PYX-201 Mechanism and Target - PYX-201 is a first-in-concept extracellular-cleaving ADC targeting EDB+FN, a non-cellular component of the tumor extracellular matrix [6, 7] - EDB+FN is highly overexpressed in various solid tumors, releasing the payload extracellularly for direct tumor killing, bystander effect, and immunogenic cell death [10, 11] - PYX-201's unique mechanism of action (MOA) may address a primary cause of drug resistance by altering the ECM [16] Clinical Trial and Tolerability - Phase 1 dose escalation study included 80 patients with 10 solid tumor types [29] - PYX-201 demonstrated a favorable tolerability profile with a low treatment discontinuation rate of 1% [6, 39] - The identified dose range for further evaluation is 3.6 - 5.4 mg/kg [6, 34] Efficacy and Responses - An overall response rate (ORR) of 26% was observed in 6 responding tumor types (n=31) at the identified dose range of 3.6-5.4 mg/kg [6, 43] - In HNSCC patients within the 3.6 – 5.4 mg/kg dose range, a 50% ORR and 100% disease control rate (DCR) were observed [6, 54] - Median time on study in Phase 1 Part 1 was approximately 12 weeks [50, 51] Future Development and Catalysts - A clinical trial collaboration will evaluate PYX-201 in combination with KEYTRUDA® (pembrolizumab) [18] - Multiple clinical catalysts are expected in the next 6-18 months, including readouts from HNSCC monotherapy and early line combination studies [6, 65] - As of Q3 2024, the company has $146 million in cash, providing runway into 2H 2026 [87]

Summary of Pyxis Oncology Inc (PYXS) 2025 Conference Call Company Overview - **Company**: Pyxis Oncology Inc (PYXS) - **Focus**: Development of an antibody-drug conjugate (ADC) called Mycvotabart pelodotin, targeting extracellular domain B (EDB) of fibronectin, currently in phase one development [3][4] Core Points and Arguments ADC Development and Mechanism - **Differentiated Approach**: Pyxis Oncology's ADC targets the tumor extracellular matrix (ECM) rather than relying solely on internalization by tumor cells, allowing for payload release in the extracellular environment [6][7] - **Clinical Data**: The phase one study included 80 patients across nine tumor types, showing tumor regression in at least six types, particularly strong signals in head and neck cancer [9][10] - **Safety Profile**: No grade five adverse events reported, with a low incidence of grade three and above neuropathies and ocular toxicity, indicating a well-tolerated treatment [10][11] Clinical Trial Insights - **Head and Neck Cancer Focus**: The confirmed overall response rate (ORR) in the heavily pretreated head and neck cohort was 50%, with a 100% disease control rate [13][14] - **Patient Population**: The study targeted a very sick population with a median of four prior lines of therapy, indicating the drug's potential effectiveness in late-stage patients [13][14] - **Future Expectations**: Two upcoming data updates are anticipated in the second half of the year, focusing on monotherapy and combination therapy with Keytruda [19][20][23] Competitive Landscape - **Market Positioning**: The company aims to differentiate itself by demonstrating efficacy in both HPV positive and negative patients, potentially gaining a competitive advantage [29][30] - **Benchmarking Against Competitors**: The company is aware of the benchmarks set by competitors like Merus and BIKARA, with expectations of achieving ORRs of 65% or more for combination therapy and 37% for monotherapy [34][35] Financial Position and Future Outlook - **Cash Position**: The company reported a cash balance of approximately $105 million, providing a runway through the second half of 2026 [57][58] - **Key Events**: Investors are advised to monitor upcoming clinical data releases and translational work that may provide insights into the drug's mechanism and efficacy [58] Additional Important Insights - **Exploratory Work**: The company is conducting research to understand responder versus non-responder characteristics, focusing on the tumor microenvironment and potential biomarkers [55][56] - **Collaboration with Merck**: A supply agreement with Merck is in place, allowing for collaboration and data sharing, which may enhance the development strategy across multiple tumor types [51][53] This summary encapsulates the key points discussed during the conference call, highlighting the company's strategic focus, clinical developments, competitive positioning, and financial outlook.

