Core Viewpoint - Pyxis Oncology, Inc. is undergoing a leadership transition with the appointment of Thomas Civik as Interim CEO, following the departure of Lara S. Sullivan, to ensure continuity in advancing the company's strategic and clinical goals [1][2][3]. Leadership Transition - Thomas Civik, a long-time member of the Board of Directors and an experienced biotechnology executive, has been appointed as Interim Chief Executive Officer [2][4]. - Lara S. Sullivan has stepped down from her roles as President, CEO, and Chief Medical Officer after six years of leadership [2][4]. - The Board of Directors is conducting a structured search for a permanent CEO while maintaining operational continuity through the established clinical development leadership team [3][4]. Company Focus and Clinical Programs - Pyxis Oncology's lead program, micvotabart pelidotin (MICVO), is currently in a Phase 1 monotherapy study for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) and a Phase 1/2 study in combination with Merck's pembrolizumab [4][8]. - The company aims to prioritize the execution of its clinical programs and upcoming milestones, focusing on improving patient outcomes in difficult-to-treat cancers [5][8]. Background of Interim CEO - Thomas Civik previously served as President and CEO of Five Prime Therapeutics, leading its acquisition by Amgen for $1.9 billion in April 2021 [5][6]. - He has extensive experience in oncology development, having held leadership roles at Genentech for 17 years, overseeing key therapies such as Avastin and Tecentriq [6]. About Pyxis Oncology - Pyxis Oncology is a clinical-stage biopharmaceutical company focused on developing therapeutics for difficult-to-treat cancers, with MICVO being a first-in-concept antibody-drug conjugate targeting extradomain-B of fibronectin [7][10]. - MICVO is designed to treat solid tumors through a multi-pronged mechanism of action, including direct tumor cell killing and mobilizing an anti-tumor immune response [10].

Core Insights - Pyxis Oncology Inc. has released preliminary data from its ongoing Phase 1 studies of micvotabart pelidotin (MICVO) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) [1][5] Group 1: Study Results - In the monotherapy cohort, the confirmed overall response rate was 46% (6 of 13 patients), with a disease control rate of 92% (12 of 13 patients) [3] - The combination therapy cohort showed a confirmed overall response rate of 71% (5 of 7 patients) and a disease control rate of 100% (7 of 7 patients) [4] Group 2: Tolerability and Safety - MICVO was generally well tolerated, with no Grade 4 or Grade 5 treatment-related adverse events reported [4] - There was a noted 28% discontinuation rate in the study, which is significantly higher than the typical 10%-15% seen in oncology trials [7] Group 3: Future Plans - Pyxis Oncology plans to present updated data from the Phase 1 monotherapy study in mid-2026 and from the Phase 1/2 study in the second half of 2026 [5] - The company is evaluating the path forward for pivotal studies of MICVO as both a monotherapy and in combination with pembrolizumab [5] Group 4: Financial Update - Pyxis Oncology completed the sale of its rights to royalties from the commercialization of Enzeshu for a one-time cash payment of $11 million, which will support the development of MICVO [6] - The current cash runway is expected to fund operations through data milestones and into the fourth quarter of 2026 [6] Group 5: Market Reaction - Following the data release, Pyxis Oncology shares closed down about 49% at $1.73, reflecting concerns over limited data interpretability and tolerability issues [7] - Analysts have reiterated a Market Perform rating on Pyxis shares due to uncertainties regarding efficacy and the small sample size of the studies [9]

Core Viewpoint - Pyxis Oncology is conducting a clinical update call regarding its MICVO treatment for recurrent metastatic head and neck squamous cell carcinoma, indicating ongoing developments in its clinical research efforts [2]. Group 1: Company Overview - Alex Kane serves as the Senior Vice President of Investor Relations and Capital Markets at Pyxis Oncology, leading the discussion on the clinical update [2]. - The call will feature remarks from Lara Sullivan, the President, CEO, and CMO of Pyxis Oncology, followed by a Q&A session with her and other team members [2]. Group 2: Clinical Update - The focus of the call is on the clinical update for MICVO, specifically targeting recurrent metastatic head and neck squamous cell carcinoma, highlighting the company's commitment to advancing its oncology pipeline [2].

