed ~~binding~~to ~~written~~be ~~agreement~~disappearance ~~between~~of ~~the~~all Ulesions.S. ~~Food~~A ~~and~~“partial ~~Drug~~response”, ~~Administration~~or ~~(FDA)~~PR, ~~and~~is aat ~~trial~~least ~~sponsor~~a ~~that~~30% ~~indicates~~decrease in the ~~study’s~~sum ~~design~~of ~~and~~the ~~analysis~~size ~~are~~of ~~adequate~~the totarget ~~support~~lesions. an“Progressive ~~application~~disease”, ~~submission.~~or APD, ~~Special~~is ~~Protocol~~at ~~Assessment~~least ~~agreement~~a ~~does~~20% ~~not~~ increase in the ~~likelihood~~sum of ~~marketing approval for~~ the ~~product~~longest ~~and~~diameter ~~may not lead to a faster~~ or ~~less~~the ~~costly~~appearance ~~development,~~of ~~review,~~new ~~or approval process~~lesions. ~~The~~“Stable ~~study population~~disease”, ~~dose,~~or ~~schedule~~SD, ~~and~~means ~~study~~that ~~design for~~ the ~~trial~~patient ~~are~~has ~~based~~neither onsufficient ~~the~~shrinkage ~~response rates observed~~ in ~~our~~the ~~Phase~~lesions 1bto ~~trial~~qualify infor ~~checkpoint~~PR ~~inhibitor~~nor ~~naïve~~sufficient ~~patients~~increase ~~with~~to ~~advanced~~qualify ~~Merkel~~for ~~cell~~PD. ~~carcinoma~~The ~~who~~term ~~exhibited~~“objective ~~primary~~response ~~resistance~~rate” tois ~~anti~~defined ~~PD(L)-1 checkpoint inhibitors such~~ as ~~Keytruda®~~the ~~The~~proportion ~~clinical~~of ~~study~~patients ~~design~~who ~~for~~have ~~the~~a ~~Phase~~partial 3or ~~registration~~complete ~~trial~~response isto ~~presented below~~therapy. ~~Based~~Furthermore, ~~on correspondence with~~ the ~~FDA,~~term ~~patients~~“pCR” ~~with~~refers ~~advanced~~to ~~Merkel cell carcinoma represent~~ a ~~patient~~pathological ~~population~~complete ~~with~~response, anwhich ~~unmet medical need. Our study~~ is ~~designed~~the toabsence ~~determine~~of ifsigns ~~IFx-2.0~~of ~~can~~cancer ~~increase~~in ~~the~~tissue ~~objective~~samples ~~response~~removed ~~rate~~during ~~when~~surgery ~~used~~or asbiopsy ~~adjunctive~~after ~~therapy~~treatment. to“Progression-free ~~Keytruda~~survival”, inor ~~first~~PFS, ~~line~~means ~~treatment~~the length of ~~checkpoint~~time ~~inhibitor~~after ~~naïve~~the ~~patients~~treatment ~~with~~that ~~advanced~~a ~~Merkel~~patient ~~cell~~lives ~~carcinoma~~without ~~when~~disease ~~compared to Keytruda alone~~progression.

Note: “FPI” means first patient in, “LPI” means last patient in, and “TLR” means top-line results. Progression Free Survival, or PFS, is defined as the time from randomization until first evidence of disease progression or death, and Overall Survival, or OS, is defined as the time between randomization to death.13

Accelerated Approval Phase 1b3 Trial infor ~~Metastatic Merkel Cell Carcinoma and Cutaneous Squamous Cell Carcinoma~~IFx-2.0

WeTuHURA ~~have~~has ~~completed~~entered ~~enrollment~~into ina Special Protocol Assessment agreement with the FDA for a ~~multicenter~~single Phase 1b3 ~~dose~~randomized placebo and ~~schedule~~injection ~~finding~~controlled trial for ~~our~~ IFx-~~Hu2~~2.0, its lead innate immune agonist, ~~candidate~~as adjunctive therapy to pembrolizumab (Keytruda®) in the first line treatment of patients with advanced or metastatic Merkel cell carcinoma, ~~(MMC)~~who orare ~~cutaneous~~checkpoint ~~Squamous~~inhibitor-naïve ~~cell~~utilizing ~~carcinoma~~the ~~(cSCC)~~FDA’s accelerated approval pathway. ~~This~~The ~~study~~Company ~~follows~~has aworked ~~two-stage~~the ~~design~~deputy ~~with~~director of the FDA’s Oncology Center of Excellence (OCE) on a ~~primary~~unique ~~goal~~trial todesign. ~~assess~~Consistent with the ~~safety~~FDA’s ~~and~~Project ~~feasibility~~Front ofRunner ~~repeated~~initiative, ~~dosing~~the ~~schemas~~FDA ofrecommended the Company consider investigating IFx-2.0. Inin the ~~first~~front ~~stage~~line ~~(exposure~~treatment ~~escalation)~~setting rather than in patients who are progressing on checkpoint inhibitor therapy, athe ~~3+3~~latter ~~trial~~of ~~design~~which was ~~utilized~~the toconduct ~~assess~~in ~~safety~~the ofphase ~~repeated~~1b ~~weekly~~trial. ~~intratumoral~~In ~~injections~~doing ~~using~~so, data from a ~~fixed~~primary ~~dose~~endpoint of ~~IFx-2.0~~objective ~~weekly~~response ~~for~~rate, 1or ORR, 2that oris 3of ~~weeks~~sufficient ~~(for~~magnitude ~~cohorts~~and 1,duration 2and orwith 3a ~~respectively).~~favorable ~~Following~~risk/benefit ~~safety~~profile ~~evaluation~~could ~~the~~be ~~protocol~~sufficient ~~was~~to ~~amended~~support accelerated approval. ORR is considered to ~~include~~be ana ~~expansion~~surrogate ~~stage~~likely to ~~increase~~predict clinical benefit, OCE requested that the ~~total~~Company ~~study~~also ~~sample~~consider ~~size~~incorporating toa ~~20.~~key Asecondary ~~total~~endpoint that is not a surrogate for but an endpoint recognized to be of 23true ~~patients~~clinical ~~were~~benefit ~~enrolled.~~such Asthat results from a key secondary endpoint of ~~June~~progression-free ~~2024~~survival, ~~follow-up~~or ~~data~~PFS, ~~was~~that ~~available~~is adequately powered with statistical assumptions in the statistical analysis plan provided to the FDA, if achieved without a detrimental effect on ~~all~~overall ~~evaluable~~survival, ~~patients~~or OS, could be adequate to support conversion to regular approval satisfying the requirement for a confirmatory trial.

~~The~~TuHURA ~~primary~~anticipates ~~objective~~that enrollment for the Phase 3 will take approximately 18 – 24 months, with topline data potentially being available 6 to 7 months following the last patient enrolled. If successful, this Phase 3 trial would form the basis of a Biologics License Application, or BLA. A Special Protocol Assessment agreement is a binding written agreement between the U.S. Food and Drug Administration (FDA) and a trial ~~was~~sponsor tothat ~~determine~~indicates the ~~safety~~FDA has agreed to the study’s design, ~~tolerability~~charters, and ~~optimal~~statistical ~~dose~~analysis plan and ~~schedule~~if the study endpoints are met within the context of ~~IFx-2~~the SPA Agreement such results would be adequate to support accelerated and regular approval.0 ~~when~~A ~~administered~~Special ~~intratumoral~~Protocol inAssessment upagreement does not increase the likelihood of marketing approval for the product and may not lead to ~~three~~a ~~lesions~~faster ~~injected~~or ~~across~~less ~~three~~costly ~~different~~development, ~~administration~~review, ~~schedules~~or approval process. ~~Safety~~The ~~was~~study ~~evaluated~~population, dose, schedule, and study design for upthe trial are based on the response rates observed in the Company’s Phase 1b trial in checkpoint inhibitor naïve patients with advanced Merkel cell carcinoma who exhibited primary resistance to 28anti ~~days~~PD(L)-1 ~~following~~checkpoint inhibitors such as Keytruda® The clinical study design for the Phase 3 registration trial is presented below. Based on correspondence with the FDA, patients with advanced Merkel cell carcinoma represent a patient population with an unmet medical need. TuHURA’s study, is designed to determine if IFx-2.0 ~~administration.~~can ~~Secondary~~increase ~~objectives~~the ~~include~~objective ~~tumor~~response ~~shrinkage~~rate ~~(injected~~when ~~and~~used ~~non-injected~~as ~~lesions)~~adjunctive ~~and~~therapy to Keytruda in first line treatment of checkpoint inhibitor naïve patients with advanced Merkel cell carcinoma when compared to Keytruda alone.

16Note: “FPI” means first patient in, “LPI” means last patient in, and “TLR” means top-line results. Progression Free Survival, or PFS, is defined as the time from randomization until first evidence of disease progression or death, and Overall Survival, or OS, is defined as the time between randomization to death.

correlative immune response analysis (transcriptomic, proteomic, humoral and cellular), pre-and post-IFx-2.0 administration to guide the choice of dose and schedule for our Phase 3 registration directed trial.14

~~Twenty-three~~Phase ~~(23)~~1b ~~patients~~Trial ~~were~~in ~~enrolled:~~Metastatic Merkel ~~cell~~Cell ~~carcinoma~~Carcinoma ~~(13), cSCC (10). Among the thirteen (13) patients with Merkel cell carcinoma, twelve (12) completed treatment~~ and ~~the~~Cutaneous ~~protocol~~Squamous ~~directed~~Cell 28 day safety evaluation follow up period; One (1) patient experienced a serious adverse event, or SAE, deemed possibly related to study drug. This patient experienced a Grade 3, or G3, adverse event, which is defined as an adverse event that is a severe or medically significant event that is not immediately life threatening, which in the case of this patient was a G3 autoimmune hepatitis that resolved with steroid treatment, and such patent has been recently treated with checkpoint inhibitors prior to study enrollment. Among the ten (10) patients with cSCC one (1) patient experienced an SAE unrelated to study drug and did not complete treatment nor the 28 day safety evaluation follow up period. All patients had received prior anti-PD(L)1 based treatment with disease progression being the reason for CPI discontinuation in all patients but one. Intra- tumoral (IT) IFx-2.0 was well tolerated at all dose schedules evaluated. As to efficacy, in the 21 patients that completed the study, best overall disease response to trial therapy was PR in 1 patient (including both injected and non-injected tumor sites), SD in 4, and PD in 16. The response assessment limited to the injected site(s) only was PR in 2 patients, SD in 8, and PD in 9. Two additional patients were not evaluable at the injected site(s) due to clinically challenging to measure dermal lesions that were not radiographically measurable. The study achieved the primary safety endpoint of the study demonstrating no grade 3 or greater toxicity in any of the 3 dose levels examined, and as a result, a recommended phase 2 dose was determined. The study also achieved its secondary endpoint of efficacy analysis demonstrating a disease control rate of 48% among injected lesions within the first 28 days post injection, and, as described below, a post-protocol efficacy analysis demonstrated an overall objective response rate of 64% (7 of 11 patients with Merkel cell carcinoma) after re-challenge with immune checkpoint inhibitors.Carcinoma

~~After~~We ~~protocol~~have ~~specified~~completed ITenrollment ~~therapy,~~in ~~eleven~~a ~~(11)~~multicenter ~~Merkel~~Phase ~~cell~~1b ~~carcinoma~~dose ~~patients~~ and ~~six~~schedule ~~(6)~~finding ~~cSCC~~trial ~~pts~~for ~~were~~our ~~treated with anti~~IFx-~~PD(L)1~~Hu2.0 ~~based~~innate ~~therapy~~immune asagonist ~~the~~candidate ~~immediate~~in ~~post-protocol~~patients ~~treatment.~~with ~~Five~~advanced ~~(5)~~Merkel ofcell ~~nine~~carcinoma (9MMC) ~~(56%)~~or ~~evaluable~~cutaneous ~~Merkel~~Squamous cell carcinoma ~~patients and one~~ (1cSCC). ofThis ~~(6)~~study ~~(17%)~~follows ~~cSCC~~a ~~patients~~two-stage ~~experienced~~design anwith ~~objective~~a ~~response~~primary goal to ~~this~~assess ~~ICI~~the ~~rechallenge,~~safety ~~with~~and ~~duration~~feasibility of ~~response~~repeated ~~ongoing~~dosing inschemas ~~four~~of ~~(4)~~IFx-2.0. ~~patients~~In the first stage (~~6+,~~exposure ~~19+~~escalation), ~~21+,~~a 233+3 ~~months)~~trial ~~and~~design ~~the~~was ~~two~~utilized ~~other~~to ~~responses~~assess ~~lasting~~safety 23of ~~and~~repeated 33weekly ~~months~~intratumoral injections using a fixed dose of IFx-2.0 ~~The~~weekly ~~two~~for (1, 2) ~~remaining~~or ~~Merkel~~3 ~~cell~~weeks ~~carcinoma~~(for ~~patients~~cohorts ~~were~~1, ~~not~~2 ~~evaluable~~or ~~for~~3 ~~response~~respectively). ~~from~~Following IOsafety ~~rechallenge~~evaluation ~~due~~the protocol was amended to ~~radiation~~include ~~administered~~an expansion stage to increase the ~~only~~total ~~measurable~~study ~~disease~~sample ~~site(s),~~size ~~but~~to ~~both~~20. ~~remain~~A ~~progression~~total ~~free~~of at23 ~~11+~~patients ~~and~~were ~~13+~~enrolled. ~~months~~As ~~with~~of ~~previously~~June ~~progressive~~2024, ~~disease~~follow-up data was available on all evaluable patients.

OfThe ~~the~~primary ~~twelve~~objective ~~(12)~~of ~~patients~~the ~~with~~trial ~~advanced~~was ~~Merkel~~to ~~cell~~determine ~~carcinoma~~the ~~who~~safety, ~~completed~~tolerability, ~~treatment~~ and ~~protocol-directed~~optimal ~~28-day~~dose ~~safety~~and ~~evaluation~~schedule ~~follow~~of IFx-up2.0 ~~period,~~when ~~seven~~administered ~~patients~~intratumoral ~~exhibited~~in ~~primary~~up ~~resistance~~ to ~~first~~three ~~line~~lesions ~~treatment~~injected ~~with~~across athree ~~checkpoint~~different ~~inhibitor~~administration ~~who~~schedules. ~~did~~Safety ~~not~~was ~~receive~~evaluated ~~subsequent~~for ~~therapies~~up ~~prior~~ to ~~receiving~~28 days following IFx-2.0 administration. ~~Five~~Secondary ofobjectives ~~seven~~include ~~patients~~tumor ~~received~~shrinkage ~~single~~(injected ~~agent~~and ~~anti~~non-~~PD(L~~injected lesions)-1 asand ~~initial~~correlative ~~therapy~~immune ~~while~~response ~~two~~analysis of(transcriptomic, ~~seven~~proteomic, ~~patients~~humoral ~~received~~and ~~multiple~~cellular), ~~CPIs as initial therapy including anti~~pre-~~PD-1,~~and ~~followed by anti~~post-PDIFx-~~1/anti-CTLA-4 therapy~~2.0 ~~All~~administration 7to ~~patients~~guide ~~exhibited~~the ~~primary~~choice ~~resistance~~of todose ~~checkpoint~~and ~~inhibitor~~schedule ~~therapy~~for ~~progressing~~our onPhase ~~average~~ 3.3 ~~months~~registration ~~while~~directed ~~receiving CPI therapy~~trial. ~~These 7 patients are graphically presented below:~~

~~This~~Twenty-three ~~data~~(23) ~~demonstrating~~patients were enrolled: Merkel cell carcinoma (13), cSCC (10). Among the ~~potential~~thirteen ~~for~~(13) ~~IFx-2~~patients with Merkel cell carcinoma, twelve (12) completed treatment and the protocol directed 28 day safety evaluation follow up period; One (1) patient experienced a serious adverse event, or SAE, deemed possibly related to study drug.0 This patient experienced a Grade 3, or G3, adverse event, which is defined as an adverse event that is a severe or medically significant event that is not immediately life threatening, which in the case of this patient was a G3 autoimmune hepatitis that resolved with steroid treatment, and such patent has been recently treated with checkpoint inhibitors prior to ~~overcome~~study ~~primary~~enrollment. ~~resistance~~Among the ten (10) patients with cSCC one (1) patient experienced an SAE unrelated to study drug and did not complete treatment nor the 28 day safety evaluation follow up period. All patients had received prior anti-PD(L)-1 ~~therapy~~based ~~and~~treatment ~~formed~~with ~~the~~disease ~~clinical~~progression ~~rationale~~being the reason for ~~examining~~CPI discontinuation in all patients but one. Intra- tumoral (IT) IFx-2.0 aswas ~~adjunctive~~well tolerated at all dose schedules evaluated. As to efficacy, in the 21 patients that completed the study, best overall disease response to trial therapy ~~with~~was ~~Keytruda®~~PR in 1 patient (~~anti~~including both injected and non-injected tumor sites), SD in 4, and PD-1 in 16. The response assessment limited to the injected site(s) only was PR in ~~first~~2 ~~line~~patients, ~~therapy~~SD in 8, and PD in 9. Two additional patients were not evaluable at the injected site(s) due to clinically challenging to measure dermal lesions that were not radiographically measurable. The study achieved the primary safety endpoint of the study demonstrating no grade 3 or greater toxicity in any of the 3 dose levels examined, and as a result, a recommended phase 2 dose was determined. The study also achieved its secondary endpoint of efficacy analysis demonstrating a disease control rate of 48% among injected lesions within the first 28 days post injection, and, as described below, a post-protocol efficacy analysis demonstrated an overall objective response rate of 64% (7 of 11 patients with Merkel cell carcinoma) after re-challenge with immune checkpoint inhibitors.

After protocol specified IT therapy, eleven (11) Merkel cell carcinoma patients and six (6) cSCC pts were treated with anti-PD(L)1 based therapy as the immediate post-protocol treatment. Five (5) of nine (9) (56%) evaluable Merkel cell carcinoma patients and one (1) of (6) (17%) cSCC patients experienced an objective response to this ICI rechallenge, with duration of response ongoing in four (4) patients (6+, 19+, 21+, 23+ months) and the two other responses lasting 23 and 33 months. The two (2) remaining Merkel cell carcinoma patients were not evaluable for response from IO rechallenge due to radiation administered to the only measurable disease site(s), but both remain progression free at 11+ and 13+ months with previously progressive disease.

~~inhibitor~~Of ~~naïve~~the twelve (12) patients with advanced ~~or metastatic~~ Merkel cell carcinoma. ~~Unlike~~who ~~the~~completed ~~phase~~treatment 1band ~~where~~protocol-directed 28-day safety evaluation follow-up period, seven patients exhibited primary resistance to first line treatment with a checkpoint inhibitor who did not receive subsequent therapies prior to receiving IFx-2.0. ~~was~~Five ~~administered~~of ~~after~~seven patients ~~progressing~~received onsingle agent anti-PD(L)-1 as initial therapy while two of seven patients received multiple CPIs as initial therapy including anti-PD-1, wefollowed ~~believe~~by ~~IFx~~anti-2PD-1/anti-CTLA-4 therapy.0 ~~could~~All ~~potentially~~7 ~~provide~~patients aexhibited ~~higher~~primary ~~response~~resistance ~~rate~~ to ~~Keytruda®~~checkpoint ~~when~~inhibitor ~~administered~~therapy ~~prior~~progressing toon ~~patients~~average ~~progressing~~3.3 ~~failing~~months ~~Keytruda®~~while receiving CPI therapy. These 7 patients are graphically presented below:

The remaining seven (7) patients received multiple checkpoint inhibitor therapy including anti- CTLA-4/anti-PD-1 therapy and/or investigational agent(s) and or chemotherapy as 2nd or 3rd line therapy prior to treatment with IFx-2.0. This patient population is not representative of patients to be enrolled in the phase 3 trial.15

~~Importantly,~~This data demonstrating the potential for IFx-2.0 isto ~~not~~overcome anprimary ~~intratumoral~~resistance ~~therapy~~to ~~like oncolytic viral therapies whose~~ anti-~~tumor~~PD(L)-1 ~~activity~~therapy isand ~~limited~~formed tothe ~~accessible,~~clinical ~~injected~~rationale ~~lesions~~for inexamining ~~limited stages of cancer. In contrast,~~ IFx-2.0’s ~~mechanism~~as ofadjunctive ~~action~~therapy iswith toKeytruda® ~~prime~~(anti-PD-1) ~~and~~in ~~activate~~first anline ~~innate~~therapy ~~immune~~among ~~response~~checkpoint ininhibitor ~~injected~~naïve ~~lesions~~patients ~~leading~~with toadvanced aor ~~systemic~~metastatic ~~anti-tumor~~Merkel ~~response~~cell carcinoma. ~~The~~Unlike ~~Company~~the ~~chose~~phase to1b ~~examine~~where IFx-2.0 inwas ~~cutaneous~~administered ~~malignancies~~after ~~because~~patients ~~human~~progressing ~~skin~~on ~~has~~anti-PD(L)-1 atherapy, ~~high~~we ~~density~~believe ~~of DCs which are very efficient in presenting foreign antigens to immune cells. Local injection of~~ IFx-2.0 ~~into~~could ~~cutaneous~~potentially ~~lesion(s)~~provide ~~has~~a ~~resulted~~higher inresponse ~~immune~~rate ~~cell infiltration, and in the context of MHCI and MHCII, tumor neoepitope presentation~~ to ~~naïve~~Keytruda® Bwhen ~~and~~administered Tprior ~~cells followed by activation of tumor specific B and T cells. The immune response has not been localized~~ to just injected lesions but rather systemic as demonstrated by production of Emm55 (pDNA encoded bacterial protein expressed on the surface of the tumor cell) and tumor specific IgM and IgG antibodies in the plasma of patients ~~post~~progressing ~~IFx-2.0~~failing ~~administration~~Keytruda®.

~~Patients~~The ~~Merkel~~remaining ~~cell~~seven ~~carcinoma-03~~(7) ~~and~~patients ~~Merkel~~received ~~cell~~multiple ~~carcinoma-05~~checkpoint ~~below~~inhibitor ~~demonstrate~~therapy ~~the~~including ~~abscopal~~anti- ~~effect of adjunctive IFx~~CTLA-~~2.0~~4/anti-PD-1 therapy, ~~These~~and/or ~~patients~~investigational ~~exhibited~~agent(s) ~~primary~~and ~~resistance~~or tochemotherapy ~~checkpoint~~as ~~inhibitor~~2nd ~~therapy,~~or ~~and~~3rd ~~subsequently~~line ~~achieved~~therapy ~~durable~~prior ~~anti-~~to ~~tumor~~treatment ~~responses~~with ~~following~~ IFx-2.0. ~~and~~This ~~rechallenge~~patient ~~with~~population ~~checkpoint~~is ~~inhibitor~~not ~~therapy~~representative of patients to be enrolled in the phase 3 trial.

~~Case~~Importantly, ~~study~~IFx-2.0 ~~(MCC~~is not an intratumoral therapy like oncolytic viral therapies whose anti-~~005~~tumor activity is limited to accessible, injected lesions in limited stages of cancer. In contrast, IFx-2.0’s mechanism of action is to prime and activate an innate immune response in injected lesions leading to a systemic anti-tumor response. The Company chose to examine IFx-2.0 in cutaneous malignancies because human skin has a high density of DCs which are very efficient in presenting foreign antigens to immune cells. Local injection of IFx-2.0 into cutaneous lesion(s) has resulted in immune cell infiltration, and in the context of MHCI and MHCII, tumor neoepitope presentation to naïve B and T cells followed by activation of tumor specific B and T cells. The immune response has not been localized to just injected lesions but rather systemic as demonstrated by production of Emm55 (pDNA encoded bacterial protein expressed on the surface of the tumor cell) and tumor specific IgM and IgG antibodies in the plasma of patients post IFx-2.0 administration.

~~Patient~~Patients ~~was~~Merkel ~~treated~~cell ~~for multifocal in~~carcinoma-~~transit~~03 ~~recurrence~~and of Merkel cell carcinoma-05 inbelow ~~left~~demonstrate ~~leg~~the ~~with~~abscopal ~~avelumab~~effect ~~x 6 doses (12 weeks) with continued rapid clinical progression as well as development~~ of ~~liver~~adjunctive ~~metastatic disease on this therapy. Subsequently the patient was enrolled on~~ IFx-2.0 ~~protocol~~therapy, ~~and~~These ~~received~~patients 3exhibited ~~weekly~~primary ~~injections~~resistance ofto ~~IFx-2.0~~checkpoint ~~without~~inhibitor ~~complication~~therapy, ~~but~~and ~~continued~~subsequently ~~clinical~~achieved ~~progression~~durable ~~(additional in~~anti-~~transit~~ ~~sites).~~tumor ~~Disease~~responses ~~status~~following ~~at time of last injection shown on the left. Following completion of~~ IFx-2.0 ~~protocol~~and ~~therapy,~~rechallenge ~~subject was rechallenged~~ with ~~pembrolizumab, a~~ checkpoint inhibitor, ~~and experienced an obvious clinical response initially apparent approximately 3-4 weeks into~~ therapy. Clinical response at 3 months (middle photo below) and 6 months (right photo below) are shown in the photos below. Concordant (near-complete) radiographic response of liver metastases has also been observed and response has been maintained to date (19 months)

18Case study (MCC-005)

~~Case~~Patient ~~study~~was treated for multifocal in-transit recurrence of Merkel cell carcinoma in left leg with avelumab x 6 doses (~~MCC~~12 weeks) with continued rapid clinical progression as well as development of liver metastatic disease on this therapy. Subsequently the patient was enrolled on IFx-~~002~~2.0 protocol and received 3 weekly injections of IFx-2.0 without complication but continued clinical progression (additional in-transit sites). Disease status at time of last injection shown on the left. Following completion of IFx-2.0

Subject was treated with adjuvant pembrolizumab for stage II Merkel cell carcinoma on the STAMP trial but developed (nodal) progression after receiving 6 doses. Subject underwent salvage surgery/XRT but developed widespread metastatic disease ~3 months later (nodal, dermal, and intramuscular sites of disease). Subject was then enrolled on IFx-2.0 protocol and received 2 weekly injections to 3 nodal/dermal metastatic sites but experienced continued rapid progression (both injected and non-injected sites) including bulky diffuse adenopathy and numerous widespread subcutaneous/dermal nodules. Representative imaging from the time of completion of protocol therapy is shown on left in photo below including several subcutaneous sites (as noted by the arrows) and bulky retroperitoneal (“RP”) conglomerate lymph node (“LN”) metastases. Post-protocol, subject was started on checkpoint inhibitor rechallenge with avelumab and experienced deep partial response that has been maintained to date (33 months). Representative images from post-checkpoint rechallenge restaging shown below on right (complete remission of subcutaneous nodules, partial response in retroperitoneal sites).16

~~IFx~~protocol therapy, subject was rechallenged with pembrolizumab, a checkpoint inhibitor, and experienced an obvious clinical response initially apparent approximately 3-24 weeks into therapy.0 ~~Planned~~Clinical ~~Basket~~response ~~Trial~~at 3 months (middle photo below) and 6 months (right photo below) are shown in the photos below. Concordant (near-complete) radiographic response of liver metastases has also been observed and response has been maintained to date (19 months)

WeCase ~~are~~study planning a Phase 1b/2a trial referred to as a “basket” trial, which is a type of clinical trial that tests a new product candidate in patients who have different types of cancer but a common biologic reason for resistance to checkpoint inhibitors. The Phase 1b stage of the trial will examine the feasibility and safety of Keytruda® and adjunctive IFx-2.0 where IFx-2.0 is administered via interventional radiology into lesions in the liver, retroperitoneal or lungs of patients who have advanced and metastatic Merkel cell carcinoma who are checkpoint inhibitor naïve. Following the Phase 1b component, the planned Phase 2a stage will extend enrollment to patients with any cancer type (soMCC-~~called “histology agnostic”~~002) who exhibit a high incidence of primary resistance to checkpoint inhibitors in cancers such as advanced triple negative breast cancer or ovarian cancer. Since the biology of primary resistance to checkpoint inhibitors is similar across tumor types. We believe that IFx-2.0’s mechanism of action should be applicable in overcoming primary resistance to checkpoint inhibitors irrespective of tumor type. We currently anticipate initiating this study in the second half of 2025. If successful, this trial could have the ability to expand the utility of IFx-2.0 beyond advanced Merkel cell carcinoma.

~~Phase~~Subject 1was ~~Trial~~treated inwith ~~Advanced~~adjuvant pembrolizumab for stage II Merkel cell carcinoma on the STAMP trial but developed (nodal) progression after receiving 6 doses. Subject underwent salvage surgery/XRT but developed widespread metastatic disease ~3 months later (nodal, dermal, and intramuscular sites of disease). Subject was then enrolled on IFx-2.0 protocol and received 2 weekly injections to 3 nodal/dermal metastatic sites but experienced continued rapid progression (~~Stage~~both ~~IIIC~~injected and non-IVinjected sites) ~~Cutaneous~~including ~~Melanoma~~bulky diffuse adenopathy and numerous widespread subcutaneous/dermal nodules. Representative imaging from the time of completion of protocol therapy is shown on left in photo below including several subcutaneous sites (as noted by the arrows) and bulky retroperitoneal (“RP”) conglomerate lymph node (“LN”) metastases. Post-protocol, subject was started on checkpoint inhibitor rechallenge with avelumab and experienced deep partial response that has been maintained to date (33 months). Representative images from post-checkpoint rechallenge restaging shown below on right (complete remission of subcutaneous nodules, partial response in retroperitoneal sites).

~~We also conducted a Phase 1 trial at the Moffitt Cancer Center in seven (7) patients with advanced (Stage IIIc/IV) cutaneous melanoma, six (6) of whom were eligible for evaluation post-~~IFx-2.0 ~~therapy.~~Phase ~~The~~1b/2a ~~primary~~Study ~~objective~~ of ~~the trial was to determine the safety and tolerability of~~ IFx-2Hu2.0 ~~when~~as ~~administered~~an ~~intratumorally~~Adjunctive ~~with~~Therapy up to ~~three~~Keytruda® lesions injected at a single time point. Safety was evaluated for 28 days following IFx-2.0 administration. Secondary objectives included tumor shrinkage, transcriptomic, proteomic, humoral, and cellular immune response pre and post IFx-2.0 administration. IFx-2.0 was well tolerated. Mild pain and swelling among injected lesions were most common reported side effect < Grade 2 in severity. Four (4pembrolizumab) ofin ~~the~~First ~~six~~Line ~~(6)~~Treatment ~~patients~~for ~~exhibited~~Metastatic ~~primary~~Merkel ~~resistance~~Cell ~~to,~~Carcinoma ~~and failed checkpoint inhibitor trials prior to IFx-2.0. Following IFx-2.0 administration three (3)~~ of ~~four~~Unknown ~~(4)~~Primary ~~patients~~Origin ~~subsequently responded to rechallenge with checkpoint inhibitor~~(sMCCUP). One patient achieved stable disease (“SD”) and 2 experienced a partial response (“PR”). As of the last follow up responses are ongoing at 1337, 608, 313 days. Two (2) patients (SD and PR) underwent surgical resections following checkpoint inhibitor therapy. Immunologic profiling data (pre-and post-IFx-2.0) demonstrated

1917

In May 2025, we initiated a ~~robust~~Phase ~~systemic~~1b/2a ~~immune~~trial ~~response~~designed ~~with~~to ~~(i)~~evaluate ~~activation~~the ofsafety ~~tumor~~and ~~specific~~feasibility Bof ~~cells~~IFx-Hu2.0 in combination with ~~tumor~~Keytruda® ~~specific~~when ~~IgM/IgG~~administered ~~antibody~~via ~~production~~Interventional ~~recognizing~~Radiology ~~hundreds~~(IR) ofin ~~previously~~patients ~~unrecognized~~with ~~melanoma~~deep- ~~tumor~~seated ~~neoepitopes~~tumors ~~and~~without ~~(ii)~~associated ~~gene~~cutaneous ~~signature~~tumors. Unlike our Phase 3 study, ~~consistent~~these are patients without skin lesions who present with ~~innate~~metastatic ~~response~~deep-seated tumors in ~~injected~~the ~~lesions~~liver, alungs ~~gene~~or ~~signature~~retropertitoneum ~~consistent~~(abdomen). Up to 30% of patients with ~~adaptive~~MCC ~~response~~present inwithout ~~un-injected~~primary lesions asin ~~well~~the asskin, ~~increased~~so ~~expression~~this ~~(up~~trial towill 11not ~~fold)~~only ofprovide ~~genes~~safety, ~~known~~feasibility, toand beefficacy ~~predictive~~data, ofbut ~~response~~may toalso ~~checkpoint~~expand ~~inhibitors~~the ~~following~~potential ~~IFx-2.0~~number ~~therapy~~of ~~but~~addressable ~~prior~~patients towho ~~checkpoint~~may ~~inhibitor~~benefit ~~rechallenge~~from IFx-Hu2.0,

~~Planned~~If ~~IND~~feasibility and safety is demonstrated for IFx-~~Enabling~~Hu2.0 ~~Studies~~and Keytruda® when radiologically administered to deep-seated tumors, we plan to extend enrollment to a variety of non-MCC cancers that are known not to respond or respond poorly to CPIs. This is termed a “Basket Trial.” Since the underlying biology of why tumors don’t respond to CPIs is for the most part the same, then we believe that the mechanism of how IFx-3Hu2.0 ~~Next~~overcomes ~~Generation~~that ~~mRNA~~resistance ~~Innate~~to ~~Immune~~CPIs ~~Agonist~~should be independent of the type of cancer treated. We have previously demonstrated that IFx-Hu2.0 can overcome CPI resistance in melanoma, squamous cell, and Merkel cell carcinoma, three unrelated types of skin cancers. If successful, this trial could expand the potential benefit of IFx-Hu2.0 to a wide variety of cancers.

