10-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-K

(Mark One)

For the fiscal year ended December 31, 2024

Commission File Number 001-40881

Pyxis Oncology, Inc.

(Exact name of Registrant as specified in its Charter)

321 Harrison AvenueBoston, Massachusetts 02118

(Address of principal executive offices) (Zip Code)

Registrant’s telephone number, including area code: (617) 453-3596

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

Title of each class TradingSymbol(s) Name of each exchange on which registered

Common Stock, par value $0.001 per share PYXS Nasdaq Global Select Market

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

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

Indicate by check mark if the Registrant is not required to file reports pursuant to Section 13 or 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, 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 was $182.9 million as of June 28, 2024, the last trading day prior to the quarter ended June 30, 2024 based on the closing price of $3.31 as reported on the Nasdaq Global Select Market on such date. Shares of the registrant's common stock held by executive officers, directors, and their affiliates have been excluded from this calculation. The determination of affiliate status is not necessarily a conclusive determination for other purposes.

As of March 17, 2025, the Registrant had 61,590,415 shares of common stock, $0.001 par value per share, outstanding.

DOCUMENTS INCORPORATED BY REFERENCE

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

Table of Contents

Page

PART I

Item 1. Business 4

Item 1A. Risk Factors 40

Item 1B. Unresolved Staff Comments 78

Item 1C. Cybersecurity 78

Item 2. Properties 79

Item 3. Legal Proceedings 79

Item 4. Mine Safety Disclosures 79

PART II

Item 6. [Reserved] 80

Item 7A. Quantitative and Qualitative Disclosures About Market Risk 90

Item 8. Financial Statements and Supplementary Data 90

Item 9A. Controls and Procedures 90

Item 9B. Other Information 91

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 91

PART III

Item 10. Directors, Executive Officers and Corporate Governance 92

Item 11. Executive Compensation 92

Item 14. Principal Accounting Fees and Services 92

PART IV

Item 15. Exhibits, Financial Statement Schedules 93

Signatures 96

CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS

This Annual Report on Form 10-K contains forward-looking statements concerning our business, operations and financial performance and condition, as well as our plans, objectives and expectations for our business, operations and financial performance and condition. Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking statements. These statements involve known and unknown risks and other important factors that are in some cases beyond our control and may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements.

Unless the context requires otherwise, references in this Annual Report on Form 10-K to “Pyxis Oncology,” the “Company,” “we,” “us,” and “our” refer to Pyxis Oncology, Inc. and its subsidiaries. In some cases, you can identify forward-looking statements by terms such as “anticipate,” “believe,” “can,” “continue,” “could,” “estimate,” “expect,” “intend,” “likely,” “may,” “might,” “objective,” “ongoing,” “plan,” “potential,” “predict,” “project,” “should,” “to be,” “will,” “would,” or the negative or plural of these words, or similar expressions or variations, although not all forward-looking statements contain these words. The forward-looking statements in this Annual Report on Form 10-K are only predictions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition and results of operations. These forward-looking statements speak only as of the date of this Annual Report on Form 10-K and are subject to a number of risks, uncertainties and assumptions described in the section titled “Risk Factors” and elsewhere in this Annual Report on Form 10-K. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Some of the key factors that could cause actual results to differ from our expectations include:

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our ability to develop and advance our current product candidate and program, and to successfully initiate and complete clinical trials;

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the ability of our clinical trials to demonstrate the safety, purity and potency of our product candidate and other positive results;

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the size of the market opportunity for our product candidate, including our estimates of the number of patients who suffer from the cancers we are targeting;

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our manufacturing, commercialization and marketing capabilities and strategy;

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the timing or likelihood of regulatory filings and approvals for our product candidate;

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regulatory developments in the United States and other foreign jurisdictions;

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our expectations and plans to obtain funding for our operations, including from our existing and potential future collaboration and licensing agreements;

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our ability to receive milestone or royalty payments under existing or future agreements;

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our expectations regarding our ability to obtain and maintain intellectual property protection for our product candidate;

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our continued reliance on third parties to manufacture our product candidate for clinical studies, and to conduct clinical trials and manufacture our product candidate for such clinical trials; and

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our estimates regarding expenses, future revenue, capital requirements and needs for additional financing.

In addition, statements such as “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this Annual Report on Form 10-K and, although we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted a thorough inquiry into, or review of, all potentially available relevant information. Furthermore, if our forward-looking statements prove to be inaccurate, the inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events or otherwise.

SUMMARY RISK FACTORS

You should consider carefully the risks described under “Risk Factors” in Part II, Item 1A of this Annual Report on Form 10-K. References to “Pyxis Oncology,” the “Company,” “we,” “us,” and “our” in this section titled “Summary Risk Factors” refer to Pyxis Oncology, Inc. and its wholly owned subsidiaries. A summary of the risks that could materially and adversely affect our business, financial condition, operating results and prospects include the following:

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We are a clinical stage oncology company with a limited operating history and have incurred significant losses since our inception and anticipate that we will continue to incur losses over at least the next several years and may never achieve or maintain profitability.

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We will require substantial additional capital to finance our operations. If we are unable to raise such capital when needed, or on acceptable terms, we may be forced to delay, reduce or eliminate one or more of our research and product development programs or future commercialization efforts.

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We are heavily dependent on the success of our lead product candidate, micvotabart pelidotin, formerly known as PYX-201, which is in the early stages of clinical development. If our lead product candidate is not successful in clinical trials or does not receive regulatory approval or licensure or is not successfully commercialized, our business will be materially and adversely affected.

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Our product candidate may fail in development or suffer delays that materially and adversely affect its commercial viability. If we or our existing or future collaborators are unable to initiate and complete clinical development of, obtain regulatory approval or licensure for or commercialize our product candidate or experience significant delays in doing so, our business will be materially harmed.

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Our product candidate may cause undesirable and unforeseen side effects or have other properties impacting safety that could halt its clinical development, delay or prevent its regulatory licensure, limit its commercial potential or result in significant negative consequences.

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We face significant competition from other biotechnology and pharmaceutical entities, and our operating results will suffer if we fail to compete effectively.

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Clinical testing and product development is a lengthy and expensive process with an uncertain outcome. We may incur unexpected costs or experience delays in completing, or ultimately be unable to complete, the clinical testing and the development and commercialization of our product candidate.

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The regulatory licensure and approval processes of the FDA and other comparable foreign regulatory authorities are lengthy, time-consuming and inherently unpredictable and, if we are unable to obtain marketing licensure or approval for our product candidate, our business will be substantially harmed.

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If we fail to attract and retain qualified senior management and key scientific personnel, our business may be materially and adversely affected.

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We rely on third parties to manufacture our product candidate. Any failure by a third party manufacturer to produce acceptable raw materials or product candidate for us or to obtain authorization from the FDA or comparable foreign regulatory authorities relating thereto may delay or impair our ability to initiate or complete our clinical trials, obtain regulatory licensure or approvals or commercialize approved products.

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If we are unable to obtain or protect our intellectual property in and to our product candidates, we may not be able to compete effectively in our markets.

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If we fail to comply with our obligations under any license, collaboration or other agreements, we may be required to pay damages and could lose intellectual property rights that are necessary for developing and protecting our product candidates or we could lose certain rights to grant sublicenses.

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Licensing of intellectual property is of critical importance to our business and involves complex legal, business and scientific issues. If we breach our Pfizer license agreement or any of the other agreements under which we acquired, or will acquire, intellectual property rights covering our product candidates, we could lose the ability to continue the development and commercialization of the related product candidate(s).

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Actual or perceived failures to comply with applicable data protection, privacy and security laws, regulations, standards and other requirements could adversely affect our business, operations and financial condition.

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Our information technology systems, or those of any of our existing or future CROs, manufacturers, other contractors, consultants, or collaborators, may be compromised, which could result in additional costs, significant liabilities, harm to our reputation and material disruption of our operations.

PART I

Item 1. Business.

Overview

Pyxis Oncology is a clinical stage oncology company executing on a development strategy designed to address unmet medical needs in patients with solid tumors with an immediate focus on head and neck squamous cell carcinoma (HNSCC) tumors.

Our lead product candidate, micvotabart pelidotin, formerly referred to as PYX-201, is an investigational novel antibody-drug conjugate (ADC) that uniquely targets Extradomain-B Fibronectin (EDB+FN), a non-cellular structural component within the tumor extra-cellular matrix (ECM). The tumor ECM is a complex network of fibrous proteins and molecules with unique composition that play an important role in cell development and tumor growth and in some instances, in supporting metastasis. The fibronectin strands within the ECM give the tumor shape and support the clustering of tumor cells.

Fibronectin is a key component of the ECM and its downstream signaling pathways regulate cell adhesion, migration, differentiation and wound healing. EDB+FN is an alternatively spliced form of fibronectin. EDB+FN regulates blood vessel morphogenesis, which provides the tumor access to nutrition and oxygen, and provides a means to remove waste and a pathway for cells to metastasize. EDB+FN is a compelling target for cancer therapeutics as the physiological expression of EDB+FN is very low in healthy adult tissues, yet it is found to be highly expressed in a large variety of solid tumor tissues. EDB+FN is also found to be expressed during embryogenesis.

By targeting EDB+FN, our goal is to destabilize the barrier that protects, feeds, and provides structure to the tumor, in addition to killing tumor cells directly while sparing healthy cells.

Our ADC, micvotabart pelidotin, consists of human Immunoglobulin G1 (IgG1) and is site-specifically conjugated with a cleavable linker and a microtubule inhibitor (optimized auristatin) payload. Micvotabart pelidotin is designed to optimize linker stability to enable delivery of the next generation auristatin payload that can be cleaved and released in the ECM and penetrate through the tumor cell membrane to kill tumor cells directly without the need for cell surface antigen-mediated internalization of the ADC. Unlike conventional ADCs which bind to the tumor cell surface antigens, micvotabart pelidotin is designed to deliver the auristatin payload to the extra-cellular environment and release the free payload to kill tumor cells as well as activated fibroblasts and vascular endothelial cells that support tumor growth. We believe the free payload kills the tumor cells through a combination of bystander effect directly killing highly proliferative cells and through stimulation of the local immune cells.

We conducted a Phase 1 dose escalation (Part 1) study, referred to as PYX-201-101 which began dosing patients in March of 2023. The study’s objective was to evaluate micvotabart pelidotin monotherapy in patients with advanced solid tumors predicted to express EDB+FN. PYX-201-101 (Part 1) is an open label, multicenter, dose escalation Phase 1 trial designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of micvotabart pelidotin, and to identify recommended doses for further study. Patients with a variety of relapsed or refractory solid tumor types were eligible to participate, including patients with recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC), hepatocellular carcinoma (HCC), hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancers, locally advanced / metastatic non-small cell lung cancer (NSCLC), ovarian cancer, pancreatic ductal adenocarcinoma (PDAC), renal cell carcinoma (RCC), sarcoma, thyroid cancer and triple negative breast cancer (TNBC). A total of 80 patients were dosed during the PYX-201-101 (Part 1) study.

In November 2024, we announced positive preliminary data from Part 1 of our Phase 1 dose escalation study of PYX-201-101 with a data cut-off date of October 4, 2024. The enrolled patients were heavily pre-treated with a median of four prior lines of systemic therapy in the advanced disease setting as many were seeking the micvotabart pelidotin experimental therapy as part of end-of-life care. Of the ten solid tumor types eligible to enroll in the study, patients across nine solid tumor types were enrolled and dosed. Tumor regression was observed in patients across all nine solid tumor types that were enrolled. The identified dose response range in the study was 3.6 mg/kg – 5.4 mg/kg IV Q3W.

While we observed evidence of tumor regression across all nine solid tumor types that were enrolled in the Phase 1 Part 1 dose escalation study, dose responses were most pronounced in six solid tumor types of interest, including R/M HNSCC, HR+/HER2- breast cancer, NSCLC, ovarian, sarcoma and TNBC, at the therapeutically active dose response range of 3.6 mg/kg – 5.4 mg/kg IV Q3W. Micvotabart pelidotin achieved a 26% ORR (n=31) in patients with these six solid tumor types dosed at 3.6 mg/kg – 5.4 mg/kg IV Q3W.

Dose-dependent responses were observed in patients who had failed to respond or had developed resistance to prior microtubule inhibitors (MTIs) such as taxanes or an ADC with Monomethyl Auristatin E (MMAE) payload. We believe this is a significant finding as

response in this patient population indicates that prior treatment with MTIs may not confer resistance to micvotabart pelidotin. Additionally, we observed tumor regression in patients who had progressed on previous treatment with ADCs with Topoisomerase 1 Inhibitor payloads, which is a significant finding given the number of ADCs with Topoisomerase 1 Inhibitor payloads that are approved and in clinical development. Finally, we observed that several R/M HNSCC patients who had been previously treated with and progressed on epidermal growth factor receptor inhibitors (EGFRi) directed therapies experienced tumor regression while being treated with micvotabart pelidotin. We believe this is a very important observation as the R/M HNSCC marketplace is evolving to potentially include new EGFRi targeting agents and the ability for our product candidate to regress tumors in patients who have relapsed on EGFRi therapies will enable us to compete in both the current and emerging standard of care landscape. We believe the totality of our preliminary data supports further development of both micvotabart pelidotin monotherapy expansion and combination therapy trials.

Our Clinical Pipeline

In February 2025, the U.S. Food and Drug Administration (FDA) granted Fast Track Designation to micvotabart pelidotin for the monotherapy treatment of adult patients with R/M HNSCC whose disease has progressed following treatment with platinum-based chemotherapy and an anti-PD-(L)1 antibody.

Fast Track Designation is an FDA program intended to facilitate and expedite the development and review of new drugs in the U.S. for the treatment of a serious or life-threatening condition. To qualify for this designation, there must be clear data demonstrating the drug has potential to address unmet medical need in the designated condition.

Based on the strength of the HNSCC signal that emerged in the Part 1 dose escalation study of PYX-201-101, we have decided to prioritize our resources to focus the next stage of development on characterizing the R/M HNSCC efficacy signal.