Summary of Pyxis Oncology Inc (PYXS) 2025 Conference Call Company Overview - **Company**: Pyxis Oncology Inc (PYXS) - **Lead Asset**: MycVo, a first-in-class antibody-drug conjugate (ADC) targeting the extracellular domain b, a splice variant of fibronectin [3][4] Key Points and Arguments Product Development and Mechanism - MycVo was developed by Pfizer and optimized for better potency, stability, and permeability [3] - The ADC utilizes site-specific conjugation chemistry, which is crucial for the quality of the dataset [4] - MycVo targets EDB, which is highly expressed in various solid tumors but minimally in normal tissue, indicating a potential for high specificity and reduced side effects [4] Clinical Data and Efficacy - Initial clinical data from a dose escalation study involving 80 patients across 10 tumor types showed tumor regression in 6 out of 9 tumor types dosed [9] - A notable 50% confirmed response rate was observed in head and neck cancer patients, with some patients having multiple prior lines of therapy [10] - The company is transitioning to cohort expansion to validate initial findings with a larger patient population [9][11] Safety Profile - The safety profile of MycVo is considered well-tolerated, with no drug-related grade five adverse events reported [15] - Only one patient out of 77 discontinued due to adverse effects, indicating a low dose reduction rate [15] - The company compared its safety data favorably against FDA-approved ADCs, showing better or comparable results in various toxicity dimensions [16] Competitive Landscape - The company is aware of competing therapies in the head and neck space, such as those from Maris and Vicara, and aims to demonstrate superior overall response rates (ORR) [18][20] - Current ORR for Maris is 37%, while MycVo has shown a 50% response rate in a heavily pretreated population [20] Future Development Plans - The company is focusing on both monotherapy and combination therapy programs, with plans to generate data from 40 head and neck patients across two arms [28][29] - Preliminary data for the monotherapy is expected in the second half of the year, while combination therapy data is anticipated shortly thereafter [30][32] Research and Mechanism Insights - Ongoing research aims to better understand the mechanism of MycVo, including its direct tumor-killing effects and local immunostimulatory effects [25][27] - The company is also investigating gene signatures to identify responsive patient populations [27] Investigator Enthusiasm - There is significant enthusiasm from the physician community, with waiting lists for patient enrollment in both monotherapy and combination studies [41] - Investigators are optimistic about MycVo's potential to address resistance in various patient populations [41] Other Important Content - The company is constrained by resources but is strategically focusing on head and neck cancer while exploring signals in other tumor types like breast, sarcoma, ovarian, and lung cancers [22][24] - The development program is designed to allow for simultaneous data collection from monotherapy and combination therapy, enhancing the interpretability of results [33] This summary encapsulates the key insights and developments discussed during the Pyxis Oncology conference call, highlighting the company's strategic focus, clinical data, safety profile, and future plans in the oncology space.

[Summary Risk Factors](index=3&type=section&id=Summary%20Risk%20Factors) The company, a clinical-stage oncology firm, faces risks from **significant losses**, heavy dependence on its primary product candidate, capital needs, third-party reliance, and intellectual property protection - The company identifies as a clinical-stage oncology firm with a history of **significant losses**, which are expected to continue for the next several years[8](index=8&type=chunk) - **Heavy dependence** on the success of its primary product candidate, **micvotabart pelidotin**, which is in the early stages of clinical development. Failure in clinical trials or regulatory approval would **materially harm the business**[8](index=8&type=chunk) - **Substantial additional capital** will be required to fund operations. Failure to raise capital when needed could force delays, reductions, or elimination of research and development programs[8](index=8&type=chunk) - The company relies on **third parties for manufacturing** its product candidates, and any failure by these manufacturers could delay or impair clinical trials and commercialization[8](index=8&type=chunk) - **Significant risks** are associated with protecting **intellectual property rights**, particularly those under **license agreements** (e.g., with Pfizer), where a breach could lead to the **loss of development and commercialization rights**[8](index=8&type=chunk) [PART I. FINANCIAL INFORMATION](index=5&type=section&id=PART%20I.