WePhase ~~are~~1 ~~also~~Trial ~~developing~~in a second innate immune agonist candidate that incorporates our codon optimized mRNA into a lipid nanoparticle coupled to an antibody f targeting the CD22 receptor. CD22 is overexpressed on a variety of B cell cancers including aggressive lymphomas like diffuse large B cell lymphoma or DLBCL. Unlike IFx-2.0Advanced, ~~which utilizes a proprietary pDNA for intratumoral administration, we are designing IFx-3.0 for intravenous~~ (orStage ~~autologous whole cell~~IIIC-IV) ~~administration.~~Cutaneous This is intended to allow extension of our innate immune agonist candidates to tumors not accessible by injection, like blood-related cancers, and could result in eliciting a more potent immune response without the need for checkpoint inhibitors. We plan to test various constructs in vitrobefore advancing to humanized immune competent murine models of aggressive lymphoma planned for 2026.Melanoma

~~Market~~We ~~Opportunity~~also conducted a Phase 1 trial at the Moffitt Cancer Center in seven (7) patients with advanced (Stage IIIc/IV) cutaneous melanoma, six (6) of whom were eligible for evaluation post-IFx-2.0 therapy. The primary objective of the trial was to determine the safety and tolerability of IFx-2.0 when administered intratumorally with up to three lesions injected at a single time point. Safety was evaluated for 28 days following IFx-2.0 administration. Secondary objectives included tumor shrinkage, transcriptomic, proteomic, humoral, and cellular immune response pre and post IFx-2.0 administration. IFx-2.0 was well tolerated. Mild pain and swelling among injected lesions were most common reported side effect < Grade 2 in severity. Four (4) of the six (6) patients exhibited primary resistance to, and failed checkpoint inhibitor trials prior to IFx-2.0. Following IFx-2.0 administration three (3) of four (4) patients subsequently responded to rechallenge with checkpoint inhibitor(s). One patient achieved stable disease (“SD”) and 2 experienced a partial response (“PR”). As of the last follow up responses are ongoing at 1337, 608, 313 days. Two (2) patients (SD and PR) underwent surgical resections following checkpoint inhibitor therapy. Immunologic profiling data (pre-and post-IFx-2.0) demonstrated a robust systemic immune response with (i) activation of tumor specific B cells with tumor specific IgM/IgG antibody production recognizing hundreds of previously unrecognized melanoma tumor neoepitopes and (ii) gene signature, consistent with innate response in injected lesions, a gene signature consistent with adaptive response in un-injected lesions as well as increased expression (up to 11 fold) of genes known to be predictive of response to checkpoint inhibitors following IFx-2.0 therapy but prior to checkpoint inhibitor rechallenge.

~~Checkpoint~~TuHURA’s inhibitors dominate oncology sales and represent the most successful oncology drug commercial launches in oncology drug development. Since their commercial launch in 2014, sales of checkpoint inhibitors have grown at an impressive compounded annual growth rate with $29.9 billion in sales in 2020 reaching $37 billion in 2022, according to Precedence Research. By 2030 the market is expected to grow to over $148 billion in world wide sales, according to Precedence Research. We believe that our technology platforms have the potential to address both primary and acquired resistance, the two major limitations to checkpoint inhibitor and cellular therapies and as such represents a large market opportunity. While upward of 15% to 60% of patients will respond to first time treatment with checkpoint inhibitors, 40% to 85% will not. It is this population of patients with primary resistance to checkpoint inhibitors that we believe represents the initial market opportunity for IFxTBS-~~2.0.~~2025 ~~The~~VISTA ~~biologic~~Inhibiting ~~basis~~Antibody ~~for~~Clinical ~~primary~~Development resistance to checkpoint inhibitors is similar across various tumor types, predominately the lack of tumor infiltration with activated tumor specific T cells. We believe that an agent that can overcome primary resistance to checkpoint inhibitors in one tumor type should overcome resistance in others, if not all, tumor types that exhibit primary resistance to them. Our initial strategy is to demonstrate the ability of IFx-2.0 to overcome primary resistance in the 50% of patients with advanced Merkel cell carcinoma receiving front line therapy with Keytruda® (pembrolizumab), the current standard of care, allowing more patients to achieve an anti-tumor response than with Keytruda® alone.Program

20TBS-2025 (f/k/a KVA-12123), a VISTA inhibiting antibody, was initially investigated by Kineta in a Phase 1 trial either as monotherapy (n=24) or in combination with pembrolizumab (n=16) among patients with advanced, therapy refractory cancers, including, breast, lung, colorectal and ovarian cancer. The Phase 1 was an open-label, multi-center, dose-escalation trial, utilizing an accelerated Bayesian Optimal Interval (BOIN) dosing design designed to evaluate the safety, tolerability, pharmacokinetics (“PK”), immunogenicity, and tumor response of TBS-2025. TBS-2025 demonstrated a favorable safety profile at the highest dose level of 1,000 mg administered every two weeks. In this trial among patients with treatment-refractory solid tumors, no significant anti-tumor activity was observed among the 40 patients treated in the trial.

According to DelveInsight, it is estimated by 2027 there will be approximately 4,245 patients in the US and 7,049 patients in the 7 major market European countries, including the UK, growing to a total of 15, 262 patients by 2034 in these geographic territories. The standard of care for patients with the advanced or metastatic Merkel cell carcinoma is therapy with a checkpoint inhibitor like Keytruda® (pembrolizumab). If the results of our above-described “basket” trial are successful, the results from that clinical trial could allow IFx-2.0 to be used in a variety of tumor types other than Merkel cell carcinoma that exhibit primary resistance to checkpoint inhibitors, which could expand the market application of IFx-2.0 significantly.18

~~Among~~An ~~patients~~overview who initially respond to treatment with checkpoint inhibitors, almost all patients will ultimately develop acquired resistance where checkpoint inhibitors no longer work and the tumor recurs and/or progresses. While the cause of ~~acquired resistance is multifactorial, a major contributor is tumor associated MDSC-induced immunosuppression of~~ the ~~tumor~~study ~~microenvironment~~results ~~leading to T cell exhaustion and failure of checkpoint inhibitors or cellular therapies. Our initial strategy~~ is toshown investigate our MDSC-targeted bi-functional ADCs in tumor types that initially responded to and subsequently progressed on or following checkpoint inhibitor therapy. If successful in overcoming acquired resistance to checkpoint inhibitors while potentially limiting their toxicity to non-tumor tissue, such an application would be expected to also represent a significant market opportunity.below:

~~Our~~Clinical ~~Manufacturing~~collaboration ~~Strategy~~with Merck

WeKineta ~~are~~previously ~~working~~entered ~~with~~into a ~~number~~clinical oftrial ~~contract~~collaboration ~~development~~ and ~~manufacturing~~supply ~~contract~~agreement ~~organizations~~with Merck (~~CDMOs)~~known ~~to produce product candidate components, clinical trial material~~ as ~~well~~MSD asoutside ~~cGMP~~the ~~drug~~U.S. ~~substance~~ and ~~drug~~Canada) ~~product~~that ~~and~~we ~~necessary~~have ~~validated~~assumed ~~analytical~~as ~~tests~~a ~~required~~part ~~for~~of ~~registration~~the ~~trials~~Kineta ~~and~~acquisition. ~~commercial~~Under ~~material.~~this Wecollaboration, ~~may~~we ~~enter~~are ~~into~~evaluating ~~development~~the ~~collaborations~~safety, ~~with~~tolerability, ~~large~~PK. ~~pharmaceutical~~and oranti-tumor ~~biotech~~activity ~~companies~~of ~~where~~TBS-2025 wealone ~~would~~and ~~look~~in tocombination ~~our~~with ~~development~~KEYTRUDA® ~~partner~~(pembrolizumab), toMerck’s ~~assume~~anti-PD-1 ~~responsibility~~therapy, ~~for~~in ~~product~~patients ~~manufacturing~~with ~~and~~advanced ~~supply~~solid tumors.

WePharmacokinetics utilize CDMOs to make the emm55-pDNA, drug substance, and drug product. The emm55-pDNA utilizes a cationic polymer as a transfectant agent excipient and is mixed with dextrose at the site of administration. As is common practice for drug products requiring mixing at site of administration, the FDA requires standard mixing studies to be published in the pharmacy manual to guide correct process for constitution of the drug product prior to administration. In addition, the FDA requires potency assay(sPK) and ~~stability~~Receptor ~~assays~~Occupancy among other standard processes to allow specifications from batch to batch to meet pre-specified agreed to assay parameters allowing product release for clinical trials. We, through our third party CDMOs, are in the process of completing development, qualification and validation of all such assays necessary for the production and release of drug product which meets cGMP requirements for use in our Phase 3 registration directed trial.(RO)

~~Intellectual~~Pharmacokinetics, ~~Property~~or PK, is the study of how the body interacts with TBS-2025 for the entire duration of exposure after administration. TBS-2025 exhibited a greater than dose-proportional pharmacokinetic profile in drug exposure across all doses, consistent with target-mediated drug disposition at lower doses and target saturation at higher doses.

~~Intellectual~~To ~~property~~guide ~~is of vital importance in our field and in biotechnology generally. We seek to protect and enhance proprietary technology, inventions, and improvements that are commercially important to~~ the ~~development~~recommended ofPhase ~~our~~2 ~~business~~dose ~~by seeking~~decision, ~~maintaining,~~Kineta ~~and defending patent rights, whether~~ developed ~~internally~~a orproprietary ~~licensed~~assay ~~from third parties. We also seek~~ to ~~rely~~evaluate on regulatory protection afforded through inclusion in expedited development and review, data exclusivity, market exclusivity and patent term extensions where available. We have sought patent protection in the United States and internationally related to our IFx-Hu2.0 platform technology as well as our IFx-Hu3.0 technology, and we license from third parties the patents and patent applications relating to our tumor microenviroment modulators technology.VISTA

Wereceptor ~~expect~~occupancy to(“RO”) ~~file additional patent applications in support of current and new clinical candidates, as well as new platform and core technologies. Our commercial success will depend in part~~ on ~~obtaining~~immune ~~and~~cells ~~maintaining~~from ~~patent~~patients ~~protection~~treated ~~and~~with ~~trade secret protection of our current and future product candidates and the methods used to develop and manufacture them, as well as successfully defending any such patents against third~~TBS-~~party challenges and operating without infringing on the proprietary rights of others~~2025. ~~Our~~This ~~ability~~is toan ~~stop~~important third parties from making, using, selling, offering to sell or importing our product candidates will depend on the extent to which we have rights under valid and enforceable patents or trade secrets that cover these activities.metric

~~The~~for ~~terms~~evaluating ofhow ~~individual~~well ~~patents~~TBS-2025 ~~depend~~is ~~upon~~blocking the ~~statutory~~VISTA ~~term of the patents in the countries in which they are issued~~target. ~~In most countries in which we file, including the United States, the patent term is 20 years from the earliest filing of a non~~TBS-~~provisional~~2025 ~~patent~~achieved ~~application. In the United States,~~ a ~~patent~~greater ~~term~~than ~~may~~90% beVISTA ~~lengthened~~RO byat ~~patent term adjustment (“PTA”), which compensates a patentee for administrative delays by~~ the ~~USPTO~~30 inmg ~~examining~~dose and ~~granting~~ a ~~patent.~~complete ~~Conversely,~~saturation ~~a patent term may be shortened if a patent is terminally disclaimed over an earlier filed patent. In the United States, the term~~ of ~~a patent that covers an FDA-approved drug may also be eligible for extension, which permits patent term restoration to account for~~ the ~~patent~~target ~~term~~between ~~lost during the FDA regulatory review process. The Hatch~~two-~~Waxman~~dosing ~~Act~~intervals ~~permits~~was aachieved ~~patent~~at ~~term~~1000 ~~extension of up to five years beyond the expiration of the patent~~mg. ~~The~~Based ~~length~~on ofthese ~~the patent term extension is related to the length of time the subject drug candidate is under regulatory review~~data. ~~Patent term extension cannot extend~~ the ~~remaining~~Company ~~term~~believes ~~of a patent beyond a total of 14 years from~~ the ~~date~~Recommended ofPhase ~~product~~2 ~~approval,~~Dose ~~only~~(RP2D) ~~one~~should ~~patent applicable to an approved drug may~~ be ~~extended~~750mg ~~and~~every ~~only~~two ~~those claims covering the approved drug, a method for using it, or a method~~ weeks.

21 Biomarkers

~~for~~In ~~manufacturing~~drug itdevelopment ~~may~~and beclinical ~~extended.~~trials, ~~Similar~~biomarkers ~~provisions~~may be useful to ~~extend~~identify ~~the~~patient ~~term~~populations offor a ~~patent~~study, ~~that~~monitor ~~covers~~therapeutic anresponse, ~~approved drug are available in Europe~~ and ~~other~~identify ~~foreign~~side ~~jurisdictions~~effects. InTBS-2025 ~~the~~demonstrated ~~future,~~dose-proportional ifon-target ~~and~~biomarker ~~when~~immune ~~our~~responses ~~products~~involved ~~receive~~in ~~FDA~~anti-tumor ~~approval,~~activity. weTBS-2025 ~~expect~~demonstrated tosignificant ~~apply~~efficacy- ~~for~~related, ~~patent~~dose-dependent ~~term~~cytokine ~~extensions~~induction onof ~~patents~~CXCL10, ~~covering~~IFNα, ~~those~~CCL2 ~~products.~~(MCP1), WeCCL3 ~~plan~~(MIP1α), toCCL4 ~~seek~~(MIP1ß) ~~patent~~and ~~term~~CXCL8 ~~extensions~~(IL8), towhich ~~any~~are ~~issued~~involved ~~patents we may obtain~~ in ~~any~~immune ~~jurisdiction~~cell ~~where~~activation ~~such~~and ~~patent~~recruitment ~~term~~to ~~extensions~~the ~~are~~tumor ~~available~~microenvironment. Additionally, ~~however~~increases ~~there~~in isanti-tumor noimmune ~~guarantee~~cell ~~that~~subpopulations ~~the~~including ~~applicable~~nonclassical ~~authorities,~~monocytes ~~including~~with ~~the~~an ~~FDA~~activated inphenotype ~~the~~(increased ~~United~~of ~~States,~~cell ~~will~~surface ~~agree~~expression ~~with~~of ~~our~~HLA-DR ~~assessment~~and ~~that~~CD80), ~~such~~NK ~~extensions~~cells, ~~should~~CD4+ beT ~~granted,~~cells and ifCD8+ ~~granted,~~T ~~the~~cells ~~length~~were ofobserved ~~such~~during ~~extensions~~treatment.

In some instances, we have submitted and expect to submit patent applications directly to the USPTO as provisional patent applications. Corresponding non-provisional patent applications must be filed not later than 12 months after the provisional application filing date. While we intend to timely file non-provisional patent applications relating to our provisional patent applications, we cannot predict whether any such patent applications will result in the issuance of patents that provide us with any competitive advantage.19

WeTBS-2025 ~~expect~~demonstrated toinduction ~~file~~of ~~U.S.~~pro-inflammatory ~~non~~myeloid-~~provisional~~derived ~~applications~~cytokines/chemokines ~~and~~involved ~~Patent~~in ~~Cooperation~~immune ~~Treaty,~~cell oractivation ~~PCT,~~and ~~applications~~recruitment ~~that~~in ~~claim~~ the ~~benefit~~tumor ~~of the priority date of earlier filed provisional applications, when applicable~~microenvironment. ~~The~~Changes ~~PCT~~in ~~system~~these ~~allows~~key abiomarkers ~~single~~and ~~application~~immune tocell bepopulations ~~filed~~are ~~within~~indicative ~~12 months~~ of the ~~original~~anti-tumor ~~priority~~effects ~~date~~ of ~~the~~blocking ~~patent~~VISTA ~~application~~that ~~and~~is toconsistent ~~designate~~with ~~all~~data offrom ~~the~~preclinical ~~PCT~~models ~~member~~(NHP ~~states~~and inKO ~~which national patent applications can later be pursued based on the international patent application filed under the PCT~~mice). AThese ~~designated~~data ~~authority~~validate ~~performs~~their anuse ~~initial search and issues a non-binding opinion~~ as topotential ~~the~~biomarker ~~patentability~~ of ~~the~~VISTA ~~subject~~target ~~matter.~~engagement ~~The~~with ~~opinion may be used to evaluate the chances of success of national phase applications in various jurisdictions, thereby informing the development of a global filing strategy.~~TBS-2025

~~Although~~Phase a1b/2 ~~PCT application does not itself issue as a patent, it allows the applicant to conveniently file applications in any of the member states through national~~trial TBS-~~phase~~2025 ~~applications. At the end of a period of 30-31 months from the earliest priority date of the patent application (varies by jurisdiction), individual applications can be filed~~ in ~~any~~mutNPM1 ~~of the PCT member states~~r/~~regions.~~r ~~Use of the PCT system is more cost-effective than direct foreign filings and permits applicants greater flexibility with respect to budgeting and the selection of foreign jurisdictions.~~AML

~~For~~Applying ~~all~~the ~~patent~~FDA’s ~~applications~~guidelines for development of drugs in AML to the pharmacokinetic and safety data from VISTA 101, wethe Phase 1 study in solid tumors can potentially be used to determine ~~claiming~~a ~~strategy~~starting ondose in a ~~case-by-case~~Phase ~~basis~~1b trial. We ~~Advice~~anticipate ofconducting ~~counsel~~an ~~and~~abbreviated ~~our~~Phase1b ~~business~~dose ~~model~~escalation ~~and~~study ~~needs~~in ~~are~~mutNPM1 ~~always~~r/r ~~considered.~~AML Wein ~~seek~~patients who failed to ~~file~~respond ~~patents~~to ~~containing~~or ~~claims~~relapsed ~~for~~following ~~protection~~therapy ofwith ~~all~~a ~~useful~~menin ~~applications~~inhibitor ofin mutNPM1 ~~our~~r/r ~~proprietary~~AML. ~~technologies~~This ~~and~~patient ~~any~~population ~~products,~~represents asan ~~well~~unmet asmedical ~~all~~need. ~~new~~We ~~applications~~believe ~~and/or~~this ~~uses~~population weof ~~discover~~patients with this genetic mutation may qualify for ~~existing~~investigation ~~technologies~~under ~~and~~the ~~products~~FDA’s Plausible Mechanism Pathway, ~~assuming~~which ~~these~~is ~~are~~a ~~strategically~~regulatory ~~valuable.~~framework Weallowing ~~continuously~~approval ~~reassess~~based ~~the~~on ~~number~~biological rationale and ~~type~~target ofengagement ~~patent~~rather ~~applications~~than traditional, aslarge ~~well~~randomized astrials. In addition to examining the ~~pending~~potential ~~and~~of ~~issued~~TBS-2025 ~~patent~~monotherapy ~~claims~~in this patient population, the Phase 1b study will also be used to ~~pursue~~establish ~~maximum~~a ~~coverage~~recommended ~~and~~dose ~~value~~to ~~for~~be ~~our~~investigated ~~processes~~in a Phase 2 trial of TBS-2025 in combination with a menin inhibitor in mutNPM1 r/rAML in patients previously untreated with a menin inhibitor. The Phase 2 study would explore whether TBS-2025, ~~and~~when ~~compositions~~used in patients with mutNPM1 r/rAML who are receiving a menin inhibitor, ~~given~~may ~~existing~~improve ~~patent~~both ~~office~~response ~~rules~~rate and ~~regulations~~duration of response by allowing immune recognition and attack against leukemic cells. ~~Further,~~The ~~claims~~Company ~~may~~plans beon ~~modified~~discussing ~~during~~its ~~patent~~development ~~prosecution~~plans towith ~~meet~~the ~~our~~FDA ~~intellectual~~in ~~property~~the first half of 2026 and ~~business~~initiating ~~needs~~the planned Phase1b/2 trial in as early as the second half 2026.

WeMarket recognize that the ability to obtain patent protection and the degree of such protection depends on a number of factors, including the extent of the prior art, the novelty and non-obviousness of the invention, and the ability to satisfy the enablement requirement of the patent laws. In addition, the coverage claimed in a patent application can be significantly reduced before the patent is issued, and its scope can be reinterpreted or further altered even after patent issuance. Consequently, we may not obtain or maintain adequate patent protection for any of our future product candidates or for our technology platform. We cannot predict whether the patent applications we are currently pursuing will issue as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient proprietary protection from competitors. Any patents that we hold may be challenged, circumvented or invalidated by third parties.Opportunity

~~The~~Checkpoint ~~patent~~inhibitors ~~positions~~dominate oncology sales and represent the most successful oncology drug commercial launches in oncology drug development. Since their commercial launch in 2014, sales of ~~biotechnology~~checkpoint ~~companies~~inhibitors ~~are~~have ~~generally~~grown ~~uncertain~~at ~~and~~an ~~involve~~impressive ~~complex~~compounded ~~legal~~annual growth rate with $29.9 billion in sales in 2020 reaching $37 billion in 2022, ~~scientific~~according ~~and~~to ~~factual~~Precedence ~~questions~~Research. ~~Our~~By ~~commercial~~2030 ~~success~~the ~~will~~market ~~also~~is ~~depend~~expected to grow to over $148 billion in ~~part~~worldwide onsales, ~~not~~according ~~infringing~~to ~~upon~~Precedence Research. We believe that our technology platforms have the ~~proprietary~~potential ~~rights~~to address both primary and acquired resistance, the two major limitations to checkpoint inhibitor and cellular therapies and as such represents a large market opportunity. While upward of ~~third~~15% ~~parties~~to 60% of patients will respond to first time treatment with checkpoint inhibitors, 40% to 85% will not. ~~Third~~It is this population of patients with primary resistance to checkpoint inhibitors that we believe represents the initial market opportunity for IFx-~~party~~2.0. ~~patents~~The ~~could~~biologic ~~require~~basis usfor primary resistance to ~~alter~~checkpoint ~~our~~inhibitors ~~development~~is orsimilar ~~commercial~~across ~~strategies~~various tumor types, orpredominately ~~our~~the ~~products~~lack orof ~~processes,~~tumor ~~obtain~~infiltration ~~licenses~~with oractivated ~~cease~~tumor ~~certain~~specific ~~activities~~T cells. ~~Our~~We ~~breach~~believe ofthat ~~any~~an ~~license~~agent ~~agreements~~that orcan ~~our~~overcome ~~failure~~primary resistance to ~~obtain~~checkpoint ainhibitors ~~license~~in one tumor type should overcome resistance in others, if not all, tumor types that exhibit primary resistance to ~~proprietary~~them. ~~rights~~Our ~~required~~initial strategy is to ~~develop~~demonstrate orthe ~~commercialize~~ability ~~our~~of ~~future~~IFx-2.0 ~~products~~to ~~may~~overcome ~~have~~primary aresistance ~~material~~in ~~adverse~~the ~~impact~~50% onof uspatients with advanced Merkel cell carcinoma receiving front line therapy with Keytruda® (pembrolizumab), the current standard of care, allowing more patients to achieve an anti-tumor response than with Keytruda® alone.

If third parties prepare and file patent applications in the United States that also claim technology to which we have rights, we may have to participate in interference or derivation proceedings in the USPTO to determine priority of invention. For more information, see “Risk Factors – Risks Relating to Our Intellectual Property.”20

~~When~~According ~~available~~ to ~~expand~~DelveInsight, it is estimated by 2027 there will be approximately 4,245 patients in the US and 7,049 patients in the 7 major market ~~exclusivity~~European countries, ~~our~~including ~~strategy~~the isUK, growing to ~~obtain~~a total of 15, or262 ~~license~~patients ~~additional~~by ~~intellectual~~2034 ~~property~~in ~~related~~these togeographic ~~current~~territories. The standard of care for patients with the advanced or ~~contemplated~~metastatic ~~development~~Merkel ~~platforms,~~cell ~~core~~carcinoma ~~elements~~is therapy with a checkpoint inhibitor like Keytruda® (pembrolizumab). If the results of ~~technology~~our ~~and/~~above-described or“basket” trial are successful, the results from that clinical ~~candidates~~trial could allow IFx-2.0 to be used in a variety of tumor types other than Merkel cell carcinoma that exhibit primary resistance to checkpoint inhibitors, which could expand the market application of IFx-2.0 significantly.

22Among patients who initially respond to treatment with checkpoint inhibitors, almost all patients will ultimately develop acquired resistance where checkpoint inhibitors no longer work and the tumor recurs and/or progresses. While the cause of acquired resistance is multifactorial, a major contributor is tumor associated MDSC-induced immunosuppression of the tumor microenvironment leading to T cell exhaustion and failure of checkpoint inhibitors or cellular therapies. Our initial strategy is to investigate our MDSC-targeted bi-functional ADCs in tumor types that initially responded to and subsequently progressed on or following checkpoint inhibitor therapy. If successful in overcoming acquired resistance to checkpoint inhibitors while potentially limiting their toxicity to non-tumor tissue, such an application would be expected to also represent a significant market opportunity.

~~Company-owned~~TuHURA's ~~Intellectual~~Manufacturing ~~Property~~Strategy

AsTuHURA ofmaintains ~~December~~established ~~31,~~relationships ~~2024,~~with wecontract ~~had~~development ~~33 issued patents over 13 jurisdictions,~~ and 9manufacturing ~~pending~~organizations ~~applications~~ (~~2 U.S. utility patent applications and 7 foreign patent applications~~CDMOs). ~~Most~~to ofmanufacture ~~such patents~~ and ~~patent~~test ~~applications relate to our~~ IFx ~~technology platform~~-Hu2.0 ~~The~~clinical ~~following~~trial ismaterial a(“CTM”), ~~summary~~including ofdrug ~~our~~substance ~~issued patents~~ and ~~pending~~drug ~~patent~~products ~~applications~~required asfor ofregistration ~~December 31, 2024 by patent family~~trials.

Patent Family

Description

Application/Publication/Patent Number

Filing Date

Issue Date/Status

Earliest Expected Expiration Date

Type of Parent Protection

DNA Vector and Transformed Tumor Cell Vaccines

Whole cell and DNAcancer vaccines

PCT/US2015/018688 (WO 2015/134577)

03/04/2015

Nationalized in CH, DE, DK, EP, FR, GB, HK, IE, NL, NO, SE, US

03/04/2035

Use CompositionComposition

US 9,555,088US 9,839,680US 10,391,158US 10,751,400

07/07/2016 01/30/2017 12/11/2017 08/26/2019

Issued 01/31/2017Issued 12/12/2017Issued 08/27/2019Issued 08/25/2020

03/4/203503/4/203503/4/203503/4/2035

Use

Cancer Vaccine Comprising mRNA Encoding a M-Like- Protein

Next generation cancer vaccine using mRNA encoding a bacterial antigen to prime anti- cancer immune responses

PCT/US2016/033235 (WO 2016/187407) US 9,636,388US 10,682,401US 18/060,605

05/19/2016 07/28/201605/01/2017 12/01/2022

Nationalized inAU, CA, CH,CN, DE, DK, EP, FR, GB, HK, IE, JP, NL, NO, SE, US Issued 05/02/2017Issued 06/16/2020pending

05/19/203605/19/203605/19/2036

Use CompositionComposition/use

Modified mRNA for Multicell Transformation

Next generation cancer vaccine using mRNA encoding a bacterial antigen to prime anti- cancer immune responses

PCT/US2021/031204 (WO 2021/226413)

05/7/2021

Nationalized in CN, JP, CA, IN, AU, EP, KR To be filed in HK

05/7/2041

Exosome Delivery of Cancer Therapeutics

Production and use of exosome preparations to systemically deliver pDNA and/or

US 18/055,724

11/15/2022

Published/pending

Composition/use

IFx-Hu2.0 is comprised of 1) the Plasmid DNA (pAc/emm55) in TE Buffer Drug Product (DP) with 10% Dextrose Injection. and 2) the Cationic Polymer DP with 10% Dextrose Injection. The Plasmid DNA (pAc/ emm55) in TE Buffer DP utilizes the Cationic Polymer DP as a transfectant agent excipient, and IFx-Hu2.0 is complexed at the site prior to patient administration. TuHURA has completed the FDA-required mixing studies demonstrating the mixing process consistently produces a product that meets a set of quality attributes. IFx- Hu2.0 preparation instructions are included in the pharmacy manual to ensure mixing at the site prior to administration results in reliably produced drug product with consistent material properties. In addition, the FDA-required potency and stability assays have been developed, qualified, and/or validated supporting product release and stability, which meets cGMP requirements for use in our Phase 3 registration trial.

~~Licensed~~TuHURA ~~Intellectual~~assumed ~~Property~~from ~~Rights~~Kineta ~~Relating~~a manufacturing agreement with Samsung Biologics to ~~Delta~~provide ~~Receptor~~manufacturing ~~Technology~~services, including CTM drug substance and drug product manufacturing and stability testing for TBS-2025. Samsung has no commercial rights to TBS-2025 or any other assets acquired from Kineta.

WeIntellectual license the intellectual property rights relating to our tumor microenviroment modulator technology platform under exclusive license agreements with H. Lee Moffitt Cancer Center and Research Institute (“Moffitt Cancer Center”) and the West Virginia University Research Corporation (“WVURC”). In particular, we are a party to a March 2019 Exclusive License Agreement with Moffitt Cancer Center under which, as amended, we license patent rights co-owned by Moffitt and University of South Florida relating to ADCs for immunotherapy and Delta receptor targeted agents for molecular imaging and immunotherapy of lung cancer. We are a party to a second Exclusive License Agreement entered into in April 2021 under which, as amended, we license Moffitt’s interest in certain patent rights relating to the applicability of our Delta receptor technology to the tumor microenvironment (these patent rights are co-owned by Moffitt and us). We are a party to a September 2022 Restated and Amended Exclusive License Agreement with WVURC pursuant to which we license from WVURC certain patent rights (including WVURC’s rights under one patent that is jointly owned by WVURC and our company) relating to Delta receptor targeted agents for molecular imaging and cancer immunotherapy.Property

These license agreements were originally entered into with Moffitt and WVURC by TuHURA Biopharma, which assigned its interest under the agreements to us as a part of the acquisition of certain TuHURA Biopharma assets in January 2023. The following are summaries of the material terms of these license agreements:21

~~2019~~Intellectual ~~License~~property ~~Agreement~~is ~~with~~of ~~Moffitt~~vital ~~Cancer~~importance ~~Center~~in our field and in biotechnology generally. We seek to protect and enhance proprietary technology, inventions, and improvements that are commercially important to the development of our business by seeking, maintaining, and defending patent rights, whether developed internally or licensed from third parties. We also seek to rely on regulatory protection afforded through inclusion in expedited development and review, data exclusivity, market exclusivity and patent term extensions where available. We have sought patent protection in the United States and internationally related to our IFx-Hu2.0 platform technology, and we license from third parties the patents and patent applications relating to our tumor microenviroment modulators technology.

InWe ~~March~~expect ~~2019,~~to ~~TuHURA~~file ~~Biopharma,~~additional aspatent ~~predecessor~~applications in ~~interest~~support toof ~~the~~current ~~Company,~~and ~~entered~~new ~~into~~clinical ancandidates, ~~Exclusive~~as ~~License~~well ~~Agreement~~as ~~with~~new ~~Moffitt~~platform ~~Cancer~~and ~~Center,~~core ~~which~~technologies. ~~agreement~~Our ~~was~~commercial ~~amended~~success will depend in ~~September~~part ~~2019,~~on ~~April~~obtaining ~~2021~~and maintaining patent protection and ~~August~~trade ~~2022~~secret ~~(as~~protection ~~amended,~~of ~~the~~our ~~“2019~~current ~~Moffitt~~and ~~Agreement”),~~future ~~for~~product candidates and the ~~worldwide~~methods used to develop and manufacture them, ~~exclusive~~as ~~license~~well ofas ~~patents~~successfully ~~for~~defending ~~the~~any ~~development,~~such ~~commercialization~~patents against third-party challenges and ~~marketing~~operating without infringing on the proprietary rights of ~~products~~others. ~~derived~~Our ability to stop third parties from ~~Moffitt’s~~making, ~~rights~~using, selling, offering to ~~patents~~sell ~~entitled~~or ~~“Conjugates~~importing ~~for~~our ~~Immunotherapy”~~product candidates will depend on the extent to which we have rights under valid and “Aenforceable ~~Delta-Opioid~~patents ~~Receptor~~or ~~Targeted~~trade secrets that cover these activities.

23The terms of individual patents depend upon the statutory term of the patents in the countries in which they are issued. In most countries in which we file, including the United States, the patent term is 20 years from the earliest filing of a non-provisional patent application. In the United States, a patent term may be lengthened by patent term adjustment (“PTA”), which compensates a patentee for administrative delays by the USPTO in examining and granting a patent. Conversely, a patent term may be shortened if a patent is terminally disclaimed over an earlier filed patent. In the United States, the term of a patent that covers an FDA-approved drug may also be eligible for extension, which permits patent term restoration to account for the patent term lost during the FDA regulatory review process. The Hatch-Waxman Act permits a patent term extension of up to five years beyond the expiration of the patent. The length of the patent term extension is related to the length of time the subject drug candidate is under regulatory review. Patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only one patent applicable to an approved drug may be extended and only those claims covering the approved drug, a method for using it, or a method for manufacturing it may be extended. Similar provisions to extend the term of a patent that covers an approved drug are available in Europe and other foreign jurisdictions. In the future, if and when our products receive FDA approval, we expect to apply for patent term extensions on patents covering those products. We plan to seek patent term extensions to any issued patents we may obtain in any jurisdiction where such patent term extensions are available, however there is no guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment that such extensions should be granted, and if granted, the length of such extensions.

~~Agent~~In ~~For~~some ~~Molecular~~instances, ~~Imaging~~we ~~And~~have ~~Immunotherapy~~submitted Ofand ~~Lung~~expect ~~Cancer”~~to ~~(the~~submit ~~“2019~~patent ~~Moffitt~~applications ~~Licensed~~directly ~~Patents”).~~to ~~The~~the ~~exclusive~~USPTO ~~nature~~as ofprovisional ~~the~~patent ~~granted~~applications. ~~licenses~~Corresponding ~~are~~non-provisional ~~subject~~patent toapplications ~~customary~~must ~~reservations~~be byfiled ~~Moffitt~~not ~~for~~later ~~non-commercial~~than ~~research,~~12 ~~development,~~months ~~and~~after ~~academic~~the ~~purposes.~~provisional ~~The~~application ~~licenses~~filing ~~granted~~date. byWhile ~~Moffitt~~we ~~are~~intend ~~sublicensable~~to bytimely usfile tonon-provisional ~~affiliates~~patent ~~and~~applications ~~third~~relating ~~parties,~~to ~~subject~~our toprovisional ~~certain~~patent ~~requirements~~applications, ~~including~~we ~~providing~~cannot ~~Moffitt~~predict ~~with~~whether aany ~~copy~~such ofpatent ~~each~~applications ~~executed~~will ~~sublicense~~result ~~agreement~~in ~~and ensuring that~~ the ~~sublicensee~~issuance ~~complies~~of ~~with~~patents ~~the~~that ~~terms~~provide ofus ~~the~~with ~~2019~~any ~~Moffitt~~competitive ~~Agreement~~advantage.

~~Pursuant~~We expect to ~~the~~file ~~terms~~U.S. ofnon-provisional ~~the~~applications ~~2019~~and ~~Moffitt~~Patent ~~Agreement~~Cooperation Treaty, inor ~~partial~~PCT, ~~consideration~~applications ofthat ~~Moffitt’s~~claim ~~grant~~the benefit of the ~~rights~~priority ~~and~~date ~~licenses~~of earlier filed provisional applications, ~~TuHURA~~when ~~Biopharma~~applicable. ~~paid~~The toPCT ~~Moffitt~~system ~~one-time,~~allows ~~non-refundable~~a ~~license~~single ~~issue~~application ~~fees~~to ofbe ~~$100,000~~filed ~~and~~within ~~$30,000.~~12 ~~Additionally,~~months ~~TuHURA~~of ~~Biopharma~~the ~~issued~~original ~~shares~~priority date of ~~its~~the ~~common~~patent ~~stock~~application and to ~~Moffitt~~designate asall ~~additional~~of ~~consideration,~~the ~~which~~PCT ~~were~~member ~~exchanged~~states ~~for~~in ~~146,397~~which ~~shares~~national ofpatent ~~our~~applications ~~common~~can ~~stock~~later asbe apursued ~~part~~based ofon the ~~TuHURA~~international ~~Biopharma~~patent ~~asset~~application ~~acquisition~~filed under the PCT. WeA ~~are~~designated ~~obligated~~authority performs an initial search and issues a non-binding opinion as to ~~pay~~the ~~Moffitt~~patentability anof ~~annual~~the ~~license~~subject ~~maintenance~~matter. ~~fee~~The ~~not~~opinion inmay ~~excess~~be used to evaluate the chances of ~~$50,000~~success ~~per~~of ~~year~~national ~~until~~phase ~~annual~~applications ~~minimum~~in ~~royalty~~various ~~payments~~jurisdictions, ~~commence~~thereby ~~following~~informing ~~commercial~~the ~~sales~~development of ~~licensed~~a ~~products~~global filing strategy.