The following table summarizes our clinical pipeline reflecting this prioritized focus:

In early January 2025, we initiated the dose expansion phase (Part 2) of the PYX-201-101 monotherapy study with a prioritized focus to confirm the preliminary efficacy signals in R/M HNSCC seen in Part 1. We are actively recruiting patients for two monotherapy R/M HNSCC expansion cohorts. The Part 2 dose expansion phase includes the following two R/M HNSCC cohorts across sites in the United States (US), European Union (EU) and other countries:

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micvotabart pelidotin monotherapy for second line (2L) and third line (3L) R/M HNSCC patients who have received prior platinum-based chemotherapy and prior PD-(L)1 inhibitor therapy. We expect to enroll patients in this expansion cohort at the 5.4 mg/kg IV Q3W dose, a pharmacologically active dose identified during Part 1 of this trial where we have seen clinically meaningful anti-tumor activity with manageable safety. We anticipate having preliminary data in the second half of 2025; and

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micvotabart pelidotin monotherapy for 2L and 3L R/M HNSCC patients who have received prior epidermal growth factor receptor (EGFR) directed therapy and prior PD-(L)1 inhibitor therapy. We expect to enroll patients in this expansion cohort also at the 5.4 mg/kg IV Q3W dose and anticipate having preliminary data in the first half of 2026.

We are planning to hold a discussion with the FDA to align on our approach for finding the optimal monotherapy dose, as required under Project Optimus and expect the dose optimization phase to commence in 2026.

In November 2024, we announced a Clinical Trial Collaboration and Supply Agreement with Merck & Co, Inc. or Merck (known as MSD outside of the US and Canada), for a Pyxis Oncology-sponsored study of micvotabart pelidotin in combination with Merck’s anti-PD-(L)1 therapy, KEYTRUDA® (pembrolizumab).

In early January 2025, we initiated the Phase 1/2 combination study with KEYTRUDA® now called PYX-201-102 and are actively recruiting patients in this study. PYX-201-102 is a Phase 1/2 open label, global, multicenter dose escalation and dose expansion study to evaluate the safety, tolerability, PK, PD and preliminary efficacy of micvotabart pelidotin in combination with pembrolizumab in patients with advanced solid tumors. Patients with histologically or cytologically confirmed advanced solid tumors, including 1L R/M HNSCC, 2L+ R/M HNSCC, cervical cancer, gastric cancer, HR+/HER2- breast cancer, sarcoma and locally advanced or metastatic TNBC, are eligible to enroll.

We are planning to conduct the dose escalation phase of PYX-201-102 covering multiple tumor types with an aim to identify the Recommended Phase 2 Dose (RP2D) of micvotabart pelidotin in combination with pembrolizumab. We plan to enroll and dose patients to clear the three doses that will be tested in combination with pembrolizumab. During Part 1 dose escalation, we anticipate testing a fixed dose of pembrolizumab in combination with 3 different doses of micvotabart pelidotin ranging from 3.6 mg/kg – 5.4 mg/kg IV Q3W. Pembrolizumab (standard dose at 200 mg IV) will be given with escalating doses of micvotabart pelidotin with a starting dose of 3.6 mg/kg IV every 3 weeks (Q3W). Upon clearance of the initial dose level of 3.6 mg/kg IV Q3W by the Dose Escalation and Steering Committee (DESC), and depending on observed safety data, we may escalate to 4.4 mg/kg IV Q3W of micvotabart pelidotin with 200 mg IV of pembrolizumab, with a potential of dosing at 5.4 mg/kg IV Q3W of micvotabart pelidotin with 200 mg IV of pembrolizumab. We aim to select a dose of micvotabart pelidotin in combination with pembrolizumab by mid-year 2025, which will guide our discussion with the FDA about potential RP2D for further combination study.

Concurrently to the Part 1 dose escalation and assuming each dose clears the escalation step, the Phase 1/2 combination study will evaluate micvotabart pelidotin and pembrolizumab in patients with 1L and 2L+ R/M HNSCC. Patients will be enrolled for each dose in their respective backfill cohort upon clearance of the dose by the DESC. Pembrolizumab (standard dose at 200 mg IV) will be given with escalating doses of micvotabart pelidotin with a starting dose of 3.6 mg/kg IV every 3 weeks, followed by dose of 4.4 mg/kg IV Q3W, if DESC clears it and then a dose of 5.4 mg/kg IV Q3W, if DESC clears it. We anticipate having preliminary data on at least a subset of these R/M HNSCC patients in the second half of 2025. Timing of data availability from the full recruitment and dosing of R/M HNSCC patients is dependent on the timing of activation of additional clinical trial sites and patient enrollment. Further guidance on anticipated timing of the full preliminary data readout will be provided in 2025.

Our Team

Our company was founded in 2018 and launched operations in 2019, with a mission to defeat difficult-to-treat cancers. We have a highly qualified team with deep expertise and proficiencies across all the core oncology research and development and administrative capabilities. The collective experience across our team spans from early to late stage development and commercialization across biotechnology and pharmaceutical companies.

Our Strategy

Our goal is to improve the lives of patients with difficult-to-treat cancers. Elements of our strategy to achieve our short and long-term goals include:

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Building a leading ADC oncology company.We believe our team, with its deep oncology knowledge, functional biology expertise, ADC modality technical know-how and biologics development capabilities, positions us to build a leading ADC-focused oncology company.

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Successfully developing our lead product candidate, micvotabart pelidotin, to address significant unmet need in R/M HNSCC. HNSCC is one of the most common cancers and it is estimated that there will be approximately one million new cases of HNSCC worldwide annually by 2030. Based on the significant need for durable therapies in this patient population and the strength of the preliminary data in our PYX-201-101 monotherapy dose escalationstudy, specifically in those patients with R/M HNSCC, we are prioritizing our development efforts towards R/M HNSCC.

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Selectively forging alliances to provide strategic or financial support to our lead micvotabart pelidotinprogram. We intend to seek strategic collaborations to facilitate the capital efficient development of our pipeline. We believe various potential alliance structures including collaborations, licenses and future agreements could potentially provide significant funding to advance our pipeline and could allow us to benefit from the additional resources, development and commercialization expertise of our collaborators.

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Monetizing our intellectual property. We continue to engage in regular dialogues with potential partners to monetize our intellectual property estate including inactive programs not currently being resourced by us. Additionally, we seek to maximize the value of our biologics technology platforms, including our Flexible Antibody Conjugation Technology (FACT) Platform for ADC development and our APXiMAB Platform for antibody development.

Unmet Need in Head and Neck Cancer and Treatment Paradigm

Head and Neck Cancer (HNC) is the sixth most common cancer in the world, with 1,464,550 new cases and 487,993 deaths from HNC globally per 2020 GLOBOCAN estimates. GLOBOCAN is a cancer surveillance branch of the World Health Organization’s International Agency for Research on Cancer. Squamous Cell Carcinoma presents as the most common HNC subtype and is derived from the mucosal lining of the oral cavity, pharynx and larynx. It is estimated that by 2030 there will be approximately one million new cases of HNSCC worldwide annually per 2022 GLOBOCAN estimates. HNC accounts for approximately 4.5% of cancer diagnoses globally and deaths with over 90% of cases presenting with squamous cell origin.

HNSCC commonly originates in the mouth and throat, from the mucosa of the oral cavity, oropharynx, hypopharynx and larynx. There are approximately 59,000 cases of HNSCC each year in the U.S. with a 13% 5-year survival rate in the R/M (Stage IVC) setting. 15% of HNSCC patients are diagnosed as de novo metastatic disease and almost 50% of locally advanced cases will suffer a recurrence post initial treatment and/or become metastatic. There are approximately 26,000 cases of R/M HNSCC each year in the U.S. The median Overall Survival (OS) for patients with R/M HNSCC ranges from 9 months (HPV-) to about 14 months (HPV+). The overall incidence of HNSCC is expected to rise with a predicted 30% increase annually by 2030. The increase has been associated with multiple factors, including but not limited to tobacco use, alcohol consumption, a rise in HPV infections and other environmental catalysts. Approximately 80% of patients in the U.S. with R/M HNSCC are HPV-, a status associated with a worse prognosis. Globally, these numbers vary with higher HPV driven cancers in countries such as New Zealand and parts of Europe.

Current Treatment Paradigm of R/M HNSCC

The standard of care first line therapy for R/M HNSCC is determined by the Combined Proportional Score (CPS) which corresponds to the number of PD-(L)1 positive cells in relation to the total number of viable tumor cells. Patients with high CPS scores tend to respond better to PD-(L)1 checkpoint inhibitors, as observed across multiple tumor types. In R/M HNSCC, pembrolizumab monotherapy is recommended for patients with a CPS > 1. However, addition of platinum-based chemotherapy is strongly considered in these patients if they are symptomatic or present with aggressive disease. Pembrolizumab combined with platinum and 5-fluorouracil is recommended for patients with any PD-(L)1 status. The addition of chemotherapy to pembrolizumab increases the response rate; however, it also significantly reduces the duration of response while increasing toxicity and leads to roughly equivalent median OS with both treatments. For patients with a CPS less than one and no PD-(L)1 expression, the typical standard of care is the EXTREME regimen (not in the U.S.), a combination of cetuximab and chemotherapy, which has low response rates and survival (10 months), as well as a difficult tolerability profile.

The Phase 3 KEYNOTE-048 trial conducted by Merck investigated pembrolizumab as a monotherapy or in combination with chemotherapy, compared to cetuximab with chemotherapy in first line R/M HNSCC. The pembrolizumab monotherapy and pembrolizumab and chemotherapy combination response rates of 19% and 36%, respectively, were comparable to the 36% ORR for cetuximab and chemotherapy combination in patients with CPS >1. In these patients, pembrolizumab monotherapy and in combination with chemotherapy led to median OS of 12.3 and 13.0 months, respectively, compared to 10.7 months in the active control arm. While this represents a step forward, there remains significant unmet need in R/M HNSCC for more efficacious therapies that can extend survival, especially for chemotherapy-free alternatives with superior tolerability.

Emerging Treatment Landscape of R/M HNSCC

Currently, a few companies are innovating next-generation EGFR assets and bi-specific antibodies to address the needs of HNSCC patients, including Merus N.V (Merus) and Bicara Therapeutics Inc. (Bicara). Both Merus and Bicara have ongoing clinical trials evaluating antibodies targeting EGFR, petosemtamab and ficerafusp alfa (BCA101), respectively, as a monotherapy or as a combination therapy with pembrolizumab for the treatment of R/M HNSCC solid tumors. Merus has two Phase 3 clinical trials ongoing, 1L treatment of R/M PD-(L)1+ (CPS>1%) HNSCC in combination with pembrolizumab and 2L/3L R/M HNSCC monotherapy. Bicara has ongoing trials for the treatment of 1L R/M HNSCC, including a Phase 2/3 combination trial with pembrolizumab in HPV- patients only (1L, CPS>1%). Additionally, other agents like Nanobiotix’s radioenhancer, NBTRX3, is in clinical development that may be used earlier in the treatment sequence such as localized or locally advanced settings as well as the pending approval of pembrolizumab in adjuvant and neo-adjuvant settings that could motivate use of immuno-oncology (IO) in early disease. Other modalities including but not limited to T cell engagers may segment market further into HPV+ specific treatments along with other emerging segmentations that may trigger a change in clinical practice. These evolving shifts naturally result in the development of new patient populations (particularly in the R/M setting) that are left with limited treatments and generate a new unmet need. For example, the use of IO in the surgical setting may limit its use in the 1L segments while the use of next-generation of EGFRi in 1L will create a growing need for therapies post IO and EGFRi. Furthermore, patients that fail existing and emerging therapies are more likely to have a poor performance status, which will necessitate that the next tranche of treatment options be tolerable so patients can stay longer on the treatment and derive a survival benefit.

Our Solution: Micvotabart Pelidotin (formerly PYX-201), a Novel ADC

Micvotabart pelidotin is an investigational novel ADC that uniquely targets EDB+FN, a non-cellular structural component within the tumor ECM. The tumor ECM is a complex network of fibrous proteins and molecules with unique composition that play an important role in cell development and tumor growth and in some instances, in supporting metastasis.

The tumor ECM provides a lifeline necessary for tumor growth in solid tumors and plays a significant role in the initiation, growth, survival, invasion and drug resistance of solid tumors, yet few therapeutics specifically target tumor associated ECM. The ECM can also form an effective barrier to entry of therapeutic agents such as some chemotherapy.

The fibronectin strands within the ECM give the tumor shape and support the clustering of tumor cells. Fibronectin is a key component of the ECM and its downstream signaling pathways regulate cell adhesion, migration, differentiation and wound healing. EDB+FN is an alternatively spliced form of fibronectin that occurs when ribonucleic acid (RNA) is re-arranged to produce multiple variants of the same protein that can accumulate around blood vessels within the tumor ECM. EDB+FN regulates blood vessel morphogenesis, which provides the tumor access to nutrition and oxygen, and provides a means to remove waste and a pathway for cells to metastasize.

Our ADC, micvotabart pelidotin, consists of human IgG1 and is site-specifically conjugated with a cleavable linker and a microtubule inhibitor (optimized auristatin) payload. Micvotabart pelidotin was developed using the FACT Platform to produce an ADC designed to be highly stable with a predictable and homogenous drug-to-antibody ratio (DAR) of four. The complementarity determining regions of the EDB+FN antibody used in micvotabart pelidotin, which is the part of the antibody responsible for binding to EDB+FN, is well characterized and has been tested clinically in the form of a radiolabel-conjugated antibody for tumor imaging demonstrating a high degree of tumor-directed specificity. Furthermore, micvotabart pelidotin is designed to optimize linker stability to enable delivery of the next generation auristatin payload that can be cleaved and released in the ECM and penetrate through the tumor cell membrane to kill tumor cells directly without the need for cell surface antigen-mediated internalization of the ADC. Unlike conventional ADCs which bind to the tumor cell surface antigens, micvotabart pelidotin is designed to deliver the auristatin payload to the extra-cellular environment and release the free payload to kill tumor cells as well as activated fibroblasts and vascular endothelial cells that support tumor growth. We believe the free payload kills the tumor cells through a combination of bystander effect directly killing highly proliferative cells and through stimulation of the local immune cells. The postulated mechanism of action for micvotabart pelidotin is illustrated in Figure 2 below.