%20FINANCIAL%20INFORMATION) Unaudited condensed consolidated financial statements and MD&A detail Q1 2025 financial performance, including increased R&D, significant net loss, and liquidity position [Item 1. Financial Statements (Unaudited)](index=5&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) Unaudited financial statements for Q1 2025 reveal a significantly increased net loss, decreased total assets due to cash usage, and an absence of revenue compared to the prior year [Condensed Consolidated Balance Sheets](index=5&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) The balance sheet as of March 31, 2025, shows a decrease in total assets, primarily in cash and marketable securities, with corresponding changes in liabilities and equity Condensed Consolidated Balance Sheet Data (in thousands) | Account | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $12,759 | $19,473 | | Marketable debt securities, short-term | $92,673 | $107,458 | | Total current assets | $111,871 | $132,440 | | Total assets | $135,867 | $157,181 | | **Liabilities & Stockholders' Equity** | | | | Total current liabilities | $14,430 | $17,680 | | Total liabilities | $32,764 | $36,430 | | Total stockholders' equity | $103,103 | $120,751 | | Accumulated deficit | $(384,714) | $(363,556) | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) Q1 2025 operations show a significantly increased net loss, driven by the absence of revenue and higher research and development expenses year-over-year Condensed Consolidated Statements of Operations (in thousands) | Account | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Total revenues | $0 | $16,146 | | Research and development | $17,044 | $13,029 | | General and administrative | $5,870 | $8,247 | | Loss from operations | $(22,914) | $(5,605) | | Net loss | $(21,158) | $(3,256) | | Net loss per common share | $(0.35) | $(0.06) | [Condensed Consolidated Statements of Cash Flows](index=8&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Q1 2025 cash flows reflect significant cash usage in operations, offset by investing activities, with no substantial financing activities during the period Condensed Consolidated Statements of Cash Flows (in thousands) | Activity | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(22,535) | $(20,710) | | Net cash provided by (used in) investing activities | $15,821 | $(18,498) | | Net cash provided by financing activities | $0 | $57,511 | | Net (decrease) increase in cash | $(6,714) | $18,303 | [Notes to Condensed Consolidated Financial Statements](index=9&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) Notes detail accounting policies, oncology focus, liquidity runway, key licensing agreements, and capital raising activities - The company is a clinical-stage oncology company focused on solid tumors, with a specific emphasis on head and neck squamous cell carcinoma (HNSCC)[23](index=23&type=chunk) - As of March 31, 2025, the company had an **accumulated deficit of $384.7 million** and expects its **existing cash, cash equivalents, and short-term investments of $105.4 million** to **fund operations for at least the next twelve months**[26](index=26&type=chunk)[28](index=28&type=chunk) - The company has **key licensing agreements**, including an amended and restated agreement with Pfizer for its ADC product candidates (**micvotabart pelidotin** and PYX-203) and a license with Biosion for PYX-106, the development of which was paused in December 2024[49](index=49&type=chunk)[52](index=52&type=chunk) - In February 2024, the company **raised $50 million through a private placement**. In January 2025, **all 1,611,215 pre-funded warrants** from this placement were **exercised for common stock**[65](index=65&type=chunk)[66](index=66&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=23&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's focus on its lead ADC candidate, **micvotabart pelidotin**, detailing Q1 2025 R&D and G&A expenses, and liquidity projections [Overview](index=23&type=section&id=Overview) Pyxis Oncology focuses on **micvotabart pelidotin** for R/M HNSCC, granted **Fast Track Designation**, with ongoing monotherapy and combination clinical studies - The company's **lead product candidate is micvotabart pelidotin**, an ADC targeting Extradomain-B Fibronectin (EDB+FN), a component of the tumor extracellular matrix[88](index=88&type=chunk) - Based on positive preliminary data from a Phase 1 dose escalation study showing a **50% ORR in R/M HNSCC patients**, the company is **prioritizing this indication**[94](index=94&type=chunk) - The **FDA granted Fast Track Designation** to **micvotabart pelidotin** for **monotherapy treatment of adult patients with R/M HNSCC** who have progressed