~~Also~~Although ~~under~~a PCT application does not itself issue as a patent, it allows the ~~2019~~applicant ~~Moffit~~to ~~Agreement~~conveniently file applications in any of the member states through national-phase applications. At the end of a period of 30-31 months from the earliest priority date of the patent application (varies by jurisdiction), weindividual ~~are~~applications ~~required~~can be filed in any of the PCT member states/regions. Use of the PCT system is more cost-effective than direct foreign filings and permits applicants greater flexibility with respect to ~~make~~budgeting and the ~~following~~selection ~~additional~~of ~~payments:~~foreign jurisdictions.

~~Various~~For ~~milestone~~all ~~royalty~~patent ~~payments~~applications, ~~based~~we determine claiming strategy on ~~specified~~a ~~development,~~case-by-case ~~approval,~~basis. ~~commercialization,~~Advice of counsel and ~~sales~~our ~~milestones,~~business ~~which~~model ~~payments~~and ~~range~~needs ~~from~~are ~~$150,000~~always considered. We seek to ~~$400,000~~file patents containing claims for ~~milestones~~protection ~~relating~~of toall ~~the~~useful ~~commencement~~applications of ~~clinical~~our ~~trials~~proprietary uptechnologies toand ~~$3.0~~any ~~million~~products, toas $5well as all new applications and/or uses we discover for existing technologies and products, assuming these are strategically valuable.0 ~~million~~We ~~based~~continuously onreassess ~~sales~~the ~~thresholds~~number inand ~~excess~~type of ~~$1.0~~patent ~~billion~~applications, inas ~~sales;~~well as the pending and issued patent claims to pursue maximum coverage and value for our processes, and compositions, given existing

Running royalties based on net sales of licensed products with a royalty percentage in the middle-single digit and with escalating minimum annual royalties that do not exceed $0.5 million per year; and22

~~Payment~~patent ofoffice ~~all~~rules and regulations. Further, claims may be modified during patent prosecution ~~and~~to ~~maintenance~~meet ~~costs~~our ~~and~~intellectual ~~fees~~property ~~for~~and ~~the~~business ~~licensed patents~~needs.

~~The~~We ~~term~~recognize ofthat the ~~2019~~ability ~~Moffitt~~to ~~Agreement~~obtain ~~will~~patent beprotection ~~until~~and the ~~later~~degree of ~~(i)~~such ~~the~~protection ~~date~~depends on ~~which~~a ~~the~~number ~~last~~ of ~~the licensed patents expire~~factors, orincluding ~~(ii) twenty (20) years after~~ the ~~date~~extent of the ~~2019~~prior ~~Moffitt~~art, ~~Agreement.~~the Wenovelty ~~may~~and ~~unilaterally~~non-obviousness ~~terminate~~of the ~~2019~~invention, ~~Moffitt~~and ~~Agreement~~the atability ~~any time on six (6) months’ notice~~ to ~~Moffitt,~~satisfy ~~provided~~the ~~that~~enablement ~~all~~requirement ~~payments~~of ~~due by us at that time have been made through~~ the ~~effective~~patent ~~date of termination~~laws. ~~Additionally~~In addition, ~~we may terminate~~ the ~~agreement~~coverage ~~with~~claimed ~~written notice to Moffitt~~ in ~~the~~a ~~event~~patent ~~Moffitt~~application ~~commits~~can abe ~~material~~significantly ~~breach~~reduced ~~and~~before ~~such~~the ~~breach~~patent is ~~not~~issued, ~~cured~~and ~~within~~its ~~sixty~~scope ~~(60)~~can ~~days~~be ~~following~~reinterpreted ~~Moffitt’s~~or ~~receipt~~further ofaltered ~~such~~even ~~notice.~~after ~~Moffitt~~patent ~~has~~issuance. ~~the right to terminate~~Consequently, ~~or convert all exclusive licenses to nonexclusive licenses in the event~~ we: ~~(x)~~may ~~fail to make payments due under the agreement within thirty (30) days following notice from Moffitt; (y) commit a material breach that is~~ not ~~cured,~~obtain or ~~capable~~maintain ofadequate ~~being~~patent ~~cured,~~protection ~~within~~for ~~sixty~~any ~~(60) days after receipt~~ of ~~notice~~our ~~from~~future ~~Moffitt;~~product ~~(z)~~candidates or ~~challenge~~for ~~the~~our ~~validity~~technology ofplatform. ~~any~~We ofcannot ~~the~~predict ~~2019~~whether ~~Moffitt~~the ~~Licensed~~patent ~~Patents~~applications ~~before~~we aare ~~court~~currently orpursuing ~~other~~will ~~administrative~~issue ~~agency~~as patents in any particular jurisdiction. ~~Upon~~or ~~any~~whether ~~termination prior to~~ the ~~expiration~~claims of ~~the agreement for~~ any ~~reason,~~issued ~~all~~patents ~~licenses~~will ~~and~~provide ~~rights~~sufficient ~~granted~~proprietary ~~pursuant~~protection tofrom ~~the agreement will automatically terminate~~competitors. AtAny ~~the~~patents ~~request~~that ~~of Moffitt,~~ we ~~are~~hold ~~obligated~~may tobe ~~provide all materials~~challenged, ~~clinical~~circumvented ~~results,~~or ~~regulatory~~invalidated ~~submissions,~~by ~~registrations~~third ~~and any other related filings for the 2019 Moffitt Licensed Patents, and all data used to support the same, to Moffitt~~parties.

~~2021~~The ~~License~~patent ~~Agreement~~positions ~~with~~of ~~Moffitt~~biotechnology ~~Cancer~~companies ~~Center~~are generally uncertain and involve complex legal, scientific and factual questions. Our commercial success will also depend in part on not infringing upon the proprietary rights of third parties. Third-party patents could require us to alter our development or commercial strategies, or our products or processes, obtain licenses or cease certain activities. Our breach of any license agreements or our failure to obtain a license to proprietary rights required to develop or commercialize our future products may have a material adverse impact on us.

InIf ~~April~~third ~~2021,~~parties ~~TuHURA~~prepare ~~Biopharma,~~and asfile ~~predecessor~~patent inapplications ~~interest to us, entered into an Exclusive License Agreement with Moffitt, which agreement was amended~~ in ~~August 2022 (collectively,~~ the ~~“2021~~United ~~Moffitt~~States ~~Agreement”),~~that ~~for~~also ~~the~~claim ~~worldwide,~~technology ~~exclusive,~~to ~~license~~which towe ~~Moffitt’s~~have rights, ~~under~~we amay ~~jointly-owned~~have ~~patent entitled “Delta Opioid Receptor Antagonist Reprogram Immunosuppressive Microenvironment~~ to ~~Boost~~participate ~~Immunotherapy”~~in ~~(the~~interference ~~“2021~~or ~~Moffitt~~derivation ~~Licensed~~proceedings ~~Patent”)~~in ~~for~~ the ~~development,~~USPTO ~~commercialization~~to ~~and~~determine ~~marketing~~priority of ~~products from covered claims of the 2021 Moffitt Licensed Patent~~invention. ~~The~~For ~~exclusive~~more ~~nature of the licenses granted are subject to customary reservations by Moffitt for non-commercial research~~information, ~~development,~~see ~~and~~“Risk ~~academic~~Factors ~~purposes.~~– ~~The~~Risks ~~licenses~~Relating ~~granted by Moffitt are sublicensable by the Company~~ to ~~affiliates~~Our ~~and~~Intellectual third parties, subject to certain requirements, including providing Moffitt with a copy of each executed sublicense agreement, and ensuring that the sublicensee comply with the terms of the 2021 Moffitt AgreementProperty.”

~~Pursuant~~When available to ~~the~~expand ~~terms~~market ~~of the 2021 Moffitt Agreement~~exclusivity, inour ~~partial~~strategy ~~consideration~~is ~~of Moffitt’s grant of the rights and licenses, TuHURA Biopharma paid~~ to ~~Moffitt a one-time~~obtain, ~~non-refundable~~or license ~~issue~~additional ~~fee~~intellectual ofproperty ~~$12,500.~~related ~~Additionally, TuHURA Biopharma issued shares of its common stock~~ to ~~Moffitt~~current asor ~~additional~~contemplated ~~consideration,~~development ~~which were exchanged for 195~~platforms,~~465~~ ~~shares~~core ofelements ~~our common stock as a part~~ of ~~the~~technology ~~TuHURA~~and/ ~~Biopharma~~or ~~asset~~clinical ~~acquisition~~candidates. ~~We are obligated to pay Moffitt an annual license maintenance fee not in excess of $25,000 per year until annual minimum royalty payments commence following commercial sales of licensed products.~~

WeCompany-owned ~~are~~Intellectual ~~also required to make the following additional payments:~~Property

24As of December 31, 2025, we had at least 33 issued patents over 13 jurisdictions, and 10 pending applications (2 U.S. utility patent applications, a pending PCT application and 7 foreign patent applications). Most of such patents and patent applications relate to our IFx technology platform. The following is a summary of our issued patents and pending patent applications as of December 31, 2025 by patent family.

Various milestone royalty payments based on specified development, approval, commercialization, and sales milestones, which payments range from $37,500 to $100,000 for milestones relating to the commencement of clinical trials up to $750,000 to $1.25 million based on sales thresholds in excess of $1.0 billion in sales; and

     Patent Family

     Description

     Application/Publication/
Patent Number

     Filing Date

     Issue Date/Status

     Earliest Expected Expiration Date

     Type of Patent Protection

     DNA Vector and Transformed Tumor Cell Vaccines

     Whole cell and DNA
cancer vaccines

     PCT/US2015/018688 (WO 2015/134577)

     03/04/2015

     Nationalized in CH, DE, DK, EP, FR, GB, HK, IE, NL, NO, SE, US

     03/04/2035 

     Use 
Composition
Composition

      
     US 9,555,088
US 9,839,680
US 10,391,158
US 10,751,400

     07/07/2016 
01/30/2017 
12/11/2017 
08/26/2019 

Issued 01/31/2017
Issued 12/12/2017
Issued 08/27/2019
Issued 08/25/2020

     03/4/2035
03/4/2035
03/4/2035
03/4/2035

     Use

     Cancer Vaccine Comprising mRNA Encoding a M-Like- Protein

     Next generation cancer vaccine using mRNA encoding a bacterial antigen to prime anti- cancer immune responses

     PCT/US2016/033235 (WO 2016/187407)
 
US 9,636,388
US 10,682,401
US 18/060,605

05/19/2016
 
07/28/2016
05/01/2017 
12/01/2022 

     Nationalized in
AU, CA, CH,
CN, DE, DK, EP, FR, GB, HK, IE, JP, NL, NO, SE, US
 
Issued 05/02/2017
Issued 06/16/2020
pending

05/19/2036
05/19/2036
05/19/2036

Use Composition
Composition/use

     Modified mRNA for Multicell Transformation

     Next generation cancer vaccine using mRNA encoding a bacterial antigen to prime anti- cancer immune responses

     PCT/US2021/031204 (WO 2021/226413)

     05/7/2021

     Nationalized in CN, JP, CA, IN, AU, EP, KR To be filed in HK

     05/7/2041

     Exosome Delivery of Cancer Therapeutics

     Production and use of exosome preparations to 

     US 18/055,724
 
     11/15/2022 

     Published/pending
 
     Composition/use

Payment of all patent prosecution and maintenance costs and fees for the licensed patents.

      
     systemically deliver pDNA and/or

     Materials and Methods for Treatment of Melanomas and Other Cancers

     Anti-cancer vaccine compositions comprising nucleic acids and methods of treating immune checkpoint inhibitor therapy resistant cancers.   

     PCT/US2025/21863

     03/27/2025

     Published/pending

     03/27/2045

     Composition/Use

~~The~~Intellectual ~~term~~Property ofAcquired the 2021 Moffitt Agreement will be until the later of (i) the date on which the last of the patents expire, or (ii) twenty (20) years after the date of the 2021 Moffitt Agreement. We may unilaterally terminate the 2021 Moffitt Agreement at any time on six (6) months’ notice to Moffitt, provided that all payments due by us at that time have been made through the effective date of termination. Additionally, we may terminate the agreement with written notice to Moffitt in ~~the~~Kineta event Moffitt commits a material breach and such breach is not cured within sixty (60) days following Moffitt’s receipt of such notice. Moffitt has the right to terminate, or convert all exclusive licenses to nonexclusive licenses in the event we: (x) fail to make payments due under the agreement within thirty (30) days following notice from Moffitt; (y) commit a material breach that is not cured, or capable of being cured, within sixty (60) days after receipt of notice from Moffitt; (z) or challenge the validity of any of the 2021 Moffitt Licensed Patent before a court or other administrative agency in any jurisdiction. Upon any termination prior to the expiration of the agreement for any reason, all licenses and rights granted pursuant to the agreement will automatically terminate. At the request of Moffitt, we are obligated to provide all materials, clinical results, regulatory submissions, registrations and any other related filings for the 2021 Moffitt Licensed Patent, and all data used to support the same, to Moffitt.Merger

~~License~~As ~~Agreement~~of ~~with~~December ~~West~~31, ~~Virginia~~2025, ~~University~~our ~~Research~~patent ~~Corporation~~portfolio acquired from Kineta as it pertains to TBS-2025 included fourteen (14) national phase applications in the KVA-001 patent family related to TBS-2025. The countries are as follows: U.S., Australia, Brazil, Canada, China, Europe (European Patent Office (“EPO”)), Hong Kong, Israel, India, Japan, Korea, Mexico, Russia, and Singapore. Its estimated expiration date without any patent term adjustment or extension is 20 years from filing, i.e., February 18, 2042.

In January 2023 but with an effective date of September 2022, TuHURA Biopharma, as predecessor in interest of us, entered into a Restated and Amended Exclusive License Agreement with WVURC (the “WVU Agreement”), which terminated and replaced the prior agreement between WVURC and TuHURA Biopharma. The ~~WVU~~table ~~Agreement~~below ~~provides~~summarizes ~~for~~ the ~~exclusive~~high-level ~~commercialization~~filing ~~rights~~strategy ~~relating~~of toour ~~Delta~~existing ~~receptor~~patent ~~targeted~~portfolio ~~agents~~ for ~~WVURC patent rights relating to molecular imaging and cancer immunotherapies (~~the ~~“WVU~~TBS-2025 ~~Patents”).~~related ~~Under~~assets ~~the~~acquired ~~WVU~~from Agreement, among other rights, WVURC granted us a worldwide, exclusive right, with limited sublicense rights, to develop and commercialize the WVU Patents in accordance with the milestone schedule therein.Kineta:

As partial consideration for the rights granted under the WVU Agreement, TuHURA Biopharma previously paid a non-refundable, upfront fee of $50,000. Under the terms of the WVU Agreement, we are required to pay WVURC a tiered running royalty in the low-to-mid single digit percentages based on levels of net sales of licensed products, including the net sales of sublicensees, with customary anti-stacking provisions. We are also required to pay annual fees of $30,000 or less and is required to fund all patent prosecution and maintenance costs and fees for the licensed patents.VISTA

The term of the WVU Agreement will expire on the later of: (i) the expiration of the date of the last to expire of the WVU Patents or (ii) twenty (20) years from the first commercial sale of a licensed product derived from the WVU Patents, unless earlier terminated pursuant to its terms. We may unilaterally terminate the WVU Agreement upon written notice to WVURC at any time on six (6) months’ notice to WVURC, provided that all payments due by us at that time have been made through the effective date of termination. Additionally, we may terminate the agreement with written notice to WVURC in the event WVURC commits a material breach and such breach is not cured within sixty (60) days following WVURC’s receipt of such notice. WVURC has the right to terminate, or convert all exclusive licenses to nonexclusive licenses in the event we fail to make payments due under the agreement within thirty (30) days following notice from WVURC; commit a material breach that is not cured, or capable of being cured, within ninety (90) days after receipt of notice from WVURC; or challenge the validity of any of the WVU Patents before a court or other administrative agency in any jurisdiction. Upon any termination prior to the expiration of the WVU Agreement for any reason, all licenses and rights granted pursuant to the agreement will automatically terminate.patents

25(TBS-2025 f/k/a KVA12123)

~~The~~Patent ~~following is a summary of the patent rights licensed from Moffitt Cancer Center and WVURC:~~Family KVA-001

Patent Family

Description

Application/Publication/Patent Number

Filing Date

Issue Date/Status

Earliest Expected Expiration Date

Type of Patent Protection

DNA Vector and Transformed Tumor Cell Vaccines

Whole cell and DNA cancer vaccines

PCT/US2015/018688 (WO 2015/134577)

03/04/2015

Nationalized in CH, DE, DK, EP, FR, GB, HK, IE, NL, NO, SE, US

03/04/2035

Use CompositionComposition/use

US 9,555,088 US9,839,680 US10,391,158 US10,751,400

07/07/2016 01/30/2017 12/11/2017 08/26/2019

Issued 01/31/2017 Issued 12/12/2017 Issued 08/27/2019 Issued 08/25/2020

3/4/20353/4/20353/4/20353/4/2035

Cancer Vaccine Comprising mRNA Encoding a M-Like-Protein

Next generation cancer vaccine using mRNA encoding a bacterial antigen to prime anti- cancer immune responses

PCT/US2016/033235 (WO 2016/187407) US 9,636,388 US10,682,401 US18/060,605

05/19/2016 07/28/201605/01/201712/01/2022

Nationalized in AU, CA, CH,CN, DE, DK, EP, FR, GB, HK, IE, JP, NL, NO, SE, US Issued 05/02/2017Issued 06/16/2020 pending

5/19/20365/19/20365/19/2036

Use CompositionComposition/use

Modified mRNA for Multicell Transformation

Next generation cancer vaccine using mRNA encoding a bacterial antigen to prime anti- cancer immune responses

PCT/US2021/031204 (WO 2021/226413)

5/7/2021

Nationalized in CN, JP, CA, IN, AU, EP, KR To be filed in HK

5/7/2041

Exosome Delivery of Cancer Therapeutics

Production and use of exosome preparations to systemically deliver pDNA and/or mRNA tumors

US 18/055,724(US 2023-0183690)

11/15/2022

Published/pending

Composition/use

Composition of matter . . . . . . . . . . . . . . . . . . . . . Y

~~Employees~~Methods ~~and~~of ~~Human~~Manufacturing ~~Capital~~. ~~Resources~~. . . . . . . . . . . . . .. Y

AsSequences/Structure . of. ~~December~~. ~~31,~~. ~~2024,~~. we. ~~had~~. 19. ~~full-time~~. ~~employees~~. ~~and~~. no. ~~part-time~~. ~~employees~~. Of. ~~these~~. ~~employees,~~. 15. ~~were~~. ~~engaged in research and development activities~~. ~~The majority of our employees are based in Tampa, Florida~~. ~~None of our employees are represented by labor unions or covered by collective bargaining agreements~~. ~~We consider our relationship with our employees to be good~~. Y

~~Our~~Indications ~~human~~. ~~capital~~. ~~resources~~. ~~objectives~~. ~~include,~~. as. ~~applicable,~~. ~~identifying,~~. ~~recruiting,~~. ~~retaining,~~. ~~incentivizing~~. ~~and~~. ~~integrating~~. ~~our~~. ~~existing~~. ~~and~~. ~~new~~. ~~employees,~~. ~~advisors~~. ~~and~~. ~~consultants~~. ~~The~~. ~~principal~~. ~~purposes~~. of. ~~our~~. ~~equity~~. ~~and~~. ~~cash~~. ~~incentive~~. plans are to attract, retain and reward personnel through the granting of stock-based and cash-based compensation awards, in order to increase stockholder value and the success of our company by motivating such individuals to perform to the best of their abilities and achieve our objectives. Y

~~Government~~Specification ~~Regulation~~on ~~and~~use ~~Product~~(mono ~~Approval~~or combo) . . . . . . . . . Y

~~Therapeutic~~Binding ~~products~~characteristics . ~~are~~. ~~subject~~. to. ~~rigorous~~. ~~regulation~~. by. ~~the~~. ~~FDA~~. ~~and~~. ~~other~~. ~~governmental~~. ~~agency~~. ~~regulations~~. in. ~~the~~. ~~United~~. ~~States~~. ~~and~~. ~~in foreign countries~~. Noncompliance with applicable requirements can result in import detentions, fines, civil monetary penalties, injunctions, suspensions or losses of regulatory approvals or licenses, recall or seizure of products, operating restrictions, denial of export applications, governmental prohibitions on entering into supply contracts, and criminal penalties and prosecution. Y ~~Failure to obtain regulatory approvals or the restriction, suspension or revocation of regulatory approvals or licenses, as well as any~~

26Immune cell regulation . . . . . . . . . . . . . . . . . . . . . Y

~~other~~ ~~failure~~Physiologic toproperties ~~comply~~. ~~with~~. ~~regulatory~~. ~~requirements,~~. ~~would~~. ~~have~~. a. ~~material~~. ~~adverse~~. ~~effect~~. on. ~~our~~. ~~business,~~. ~~financial~~. ~~condition~~. ~~and~~. ~~results~~. of. ~~operations~~. In connection with seeking therapeutic approval, we will have to comply with the many regulations and requirements associated with the conduct of preclinical and clinical trials, the FDA application process, the terms of any pre-certification protocols and agreements, FDA manufacturing requirements for investigational products, and testing. Upon approval of a Biologics License Application, or BLA, and similar approvals in other jurisdictions, there will be additional regulations that must be complied with, including regulations relating to the packaging, distribution, marking, marketing and claims of our potential products. ~~These later regulations are not only found in federal regulation but many states and, of course, foreign countries~~. Y

~~The~~Discovery UCandidates .S . ~~FDA~~. ~~Process~~. . . . . . . . . . . . . . . . . . . To be added on a rolling basis

~~The~~We ~~FDA~~strive ~~regulates~~to protect the ~~clinical~~proprietary ~~testing~~technologies ~~and~~that ~~design~~we ofbelieve ~~therapeutics~~are important to ~~ensure~~TBS-2025, ~~that~~including ~~medical~~by ~~products~~seeking, ~~distributed~~maintaining and defending patent rights, whether developed internally or in ~~the~~conjunction ~~United~~with ~~States~~or ~~are~~in- ~~safe~~licensed from third parties. As to TBS-2025, we also rely on trade secrets relating to our monoclonal antibodies, know-how, continuing technological innovation and ~~effective~~in-licensing ~~for~~opportunities ~~their~~to ~~intended~~develop, ~~uses.~~strengthen ~~The~~and ~~application~~maintain ~~process~~our ~~for~~proprietary aposition ~~new~~in ~~therapeutic~~the isfield ~~highly~~of ~~regulated.~~innate immunity and fully human antibodies

As amore ~~biopharmaceutical~~fully ~~company~~described ~~that operates in the United States~~above, weas ~~are~~of ~~subject~~December ~~to extensive regulation by relevant authorities~~31, ~~including the FDA. Our potential products will be regulated as biologics. With this classification~~2025, ~~commercial~~our ~~production~~patent ofportfolio ~~its~~related ~~potential products will need~~ to ~~occur~~TBS-2025 inincluded ~~registered~~14 ~~and licensed facilities in compliance with current good manufacturing practices (cGMP) established by the FDA for biologics~~U.S. ~~The~~and ~~FDA~~foreign ~~categorizes human cell- or tissue-based products as either minimally manipulated or more than minimally manipulated~~applications, ~~and~~which ~~has~~entered ~~determined~~national ~~that~~phase ~~more~~in ~~than minimally manipulated products require clinical trials to demonstrate product safety and efficacy and the submission of a BLA for marketing authorization~~2023.

~~Government~~Licensed ~~authorities~~Intellectual inProperty ~~the~~Rights ~~United~~Relating States (at the federal, state and local levels) and in other countries extensively regulate, among other things, the research, development, testing, manufacturing, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing and export and import of biopharmaceutical products such as those we are developing. Our candidates must be approved by the FDA before they may be legally marketed in the United States and by the appropriate foreign regulatory agency before they may be legally marketed in a foreign country. Generally, our activities in other countries will be subject to ~~regulation~~DOR that is similar in nature and scope as that imposed in the United States, although there can be important differences. Additionally, some significant aspects of regulation in Europe are addressed in a centralized way, but country-specific regulation remains essential in many respects. The process for obtaining regulatory marketing approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources.Technology

UTuHURA licenses the intellectual property rights relating to its DOR technology platform under exclusive license agreements with H.S Lee Moffitt Cancer Center and Research Institute (“Moffitt Cancer Center”) and the West Virginia University Research Corporation (“WVURC”). ~~Product~~In ~~Development~~particular, ~~Process~~TuHURA is a party to a March 2019 Exclusive License Agreement with Moffitt Cancer Center under which, as amended, we license patent rights co- owned by Moffitt and University of South Florida relating to ADCs for immunotherapy and Delta receptor targeted agents for molecular imaging and immunotherapy of lung cancer. TuHURA is a party to a second Exclusive License Agreement entered into in April 2021 under which, as amended, we license Moffitt’s interest in certain patent rights relating to the applicability of TuHURA’s Delta receptor technology to the tumor microenvironment (these patent rights are co-owned by Moffitt and us). TuHURA is a party to a September 2022 Restated and Amended Exclusive

In the United States, the FDA regulates pharmaceutical and biological products under the Federal Food, Drug, and Cosmetic Act, or FDCA, the Public Health Service Act, or PHSA, and their respective implementing regulations. Products are also subject to other federal, state and local statutes and regulations. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require 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 after approval, may subject an applicant to administrative or judicial sanctions. FDA sanctions could include, among other actions, refusal to approve pending applications, withdrawal of an approval, a clinical hold, warning letters, product recalls or withdrawals from the market, product seizures, total or partial suspension of production or distribution injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties. Any agency or judicial enforcement action could have a material adverse effect on us. The FDA has limited experience with commercial development of T cell therapies for cancer, including direct- injectable technologies such as AIM INJ. The process required by the FDA before a biological product may be marketed in the United States generally involves the following:24

~~completion~~License ofAgreement ~~nonclinical~~with ~~laboratory~~WVURC ~~tests~~pursuant to which TuHURA licenses from WVURC certain patent rights (including WVURC’s rights under one patent that is jointly owned by WVURC and ~~animal~~the ~~studies~~company) ~~according~~relating to ~~Good~~Delta ~~Laboratory~~receptor ~~Practices,~~targeted oragents ~~GLPs,~~for molecular imaging and ~~applicable~~cancer ~~requirements~~immunotherapy. ~~for~~These license agreements were originally entered into with Moffitt and WVURC by TuHURA Biopharma which assigned its interest under the ~~humane~~agreements ~~use~~to TuHURA as a part of ~~laboratory~~the ~~animals~~acquisition orof ~~other~~certain ~~applicable~~TuHURA ~~regulations;~~Biopharma assets in January 2023. The following are summaries of the material terms of these license agreements:

~~submission~~2019 toLicense ~~the~~Agreement ~~FDA~~with ofMoffitt anCancer ~~investigational new drug, or IND, application, which must become effective before human clinical trials may begin;~~Center

~~approval~~In byMarch 2019, TuHURA Biopharma, as predecessor in interest to the Company, entered into an ~~independent~~Exclusive ~~institutional~~License ~~review~~Agreement ~~board~~with Moffitt Cancer Center, orwhich ~~IRB~~agreement was amended in September 2019, orApril ~~ethics~~2021 ~~committee~~and atAugust ~~each~~2022 ~~clinical~~(as ~~trial~~amended, ~~site~~the ~~before~~“2019 Moffitt Agreement”), for the worldwide, exclusive license of patents for the development, commercialization and marketing of products derived from Moffitt’s rights to patents entitled “Conjugates for Immunotherapy” and “A Delta-Opioid Receptor Targeted Agent For Molecular Imaging And Immunotherapy Of Lung Cancer” (the “2019 Moffitt Licensed Patents”). The exclusive nature of the granted licenses are subject to customary reservations by Moffitt for non-commercial research, development, and academic purposes. The licenses granted by Moffitt are sublicensable by us to affiliates and third parties, subject to certain requirements, including providing Moffitt with a copy of each ~~clinical~~executed ~~trial~~sublicense ~~may~~agreement beand ~~initiated;~~ensuring that the sublicensee complies with the terms of the 2019 Moffitt Agreement.

27Pursuant to the terms of the 2019 Moffitt Agreement, in partial consideration of Moffitt’s grant of the rights and licenses, TuHURA Biopharma paid to Moffitt one-time, non-refundable license issue fees of $100,000 and $30,000. Additionally, TuHURA Biopharma issued shares of its common stock to Moffitt as additional consideration, which were exchanged for 146,397 shares of our common stock as a part of the TuHURA Biopharma asset acquisition. We are obligated to pay Moffitt an annual license maintenance fee not in excess of $50,000 per year until annual minimum royalty payments commence following commercial sales of licensed products.

~~performance~~Also ofunder ~~adequate and well-controlled human clinical trials according to~~ the ~~FDA’s~~2019 ~~regulations~~Moffit ~~commonly referred to as Good Clinical Practice~~Agreement, orwe ~~GCP,~~are ~~and~~required ~~any additional requirements for the protection of human research patients and their health information,~~ to ~~establish~~make the ~~safety~~following ~~and~~additional ~~efficacy of the proposed biological product for its intended use;~~payments:

•

~~submission~~Various tomilestone ~~the~~royalty ~~FDA~~payments ofbased aon ~~BLA~~specified ~~for~~development, ~~marketing~~ approval, ~~that~~commercialization, ~~includes~~and ~~substantive~~sales ~~evidence~~milestones, ofwhich ~~safety,~~payments ~~purity~~range from $150,000 ~~and~~to ~~potency~~$400,000 ~~from~~for ~~results~~milestones ofrelating ~~nonclinical~~to ~~testing~~the ~~and~~commencement of clinical trials up to $3.0 million to $5.0 million based on sales thresholds in excess of $1.0 billion in sales;

•

~~satisfactory~~Running ~~completion~~royalties ofbased anon ~~FDA~~net ~~inspection~~sales of ~~the~~licensed ~~manufacturing~~products ~~facility or facilities where the biological product is produced to assess compliance~~ with ~~cGMP~~a toroyalty ~~assure~~percentage ~~that~~in the ~~facilities,~~middle-single ~~methods~~digit and ~~controls~~with ~~are~~escalating ~~adequate~~minimum toannual ~~preserve~~royalties ~~the~~that ~~biological~~do ~~product’s~~not ~~identity,~~exceed ~~strength,~~$0.5 ~~quality~~million ~~and~~per ~~purity~~year; and~~, if applicable, the FDA’s current Good Tissue Practices, or cGTPs, for the use of human cellular and tissue products;~~

•

~~potential~~Payment ~~FDA audit~~ of ~~the~~all ~~trial~~patent prosecution and ~~clinical~~maintenance ~~trial~~costs ~~sites~~and ~~that~~fees ~~generated~~for the ~~data~~licensed ~~in support of the BLA; and~~patents.

~~FDA~~The ~~review~~term of the 2019 Moffitt Agreement will be until the later of (i) the date on which the last of the licensed patents expire, or (ii) twenty (20) years after the date of the 2019 Moffitt Agreement. We may unilaterally terminate the 2019 Moffitt Agreement at any time on six (6) months’ notice to Moffitt, provided that all payments due by us at that time have been made through the effective date of termination. Additionally, we may terminate the agreement with written notice to Moffitt in the event Moffitt commits a material breach and ~~approval~~such breach is not cured within sixty (60) days following Moffitt’s receipt of such notice. Moffitt has the right to terminate, or ~~licensure~~convert all exclusive licenses to nonexclusive licenses in the event we: (x) fail to make payments due under the agreement within thirty (30) days following notice from Moffitt; (y) commit a material breach that is not cured, or capable of being cured, within sixty (60) days after receipt of notice from Moffitt; (z) or challenge the ~~BLA~~validity of any of the 2019 Moffitt Licensed Patents before a court or other administrative agency in any jurisdiction. Upon any termination prior to the expiration of the agreement for any reason, all licenses and rights granted pursuant to the agreement will automatically terminate. At the request of Moffitt, we are obligated to provide all materials, clinical results, regulatory submissions, registrations and any other related filings for the 2019 Moffitt Licensed Patents, and all data used to support the same, to Moffitt.

~~Preclinical~~2021 ~~studies~~License Agreement with Moffitt Cancer Center

~~Before~~In ~~testing~~April ~~any~~2021, ~~biological~~TuHURA ~~product candidate~~Biopharma, ~~including~~as ~~our~~predecessor ~~drug~~in ~~candidates,~~interest into ~~humans~~us, ~~the~~entered ~~drug~~into ~~candidate~~an ~~enters~~Exclusive ~~the~~License ~~preclinical~~Agreement ~~testing~~with ~~stage.~~Moffitt, ~~Preclinical~~which ~~tests,~~agreement ~~also~~was ~~referred~~amended toin asAugust ~~nonclinical~~2022 ~~studies~~(collectively, ~~include~~the ~~laboratory~~“2021 ~~evaluations~~Moffitt ~~of product chemistry~~Agreement”), ~~toxicity~~for ~~and~~the ~~formulation~~worldwide, asexclusive, ~~well~~license ~~as animal studies~~ to ~~assess~~Moffitt’s ~~the~~rights ~~potential~~under ~~safety~~a ~~and~~jointly-owned ~~activity~~patent ofentitled ~~the~~“Delta ~~drug~~Opioid ~~candidate.~~Receptor ~~The~~Antagonist ~~conduct~~Reprogram ofImmunosuppressive ~~the~~Microenvironment ~~preclinical~~to ~~tests~~Boost ~~must~~Immunotherapy” ~~comply~~(the ~~with~~“2021 ~~federal~~Moffitt ~~regulations~~Licensed ~~and~~Patent”) ~~requirements,~~for ~~including GLP. The clinical trial sponsor must submit~~ the ~~results of the preclinical tests~~development, ~~together~~commercialization ~~with manufacturing information, analytical data, any available clinical data or literature~~ and amarketing ~~proposed~~of ~~clinical~~products ~~protocol,~~from tocovered ~~the~~claims ~~FDA as part~~ of the ~~IND.~~2021 ~~Some~~Moffitt ~~preclinical~~Licensed ~~testing~~Patent. ~~may~~The ~~continue~~exclusive ~~even~~nature ~~after~~of the ~~IND~~licenses isgranted ~~submitted.~~are Ansubject ~~IND~~to iscustomary areservations ~~request~~by Moffitt for ~~authorization~~non-commercial ~~from~~research, ~~the FDA to administer an investigational product to humans~~development, and ~~must~~academic ~~become~~purposes. ~~effective~~The ~~before~~licenses ~~human~~granted ~~clinical trials may begin.~~

~~Human clinical trials in support of a BLA~~25

~~Clinical trials involve the administration of the biological product candidate to human research subjects under the supervision of qualified investigators, generally licensed physicians not employed~~ by orMoffitt ~~under the trial sponsor’s control. Clinical trials~~ are ~~conducted~~sublicensable ~~under~~by ~~protocols detailing, among other things,~~ the ~~objectives~~Company ofto ~~the~~affiliates ~~clinical~~and ~~trial,~~third ~~dosing procedures~~parties, subject ~~selection, inclusion and exclusion criteria, and the parameters~~ to becertain ~~used to monitor subject safety~~requirements, including ~~stopping~~providing ~~rules~~Moffitt ~~that~~with ~~assure~~ a ~~clinical~~copy ~~trial will be stopped if certain adverse events should occur. Each protocol and any amendments to the protocol must be submitted to the FDA as part~~ of ~~the~~each ~~IND.~~executed Ansublicense ~~IND automatically becomes effective 30 days after receipt by the FDA~~agreement, ~~unless the FDA raises concerns or questions regarding the proposed clinical trials~~ and ~~places~~ensuring ~~the trial on a clinical hold within~~ that ~~30-day time period. In such a case,~~ the ~~IND~~sublicensee ~~sponsor~~comply ~~and~~with the FDA must resolve any outstanding concerns before the clinical trial can begin. The FDA may also impose clinical holds on a biological product candidate at any time before or during a clinical trial due to safety concerns or non-compliance. If the FDA imposes a clinical hold, the trial may not recommence without FDA authorization and then only under terms ~~authorized by the FDA. Accordingly, we cannot be sure that submission~~ of ~~an IND will result in~~ the ~~FDA~~2021 ~~allowing~~Moffitt ~~clinical trials to begin or that, once begun, issues will not arise that suspend or terminate such trials~~Agreement.