We believe EDB+FN is a compelling target for cancer therapeutics as the physiological expression of EDB+FN is very low in healthy adult tissues, yet it is found to be highly expressed in a large variety of solid tumor tissues. EDB+FN is also found to be expressed during embryogenesis. By targeting EDB+FN and specifically attacking the tumor ECM, our goal is to destabilize the barrier that protects, feeds and provides structure to the tumor in addition to killing tumor cells directly while sparing healthy cells.

EDB+FN is highly expressed in a variety of cancers, including, but not limited to, cancers of the head and neck, breast, lung, ovary, pancreas, and thyroid as compared to a matched set of normal tissues. In vitro studies have shown that down regulation of EDB+FN resulted in a significant reduction in cancer motility. Furthermore, EDB+FN expression is maintained in distant metastasis in human cancer. EDB+FN protein expression is also upregulated in the ECM of many tumor types, as compared to normal adult tissue (refer to Figure 1 below).

Figure 1

EDB+FN protein is upregulated in tumor ECM and is highly expressed in a large variety of solid tumors, with low expression in normal adult tissue.

Figure 2

Micvotabart pelidotin is designed to exhibit anti-tumor activity through three distinct modes of action:

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Tumor killing activity: The EDB+FN within the tumor ECM attracts micvotabart pelidotin to the tumor and the linker payload of the ADC is cleaved within the ECM, discharging its cytotoxic chemotherapy payload and killing the tumor cells.

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Additional bystander killing: Releasing the payload extra-cellularly within the tumor microenvironment (TME) may also kill the activated fibroblasts, vascular endothelial cells and other tumor ECM cells leading to a reduction of ECM density and inhibition of tumor angiogenesis. Re-release of payload from killed tumor cells may also confer added cytotoxicity via bystander activity.

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Immunogenic cell death: Lastly, auristatin has been shown in preclinical models to attract immune cells such as T cells into TME possibly through immunogenic cell death, which then initiates an anti-tumor immune response.

Taken together, we believe that micvotabart pelidotin may generate a multi-pronged attack on difficult-to-treat cancers by directly killing cancer cells, reducing ECM density, inhibiting tumor angiogenesis and mobilizing an anti-tumor immune response (as illustrated in Figure 2 above). Further, we believe that the non-cellular approach altering the ECM may potentially address a primary cause of drug resistance. A primary resistance mechanism to therapeutics targeting cell surface receptors expressed on tumor cells such as HER2 and EGFR that directly promote proliferation has been demonstrated to be down regulation of target expression. Given the non-cellular expression profile of EDB+FN, we believe this resistance mechanism does not apply to micvotabart pelidotin.

Clinical Development of Micvotabart Pelidotin

PYX-201-101 Phase 1 Trial

In December 2022, we announced clearance of our Investigational New Drug Application (IND) by the FDA to initiate a Phase 1 clinical trial. In March 2023, we dosed the first patient in the Phase 1 trial of micvotabart pelidotin, referred to as PYX-201-101. The study’s objective was to evaluate micvotabart pelidotin monotherapy in patients with advanced solid tumors predicted to express EDB+FN. As illustrated below in Figure 3, PYX-201-101 (Part 1) is an open label, multicenter, dose escalation Phase 1 monotherapy trial designed to evaluate the safety, tolerability, PK, PD and preliminary efficacy of micvotabart pelidotin, and to identify recommended doses for further study. Patients with a variety of relapsed or refractory solid tumor types were eligible to participate, including patients with R/M HNSCC, HCC, HR+/HER2- breast cancers, locally advanced / metastatic NSCLC, ovarian cancer, PDAC, RCC, sarcoma, thyroid cancer and TNBC. A total of 80 patients were dosed during the PYX-201-101 (Part 1) study. Information on this clinical trial is available on ClinicalTrials.gov (NCT05720117).

Figure 3

PYX-201-101 Phase 1 Dose Escalation Preliminary Clinical Data

In November 2024, we announced positive preliminary data from Part 1 of our Phase 1 dose escalation study of PYX-201-101 with a data cut-off of October 4, 2024. 80 patients were enrolled and received doses of micvotabart pelidotin ranging from 0.3 mg/kg up to 8.0 mg/kg IV Q3W across multiple solid tumor types. We identified a therapeutically active dose response range of 3.6 mg/kg – 5.4 mg/kg IV Q3W where we observed clinical benefit and a manageable safety profile. We proactively managed our enrollment around the 5.4 mg/kg IV Q3W dose level and 52% (n=42) of patients were dosed at this level. We have high comfort and appreciation for the 5.4 mg/kg IV Q3W dose level based on patient experience at this dose. We may continue to explore additional doses between 5.4 mg/kg IV Q3W and 6.6 mg/kg IV Q3W based on observed safety and efficacy signal. The dose escalation and number of patients by dose since initiating the trial in March 2023 through our data cut-off of October 4, 2024, is provided in Figure 4 below.

Figure 4

Escalation Study identified dose response range

The preliminary data set consisted of 77 patients, as 3 patients were dosed after the data cut-off date of October 4, 2024. Our Phase 1 trial patient demographics show a heavily pretreated, heterogeneous population (as illustrated in Figure 5 below) with a median of four prior

lines of systemic therapy in the advanced disease setting as many were seeking the micvotabart pelidotin experimental therapy as part of end-of-life care.Of the ten solid tumor types eligible to enroll in the study, patients across nine solid tumor types were enrolled and dosed.

Figure 5

Phase 1 PYX-201-101 Study Patient Demographics

Stability and bioavailability

Micvotabart pelidotin’s PK profile demonstrated stability in circulation due to its proprietary site-specific conjugation approach compared to approved ADCs using an MMAE payload created with non-site-specific conjugation, as illustrated in Figure 6 below.

Figure 6

Micvotabart pelidotin also presents a high systemic bioavailability. As illustrated below in Figure 7, the dose linear PK demonstrated the absence of a peripheral antigen sink that is present for many other ADCs, consistent with differentiated EDB+FN target expression in tumor ECM and negligible expression in normal tissue.

Figure 7

Safety and Tolerability

The following preliminary safety data presents key treatment-related adverse effects (TRAEs) that were monitored in the trial. Out of the 77 efficacy evaluable patients, 53 patients were treated at doses between 3.6 mg/kg IV Q3W and 5.4 mg/kg IV Q3W. Only one patient discontinued the trial for a TRAE and there were no Grade 5 TRAEs (as illustrated in Figure 8 below). Based on the preliminary safety data, we believe micvotabart pelidotin demonstrates a favorable safety and tolerability profile at therapeutically active dose response range of 3.6 mg/kg – 5.4 mg/kg IV Q3W.

Figure 8

Summary of PYX-201-101 TRAEs

Figure 9 below presents Grade 3 and 4 TRAEs. Neuropathy and ocular toxicity can be common reasons for patients to discontinue trials of many approved and clinical development ADCs; however, in PYX-201-101 we noted a 0% incidence rate in the dose response range of 3.6 mg/kg – 5.4 mg/kg IV Q3W for those Grade 3 and 4 TRAEs. The cutaneous and neutropenia toxicity events noted in our trial were reversible and generally easily treated.

Figure 9

Grade 3/4 TRAE profile

Figure 10 below presents Grade 1 and 2 TRAEs, most of which were mild to moderate, reversible and easily treatable.

Figure 10

Grade 1/2 TRAE profile

Preliminary Efficacy

The preliminary efficacy analysis data set consisted of 65 patients, of which 44 patients were dosed within the identified therapeutic dose response range of 3.6 mg/kg – 5.4 mg/kg IV Q3W. Figure 11 and Figure 12 below are waterfall charts that shows the percentage of target lesion size change from baseline, which illustrates the preliminary clinical response data across the identified therapeutic dose response range presented by each of the nine tumor types that were dosed. We observed evidence of tumor regression in patients across all nine tumor types including one confirmed cCR and two confirmed cPRs in R/M HNSCC by RECIST 1.1 criteria; a number of responses in HR+/HER2- breast cancer, NSCLC, ovarian cancer, and sarcoma; and tumor regression in TNBC. The median treatment duration for the efficacy evaluable patients across all tumor types and all doses (n=69) as of the data cut-off date of October 4, 2024 was 85 days (or 12 weeks) (as illustrated in Figure 13 below). In addition to the 65 patients in the preliminary efficacy analysis data set, four patients discontinued on the study due to progressive disease prior to receiving their first scan and were therefore included in the efficacy evaluable patient population but not the preliminary efficacy analysis set.

While we observed evidence of tumor regression across all nine solid tumor types that were enrolled in the Phase 1 Part 1 dose escalation study, dose responses were most pronounced in six solid tumor types of interest including R/M HNSCC, HR+/HER2- breast cancer, NSCLC, ovarian, sarcoma and TNBC, at the therapeutically active dose response range of 3.6 mg/kg – 5.4 mg/kg IV Q3W. Micvotabart pelidotin achieved a 26% ORR (n=31) in patients with these six solid tumor types dosed at 3.6 mg/kg – 5.4 mg/kg IV Q3W.

Dose-dependent responses were observed in patients who had failed to respond or had developed resistance to prior MTIs such as taxanes or an ADC with MMAE payload. We believe this is a significant finding as response in this patient population indicates that prior treatment with MTIs may not confer resistance to micvotabart pelidotin. Additionally, we observed tumor regression in patients who had progressed on previous treatment with ADCs with Topoisomerase 1 Inhibitor payloads, which is a significant finding given the number of ADCs with Topoisomerase 1 Inhibitor payloads that are approved and in clinical development.

Figure 11

PYX-201-101 Phase 1 Part 1 RECIST 1.1 responses by tumor histology across all dose levels

Figure 12

Waterfall Chart of PYX-201-101 Phase 1 Part 1 RECIST 1.1 responses by tumor histology across all dose levels

Figure 13

Preliminary Efficacy Data in Patients with R/M HNSCC

The R/M HNSCC patients were observed to show the strongest tumor regression response during this Part 1 phase of the study. Among the six efficacy evaluable patients with R/M HNSCC at the therapeutically active dose response range of 3.6 mg/kg – 5.4 mg/kg IV Q3W, the study achieved a confirmed 50% ORR based on RECIST 1.1 criteria, including one confirmed cCR and two confirmed cPRs, and yielded a DCR of 100%. The R/M HNSCC patients were at end-of-life with a median of four prior lines of systemic therapy in the advanced disease setting. In addition to the encouraging ORR and DCR, we observed that responses in these efficacy evaluable patients were durable with a median duration of 115 days (or 16 weeks) as of the data cut-off date of October 4, 2024 (as illustrated in Figure 14 below). Additionally, the data was observed to show preliminary clinical activity in patients with either HPV+ or HPV- tumors, indicating we may have the ability to treat R/M HNSCC patients regardless of HPV status. Further, we observed that several R/M HNSCC patients who had been previously treated with and progressed on EGFRi directed therapies experienced tumor regression while being treated with micvotabart pelidotin. We believe this is a very important observation as the R/M HNSCC marketplace is evolving to potentially include new EGFRi targeting agents and the ability for our product candidate to regress tumors in patients who have relapsed on EGFRi therapies will enable us to compete in both the current and emerging standard of care landscape. We believe the totality of our preliminary data supports further development of both micvotabart pelidotin monotherapy expansion and combination therapy trials.

Figure 14

Further Clinical Development of micvotabart pelidotin in R/M HNSCC

Our clinical development plan in R/M HNSCC is provided in Figure 15 below.

Figure 15

Monotherapy

In early January 2025, we initiated the dose expansion phase (Part 2) of the PYX-201-101 monotherapy study (NCT05720117) with a prioritized focus to confirm the preliminary efficacy signals in R/M HNSCC seen in Part 1. For Part 2 of PYX-201-101, we are actively recruiting patients for two monotherapy R/M HNSCC expansion cohorts. The clinical trial design of micvotabart pelidotin monotherapy in R/M HNSCC is provided in Figure 16 below.

Figure 16

The Part 2 dose expansion phase includes the following two R/M HNSCC cohorts across sites in the US, EU and other countries:

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micvotabart pelidotin monotherapy for 2L and 3L R/M HNSCC patients who have received prior platinum-based chemotherapy and prior PD-(L)1 inhibitor therapy. We expect to enroll patients in this expansion cohort at the 5.4 mg/kg IV Q3W dose, a pharmacologically active dose identified during Part 1 of this trial where we have seen clinically meaningful anti-tumor activity with manageable safety. We anticipate having preliminary data in the second half of 2025; and

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micvotabart pelidotin monotherapy for 2L and 3L R/M HNSCC patients who have received prior EGFR directed therapy and prior PD-(L)1 inhibitor therapy. We expect to enroll patients in this expansion cohort also at the 5.4 mg/kg IV Q3W dose and anticipate having preliminary data in the first half of 2026.

In February 2025, the FDA granted Fast Track Designation to micvotabart pelidotin for the monotherapy treatment of adult patients with R/M HNSCC whose disease has progressed following treatment with platinum-based chemotherapy and an anti-PD-(L)1 antibody.

Combination Therapy

In early January 2025, we initiated the Phase 1/2 combination study with KEYTRUDA® now called PYX-201-102 and are actively recruiting patients in this study. PYX-201-102 is a Phase 1/2, open label, global, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of micvotabart pelidotin in combination with pembrolizumab in patients with advanced solid tumors. Patients with histologically or cytologically confirmed advanced solid tumors, including 1L R/M HNSCC, 2L+ R/M HNSCC, cervical cancer, gastric cancer, HR+/HER2- breast cancer, sarcoma, and locally advanced or metastatic TNBC, are eligible to enroll. Information on this clinical trial is available on ClinicalTrials.gov (NCT06795412). The clinical trial design of micvotabart pelidotin combination therapy in R/M HNSCC and other tumor types is provided in Figure 17 below.