Summary of Pyxis Oncology Clinical Update Call Company Overview - **Company**: Pyxis Oncology (NasdaqGS:PYXS) - **Focus**: Development of MCVO for treating Recurrent Metastatic Head and Neck Squamous Cell Carcinoma Key Points from the Call Clinical Data Updates - **Monotherapy Results**: - Confirmed objective response rate (ORR) of **46%** and disease control rate (DCR) of **92%** in a cohort of **13 patients** at a dose of **5.4 mg/kg** [4][20] - Initial data indicates rapid tumor regression and durability of response [4] - **Combination Therapy with Pembro**: - Achieved a **71%** confirmed ORR and **100%** DCR in a cohort of **7 patients** at doses of **3.6 mg/kg** and **4.4 mg/kg** [5][37] - Ongoing evaluation of the **5.4 mg/kg** dose in combination therapy [5] Mechanism of Action - **MCVO**: A first-in-concept extracellular targeting antibody-drug conjugate (ADC) that targets EDB plus FN, a variant of fibronectin associated with tumor growth [6][10] - **Mechanism**: - Payload cleaves in the tumor microenvironment, diffusing into tumor cells and triggering bystander effects [10] - Activates T cells, enhancing immune response against tumors [10] Market Analysis - **Head and Neck Cancer Market**: - The sixth largest oncology market with limited competition and significant opportunities for new therapies [12] - Anticipated market shifts with the introduction of next-gen EGFR therapies, creating gaps for MCVO in second and third-line treatments [15][42] Clinical Development Strategy - **Current Studies**: - Two ongoing studies: monotherapy and combination with Pembro, focusing on second-line plus patients [16][17] - Plans for pivotal studies based on emerging data [5][42] Safety Profile - **Safety Observations**: - No grade 4 or 5 adverse events reported; some grade 3 events noted [32][40] - Adjusted ideal body weight dosing strategy being implemented to optimize safety and efficacy [33][34] Future Outlook - **Data Expectations**: - Mature data from the monotherapy study expected in mid-2026, with additional updates on combination therapy [43][56] - Anticipated discussions with the FDA regarding registrational study design, focusing on a randomized approach with control arms [58] Additional Insights - **Patient Demographics**: - Current patient population is heavily weighted towards HPV-positive individuals, with plans to diversify as more expert clinical trial sites are activated [22][23] - **Operational Progress**: - Transitioning from generalist to specialized clinical trial sites has led to increased enrollment efficiency [19][56] This summary encapsulates the critical insights and data shared during the Pyxis Oncology clinical update call, highlighting the company's advancements in treating head and neck cancer with MCVO.

MICVO Monotherapy Efficacy - MICVO monotherapy demonstrated a validated efficacy signal in 2L+ R/M HNSCC, with a 46% confirmed ORR and a 92% DCR (n=13, 5.4 mg/kg)[4] - In the Phase 1 monotherapy dose expansion study at 5.4 mg/kg, Arm 1 (post-PD1/post-Platinum) showed a 60% confirmed ORR (N=5)[32] - Arm 2 (post-PD1/post-EGFRi) in the monotherapy study showed a 25% confirmed ORR (N=4), exceeding the PI benchmark of 20%+[32] - MICVO monotherapy at 5.4 mg/kg demonstrated clear activity with deep responses and exceptional disease control[35] MICVO + KEYTRUDA® Combination Efficacy - MICVO combined with KEYTRUDA® showed a promising emerging efficacy profile in 1L/2L+ R/M HNSCC, with a 71% confirmed ORR and 100% DCR (n=7, 3.6 mg/kg & 4.4 mg/kg)[4] MICVO Safety and Tolerability - MICVO at 5.4 mg/kg in R/M HNSCC showed no Grade 4 or Grade 5 ADC payload TRAEs of interest[40] - Initial data supports a lack of overlapping toxicities observed between MICVO and KEYTRUDA®[52] Market and Clinical Development - FDA aligned on a 2L+ monotherapy pivotal trial design for MICVO[4] - The US R/M HNSCC market is large, growing, and relatively uncrowded, making it ripe for innovation[17] - Projected 2029 US market data shows a significant number of drug-treatable patients, with ~31K in 1L, ~21K in 2L, and ~8K in 3L[18]