~~Clinical~~Pursuant ~~trials~~to ~~must~~the beterms ~~conducted~~of ~~and~~the ~~monitored~~2021 Moffitt Agreement, in ~~accordance~~partial ~~with~~consideration ~~the~~of ~~FDA~~Moffitt’s ~~regulations~~grant ~~comprising~~of the ~~GCP~~rights ~~requirements~~and licenses, ~~including~~TuHURA ~~the~~Biopharma ~~requirement~~paid ~~that~~to ~~all~~Moffitt ~~research~~a ~~participants provide informed consent. Further~~one-time, ~~each~~non-refundable ~~clinical~~license ~~trial~~issue ~~must~~fee beof ~~reviewed and approved by an independent institutional review board~~$12,500. ~~or IRB~~Additionally, atTuHURA orBiopharma ~~servicing~~issued ~~each~~shares ~~institution~~of atits ~~which~~common ~~the~~stock ~~clinical~~to ~~trial~~Moffitt ~~will~~as beadditional ~~conducted.~~consideration, Anwhich ~~IRB~~were isexchanged ~~charged~~for ~~with~~195,465 ~~protecting~~shares ~~the welfare and rights~~ of ~~trial~~our ~~participants~~common ~~and considers such items~~ stock as ~~whether~~a ~~the~~part ~~risks~~of ~~to individuals participating in~~ the ~~clinical~~TuHURA ~~trials~~Biopharma ~~are~~asset ~~minimized~~acquisition. ~~and~~We are ~~reasonable~~obligated ~~in relation~~ to ~~anticipated~~pay ~~benefits.~~Moffitt ~~The~~an ~~IRB~~annual ~~also~~license ~~approves~~maintenance ~~the~~fee ~~form~~not ~~and~~in ~~content~~excess of ~~the~~$25,000 ~~informed~~per ~~consent~~year ~~form that must be signed by each clinical trial subject or the participant’s legal representative and must monitor the clinical trial~~ until ~~completed.~~annual ~~For~~minimum ~~certain~~royalty ~~clinical~~payments ~~trials~~commence ~~involving~~following ~~biologics,~~commercial ~~they~~sales also must be reviewed by an institutional biosafety committee, or IBC, a local institutional committee that reviews and oversees basic and clinical research conducted at that institution. The IBC assesses the safety of ~~the~~licensed ~~research and identifies any potential risk to public health or the environment~~products.

28We are also required to make the following additional payments:

•

~~Information~~Various ~~about~~milestone ~~certain~~royalty ~~clinical~~payments ~~trials,~~based ~~including~~on ~~details~~specified ofdevelopment, ~~the~~approval, ~~protocol~~commercialization, and ~~eventually~~sales ~~study results~~milestones, ~~also~~which ~~must~~payments berange ~~submitted~~from ~~within~~$37,500 ~~specific timeframes~~ to ~~the National Institutes of Health~~$100,000 ~~or NIH,~~ for ~~public~~milestones ~~dissemination~~relating ~~on the ClinicalTrials.gov data registry. Information related~~ to the ~~investigational~~commencement ~~product, patient population, phase~~ of ~~investigation, study sites and investigators and other aspects of the~~ clinical ~~trial~~trials isup ~~made~~to ~~public~~$750,000 asto ~~part of the registration of the clinical trial~~$1.25 ~~Sponsors~~million ~~are~~based ~~also~~on ~~obligated~~sales tothresholds ~~disclose~~in ~~the~~excess ~~results~~ of ~~their clinical trials after completion~~$1.0 ~~Disclosure~~billion ~~of the results of these trials can be delayed~~ in ~~some~~sales; ~~cases for up to two years after the date of completion of the trial.~~and

•

~~Human~~Running ~~clinical~~royalties ~~trials~~based ~~are~~on ~~typically~~net ~~conducted~~sales of licensed products with a royalty percentage in ~~three~~the ~~sequential~~middle-single ~~phases~~digit and with escalating minimum annual royalties that ~~may~~do ~~overlap~~not orexceed be$0.1 ~~combined:~~million per year; and

•

~~phase~~Payment 1.of ~~The~~all ~~investigational~~patent ~~biological~~prosecution ~~product~~and ~~candidate~~maintenance iscosts ~~initially~~and ~~introduced~~fees ~~into human subjects to test~~ for ~~safety, dosage tolerance, absorption, metabolism, distribution and excretion. The initial human testing is often conducted in patients, rather than in healthy volunteers, in~~ the ~~case~~licensed ~~of products for severe or life-threatening diseases~~patents.

~~phase~~The 2term of the 2021 Moffitt Agreement will be until the later of (i) the date on which the last of the patents expire, or (ii) twenty (20) years after the date of the 2021 Moffitt Agreement. ~~The~~We ~~biological~~may ~~product~~unilaterally isterminate ~~evaluated~~the 2021 Moffitt Agreement at any time on six (6) months’ notice to Moffitt, provided that all payments due by us at that time have been made through the effective date of termination. Additionally, we may terminate the agreement with written notice to Moffitt in the event Moffitt commits a ~~limited~~material ~~patient~~breach ~~population~~and such breach is not cured within sixty (60) days following Moffitt’s receipt of such notice. Moffitt has the right to ~~identify~~terminate, ~~possible~~or ~~safety~~convert ~~risks~~all exclusive licenses to nonexclusive licenses in the event we: (~~adverse~~x) ~~effects~~fail to make payments due under the agreement within thirty (30) days following notice from Moffitt; (y) commit a material breach that is not cured, ~~optimize~~or ~~dosing~~capable ~~and~~of ~~preliminarily~~being ~~evaluate~~cured, within sixty (60) days after receipt of notice from Moffitt; (z) or challenge the ~~efficacy~~validity of any of the ~~product~~2021 Moffitt Licensed Patent before a court or other administrative agency in any jurisdiction. Upon any termination prior to the expiration of the agreement for ~~specific~~any ~~targeted~~reason, ~~diseases~~all licenses and rights granted pursuant to the agreement will automatically terminate. At the request of Moffitt, we are obligated to provide all materials, clinical results, regulatory submissions, registrations and any other related filings for the 2021 Moffitt Licensed Patent, and all data used to support the same, to Moffitt.

~~phase~~License 3.Agreement Clinical trials are undertaken in an expanded patient population to further evaluate dosage, clinical efficacy, and safety, often at geographically dispersed trial sites. These clinical trials are intended to establish the overall risk to benefit ratio of the investigational product and provide, if appropriate, an adequate basis for product labeling. These trials may include comparisons with ~~placebo~~West ~~and/or~~Virginia ~~other~~University ~~comparator~~Research ~~treatments. The duration of treatment is often extended to mimic the actual use of a product during marketing.~~Corporation

~~Post-approval~~In ~~clinical~~January ~~trials,~~2023 ~~sometimes~~but ~~referred~~with toan effective date of September 2022, TuHURA Biopharma, as ~~phase~~predecessor 4in ~~clinical~~interest ~~trials~~of us, ~~may~~entered beinto ~~conducted~~a ~~after~~Restated ~~initial~~and ~~marketing~~Amended ~~approval.~~Exclusive ~~These~~License ~~clinical~~Agreement ~~trials~~with ~~are~~WVURC ~~used~~(the to“WVU ~~gain~~Agreement”), ~~additional~~which ~~experience~~terminated ~~from~~and replaced the ~~treatment~~prior ofagreement ~~patients~~between inWVURC and TuHURA Biopharma. The WVU Agreement provides for the ~~intended~~exclusive ~~therapeutic~~commercialization ~~indication,~~rights ~~particularly~~relating to Delta receptor targeted agents for ~~long-term~~WVURC ~~safety~~patent ~~follow-up.~~rights Inrelating ~~certain~~to ~~instances,~~molecular imaging and cancer immunotherapies (the ~~FDA~~“WVU ~~may~~Patents”). ~~mandate~~Under the ~~performance~~WVU ofAgreement, ~~phase~~among 4other ~~clinical~~rights, ~~trials~~WVURC asgranted us a ~~condition~~worldwide, ofexclusive ~~approval~~right, ofwith alimited ~~BLA~~sublicense rights, to develop and commercialize the WVU Patents in accordance with the milestone schedule therein.

~~Progress~~As ~~reports~~partial ~~detailing~~consideration ~~the~~for ~~results of~~ the ~~clinical~~rights ~~trial~~granted ~~must~~under ~~be submitted at least annually to~~ the ~~FDA~~WVU ~~and more frequently if serious adverse events~~Agreement, orTuHURA ~~SAEs,~~Biopharma ~~occur.~~previously ~~The~~paid ~~FDA or the trial sponsor may suspend or terminate~~ a ~~clinical~~non-refundable, ~~trial~~upfront atfee ~~any~~of ~~time on various grounds~~$50,000. ~~including~~Under athe ~~finding~~terms ~~that~~of the ~~research~~WVU ~~participants~~Agreement, we are ~~being~~required ~~exposed~~ to anpay ~~unacceptable~~WVURC ~~health risk. Similarly, an IRB can suspend or terminate approval of~~ a ~~clinical~~tiered ~~trial~~running atroyalty ~~its~~in ~~institution if~~ the ~~clinical~~low-to-mid ~~trial~~single isdigit ~~not~~percentages ~~being~~based ~~conducted~~on inlevels ~~accordance~~of ~~with~~net ~~the~~sales ~~clinical~~of ~~protocol,~~licensed ~~GCP~~products, orincluding ~~other IRB requirements, or if~~ the ~~investigational~~net ~~product~~sales ~~has~~of ~~been~~sublicensees, ~~associated~~ with ~~unexpected~~customary ~~serious~~anti-stacking ~~harm to patients~~provisions. ~~Additionally,~~We ~~some trials~~ are ~~overseen~~also byrequired anto ~~independent~~pay ~~group~~annual fees of ~~qualified~~$30,000 ~~experts~~or ~~organized~~less byand ~~the~~is ~~trial~~required ~~sponsor~~to ~~known~~fund asall ~~the~~patent ~~data~~prosecution ~~safety~~and ~~monitoring~~maintenance ~~board~~costs orand ~~committee.~~fees ~~This group provides authorization~~ for ~~whether~~the alicensed ~~trial may move forward at designated checkpoints~~patents.

~~During~~The term of the ~~development~~WVU ofAgreement awill ~~new~~expire ~~drug~~on orthe ~~biological~~later ~~product,~~of: ~~sponsors~~(i) ~~have~~the expiration of the ~~opportunity~~date of the last to ~~meet~~expire ~~with~~of the ~~FDA~~WVU atPatents ~~certain~~or ~~points,~~(ii) ~~including~~twenty ~~prior~~(20) toyears ~~submission~~from the first commercial sale of ana ~~IND,~~licensed atproduct ~~the~~derived ~~end~~from ofthe ~~phase~~WVU 2Patents, ~~and~~unless ~~before~~earlier ~~submission~~terminated ofpursuant ato ~~BLA~~its terms. ~~These~~We ~~meetings~~may ~~can~~unilaterally ~~provide~~terminate anthe ~~opportunity~~WVU ~~for~~Agreement ~~the~~upon ~~sponsor~~written notice to ~~share~~WVURC ~~information~~at ~~about~~any ~~the~~time ~~data~~on ~~gathered~~six (6) months’ notice to ~~date~~WVURC, ~~for~~provided that all payments due by us at that time have been made through the ~~FDA~~effective todate ~~provide~~of ~~guidance~~termination. Additionally, ~~and~~we ~~for~~may terminate the ~~sponsor~~agreement ~~and~~with ~~the~~written ~~FDA~~notice to ~~reach~~WVURC ~~agreement~~in on the ~~next~~event ~~phase~~WVURC ofcommits ~~development.~~a ~~Sponsors~~material ~~typically~~breach ~~use~~and ~~the~~such ~~end~~breach is not cured within sixty (60) days following WVURC’s receipt of ~~phase~~such 2notice. ~~meeting~~WVURC has the right to ~~discuss~~terminate, ~~their~~or ~~phase~~convert 2all ~~clinical~~exclusive ~~results~~licenses ~~with~~to nonexclusive licenses in the ~~agency~~event ~~and~~we fail to ~~present~~make ~~their~~payments ~~plans~~due ~~for~~under the ~~pivotal~~agreement ~~phase~~within 3thirty ~~studies~~(30) days following notice from WVURC; commit a material breach that ~~they~~is ~~believe~~not ~~will~~cured, ~~support~~or ~~approval~~capable of being cured, within ninety (90) days after receipt of notice from WVURC; or challenge the ~~new~~validity ~~drug~~of any of the WVU Patents before a court or ~~biological~~other ~~product.~~

Human immunotherapy products are a new category of therapeutics. Because this is a relatively new and expanding area of novel therapeutic interventions, there can be no assurance as to the length of the clinical trial period, the number of participants the FDA will require to be enrolled in the trials in order to establish the safety, efficacy, purity and potency of immunotherapy products, or that the data generated in these trials will be acceptable to the FDA to support marketing approval.26

~~Concurrently~~administrative ~~with~~agency clinical trials, companies usually complete additional studies and must also develop additional information about the physical characteristics of the biological product as well as finalize a process for manufacturing the product in ~~commercial~~any ~~quantities in accordance with cGMP requirements~~jurisdiction. ToUpon ~~help~~any ~~reduce~~termination ~~the~~prior ~~risk~~to of the ~~introduction~~expiration of ~~adventitious agents with use of biological products,~~ the ~~PHSA~~WVU ~~emphasizes~~Agreement ~~the importance of manufacturing control~~ for ~~products~~any ~~whose attributes cannot be precisely defined. The manufacturing process must be capable of consistently producing quality batches of the drug candidate and~~reason, ~~among~~all ~~other~~licenses ~~things, the sponsor must develop methods for testing the identity, strength, quality, potency~~ and ~~purity~~rights ofgranted ~~the~~pursuant ~~final biological product. Additionally, appropriate packaging must be selected and tested and stability studies must be conducted~~ to ~~demonstrate that~~ the ~~biological~~agreement ~~drug~~will ~~candidate~~automatically ~~does not undergo unacceptable deterioration over its shelf life~~terminate.

2927

~~U.S.~~The ~~Review~~following ~~and~~is ~~Approval~~a ~~Processes~~summary of the patent rights licensed from Moffitt Cancer Center and WVURC:

~~Assuming~~Patents ~~successful~~Under ~~completion~~License ofAgreement ~~the required clinical testing, the results of the preclinical studies and clinical trials, along~~ with ~~information~~West ~~relating~~Virginia toUniversity ~~the~~Research ~~product’s~~Corporation ~~chemistry,~~PCT/US2022/070893 ~~manufacturing,~~(filed ~~and~~3/1/2022) ~~controls~~– ~~and proposed labeling, are submitted to the FDA as part of a BLA requesting approval to market the product for one or more indications.~~ “A ~~BLA~~Delta-Opioid inReceptor ~~particular~~Targeted ~~must~~Agent ~~contain proof of the biological product candidate’s safety, purity, potency and efficacy~~ for ~~its~~Molecular ~~proposed~~Imaging ~~indication or indications. Data may come from company-sponsored clinical trials intended to test the safety~~ and ~~efficacy~~Immunotherapy of a product’s use or from a number of alternative sources, including studies initiated by investigators. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of the investigational product to the satisfaction of the FDA. The testing and approval processes require substantial time and effort and there can be no assurance that the FDA will accept the BLA for filing and, even if filed, that any approval will be granted on a timely basis, if at all.Cancer”

~~Under~~Applicant: ~~the~~West ~~Prescription~~Virginia ~~Drug~~University ~~User~~Board ~~Fee Act, as amended, or PDUFA, each BLA must be accompanied by a significant user fee, and the sponsor~~ of anGovernors ~~approved BLA is also subject to an annual program fee. The FDA adjusts the PDUFA user fees~~ on anbehalf ~~annual basis. Fee waivers or reductions are available in certain circumstances, including a waiver~~ of ~~the~~West ~~application~~Virginia fee for the first application filed by a small business. Additionally, no user fees are assessed on BLAs for products designated as orphan drugs, unless the product also includes a non-orphan indication.University

~~According~~Summary: toRelates ~~the goals and policies for original BLAs agreed~~ to bymolecular ~~the~~conjugates ~~FDA~~of ~~under~~anticancer ~~PDUFA,~~compounds ~~the~~and ~~FDA~~imaging ~~has~~agents ~~ten~~and ~~months~~methods ~~from~~of ~~the~~use ~~accepted~~as ~~for~~a ~~filing~~cancer ~~date~~therapy incomprising ~~which~~an toantagonist ~~complete its initial review~~ of a ~~standard~~cell ~~application~~surface ~~and~~opioid ~~respond~~receptor tosuch ~~the~~as ~~applicant,~~a ~~and~~delta ~~six~~opioid ~~months~~receptor ~~from~~(DOR), ~~the~~specific ~~filing~~to ~~date~~a ~~for~~target cell, an ~~application~~imaging ~~with priority review. For all BLAs~~agent, ~~the ten~~ and ~~six-month~~an ~~time~~immune ~~periods~~modulatory ~~run from the filing date; for most other original applications~~molecule, ~~the~~such ~~ten~~as ~~and~~a ~~six-month~~T ~~time~~cell ~~periods run from the submission date. Despite these review goals~~modulator, itconjugated ~~is not uncommon for FDA review of a BLA~~ to ~~extend beyond~~ the ~~goal~~DOR ~~date~~antagonist.

~~Within~~Earliest 60Expected ~~days~~Expiration ~~following~~Date: submission of the application, the FDA reviews a BLA submitted to determine if it is substantially complete before the agency accepts it for filing. The FDA may refuse to file any BLA that it deems incomplete or not properly reviewable at the time of submission and may request additional information. In this event, the BLA must be resubmitted with the additional information. The resubmitted application also is subject to review before the FDA accepts it for filing. Once the submission is accepted for filing, the FDA begins an in-depth substantive review of the BLA. The FDA reviews the BLA to determine, among other things, whether the proposed product is safe, potent, and3/or effective for its intended use, and has an acceptable purity profile, and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s identity, safety, strength, quality, potency and purity. The review process may be extended by the FDA for three additional months to consider new information or in the case of a clarification provided by the applicant to address an outstanding deficiency identified by the FDA following the original submission.1/2042

The FDA may refer applications for novel biological products or biological products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making final decisions on approval. The FDA likely will re-analyze the clinical trial data, which could result in extensive discussions between the FDA and the applicant during the review process. The FDA also may require submission of a risk evaluation and mitigation strategy, or REMS, if it determines that a REMS is necessary to ensure that the benefits of the drug outweigh its risks and to assure the safe use of the drug or biological product. The REMS could include medication guides, physician communication plans, assessment plans and/or elements to assure safe use, such as restricted distribution methods, patient registries or other risk minimization tools. The FDA determines the requirement for a REMS, as well as the specific REMS provisions, on a case-by-case basis. If the FDA concludes a REMS is needed, the sponsor of the BLA must submit a proposed REMS. The FDA will not approve a BLA without a REMS, if required.


Country	App. No.	Filing Date	Grant Date	Patent No.	Status
AU	2022229527	8/23/2023			Pending
CA	3209499	8/23/2023			Pending
CN	202280018635.7	10/8/2023			Pending
HK	62024085712.3	1/19/2024			Pending
EPO	22764254.3	9/28/2023			Pending
IN	202317063261	9/20/2023			Pending
JP	2023-553656	8/31/2023			Pending
KR	10-2023-7033553	9/27/2023			Pending
US	18/548724	9/1/2023			Pending

~~Before~~PCT/US2022/070894 approving a BLA, the FDA will typically conduct a pre-approval inspection of the facilities at which the product is manufactured. The FDA will not approve the product unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. For immunotherapy products, the FDA also will not approve the product if the manufacturer is not in compliance with the cGTPs, to the extent applicable. These are FDA regulations and guidance documents that govern the methods used in, and the facilities and controls used for, the manufacture of human cells, tissues, and cellular and tissue based products (~~HCT~~filed 3/Ps1/2022), ~~which~~– ~~are~~“A ~~human cells or tissue intended for implantation, transplant, infusion, or transfer into a human recipient. The primary intent of the cGTP requirements is to ensure that cellular tissue~~Delta-~~based~~Opioid ~~products~~Receptor ~~are~~Targeted ~~manufactured~~Agent in a manner designed to prevent the introduction, transmission and spread of communicable disease. Additionally, before approving a BLA, the FDA will typically inspect one or more clinical sites to assure that the clinical trials were conducted in compliance with IND trial requirements and GCP requirements. To assure cGMP, cGTP and GCP compliance, an applicant must incur significant expenditure of time, money and effort in the areas of training, record keeping, production, and quality control.for

30Molecular Imaging and Immunotherapy of Cancer”

InApplicants: ~~addition,~~West ~~under~~Virginia ~~the~~University ~~Pediatric~~Board ~~Research Equity Act, or PREA, a BLA or supplement to a BLA must contain data to assess the safety and effectiveness~~ of ~~the~~Governors ~~product~~on ~~for~~behalf the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The FDA may grant deferrals for submission of ~~data~~West orVirginia ~~full~~University or partial waivers. A sponsor who is planning to submit a marketing application for a product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration is required to submit an initial Pediatric Study Plan, or iPSP, within sixty days of an end-of-phase 2 meeting or, if there is no such meeting, as early as practicable before the initiation of the phase 3 or phase 2/3 clinical trial. The iPSP must include an outline of the pediatric study or studies that the sponsor plans to conduct, including trial objectives and ~~design,~~TuHURA ~~age~~Biopharma groups, relevant endpoints and statistical approach, or a justification for not including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting informationInc. The FDA and the sponsor must reach an agreement on the iPSP. A sponsor can submit amendments to an agreed upon iPSP at any time if changes to the pediatric plan need to be considered based on data collected from preclinical studies, early phase clinical trials or other clinical development programs. Unless otherwise required by regulation, the PREA does not apply to any product for an indication for which orphan designation has been granted. However, if only one indication for a product has orphan designation, a pediatric assessment may still be required for any applications to market that same product for the non-orphan indication(s).

~~Notwithstanding~~Summary: ~~the~~Relates ~~submission~~to ofmolecular ~~relevant~~conjugates ~~data~~of ~~and~~anticancer ~~information,~~compounds ~~the FDA may ultimately decide that the BLA does not satisfy its regulatory criteria for approval~~ and ~~deny~~imaging ~~approval~~agents ~~or may require additional clinical or other data~~ and ~~information.~~methods ~~Data obtained from clinical trials are not always conclusive and the FDA may interpret data differently than we interpret the same data. On the basis~~ of ~~the~~use ~~FDA’s~~as ~~evaluation~~a ofcancer ~~the~~therapy ~~BLA~~comprising ~~and~~an ~~accompanying~~antagonist ~~information, including the results~~ of ~~the~~a ~~inspection~~cell ofsurface ~~the~~opioid ~~manufacturing~~receptor ~~facilities,~~such ~~the~~as ~~FDA may issue either an approval letter or~~ a ~~Complete~~DOR ~~Response Letter,~~ or ~~CRL.~~agents ~~An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications. A CRL indicates~~ that ~~the~~are ~~review~~kinase ~~cycle~~inhibitors ~~of the application is complete and the application will not be approved in its present form. A CRL generally outlines the deficiencies in the submission and may require substantial additional testing~~ or ~~information~~JAK/STAT3 ininhibitors, ~~order~~specific ~~for the FDA~~ to ~~reconsider~~a ~~the~~target ~~application.~~cell, ~~The~~an ~~CRL~~imaging ~~may require additional clinical or other data~~agent, ~~additional pivotal phase 3 clinical trial(s)~~ and~~/or~~ ~~other~~an ~~significant~~immune ~~and~~modulatory ~~time-consuming requirements related to clinical trials~~molecule, ~~preclinical~~such ~~studies~~as ~~or manufacturing. If~~ a ~~CRL~~T iscell ~~issued~~modulator, ~~the~~conjugated ~~applicant may choose~~ to ~~either resubmit~~ the ~~BLA~~DOR ~~addressing~~antagonist ~~all of the deficiencies identified in the letter,~~ or ~~withdraw~~kinase ~~the~~inhibitors application. If and when those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the BLA, the FDA will issue an approval letter. The FDA has committed to reviewing such resubmissions in response to an issued CRL in either two or ~~six~~JAK/STAT3 ~~months depending on the type of information included~~inhibitors. ~~Even with the submission of this additional information, however, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.~~

IfEarliest aExpected ~~product~~Expiration ~~receives~~Date: regulatory approval from the FDA, the approval is limited to the conditions of use (e.g., patient population, indication) described in the application. Further, depending on the specific risk(s) to be addressed, the FDA may require that contraindications, warnings or precautions be included in the product labeling, require that post-approval trials, including phase 4 clinical trials, be conducted to further assess a product’s safety after approval, require testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution and use restrictions or other risk management mechanisms under a REMS, which can materially affect the potential market and profitability of the product. The FDA may prevent or limit further marketing of a product based on the results of post-marketing trials or surveillance programs. After approval, some types of changes to the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements and FDA review and approval.3/1/2042

Fast Track, Breakthrough Therapy and Priority Review Designations


Country	App. No.	Filing Date	Grant Date	Patent No.	Status
AU	2022231182	8/23/2023			Pending
CA	3210556	8/31/2023			Pending
CN	202280018634.2	10/20/2023			Pending
EPO	22764255.0	9/28/2023			Pending
IN	202317062268	9/15/2023			Pending
JP	2023-553657	8/31/2023			Pending
KR	10-2023-7033611	9/27/2023			Pending
US	18/548729	9/1/2023			Pending

The FDA is authorized to designate certain products for expedited development or review if they are intended to address an unmet medical need in the treatment of a serious or life-threatening disease or condition. These programs include fast track designation, Breakthrough Therapy Designation and priority review designation and regenerative medicine advanced therapy designation.28

ToPatents beUnder ~~eligible~~License ~~for~~Agreements a fast track designation, the FDA must determine, based on the request of a sponsor, that a product is intended to treat a serious or life-threatening disease or condition and demonstrates the potential to address an unmet medical need by providing a therapy where none exists or a therapy that may be potentially superior to existing therapy based on efficacy or safety factors. Fast track designation provides opportunities for more frequent interactions with ~~the FDA review team to expedite development and review of the product~~H. ~~The~~Lee ~~FDA~~Moffitt ~~may~~Cancer ~~also~~Center review sections of the BLA for a fast track product on a rolling basis before the complete application is submitted, if the sponsor and the FDA agree on a schedule for the submission of the application sections and the sponsor pays any required user fees upon submission of the first section of the NDA or BLA. In addition, fast track designation may be withdrawn by the sponsor or rescinded by the FDA if the designation is no longer supported by data emerging from the clinical trial process.

31PCT/US2017/030962 (filed 5/4/2017) – “A Delta-Opioid Receptor Targeted Agent for Molecular Imaging and Immunotherapy of Cancer”

InApplicants: ~~addition,~~University ~~with the enactment~~ of ~~the~~South ~~Food~~Florida and Drug Administration Safety and Innovation Act, or FDASIA, in 2012, Congress created a new regulatory program for product candidates designated by FDA as “breakthrough therapies” upon a request made by the ~~IND sponsors~~H. ALee ~~breakthrough~~Moffitt ~~therapy~~Cancer is defined as a drug or biologic that is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug or biologic may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. Drugs or biologics designated as breakthrough therapies are also eligible for accelerated approval of their respective marketing applications. The FDA must take certain actions with respect to breakthrough therapies, such as holding timely meetings with and providing advice to the product sponsor, which are intended to expedite the development and review of an application for approval of a breakthrough therapy.Center

~~Next,~~Summary: ~~the~~Relates ~~FDA~~to ~~may~~compounds ~~designate~~comprising ~~a product for priority review if it is a drug or biologic that treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness. The FDA determines~~ at ~~the~~least ~~time~~one ~~that the marketing application is submitted, on a case~~delta-~~by-case~~opioid ~~basis,~~receptor ~~whether the proposed drug represents a significant improvement in treatment~~ligand, ~~prevention~~such oras diagnosis of disease when compared with other available therapies. Significant improvement may be illustrated by evidence of increased effectiveness in the treatment of a condition, elimination or substantial reduction of a treatmentDmt-~~limiting drug reaction~~Tic, ~~documented~~conjugated ~~enhancement of patient compliance that may lead~~ to ~~improvement~~an inanti-PDl ~~serious~~checkpoint ~~outcomes,~~inhibitor orantibody ~~evidence of safety~~ and ~~effectiveness~~Dmt-Tic-antibody inconjugates ~~a new subpopulation. A priority review designation is intended to direct overall attention~~ and ~~resources~~methods ~~to the evaluation~~ of ~~such~~use ~~applications,~~thereof ~~and~~ to ~~shorten~~treat ~~the FDA’s goal for taking action on a marketing application from ten months to six months for an original BLA from the date of filing~~cancer.

~~Even~~Earliest ifExpected aExpiration ~~product~~Date: qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened. Furthermore, fast track designation, breakthrough therapy designation and priority review do not change the standards for approval and may not ultimately expedite the development or approval process.5/4/2037

As part of the 21st Century Cures Act, congress created an accelerated approval pathway for regenerative medicine advanced therapies, or RMATs, which includes therapeutic tissue engineered products, human cell and tissue products, cell therapies and combination products using any such therapies. The program is intended to facilitate expedited development and review of RMATs intended to address serious diseases or conditions.


Country	App. No.	Filing Date	Grant Date	Patent No.	Status
US	16/098906	11/5/2018	10/1/2019	10426843	Granted
US	16/587720	9/30/2019			Abandoned
US	17/830781	6/2/2022	1/7/2025	12186404	Granted
US	19/011258	1/6/2025			Pending

APCT/US2015/038057 ~~sponsor~~(filed ~~may~~6/26/2015) ~~request~~– a“Conjugates RMAT designation from the FDA concurrently with or any time after the IND submission. The FDA has 60 calendar days to determine if the drug product meets the required criteria. Preliminary clinical evidence that the product has the potential to address a serious unmet need or condition is expected, is not required to indicate that the drug product may offer significant improvement over current therapies. The RMAT designation provides the same benefits of the fast track and breakthrough designation programs and programs may be eligible for ~~priority review. Products with the RMAT designation may also be eligible for accelerated approval if pre-agreed criteria are met.~~Immunotherapy”

~~Accelerated~~Applicants: ~~Approval~~University ~~Pathway~~of South Florida and the H. Lee Moffitt Cancer Center

InSummary: ~~addition,~~Relates ~~products~~to ~~studied~~molecular ~~for~~conjugates ~~their~~comprising ~~safety~~agonists and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may receive accelerated approval from the FDA and may be approved on the basis of ~~adequate~~cell ~~and~~surface ~~well-controlled~~receptors ~~clinical~~specific ~~trials~~to ~~establishing that the drug product has an effect on~~ a ~~surrogate~~target ~~endpoint~~cell, ~~that is reasonably likely to predict clinical benefit. The FDA may also grant accelerated approval for~~ such aas ~~drug~~DOR ~~or biologic when the product has an effect on an intermediate clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality~~agonists, ~~or IMM,~~ and ~~that is reasonably likely to predict~~ an ~~effect~~immune ~~on IMM or other clinical benefit~~effector, ~~taking~~such ~~into~~as ~~account~~a ~~the~~T ~~severity,~~cell ~~rarity~~modulator, orcompositions ~~prevalence~~comprising of the ~~condition~~same and ~~the~~methods ~~availability or lack~~ of ~~alternative~~treating ~~treatments. As~~ a ~~condition of approval~~disease, ~~the~~such ~~FDA~~as ~~may require that a sponsor of a drug receiving accelerated approval perform post-marketing clinical trials to verify and describe the predicted effect on IMM or other clinical endpoint~~cancer, ~~and~~by ~~the~~administering ~~product may be subject to expedited withdrawal procedures. Drugs and biologics granted accelerated approval must meet~~ the ~~same~~molecular ~~statutory standards for safety and effectiveness as those granted traditional approval~~conjugates.