Figure 17

We are planning to conduct the dose escalation phase of PYX-201-102 covering multiple tumor types with an aim to identify the RP2D of micvotabart pelidotin in combination with pembrolizumab. We plan to enroll and dose patients to clear the three doses that will be tested in combination with pembrolizumab. During Part 1 dose escalation, we anticipate testing a fixed dose of pembrolizumab in combination with 3 different doses of micvotabart pelidotin ranging from 3.6 mg/kg – 5.4 mg/kg IV Q3W. Pembrolizumab (standard dose at 200 mg IV) will be given with escalating doses of micvotabart pelidotin with a starting dose of 3.6 mg/kg IV every 3 weeks. Upon clearance of the initial dose level of 3.6 mg/kg IV Q3W by the DESC, and depending on observed safety data, we may escalate to 4.4 mg/kg IV Q3W of micvotabart pelidotin with 200 mg IV of pembrolizumab, with a potential of dosing at 5.4 mg/kg IV Q3W of micvotabart pelidotin with 200 mg IV of pembrolizumab. We aim to select a dose of micvotabart pelidotin in combination with pembrolizumab by mid-year 2025, which will guide our discussion with the FDA about potential RP2D for further combination study.

Assets and Programs Available for Partnership or Collaboration

In addition to micvotabart pelidotin, we have certain clinical programs, assets and preclinical programs that we have chosen to pause for the foreseeable future. The decision to pause these programs and assets allows us to refocus development efforts and resources towards the clinical development of micvotabart pelidotin. We are seeking partnership opportunities that maximize potential value for patients and for our shareholders.

PYX-106 is an investigational fully human IgG1 Siglec-15-targeting antibody designed to block Siglec-15 mediated suppression of T-cell proliferation and function. PYX-106 has high binding affinity to a unique epitope and high potency. By binding and blocking Siglec-15 activity on myeloid cells and tumors, our Siglec-15 targeting antibody is designed to enhance immune cell mediated tumor cell killing. We licensed worldwide rights other than in Greater China (mainland China, Hong Kong, Macau and Taiwan) to PYX-106 from Biosion. In December 2024, as a part of portfolio prioritization, PYX-106 was deprioritized to allocate resources toward advancing micvotabart pelidotin. At the time of deprioritization, the Phase 1 study of PYX-106, called PYX-106-101, was not complete. PYX-106-101 enrolled 45 patients with advanced solid tumors and PYX-106 was observed as generally safe and well-tolerated across all tested doses, ranging from 0.5 mg/kg – 22.5 mg/kg. At the time of deprioritization, MTD had not been established. As a result of portfolio prioritization, we decided to suspend further clinical investment in PYX-106 and not to open Part 2 dose expansion phase of the study.

Sotigalimab or PYX-107, acquired as partof the acquisition of Apexigen Inc. (Apexigen), isa CD40 agonist with demonstrated anti-cancer activity in patients with several cancer indications. PYX-107 has been evaluated in more than 500 patients in clinical trials and demonstrated strong activity, including rapid, deep and durable responses and a favorable tolerability profile, across multiple difficult-to-treat tumor types. In a Phase II trial, PYX-107 in combination with nivolumab has demonstrated strong activity in melanoma patients who are refractory to anti-PD-(L)1, with a 15.2% PR rate and a 30.3% stable disease rate along with a favorable tolerability profile. The FDA has granted Orphan Drug Designation for PYX-107 for the treatment of soft tissue sarcoma (STS), esophageal and gastroesophageal junction (EGJ) cancers and PDAC.

PYX-203, licensed from Pfizer, is an investigational ADC that targets and binds to the interleukin-3 receptor, also known as CD123, a rapidly internalizing target that is overexpressed in hematologic cancers by leukemic blasts and stem cells. After internalization, its highly potent cyclopropylpyrroloindoline (CPI) payload is enzymatically released and trafficked to the nucleus, where it crosslinks DNA. CPI is engineered for enhanced tolerability and may allow PYX-203 to reach a broader patient population. CPI is resistant to drug efflux pumps and could confer superior cancer-killing activity. The antibody is also engineered to have a modified Fc region to mitigate off-tumor toxicity.

PYX-102 is an investigational immune-therapeutic that targets killer cell lectin-like receptor subfamily G member 1 (KLRG1), an inhibitory receptor expressed on T cells and NK cells. Its ligands, E- and N-cadherin are expressed in numerous solid cancers. By blocking KLRG1 signaling, PYX-102 may relieve immune inhibition in these tumors while rescuing KLRG1-mediated suppression of human CD8+ T cells. PYX-102 has significant potential as a monotherapy and in combination treatment strategies.

APX601, acquired as partof the acquisition of Apexigen, is a TNFR2 antagonist antibody designed to reverse immune suppression in the TME and unleash immune-mediated tumor killing activity through a unique mechanism of action. APX601 may deplete and inactivate TNFR2-expressing Tregs, reverse myeloid-mediated T cell suppression and directly kill TNFR2-expressing tumor cells. In preclinical models, APX601 has demonstrated anti-tumor activity and may have applicability for the treatment of multiple tumor indications of unmet medical need.The IND-enabling work for APX601 had been completed prior to the acquisition of Apexigen.

Our Technology Platforms

We are capitalizing on years of industry innovation and advancement in ADC platforms to develop and design our product candidates. Our micvotabart pelidotin product candidate was built utilizing the FACT Platform, initially licensed from Pfizer in December 2020, before securing an exclusive license to the FACT Platform in October 2022. The FACT Platform leverages over a decade of investment by Pfizer in refining the technical components of ADCs to improve the clinical properties of ADCs. Using our expertise in site-specific antibody conjugation, we are developing next-generation ADCs with customized linker-payload combinations aimed at increasing stability and, consequently, a reduced off target side-effect profile potentially enhancing the Therapeutic Index (TI).

The acquisition of Apexigen enhanced our ADC capabilities with the addition of Apexigen’s antibody-discovery platform (APXiMAB) Platform, to use with our FACT Platform to support and potentially accelerate our existing ADC initiatives and our end-to-end capabilities to design and produce novel next-generation ADC candidates with improved potency, stability and tolerability.

The APXiMAB Platform was used to enable the discovery of multiple protein therapeutic product candidates against a variety of molecular targets, including targets that are difficult to generate antibodies with conventional antibody technologies. In addition to certain product candidates that we wholly own, several product candidates that were discovered through the use of the APXiMAB Platform are in clinical development by our licensees. The most advanced of these programs is Novartis’ Beovu® (brolucizumab-dbll) product, which received FDA approval in 2019 and is marketed in over 70 countries. Two other programs being developed by our licensees are in later-stage development; Simcere’s Phase 3 clinical trial of suvemcitug (BD0801) combined with chemotherapy in patients with recurrent, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer, which met the primary endpoints of the Phase 3 trial in January 2024, and Mabwell’s Phase 3 clinical trial of 9MW0211 in wet age-related macular degeneration. Other than already approved programs (i.e. Novartis’ Beovu®) there is no guarantee that any of the other product candidates discovered using our APXiMAB Platform, whether developed by us or our licensees, will receive regulatory approval.

Target Catalog and Discovery Efforts

We have a large proprietary target catalog that we have assembled through both our own discovery activities and through an exclusive license from the University of Chicago for the work on immunotherapy targets out of Dr. Thomas Gajewski’s laboratory. We are also building a large “cold” tumor target discovery database leveraging several human tumor databases.

The target catalog is based upon findings from an in vivo mouse model system which examined tumor tissue for functional and dysfunctional T cells based on the ability of the T cells to produce the cytokine IL-2. Furthermore, since 4-1BB and LAG3 positive T cells do not secrete IL-2, the CD8+ T cells were sorted based on cell surface marker expression i.e., 4-1BB and LAG3, which further defined functional or dysfunctional T cells. Gene expression analysis identified upregulated cell surface molecules in dysfunctional cells which included well established markers such as PD1, CTLA4, and TIM3 and many other novel targets were identified based on bioinformatics and deep biological rationale.

Our cold tumor target discovery database used RNA-seq transcriptome analysis of human tumor databases to identify potential novel targets involved in regulation of T cell function and/or infiltration leading to cold tumors. We have supplemented this database with additional resources which we continue to mine to identify additional novel targets for immunomodulation. These cold tumor targets are potentially dominant immune suppressors that are expressed across a variety of tumor associated cells, including immune cells, tumors cells, and stroma, offering the potential to uncover novel immuno-oncology (IO) mechanisms and additional novel targets for our ADC platform.

We have large opportunities to advance product candidates based on the target catalog, however, we have chosen not to conduct additional discovery efforts to refocus our development efforts and resources toward clinical development of micvotabart pelidotin.

Competition

The biotechnology and pharmaceutical industries, including the oncology subsector, are characterized by rapidly evolving technologies, intense competition, and strong defense of intellectual property and proprietary technologies. Any product candidate that we successfully commercialize may be competitive with currently marketed therapies and any new therapies commercialized in the future. While we believe our technology, drug development expertise, leadership team and strong scientific understanding of cancer targets and biology provides us with certain competitive advantages, we face potential competition from many sources, including major pharmaceutical companies, biotechnology companies, academic institutions, and other public and private research institutions.

Many companies are active across various stages of development in the oncology subsector and are marketing and developing products that employ similar ADC approach. As of February 2025, there were approximately 650 ADCs in clinical or preclinical development worldwide, of which the vast majority are being developed for the treatment of various cancer indications. Multiple companies are also involved in the development of ADCs, including, but not limited to, AbbVie Inc., Abcure, Inc., ADC Therapeutics SA, Alligator Bioscience AB, Astellas Pharma, Inc., AstraZeneca plc, Celldex Therapeutics, Inc., Daiichi Sankyo Company, Ltd., Eucure Biopharma, a subsidiary of Biocytogen, Genentech, Inc., Gilead Sciences, Inc, GlaxoSmithKline, plc, Lyvgen Biopharma, Nextcure, Inc., Pfizer Inc., Philogen S.p.A., Merck Sharpe and Dohme (MSD) and Rakuten Medical, Inc.

We may also face competition from alternative therapeutic modalities, such as cell therapies, bispecific antibodies, vaccine, radiopharmaceuticals and small molecules that are being developed for the same cancer types that we are targeting with our pipeline candidate. These approaches could achieve regulatory approval before our product candidate or prove to be more effective, safer, or convey other advantages over any products resulting from our technology. They could potentially result in shifts in the treatment paradigms eroding or reducing the addressable market available to our product candidate.

We could also face competition with respect to specific targets, including the target of our ADC, micvotabart pelidotin, EDB+FN, by Philogen S.p.A., a Swiss based Biotechnology company, focused on generating antibody-cytokine fusions (immunocytokines) against cancers, using the L19 antibody specific to the EDB domain of Fibronectin fused to TNF, a potent inflammatory cytokine, which could pursue similar indications targeting EDB and stand out as the first non-ADC therapy pursuing EDB+FN.

There are other emerging agents in our lead indication of HNSCC. Merus’s EGFR and LGR5 targeting biclonic, petosemtamab, and Bicara’s EGFR/TGF-beta targeting bifunctional, ficerafusp alfa (BCA101), are notable competitors that are targeting HNSCC patient populations of interest to micvotabart pelidotin and pose a potentially significant threat to our clinical development strategy.

Other competitors may also include agents targeting specific segments such as HPV+ HNSCC, namely Hookipa’s and PDS Biotech’s vaccines and agents such as Nanobiotix’s radioenhancer that may be used earlier in the treatment sequence such as localized or locally advanced settings. MSD’s anti-PD1 agent, pembrolizumab (Keytruda) has also received a Priority Review from the FDA for use in the perioperative setting in HNSCC based off the Keynote-689 trial, which would encourage use of IO in the adjuvant and neo-adjuvant setting.

Furthermore, ADCs such as Gilead’s TROP-2 ADC, sacituzumab govitecan, Pfizer’s Nectin-4 targeting ADC, enfortamab vedotin and AZ’s AZD9592, a dual targeting ADC against EGFR and cMET are in clinical development in HNSCC and have shown preliminary clinical efficacy in early stage trials. Enfortamab vedotin is currently pursuing a 1L HNSCC trial in combination with pembrolizumab thus adding to the crowded landscape of combo studies in the frontline setting. Additional competition may arise from other combination regimens being evaluated including but not limited to ficlatuzumab + cetuximab (2L), ivonescimab + ligufalimab (1L, CPS>1%) and LN-145 + pembrolizumab (1L), Additionally, there is a wide array of activity in the development of immunotherapies for oncology which may be competitive with our preclinical discovery programs. Furthermore, if our product candidate is approved in oncology indications such as lung, hematological and other cancers, they may compete with existing approaches to treating cancer including surgery, radiation, and drug therapy, including conventional chemotherapy, biological products, and targeted drug small molecule therapies.

Our competitors may possess greater scientific, research and development capabilities, as well as greater financial, technical, manufacturing, marketing, sales and supply resources or experience than we do. These competitors may compete with us on the basis of establishing clinical trial sites and patient registration, recruiting and retaining qualified scientific and management personnel, and acquiring new technologies that may be complementary to, or necessary for, our programs. If we achieve regulatory approval, commercial opportunity for our product candidate may be dependent on the ability of our competitors to develop new products that may be more effective, safer, or less expensive than any products that we may develop. Our competitors may succeed in developing competing products before we do, obtaining marketing approval for products and gaining acceptance for such products in the same markets that we are targeting. Smaller or earlier-stage companies that seek collaborative arrangements with large and established companies, may prove to be significant competitors. In addition, our ability to compete may be affected by the availability of reimbursement from government and other third party payors. Competitive factors affecting the success of our programs, if approved, will likely be based on their safety and effectiveness, the timing and scope of marketing approvals, the availability and cost of supply, the depth of marketing and sales capabilities, and reimbursement coverage, among other considerations.