after platinum-based chemotherapy and an anti-PD-(L)1 antibody[103](index=103&type=chunk) - Clinical development includes two monotherapy expansion cohorts in R/M HNSCC and a Phase 1/2 **combination study (PYX-201-102) with Merck's KEYTRUDA®** across various solid tumors[104](index=104&type=chunk)[106](index=106&type=chunk) [Results of Operations](index=31&type=section&id=Results%20of%20Operations) Q1 2025 results show **zero revenue**, increased R&D expenses due to **micvotabart pelidotin**, and decreased G&A expenses primarily from **lower stock-based compensation** Comparison of Results of Operations (in thousands) | Account | Q1 2025 | Q1 2024 | Change | | :--- | :--- | :--- | :--- | | Total revenues | $0 | $16,146 | $(16,146) | | Research and development | $17,044 | $13,029 | $4,015 | | General and administrative | $5,870 | $8,247 | $(2,377) | | Net loss | $(21,158) | $(3,256) | $(17,902) | - The **$4.0 million increase in R&D expenses** was driven by a **$2.7 million increase in micvotabart pelidotin program costs** (manufacturing and clinical trial expenses) and a **$2.0 million increase in unallocated costs**, including **$1 million in severance** from a March 2025 **workforce reduction**[121](index=121&type=chunk)[122](index=122&type=chunk)[124](index=124&type=chunk) - The **$2.4 million decrease in G&A expenses** was primarily due to a **$1.2 million decrease in stock-based compensation**, along with lower professional fees and corporate insurance costs[125](index=125&type=chunk) [Liquidity and Capital Resources](index=32&type=section&id=Liquidity%20and%20Capital%20Resources) As of March 31, 2025, the company had **$105.4 million in cash**, projected to fund operations into H2 2026, with an available ATM offering program - The company's **cash, cash equivalents, and short-term investments totaled $105.4 million** as of March 31, 2025[127](index=127&type=chunk) - Management projects the **current cash position will be sufficient to fund operations into the second half of 2026**[138](index=138&type=chunk) Cash Flow Summary (in thousands) | Activity | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(22,535) | $(20,710) | | Net cash provided by (used in) investing activities | $15,821 | $(18,498) | | Net cash provided by financing activities | $0 | $57,511 | - The company has an effective **ATM offering program with $106.2 million of remaining capacity** as of March 31, 2025[128](index=128&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=38&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a "**smaller reporting company**," Pyxis Oncology is exempt from providing market risk disclosures - The company is a "**smaller reporting company**" and is therefore **not required to provide quantitative and qualitative disclosures about market risk**[149](index=149&type=chunk) [Item 4. Controls and Procedures](index=38&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded **disclosure controls were effective** as of March 31, 2025, with **no material changes in internal control** over financial reporting - Management concluded that the company's **disclosure controls and procedures were effective** at a reasonable assurance level as of the end of the period covered by the report[150](index=150&type=chunk) - **No changes in internal control over financial reporting occurred** during the quarter that have materially affected, or are reasonably likely to materially affect, the company's internal control over financial reporting[151](index=151&type=chunk) [PART II. OTHER INFORMATION](index=39&type=section&id=PART%20II.%20OTHER%20INFORMATION) This section covers legal proceedings, extensive risk factors including financial, clinical, regulatory, and IP risks, and details on equity sales and exhibits [Item 1. Legal Proceedings](index=39&type=section&id=Item%201.%20Legal%20Proceedings) The company is **not currently involved in any material legal proceedings**, nor is it aware of any pending or threatened actions - The company reports that it is **not currently a party to any material legal proceedings**[155](index=155&type=chunk) [Item 1A. Risk Factors](index=39&type=section&id=Item%201A.