~~For~~Earliest ~~the~~Expected ~~purposes~~Expiration ofDate: accelerated approval, a surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign, or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit. Surrogate endpoints can often be measured more easily or more rapidly than clinical endpoints. An intermediate clinical endpoint is a measurement of a therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug, such as an effect on IMM. The FDA has limited experience with accelerated approvals based on intermediate clinical endpoints, but has indicated that such endpoints generally may support accelerated approval when the therapeutic effect measured by the endpoint is not itself a clinical benefit and basis for traditional approval, if there is a basis for concluding that the therapeutic effect is reasonably likely to predict the ultimate long-term clinical benefit of a drug.6/26/2035


Country	App. No.	Filing Date	Grant Date	Patent No.	Status
US	15/321316	12/22/2016	10/22/2019	10449227	Granted
US	16/659207	10/21/2019			Abandoned
US	17/889456	8/17/2022			Abandoned
US	18/130049	4/3/2023			Pending

~~The~~PCT/US2021/022464 ~~accelerated~~(filed ~~approval~~3/16/2021) ~~pathway~~– is“Delta ~~most~~opioid ~~often~~receptor ~~used~~antagonists inreprogram ~~settings~~immunosuppressive inmicroenvironment ~~which the course of a disease is long and an extended period of time is required~~ to ~~measure~~boost the intended clinical benefit of a drug, even if the effect on the surrogate or intermediate clinical endpoint occurs rapidly. For example, accelerated approval has been used extensively in the development and approval of drugs for treatment of a variety of cancers in which the goal of therapy is generally to improve survival or decrease morbidity and the duration of the typical disease course requires lengthy and sometimes large clinical trials to demonstrate a clinical or survival benefit.immunotherapy”

~~The~~Applicants: accelerated approval pathway is usually contingent on a sponsor’s agreement to conduct, in a diligent manner, additional post-approval confirmatory studies to verify and describe the drug’s clinical benefitH. AsLee aMoffitt ~~result,~~Cancer a product candidate approved on this basis is subject to rigorous post-marketing compliance requirements, including the completion of phase 4 or post-approval clinical trials to confirm the effect on the clinical endpoint. Failure to conduct required post-approval studies, or to confirm the predicted clinical benefit of the product during post-marketing studies, would allow the FDA to withdraw approval of the drug. All promotional materials for product candidates being considered and approved under the accelerated approval program are subject to prior review by the FDA.Center

~~Orphan~~Summary: ~~Drug~~Relates ~~Designation~~to (a) methods of stimulating endogenous T cells, increasing the efficacy of adoptive immunotherapy, or reprogramming immunosuppressive tumor microenvironments, immunosuppressive myelopoiesis, or myeloid-derived suppressor cells by administering a DOR antagonist; (b) combination immunotherapies comprising an adoptive immunotherapy or an immune system activator and ~~Exclusivity~~a DOR antagonist and methods of using the same to treat cancer; (c) methods of treating autoimmune disease or microbial infection by administering a DOR agonist, optionally with an immunosuppressor; and (d) combination therapies comprising a DOR agonist and an immunosuppressor.

Under the Orphan Drug Act, the FDA may grant orphan drug designation to a drug or biologic product intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than29

~~200,000~~Earliest ~~individuals~~Expected inExpiration ~~the~~Date: United States, or more than 200,000 individuals 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 or biologic for this type of disease or condition will be recovered from sales in the United States for that drug or biologic. Orphan drug designation must be requested before submitting an NDA or BLA. After the FDA grants orphan drug designation, the identity of the therapeutic agent and its potential orphan use will be disclosed publicly by the FDA; the posting will also indicate whether the drug or biologic is no longer designated as an orphan drug. More than one product candidate may receive an orphan drug designation for the same indication. Orphan drug designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.3/16/2041

If a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to seven years of orphan product exclusivityCountry App. During the seven-year exclusivity period, the FDA may not approve any other applications to market a product containing the same active moiety for the same disease, except in very limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivityNo. Filing ADate Grant ~~product~~Date Patent ~~is clinically superior if it is safer, more effective or makes a major contribution to patient care~~No. Thus, orphan drug exclusivity could block the approval of one of our potential products for seven years if a competitor obtains approval of the same product as defined by the FDA and we are not able to show the clinical superiority of our product candidate or if our product candidate’s indication is determined to be contained within the competitor’s product orphan indication. Status

In addition, the FDA will not recognize orphan drug exclusivity if a sponsor fails to demonstrate upon approval that the product is clinically superior to a previously approved product containing the same active moiety for the same orphan condition, regardless of whether or not the approved product was designated an orphan drug or had orphan drug exclusivity.US 17/912300 9/16/2022 Pending

~~Patent~~Employees ~~Term~~and ~~Restoration~~Human Capital Resources

~~Depending~~As ~~upon~~of ~~the~~December ~~timing~~31, ~~duration and specifics of FDA approval of our biological products~~2025, ~~some~~we ofhad ~~our~~22 USfull-time ~~patents~~employees ~~may~~and beno ~~eligible~~part-time ~~for limited patent term extension~~employees. ~~These~~Of ~~patent~~these ~~term~~employees, ~~extensions~~18 ~~permit~~were aengaged ~~patent~~in ~~restoration~~research ~~term~~and ~~of up to five years as compensation for any patent term lost during product~~ development ~~and the FDA regulatory review process~~activities. ~~However, patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date.~~ The ~~patent~~majority ~~term restoration period is generally one-half the time between the effective date~~ of anour ~~IND,~~employees ~~and~~are ~~the~~based ~~submission~~in ~~date of a BLA~~Tampa, ~~plus~~Florida. ~~the~~None ~~time between the submission date~~ of aour ~~BLA~~employees ~~and~~are ~~the~~represented ~~approval~~by oflabor ~~that~~unions ~~application.~~or ~~Only~~covered ~~one~~by ~~patent~~collective ~~applicable~~bargaining ~~to an approved biological product is eligible for the extension, and the extension must be applied for prior to expiration of the patent~~agreements. ~~The~~We ~~United~~consider ~~States~~our ~~Patent~~relationship ~~and Trademark Office, in consultation~~ with ~~the~~our ~~FDA,~~employees ~~reviews~~to ~~and~~be ~~approves the application for any patent term extension or restoration~~good.

~~Pediatric~~ ~~Exclusivity~~TuHURA's human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and new employees, advisors and consultants. The principal purposes of our equity and cash incentive plans are to attract, retain and reward personnel through the granting of stock-based and cash-based compensation awards, in order to increase stockholder value and the success of our company by motivating such individuals to perform to the best of their abilities and achieve our objectives.

Pediatric exclusivity is a type of non-patent marketing exclusivity available in the United States and, if granted, it provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity or listed patents. This six-month exclusivity may be granted if a sponsor submits pediatric data that fairly respond to a written request from the FDA for such data. The data do not need to show the product to be effective in the pediatric population studied; rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the additional protection is granted. If reports of requested pediatric studies are Facilities

33TuHURA's principal office is located in Tampa, Florida. TuHURA currently leases approximately 12,199 square feet of office and laboratory space under a lease that is due to expire in March 2028. TuHURA believes that such office and laboratory space will be sufficient for TuHURA’s planned operations for the foreseeable future.

~~submitted~~Government toRegulation and ~~accepted~~Product by the FDA within the statutory time limits, whatever statutory or regulatory periods of exclusivity or patent protection cover the product are extended by six months. This is not a patent term extension, but it effectively extends the regulatory period during which the FDA cannot approve another application. The issuance of a Written Request does not require the sponsor to undertake the described studies.Approval

~~Reference~~Therapeutic ~~Product~~products ~~Exclusivity~~are subject to rigorous regulation by the FDA and other governmental agency regulations in the United States and in foreign countries. Noncompliance with applicable requirements can result in import detentions, fines, civil monetary penalties, injunctions, suspensions or losses of regulatory approvals or licenses, recall or seizure of products, operating restrictions, denial of export applications, governmental prohibitions on entering into supply contracts, and criminal penalties and prosecution. Failure to obtain regulatory approvals or the restriction, suspension or revocation of regulatory approvals or licenses, as well as any other failure to comply with regulatory requirements, would have a material adverse effect on our business, financial condition and results of operations. In connection with seeking therapeutic approval, we will have to comply with the many regulations and requirements associated with the conduct of preclinical and clinical trials, the FDA application process, FDA manufacturing requirements for ~~Biological~~investigational ~~Products~~products, and testing. Upon approval of a New Drug Application (NDA), Biologics License Application (NDA/BLA), and similar approvals in other jurisdictions, there will be additional regulations that must be complied with, including regulations relating to the packaging, distribution, labelling, marketing and claims of our potential products. These later regulations are not only found in federal regulation but many states and, of course, foreign countries.

~~In March 2010, the Patient Protection and Affordable Care Act was enacted in the United States and included the Biologics Price Competition and Innovation Act of 2009, or the BPCIA.~~ The ~~BPCIA amended the PHSA to create an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-licensed reference biological product~~U. ~~To date, the FDA has approved a number of biosimilars, and numerous biosimilars have been approved in Europe~~S. ~~The~~ FDA ~~has also issued several guidance documents outlining its approach to reviewing and approving biosimilars and interchangeable biosimilars.~~Process

AThe ~~biosimilar~~FDA ~~product~~regulates ~~is defined as one that is highly similar to a reference product notwithstanding minor differences in clinically inactive components and for which there are no clinically meaningful differences between~~ the ~~biological~~clinical ~~product~~trials and ~~the~~design ~~reference product in terms~~ of ~~the~~therapeutics ~~safety,~~to ~~purity~~ensure ~~and potency of the product. An interchangeable product is a biosimilar product~~ that ~~can~~medical beproducts ~~expected~~distributed toin ~~produce~~ the ~~same~~United ~~clinical~~States ~~results~~are assafe ~~the reference product in any given patient~~ and, effective for ~~products~~their ~~administered~~intended multiple times to an individual, that the product and the reference product may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biological product without such alternation or switchuses. ~~Upon~~The ~~licensure~~application byprocess ~~the FDA, an interchangeable biosimilar may be substituted~~ for ~~the~~a ~~reference~~new ~~product~~therapeutic ~~without~~is ~~the~~highly ~~intervention of the health care provider who prescribed the reference product~~regulated.

~~The~~As ~~biosimilar~~a ~~applicant~~biopharmaceutical ~~must~~company ~~demonstrate~~ that operates in the ~~product~~United isStates, ~~biosimilar~~we ~~based~~are onsubject ~~data~~to ~~from~~extensive ~~(i)~~regulation ~~analytical~~by ~~studies~~relevant ~~showing~~authorities, ~~that~~including the ~~biosimilar~~FDA. ~~product~~Our ispotential ~~highly~~products ~~similar~~will tobe ~~the~~regulated ~~reference~~as ~~product;~~combination ~~(ii)~~products, ~~animal~~depending ~~studies~~on ~~(including~~the ~~toxicity);~~product composition and ~~(iii)~~mechanism ~~one~~of action, or ~~more~~biologics. ~~clinical~~With ~~studies~~this ~~to demonstrate safety~~classification, ~~purity~~commercial ~~and~~production ~~potency~~of inits ~~one~~potential orproducts ~~more~~will ~~appropriate~~need ~~conditions~~to ofoccur ~~use~~in ~~for~~registered ~~which~~and ~~the~~licensed ~~reference~~facilities ~~product~~in iscompliance ~~approved.~~with Incurrent ~~addition,~~good ~~the~~manufacturing ~~applicant~~practices ~~must~~(cGMP) ~~show~~established ~~that~~by the ~~biosimilar~~FDA.. ~~and~~The ~~reference~~FDA ~~products~~categorizes ~~have~~human ~~the~~cell- ~~same~~or ~~mechanism~~tissue-based ofproducts ~~action~~as ~~for~~either ~~the~~minimally ~~conditions~~manipulated, ofhomologous use, oncombination ~~the~~with ~~label~~other articles, ~~route~~or ofsystemic ~~administration,~~effect ~~dosage~~ and ~~strength,~~has ~~and~~determined ~~the~~that ~~production~~more ~~facility~~than ~~must~~minimally ~~meet~~manipulated ~~standards~~products ~~designed~~require clinical trials to ~~assure~~demonstrate product safety, ~~purity~~and efficacy and ~~potency~~the submission of a BLA for marketing authorization.

AGovernment ~~reference~~authorities biological product is granted 12 years of regulatory exclusivity from the time of first licensure of the product, and the first approved interchangeable biologic product to a reference product will be granted an exclusivity period of up to one year after it is first commercially marketed. If pediatric studies are performed and accepted by the FDA as responsive to a Written Request, the 12-year exclusivity period will be extended for an additional six months. In addition, the FDA will not accept an application for a biosimilar or interchangeable product based on the reference biological product until four years after the date of first licensure of the reference product. “First licensure” typically means the initial date the particular product at issue was licensed in the United States. ~~Date~~(at ~~of first licensure does not include~~ the ~~date~~federal, ofstate ~~licensure of (~~and alocal ~~new period of exclusivity is not available for~~levels) aand ~~supplement~~in ~~for~~other ~~the~~countries ~~reference~~extensively ~~product for a subsequent application filed by the same sponsor or manufacturer of the reference product (or licensor~~regulate, ~~predecessor~~among ~~in interest or~~ other ~~related~~things, ~~entity) for a change (not including a modification to~~ the ~~structure~~research, ofdevelopment, ~~the~~testing, ~~biological~~manufacturing, ~~product)~~quality ~~that~~control, ~~results~~approval, inlabeling, ~~a new indication~~packaging, ~~route of administration~~storage, ~~dosing schedule~~record-keeping, ~~dosage form~~promotion, ~~delivery system~~advertising, ~~delivery device or strength or for a modification to the structure of the biological product that does not result in a change in safety~~distribution, ~~purity~~post-approval ormonitoring ~~potency.~~and ~~Therefore~~reporting, ~~one~~marketing ~~must~~and ~~determine~~export ~~whether~~and aimport ~~new product includes a modification to the structure~~ of apharmaceutical ~~previously licensed product that results in a change in safety, purity~~ and/or ~~potency~~biopharmaceutical toproducts ~~assess~~such ~~whether~~as ~~the~~those ~~licensure~~we ofare ~~the new product is a first licensure that triggers its own period of exclusivity~~developing. ~~Whether~~Our acandidates ~~subsequent~~must ~~application,~~be if approved, ~~warrants exclusivity as the “first licensure” of a biological product is determined on a case-~~by~~-case~~ ~~basis with data submitted by~~ the ~~sponsor.~~FDA

The BPCIA is complex and is still being interpreted and implemented by the FDA. In addition, recent government proposals have sought to reduce the 12-year reference product exclusivity period. Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the subject of recent litigation. As a result, the ultimate impact, implementation and meaning of the BPCIA is subject to continued uncertainty.30

~~Post~~before they may be legally marketed in the United States and by the appropriate foreign regulatory agency before they may be legally marketed in a foreign country. Generally, our activities in other countries will be subject to regulation that is similar in nature and scope as that imposed in the United States, although there can be important differences. Additionally, some significant aspects of regulation in Europe are addressed in a centralized way, but country-~~Approval~~specific ~~Requirements~~regulation remains essential in many respects. The process for obtaining regulatory marketing approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources.

Any potential products for which we receive FDA approvals are subject to continuing regulation by the FDA, including, among other things, record-keeping requirements, reporting of adverse experiences with the product, providing the FDA with updated safety and efficacy information, product sampling and distribution requirements, and complying with FDA promotion and advertising requirements, which include, among others, standards for direct-to-consumer advertising, restrictions on promoting products for uses or in patient populations that are not described in the product’s approved uses (known as off-label use), limitations on industry-sponsored scientific and educational activities, and requirements for promotional activities involving the internetU.S. ~~Although~~Product ~~physicians~~Development ~~may prescribe legally available products for off-label uses, if the physicians deem to be appropriate in their professional medical~~ Process

34In the United States, the FDA regulates pharmaceutical and/or biological products under the Federal Food, Drug, and Cosmetic Act, or FDCA, the Public Health Service Act, or PHSA, and their respective implementing regulations. Products are also subject to other federal, state and local statutes and regulations. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require 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 after approval, may subject an applicant to administrative or judicial sanctions. FDA sanctions could include, among other actions, refusal to approve pending applications, withdrawal of an approval, a clinical hold, warning letters, product recalls or withdrawals from the market, product seizures, total or partial suspension of production or distribution injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties. Any agency or judicial enforcement action could have a material adverse effect on us. The process required by the FDA before a pharmaceutical and/or biological products may be marketed in the United States generally involves the following:

•

~~judgment,~~completion ~~it is FDA’s position that manufacturers may not market or promote such off-label uses. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion~~ of ~~off-label~~nonclinical ~~uses,~~laboratory ~~and~~tests ~~a company that is found to have improperly promoted off-label uses may be subject to significant liability, including liability under federal fraud~~ and ~~abuse~~animal ~~and~~studies ~~civil~~according ~~and criminal false claims laws. If there are any modifications~~ to ~~the~~Good ~~product,~~Laboratory ~~including changes in indications~~Practices, ~~labeling~~ or ~~manufacturing processes or facilities~~GLPs, ~~the applicant may be required to submit~~ and ~~obtain~~applicable ~~FDA~~requirements approval of a new BLA or a supplement, which may require the applicant to develop additional data or conduct additional preclinical studies and clinical trials. The FDA may also place other conditions on approvals including the requirement for ~~a REMS to assure~~ the ~~safe~~humane use of ~~the~~laboratory ~~product.~~animals ~~A REMS could include medication guides, physician communication plans~~ or ~~elements to assure safe use, such as restricted distribution methods, patient registries and~~ other ~~risk~~applicable minimization tools. Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription or dispensing of products. Product approvals may be withdrawn for non-compliance with regulatory standards or if problems occur following initial marketing.regulations;

•

Insubmission ~~addition, quality control and manufacturing procedures must continue~~ to ~~conform to applicable manufacturing requirements after approval to ensure~~ the ~~quality~~FDA ~~and long-term stability~~ of ~~the~~an ~~product.~~investigational Wenew expect to rely on third parties for the production of clinical and commercial quantities of our potential products in accordance with cGMP regulations. The cGMP regulations include requirements relating to organization of personnel, buildings and facilities, equipment, control of components and drug ~~product containers and closures~~, ~~production~~or ~~and process controls~~IND, ~~packaging and labeling controls~~application, ~~holding~~which ~~and distribution, laboratory controls, records and reports and returned or salvaged products. The manufacturing facilities for our product candidates~~ must ~~meet~~become ~~cGMP~~effective ~~requirements and satisfy the FDA or comparable foreign regulatory authorities~~ before ~~any~~human ~~product is approved and our commercial products can be manufactured. We rely, and expects to continue to rely, on third parties for the production of~~ clinical ~~and~~trials commercial quantities of our products in accordance with cGMP regulations. These manufacturers must comply with cGMP regulations that require, among other things, quality control and quality assurance, the maintenance of records and documentation and the obligation to investigate and correct any deviations from cGMP. Manufacturers and other entities involved in the manufacture and distribution of approved products are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP and other laws. Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain cGMP compliance. Future inspections by the FDA and other regulatory agencies may identify compliance issues at the facilities of our contract manufacturing organizations, or CMOs, that may disrupt production or distribution or require substantial resources to correct. In addition, the discovery of conditions that violate these rules, including failure to conform to cGMP regulations, could result in enforcement actions, and the discovery of problems with a product after approval may result in restrictions on a product, manufacturer, or holder of an approved BLA, including, among other things, voluntary recall and regulatory sanctions as described below.begin;

•

~~Once an~~ approval ofby aan ~~product~~independent isinstitutional ~~granted,~~review the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a productboard, ~~including adverse events of unanticipated severity~~ or ~~frequency~~IRB, or ~~with~~ethics ~~manufacturing~~committee ~~processes,~~at oreach ~~failure~~clinical totrial ~~comply~~site ~~with~~before ~~regulatory~~each ~~requirements, may result in mandatory revisions to the approved labeling to add new safety information; imposition of post-market or~~ clinical ~~trials~~trial tomay ~~assess~~be ~~new safety risks~~initiated; ~~or imposition of distribution or other restrictions under a REMS program. Other potential consequences include, among other things:~~

•

~~restrictions~~performance onof ~~the~~adequate ~~marketing~~and orwell-controlled ~~manufacturing~~human ofclinical trials according to the ~~product~~FDA’s regulations commonly referred to as Good Clinical Practice, ~~complete~~or ~~withdrawal~~GCP, and any additional requirements for the protection of human research patients and their health information, to establish the ~~product~~safety ~~from~~and efficacy of the ~~market~~proposed orbiological product ~~recalls~~for its intended use;

•

~~fines,~~submission ~~warning~~to ~~letters~~the orFDA ~~other~~of ~~enforcement-related~~an ~~letters~~NDA/NDA/BLA orfor ~~clinical~~marketing ~~holds~~approval onthat ~~post-approval~~includes substantive evidence of safety, purity, and potency from results of nonclinical testing and clinical trials;

•

~~refusal~~satisfactory completion of ~~the~~an FDA toinspection ~~approve~~of ~~pending~~the ~~BLAs~~manufacturing facility or ~~supplements~~facilities where the pharmaceutical and/or biological products is produced to ~~approved~~assess ~~BLAs~~compliance with cGMP to assure that the facilities, ormethods ~~suspension~~and controls are adequate to preserve the biological product’s identity, strength, quality and purity and, if applicable, the FDA’s current Good Tissue Practices, or ~~revocation~~cGTPs, for the use of ~~product~~human ~~approvals~~cellular and tissue products;

•

~~product~~potential ~~seizure~~FDA oraudit ~~detention,~~of orthe ~~refusal~~trial toand ~~permit~~clinical trial sites that generated the ~~import~~data orin ~~export~~support of ~~products~~the NDA/NDA/BLA; and

•

~~injunctions~~FDA orreview ~~the~~and ~~imposition~~approval, ~~of civil~~ or ~~criminal~~licensure, ~~penalties;~~of ~~and~~the NDA/NDA/BLA.

~~consent~~Preclinical decrees, corporate integrity agreements, debarment, or exclusion from federal health care programs; or mandated modification of promotional materials and labeling and the issuance of corrective information.studies

35Before testing any pharmaceutical and/or biological products candidate, in humans, the product candidate enters the preclinical testing stage. Preclinical tests, also referred to as non-clinical studies, include laboratory evaluations (product chemistry, toxicity and formulation), as well as animal studies to assess the potential safety and activity of the product candidate. The conduct of the preclinical tests must comply with federal regulations and requirements, including GLP. The clinical trial sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, to the FDA as part of the IND. Some preclinical testing may continue even after the IND is submitted (i.e., long term toxicology or additional studies can run in parallel). An IND is a request for authorization from the FDA to administer an investigational product to humans, and must become effective before human clinical trials may begin.

In addition, the Drug Supply Chain Security Act, or DSCSA, was enacted with the aim of building an electronic system to identify and trace certain prescription drugs distributed in the United States, including most biological products. The DSCSA mandates phased-in and resource-intensive obligations for pharmaceutical manufacturers, wholesale distributors, and dispensers over a 10-year period that has been extended an additional year to be implemented in November 2024. In the Fall of 2024, the FDA granted an additional extension to 2025 based on the type of activities being performed. From time to time, new legislation and regulations may be implemented that could significantly change the statutory provisions governing the approval, manufacturing and marketing of products regulated by the FDA. It is impossible to predict whether further legislative or regulatory changes will be enacted, or FDA regulations, guidance or interpretations changed or what the impact of such changes, if any, may be.31

~~Regulation~~Human ~~Outside~~clinical oftrials ~~the~~in ~~United~~support ~~States~~of a BLA

InClinical ~~addition~~trials involve the administration of the pharmaceutical and/or biological products candidate to ~~regulations~~human ~~within~~research subjects under the ~~United~~supervision ~~States~~of qualified investigators, wegenerally ~~will~~licensed bephysicians ~~subject~~not toemployed aby ~~variety~~or ofunder ~~foreign~~the ~~regulations~~trial ~~governing~~sponsor’s ~~clinical~~control. Clinical trials ~~and~~are ~~the~~conducted ~~commercial~~under ~~sale~~protocols ~~and~~detailing, ~~distribution~~among ofother ~~our~~things, ~~products~~the ~~outside~~objectives of the ~~United~~clinical ~~States.~~trial, ~~Whether~~dosing orprocedures, ~~not~~subject weselection, ~~obtain~~inclusion ~~FDA~~and ~~approval~~exclusion ~~for~~criteria, aand ~~product~~the ~~candidate~~parameters to be used to monitor subject safety, weincluding ~~must~~stopping ~~obtain~~rules ~~approval~~that byassure ~~the~~a ~~comparable~~clinical ~~regulatory~~trial ~~authorities~~will ofbe ~~foreign~~stopped ~~countries~~if orcertain ~~economic~~adverse ~~areas,~~events ~~such~~should occur. Each protocol and any amendments to the protocol must be submitted to the FDA as part of the ~~27-member~~IND. ~~European~~An ~~Union,~~IND ~~before~~becomes weeffective ~~may~~30 ~~commence~~days ~~clinical~~after ~~trials~~receipt orby ~~market~~the ~~products~~FDA, inunless ~~those~~the ~~countries~~FDA raises concerns or ~~areas.~~questions ~~The~~regarding ~~approval~~the ~~process~~proposed ~~and~~clinical ~~requirements~~trials ~~governing~~and places the ~~conduct~~trial ofon a clinical ~~trials,~~hold ~~product~~within ~~licensing,~~that ~~pricing~~30-day ~~and~~time ~~reimbursement~~period. ~~vary~~In ~~greatly~~such ~~between~~a ~~countries~~case, ~~and~~the ~~jurisdictions~~IND sponsor and ~~can~~the ~~involve~~FDA ~~additional~~must ~~testing~~resolve ~~and~~any ~~additional~~outstanding ~~administrative~~concerns ~~review~~before ~~periods~~the clinical trial can begin. The ~~time~~FDA ~~required~~may toalso ~~obtain~~impose ~~approval~~clinical inholds ~~other~~on ~~countries~~a pharmaceutical and/or ~~jurisdictions~~biological ~~might~~products/candidate ~~differ~~at ~~from~~any ~~and~~time bebefore ~~longer~~or ~~than~~during ~~that~~a ~~required~~clinical trial due to ~~obtain~~safety ~~FDA~~concerns ~~approval~~or non-compliance. ~~Regulatory~~If ~~approval~~the inFDA ~~one~~imposes ~~country~~a orclinical ~~jurisdiction~~hold, ~~does~~the trial may not ~~ensure~~recommence ~~regulatory~~without ~~approval~~FDA inauthorization ~~another~~and then only under terms authorized by the FDA. Accordingly, ~~but~~we acannot ~~failure~~be orsure ~~delay~~that insubmission ~~obtaining~~of ~~regulatory~~an ~~approval~~IND will result in ~~one~~the ~~country~~FDA allowing clinical trials to begin or ~~jurisdiction~~that, ~~may~~once ~~negatively~~begun, ~~impact~~issues ~~the~~will ~~regulatory~~not ~~process~~arise inthat ~~others~~suspend or terminate such trials.

~~European~~Clinical ~~Union~~trials ~~drug~~must ~~development~~be conducted and monitored in accordance with the FDA’s regulations comprising the GCP requirements, including the requirement that all research participants provide informed consent. Further, each clinical trial must be reviewed and approved by an independent institutional review board, or IRB, at or servicing each institution at which the clinical trial will be conducted. An IRB is charged with protecting the welfare and ~~approval~~rights of trial participants and considers such items as whether the risks to individuals participating in the clinical trials are minimized and are reasonable in relation to anticipated benefits. The IRB also approves the form and content of the informed consent form that must be signed by each clinical trial subject or the participant’s legal representative and must monitor the clinical trial until completed. For certain clinical trials involving gener therapy or recombinant DNA, they also must be reviewed by an institutional biosafety committee, or IBC, a local institutional committee that reviews and oversees basic and clinical research conducted at that institution. The IBC assesses the safety of the research and identifies any potential risk to public health or the environment.

InInformation ~~the~~about ~~European~~certain ~~Union~~clinical trials, ~~our~~including ~~product~~details ~~candidates~~of the protocol and eventually study results, also ~~may~~must be ~~subject~~submitted within specific timeframes to ~~extensive~~the ~~regulatory~~National ~~requirements~~Institutes of Health, or NIH, for public dissemination on the ClinicalTrials.gov Asdata inregistry. Information related to the ~~United~~investigational ~~States~~product, ~~medicinal~~patient ~~products~~population, ~~can~~phase beof ~~marketed~~investigation, ~~only~~study ifsites aand ~~marketing~~investigators ~~authorization~~and ~~from~~other aspects of the ~~competent~~clinical ~~regulatory~~trial ~~agencies~~is ~~has~~made ~~been~~public ~~obtained.~~as ~~Similar~~part toof the ~~United~~registration ~~States,~~of the ~~various~~clinical ~~phases~~trial. ofSponsors ~~preclinical~~are ~~and~~also obligated to disclose the results of their clinical ~~research~~trials inafter completion. Disclosure of the ~~European~~results ~~Union~~of ~~are~~these ~~subject~~trials can be delayed for one year, with possible extensions in some cases for up to ~~significant~~two ~~regulatory~~years ~~controls~~after the date of completion of the trial.

~~The~~Human ~~Clinical Trials Directive 2001/20/EC, the Directive 2005/28/EC on GCP, and the related national implementing provisions of the individual EU Member States govern the system for the approval of~~ clinical trials inare ~~the~~typically ~~European Union. Under this system, an applicant must obtain prior approval from the competent national authority of the EU Member States in which the clinical trial is to be~~ conducted. Furthermore, the applicant may only start a clinical trial at a specific study site after the competent ethics committee has issued a favorable opinion. The clinical trial application must be accompanied by, among other documents, an IMPD (the Common Technical Document) with supporting information prescribed by Directive 2001/20/EC, Directive 2005/28/EC, where relevant the implementing national provisions of the individual EU Member States and further detailed in ~~applicable~~three ~~guidance~~sequential ~~documents.~~phases ~~All suspected unexpected serious adverse reactions to the investigated drug~~ that ~~occur~~may ~~during~~overlap ~~the~~or ~~clinical trial have to~~ be ~~reported to the competent national authority and the Ethics Committee of the Member State where they occurred.~~combined:

•

Inphase ~~April~~1. ~~2014,~~The ~~the~~investigational ~~new~~product ~~Clinical~~candidate ~~Trials~~is ~~Regulation,~~initially ~~(EU)~~introduced Nointo ~~536/2014~~human ~~(Clinical~~subjects ~~Trials~~to ~~Regulation)~~test ~~was~~for ~~adopted~~safety, ~~and~~dosage ~~came~~tolerance, ~~into~~absorption, ~~application~~metabolism, indistribution ~~January~~and ~~2022~~excretion. The ~~Clinical~~initial ~~Trials~~human ~~Regulation~~testing is ~~directly~~often ~~applicable~~conducted in ~~all~~patients, ~~the~~rather EUthan ~~Member~~in ~~States~~healthy volunteers, ~~repealing~~in the ~~prior~~case ~~Clinical~~of ~~Trials~~products ~~Directive~~for ~~2001/20/EC~~severe or life-threatening diseases.

•

~~The~~phase ~~new Clinical Trials Regulation simplifies and streamlines the approval of clinical trials in the European Union~~2. The ~~main~~product ~~characteristics~~is ofevaluated ~~the~~in ~~regulation include:~~ a ~~streamlined~~limited ~~application~~patient ~~procedure~~population ~~via a single entry point, the “EU portal”; a single set of documents~~ to beidentify ~~prepared~~possible ~~and~~safety ~~submitted~~risks ~~for~~(adverse ~~the~~effects), ~~application~~optimize asdosing ~~well as simplified reporting procedures for clinical trial sponsors;~~ and apreliminarily ~~harmonized~~evaluate ~~procedure for~~ the ~~assessment~~efficacy of ~~applications for clinical trials, which is divided in two parts. Part I is assessed by~~ the ~~competent~~product ~~authorities of all EU Member States in which an application~~ for ~~authorization~~specific oftargeted ~~a clinical trial has been submitted (Member States concerned)~~diseases. Part II is assessed separately by each Member State concerned. Strict deadlines have been established for the assessment of clinical trial applications. The role of the relevant ethics committees in the assessment procedure will continue to be governed by the national law of the concerned EU Member State. However, overall related timelines will be defined by the Clinical Trials Regulation.

•

Tophase ~~obtain~~3. aClinical ~~marketing~~trials ~~authorization~~are ofundertaken ain ~~drug~~an inexpanded patient population to further evaluate dosage, clinical efficacy, and safety, often at geographically dispersed trial sites. These clinical trials are intended to establish the ~~European~~overall ~~Union~~risk to benefit ratio of the investigational product and provide, weif appropriate, an adequate basis for product labeling. These trials may ~~submit~~include ~~marketing~~comparisons ~~authorization~~with ~~applications,~~placebo and/or ~~MAA,~~other ~~either~~comparator ~~under~~treatments. The duration of treatment is often extended to mimic the ~~so-called~~actual ~~centralized~~use orof ~~national~~a ~~authorization~~product ~~procedures~~during marketing.

36Postmarketing Requirements (PMRs) and Postmarking Commitments (PMCs), sometimes referred to as phase 4 clinical trials, may be conducted after initial marketing approval. These clinical trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for long-term safety follow-up. In certain instances, the FDA may mandate the performance of phase 4 clinical trials as a condition of approval of a BLA.

~~Centralized~~Progress ~~Procedure~~reports detailing the results of the clinical trial must be submitted at least annually to the FDA and more frequently if serious adverse events, or SAEs, occur. The FDA or the trial sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research participants are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the

The centralized procedure provides for the grant of a single marketing authorization following a favorable opinion by the European Medicines Agency, or EMA, that is valid in all 27 European Union member states, or EU member states, as well as Iceland, Liechtenstein and Norway. The centralized procedure is compulsory for medicines produced by specified biotechnological processes, products designated as orphan medicinal products, advanced-therapy medicines (such as gene-therapy, somatic cell-therapy or tissue-engineered medicines) and products with a new active substance indicated for the treatment of specified diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative disorders or autoimmune diseases and other immune dysfunctions and viral diseases. The centralized procedure is optional for products that represent a significant therapeutic, scientific or technical innovation, or whose authorization would be in the interest of public health. Under the centralized procedure the maximum timeframe for the evaluation of an MAA by the EMA is 210 days, excluding clock stops, when additional written or oral information is to be provided by the applicant in response to questions asked by the Committee for Medicinal Products for Human Use, or the CHMP. Accelerated assessment 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 the point of view of therapeutic innovation. The timeframe for the evaluation of an MAA under the accelerated assessment procedure is of 150 days, excluding stop-clocks.32

~~National~~clinical ~~authorization~~protocol, ~~procedures~~GCP, or other IRB requirements, or if the investigational product has been associated with unexpected serious harm to patients. Additionally, some trials are overseen by an independent group of qualified experts organized by the trial sponsor known as the data safety monitoring board or committee. This group provides recommend continuation, modification, or termination for whether a trial may move forward at designated checkpoints.

~~There~~During ~~are~~the ~~also~~development ~~two~~of ~~other~~a ~~possible~~new ~~routes~~pharmaceutical and/or biological products, sponsors have the opportunity to ~~authorize~~meet ~~medicinal~~with ~~products~~the inFDA ~~several~~at EUcertain ~~countries~~points, ~~which~~including ~~are~~prior ~~available~~to submission of an IND, at the end of phase 2, and before submission of a NDA/NDA/BLA. These meetings can provide an opportunity for ~~investigational~~the ~~medicinal~~sponsor ~~products~~to ~~that~~share ~~fall~~information ~~outside~~about the ~~scope~~data gathered to date, for the FDA to provide guidance, and for the sponsor and the FDA to reach agreement on the next phase of development. Sponsors typically use the ~~centralized~~end ~~procedure:~~of phase 2 meeting to discuss their phase 2 clinical results with the agency and to present their plans for the pivotal phase 3 studies that they believe will support approval of the new drug or biological product.