Chemistry, Manufacturing and Controls

We believe the manufacturing of our ADCs and monoclonal antibodies requires considerable expertise, know-how, and resources. We do not own or operate and currently have no plans to establish any Current Good Manufacturing Practice (cGMP) compliant manufacturing facilities. We currently rely, and expect to continue to rely, on external contract development manufacturing organization (CDMOs) for the manufacture of our product candidate to support non-clinical and clinical testing, as well as for commercial manufacture if our product candidate receives marketing approval. Furthermore, the raw materials and intermediates for our product candidate may be sourced, in some cases, from a single-source supplier. As part of the manufacture and design process for our product candidate, we rely on internal scientific and manufacturing know-how and trade secrets and the know-how and trade secrets of third party manufacturers. We believe that this strategy allows us to maintain a more efficient and flexible infrastructure by eliminating the need for us to invest in our own manufacturing facilities, equipment and personnel while also enabling us to focus our expertise and resources on the development of our current product candidate. We maintain agreements with our CDMOs that include confidentiality and intellectual property provisions to protect our proprietary rights related to our product candidate. We have personnel with significant technical, manufacturing, analytical, quality, including cGMP and project management experience to oversee our CDMOs and to manage manufacturing and quality data and information for regulatory compliance purposes.

Commercialization Plans

If our product candidate achieves FDA approval, we intend to retain full commercialization rights for our product candidate, including those obtained through exclusive collaboration agreements. We currently have no sales, marketing, or commercial product distribution capabilities. We intend to build our own specialized sales and marketing organization over time to support the commercialization of any approved product candidate. We may also pursue collaboration, co-promotion, distribution and/or other marketing arrangements with one or more third parties to commercialize our product candidate in markets the United States, and potentially other regions. We may also pursue these arrangements for situations in which a larger sales and marketing organization is necessary to realize the full commercial value of any approved wholly owned or collaboration product candidate.

Licensing and Collaboration Agreements

The University of Chicago Agreement

In April 2020, we entered into a license agreement (the University License Agreement) with the University of Chicago (the University) to obtain an exclusive license under certain patents resulting from research performed, in-part, by our scientific founder, Dr. Thomas Gajewski, as well as a non-exclusive license to certain know-how and materials. Under the terms of the license, we have the exclusive global right to develop and commercialize products that are covered by a valid claim of a licensed patent, incorporate or use the licensed know-how and materials or are known to assess, modulate or utilize the activity of certain specified biological targets.

In partial consideration for the license from the University, we issued to the University 48,919 shares of our common stock in 2020. Pursuant to the University License Agreement, we are obligated to pay to the University an annual maintenance fee of $10,000 commencing on the third anniversary of the effective date, potential development and commercial milestones of up to an aggregate of $7.7 million as well as running royalties on net sales of licensed products at varying rates ranging from less than a percent to the low single digits, subject to a minimum annual royalty ranging from $1.0 million to $3.0 million during certain years following the first commercial sale of a licensed product. Our royalty obligations apply on a licensed product-by-licensed product and country-by-country basis until: (1) for licensed products covered by a valid claim of a licensed patent in a given country, the expiration of such valid claims; and (2) for all other licensed products, 10 years from the first commercial sale of a licensed product in a given country. We are also obligated to pay the University a percentage of certain sublicensing revenue ranging from low- to mid-teens based on the date of entering into the applicable sublicense.

Under the University License Agreement, we are obligated to use commercially reasonable efforts to develop and bring licensed products to market, meet certain preclinical and clinical development milestones by specific dates, and promote and sell licensed products after receipt of regulatory approval, subject to certain free and payment-based extensions. The University controls prosecution of the licensed patents at our cost and we have the first right to enforce the licensed patents subject to the University’s backup enforcement rights.

The University License Agreement will remain in effect on a licensed product-by-licensed product basis until the expiration of all royalty obligations with respect to a licensed product, unless terminated in accordance with the following: (1) by the University upon 30 days’ prior written notice for any uncured payment breaches or 90 days’ prior written notice for all other uncured breaches; (2) by the University upon certain insolvency events or dissolution by us or any affiliate; or (3) by us in full or with respect to a particular licensed product at the end of the calendar quarter following the calendar quarter when we provide written notice of termination.

Pfizer Inc. Agreement

In December 2020, we entered into a license agreement (as amended, the Pfizer License Agreement) with Pfizer Inc. (Pfizer) for worldwide development and commercialization rights to two of Pfizer’s proprietary ADC product candidates (now referred to as micvotabart pelidotin and PYX-203), as well as other ADC product candidates directed to the licensed targets. The initial exclusively licensed targets are Extradomain-B Fibronectin (EDB+FN) and CD123 and we have the option to expand the scope of our license to add other licensed targets. Pfizer also granted us a non-exclusive license to use Pfizer’s FACT Platform technology to develop and commercialize the licensed ADCs. In March 2021, we entered into an amendment to the Pfizer License Agreement to include additional know-how within the scope of our license. The Pfizer License Agreement, as amended, became effective for us in March 2021. Pursuant to the Pfizer License Agreement, we paid a combined $25.0 million for the license fee, consisting of an upfront fee of $5.0 million and issued 12,152,145 shares of Series B convertible preferred stock, which was converted into 1,911,015 shares of our common stock upon our initial public offering (IPO) in October 2021, with a value of $20.0 million to Pfizer.

On October 6, 2022, we entered into an amended and restated license agreement (the A&R License Agreement) with Pfizer, which amends and restates the Pfizer License Agreement. Pursuant to the A&R License Agreement, Pfizer granted us exclusive worldwide rights under Pfizer’s FACT Platform technology to develop and commercialize ADC product candidates directed to certain licensed targets, including micvotabart pelidotin and PYX-203, and products containing the ADC product candidates. Additional ADC targets may be licensed for a nominal upfront payment and milestones. In accordance with the terms of the A&R License Agreement, we issued 2,229,654 shares of common stock to Pfizer in October 2022, paid $8.0 million to Pfizer in January 2023 and issued 1,811,594 shares of common stock to Pfizer in March 2023.

We are also obligated to pay future contingent payments, including development, regulatory, and commercial milestone up to an aggregate of $665 million for the first four licensed ADCs. In addition, we are required to pay future contingent payments including development, regulatory and commercial milestones for ADCs to each additional licensed target beyond the first four licensed ADC targets developed and commercialized via the FACT Platform. Additionally, if ADC licensed products are launched, we will pay Pfizer tiered royalties on net sales of licensed products in varying royalty rates ranging from low single digits to mid-teens. Our royalty obligations apply on a licensed product-by-licensed product and country-by-country basis from first commercial sale until the latest to occur of: (1) 12 years from first commercial sale; (2) the expiration of all regulatory or data exclusivity; and (3) the expiration of the last valid claim of a licensed patent covering the licensed product in a country. We are also obligated to pay Pfizer a percentage of certain sublicensing revenue ranging from low-double digits to twenty percent based on the stage of development of the licensed product at the time of entering into the applicable sublicense.

Under the Pfizer License Agreement, we are obligated to use commercially reasonable efforts to nominate a clinical candidate within four years of a target becoming a licensed target. We are also required to use commercially reasonable efforts to develop and seek regulatory approval for at least one licensed product directed to each licensed target in the United States and at least one other major market country (France, Germany, Italy, Japan, Spain and the United Kingdom), and to commercialize any licensed product in each such country after receiving regulatory approval. We control prosecution and enforcement with respect to any exclusively licensed patents, and Pfizer has prosecution and enforcement rights if we elect not to exercise such rights.

The Pfizer License Agreement will remain in effect until the expiration of the last to expire royalty term, unless terminated in accordance with the following: (1) by either party for the other party’s material breach if such party fails to cure such breach within the specified cure period; (2) by either party upon certain insolvency events of the other party; or (3) prior to receipt of the first regulatory approval for a licensed product, by us for any reason upon 90 days’ prior written notice, or after receipt of the first regulatory approval for a licensed product, by us for any reason upon one year’s prior written notice.

License Agreement with Biosion USA, Inc.

On March 28, 2022, we entered into a license agreement (the Biosion License Agreement) with Biosion USA, Inc. (Biosion) pursuant to which we obtained an exclusive, worldwide (other than Greater China (mainland China, Hong Kong, Macau and Taiwan)), license for development, manufacturing and commercialization rights for BSI-060T, a Siglec-15 targeting antibody, an IO product candidate (now referred to as PYX-106), and products containing the licensed compound. Under the terms of the Biosion License Agreement, each party granted to the other party a right of first offer to obtain an exclusive license in the other party’s territory (Greater China for Biosion and the rest of the world for us) to develop, manufacture and commercialize any bi-specific or multi-specific antibody any antibody-drug conjugate controlled by a party or its affiliate that inhibits, modulates or binds to Siglec-15 as an intended mechanism of action.

Pursuant to the Biosion License Agreement, we paid an upfront fee of $10.0 million and are obligated to pay future contingent payments including development, regulatory and commercial milestones up to an aggregate of $217.5 million in case of normal approval and $222.5 million in case of Accelerated Approval. Additionally, if products are launched, we will pay Biosion tiered royalties on net sales of licensed products in varying royalty rates ranging from low single digits to low teens. Our royalty obligations apply on a licensed product-by-licensed product and country-by-country basis from first commercial sale until the latest to occur of: (1) 12 years from first commercial sale; (2) the expiration of all regulatory or data exclusivity; and (3) the expiration of the last valid claim of a licensed patent covering the licensed product in a country. We are also obligated to pay Biosion a percentage of certain sublicensing revenue ranging from low-double to mid-double digits based on the stage of development of the licensed product at the time of entering into the applicable sublicense.

Under the Biosion License Agreement, we are obligated to use commercially reasonable efforts to clinically develop and seek regulatory approval for at least one licensed product in the licensed territory, and to commercialize such licensed product following receipt of regulatory approval. We control prosecution and enforcement with respect to the licensed patents in the licensed territory.

The Biosion License Agreement will remain in effect on a licensed product-by-licensed product and country-by-country basis until the expiration of the applicable royalty term, unless terminated in accordance with the following: (1) by either party for the other party’s material breach if such party fails to cure such breach within the specified cure period; (2) by either party upon certain insolvency events of the other party; (3) by us for scientific or safety reasons; (4) any time following completion of our first clinical trial for a licensed product, by us for convenience; or (5) by Biosion if we cease development and commercialization activities for licensed products for a specified period of time, subject to certain exceptions.

Out-License Relationships

In August 2023, we completed the acquisition of Apexigen contemplated by the Merger Agreement, with Apexigen surviving as a wholly owned subsidiary of the Company. Upon the Merger Agreement, we assumed all out-licensing agreements of Apexigen. The assumed agreements consist of licenses with several biopharmaceutical companies that are developing product candidates that were discovered using our APXiMAB platform, which has been important to prosecuting the full value of our platform. We believe the licenses for the programs for the development of product candidates we have generate and demonstrate the productivity and utility of our platforms and position us to receive meaningful milestone and royalty payments if those product candidates are approved and successfully commercialized.

Described below are the out-license relationships and the related agreements under which we may receive milestone or royalty payments.

Simcere License and Collaboration Agreement

In December 2008, Epitomics (Apexigen’s predecessor) and Jiangsu Simcere Pharmaceutical R&D Co., Ltd. (Simcere) entered into a license and collaboration agreement (the Simcere Agreement) for the development and commercialization of suvemcitug (BD0801) for oncology in China. Suvemcitug is a humanized anti-VEGF monoclonal antibody molecule derived from APXiMAB technology. Simcere is responsible for conducting the development and commercialization of suvemcitug in China at its cost. Under the terms of the Simcere Agreement, Apexigen had, and now we have, reserved the right to develop and commercialize suvemcitug outside of China at our discretion. If we develop and commercialize suvemcitug outside of China, we will share with Simcere costs incurred and revenue earned outside of China. Under the Simcere Agreement, Simcere has an exclusive, royalty-bearing license (without the right to sublicense) to Apexigen's rights in certain intellectual property to develop and commercialize suvemcitug in the field of oncology therapeutics in China.

Simcere granted Apexigen a non-exclusive, royalty-free, worldwide license (without the right to sublicense) to improvements derived from suvemcitug using the intellectual property licensed to Simcere for any purpose outside of China and for purposes outside of oncology therapeutics in China. Intellectual property created in the collaboration program with Simcere is jointly owned by Apexigen and Simcere. Simcere is obligated to pay milestone payments for achievement of certain clinical development milestones and low to high single digit percentage royalties on net sales of suvemcitug in China until 15 years after the first commercial sale of suvemcitug. If we choose to commercialize suvemcitug outside of China, we will share with Simcere a mid-double-digit percentage of costs and revenue arising from the development and commercialization of suvemcitug outside of China. Unless terminated earlier, the Simcere Agreement continues until 15 years after the first commercial sale of suvemcitug. Either party may terminate the Simcere Agreement for the other party’s uncured material breach. Simcere may terminate the Simcere Agreement upon a decision by an appellate court in China that suvemcitug infringes a third party patent and such dispute cannot be resolved by settlement, licensing or other alternatives.

In January 2024, Simcere announced that the Phase 3 clinical trial of Suvemcitug for injection combined with chemotherapy in patients with recurrent, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer met its primary endpoints of the progression-free survival. In March 2024, Simcere announced the New Drug Application (NDA) for Suvemcitug for injection was accepted by the China National Medical Products Administration (NMPA).

T-Mab/Mabwell Agreement

In May 2008, Epitomics and Jiangsu T-Mab Biotechnology Ltd., Co. (T-Mab) entered into a license, co-development and contract manufacture agreement (the T-Mab Agreement) for the development and commercialization of therapeutic candidates in two therapeutic programs, each directed to a specified target for specified fields, including VEGF for the treatment of ocular diseases, in China. Mabwell (Shanghai) Bioscience Co., Ltd. (Mabwell) acquired T-Mab in 2015. Mabwell is responsible for conducting the development and commercialization of the therapeutic candidates in China. We may, at our discretion, develop and commercialize such therapeutic candidates outside of China; however, we must pay Mabwell a royalty on sales of such therapeutic candidates made outside of China if we do so.