%20Risk%20Factors) This section outlines **significant risks** including financial position, product candidate development, regulatory compliance, dependence on third parties, and intellectual property protection [Risks Related to Financial Position and Capital Needs](index=39&type=section&id=Risks%20Related%20to%20Our%20Financial%20Position%20and%20Need%20for%20Additional%20Capital) The company faces risks from its **history of significant losses**, ongoing capital needs, and the uncertainty of its cash runway projections - The company has a **history of significant operating losses**, with a **net loss of $21.2 million** for Q1 2025 and an **accumulated deficit of $384.7 million**[159](index=159&type=chunk) - **Substantial additional capital** is needed to finance operations. The **current cash of $105.4 million** is **projected to fund operations into the second half of 2026**, but this is based on assumptions that could change[164](index=164&type=chunk) [Risks Related to Product Candidate Development](index=43&type=section&id=Risks%20Related%20to%20the%20Development%20of%20our%20Product%20Candidate) Success hinges on its sole clinical candidate, **micvotabart pelidotin**, facing lengthy, expensive, and uncertain clinical development with **significant competition** - The company is **heavily dependent on the success of its single clinical product candidate, micvotabart pelidotin**[183](index=183&type=chunk) - **Clinical testing is a long, expensive process with an uncertain outcome**. The company may incur unexpected costs or delays and may ultimately be unable to complete development[174](index=174&type=chunk) - **Interim and preliminary data from clinical trials may change** as more patient data becomes available, and should be viewed with caution[196](index=196&type=chunk) - The company faces **significant competition from other oncology-focused companies**, including those developing ADCs and immunotherapies for HNSCC, such as Philogen S.p.A., Merus, and Bicara[211](index=211&type=chunk)[217](index=217&type=chunk) [Risks Related to Regulatory and Legal Compliance](index=61&type=section&id=Risks%20Related%20to%20Regulatory%20Licensure%20or%20Approval%20and%20Other%20Legal%20Compliance%20Matters) Regulatory approval is lengthy and unpredictable, with ongoing compliance obligations, pricing challenges, and risks from healthcare fraud and data privacy laws - The **regulatory licensure process is lengthy, time-consuming, and inherently unpredictable**, and the company may never obtain marketing approval for its product candidate[224](index=224&type=chunk) - Even if granted, **expedited pathways like Fast Track Designation or Accelerated Approval do not guarantee a faster review or ultimate approval** and come with rigorous post-marketing requirements[231](index=231&type=chunk)[239](index=239&type=chunk) - The company's ability to commercialize its products will depend on **securing adequate coverage and reimbursement from third-party payors**, which is uncertain[263](index=263&type=chunk) - The company is **subject to numerous data protection and privacy laws** (e.g., HIPAA, CCPA, GDPR), and **failure to comply could result in significant penalties and reputational harm**[276](index=276&type=chunk)[277](index=277&type=chunk)[282](index=282&type=chunk) [Risks Related to Dependence on Third Parties](index=85&type=section&id=Risks%20Related%20to%20Our%20Dependence%20on%20Third%20Parties) Reliance on third parties for manufacturing, clinical trials, and licensing creates risks of disruption, supply chain issues, and loss of intellectual property rights - The company **relies on third-party CDMOs for manufacturing** and does not have its own capabilities. Any failure by these manufacturers to comply with cGMP or meet supply needs could delay or halt clinical trials[324](index=324&type=chunk)[326](index=326&type=chunk) - A portion of **manufacturing occurs in China, creating risks related to geopolitical tensions, trade restrictions** (e.g., the proposed BIOSECURE Act), and supply chain disruptions[335](index=335&type=chunk) - The company **relies on third-party CROs to conduct its clinical trials**. Poor performance by these CROs could compromise trial data and delay regulatory submissions[340](index=340&type=chunk)[342](index=342&type=chunk) - **Failure to comply with obligations under license agreements** (e.g., with Pfizer) could result in the **loss of essential intellectual property rights** necessary for developing its product candidates[319](index=319&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=110&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company details the use of **$152.3 million net IPO proceeds**, now reprioritized to **advance micvotabart pelidotin** and for **general corporate purposes** - The company's **IPO in October 2021 generated net proceeds of $152.3 million**[402](index=402&type=chunk) - The **planned use of IPO proceeds has been updated due to pipeline reprioritizations**. The **funds are now primarily allocated to advance the clinical development of micvotabart pelidotin and for general corporate purposes**[403](index=403&type=chunk) [Item 6. Exhibits](index=111&type=section&id=Item%206.%20Exhibits) This section lists filed exhibits, including a separation agreement and required Sarbanes-Oxley Act certifications from the CEO and CFO - The report includes **required certifications from the CEO and CFO pursuant to Sections 302 and 906 of the Sarbanes-Oxley Act**[407](index=407&type=chunk) - A **Separation Agreement and General Release for Ken Kobayashi is filed as an exhibit**[407](index=407&type=chunk)