~~Decentralized~~Human ~~procedure~~immunotherapy products are rapidly evolving category of therapeutics. ~~Using~~Because ~~the~~this ~~decentralized~~is ~~procedure~~a relatively new and expanding area of novel therapeutic interventions, anthere ~~applicant~~can ~~may~~be ~~apply~~no ~~for~~assurance ~~simultaneous~~as ~~authorization~~to inthe ~~more~~length ~~than~~of ~~one~~the EUclinical ~~country~~trial period, the number of ~~medicinal~~participants ~~products~~the ~~that~~FDA ~~have~~will ~~not~~require ~~yet~~to ~~been~~be ~~authorized~~enrolled in ~~any~~the EUtrials ~~country~~in order to establish the safety, efficacy, purity and ~~that~~potency doof ~~not~~immunotherapy ~~fall~~products, ~~within~~or that the ~~mandatory~~data ~~scope~~generated ofin these trials will be acceptable to the ~~centralized~~FDA ~~procedure~~to support marketing approval.

~~Mutual~~Concurrently ~~recognition~~with ~~procedure.~~clinical Intrials, companies usually complete additional studies and must also develop additional information about the ~~mutual~~physical ~~recognition~~characteristics ~~procedure,~~of athe ~~medicine~~pharmaceutical isand/or ~~first~~biological ~~authorized~~products inas ~~one~~well EUas ~~Member~~finalize ~~State,~~a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. To help reduce the ~~national~~risk ~~procedures~~of the introduction of ~~that~~adventitious ~~country.~~agents ~~Following~~with ~~this~~use of biological products, ~~further~~the ~~marketing~~PHSA ~~authorizations~~emphasizes ~~can~~the importance of manufacturing control for products whose attributes cannot be ~~sought~~precisely ~~from~~defined. ~~other~~The EUmanufacturing ~~countries~~process inmust abe ~~procedure~~capable ~~whereby~~of consistently producing quality batches of the ~~countries~~candidate ~~concerned~~and, ~~agree~~among toother ~~recognize~~things, the ~~validity~~sponsor must develop methods for testing the identity, strength, quality, potency and purity of the ~~original~~final product. Additionally, ~~national~~appropriate ~~marketing~~packaging ~~authorization~~must be selected and tested and stability studies must be conducted to demonstrate that the final product does not undergo unacceptable deterioration over its retest date or shelf life.

~~Under~~U.S. ~~the~~Review above-described procedures, before granting the marketing authorization, the EMA or the competent authorities of the Member States of the EEA make an assessment of the risk-benefit balance of the product on the basis of scientific criteria concerning its quality, safety and ~~efficacy.~~Approval Processes

~~Conditional~~Assuming ~~Approval~~successful completion of the required clinical testing, the results of the preclinical studies and clinical trials, along with information relating to the product’s chemistry, manufacturing, and controls (CMC) are submitted to the FDA as part of an NDA/NDA/BLA requesting approval to market the product for one or more indications. An NDA/NDA/BLA must contain proof of the product candidate’s safety, purity, potency and potency (efficacy) for its proposed indication or indications. Data may come from company-sponsored clinical trials intended to test the safety and efficacy of a product’s use or from a number of alternative sources, including studies initiated by investigators. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of the investigational product to the satisfaction of the FDA. The testing and approval processes require substantial time and effort and there can be no assurance that the FDA will accept the NDA/NDA/BLA for filing and, even if filed, that any approval will be granted on a timely basis, if at all.

InUnder specific circumstances, E.U. legislation (Article 14(7) Regulation (EC) No 726/2004 and Regulation (EC) No 507/2006 on Conditional Marketing Authorizations for Medicinal Products for Human Use) enables applicants to obtain a conditional marketing authorization prior to obtaining the ~~comprehensive~~Prescription ~~clinical~~Drug ~~data~~User ~~required~~Fee ~~for~~Act, ~~an application for a full marketing authorization. Such conditional approvals may be granted for product candidates (including medicines designated~~ as ~~orphan~~amended, ~~medicinal~~or ~~products) if (i) the risk-benefit balance of the product candidate is positive~~PDUFA, ~~(ii)~~each itNDA/NDA/BLA ismust ~~likely that the applicant will~~ be inaccompanied by a ~~position~~significant touser ~~provide the required comprehensive clinical trial data~~fee, ~~(iii) the product fulfills unmet medical needs~~ and ~~(iv)~~ the ~~benefit~~sponsor ~~to public health~~ of ~~the~~an ~~immediate~~approved ~~availability~~NDA/NDA/BLA onis ~~the~~also ~~market~~subject ofto ~~the~~an ~~medicinal~~annual ~~product~~program ~~concerned~~fee. ~~outweighs~~The ~~the~~FDA ~~risk~~adjusts ~~inherent in~~ the ~~fact~~PDUFA ~~that~~user ~~additional~~fees ~~data~~on ~~are~~an ~~still~~annual ~~required~~basis. AFee ~~conditional~~waivers ~~marketing~~or ~~authorization~~reductions ~~may~~are ~~contain~~available ~~specific~~in ~~obligations~~certain ~~to be fulfilled by the marketing authorization holder~~circumstances, including ~~obligations~~a ~~with~~waiver ~~respect to the completion~~ of ~~ongoing or new studies, and with respect to~~ the ~~collection~~application offee ~~pharmacovigilance data. Conditional marketing authorizations are valid~~ for ~~one~~the ~~year,~~first ~~and~~application ~~may~~filed beby ~~renewed~~a ~~annually,~~small ifbusiness. ~~the risk-benefit balance remains positive~~Additionally, ~~and~~no ~~after~~user anfees ~~assessment~~are ofassessed ~~the~~on ~~need~~NDA/NDA/BLAs for ~~additional~~products ordesignated ~~modified~~as ~~conditions~~orphan ordrugs, ~~specific~~unless ~~obligations. The timelines for~~ the ~~centralized~~product ~~procedure described above~~ also ~~apply~~includes ~~with respect to the review by the CHMP of applications for~~ a ~~conditional~~non-orphan ~~marketing authorization~~indication.

~~Pediatric~~According ~~Studies~~to the goals and policies for original NDA/NDA/BLAs agreed to by the FDA under PDUFA, the FDA has ten months (Standard timeframe) from the accepted filing date to complete an initial review of the application and respond to the applicant, and six months from the filing date for an application with priority review. For all NDA/NDA/BLAs, the ten and six-month time periods run from the filing date; for most other original applications, the ten and six-month time periods run from the submission date. Despite these review goals, it is not uncommon for FDA review of a NDA/NDA/BLA to extend beyond the goal date.

~~Prior~~Within to60 ~~obtaining~~days afollowing ~~marketing~~submission ~~authorization~~of in the ~~European Union~~application, ~~applicants~~the ~~have~~FDA toreviews ~~demonstrate compliance with all measures included in~~ an ~~EMA-approved~~NDA/BLA ~~Pediatric~~submitted ~~Investigation~~to ~~Plan,~~determine orif ~~PIP,~~it ~~covering~~is ~~all~~substantially ~~subsets~~complete ofbefore the ~~pediatric~~agency ~~population,~~accepts ~~unless~~it ~~the~~for ~~EMA~~filing. ~~has~~The ~~granted~~FDA amay ~~product~~Refuse-~~specific~~to-File ~~waiver,~~(RTF) aany ~~class~~NDA/NDA/BLA ~~waiver,~~that orit adeems ~~deferral~~incomplete ~~for one~~ or ~~more~~not ofproperly ~~the~~reviewable ~~measures~~at ~~included in~~ the ~~PIP.~~time ~~The~~of ~~respective~~submission ~~requirements~~and ~~for~~may ~~all~~request ~~marketing~~additional ~~authorization~~information. ~~procedures~~In ~~are~~this ~~set~~event, ~~forth~~the ~~in Regulation (EC) No 1901~~NDA/~~2006,~~NDA/BLA ~~which~~must isbe ~~referred~~resubmitted towith as the ~~Pediatric~~additional ~~Regulation~~information. ~~This~~The ~~requirement~~resubmitted ~~also~~application ~~applies~~is ~~when~~subject ato ~~company~~review ~~wants~~before tothe ~~add~~FDA aaccepts ~~new~~it ~~indication,~~for ~~pharmaceutical~~filing. ~~form~~Once orthe ~~route~~submission ofis ~~administration~~accepted for afiling, ~~medicine~~the ~~that~~FDA isbegins ~~already~~an ~~authorized.~~in-depth ~~The~~substantive ~~Pediatric~~review ~~Committee~~ of the ~~EMA,~~NDA/NDA/BLA. orThe ~~PDCO,~~FDA ~~may~~reviews ~~grant~~the ~~deferrals~~NDA/NDA/BLA ~~for~~to ~~some medicines~~determine, ~~allowing~~among aother ~~company~~things, towhether ~~delay development of~~ the ~~medicine~~proposed inproduct ~~children until there~~ is ~~enough~~safe, ~~information~~potent, toand/or ~~demonstrate~~effective for its ~~effectiveness~~intended use, and ~~safety~~has inan ~~adults.~~acceptable ~~The~~purity ~~PDCO~~profile, ~~may~~and ~~also~~whether ~~grant~~the ~~waivers~~product ~~when~~is ~~development~~being ofmanufactured ain ~~medicine~~accordance inwith ~~children~~cGMP isto ~~not~~assure ~~needed~~and orpreserve isthe ~~not~~product’s ~~appropriate~~identity, ~~such~~safety, asstrength, ~~for~~quality, ~~diseases~~potency ~~that~~and ~~only~~purity. ~~affect~~The ~~the~~review ~~elderly~~process ~~population.~~

3733

~~Before~~may abe ~~marketing~~extended ~~authorization~~by ~~application~~the ~~can~~FDA befor ~~filed,~~three oradditional anmonths ~~existing~~for ~~marketing~~major ~~authorization~~amendments ~~can~~or bein ~~amended,~~ the ~~EMA~~case ~~determines~~of ~~that~~a ~~companies~~clarification ~~actually~~provided ~~comply~~by ~~with~~ the ~~agreed~~applicant ~~studies~~to ~~and~~address ~~measures~~an ~~listed~~outstanding indeficiency ~~each~~identified ~~relevant~~by ~~PIP~~the FDA following the original submission.

~~European~~The ~~Union~~FDA ~~Regulatory~~may ~~Exclusivity~~refer applications for novel products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making final decisions on approval. The FDA may independently analyze or validate submitted data, which could result in extensive discussions between the FDA and the applicant during the review process. The FDA also may require submission of a risk evaluation and mitigation strategy, or REMS, if it determines that a REMS is necessary to ensure that the benefits of the drug outweigh its risks and to assure the safe use of the drug or biological product. The REMS could include medication guides, physician communication plans, assessment plans and/or elements to assure safe use, such as restricted distribution methods, patient registries or other risk minimization tools. The FDA determines the requirement for a REMS, as well as the specific REMS provisions, on a case-by-case basis. If the FDA concludes a REMS is needed, the sponsor of the NDA/BLA must submit a proposed REMS. The FDA NDA/NDA/BLA approval is contingent on agreeing to REMS, if required.

InBefore ~~the~~approving ~~European~~an ~~Union~~NDA/NDA/BLA, ~~new~~the ~~products~~FDA ~~authorized~~will ~~for~~typically ~~marketing~~conduct ~~(i.e.,~~a ~~reference~~pre-approval ~~products)~~inspection ~~qualify~~of ~~for~~the ~~eight~~facilities ~~years~~at ofwhich ~~data~~the ~~exclusivity~~product ~~and~~is anmanufactured. ~~additional~~The ~~two~~FDA ~~years~~will ofnot ~~market~~approve ~~exclusivity~~the ~~upon~~product ~~marketing~~unless ~~authorization.~~it ~~The~~determines ~~data~~that ~~exclusivity~~the ~~period~~manufacturing ~~prevents~~processes ~~generic~~and orfacilities ~~biosimilar~~are ~~applicants~~compliant ~~from~~with ~~relying~~cGMP onrequirements ~~the preclinical~~ and ~~clinical~~adequate ~~trial~~to ~~data~~assure ~~contained~~consistent inproduction ~~the dossier~~ of the ~~reference~~ product ~~when~~within ~~applying~~required ~~for~~specifications. aFor ~~generic~~immunotherapy orproducts, ~~biosimilar marketing authorization in~~ the ~~European~~FDA ~~Union~~also ~~during~~will anot ~~period~~approve ofthe ~~eight~~product ~~years~~if ~~from~~ the ~~date~~manufacturer onis ~~which~~not ~~the~~in ~~reference~~compliance ~~product~~with ~~was~~the ~~first~~cGTPs, ~~authorized~~to in the ~~European~~extent ~~Union~~applicable. ~~The~~These ~~market~~are ~~exclusivity~~FDA ~~period~~regulations ~~prevents~~and aguidance ~~successful~~documents ~~generic~~that orgovern ~~biosimilar~~the ~~applicant~~methods ~~from~~used ~~commercializing its product~~ in, and the EUfacilities ~~until~~and ~~ten~~controls ~~years~~used ~~have~~for, ~~elapsed from~~ the ~~initial~~manufacture ~~authorization~~ of ~~the~~human ~~reference~~cells, ~~product~~tissues, inand ~~the~~cellular ~~EU.~~and ~~The ten~~tissue-~~year~~based ~~market~~products ~~exclusivity~~(HCT/Ps), ~~period~~which ~~can~~are behuman ~~extended~~cells toor atissue ~~maximum~~intended offor ~~eleven~~implantation, ~~years~~transplant, ifinfusion, ~~during~~or ~~the~~transfer ~~first~~into ~~eight~~a ~~years~~human ofrecipient. ~~those~~The ~~ten~~primary ~~years,~~intent of the ~~marketing~~cGTP ~~authorization~~requirements ~~holder~~is ~~obtains~~to anensure ~~authorization~~that ~~for~~cellular ~~one~~tissue-based orproducts ~~more~~are ~~new~~manufactured ~~therapeutic~~in ~~indications~~a ~~which,~~manner ~~during~~designed ~~the scientific evaluation prior~~ to ~~their~~prevent ~~authorization~~the introduction, ~~are~~transmission ~~held~~and tospread ~~bring~~of acommunicable ~~significant~~disease. ~~clinical~~Additionally, ~~benefit~~before inapproving ~~comparison~~an ~~with existing therapies. In 2024~~NDA/NDA/BLA, the ~~European~~FDA ~~Parliament~~will ~~voted~~typically toinspect ~~adopt~~one aor ~~new~~more ~~draft~~clinical ~~Regulation~~sites ~~and~~to ~~draft~~assure ~~Directive~~that ~~from~~ the ~~European~~clinical ~~Commission.~~trials ~~These~~were ~~proposals~~conducted ~~set~~in ~~out~~compliance ~~significant~~with ~~amendments~~IND totrial ~~the~~requirements ~~rules regarding regulatory data exclusivity~~ and ~~market~~GCP ~~protection~~requirements. ~~for~~To ~~new~~assure ~~medicines~~cGMP, incGTP ~~Europe.~~and ~~The~~GCP ~~draft~~compliance, ~~legislation~~an ~~will~~applicant ~~need~~must toincur besignificant ~~approved~~expenditure byof ~~the European Council~~time, ~~before~~money ~~implementation~~and effort in the ~~EU.~~areas ~~Once~~of ~~implemented~~training, ~~the~~record ~~Regulation~~keeping, ~~will take effect in all EU Member States on a defined date~~production, ~~likely~~and toquality ~~be approximately in three to four years~~control.

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

~~The~~Notwithstanding ~~criteria~~the ~~for~~submission ~~designating~~of anrelevant ~~orphan~~data ~~medicinal~~and ~~product~~information, in the ~~European~~FDA ~~Union,~~may ~~are~~ultimately ~~similar~~decide inthat ~~principle to those in~~ the ~~United~~NDA/BLA ~~States.~~does ~~Under~~not ~~Article~~satisfy 3its ofregulatory ~~Regulation~~criteria ~~(EC)~~for ~~141/2000,~~approval aand ~~medicinal~~deny ~~product~~approval or may berequire ~~designated~~additional asclinical ~~orphan~~or ifother ~~(i)~~data itand isinformation. ~~intended~~Data ~~for~~obtained ~~the~~from ~~diagnosis,~~clinical ~~prevention~~trials orare ~~treatment~~not ofalways aconclusive ~~life-threatening~~and orthe ~~chronically~~FDA ~~debilitating~~may ~~condition;~~interpret ~~(ii)~~data ~~either~~differently ~~(a)~~than ~~such~~we ~~condition~~interpret ~~affects~~the nosame ~~more~~data. ~~than~~Based ~~five~~on ~~in 10,000 persons in~~ the ~~European~~FDA’s ~~Union~~evaluation ~~when~~of the ~~application~~NDA/BLA isand ~~made~~accompanying information, orincluding ~~(b)~~ the ~~product,~~results ~~without~~of the ~~benefits~~inspection ~~derived~~of ~~from~~the ~~orphan~~manufacturing ~~status~~facilities, ~~would~~the ~~not~~FDA ~~generate~~may ~~sufficient~~issue ~~return~~either inan ~~the~~approval ~~European~~letter ~~Union~~or toa ~~justify~~Complete ~~investment;~~Response ~~and~~Letter, ~~(iii)~~or ~~there~~CRL. ~~exists~~An noapproval ~~satisfactory~~letter ~~method~~authorizes ofcommercial ~~diagnosis,~~marketing ~~prevention~~of orthe ~~treatment~~product ofwith ~~such~~specific ~~condition~~prescribing ~~authorized~~information for ~~marketing~~specific inindications. A CRL indicates that the ~~European~~review ~~Union,~~cycle orof ifthe ~~such~~application ais ~~method~~complete ~~exists,~~and the ~~product~~application will not be ofapproved ~~significant~~in ~~benefit~~its topresent ~~those~~form. ~~affected~~CRL bygenerally outlines the ~~condition,~~deficiencies asin ~~defined~~the insubmission ~~Regulation~~and ~~(EC)~~may ~~847/2000.~~require ~~Orphan~~substantial ~~medicinal~~additional ~~products~~testing ~~are~~or ~~eligible~~information in order for ~~financial~~the ~~incentives~~FDA ~~such~~to asreconsider ~~reduction~~the ofapplication. ~~fees~~The orCRL ~~fee~~may ~~waivers~~require ~~and~~additional ~~are,~~clinical ~~upon~~or ~~grant~~other ofdata, aadditional ~~marketing~~pivotal ~~authorization,~~phase ~~entitled~~3 toclinical ~~ten~~trial(s) ~~years~~and/or ofother ~~market~~significant ~~exclusivity~~and ~~for~~time-consuming ~~the~~requirements ~~approved~~related ~~therapeutic~~to ~~indication.~~clinical ~~The~~trials, ~~application~~preclinical ~~for~~studies ~~orphan~~or ~~designation~~manufacturing. ~~must~~If bea ~~submitted~~CRL ~~before~~is issued, the ~~application~~applicant ~~for~~may ~~marketing~~choose ~~authorization.~~to ~~The~~either ~~applicant~~resubmit ~~will~~the ~~receive~~NDA/BLA aaddressing ~~fee~~all ~~reduction~~the ~~for~~deficiencies ~~the~~identified ~~marketing~~in ~~authorization~~the ~~application~~letter, ifor withdraw the ~~orphan~~application. ~~designation~~If ~~has~~and ~~been~~when ~~granted,~~those ~~but~~deficiencies ~~not~~have ifbeen addressed to the ~~designation~~FDA’s issatisfaction ~~still~~in ~~pending~~a atresubmission of the ~~time~~NDA/BLA, the ~~marketing~~FDA ~~authorization~~will isissue ~~submitted~~an approval letter. ~~Orphan~~The ~~designation~~FDA ~~does~~has ~~not~~committed ~~convey~~to ~~any~~reviewing ~~advantage~~such resubmissions in, orresponse ~~shorten~~to ~~the~~an ~~duration~~issued ~~of,~~CRL ~~the~~in ~~regulatory~~either ~~review~~two ~~and~~or ~~approval~~six ~~process.~~months

The ten-year market exclusivity in the European Union 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, for example, if the product is sufficiently profitable not to justify maintenance of market exclusivity. Additionally, marketing authorization may be granted to a similar product for the same indication at any time if:34

depending on the ~~second~~type ~~applicant~~of ~~can~~information ~~establish~~included. ~~that~~Even ~~its~~with ~~product,~~the ~~although~~submission ~~similar,~~of isthis ~~safer~~additional information, ~~more~~however, ~~effective~~the orFDA ~~otherwise~~ultimately ~~clinically~~may ~~superior;~~decide that the application does not satisfy the regulatory criteria for approval.

If a product receives regulatory approval from the ~~applicant~~FDA, ~~consents~~the approval is limited to the conditions of use (e.g., patient population, indication) described in the application. Further, depending on the specific risk(s) to be addressed, the FDA may require that contraindications, warnings or precautions be included in the product labeling, require that post-approval trials, including phase 4 clinical trials, be conducted to further assess a ~~second~~product’s ~~orphan~~safety ~~medicinal~~after approval, require testing and surveillance programs to monitor the product ~~application;~~after commercialization, or impose other conditions, including distribution and use restrictions or other risk management mechanisms under a REMS, which can materially affect the potential market and profitability of the product. The FDA may prevent or limit further marketing of a product based on the results of post-marketing trials or surveillance programs. After approval, some types of changes to the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements and FDA review and approval.

~~the~~Fast ~~applicant~~Track, ~~cannot~~Breakthrough ~~supply~~Therapy ~~enough~~and ~~orphan~~Priority ~~medicinal~~Review ~~product.~~Designations

~~PRIME~~The FDA is authorized to designate certain products for expedited development or review if they are intended to address an unmet medical need in the treatment of a serious or life-threatening disease or condition. These programs include fast track designation, Breakthrough Therapy Designation, priority review designation, and regenerative medicine advanced therapy designation.

~~The~~To ~~EMA~~be ~~grants~~eligible ~~access~~for toa fast-track designation, the ~~Priority~~FDA ~~Medicines~~must determine, orbased ~~PRIME,~~on ~~program~~the torequest ~~investigational~~of ~~medicines~~a ~~for~~sponsor, ~~which~~that ita ~~determines~~product ~~there~~is intended to betreat ~~preliminary~~a ~~data~~serious ~~available~~or ~~showing~~life-threatening disease or condition and demonstrates the potential to address an unmet medical need ~~and~~by ~~bring~~providing a ~~major~~therapy ~~therapeutic~~where ~~advantage~~none exists or a therapy that may be potentially superior to ~~patients~~existing therapy based on efficacy or safety factors. AsFast ~~part~~track designation provides opportunities for more frequent interactions with the FDA review team to expedite development and review of the ~~program~~product. The FDA may also review sections of the NDA/BLA for a fast-track product on a rolling basis before the complete application is submitted, ~~EMA~~if ~~provides~~the ~~early~~sponsor and ~~enhanced~~the ~~dialogue~~FDA ~~and~~agree ~~support~~on toa ~~optimize~~schedule for the ~~development~~submission of ~~eligible~~the ~~medicines~~application sections and ~~speed~~the upsponsor ~~their~~pays ~~evaluation~~any required user fees upon submission of the first section of the NDA or NDA/BLA. In addition, ~~aiming~~fast totrack ~~bring~~designation ~~promising~~may ~~treatments~~be towithdrawn ~~patients~~by ~~sooner~~the sponsor or rescinded by the FDA if the designation is no longer supported by data emerging from the clinical trial process.

38In addition, with the enactment of the Food and Drug Administration Safety and Innovation Act, or FDASIA, in 2012, Congress created a new regulatory program for product candidates designated by FDA as “breakthrough therapies” upon a request made by the IND sponsors. A breakthrough therapy is defined as a drug or biologic that is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug or biologic may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. Drugs or biologics designated as breakthrough therapies are also eligible for accelerated approval of their respective marketing applications. The FDA must take certain actions with respect to breakthrough therapies, such as holding timely meetings with and providing advice to the product sponsor, which are intended to expedite the development and review of an application for approval of a breakthrough therapy.

~~Periods~~Next, the FDA may designate a product for priority review if it is a drug or biologic that treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness. The FDA determines at the time that the marketing application is submitted, on a case-by-case basis, whether the proposed drug represents a significant improvement in treatment, prevention or diagnosis of ~~Authorization~~disease when compared with other available therapies. Significant improvement may be illustrated by evidence of increased effectiveness in the treatment of a condition, elimination or substantial reduction of a treatment-limiting drug reaction, documented enhancement of patient compliance that may lead to improvement in serious outcomes, or evidence of safety and ~~Renewals~~effectiveness in a new subpopulation. A priority review designation is intended to direct overall attention and resources to the evaluation of such applications, and to shorten the FDA’s goal for taking action on a marketing application from ten months to six months for an original NDA/BLA from the date of filing.

AEven ~~marketing~~if ~~authorization~~a isproduct ~~valid~~qualifies for ~~five~~one ~~years in principle and the marketing authorization may be renewed after five years on the basis of a re-evaluation of the risk-benefit balance by the EMA~~ or bymore ~~the competent authority~~ of ~~the~~these ~~authorizing member state. To this end~~programs, the ~~marketing~~FDA ~~authorization~~may ~~holder~~later ~~must~~decide ~~provide~~that the ~~EMA~~product orno ~~the~~longer ~~competent~~meets ~~authority with a consolidated version of~~ the ~~file~~conditions infor ~~respect~~qualification ofor ~~quality,~~decide ~~safety~~that ~~and efficacy, including all variations introduced since~~ the ~~marketing~~time ~~authorization~~period ~~was~~for ~~granted,~~FDA atreview ~~least~~or ~~six~~approval ~~months~~will ~~before~~not ~~the marketing authorization ceases to~~ be ~~valid~~shortened. ~~Once renewed~~Furthermore, ~~the~~fast ~~marketing~~track ~~authorization~~designation, isbreakthrough ~~valid~~therapy ~~for~~designation anand ~~unlimited~~priority ~~period,~~review ~~unless~~do ~~the~~not ~~European~~change ~~Commission or~~ the ~~competent~~standards ~~authority~~for ~~decides,~~approval onand ~~justified~~may ~~grounds relating to pharmacovigilance, to proceed with one additional five-year renewal. Any authorization which is~~ not ~~followed~~ultimately byexpedite the ~~actual~~development ~~placing of the drug on the EU market (in case of centralized procedure)~~ or onapproval ~~the market of the authorizing member state within three years after authorization ceases to be valid (the so-called sunset clause)~~process.

~~Rest~~As part of the ~~World~~21st ~~Regulation~~Century Cures Act, congress created an accelerated approval pathway for regenerative medicine advanced therapies, or RMATs, which includes therapeutic tissue engineered products, human cell and tissue products, cell therapies and

For other countries outside of the European Union and the United States, 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 jurisdiction to jurisdiction. Additionally, the clinical trials must be conducted in accordance with GCP requirements and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.35

Ifcombination weproducts ~~fail~~using toany ~~comply~~such ~~with~~therapies. ~~applicable~~The ~~foreign~~program ~~regulatory~~is ~~requirements,~~intended ~~we may be subject~~ to, ~~among~~facilitate ~~other~~expedited ~~things,~~development ~~fines,~~and ~~suspension~~review ~~or withdrawal~~ of ~~regulatory~~RMATs ~~approvals,~~intended ~~product~~to ~~recalls,~~address ~~seizure~~serious ofdiseases ~~products,~~or ~~operating restrictions and criminal prosecution~~conditions.

~~Coverage~~A sponsor may request a RMAT designation from the FDA concurrently with or any time after the IND submission. The FDA has 60 calendar days to determine if the drug product meets the required criteria. Preliminary clinical evidence that the product has the potential to address a serious unmet need or condition is expected, ~~Pricing~~is not required to indicate that the drug product may offer significant improvement over current therapies. The RMAT designation provides the same benefits of the fast track and ~~Reimbursement~~breakthrough designation programs and programs may be eligible for priority review. Products with the RMAT designation may also be eligible for accelerated approval if pre-agreed criteria are met.

~~Sales~~Accelerated ofApproval pharmaceutical products approved by the FDA will depend, in significant part, on the availability of third-party coverage and reimbursement for the products. Third-party payors include government healthcare programs in the United States such as Medicare and Medicaid, managed care providers, private health insurers and other organizations. These third-party payors are increasingly challenging the prices of products and examining the cost-effectiveness of medical products and services. In addition, significant uncertainty exists as to the reimbursement status of newly approved healthcare products. The process for determining whether a payor will provide coverage for a product may be separate from the process for setting the price or reimbursement rate that the payor will pay for the product once coverage is approved. Further, there is no uniform policy for coverage and reimbursement in the United States by third-party payors. Third-party payors may limit coverage to specific products on an approved list, or formulary, which might not include all of the approved products for a particular indication. We may need to conduct expensive pharmacoeconomic studies to demonstrate the medical necessity and cost-effectiveness of our products, in addition to the costs required to obtain FDA or other comparable regulatory approvals.Pathway

~~Moreover~~In addition, products studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may receive accelerated approval from the FDA and may be approved on the basis of adequate and well-controlled clinical trials establishing that the drug product has an effect on a ~~payor’s~~surrogate ~~decision~~endpoint that is reasonably likely to ~~provide~~predict ~~coverage~~clinical benefit. The FDA may also grant accelerated approval for such a drug or biologic when the product ~~does~~has ~~not~~an ~~imply~~effect ~~that~~on an ~~adequate~~intermediate ~~reimbursement~~clinical ~~rate~~endpoint ~~will~~that can be ~~approved.~~measured ~~Third-party~~earlier ~~reimbursement~~than ~~may~~an ~~not~~effect beon ~~sufficient~~irreversible tomorbidity ~~maintain~~or ~~price~~mortality, ~~levels~~or ~~high~~IMM, ~~enough~~and that is reasonably likely to ~~realize~~predict an ~~appropriate~~effect ~~return~~ on ~~investment~~IMM inor ~~product~~other ~~development~~clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments. ~~Our~~As ~~product~~a ~~candidates~~condition of approval, the FDA may ~~not~~require bethat ~~considered~~a ~~cost~~sponsor of a drug receiving accelerated approval perform post-~~effective.~~marketing Itclinical istrials ~~time~~to ~~consuming~~verify and ~~expensive~~describe tothe ~~seek~~predicted ~~coverage~~effect ~~and~~on ~~reimbursement~~IMM ~~from~~or ~~third-party~~other ~~payors.~~clinical ~~Coverage~~endpoint, and ~~reimbursement~~the product may ~~not~~ be ~~available~~subject orto ~~sufficient~~expedited towithdrawal ~~allow~~procedures. usDrugs and biologics granted accelerated approval are subject to ~~sell~~the ~~our~~same ~~products~~statutory standards, but approval is based on asurrogate ~~competitive~~endpoints ~~and~~reasonably ~~profitable~~likely ~~basis~~to predict benefit.

InFor ~~addition,~~the inpurposes ~~some~~of ~~foreign~~accelerated ~~countries~~approval, ~~the~~a ~~proposed~~surrogate ~~pricing~~endpoint ~~for~~is a ~~drug~~marker, ~~must~~such beas ~~approved~~a ~~before~~laboratory itmeasurement, ~~may~~radiographic beimage, ~~lawfully~~physical ~~marketed.~~sign, ~~The~~or ~~requirements~~other ~~governing~~measure ~~drug~~that ~~pricing~~is ~~vary~~thought ~~widely from country~~ to ~~country.~~predict ~~Some~~clinical ~~countries~~benefit, ~~provide~~but ~~that~~is ~~drug~~not ~~products~~itself ~~may be marketed only after~~ a ~~reimbursement~~measure ~~price~~of ~~has~~clinical ~~been agreed~~benefit. ~~Some~~Surrogate ~~countries~~endpoints ~~may~~can ~~require~~often ~~the~~be ~~completion~~measured ofmore ~~additional~~easily ~~studies that compare the cost-effectiveness of our product candidate to currently available therapies (so called health technology assessment,~~ or ~~HTA)~~more inrapidly ~~order~~than toclinical ~~obtain reimbursement or pricing approval~~endpoints. ~~For~~An ~~example,~~intermediate ~~the~~clinical ~~European~~endpoint ~~Union~~is ~~provides~~a ~~options~~measurement ~~for its member states to restrict the range~~ of ~~medicinal~~a ~~products~~therapeutic ~~for~~effect ~~which~~that ~~their~~is ~~national~~considered ~~health~~reasonably ~~insurance~~likely ~~systems provide reimbursement and~~ to ~~control~~predict the ~~prices~~clinical benefit of ~~medicinal products for human use. An EU Member State may approve~~ a ~~specific~~drug, ~~price~~such ~~for~~as ~~the~~an ~~medicinal~~effect ~~product or it may instead adopt a system of direct or indirect controls~~ on ~~the profitability of the ompany placing the medicinal product on the market~~IMM. ~~Other~~The EUFDA ~~Member~~experience ~~States~~is ~~allow~~evolving ~~companies~~with toaccelerated ~~fix~~approvals ~~their~~based ~~own~~on ~~prices~~intermediate ~~for~~clinical ~~drug~~endpoints, ~~products~~ but ~~monitor~~has ~~and~~indicated ~~control~~that ~~prescription~~such ~~volumes~~endpoints ~~and~~generally ~~issue~~may ~~guidance~~support toaccelerated ~~physicians~~approval towhen ~~limit~~the ~~prescriptions.~~therapeutic ~~There~~effect ~~can~~measured beby nothe ~~assurance~~endpoint ~~that~~is ~~any~~not ~~country~~itself ~~that~~a ~~has~~clinical ~~price~~benefit ~~controls~~and orbasis ~~reimbursement limitations~~ for ~~pharmaceutical~~traditional ~~products~~approval, ~~will~~if ~~allow~~there ~~favorable~~is ~~reimbursement~~a ~~and~~basis ~~pricing arrangements~~ for ~~any~~concluding ofthat ~~our products. Historically, products launched in~~ the ~~European~~therapeutic ~~Union~~effect dois ~~not~~reasonably ~~follow~~likely ~~price~~to ~~structures~~predict of the ~~United~~ultimate ~~States~~long-term ~~and~~clinical ~~generally~~benefit ~~tend~~of toa ~~be significantly lower~~drug.

39The accelerated approval pathway is most often used in settings in which the course of a disease is long and an extended period of time is required to measure the intended clinical benefit of a drug, even if the effect on the surrogate or intermediate clinical endpoint occurs rapidly. For example, accelerated approval has been used extensively in the development and approval of drugs for treatment of a variety of cancers in which the goal of therapy is generally to improve survival or decrease morbidity and the duration of the typical disease course requires lengthy and sometimes large clinical trials to demonstrate a clinical or survival benefit.