Under the T-Mab Agreement, Mabwell was granted an exclusive, royalty-bearing, perpetual license (without the right to sublicense) to its rights in certain intellectual property that it licensed from Epitomics to develop and commercialize such therapeutic candidates. Mabwell is obligated to pay us a mid-single-digit percentage royalty on net sales of such therapeutic candidates in China. If we choose to commercialize such therapeutic candidates outside of China, we would be obligated to pay Mabwell a mid-single-digit percentage royalty on net sales of such therapeutic candidates outside of China that we sell directly to end users and a mid-single-digit percentage of revenue we receive as sublicense fees, milestone payments and royalties related to the sale of such therapeutic candidate. Each party’s obligations to pay royalties to the other party continue until 15 years after the first commercial sale of licensed product in each party’s respective territory. The term of the T-Mab Agreement expired in May 2013; however, Mabwell’s royalty payment obligations under the agreement survive expiration. The royalty term for 9MW0211, an anti-VEGF antibody licensed under the T-Mab Agreement, will begin with the first commercial sale in China and end after a low two-digit number of years.

Mabwell is currently in Phase 3 development of 9MW0211.

Toray Sublicense Agreement

In May 2012, Apexigen and Toray Industries, Inc. (Toray), entered into a non-exclusive sublicense agreement (the Toray Agreement) under which Apexigen granted Toray a non-exclusive, worldwide sublicense, with the right to grant further sublicenses, to develop and commercialize drug product candidates that Toray developed using antibodies created using the APXiMAB platform that target certain molecules to use in the development of its drug product candidates. Under the Toray Agreement, Toray paid an upfront fee and agreed to pay certain development- and regulatory-related milestone payments and a low single-digit percentage royalty on net sales of licensed products by Toray or its affiliates. Toray is also obligated to pay us a mid-teens percentage of certain payments Toray receives from sublicensees under the Toray Agreement, which payments may limit Toray’s obligations to pay the milestone payments described above. Subject to certain termination rights, including Toray’s right to terminate the agreement for convenience upon 60 days’ prior written notice, the Toray Agreement continues on a product-by-product and country-by-country basis until 10 years after the first commercial sale of such product in

such country. Upon expiration or early termination of the agreement, Toray’s sublicense and any further sublicenses granted by Toray will automatically terminate.

Toray is currently in Phase 2 development of TRK-950, an antibody licensed under the Toray Agreement.

Intellectual Property

Our intellectual property is critical to our business, and we strive to protect it, including by obtaining and maintaining patent protection in the U.S. and internationally for our product candidates, new therapeutic approaches, platform technologies, potential methods of use in our indications of interest and other inventions that are important to our business. We also rely on trade secrets and proprietary know-how to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection.

Our patent portfolio includes patents and patent applications that are exclusively licensed from the University of Chicago, Pfizer and Biosion, and patents and patent applications that are wholly owned by us. Our patent portfolio includes patents and patent applications that cover our product candidates micvotabart pelidotin (formerly PYX-201), PYX-203, PYX-106, PYX-107 and PYX-102, and the use of these candidates for therapeutic purposes in certain territories. Our proprietary technology has been developed primarily through internal development efforts and relationships with academic institutions, Pfizer, Biosion and contract research organizations.

For our product candidates, we will, in general, initially pursue patent protection covering compositions of matter and methods of use. Throughout the development of our product candidates, we seek to identify additional means of obtaining patent protection that would potentially enhance commercial success, including through additional methods of use for particular indications, process of making, formulation and dosing regimen-related claims.

For all patent applications, we determine claiming strategy on a case-by-case basis. Advice of counsel and our business model and needs are always considered. We file patent applications containing claims for protection of useful applications of our proprietary technologies and any products, as well as new applications and/or uses we discover for existing technologies and products, assuming these are strategically valuable. We continuously reassess the number and type of patent applications, as well as the existing patent claims to ensure that maximum coverage and value are obtained for our processes and compositions, given existing patent office rules and regulations. Further, claims may be modified during patent prosecution to meet our intellectual property and business needs.

We 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. The patent positions of immuno-oncology companies like ours are generally uncertain and involve complex legal, scientific and factual questions. 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 current or future product candidates or for our platform technologies. 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.

Regardless of the coverage we seek under our existing patent applications, there is always a risk that an alteration to the product or process may provide sufficient basis for a competitor to avoid infringement claims. In addition, the coverage claimed in a patent application can be significantly reduced before a patent is issued, and courts can reinterpret patent scope after issuance. Moreover, many jurisdictions, including the United States, permit third parties to challenge allowed or issued patents in administrative proceedings, which may result in further narrowing or even cancellation of patent claims. Moreover, we cannot provide any assurance that any patents will be issued from our pending or any future applications or that any current or future issued patents will adequately protect our products.

In total, our patent portfolio, including patents licensed from the University of Chicago, Pfizer and Biosion, and patents owned by us, comprises 33 different patent families, filed in various jurisdictions worldwide, including families directed to compositions of matter for antibodies and antibody-drug conjugates, families directed towards the compositions, manufacture, and use, of antibodies and antibody-drug conjugates generally, families directed towards methods of identifying patients for treatment with compositions of antibodies and antibody-drug conjugates and subsequently treating said patients, and families directed to methods of treating cancer and identifying potential targets.

Micvotabart Pelidotin (formerly PYX-201) Patent Families, Status, and Potential Expiration

Micvotabart pelidotin is covered by a growing portfolio of patent families, some of which are in-licensed from Pfizer and some of which we have sole ownership of.

Details, status, and potential expiration dates of micvotabart pelidotin patent families are summarized below:

Micvotabart Pelidotin Antibody-Drug Conjugate Composition of Matter (Drug Product) Patent Coverage

Micvotabart Pelidotin Related Patent Families – Constructs, Methods, and Components

Micvotabart Pelidotin Anti-EDB+FN Antibody-Drug Conjugate Composition of Matter and Methods of Using the Same. We have exclusively licensed from Pfizer a patent family for antibodies and antibody-drug conjugates that bind to the extra domain B splice variant of fibronectin, including the composition of matter for micvotabart pelidotin and methods of using micvotabart pelidotin in treating certain cancer including NSCLC, colorectal cancer, PDAC and generic breast cancer, that includes granted patents in Australia, Austria, Belgium, Bulgaria, China, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Great Britian, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Latvia, Lithuania, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Russia, Serbia, Slovak Republic, Slovenia, South Korea, Spain, Sweden, Switzerland, Turkey, and the United States, and pending applications in Australia, Brazil, Canada, China, European Patent Organization (Europe), Hong Kong, Israel, Japan, Mexico, Singapore, South Africa, and the United States. The 20-year term of the patents in this family runs through 2037, absent any available patent term adjustments or extensions.

Methods of using Micvotabart Pelidotin - Constructs and Compositions for Treating EDB+FN Expressing Disease and Disorders in Certain Cancer Indications. We have sole ownership of a patent family for constructs, compositions, and methods of treating EDB+FN expressing diseases and disorders, including but not limited to HNSCC, sarcoma, TNBC, HR+ breast cancer, ovarian cancer, and

thyroid cancer, with micvotabart pelidotin and similar constructs, that includes provisional patent applications filed in the United States. The 20-year term of this patent family runs through 2045, absent any available patent term adjustments or extensions.

Dosage and Treatment Regimens of Micvotabart Pelidotin. We have sole ownership of a patent family for dosage and treatment regimens of micvotabart pelidotin and similar constructs, that includes a provisional patent application filed in the United States. The 20-year term of this patent family runs through 2045, absent any available patent term adjustments or extensions.

Cytotoxic Peptides and Antibody-Drug Conjugates Thereof. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward cytotoxic pentapeptides, including the auristatin 0101 (Aur0101) payload and MC-VC-PABC-Aur0101 linker-payload (vc0101, pelidotin) found in micvotabart pelidotin, and to antibody-drug conjugates thereof, that includes granted patents in Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Czech Republic, Denmark, Finland, France, Germany, Great Britain, Greece, Hong Kong, Hungary, Iceland, Indonesia, Ireland, Israel, Italy, Japan, Luxembourg, Malaysia, Mexico, Netherlands, New Zealand, Norway, Peru, Philippines, Poland, Portugal, Romania, Russia, Saudi Arabia, Singapore, Slovak Republic, Slovenia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey, and the United States, and pending applications in India, and Venezuela. The 20-year term of the patents in this family runs through 2032, absent any available patent term adjustments or extensions.

Antibodies and Antibody Fragments for Site-Specific Conjugation. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward polypeptides, antibodies, and antigen-binding fragments thereof, that comprise a engineered cysteine for site-specific conjugation, including the K290C engineered cysteine found in micvotabart pelidotin, that includes granted patents in Australia, China, Colombia, Hong Kong, India, Israel, Japan, Malaysia, Mexico, Russia, Saudi Arabia, South Africa, South Korea, and Taiwan, and pending applications in Canada, Europe, Indonesia, Peru, Philippines, Singapore, and Venezuela. The 20-year term of the patents in this family runs through 2036, absent any available patent term adjustments or extensions.

Engineered Antibody Constant Regions for Site-Specific Conjugation and Methods and Uses Therefor. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward antibodies, and antigen-binding portions thereof, engineered to introduce amino acids for site-specific conjugation, including the kK183C engineered cysteine found in micvotabart pelidotin, that includes granted patents in Canada, France, Germany, Great Britain, Ireland, Italy, Japan, Spain, and the United States, and pending applications in Canada, Europe and Japan. The 20-year term of the patents in this family runs through 2032, absent any available patent term adjustments or extensions.

Composition of Matter Patents for Additional Assets (excluding micvotabart pelidotin)

PYX-203 Anti-CD123 Antibody-Drug Conjugate. We have exclusively licensed from Pfizer a patent family for antibodies and antibody-drug conjugates that specifically bind to CD123, that includes granted patents in Canada, China, Colombia, India, Indonesia, Israel, Japan, Russia, South Korea, Taiwan, and the United States, and pending applications in Australia, Brazil, Canada, China, Europe, Hong Kong, Japan, Mexico, New Zealand, Philippines, Singapore, South Africa, and the United States, that claim the composition of matter and certain methods of use with respect to PYX-203. The 20-year term of the patents in this family runs through 2038, absent any available patent term adjustments or extensions.

PYX-106 Anti-Siglec-15 Antibody. We have exclusively licensed from Biosion USA, Inc. a patent family for monoclonal antibodies that specifically bind human Siglec15, including PYX-106, that includes granted patents in Australia, China, Israel, Japan, New Zealand, South Korea, and the United States, and pending applications in Australia, Brazil, Canada, Egypt, Europe, Hong Kong, India, Indonesia, Japan, Malaysia, Mexico, New Zealand, Philippines, Russia, Saudi Arabia, Singapore, South Africa, United Arab Emirates, and the United States. The 20-year term of the patents in this family runs through 2041, absent any available patent term adjustments or extensions.

PYX-107A/B “Sotigalimab” CD40 Agonist Antibodies. Through our acquisition of Apexigen, Inc. we have acquired sole ownership of two patent families for high affinity CD40 agonist monoclonal antibodies and related compositions, including PYX-107 (also known as sotigalimab) which may be used in any of a variety of therapeutic methods for the treatment of cancer and other diseases. The first patent family includes granted patents in Australia, Belgium, Brazil, Canada, China, France, Germany, Great Britain, Hong Kong, India, Italy, Japan, Mexico, New Zealand, Russia, Singapore, South Africa, South Korea, Spain, Switzerland, and the United States, with pending applications in Europe, Israel, and the United States. The 20-year term of this first patent family runs through 2032, absent any available patent term adjustments or extensions. The second patent family includes granted patents in Australia, Belgium, China, Denmark, France, Germany, Great Britain, Hong Kong, India, Ireland, Italy, Japan, Luxembourg, Macau, Mexico, Monaco, Netherlands, New Zealand, Norway, South Africa, South Korea, Spain, Sweden, Switzerland, and the United States, with pending applications in Canada, Europe, Japan and the United States. The 20-year term of this second patent family runs through 2033, absent any available patent term adjustments or extension.

APX-601 Anti-TNFR2 Antibodies and Methods of Use. Through our acquisition of Apexigen, Inc. we have acquired sole ownership of a patent family for anti-tumor necrosis factor receptor 2 (TNFR2) antibodies and related compositions, which may be used in any of a variety of therapeutic or diagnostic methods, including the treatment or diagnosis of oncological diseases, inflammatory and/or autoimmune diseases, that includes pending applications in Australia, Brazil, Canada, China, Eurasia, Europe, India, Israel, Japan, Mexico, New Zealand, Singapore, South Africa, South Korea, Taiwan, and the United States. The 20-year term of the patents in this family runs through 2040, absent any available patent term adjustments or extension.

PYX-102 Anti-KLRG1 Antibody. We have sole ownership of a patent family for monoclonal antibodies that specifically bind human KLRG1, that includes a pending international Patent Cooperation Treaty patent application. The 20-year term of this patent family runs through 2044, absent any available patent term adjustments or extensions.

Certain Methods Patents Related to Compositions of Matter

PYX-107D Methods of Treating Cancer with CD-40 Agonists. Through our acquisition of Apexigen we have acquired sole ownership of a patent family for methods of identifying a sub-population of cancer patients amenable for a combination therapy with a CD40 agonist and one or more chemotherapy drugs and subsequently treating the sub-population of cancer patients with said combination therapy, that includes pending patent applications in Canada, China, Europe, Japan, and the United States. The 20-year term of the patents in this family runs through 2042, absent any available patent term adjustments or extensions.

PYX-107F Biomarkers for CD40 Agonist Therapy. Through our acquisition of Apexigen we have acquired sole ownership of a patent family for biomarkers and other characteristics for predicting tumor responsiveness to CD40 agonist therapy in melanomas, and related kits, compositions, and methods of treating said melanomas, including PD-(L)1 refractory melanomas, that includes pending applications in Europe and the United States. The 20-year term of the patents in this family runs through 2042, absent any available patent term adjustments or extensions.