Core Insights - Pyxis Oncology is advancing its lead candidate micvotabart pelidotin (MICVO), demonstrating a unique three-pronged mechanism of action that includes direct tumor killing, bystander effect, and immunogenic cell death [1][5] - The company is on track to report preliminary data from Phase 1 trials for MICVO in various patient cohorts, with significant milestones expected in the second half of 2025 and early 2026 [1][5] - Financial results indicate a net loss of $21.2 million for Q1 2025, a significant increase from a net loss of $3.3 million in Q1 2024, primarily due to increased research and development expenses [10][13] Pipeline Updates - MICVO has shown broad anti-tumor activity across ten solid tumor indications in preclinical models, attributed to its unique targeting and cytotoxic payload [5] - The company is focusing on recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) as a key area of development, with ongoing Phase 1 studies evaluating MICVO as a monotherapy and in combination with pembrolizumab [7][5] - Preliminary data from the ongoing Phase 1 clinical trial is expected to be reported in the second half of 2025 for patients who have received prior platinum and PD-1 inhibitor therapy [5][1] Financial Overview - As of March 31, 2025, Pyxis Oncology reported cash and cash equivalents of $106.9 million, which is expected to fund operations into the second half of 2026 [4][6] - Research and development expenses increased to $17.0 million in Q1 2025 from $13.0 million in Q1 2024, reflecting heightened clinical trial activities [10] - General and administrative expenses decreased to $5.9 million in Q1 2025 from $8.2 million in Q1 2024, primarily due to lower stock-based compensation and corporate insurance costs [10]

Core Insights - Pyxis Oncology, Inc. announced robust preclinical data supporting the unique mechanism of action of micvotabart pelidotin (MICVO), an antibody-drug conjugate (ADC) targeting extradomain-B fibronectin (EDB+FN), which is highly expressed in various solid tumors [1][5] - MICVO demonstrated significant anti-tumor activity across multiple solid tumor indications, with 45% of models showing strong to very strong tumor growth inhibition (TGI) and complete responses observed in several tumor types [2][3] - The combination of MICVO with anti-PD-1 therapy showed enhanced tumor clearance and longer immunological memory compared to either treatment alone, reinforcing the potential for MICVO as both a monotherapy and in combination therapies [1][3] Preclinical Findings - Evaluation of MICVO in patient-derived xenograft (PDX) models identified gene signatures associated with anti-tumor activity, with 45% of models showing TGI between 70% and 90% or greater than 90% [2][3] - The preclinical studies indicated that MICVO is well-tolerated at a dosage of 3 mg/kg, with significant tumor regression responses confirmed in Phase 1 studies [2][4] - Upregulation of certain proteases may enhance linker cleavage, contributing to increased MICVO activity, supporting the hypothesis for its extracellular mechanism [3] Clinical Development - MICVO is currently being evaluated in Phase 1 studies as a monotherapy and in combination with KEYTRUDA® (pembrolizumab) for advanced solid tumors, particularly recurrent and metastatic head and neck squamous cell carcinoma [4][5][8] - The company has received Fast Track Designation from the U.S. FDA for MICVO in treating adult patients with recurrent and metastatic head and neck squamous cell carcinoma whose disease has progressed after prior treatments [8]

Industry Overview - The cancer market is experiencing significant growth due to rising demand for targeted and less toxic cancer medicines, with new cancer cases in the U.S. expected to exceed 2 million for the first time in 2024, leading to increased global spending on cancer treatments [1][3] - Innovative cancer treatments such as immunotherapy, targeted therapies, and personalized vaccines are emerging, utilizing the body's immune system and focusing on specific genetic mutations to provide more effective and less harmful alternatives to traditional chemotherapy [2][3] Company Developments - Major pharmaceutical companies like Novartis, AstraZeneca, Pfizer, AbbVie, and Eli Lilly are actively developing new cancer therapies, including antibody-drug conjugates and immune-oncology agents, while smaller biotech firms are also making significant advancements [4] - Verastem Oncology is seeking FDA approval for its combination regimen of avutometinib and defactinib for treating KRAS mutant recurrent low-grade serous ovarian cancer, with a decision expected by June 30, 2025 [6][7] - Relay Therapeutics has reported positive interim data for its RLY-2608 breast cancer program, leading to plans for a pivotal study in mid-2025 [9][10] - Pyxis Oncology is focused on developing next-generation therapeutics, with its lead candidate showing significant tumor regression in patients with recurrent and metastatic head and neck squamous cell carcinoma, and has received Fast Track Designation from the FDA [12][13][14]