The ~~downward~~accelerated ~~pressure~~approval onpathway ~~health~~is ~~care~~usually ~~costs~~contingent inon ~~general,~~a ~~particularly~~sponsor’s ~~prescription~~agreement ~~drugs~~to conduct, ~~has~~in ~~become intense. As~~ a ~~result~~diligent manner, ~~increasingly~~additional ~~high~~post-approval ~~barriers~~confirmatory ~~are~~studies ~~being~~to ~~erected~~verify toand describe the ~~entry~~drug’s ofclinical ~~new products~~benefit. InAs ~~addition~~a result, ~~there~~a ~~can~~product becandidate ~~considerable~~approved ~~pressure~~on bythis ~~governments~~basis ~~and~~is ~~other~~subject ~~stakeholders~~to onrigorous ~~prices~~post-marketing ~~and~~compliance ~~reimbursement levels~~requirements, including asthe ~~part~~completion of ~~cost~~phase ~~containment~~4 ~~measures.~~or ~~Political,~~post-approval ~~economic~~clinical ~~and~~trials ~~regulatory~~to ~~developments~~confirm ~~may~~the ~~further~~effect ~~complicate~~on ~~pricing~~the ~~negotiations,~~clinical ~~and~~endpoint. ~~pricing~~Failure ~~negotiations~~to ~~may~~conduct ~~continue~~required ~~after~~post-approval ~~reimbursement~~studies, ~~has~~or ~~been~~to ~~obtained.~~confirm ~~Reference~~the ~~pricing~~predicted ~~used~~clinical bybenefit ~~various~~of EUthe ~~Member~~product ~~States~~during ~~and~~post-marketing ~~parallel~~studies, ~~distribution~~would ~~(arbitrage~~allow ~~between~~the ~~low-priced~~FDA ~~and~~to ~~high-~~withdraw ~~priced~~approval ~~member~~of ~~states)~~the ~~can~~drug. ~~further~~All ~~reduce~~promotional ~~prices.~~materials ~~Any~~for ~~country~~product ~~that~~candidates ~~has~~being ~~price~~considered ~~controls~~and orapproved ~~reimbursement~~under ~~limitations~~the ~~for~~accelerated ~~drug~~approval ~~products~~program ~~may~~are ~~not~~subject ~~allow~~to ~~favorable~~prior ~~reimbursement~~review ~~and~~by ~~pricing~~the ~~arrangements~~FDA.

~~Other~~Orphan ~~U.S.~~Drug ~~Health~~Designation ~~Care Laws~~ and ~~Regulations~~Exclusivity

~~Although~~Under ~~we currently do not have any products on~~ the ~~market,~~Orphan ~~our~~Drug ~~current and future arrangements with healthcare professionals~~Act, ~~investigators,~~the ~~consultants,~~FDA ~~customers~~may ~~and~~grant ~~third-party~~orphan ~~payors~~drug ~~expose~~designation us to ~~broadly~~a ~~applicable~~drug ~~healthcare~~or ~~regulation~~biologic ~~and~~product ~~enforcement~~intended byto ~~the~~treat ~~U.S.~~a ~~federal~~rare ~~government~~disease ~~and~~or ~~the~~condition, ~~states and foreign governments in~~ which weis ~~conducts~~generally ~~our~~a ~~business,~~disease ~~such~~or ascondition ~~fraud~~that ~~and~~affects ~~abuse~~fewer ~~laws, transparency and health information privacy rules and regulations. These laws include, without limitation:~~than

~~The federal Anti-Kickback Statute – or AKS~~200,000 42individuals ~~U.S.C.~~in ~~§ 1320a-7b(b):~~ the ~~federal~~United ~~AKS is a criminal law which~~States, ~~prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving~~ or ~~paying~~more ~~remuneration,~~than ~~directly or indirectly~~200,000 inindividuals ~~cash or~~ in ~~kind,~~the toUnited ~~induce~~States orand ~~reward~~for ~~either~~which ~~the~~there ~~referral~~is ofno anreasonable ~~individual~~expectation ~~for~~that the ~~furnishing~~cost of ~~any~~developing ~~item~~and ormaking ~~service,~~available orin ~~for~~the ~~purchasing,~~United ~~leasing,~~States ~~ordering,~~a drug or ~~arranging~~biologic for orthis ~~recommending~~type ~~purchasing,~~of ~~leasing,~~disease or ~~ordering~~condition ~~any~~will ~~good or service, for which payment may~~ be ~~made,~~recovered infrom ~~whole~~sales or in ~~part,~~the ~~under~~United aStates ~~federal~~for ~~health~~that ~~care~~drug ~~program~~or ~~such as Medicare and Medicaid~~biologic. ~~Remuneration~~Orphan ~~includes~~drug ~~anything~~designation ofmust ~~value~~be ~~and~~requested ~~can~~before ~~take~~submitting ~~many~~an ~~forms~~NDA/BLA. ~~besides~~After ~~cash,~~the ~~such~~FDA asgrants ~~free~~orphan ~~rent,~~drug ~~expensive hotel stays and meals~~designation, ~~and excessive compensation for medical directorships or consultancies. The AKS covers~~ the ~~payers~~identity of ~~kickbacks-those who offer or pay remuneration- as well as~~ the ~~recipients~~therapeutic ofagent ~~kickbacks-those~~and ~~who~~its ~~solicit~~potential ororphan ~~receive~~use ~~remuneration.~~will ~~While each party’s intent is a key element of their liability under the AKS, a person or entity can~~ be ~~found~~disclosed ~~guilty~~publicly ofby ~~violating~~ the ~~statute~~FDA; ~~without actual knowledge of~~ the ~~statute~~posting orwill ~~specific~~also ~~intent~~indicate towhether ~~violate it. A conviction for violation of~~ the ~~AKS~~drug ~~can result in criminal fines and/~~or ~~imprisonment~~biologic ~~and~~is ~~requires~~no ~~mandatory~~longer ~~exclusion~~designated ~~from participation in federal healthcare programs;~~

many US states have laws and regulations analogous to US federal fraud and abuse laws, such as individual state anti-kickback, fee-splitting and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payers;36

~~The~~as ~~Federal~~an ~~civil~~orphan ~~and criminal false claims laws, including the civil False Claims Act, or the FCA,—31 U~~drug.~~S.C.~~ §More §than ~~3729-3733,~~one ~~which~~product ~~prohibits~~candidate ~~individuals~~may orreceive ~~entities from knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal~~ an ~~obligation~~orphan todrug ~~pay~~designation ~~money to the federal government, and provides~~ for ~~civil whistleblower or qui tam actions that allow a private individual to file a lawsuit on behalf of~~ the ~~United~~same ~~State and entitles the whistleblower to a percentage of any recoveries~~indication. ~~Under~~Orphan ~~the~~drug ~~FCA~~designation itdoes is illegal to submit claims for payment to Medicare or Medicaid that an individual knows or should know are false or fraudulent; no specific intent to defraud is required. The civil FCA defines “knowing” to include not ~~only~~convey ~~actual~~any ~~knowledge~~advantage ~~but also instances~~ in ~~which the person acted in deliberate ignorance~~ or ~~reckless~~shorten ~~disregard of~~ the ~~truth~~duration ~~or falsity~~ of the ~~information.~~regulatory ~~Filing~~review false claims may result in fines of up to three times the programs’ loss plus $11,000 per claim filed. Under the civil FCA, each instance of an item or a service billed to Medicare or Medicaid counts as a claim. The fact that a claim results from a kickback or is made in violation of the Stark law also may render it false or fraudulent, creating liability under the civil FCA as well as the AKS or Stark law. Under the criminal FCA (18 U.S.C. § 287) penalties for submitting false claims include imprisonment and ~~criminal~~approval ~~fines; the OIG also may impose administrative civil monetary penalties for false or fraudulent claims;~~process.

If a product that has orphan drug designation subsequently receives the ~~federal~~first ~~civil~~FDA ~~monetary~~approval ~~penalties~~for ~~law~~the disease for which it has such designation, orthe ~~CMP~~product ~~(42~~is Uentitled to seven years of orphan product exclusivity.~~S.C.~~ §During ~~1320a~~the seven-~~7a)~~year exclusivity period, ~~prohibits~~the aFDA ~~person~~may ~~from~~not ~~presenting~~approve orany ~~causing~~other applications to bemarket ~~presented~~ a ~~claim~~product ~~that~~containing the ~~provider~~same ~~knows~~active ormoiety ~~should~~for ~~know~~the issame ~~improper~~disease, ~~presenting~~except in very limited circumstances, such as a ~~claim~~showing ~~that~~of clinical superiority to the ~~person~~product ~~knows~~with ororphan ~~should~~drug ~~know~~exclusivity. A product is ~~for~~clinically ansuperior ~~item~~if it is safer, more effective or ~~service~~makes ~~for~~a ~~which~~major ~~payment~~contribution ~~may~~to ~~not~~patient becare. ~~made~~Thus, ~~and~~orphan ~~violating~~drug exclusivity could block the ~~AKS.~~approval ~~The~~of ~~Office~~one of ~~Inspector~~our ~~General,~~potential orproducts ~~OIG~~for ofseven ~~the~~years USif ~~Department~~a ofcompetitor ~~Health~~obtains ~~and~~approval ~~Human~~of ~~Services,~~the orsame ~~DHHS,~~product ~~may~~as ~~seek~~defined ~~civil~~by ~~monetary~~the ~~penalties~~FDA and ~~sometimes~~we ~~exclusion~~are ~~for~~not aable ~~wide~~to ~~variety~~show the clinical superiority of ~~conduct~~our ~~and~~product iscandidate ~~authorized~~or toif ~~seek~~our ~~different~~product ~~amounts~~candidate’s ofindication ~~penalties~~is ~~and~~determined ~~assessments~~to ~~based~~be oncontained within the ~~type~~competitor’s ofproduct ~~violation~~orphan ~~at issue;~~indication.

In addition, the ~~federal~~FDA ~~Health~~will ~~Insurance~~not ~~Portability~~recognize ~~and~~orphan ~~Accountability~~drug ~~Act~~exclusivity ofif ~~1996~~a ~~and~~sponsor ~~its~~fails ~~implementing~~to ~~regulations,~~demonstrate orupon ~~HIPAA,~~approval ~~imposes~~that ~~criminal~~the ~~and~~product ~~civil~~is ~~liability~~clinically ~~for~~superior ~~executing~~to a ~~scheme~~previously toapproved ~~defraud~~product ~~any~~for ~~health~~the ~~care~~same ~~benefit~~orphan ~~program~~condition, regardless of whether or ~~making~~not ~~false~~the ~~statements~~approved ~~relating~~product towas ~~health~~designated ~~care~~an ~~matters;~~orphan drug or had orphan drug exclusivity.

40Patent Term Restoration

~~HIPAA,~~Depending asupon ~~amended~~the bytiming, ~~the~~duration ~~Health~~and ~~Information~~specifics ~~Technology~~of ~~for~~FDA ~~Economic~~approval ~~and~~of ~~Clinical~~our ~~Health~~biological ~~Act~~products, orsome ~~HITECH~~of ~~Act,~~our ~~and~~US ~~its~~patents ~~implementing~~may ~~regulations,~~be ~~also~~eligible ~~imposes~~for ~~obligations,~~limited ~~including~~patent ~~mandatory~~term ~~contractual~~extension. ~~terms,~~These ~~with~~patent ~~respect~~term extensions permit a patent restoration term of up to ~~safeguarding~~five years as compensation for any patent term lost during product development and the ~~privacy~~FDA regulatory review process. However, ~~security~~patent ~~and~~term ~~transmission~~restoration cannot extend the remaining term of ~~individually~~a ~~identifiable~~patent ~~health~~beyond ~~information,~~a ~~for~~total ~~covered~~of ~~entities,~~14 ~~including~~years ~~certain~~from ~~healthcare~~the ~~providers,~~product’s ~~health~~approval ~~plans~~date. The Patent Term Extension (PTE) period is generally one-half the time between the effective date of an IND, and ~~healthcare~~the ~~clearinghouses~~submission date of a NDA/BLA, ~~and~~plus ~~their~~the ~~business~~time ~~associates~~between the submission date of a NDA/BLA and ~~covered~~the ~~subcontractors~~approval of that ~~provide~~application. ~~services~~Only one patent applicable to an approved biological product is eligible for the extension, orand onthe ~~behalf~~extension must be filed within 60 days of FDA approval. The United States Patent and Trademark Office, in consultation with the ~~covered~~FDA, ~~entity~~reviews ~~that~~and ~~involve~~approves ~~individually~~the ~~identifiable~~application ~~health~~for ~~information;~~any patent term extension or restoration.

~~The~~Pediatric Physician Payments Sunshine Act (42 USC 1320a-7h) as known as “Open Payments” is a national disclosure program created by the Affordable Care Act, or ACA, that increases transparency into financial relationships between the health care industry (such as medical device manufacturers and pharmaceutical companies) and physicians or teaching hospitals. Drug, device, biological, and medical supply manufacturers, and group purchasing organizations are required to report payments or other transfers of value they make to physicians or teaching hospitals, as well as ownership or investment interests that a physician or his or her family members have in those entities. The Centers for Medicare & Medicaid Services, or CMS, collects data annually, and makes it publicly available and searchable online at openpaymentsdata.cms.gov. Applicable manufacturers are also be required to report information related to payments and other transfers of value provided in the previous year to physician assistants, nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists, and certified nurse midwives. Individual states have their own “sunshine act reporting laws” which vary from state to state;Exclusivity

Pediatric exclusivity is a type of non-patent marketing exclusivity available in the ~~U.S.~~United ~~Foreign~~States ~~Corrupt~~and, ~~Practices~~if ~~Act~~granted, it provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity or ~~FCPA,~~listed ~~and~~patents. ~~other~~This ~~anti~~six-~~corruption~~month ~~laws~~exclusivity ~~and~~may ~~regulations~~be ~~pertaining~~granted toif ~~our~~a ~~financial~~sponsor ~~relationships~~submits ~~and~~pediatric ~~interactions~~data ~~with~~that ~~foreign~~fairly ~~government~~respond ~~officials,~~to ~~which~~a ~~prohibit~~written Urequest from the FDA for such data.S. ~~companies~~The ~~and~~data ~~their~~do ~~employees,~~not ~~officers,~~need ~~and~~to ~~representatives~~show ~~from~~the ~~paying~~product to be effective in the pediatric population studied; rather, ~~offering~~if the clinical trial is deemed to ~~pay,~~fairly ~~promising,~~respond orto ~~authorizing~~the FDA’s request, the ~~payment~~additional ofprotection ~~anything~~is granted. If reports of ~~value~~requested pediatric studies are submitted to ~~any~~and ~~foreign~~accepted ~~government~~by ~~official~~the ~~(including,~~FDA ~~potentially,~~within ~~healthcare~~the ~~professionals~~statutory intime ~~countries~~limits, inwhatever ~~which~~statutory weor ~~operate~~regulatory periods of exclusivity or ~~may~~patent ~~sell~~protection ~~our~~cover ~~products),~~the ~~government~~product ~~staff~~are ~~member,~~extended ~~political~~by ~~party~~six months. This is not a patent term extension, orbut ~~political~~it ~~candidate~~effectively toextends ~~obtain~~the orregulatory ~~retain~~period ~~business~~during orwhich the FDA cannot approve another application. The issuance of a Written Request does not require the sponsor to ~~otherwise~~undertake ~~seek~~the ~~favorable~~described ~~treatment;~~studies.

~~per the Exclusion Statute (42 U.S.C. § 1320a~~Post-7)Approval the OIG is legally required to exclude from participation in all Federal health care programs individuals and entities convicted of the following types of criminal offenses: (1) Medicare or Medicaid fraud, as well as any other offenses related to the delivery of items or services under Medicare or Medicaid; (2) patient abuse or neglect; (3) felony convictions for other health-care-related fraud, theft, or other financial misconduct; and (4) felony convictions for unlawful manufacture, distribution, prescription, or dispensing of controlled substances. OIG has discretion to exclude individuals and entities on several other grounds, including misdemeanor convictions related to health care fraud other than Medicare or Medicaid fraud or misdemeanor convictions in connection with the unlawful manufacture, distribution, prescription, or dispensing of controlled substances; suspension, revocation, or surrender of a license to provide health care for reasons bearing on professional competence, professional performance, or financial integrity; provision of unnecessary or substandard services; submission of false or fraudulent claims to a Federal health care program; engaging in unlawful kickback arrangements; and defaulting on health education loan or scholarship obligations. If a person or entity is excluded by OIG from participation in the Federal health care programs, then Medicare, Medicaid, and other Federal health care programs, such as TRICARE and the Veterans Health Administration, will not pay for items or services that are furnished, ordered, or prescribed. Excluded physicians may not bill directly for treating Medicare and Medicaid patients, nor may their services be billed indirectly through an employer or a group practice. In addition, if you furnish services to a patient on a private-pay basis, no order or prescription that you give to that patient will be reimbursable by any Federal health care program;Requirements

~~the~~Any ~~Physician~~potential ~~Self-Referral~~products ~~Law,~~for orwhich ~~the~~we ~~Stark~~receive ~~Law~~FDA -approvals 42are ~~U.S.C.~~subject §to ~~1395nn,~~continuing ~~prohibits~~regulation by the ~~submission~~FDA, orincluding, ~~causing~~among ~~the~~other ~~submission~~things, record-keeping requirements, reporting of ~~claims~~adverse inexperiences ~~violation~~with ofthe product, providing the ~~law’s~~FDA ~~restrictions~~with onupdated ~~referrals.~~safety ~~The~~and ~~Stark~~efficacy ~~Law~~information, ~~prohibits~~product asampling ~~physician~~and ~~from~~distribution ~~referring~~requirements, ~~Medicare~~and ~~patients~~complying towith anFDA ~~entity~~promotion ~~(including~~and ~~pharmacies)~~advertising ~~for~~requirements, ~~the~~which ~~furnishing~~include, ofamong ~~“designated~~others, ~~health~~standards ~~services~~for direct-to-consumer advertising,” ifrestrictions ~~the~~on ~~physician~~promoting products for uses or ain ~~member~~patient ofpopulations that are not described in the ~~physician~~product’s ~~immediate~~approved ~~family~~uses ~~has~~(known aas ~~direct~~off-label oruse), ~~indirect~~limitations ~~“financial~~on ~~relationship”~~industry-sponsored ~~with~~scientific ~~the~~and ~~entity~~educational activities, ~~unless~~and arequirements ~~specific~~for ~~exception~~promotional ~~applies.~~activities ~~Financial~~involving ~~relationships~~the ~~include~~internet. ~~both~~Although ~~ownership/investment~~physicians ~~interests~~may ~~and~~prescribe ~~compensation~~legally ~~arrangements.~~available ~~The~~products ~~law~~for ~~further~~off-label ~~prohibits~~uses, if the ~~entity~~physicians ~~from~~deem ~~billing~~to ~~for~~be ~~any~~appropriate ~~services~~in their professional medical judgment, it is FDA’s position that ~~arise~~manufacturers ~~out~~cannot ofmarket ~~such~~or ~~prohibited~~promote ~~referrals~~off-label uses. ~~Certain~~The ofFDA ~~these~~and ~~provisions~~other ~~are~~agencies ~~applicable~~actively toenforce the ~~referral~~laws and regulations prohibiting the promotion of ~~Medicaid~~off-label ~~patients~~uses, asand ~~well.~~a ~~Designated~~company ~~health~~that ~~services~~is ~~include~~found ~~outpatient~~to ~~prescription~~have ~~drug~~improperly ~~services;~~promoted ~~clinical~~off-label ~~laboratory~~uses ~~services;~~may ~~physical~~be ~~therapy,~~subject ~~occupational~~to ~~therapy~~significant liability, ~~and~~including ~~outpatient~~liability ~~speech-language~~under ~~pathology~~federal ~~services;~~fraud ~~radiology~~ and ~~certain~~abuse ~~other~~and ~~imaging~~civil ~~services;~~and ~~radiation~~criminal ~~therapy~~false ~~services~~claims ~~and~~laws. ~~supplies;~~If ~~DME~~there ~~and~~are ~~supplies;~~any ~~parenteral~~modifications ~~and~~to ~~enteral~~the ~~nutrients~~product, ~~equipment,~~including ~~and~~changes ~~supplies;~~in ~~prosthetics~~indications, ~~orthotics,~~labeling ~~and~~or ~~prosthetic~~manufacturing ~~devices~~processes ~~and~~or ~~supplies;~~facilities, ~~home~~the ~~health~~applicant ~~services;~~may ~~and~~be ~~inpatient~~required to submit and ~~outpatient~~obtain ~~hospital~~FDA ~~services.~~approval ~~The~~of ~~Stark~~a ~~Law~~new isNDA/BLA or a ~~strict~~supplement, ~~liability~~which ~~statute~~may ~~thus~~require the ~~prohibition~~applicant ~~applies~~to ~~regardless~~develop ofadditional ~~the~~data ~~rationale~~or ~~for~~conduct ~~the~~additional ~~financial~~preclinical ~~relationship~~studies and clinical trials. The FDA may also place other conditions on approvals including the ~~reason~~requirement for ~~ordering~~a REMS to assure the ~~service;~~safe ~~and~~use ~~analogous~~of ~~state~~the ~~and~~product. ~~foreign~~A ~~laws~~REMS ~~and~~could ~~regulations~~include medication guides, ~~such~~physician ascommunication ~~state~~plans ~~anti-kickback~~or ~~and~~elements ~~false~~to ~~claims~~assure ~~laws~~safe use, ~~may~~such ~~apply~~as torestricted ~~sales~~distribution ormethods, ~~marketing~~patient ~~arrangements~~registries and ~~claims~~other ~~involving~~risk ~~health~~minimization ~~care~~tools. ~~items~~Any orof ~~services~~these ~~reimbursed~~limitations byon ~~nongovernmental~~approval ~~third-party~~or ~~payors,~~marketing ~~including~~could ~~private~~restrict ~~insurers.~~the commercial

4137

~~Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines~~promotion, ~~such as the PhRMA Code~~distribution, orprescription the relevant compliance guidance promulgated by the federal government, in addition to requiring drug manufacturers to report information related to payments to physicians and other health care providers or ~~marketing~~dispensing ~~expenditures~~of ~~to the extent that those laws impose requirements that are more stringent than the Physician Payments Sunshine Act~~products. InProduct ~~addition,~~approvals ~~state and local laws~~ may ~~require~~be ~~the~~withdrawn ~~registration~~for ofnon-compliance ~~pharmaceutical~~with ~~sales~~regulatory ~~representatives.~~standards ~~State~~or ~~and~~if ~~foreign~~problems ~~laws~~occur ~~also~~following ~~govern~~initial the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance effortsmarketing.

~~Violations~~In ofaddition, ~~any~~quality control and manufacturing procedures must continue to conform to applicable manufacturing requirements after approval to ensure the quality and long-term stability of ~~such~~the ~~laws~~product. orWe ~~any~~expect ~~other~~to ~~governmental~~rely ~~regulations~~on ~~that~~third ~~apply~~parties to usproduce clinical and commercial quantities of our potential products in accordance with cGMP regulations. However, ~~may~~the ~~subject~~sponsor usremains legally responsible for product quality and cGMP compliance. The cGMP regulations include requirements relating to ~~significant~~organization ~~penalties,~~of ~~including~~personnel, ~~without~~buildings ~~limitation~~and facilities, ~~civil~~equipment, ~~criminal~~control of components and ~~administrative~~drug ~~penalties~~product containers and closures, ~~damages~~production and process controls, ~~fines~~packaging and labeling controls, ~~disgorgement~~holding and distribution, ~~additional~~laboratory ~~reporting~~controls, records and reports and returned or salvaged products. The manufacturing facilities for our product candidates must meet cGMP requirements and ~~oversight~~satisfy ifthe FDA or comparable foreign regulatory authorities before any product is approved and our commercial products can be manufactured. These manufacturers must comply with cGMP regulations that require, among other things, quality control and quality assurance, the ~~Company~~maintenance ~~becomes~~of ~~subject~~records and documentation and the obligation to ainvestigate ~~corporate~~and ~~integrity~~correct ~~agreement~~any ordeviations ~~similar~~from ~~agreement~~cGMP. toManufacturers ~~resolve~~and ~~allegations~~other entities involved in the manufacture and distribution of ~~non~~approved products are required to register their establishments with the FDA and certain state agencies and are subject to risk-based, periodic unannounced inspections by the FDA and certain state agencies for compliance with ~~these~~cGMP and other laws. Accordingly, manufacturers must continue to expend time, money, and effort in the ~~curtailment~~area orof ~~restructuring~~production and quality control to maintain cGMP compliance. Future inspections by the FDA and other regulatory agencies may identify compliance issues at the facilities of our ~~operations~~contract development and manufacturing organizations, ~~exclusion~~or ~~from~~CDMOs, ~~participation~~that may disrupt production or distribution or require substantial resources to correct. In addition, the discovery of conditions that violate these rules, including failure to conform to cGMP regulations, could result in ~~federal~~enforcement actions, and ~~state~~the ~~healthcare~~discovery ~~programs~~of ~~and~~problems ~~imprisonment~~with a product after approval may result in restrictions on a product, ~~any~~manufacturer, or holder of ~~which~~an ~~could~~approved ~~adversely~~NDA/BLA, ~~affect~~including, ~~our~~among ~~ability~~other tothings, ~~operate~~voluntary ~~our~~recall ~~business~~and regulatory sanctions as described below.

~~Health~~Once ~~Care~~approval ~~Reform~~of ina product is granted, the ~~United~~FDA ~~States~~may withdraw the approval if compliance with regulatory requirements and ~~Potential~~standards ~~Changes~~is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to ~~Health~~comply ~~Care~~with ~~Laws~~regulatory requirements, may result in mandatory revisions to the approved labeling to add new safety information; imposition of post-market or clinical trials to assess new safety risks; or imposition of distribution or other restrictions under a REMS program. Other potential consequences include, among other things:

•

~~The~~restrictions ~~FDA’s~~on ~~and~~the ~~other~~marketing ~~regulatory~~or ~~authorities’~~manufacturing ~~policies~~of ~~may~~the ~~change and additional government regulations may be enacted that could prevent~~product, ~~limit~~complete orwithdrawal ~~delay regulatory approval~~ of ~~our~~the product ~~candidates.~~from ~~If we are slow or unable to adapt to changes in existing requirements or~~ the ~~adoption~~market ~~of new requirements~~ or ~~policies,~~product or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we otherwise may have obtained and may not achieve or sustain profitability, which would adversely affect our business, prospects, financial condition and results of operations.recalls;

•

~~As previously mentioned~~fines, awarning ~~primary~~letters ~~trend~~or ~~in the U.S. health care industry and elsewhere is cost containment. Government authorities and~~ other ~~third~~enforcement-~~party~~related ~~payors~~letters have attempted to control costs by limiting coverage and the amount of reimbursement for particular medical products and services, implementing reductions in Medicare and other health care funding and applying new payment methodologies. For example, in March 2010, the ACA was enacted, which, among other things, increased the minimum Medicaid rebates owed by most manufacturers under the Medicaid Drug Rebate Program; introduced 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;~~clinical ~~extended~~holds ~~the~~on ~~Medicaid~~post-marking ~~Drug~~(Phase ~~Rebate~~4) ~~Program to utilization of prescriptions of individuals enrolled in Medicaid managed care plans~~studies; imposed mandatory discounts for certain Medicare Part D beneficiaries as a condition for manufacturers’ outpatient drugs coverage under Medicare Part D; and established a Center for Medicare Innovation at CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending.

•

Inrefusal addition, other legislative changes have been proposed and adopted in the United States since the ACA that affect health care expenditures. There has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries, presidential executive orders and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs and reform government program reimbursement methodologies for pharmaceutical and biologic products. Notably, on December 20, 2019, President Trump signed the Further Consolidated Appropriations Act for 2020 into law (P.L. 116-94) that includes a piece of ~~bipartisan legislation called~~ the ~~Creating~~FDA ~~and Restoring Equal Access~~ to ~~Equivalent~~approve ~~Samples~~pending ~~Act~~NDA/BLAs ~~of 2019~~ or ~~the~~supplements ~~“CREATES Act.” The CREATES Act aims~~ to ~~address~~approved ~~the concern articulated by both the FDA and others in the industry that some brand manufacturers have improperly restricted the distribution of their products~~NDA/BLAs, ~~including~~or bysuspension ~~invoking~~or ~~the~~revocation ~~existence~~ of ~~a REMS for certain products, to deny generic and biosimilar~~ product developers access to samples of brand products. Because generic and biosimilar product developers need samples to conduct certain comparative testing required by the FDA, some have attributed the inability to timely obtain samples as a cause of delay in the entry of generic and biosimilar products. To remedy this concern, the CREATES Act establishes a private cause of action that permits a generic or biosimilar product developer to sue the brand manufacturer to compel it to furnish the necessary samples on “commercially reasonable, market-based terms.” Whether and how generic and biosimilar product developments will use this new pathway, as well as the likely outcome of any legal challenges to provisions of the CREATES Act, remain highly uncertain and its potential effects on our future commercial products are unknown. The FDA also released a final rule on September 24, 2020 providing guidance for states to build and submit importation plans for drugs from Canada. This final rule became effective November 30, 2020. In January 2024, FDA authorized the state of Florida’s Section 804 Importance Program to allow Florida to import drugs from Canada for a period of two years. The ongoing impact of this and potentially other state programs is still unclear.approvals;

•

Weproduct ~~cannot~~seizure ~~predict the likelihood, nature~~ or ~~extent of government regulation that may arise from future legislation or administrative or executive action~~detention, ~~either in the United States~~ or ~~abroad.~~refusal ~~It is also possible that additional governmental action is taken in response~~ to ~~the~~permit ~~COVID-19 pandemic. We expect that additional state and federal health care reform measures will be adopted in~~ the ~~future,~~import ~~any~~or export of ~~which could limit the amounts that federal and state governments will pay for health care~~ products ~~and services.~~;

•

42injunctions or the imposition of civil or criminal penalties; and

•

~~Facilities~~consent decrees, corporate integrity agreements, debarment, or exclusion from federal health care programs; or mandated modification of promotional materials and labeling and the issuance of corrective information.

~~Our~~In ~~principal~~addition, ~~office~~the isDrug ~~located~~Supply inChain ~~Tampa~~Security Act, ~~Florida.~~or WeDSCSA, ~~currently~~was ~~lease~~enacted ~~approximately~~with 12the aim of building an electronic system to identify and trace certain prescription drugs distributed in the United States,~~199~~ ~~square~~including ~~feet~~most ofbiological ~~office~~products depending on classification and ~~laboratory~~product ~~space~~type. ~~under~~The DSCSA mandates phased-in and resource-intensive obligations for pharmaceutical manufacturers, wholesale distributors, and dispensers over a ~~lease~~10-year period that ishas ~~due~~been extended by a stabilization period extending enforcement discretion to ~~expire~~November in2024. ~~March~~In ~~2026~~the Fall of 2024, the FDA granted additional flexibility into 2025 based on the type of activities being performed. WeFrom ~~believe~~time to time, new legislation and regulations may be implemented that ~~such~~could ~~office~~significantly change the statutory provisions governing the approval, manufacturing and ~~laboratory~~marketing ~~space~~of products regulated by the FDA. It is impossible to predict whether further legislative or regulatory changes will be ~~sufficient~~enacted, ~~for~~or ~~our~~FDA ~~planned~~regulations, ~~operations~~guidance ~~for~~or interpretations changed or what the ~~foreseeable~~impact ~~future~~of such changes, if any, may be.

~~Corporate Information~~38

~~Our principal executive offices are located at 10500 University Center Drive~~Coverage, ~~Suite~~Pricing 110, Tampa, Florida 33612. Our telephone number is (813) 875-6600. Our principal website address is www.tuhurabio.com. Information contained on or accessible through our website is not a part of this Annual Report on Form 10-K, and the inclusion of our website address in this Annual Report on Form 10-K is for convenience only and the information on the referenced website does not constitute a part of nor is incorporated by reference into this report. Reimbursement

~~Our~~Sales ~~reports~~of ~~filed~~pharmaceutical orproducts ~~furnished~~approved ~~pursuant~~by tothe ~~Section~~FDA ~~13(a)~~will ordepend, ~~15(d)~~in significant part, on the availability of third-party coverage and reimbursement for the ~~Securities~~products. ~~Exchange~~Third-party ~~Act~~payors ofinclude ~~1934,~~government healthcare programs in the United States such as ~~amended~~Medicare and Medicaid, ~~including~~managed ~~our~~care ~~annual~~providers, ~~reports~~private onhealth ~~Form~~insurers 10and other organizations. These third-K,party ~~our~~payors ~~quarterly~~are ~~reports~~increasingly onchallenging ~~Form~~the ~~10-Q~~prices of products and ~~our~~examining ~~current~~the ~~reports~~cost-effectiveness onof ~~Form~~medical ~~8-K,~~products and ~~amendments~~services. toIn ~~those reports~~addition, ~~are~~significant ~~accessible~~uncertainty ~~through~~exists ~~our~~as ~~website,~~to ~~free~~the reimbursement status of ~~charge,~~newly asapproved ~~soon~~healthcare asproducts. ~~reasonably~~The ~~practicable~~process ~~after~~for ~~these~~determining ~~reports~~whether ~~are~~a ~~filed~~payor ~~electronically~~will ~~with,~~provide coverage for a product may be separate from the process for setting the price or ~~otherwise~~reimbursement ~~furnished~~rate that the payor will pay for the product once coverage is approved. Further, there is no uniform policy for coverage and reimbursement in the United States by third-party payors. Third-party payors may limit coverage to specific products on an approved list, or formulary, which might not include all of the ~~SEC~~approved products for a particular indication. ~~These~~We ~~SEC~~may ~~reports~~need ~~can~~to beconduct ~~accessed~~expensive ~~through~~pharmacoeconomic studies to demonstrate the ~~“Investors”~~medical ~~section~~necessity and cost-effectiveness of our ~~website~~products, in addition to the costs required to obtain FDA or other comparable regulatory approvals.

~~Item~~Moreover, 1Aa payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved. ~~Risk~~Third-party ~~Factors~~reimbursement may not be sufficient to maintain price levels high enough to realize an appropriate return on investment in product development. Our product candidates may not be considered cost-effective. It is time consuming and expensive to seek coverage and reimbursement from third-party payors. Coverage and reimbursement may not be available or sufficient to allow us to sell our products on a competitive and profitable basis.

~~Investing~~In addition, in ~~our~~some ~~common~~foreign ~~stock~~countries, ~~involves~~the proposed pricing for a ~~high~~drug ~~degree~~must ofbe ~~risk~~approved before it may be lawfully marketed. ~~You~~The ~~should~~requirements ~~carefully~~governing ~~consider~~drug pricing vary widely from country to country. Some countries provide that drug products may be marketed only after a reimbursement price has been agreed. Some countries may require the ~~risks~~completion ~~described~~of ~~below,~~additional asstudies ~~well~~that ascompare the ~~other~~cost-effectiveness ~~information~~of inour ~~this~~product ~~Annual~~candidate ~~Report~~to currently available therapies (so called health technology assessment, ~~including~~or ~~our~~HTA) ~~audited~~in ~~financial~~order ~~statements~~to ~~and~~obtain ~~the~~reimbursement ~~related~~or ~~notes~~pricing approval. For example, asthe ~~well~~European asUnion ~~our~~provides ~~other~~options ~~public~~for ~~filings~~its ~~with~~member states to restrict the ~~SEC,~~range ~~before~~of ~~deciding~~medicinal products for which their national health insurance systems provide reimbursement and to ~~invest~~control inthe ~~our~~prices ~~common~~of ~~stock~~medicinal products for human use. IfAn ~~any~~EU ofMember State may approve a specific price for the ~~following~~medicinal ~~risks~~product ~~are~~or ~~realized,~~it ~~our~~may ~~business,~~instead ~~financial~~adopt ~~condition,~~a ~~results~~system of ~~operations~~direct ~~and~~or ~~prospects,~~indirect ascontrols ~~well~~on asthe profitability of the company placing the medicinal product on the market. Other EU Member States allow companies to fix their own prices for drug products but monitor and control prescription volumes and issue guidance to physicians to limit prescriptions. 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 ~~common~~products. ~~stock~~Historically, ~~could~~products belaunched ~~materially~~in the European Union do not follow price structures of the United States and ~~adversely~~generally ~~affected~~tend to be significantly lower.