PYX-002 Site Specific Ligand-Payload Conjugates. We have sole ownership of a patent family for ligand-payload conjugates, and compositions and use thereof for treating diseases, disorders, or conditions, such as cancers, autoimmune diseases, or infectious diseases, that includes pending applications in Europe and the United States. The 20-year term of the patents in this family runs through 2043, absent any available patent term adjustments or extensions.

Antibody-Drug Candidate Patent Rights

Spliceostatin analogs. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture useful in antibody-drug conjugates generally, directed toward novel cytotoxic spliceostatin analogs and derivatives, that includes granted patents in Australia, Belgium, Brazil, Canada, China, Denmark, Finland, France, Germany, Great Britain, Hong Kong, India, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Russia, South Korea, Spain, Sweden, Turkey, and the United States, and no pending applications. The 20-year term of the patents in this family runs through 2033, absent any available patent term adjustments or extensions.

Tubulysin analogs and methods for their preparation. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture useful in antibody-drug conjugates generally, directed toward cytotoxic tubulysin analogs and derivatives, that includes a granted patent in the United States, and no pending applications. The 20-year term of the patent in this family runs through 2037, absent any available patent term adjustments or extensions.

Heteroaryl Sulfone-based Conjugation Handles, Methods for Their Preparation, and Their Use in Synthesizing Antibody-Drug Conjugates. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture useful in antibody-drug conjugates generally, directed toward heteroaryl sulfone-based conjugation handles for use in synthesizing antibody-drug conjugates, that includes granted patents in Canada, Japan, and the United States, and pending applications in Europe and Japan. The 20-year term of the patents in this family runs through 2037, absent any available patent term adjustments or extensions.

Purification of Antibody-Drug Conjugates Using a Sodium Phosphate Gradient. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture useful in antibody-drug conjugates generally, directed toward methods of removing high molecular weight species, in particular aggregates, from antibody-drug conjugate preparations, by contacting preparations of the antibody-drug conjugate reaction mixture with a hydroxyapatite resin and selectively eluting the antibody-drug conjugate from the resin using a gradient comprising sodium phosphate, that includes granted patents in France, Germany, Great Britain, Ireland, Italy, Spain, and the United States, and a pending application in the United States. The 20-year term of the patents in this family runs through 2036, absent any available patent term adjustments or extensions.

Bifunctional Cytotoxic Agents Containing the CTI Pharmacophore. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture useful in antibody-drug conjugates generally, directed toward bifunctional CTI-CTI and CBI-CTI dimers that can function as stand-alone drugs, payloads in antibody-drug conjugates, and linker-payload compounds useful in connection with the production or administration of such antibody-drug conjugates, that includes granted patents in Australia, Belgium, Canada, China, Denmark, Finland, France, Germany, Great Britian, Hong Kong, India, Ireland, Israel, Italy,

Japan, Mexico, Netherlands, Norway, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey, and the United States, and a pending application in Brazil. The 20-year term of the patents in this family runs through 2036, absent any available patent term adjustments or extensions.

Calicheamicin Derivatives and Antibody-Drug Conjugates Thereof. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture useful in antibody-drug conjugates generally, directed toward calicheamicin derivatives useful as payloads in antibody drug-conjugates, that includes granted patents in Canada, Japan, and the United States, and pending applications in the U.S. and Europe. The 20-year term of the patents in this family runs through 2038, absent any available patent term adjustments or extensions.

Cysteine Engineered Antibody-Drug Conjugate. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture useful in antibody-drug conjugates generally, directed toward anti-CD33 antibody-drug conjugates with an engineered cysteine residue, that includes a granted patent in the United States, and no pending applications. The 20-year term of the patent in this family runs through 2038, absent any available patent term adjustments or extensions.

Platform Patent Rights

Engineered Polypeptide Conjugates Using Transglutaminase. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward engineered polypeptide conjugates comprising specific acyl donor glutamine-containing tags and amine donor agents, that includes granted patents in Canada, France, Germany, Great Britain, Ireland, Italy, Japan, Spain, and the United States, and a pending application in the United States. The 20-year term of the patents in this family runs through 2034, absent any available patent term adjustments or extensions.

Stability-Modulating Linkers for Use with Antibody-Drug Conjugates. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward stability-modulating linker components used to make these stability-modulated antibody-drug conjugates, that includes granted patents in Australia, Austria, Belgium, Brazil, Canada, China, Denmark, France, Germany, Great Britain, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Poland, Russia, South Korea, Spain, Sweden, Switzerland, Turkey, and the United States, and pending applications in Mexico and the United States. The 20-year term of the patents in this family runs through 2035, absent any available patent term adjustments or extensions.

Synergistic Auristatin Combinations. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward combinations of an auristatin or an auristatin-based antibody-drug conjugate with second active agents including PI3K/mTOR inhibitors, MEK inhibitors, taxanes, or other anti-cancer agents, that includes granted patents in the United States and Japan, and pending applications in Canada and Europe. The 20-year term of the patents in this family runs through 2035, absent any available patent term adjustments or extensions.

Capped and Uncapped Antibody Cysteines, and Their Use in Antibody-Drug Conjugation. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward antibody production process in which engineered unpaired cysteine residues are post-translationally modified and capped with particular chemical entities, which capped antibodies are well suited to further site-specific conjugation steps to form antibody-drug conjugates, that includes granted patents in Australia, Austria, Belgium, Brazil, China, Denmark, France, Germany, Great Britain, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Poland, Russia, South Korea, Spain, Sweden, Switzerland, Turkey, and the United States, and pending applications in Canada, Europe, Russia, and the United States. The 20-year term of the patents in this family runs through 2036, absent any available patent term adjustments or extensions.

Large Scale Production Process for Capped and Un-capped Antibody Cysteines and Their Use in Therapeutic Protein Conjugation. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward optimizing production of selectively capped, and uncapped, cysteines on antibodies by manipulation of cell growth conditions, that includes granted patents in Japan, South Korea, and the United States, and no pending applications. The 20-year term of the patents in this family runs through 2038, absent any available patent term adjustments or extensions.

Bifunctional Cytotoxic Agents. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward cytotoxic dimers comprising CBI-based and/or CPI-based sub-units, and antibody-drug conjugates comprising such dimers, that includes granted patents in Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Czech Republic, Denmark, Finland, France, Germany, Great Britain, Greece, Hong Kong, Hungary, Iceland, India, Indonesia, Ireland, Israel, Italy, Japan, Luxembourg, Malaysia, Mexico, Netherlands, New Zealand, Norway, Peru, Philippines, Poland, Portugal, Romania, Russia, Saudi Arabia, Singapore, Slovak Republic, Slovenia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey, the United States and Venezuela, and a pending application in Argentina. The 20-year term of the patents in this family runs through 2035, absent any available patent term adjustments or extensions.

Engineered Polypeptide Conjugates and Methods for Making Thereof Using Transglutaminase. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward engineered polypeptide conjugates comprising acyl donor glutamine-containing tags and amine donor agents, that includes granted patents in Canada, Japan, and the United States, and a pending application in Europe. The 20-year term of the patents in this family runs through 2031, absent any available patent term adjustments or extensions.

Antibody-Drug Conjugates with High Drug Loading. We have exclusively licensed from Pfizer, subject to certain reservations, a patent family for compositions, methods of use, and/or methods of manufacture related to the FACT Platform, directed toward transglutaminase-mediated antibody-drug conjugates with high anti-body-drug ratio, that includes granted patents in Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, Denmark, Finland, France, Germany, Great Britain, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Luxembourg, Mexico, Netherlands, Poland, Portugal, Romania, Russia, Slovak Republic, Slovenia, South Korea, Spain, Sweden, Switzerland, Turkey, and the United States, and a pending application in South Korea. The 20-year term of the patents in this family runs through 2035, absent any available patent term adjustments or extensions.

Methods in Immuno-Oncology

Methods and Compositions Related to T-Cell Activity. We have exclusively licensed from the University of Chicago a patent family for methods for treating patients with immunotherapy based on the identification of the patient as having non-anergic T cells after measuring expression levels of various genes that includes granted patents in France, Germany, Great Britian, Italy, Spain, and the United States, and a pending application in the United States. The 20-year term for patents in this family runs through 2034, absent any available patent term adjustments or extensions.

Beta-catenin Inhibitors in Cancer Immunotherapy. We have exclusively licensed from the University of Chicago a patent family for methods for treating solid tumor cancers that includes two granted patents in the United States, and no pending applications. The 20-year term for patents in this family runs through 2036, absent any available patent term adjustments or extensions.

Dysfunctional Antigen-specific CD8+ T Cells in the Tumor Microenvironment. We have exclusively licensed from the University of Chicago a patent family for methods of treating cancer comprising administering an agent that specifically targets dysfunctional tumor antigen-specific CD8+T cells that includes pending applications in Canada, and Europe, and a granted patent in the United States. The 20-year term for patents in this family runs through 2038, absent any available patent term adjustments or extensions.

Patent Term and Term Extensions

Individual patents have terms for varying periods depending on the date of filing of the patent application or the date of patent issuance and the legal term of patents in the countries in which they are obtained. Generally, utility patents issued for applications filed in the United States, and most countries around the world, are granted a term of 20 years from the earliest effective filing date of a non-provisional patent application. In addition, in certain instances, the term of a U.S. patent can be extended to recapture a portion of the United States Patent and Trademark Office (USPTO) delay in issuing the patent as well as a portion of the term effectively lost as a result of the FDA regulatory review period. However, as to the FDA component, the restoration period cannot be longer than five years, and is typically less, and the restoration period cannot extend the patent term beyond 14 years from FDA approval. In addition, only one patent applicable to an approved drug is eligible for the extension, and only those claims covering the approved drug, a method for using it, or a method of manufacturing may be extended. Similar provisions are available in Europe and other foreign jurisdictions to extend the term of a patent that covers an approved drug. We will, in general, pursue available patent term extensions in the U.S. and in foreign jurisdictions that provide for patent term extensions, however, there is no guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment of whether such extensions should be granted, and if granted, the length of such extensions. All taxes, annuities or maintenance fees for a patent, as required by the USPTO and various foreign jurisdictions, must be timely paid in order for the patent to remain in force during this period of time.

The actual protection afforded by a patent may vary on a product-by-product basis, from country to country, and can depend upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions and the availability of legal remedies in a particular country and the validity and enforceability of the patent.

Our patents and patent applications may be subject to procedural or legal challenges by others. We may be unable to obtain, maintain and protect the intellectual property rights necessary to conduct our business, and we may be subject to claims that we infringe or otherwise violate the intellectual property rights of others, which could materially harm our business. For more information, see the section titled “Risk Factors—Risks Related to Our Intellectual Property.”

Trademarks and Know-How

In connection with the ongoing development and advancement of our product candidate in the United States and various international jurisdictions, we seek to create protection for our marks and enhance their value by pursuing trademarks where available and when appropriate. In addition to patent and trademark protection, we rely upon trade secrets and know-how and continuing technological innovation to develop and maintain our competitive position. We seek to protect our proprietary information, in part, using confidentiality agreements with our commercial partners, collaborators, employees and consultants and invention assignment agreements with our

employees and selected consultants. We also seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems. While we have confidence in these individuals, organizations and systems, agreements or security measures may be breached, and our trade secrets and other proprietary information may be disclosed. We may not have adequate remedies for any breach and could lose our trade secrets and other proprietary information through such a breach. In addition, our trade secrets may otherwise become known or be independently discovered by competitors. To the extent that our consultants, contractors or collaborators use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting trade secrets, know-how and inventions.

Our commercial success will also depend in part on not infringing the proprietary rights of third parties. In addition, we have licensed rights under proprietary technologies of third parties to develop, manufacture and commercialize specific aspects of our future products and services. It is uncertain whether the issuance of any third party patent would require us to alter our development or commercial strategies, alter our processes, obtain licenses or cease certain activities. The expiration of patents or patent applications licensed from third parties or our breach of any license agreements or failure to obtain a license to proprietary rights that we may require to develop or commercialize our future technology may have a material adverse impact on us. 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 proceedings in the USPTO to determine priority of invention.

For more information regarding the risks related to our intellectual property, please see “Risk Factors—Risks Related to Our Intellectual Property.”

Government Regulation

The research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, recordkeeping, serialization and tracking, promotion, advertising, distribution and marketing, postapproval or licensure monitoring and reporting, and export and import, among other things, of our product candidates are extensively regulated by governmental authorities in the United States and in other countries and jurisdictions, including the EU. In the United States, the FDA regulates biological products under the Federal Food, Drug, and Cosmetic Act (FDCA) and its implementing regulations, and the Public Health Service Act (PHSA) and its implementing regulations. Failure to comply with the applicable U.S. requirements may subject us to administrative or judicial sanctions, such as the FDA’s refusal to approve a Biologics License Application (BLA), warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions and/or criminal prosecution.

Preclinical Studies

Before testing any biologic product candidate in humans, the product candidate undergoes preclinical testing. Preclinical tests, also referred to as nonclinical studies, include laboratory evaluations of the product chemistry, pharmacology, toxicity and formulation, as well as animal studies to assess the pharmacokinetics, metabolism, bio-distribution, elimination and toxicity of the product candidate. The conduct of the preclinical tests and formulation of the compounds for testing must comply with federal regulations and requirements and certain preclinical trials must conform to the FDA’s Good Laboratory Practice requirements (GLP).

The results of preclinical testing, manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, among other things, must be submitted to the FDA as part of an IND that must be reviewed and cleared by the FDA before clinical testing can begin. The IND will become effective 30 days after the FDA receives the application, unless the FDA raises concerns or questions related to the investigations in the application and places the trial on clinical hold. In this situation, the IND sponsor must resolve any outstanding FDA concerns before clinical trials can proceed. As a result, submission of an IND may or may not result in the FDA authorizing clinical trials to commence.

Clinical Development

The FDA and comparable regulatory agencies in state and local jurisdictions and in foreign countries impose substantial requirements upon the clinical development, manufacture and marketing of pharmaceutical products. These agencies and other federal, state and local entities regulate, among other things, research and development activities and the testing, manufacture, export, import, quality control, marketing approval, safety, effectiveness, labeling, storage, record keeping, promotion, advertising, distribution and marketing and post-marketing safety reporting.