Core Insights - Pyxis Oncology, Inc. is a clinical-stage company focused on developing next-generation therapeutics for difficult-to-treat cancers [3] - The company will participate in the Stifel 2025 Virtual Targeted Oncology Forum on April 9, 2025, featuring a fireside chat with CEO Lara S. Sullivan [1] - The lead product candidate, micvotabart pelidotin (MICVO), is an antibody-drug conjugate targeting Extradomain-B Fibronectin, currently in Phase 1 clinical studies for various solid tumors [3] Company Overview - Pyxis Oncology is dedicated to creating differentiated mono and combination therapies for challenging cancers [3] - MICVO aims to combat difficult-to-treat cancers through multiple mechanisms, including direct cancer cell killing and enhancing anti-tumor immune response [3] - The company is focusing on recurrent and metastatic head and neck squamous cell carcinoma based on promising clinical signals [3] Event Participation - The company will hold one-on-one investor meetings during the Stifel 2025 Virtual Targeted Oncology Forum [1] - A live webcast of the fireside chat will be available on the company's Investor Relations website [2]

Core Insights - Pyxis Oncology, Inc. is advancing micvotabart pelidotin (MICVO), an antibody-drug conjugate (ADC) targeting EDB+FN, into clinical trials for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) [1][6] - Preliminary data from ongoing clinical trials are expected in the second half of 2025 and the first half of 2026, focusing on patients who have previously received platinum and PD-1 inhibitor therapy [3][4] Company Developments - The company has initiated Part 2 of the Phase 1 clinical trial to evaluate MICVO in patients with R/M HNSCC who have received prior treatments [2][6] - A Phase 1/2 combination study of MICVO and Merck's anti-PD-1 therapy, KEYTRUDA®, has been launched, with preliminary data expected in the second half of 2025 [3][4] Mechanism of Action - MICVO utilizes a unique non-cellular mechanism to drive anti-tumor activity, potentially addressing resistance to other therapies by altering the tumor extracellular matrix [2][6] - The combination of MICVO and a mouse analog of anti-PD-1 therapy has shown significantly greater tumor regression compared to either treatment alone [1][5] Regulatory Status - MICVO has received Fast Track Designation from the U.S. FDA for treating adult patients with R/M HNSCC whose disease has progressed after platinum-based chemotherapy and anti-PD-(L)1 therapy [4][6] Upcoming Presentations - New preclinical data will be presented at the AACR Annual Meeting in April 2025, highlighting the potential of MICVO and its mechanism of action [1][2]

Product Development - Pyxis Oncology's lead product candidate, micvotabart pelidotin, targets EDB+FN, a component highly expressed in various solid tumors, aiming to destabilize tumor structure while sparing healthy cells [19]. - The company aims to prioritize development efforts towards R/M HNSCC, with an estimated one million new cases worldwide annually by 2030 [36]. - The company initiated the dose expansion phase (Part 2) of the PYX-201-101 study, focusing on R/M HNSCC patients, expecting preliminary data in the second half of 2025 [30]. - The company aims to address the unmet need for more efficacious therapies in R/M HNSCC, particularly those that are chemotherapy-free and have superior tolerability [41]. - The company has deprioritized certain clinical programs and assets to focus resources on the development of micvotabart pelidotin [94]. Clinical Trials - In the Phase 1 dose escalation study (PYX-201-101), 80 patients were dosed, with a confirmed 50% objective response rate (ORR) in R/M HNSCC patients at the therapeutically active dose range of 3.6 mg/kg – 5.4 mg/kg IV Q3W [24][25]. - The study observed tumor regression across nine solid tumor types, with a 26% ORR in six solid tumor types of interest at the same dose range [25]. - The Phase 1 trial of micvotabart pelidotin (PYX-201-101) enrolled 80 patients, with a therapeutically active dose response range identified between 3.6 mg/kg and 5.4 mg/kg IV Q3W [55]. - The preliminary efficacy analysis included 65 patients, showing evidence of tumor regression across all nine solid tumor types, with a 26% overall response rate (ORR) in six solid tumor types at the therapeutic dose range of 3.6 mg/kg – 5.4 