~~SUMMARY~~The OFdownward ~~RISK~~pressure ~~FACTORS~~on health care costs in general, particularly prescription drugs, has become intense. As a result, increasingly high barriers are being erected to the entry of new products. In addition, there can be considerable pressure by governments and other stakeholders on prices and reimbursement levels, including as part of cost containment measures. Political, economic and regulatory developments may further complicate pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained. Reference pricing used by various EU Member States and parallel distribution (arbitrage between low-priced and high- priced member states) can further reduce prices. Any country that has price controls or reimbursement limitations for drug products may not allow favorable reimbursement and pricing arrangements.

~~We have a limited operating history, are not profitable and may never become profitable.~~39

WeOther ~~have~~U.S. ~~expressed~~Health ~~substantial~~Care ~~doubt~~Laws ~~about~~and ~~our ability to continue as a going concern.~~Regulations

WeAlthough ~~may~~we currently do not ~~realize~~have any products on the ~~anticipated~~market, ~~benefits~~our ofcurrent and future arrangements with healthcare professionals, investigators, consultants, customers and third-party payors expose us to broadly applicable healthcare regulation and enforcement by the ~~Kintara~~U.S. ~~Merger~~federal government and the states and foreign governments in which we conducts our business, such as fraud and abuse laws, transparency and health information privacy rules and regulations. These laws include, without limitation:

•

~~Our~~The ~~business~~federal Anti-Kickback Statute – or AKS, 42 U.S.C. § 1320a-7b(b): the federal AKS is ~~heavily~~a ~~dependent~~criminal onlaw which, prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or paying remuneration, directly or indirectly, in cash or in kind, to induce or reward either the ~~successful~~referral ~~development~~of an individual for the furnishing of any item or service, ~~regulatory~~or ~~approval~~for purchasing, leasing, ordering, or arranging for or recommending purchasing, leasing, or ordering any good or service, for which payment may be made, in whole or in part, under a federal health care program such as Medicare and ~~commercialization~~Medicaid. Remuneration includes anything of ~~our~~value ~~product~~and ~~candidates~~can take many forms besides cash, such as free rent, expensive hotel stays and meals, and excessive compensation for medical directorships or consultancies. The AKS covers the payers of kickbacks-those who offer or pay remuneration- as well as the recipients of kickbacks-those who solicit or receive remuneration. While each party’s intent is a key element of their liability under the AKS, a person or entity can be found guilty of violating the statute without actual knowledge of the statute or specific intent to violate it. A conviction for violation of the AKS can result in criminal fines and/or imprisonment and requires mandatory exclusion from participation in federal healthcare programs;

•

Wemany ~~will~~US ~~require~~states ~~substantial~~have ~~additional~~laws ~~capital~~and regulations analogous to ~~fund~~US ~~our~~federal ~~operations,~~fraud and ifabuse welaws, ~~fail~~such toas ~~obtain~~individual ~~necessary~~state ~~financing~~anti-kickback, wefee-splitting ~~may~~and ~~not~~false beclaims ~~able~~laws, which may apply to ~~complete~~sales ~~the~~or ~~development~~marketing arrangements and ~~commercialization~~claims ofinvolving ~~any~~healthcare ofitems ~~our~~or ~~product~~services ~~candidates.~~reimbursed by non-governmental third-party payers;

•

~~Our~~The ~~product~~Federal ~~candidates~~civil ~~will~~and ~~face~~criminal ~~significant~~false ~~competition~~claims laws, including the civil False Claims Act, or the FCA,—31 U.S.C. § § 3729-3733, which prohibits individuals or entities from knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government, and provides for civil whistleblower or qui tam actions that allow a private individual to file a lawsuit on behalf of the United State and entitles the whistleblower to a percentage of any recoveries. Under the FCA it is illegal to submit claims for payment to Medicare or Medicaid that an individual knows or should know are false or fraudulent; no specific intent to defraud is required. The civil FCA defines “knowing” to include not only actual knowledge but also instances in which the person acted in deliberate ignorance or reckless disregard of the truth or falsity of the information. Filing false claims may beresult ~~unable~~in fines of up to ~~compete~~three ~~effectively~~times the programs’ loss plus $11,000 per claim filed. Under the civil FCA, each instance of an item or a service billed to Medicare or Medicaid counts as a claim. The fact that a claim results from a kickback or is made in violation of the Stark law also may render it false or fraudulent, creating liability under the civil FCA as well as the AKS or Stark law. Under the criminal FCA (18 U.S.C. § 287) penalties for submitting false claims include imprisonment and criminal fines; the OIG also may impose administrative civil monetary penalties for false or fraudulent claims;

•

~~Various~~the ~~government~~federal ~~regulations~~civil ~~could~~monetary ~~limit~~penalties law, or ~~delay~~CMP ~~our~~(42 ~~ability~~U.S.C. § 1320a-7a), prohibits a person from presenting or causing to ~~develop~~be ~~and~~presented ~~commercialize~~a ~~our~~claim ~~products~~that the provider knows or ~~otherwise~~should ~~negatively~~know ~~impact~~is ~~our~~improper, ~~business~~presenting a claim that the person knows or should know is for an item or service for which payment may not be made, and violating the AKS. The Office of Inspector General, or OIG of the US Department of Health and Human Services, or DHHS, may seek civil monetary penalties and sometimes exclusion for a wide variety of conduct and is authorized to seek different amounts of penalties and assessments based on the type of violation at issue;

•

~~The~~the ~~commercial~~federal ~~potential~~Health ofInsurance ~~our~~Portability ~~products~~and isAccountability ~~difficult~~Act toof ~~predict.~~1996 ~~The~~and ~~market~~its ~~for~~implementing ~~any product~~regulations, or ~~for~~HIPAA, ~~companion~~imposes ~~animal~~criminal ~~diagnostics~~ and ~~medical~~civil ~~devices~~liability ~~overall,~~for isexecuting ~~uncertain~~a ~~and~~scheme ~~may~~to bedefraud ~~smaller~~any ~~than~~health wecare ~~anticipate,~~benefit ~~which~~program ~~could~~or ~~significantly~~making ~~and~~false ~~negatively~~statements ~~impact~~relating ~~our~~to ~~revenue,~~health ~~results~~care ~~of operations and financial condition.~~matters;

•

~~Our~~HIPAA, ~~ability~~as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH Act, and its implementing regulations, also imposes obligations, including mandatory contractual terms, with respect to ~~obtain~~safeguarding ~~intellectual~~the ~~property~~privacy, ~~protection~~security and transmission of individually identifiable health information, for ~~our~~covered ~~products~~entities, isincluding ~~limited.~~certain healthcare providers, health plans, and healthcare clearinghouses, and their business associates and covered subcontractors that provide services to, or on behalf of, the covered entity that involve individually identifiable health information;

We will rely on third parties to conduct certain portions of our development activities. If these third parties do not successfully carry out their contractual duties or meet expected deadlines, we may be unable to obtain regulatory approval for or commercialize our product candidates.40

•

43The Physician Payments Sunshine Act (42 USC 1320a-7h) as known as “Open Payments” is a national disclosure program created by the Affordable Care Act, or ACA, that increases transparency into financial relationships between the health care industry (such as medical device manufacturers and pharmaceutical companies) and physicians or teaching hospitals. Drug, device, biological, and medical supply manufacturers, and group purchasing organizations are required to report payments or other transfers of value they make to physicians or teaching hospitals, as well as ownership or investment interests that a physician or his or her family members have in those entities. The Centers for Medicare & Medicaid Services, or CMS, collects data annually, and makes it publicly available and searchable online at openpaymentsdata.cms.gov. Applicable manufacturers are also required to report information related to payments and other transfers of value provided in the previous year to physician assistants, nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists, and certified nurse midwives. Individual states have their own “sunshine act reporting laws” which vary from state to state;

•

Ifthe weU.S. ~~fail~~Foreign Corrupt Practices Act, or FCPA, and other anti-corruption laws and regulations pertaining to ~~attract~~our financial relationships and ~~keep~~interactions ~~key~~with ~~personnel~~foreign government officials, which prohibit U.S. companies and ~~members~~their ofemployees, ~~management~~officers, weand ~~may~~representatives befrom ~~unable~~paying, offering to ~~successfully~~pay, ~~develop~~promising, ~~any~~or authorizing the payment of ~~our~~anything ~~existing~~of orvalue ~~future~~to ~~product~~any ~~candidates~~foreign government official (including, ~~conduct~~potentially, ~~our~~healthcare professionals in~~-licensing~~ ~~and~~countries ~~development~~in ~~efforts~~which ~~and~~we ~~commercialize~~operate ~~any~~or ofmay sell our ~~existing~~products), government staff member, political party, or ~~future~~political ~~products.~~candidate to obtain or retain business or to otherwise seek favorable treatment;

•

~~Any~~per ~~failure~~the byExclusion usStatute (42 U.S.C. § 1320a-7) the OIG is legally required to ~~protect~~exclude ~~our~~from ~~intellectual~~participation ~~property~~in ~~rights~~all Federal health care programs individuals and entities convicted of the following types of criminal offenses: (1) Medicare or ~~maintain~~Medicaid fraud, as well as any other offenses related to the ~~right~~delivery of items or services under Medicare or Medicaid; (2) patient abuse or neglect; (3) felony convictions for other health-care-related fraud, theft, or other financial misconduct; and (4) felony convictions for unlawful manufacture, distribution, prescription, or dispensing of controlled substances. OIG has discretion to ~~use~~exclude ~~certain~~individuals ~~intellectual~~and ~~property~~entities ~~may~~on ~~negatively~~several ~~affect~~other ~~our~~grounds, ~~ability~~including misdemeanor convictions related to ~~compete~~health care fraud other than Medicare or Medicaid fraud or misdemeanor convictions in connection with the unlawful manufacture, distribution, prescription, or dispensing of controlled substances; suspension, revocation, or surrender of a license to provide health care for reasons bearing on professional competence, professional performance, or financial integrity; provision of unnecessary or substandard services; submission of false or fraudulent claims to a Federal health care program; engaging in unlawful kickback arrangements; and defaulting on health education loan or scholarship obligations. If a person or entity is excluded by OIG from participation in the Federal health care programs, then Medicare, Medicaid, and other Federal health care programs, such as TRICARE and the Veterans Health Administration, will not pay for items or services that are furnished, ordered, or prescribed. Excluded physicians may not bill directly for treating Medicare and Medicaid patients, nor may their services be billed indirectly through an employer or a group practice. In addition, if you furnish services to a patient on a private-pay basis, no order or prescription that you give to that patient will be reimbursable by any Federal health care program;

•

~~Failure~~the Physician Self-Referral Law, or the Stark Law - 42 U.S.C. § 1395nn, prohibits the submission, or causing the submission, of claims in violation of the law’s restrictions on referrals. The Stark Law prohibits a physician from referring Medicare patients to ~~complete~~an entity (including pharmacies) for the ~~Kineta~~furnishing ~~Merger~~of ~~could~~“designated ~~negatively~~health ~~impact~~services,” ~~our~~if ~~stock~~the ~~price~~physician or a member of the physician’s immediate family has a direct or indirect “financial relationship” with the entity, ~~future~~unless ~~business~~a specific exception applies. Financial relationships include both ownership/investment interests and ~~financial~~compensation ~~results~~arrangements. The law further prohibits the entity from billing for any services that arise out of such prohibited referrals. Certain of these provisions are applicable to the referral of Medicaid patients as well. Designated health services include outpatient prescription drug services; clinical laboratory services; physical therapy, occupational therapy, and outpatient speech-language pathology services; radiology and certain other imaging services; radiation therapy services and supplies; DME and supplies; parenteral and enteral nutrients, equipment, and supplies; prosthetics, orthotics, and prosthetic devices and supplies; home health services; and inpatient and outpatient hospital services. The Stark Law is a strict liability statute thus the prohibition applies regardless of the rationale for the financial relationship and the reason for ordering the service; and analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, may apply to sales or marketing arrangements and claims involving health care items or services reimbursed by nongovernmental third-party payors, including private insurers.

~~Even if we consummate the Kineta Merger, we may not realize the anticipated benefits of the Kineta Merger.~~ 41

WeSome ~~expect~~state tolaws ~~obtain~~require ~~financing~~pharmaceutical incompanies ~~connection~~to comply with the ~~Kineta~~pharmaceutical ~~Merger~~industry’s voluntary compliance guidelines, such as the PhRMA Code, or the relevant compliance guidance promulgated by the federal government, in addition to requiring drug manufacturers to report information related to payments to physicians and ~~cannot~~other ~~guarantee~~health ~~that~~care weproviders ~~will~~or bemarketing ~~able~~expenditures to ~~complete~~the ~~such~~extent ~~financing~~that those laws impose requirements that are more stringent than the Physician Payments Sunshine Act. In addition, state and local laws may require the registration of pharmaceutical sales representatives. State and foreign laws also govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

WeViolations ~~expect~~of any of such laws or any other governmental regulations that apply to us, may subject us to significant penalties, including, without limitation, civil, criminal and administrative penalties, damages, fines, disgorgement, additional reporting requirements and oversight if the ~~price~~Company becomes subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, the curtailment or restructuring of our ~~common~~operations, ~~shares~~exclusion ~~will~~from ~~fluctuate~~participation ~~substantially~~in federal and state healthcare programs and imprisonment, any of which could adversely affect our ability to operate our business.

~~The~~Health ~~potential~~Care ~~significant~~Reform ~~amount~~in ofthe ~~any~~United ~~costs,~~States ~~fees,~~and ~~expenses,~~Potential ~~impairments~~Changes ~~or charges related~~ to ~~the~~Health ~~Kineta~~Care ~~Merger.~~Laws

AnThe ~~investment~~FDA’s inand ~~our~~other ~~common~~regulatory ~~stock~~authorities’ ~~involves~~policies amay ~~high~~change ~~degree~~and ofadditional ~~risk.~~government Inregulations ~~determining~~may ~~whether~~be toenacted ~~purchase~~that could prevent, limit or delay regulatory approval of our ~~common~~product ~~stock,~~candidates. anIf ~~investor~~we ~~should~~are ~~carefully~~slow ~~consider~~or ~~all~~unable ofto ~~the~~adapt ~~material~~to ~~risks~~changes ~~described~~in ~~below,~~existing ~~together~~requirements ~~with~~or the ~~other~~adoption ~~information~~of ~~contained~~new inrequirements ~~this~~or ~~Annual~~policies, ~~Report~~or ~~before~~if ~~making~~we aare ~~decision~~not able to ~~purchase~~maintain ~~our~~regulatory ~~securities.~~compliance, Anwe ~~investor~~may ~~should~~lose ~~only~~any ~~purchase~~marketing ~~our~~approval ~~securities~~that ifwe ~~he,~~otherwise ~~she~~may have obtained and may not achieve or itsustain ~~can~~profitability, ~~afford~~which towould ~~suffer~~adversely ~~the~~affect ~~loss~~our ofbusiness, ~~his~~prospects, ~~her~~financial orcondition ~~its~~and ~~entire~~results ~~investment~~of operations.

~~Risks~~As ~~Relating~~previously mentioned, a primary trend in the U.S. health care industry and elsewhere is cost containment. Government authorities and other third-party payors have attempted to ~~Our~~control ~~Business~~costs by limiting coverage and ~~Industry~~the amount of reimbursement for particular medical products and services, implementing reductions in Medicare and other health care funding and applying new payment methodologies. For example, in March 2010, the ACA was enacted, which, among other things, increased the minimum Medicaid rebates owed by most manufacturers under the Medicaid Drug Rebate Program; introduced 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; extended the Medicaid Drug Rebate Program to utilization of prescriptions of individuals enrolled in Medicaid managed care plans; imposed mandatory discounts for certain Medicare Part D beneficiaries as a condition for manufacturers’ outpatient drugs coverage under Medicare Part D; and established a Center for Medicare Innovation at CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending.

WeIn ~~are~~addition, aother ~~clinical-stage~~legislative ~~company~~changes have been proposed and adopted in the United States since the ACA that affect health care expenditures. There has abeen ~~limited~~heightened ~~operating~~governmental ~~history~~scrutiny over the manner in which manufacturers set prices for their marketed products, which ~~may~~has ~~make~~resulted in several Congressional inquiries, presidential executive orders and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs and reform government program reimbursement methodologies for pharmaceutical and biologic products. Notably, on December 20, 2019, President Trump signed the Further Consolidated Appropriations Act for 2020 into law (P.L. 116-94) that includes a piece of bipartisan legislation called the Creating and Restoring Equal Access to Equivalent Samples Act of 2019 or the “CREATES Act.” The CREATES Act aims to address the concern articulated by both the FDA and others in the industry that some brand manufacturers have improperly restricted the distribution of their products, including by invoking the existence of a REMS for certain products, to deny generic and biosimilar product developers access to samples of brand products. Because generic and biosimilar product developers need samples to conduct certain comparative testing required by the FDA, some have attributed the inability to timely obtain samples as a cause of delay in the entry of generic and biosimilar products. To remedy this concern, the CREATES Act establishes a private cause of action that permits a generic or biosimilar product developer to sue the brand manufacturer to compel it ~~difficult~~to furnish the necessary samples on “commercially reasonable, market-based terms.” Whether and how generic and biosimilar product developments will use this new pathway, as well as the likely outcome of any legal challenges to ~~evaluate~~provisions ~~our~~of ~~current~~the ~~business~~CREATES Act, remain highly uncertain and ~~predict~~its potential effects on our future ~~performance~~commercial products are unknown. The FDA also released a final rule on September 24, 2020 providing guidance for states to build and submit importation plans for drugs from Canada. This final rule became effective November 30, 2020. In January 2024, FDA authorized the state of Florida’s Section 804 Importance Program to allow Florida to import drugs from Canada for a period of two years. The ongoing impact of this and potentially other state programs is still unclear.

We ~~are~~cannot apredict ~~clinical-stage~~the ~~pharmaceutical~~likelihood, ~~company~~nature ~~and~~or ~~have~~extent noof ~~products~~government ~~approved~~regulation ~~for~~that ~~commercial~~may ~~sale.~~arise Wefrom ~~employ~~future alegislation ~~multi-indication~~or ~~immunomodulator~~administrative ~~platform~~or ~~(ImmuneFx)~~executive ~~that utilizes both cell and gene therapies~~action, ~~together,~~either toin ~~stimulate~~ the ~~immune~~United ~~system~~States toor ~~recognize~~abroad. ~~and~~It ~~combat~~is ~~tumor~~also ~~cells.~~possible ~~Although~~that ~~there~~additional ~~have~~governmental ~~been~~action ~~significant~~is ~~advances~~taken in ~~cell~~response ~~and gene-based immunotherapies, our immunomodulatory platforms are new and largely unproven. Our operations~~ to ~~date have been limited to organizing and staffing~~ the ~~Company,~~COVID-19 ~~business planning, raising capital, developing our technology, identifying potential product candidates, undertaking preclinical studies, and conducting clinical trials~~pandemic. IfWe ~~one~~expect ofthat ~~our~~additional ~~product~~state ~~candidates received regulatory approval, we would need to transition from a company with a research~~ and ~~development~~federal ~~focus~~health tocare areform ~~company~~measures ~~capable~~will ~~of supporting commercial activities. We may not~~ be ~~successful~~adopted in ~~such~~the ~~a transition. In addition~~future, ~~our~~any ~~limited~~of ~~operating~~which ~~history,~~could ~~particularly~~limit ~~in light of~~ the ~~rapidly~~amounts ~~evolving~~that ~~cancer~~federal ~~immunotherapy field, may make it difficult to evaluate our current business~~ and ~~predict~~state ~~our~~governments ~~future~~will ~~performance.~~pay Wefor ~~will~~health ~~encounter~~care ~~risks~~products and ~~difficulties frequently experienced by early-stage companies in rapidly evolving fields~~services. ~~If it does not address these risks successfully, our business will suffer.~~

Legacy TuHURA, our main operating subsidiary, has incurred significant losses since inception and expects to incur significant losses for the foreseeable future and may not be able to achieve or sustain profitability in the future.42

Legacy TuHURA is not profitable and has incurred significant losses in each period since its inception, including net losses of $22.6 million for the year ended December 31, 2024, and $29.3 million for the year ended December 31, 2023 (which includes the expensing of the entire $16.2 million purchase price for the assets of TuHURA Biopharma, of which $15.0 million was paid in the form of our common stock). To date, we have financed our operations primarily through private placements of our preferred stock and convertible notes. We have not commercialized any products and has never generated any revenue from product sales. We expect these losses to increase as it continues to incur significant research and development and other expenses related to our ongoing operations, seeks regulatory approvals for our product candidates, scales-up manufacturing capabilities and hires additional personnel to support the development of our product candidates and to enhance our operational, financial and information management systems.Facilities

44Our principal office is located in Tampa, Florida. We currently lease approximately 12,199 square feet of office and laboratory space under a lease that is due to expire in March 2028. We believe that such office and laboratory space will be sufficient for our planned operations for the foreseeable future.

ACorporate critical aspect of our strategy is to invest significantly in our technology platform to improve the efficacy and safety of our product candidates. To become and remain profitable, we must develop and eventually commercialize products with significant market potential, which it may never achieve. Even if we succeed in commercializing one or more of these product candidates, we will continue to incur losses for the foreseeable future relating to our substantial research and development expenditures to develop our technologies. We may encounter unforeseen expenses, difficulties, complications, delays and 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 revenue. Our prior losses and expected future losses have had and will continue to have an adverse effect on our stockholders’ equity and working capital. Further, the net losses we incur may fluctuate significantly from quarter to quarter and year to year, such that a period-to-period comparison of our results of operations may not be a good indication of our future performance. If we do not achieve profitability, it 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 and clinical 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 the value of our could also cause you to lose all or part of your investment.Information

Our ~~recurring~~principal ~~losses~~executive ~~from~~offices ~~operations~~are ~~and~~located ~~financial~~at ~~condition~~10500 ~~raise~~University ~~substantial~~Center ~~doubt~~Drive, ~~about~~Suite 110, Tampa, Florida 33612. Our telephone number is (813) 875-6600. Our principal website address is www.tuhurabio.com. Information contained on or accessible through our ~~ability~~website tois ~~continue~~not asa part of this Annual Report on Form 10-K, and the inclusion of our website address in this Annual Report on Form 10-K is for convenience only and the information on the referenced website does not constitute a ~~going~~part ~~concern~~of nor is incorporated by reference into this report.

Our ~~recurring~~reports ~~losses~~filed ~~from~~or ~~operations~~furnished ~~and~~pursuant ~~financial condition raise substantial doubt about our ability~~ to ~~continue~~Section as 13(a) ~~going~~or ~~concern.~~15(d) Inof ~~our financial statements for~~ the ~~years~~Securities ~~ended~~Exchange ~~December~~Act 31of 1934, ~~2024~~as ~~and 2023~~amended, weincluding ~~concluded that~~ our ~~recurring~~annual ~~losses~~reports ~~from~~on ~~operations~~Form ~~and~~10-K, ~~need for additional financing to fund future operations raise substantial doubt about~~ our ~~ability~~quarterly toreports ~~continue~~on asForm a10-Q ~~going~~and ~~concern. Similarly,~~ our ~~independent~~current ~~registered~~reports ~~public accounting firm included an explanatory paragraph in its report~~ on ~~our~~Form ~~financial statements for the year ended December 31~~8-K, ~~2024~~and ~~with~~amendments ~~respect~~ to ~~this~~those ~~uncertainty.~~reports, ~~Our ability to continue as a going concern will require us to obtain additional funding. If we~~ are ~~unable~~accessible tothrough ~~obtain sufficient funding,~~ our ~~business~~website, ~~prospects,~~free ~~financial condition and results~~ of ~~operations will be materially and adversely affected~~charge, ~~and~~as wesoon ~~may be unable to continue~~ as areasonably ~~going~~practicable ~~concern.~~after Ifthese wereports are ~~unable~~filed toelectronically ~~raise capital when needed or on acceptable terms~~with, ~~we would be forced to delay, limit, reduce~~ or ~~terminate~~otherwise ~~our~~furnished ~~product development or future commercialization efforts of one or more of our product candidates, or may be forced~~ to ~~reduce 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 part of their investment~~SEC. IfThese weSEC ~~seek~~reports ~~additional~~can ~~financing~~be toaccessed ~~fund~~through ~~our business activities in~~ the ~~future~~“Investors” ~~and~~section ~~there~~of ~~remains substantial doubt about~~ our ~~ability to continue as a going concern, investors and other financing sources may be unwilling to provide additional funding to it on commercially reasonable terms, if at all~~website.

WeInformation ~~have~~About ~~never~~Our ~~generated~~Executive ~~any~~Officers ~~revenue from product sales for our human drug candidates~~ and ~~our ability to generate revenue from product sales and become profitable depends significantly on our success in numerous endeavors.~~Directors

WeThe ~~have~~following notable ~~products~~sets ~~approved~~forth ~~for~~the ~~commercial~~persons ~~sale,~~who ~~has~~serve ~~not~~as ~~generated~~our ~~any~~executive ~~revenue~~officers ~~from~~and ~~product sales~~directors, and ~~does~~their ~~not~~ages ~~anticipate~~as ~~generating any revenue from product sales until sometime after we have received regulatory approval for the commercial sale~~ of aMarch ~~product candidate. Our ability to generate revenue and achieve profitability depends significantly on our success in many endeavors~~31, ~~including~~2026:

completing research regarding, and nonclinical and clinical development of, our product candidates;


Name	Age	Position(s)
Executive Officers
James Bianco, M.D.	69	Chief Executive Officer and Director
Dan Dearborn	59	Chief Financial Officer
Non-Employee Directors
James Manuso, Ph.D., MBA	77	Director and Chairman of the Board
Alan List, M.D.	71	Director
George Ng	52	Director
Robert E. Hoffman	60	Director
Craig Tendler, M.D.	67	Director

~~obtaining~~Executive ~~regulatory approvals and marketing authorizations for product candidates for which we complete clinical trials;~~Officers

~~developing~~James Bianco, M.D. has served as our Chief Executive Officer and as a ~~sustainable~~director since the completion of the Kintara Merger and ~~scalable~~for ~~manufacturing~~Legacy ~~process~~TuHURA since July 1, 2021. Dr. Bianco was also the founder, Chief Executive Officer and Chairman of Morphogenesis Biopharma, Inc., a biotechnology company, from its inception in November 2018 through its dissolution in January 2023, following the transfer of its assets to us. Dr. Bianco is a 30-year veteran of the biopharmaceutical industry. In 1991, Dr. Bianco founded CTI Biopharma, Inc. (“CTI”) and from 1992 to 2016 was the Chief Executive Officer of CTI. During his tenure at CTI, Dr. Bianco was responsible for ~~our~~strategic ~~product~~portfolio ~~candidates~~development and identifying, ~~including~~acquiring, ~~establishing~~licensing, purchasing, or acquiring through international merger and ~~maintaining~~acquisition, ~~commercially~~five ~~viable~~drug ~~supply~~candidates, ~~relationships~~four ~~with~~of ~~third~~which ~~parties~~have since been approved by the FDA and ~~establishing~~with ~~our~~three ~~own~~receiving ~~manufacturing~~accelerated ~~capabilities~~or conditional regulatory approval in the U.S. and/or ~~infrastructure;~~E.U.

~~launching~~Dr. ~~and~~Bianco ~~commercializing~~earned ~~product~~his ~~candidates~~M.D. ~~for~~from ~~which~~the weMount ~~obtain~~Sinai ~~regulatory~~Icahn ~~approvals~~School of Medicine and ~~marketing~~completed ~~authorizations~~his residency and chief residency at the Mount Sinai Medical Center in New York City. He completed his fellowship in Hematology/Oncology at the University of Washington/Fred Hutchinson Cancer Research Center (FHCRC) where he was appointed Assistant Professor of Medicine, ~~either~~Assistant ~~directly~~Member orFHCRC ~~with~~and Director of the Bone Marrow Transplant Unit at a ~~collaborator~~“Hutch” oraffiliate ~~distributor;~~(SVAMC).

~~obtaining~~Dan ~~market~~Dearborn ~~acceptance~~joined Legacy TuHURA in 2018 as its Chief Financial Officer and has served in this role for our company since the completion of the Kintara Merger. Mr. Dearborn is a CPA with over 25 years of finance experience exclusively with health care and biotechnology companies. Prior to joining our ~~product~~company, ~~candidates~~from as2015 ~~viable~~to ~~treatment~~2017, ~~options;~~Mr. Dearborn was Chief Financial Officer at MYMD Pharmaceuticals, Inc., an emerging biotechnology firm. Mr. Dearborn is an alumnus of Loyola University in Maryland and joined Ernst & Young early in his career. He was with Pharmerica, a long-term care pharmaceutical company, for fifteen years and

~~addressing any competing technological and market developments;~~43

~~identifying~~advanced quickly to a Director role. He then moved to BioDelivery Sciences International as Controller. During his time at BioDelivery Sciences International, ~~assessing~~the company signed two very large commercial partnership agreements and was listed on Nasdaq. Mr. Dearborn later joined Welldyne, ~~acquiring~~Inc. (“Welldyne”) as its Chief Financial Officer. Welldyne is a pharmacy benefit manager that also had several related health care businesses and~~/or~~ ~~developing~~employed ~~new~~associates ~~product~~in ~~candidates;~~Florida and Colorado. During his time with Welldyne, the company was sold to Carlyle Group, Inc., one of the largest private equity firms in the world.

45Non-Employee Directors

~~negotiating~~James ~~favorable~~S. ~~terms~~Manuso, inPh.D., ~~any~~MBA, ~~collaboration~~has served as a director of Legacy TuHURA since November 2022 and as our director and Chairman since the completion of the Kintara Merger. Dr. Manuso has also served as Chairman and Chief Executive Officer of Talfinium Investments, ~~licensing~~Inc., oran ~~other~~investment ~~arrangements~~entity ~~into~~and financial consultancy, since 2014. Since 2018, Dr. Manuso has served as managing member of Laurelside LLC, a family office, which wehe ~~may~~founded. ~~enter~~Dr. Manuso has served on the board of Ocuphire Pharma, Inc., a public company (NASDAQ:OCUP) developing Nyxol in advanced clinical trials for the treatment of multiple visual disorders, since November 2020. From 2015 until 2018, Dr. Manuso served as President, Chief Executive Officer and Vice Chairman of RespireRx Pharmaceuticals Inc. (OTC QB:RSPI), a Phase 3-ready, clinical-stage respiratory and neurological pharmaceutical company. From July 2011 until October 2013, Dr. Manuso served as Chairman and Chief Executive Officer of Astex Pharmaceuticals, Inc. (Nasdaq:ASTX) and led the sale of Astex Pharmaceuticals, Inc. to Otsuka Pharmaceutical Co., Ltd. (“Otsuka Pharmaceutical”). In 2013, he was a senior mergers and acquisitions advisor to Otsuka Pharmaceuticals’ executive management. Dr. Manuso has served as board chairman and chairman of the audit, governance and nominating, pricing and compensation committees of multiple companies’ boards, including Biotechnology Industry Organization, Novelos Therapeutics, Inc., Merrion Pharmaceuticals Ltd. (MERR:IEX; Dublin, Ireland), Inflazyme Pharmaceuticals, Inc. (IZP-TSE; Vancouver, Canada), Symbiontics, Inc., which he co-founded (sold to BioMarin Pharmaceutical Inc. as ZyStor, Inc.), Montigen Pharmaceuticals, Inc., Quark Pharmaceuticals, Inc., Galenica Pharmaceuticals, Inc., Supratek Pharma, Inc., EuroGen, Ltd. (London, UK), where he was chairman, and the Greater San Francisco Bay Area Leukemia & Lymphoma Society, where he also served as vice president.

~~maintaining~~Dr. Manuso holds a B.A. with honors in Economics and Chemistry from New York University, ~~protecting~~a Ph.D. in Experimental Psychology and Genetics from the New School University, and ~~expanding~~an ~~our~~Executive ~~portfolio~~M.B.A. offrom ~~intellectual~~Columbia ~~property~~Business ~~rights,~~School. ~~including~~Dr. ~~patents,~~Manuso ~~trade~~is ~~secrets~~the author of numerous chapters, articles and ~~know-how;~~books on topics including health care cost containment and biotechnology company management.

~~attracting~~George Ng has served as a director of Legacy TuHURA since February 2020 and as a director of our company since the completion of the Kintara Merger. Mr. Ng has also served as a director of Calidi Biotherapeutics, ~~hiring~~Inc. (NYSE American: CLDI) since October 2019 and as its President and Chief Operating Officer since February 1, 2022, as well as a director and ~~retaining~~Chief ~~qualified~~Executive ~~personnel~~Officer of Processa Pharmaceuticals, Inc. (Nasdaq: PCSA) since August 8, 2023. In addition, Mr. Ng is currently a partner at PENG Life Science Ventures since September 2013, a director, co-founder, and chief business officer at IACTA Pharmaceuticals, Inc. since January 2020. Mr. Ng’s experience further includes serving in various executive-level positions for multiple publicly-traded and private global biotechnology and pharmaceutical firms. Mr. Ng previously served as a director of Inflammatory Response Research, Inc. from May 2019 to April 2020, as a director of Invent Medical Corp from July 2019 to January 2020, as a director of ImmuneOncia Therapeutics Inc. from June 2016 to 2019, and as a director of Virttu Biologics Limited from April 2017 to April 2019. Mr. Ng was also the Executive Vice President and Chief Administrative Officer of Sorrento Therapeutics, Inc. (Nasdaq: SRNE) from March 2015 to April 2019, the Co-Founder and President, Business of Scilex Pharmaceuticals Inc. from September 2012 to April 2019, and the Senior Vice President and General Counsel of BioDelivery Sciences International Inc. (Nasdaq: BDSI) from December 2012 to March 2015. Mr. Ng holds a JD degree from the University of Notre Dame School of Law, as well as a B.AS double degree in Biochemistry and Economics from the University of California, Davis.

~~Because~~Alan List, M.D. has served as a director of Legacy TuHURA since November 2022 and as director of our company since the ~~numerous~~completion ~~risks~~of the Kintara Merger. Dr. List has also served as Chief Medical Officer of Precision BioSciences, Inc. (Nasdaq: DTIL) (“Precision BioSciences”), a clinical stage gene editing company, since April 2021 and, ~~uncertainties~~prior ~~associated~~to ~~with~~that, ~~biopharmaceutical~~had ~~product~~been ~~development~~a strategic clinical advisor to Precision BioSciences and its board since April 2020, weproviding ~~are~~advice ~~unable~~regarding its clinical stage and pre-clinical allogeneic CAR T programs. Prior to ~~accurately~~joining ~~predict~~Precision BioSciences, Dr. List served in various roles at the ~~timing~~Moffitt orCancer ~~amount~~Center, ofincluding ~~incr~~

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