The process required by the FDA before product candidates may be marketed in the U.S. generally involves the following:

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nonclinical laboratory and animal tests, some of which must be conducted in accordance with GLP ;

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submission of an Investigational New Drug (IND) application, which contains results of nonclinical studies (e.g., laboratory evaluations of the chemistry, formulation, stability and toxicity of the product candidate), together with Investigator’s Brochure, manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, and must become effective before human clinical trials may begin;

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approval by an independent Institutional Review Board (IRB) or ethics committee for each clinical trial site before each trial may be initiated;

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adequate and well-controlled human clinical trials conducted in accordance with the protocol and Good Clinical Practice (GCP) to establish the safety and efficacy of the product candidate for its proposed intended use;

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for drug products, submission of a New Drug Application (NDA) to the FDA for commercial marketing, or generally of a supplemental New Drug Application (sNDA), for approval of a new indication if the product is already approved for another indication;

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for biotherapeutic products, submission of a Biologics License Application (BLA) to the FDA for commercial marketing, or generally a supplemental Biologics License Application (sBLA) for approval of a new indication if the product is already approved for another indication;

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pre-approval inspection of manufacturing facilities and selected clinical investigators, clinical trial sites and/or Pyxis Oncology as the clinical trial sponsor for their compliance with cGMP and GCP, respectively;

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payment of user fees for FDA review of an NDA or BLA unless a fee waiver applies;

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agreement with the FDA on the final labeling for the product and design and implementation of any required Risk Evaluation and Mitigation Strategy;

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if the FDA convenes an advisory committee, satisfactory completion of the advisory committee review; and

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FDA approval of the NDA or sNDA, or BLA or sBLA.

Clinical Trials

Clinical trials involve the administration of the biologic product candidate to volunteers or patients under the supervision of qualified investigators in accordance with GCP requirements, which include the requirement that all research patients provide their informed consent for their participation in any clinical trial. Clinical trials are conducted under protocols detailing the objectives of the study, dosing procedures, inclusion and exclusion criteria, study procedures, parameters to be used in monitoring safety and the effectiveness criteria to be evaluated.

Further, the study protocol and informed consent information for patients in clinical trials must also be submitted to an IRB for approval covering each institution at which the clinical trial will be conducted. The IRB will consider, among other requirements, rationale for conducting the trial, clinical trial design, patient informed consent, ethical factors, the safety and rights of human patients and the possible liability of the institution. The FDA can temporarily or permanently halt a clinical trial at any time, or impose other sanctions, if it believes that the clinical trial is not being conducted in accordance with FDA requirements or presents an unacceptable risk to the clinical trial patients. The IRB may also require the clinical trial at a particular site be halted, either temporarily or permanently, or impose other conditions, for failure to comply with GCP or the IRB’s requirements.

For purposes of NDA or BLA approval, human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

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Phase 1 clinical trials, which involve the initial introduction of a new drug product candidate into humans, are initially conducted in a small number of volunteers or patients to assess the product candidate for early tolerability, safety, pattern of drug absorption, distribution and metabolism, the mechanism of action in humans, and may include studies where investigational drugs are used as research to explore biological phenomena or disease processes.

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Phase 2 clinical trials typically are conducted in a limited patient population with a specific disease in order to provide enough data to evaluate the preliminary efficacy, optimal dosage, and common short-term side effects and risks associated with the drug. Multiple phase 2 clinical trials may be conducted to obtain information prior to beginning larger and more expensive phase 3 clinical trials.

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Phase 3 clinical trials typically are larger scale, multicenter, well-controlled trials conducted on patients with a specific disease to gather additional information about effectiveness and safety across a higher number of patients and evaluate the overall benefit-risk relationship of the product candidate following earlier phase evaluations, which will have provided preliminary evidence suggesting an effective dosage range and acceptable safety profile for the product candidate. Phase 3 trials are also intended to provide an adequate basis for the product labeling if it is approved.

Postapproval clinical trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval. These clinical trials may be conducted to fulfill mandatory conditions of product approval or used to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for long-term safety follow-up. The mandatory studies are used to confirm clinical benefit in the case of drugs approved under the accelerated approval regulations or to provide additional clinical safety or efficacy data for “full” approvals. Failure to promptly conduct and complete mandatory Phase 4 clinical trials could result in withdrawal of approval for products approved under accelerated approval regulations.

A therapeutic product candidate being studied in clinical trials may be made available for treatment of individual patients, intermediate-size patient populations, or for widespread treatment use under an expanded access protocol, under certain circumstances. Pursuant to the 21st Century Cures Act, or Cures Act, which was signed into law in December 2016, the manufacturer of one or more investigational products for

the diagnosis, monitoring, or treatment of one or more serious diseases or conditions is required to make available, such as by posting on its website, its policy on evaluating and responding to requests for individual patient access to such investigational product.

Additionally, on May 30, 2018, the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017 was signed into law. The law, among other things, provides a federal framework for certain patients to access certain investigational new drug products that have completed a Phase 1 clinical trial and that are undergoing investigation for FDA approval. Under certain circumstances, eligible patients can seek treatment without enrolling in clinical trials and without obtaining FDA authorization under an FDA expanded access program; however, manufacturers are not obligated to provide investigational new drug products under the current federal right to try law.

Disclosure of Clinical Trial Information

Under the PHSA, sponsors of certain clinical trials of FDA-regulated products are required to register and disclose certain clinical trial information. Information related to the product, patient population, phase of investigation, trial sites and investigators, and other aspects of the clinical trial are then made public as part of the registration on a public registry (clinicaltrials.gov) maintained by the U.S. National Institutes of Health (the NIH). Sponsors are also obligated to disclose the results of their clinical trials after completion. Competitors may use this publicly available information to gain knowledge regarding the progress of development programs. Information for certain clinical trials also must be publicly disclosed within certain time limits on the clinical trial registry and results databank maintained by the NIH.

Expedited Development and Review Programs

The FDA has a number of programs intended to expedite the process for developing and reviewing promising drugs, or to provide for the approval of a drug on the basis of a surrogate endpoint. Generally, drugs that are eligible for these programs are those for serious or life-threatening conditions, those with the potential to address unmet medical needs and those that offer meaningful benefits over existing treatments. Examples of such programs include Fast Track Designation, Breakthrough Therapy Designation, Priority Review designation and Accelerated Approval, and the eligibility criteria of and benefits of each program vary:

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Fast Track is a process designed to facilitate the development and expedite the review of drugs intended to treat a serious or life-threatening conditions that demonstrate the potential to address unmet medical needs, by providing, among other things, potential actions to expedite development and review, and rolling review, which allows submission of individually completed sections of an NDA for FDA review before the entire submission is completed. The FDA may revoke the Fast Track Designation if it believes that the designation is no longer supported by data emerging in the clinical trial process.

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Breakthrough Therapy Designation is a process designed to expedite the development and review of drugs intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence demonstrates that the drug may have substantial improvement on one or more clinically significant endpoints over existing therapies. Drugs designated as breakthrough therapies are also eligible for other actions to expedite review. The FDA will seek to ensure the sponsor of a Breakthrough Therapy product candidate receives intensive guidance on an efficient drug development program, intensive involvement of senior managers and experienced staff on a proactive, collaborative and cross-disciplinary review, and rolling review.

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Priority Review is designed to shorten the review period for drugs that are intended to treat a serious conditions and, if approved or licensed, would provide a significant improvement in safety or effectiveness. The FDA intends to take action on a Priority Review marketing application within six months of receipt, compared to 10 months for regular review submissions.

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Accelerated Approval provides for an earlier approval of a new drug intended to treat a serious or life-threatening disease or condition and that provides a meaningful therapeutic benefit over existing treatments and demonstrates an effect on a surrogate endpoint, or an intermediate clinical endpoint, which is considered reasonably likely to predict a clinical benefit. As a condition of approval, the FDA requires that a sponsor of a product candidate receiving Accelerated Approval perform post-marketing clinical trials or provide data on established clinical endpoints from the same trial to confirm the clinical benefit as predicted by the surrogate marker trial and may require that these studies be underway prior to approval. In addition, the FDA requires, as a condition for Accelerated Approval, the submission of promotional materials in advance, which could adversely impact the timing of the commercial launch of the product. The FDA can also withdraw an Accelerated Approval on an expedited basis provided it follows certain procedures.

Fast Track Designation, Breakthrough Therapy Designation, Priority Review and Accelerated Approval do not change the standards for licensure but may expedite the review process.

In February 2025, the FDA granted Fast Track Designation for use of micvotabart pelidotin for the treatment of adults with R/M HNSCC whose disease has progressed following treatment with platinum-based chemotherapy and an anti-PD-(L)1 antibody.

Additionally, with respect to oncology products, the FDA may review applications under the Real-Time Oncology Review (RTOR) program established by the FDA’s Oncology Center of Excellence. The RTOR program, which allows an applicant to pre-submit components of the NDA or BLA to allow the FDA to review clinical data before the complete filing is submitted, aims to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible, while maintaining and improving review quality. Drugs considered for review under the RTOR program must be likely to demonstrate substantial improvements over available

therapy, which may include drugs previously granted breakthrough therapy designation for the same or other indications and must have straight-forward study designs and endpoints that can be easily interpreted.

Orphan Drugs

Under the Orphan Drug Act, the FDA may grant orphan drug designation to therapeutic candidates (drugs or biological products) intended to treat a disease or condition that affects fewer than 200,000 individuals in the U.S. (or for which there is no reasonable expectation that the cost of developing and making available in the U.S. for such disease or condition will be recovered from sales in the U.S.). To be eligible for orphan drug designation, the FDA must not have previously approved a drug considered the “same drug,” as defined in the FDA’s orphan drug regulations, for the same orphan-designated indication or the sponsor of the subsequent drug must provide a plausible hypothesis of clinical superiority over the previously approved same drug. Upon receipt of Orphan Drug Designation, the sponsor is eligible for tax credits for certain clinical trial expenses, waiver of pediatric studies, and an exemption from the BLA application fee.

In addition, upon marketing approval, an Orphan Drug Designation could be eligible for seven years of market exclusivity if no drug considered the same drug was previously approved for the same orphan condition (or if the subsequent drug is demonstrated to be clinically superior to any such previously approved same drug). Such orphan drug exclusivity, if awarded, would only block the approval of any drug considered the same drug for the same orphan indication. Orphan drug exclusivity does not prevent the FDA from approving a different biological product for the same disease or condition, or the same biological product for a different disease or condition.

In May 2023, the FDA granted Orphan Drug Designation for use of micvotabart pelidotin in the treatment of pancreatic cancer.

Additional controls for biologics

To help reduce the increased risk of the introduction of adventitious agents, the PHSA emphasizes the importance of manufacturing controls for products whose attributes cannot be precisely defined. The PHSA also provides authority to the FDA to immediately suspend biologics licenses in situations where there exists a danger to public health, to prepare or procure products in the event of shortages and critical public health needs, and to authorize the creation and enforcement of regulations to prevent the introduction or spread of communicable diseases within the United States.

After a BLA is approved, the product may also be subject to official lot release as a condition of approval. As part of the manufacturing process, the manufacturer is required to perform certain tests on each lot of the product before it is released for distribution. If the product is subject to official release by the FDA, the manufacturer submits samples of each lot of product to the FDA together with a release protocol showing a summary of the lot manufacturing history and the results of all of the manufacturer’s tests performed on the lot.

The FDA may also perform certain confirmatory tests on lots of some products, such as viral vaccines, before allowing the manufacturer to release the lots for distribution. In addition, the FDA conducts laboratory research related to the regulatory standards on the safety, purity, potency, and effectiveness of biological products. As with drugs, after approval of a BLA, biologics manufacturers must address any safety issues that arise, are subject to recalls or a halt in manufacturing, and are subject to periodic inspection after approval.

FDA Review of BLAs

After completion of the required clinical testing, a BLA is prepared and submitted to the FDA. FDA approval of the BLA is required before marketing of the product may begin in the United States. The BLA must include the results of all preclinical, clinical and other testing and a compilation of data relating to the product’s pharmacology, chemistry, manufacture and controls. The cost of preparing and submitting a BLA is substantial. The submission of most BLAs is additionally subject to a substantial application user fee, currently $4,310,002 for BLAs requiring clinical data for fiscal year 2025, and the manufacturer and sponsor under an approved BLA are also subject to annual program fees, currently $403,889 (fiscal year 2025) for each prescription product. Sponsors of applications for drugs granted Orphan Drug Designation are exempt from these user fees.

The FDA has 60 days from its receipt of a BLA to determine whether the application will be accepted for filing based on the Agency’s threshold determination that it is sufficiently complete to permit substantive review. The FDA may request additional information rather than accept a BLA for filing. In this event, the application must be resubmitted with the additional information. The resubmitted application is also subject to review before the FDA accepts it for filing. If the application is accepted for review, the FDA reviews the application to determine, among other things, whether a product is safe and effective for its intended use and whether the manufacturing controls are adequate to assure and preserve the product's identity, strength, quality, and purity.

The FDA has agreed to certain performance goals in the review of BLAs to encourage timeliness. Applications for standard review biological products are meant to be reviewed within ten months; applications for Priority Review drugs are meant to be reviewed in six months. Priority Review can be applied to biological products that the FDA determines offer major advances in treatment or provide a treatment where no adequate therapy exists. The review process for both standard and Priority Review may be extended by the FDA for three additional months (“major amendment”) to consider certain late-submitted information, or information intended to clarify information already provided in the submission.

The FDA is required to refer an application for a novel biological product to an advisory committee or explain why such referral was not made. An advisory committee is typically a panel that includes clinicians and other experts—for review, evaluation and a

PYXS US Equity

PYXS · 10-K · period ended 2024-12-31

Item 1. Business.

PYXS US Equity☆

PYXS · 10-K · period ended 2024-12-31

Item 1. Business.

PYXS US Equity