mg/kg IV Q3W [71]. - The study achieved a confirmed 50% overall response rate (ORR) in patients with R/M HNSCC, with a disease control rate (DCR) of 100% based on RECIST 1.1 criteria [78]. Safety and Efficacy - Preliminary data from the Phase 1 trial indicated a manageable safety profile, with 52% of patients dosed at the 5.4 mg/kg level [55]. - Micvotabart pelidotin demonstrated a favorable safety profile, with only 1 patient discontinuing due to treatment-related adverse effects (TRAEs) and no Grade 5 TRAEs observed [62]. - The trial reported a 0% incidence rate of Grade 3 and 4 TRAEs in the therapeutic dose range of 3.6 mg/kg – 5.4 mg/kg IV Q3W [64]. - The median duration of response in efficacy evaluable patients was 115 days (16 weeks) as of the data cut-off date of October 4, 2024 [78]. - The drug's pharmacokinetic profile showed high systemic bioavailability and stability in circulation, differentiating it from other approved antibody-drug conjugates (ADCs) [60]. Regulatory Designations - The FDA granted Fast Track Designation to micvotabart pelidotin for treating adult patients with R/M HNSCC whose disease progressed after platinum-based chemotherapy and anti-PD-(L)1 therapy [27]. - The FDA granted Fast Track Designation for micvotabart pelidotin for treating adults with R/M HNSCC in February 2025 [203]. - In May 2023, the FDA granted Orphan Drug Designation for micvotabart pelidotin in the treatment of pancreatic cancer [208]. - Orphan Drug Designation provides seven years of market exclusivity if no same drug was previously approved for the same orphan condition [207]. Collaborations and Partnerships - A Clinical Trial Collaboration and Supply Agreement was established with Merck for a study of micvotabart pelidotin in combination with KEYTRUDA® [31]. - The company is actively engaging with potential partners to monetize its intellectual property estate, including inactive programs and biologics technology platforms [37]. - The company has entered into a license agreement with the University of Chicago, which includes potential development and commercial milestones of up to $7.7 million and annual maintenance fees starting at $10,000 [118]. - The company has entered into a license agreement with Biosion USA, Inc. for the development and commercialization rights for a Siglec-15 targeting antibody, now referred to as PYX-106 [126]. Market and Competitive Landscape - The company faces competition from major pharmaceutical and biotechnology companies, as well as alternative therapeutic modalities such as cell therapies and bispecific antibodies [109]. - The company has significant competition in the HNSCC indication, with notable competitors including Merus and Bicara targeting similar patient populations [111]. - Head and Neck Cancer (HNC) accounts for approximately 4.5% of global cancer diagnoses, with an estimated 1,464,550 new cases and 487,993 deaths in 2020 [38]. - In the U.S., there are approximately 59,000 cases of HNSCC annually, with a 13% 5-year survival rate in the R/M (Stage IVC) setting [39]. Financial Obligations and Fees - Under the Pfizer License Agreement, the company is obligated to pay up to $665 million in future contingent payments for the first four licensed ADCs, along with tiered royalties on net sales ranging from low single digits to mid-teens [123]. - The company paid an upfront fee of $10.0 million under the Biosion License Agreement and is obligated to pay up to $217.5 million in future contingent payments for normal approval and $222.5 million for Accelerated Approval [127]. - The cost of preparing and submitting a BLA is substantial, with a user fee of $4,310,002 for BLAs requiring clinical data for fiscal year 2025 [212]. - Annual program fees for each prescription product under an approved BLA are currently $403,889 for fiscal year 2025 [212]. Intellectual Property - The company has a patent portfolio comprising 33 different patent families, including those directed to compositions of matter for antibodies and antibody-drug conjugates [146]. - The patent family for micvotabart pelidotin includes granted patents in multiple countries, with a 20-year term running through 2037, absent any available patent term adjustments [149]. - The company has sole ownership of a patent family for dosage and treatment regimens of micvotabart pelidotin, with a provisional patent application filed in the United States, running through 2045 [152]. - The company has exclusively licensed a patent family related to cytotoxic peptides and antibody-drug conjugates from Pfizer, with granted patents in multiple countries and a 20-year term running through 2032 [153]. - The company has acquired a patent family for anti-CD123 antibody-drug conjugates, with granted patents in several countries and a term running through 2038 [156].