Core Insights - Pyxis Oncology announced positive preliminary data from Phase 1 clinical studies of micvotabart pelidotin (MICVO), an antibody-drug conjugate targeting extradomain-B of fibronectin, in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) [1][2] Monotherapy Findings - In the Phase 1 monotherapy study, MICVO demonstrated a 46% confirmed objective response rate (ORR) and a 92% disease control rate (DCR) at a dose of 5.4 mg/kg in 2L+ R/M HNSCC [4] - The study included 18 patients, all of whom had prior systemic therapy, with a median of 3 prior lines of therapy [5] Combination Therapy Findings - In the Phase 1/2 study combining MICVO with pembrolizumab, the confirmed ORR was 71% and the DCR was 100% at doses of 3.6 mg/kg and 4.4 mg/kg [4][8] - The combination therapy included patients with varying PD(L)-1 CPS scores, and responses were observed even in those who had previously progressed on checkpoint inhibitors [8] Future Developments - Updated data from the ongoing Phase 1 monotherapy study is expected in mid-2026, while updated data from the combination study is anticipated in the second half of 2026 [9] - The company has received FDA alignment on the clinical trial design for a pivotal monotherapy study in 2L+ R/M HNSCC and is evaluating the path forward for pivotal studies [10] Financial Update - Pyxis Oncology completed the sale of rights to royalties from the commercialization of Enzeshu for a one-time cash payment of $11 million, which will support the development of MICVO [11]

Summary of Pyxis Oncology Conference Call Company Overview - **Company**: Pyxis Oncology - **Focus**: ADC (Antibody-Drug Conjugate) development - **Lead Asset**: Novel ADC targeting extracellular domain B (EDB), a splice variant of fibronectin in the tumor microenvironment - **Mechanism**: Extracellular cleaving ADC that kills tumors through direct tumor killing, bystander effect, and immunogenic cell death - **Clinical Development**: Asset brought into the clinic in early 2023, with dose escalation data showing a confirmed overall response rate (ORR) of 50% in head and neck cancer [4][65] Clinical Data and Trials - **Basket Trial**: Conducted with 80 patients across nine tumor types, showing strong tumor regression in head and neck, breast, sarcoma, ovarian, and lung cancers [15][16] - **Efficacious Dose Range**: Identified as 3.6-5.4 mg/kg, with a well-tolerated safety profile [14][15] - **Combination Therapy**: Initiated trials combining the ADC with Pembrolizumab (Pembro) [66] Mechanistic Insights - **Differentiation from Conventional ADCs**: Unlike traditional ADCs that target cell surfaces, Pyxis's ADC cleaves in the extracellular matrix, allowing for direct tumor cell killing [7][8] - **Bystander Effect**: The ADC's mechanism includes a significant bystander effect, which has been validated through translational biology work [9][10] - **Translational Data**: Ten biology and translational posters presented at major conferences, supporting the proof of mechanism for the novel ADC [8][9] Safety and Tolerability - **Adverse Events (AEs)**: Modest AE profile with no grade three treatment-related ocular toxicity or neuropathy; manageable AEs include neutropenia and cutaneous lesions [15][24] - **Comparison with Other ADCs**: Safety profile appears favorable compared to other ADCs, with a stable drug-to-antibody ratio (DAR) of 4 [26][27] Market Position and Strategy - **Head and Neck Cancer**: Identified as an underserved market with significant unmet needs; ongoing trials aim to establish the ADC's role in both current and future treatment paradigms [28][29] - **Monotherapy and Combination Trials**: Two arms in monotherapy targeting platinum and PD-1 resistant patients, and a combination arm with PD-1 inhibitors [30][31] - **Competitive Landscape**: Aiming for an ORR of 35-45% in monotherapy to be competitive, and 60-65% in combination therapy [33][34] Future Directions - **Data Disclosure**: Preliminary data expected by year-end, with insights into market opportunities and regulatory strategies [52] - **Cash Position**: Current cash balance of $77 million, providing runway into the second half of 2026 [54] Additional Insights - **Biomarker Development**: No single biomarker expected to predict response; multiple factors such as protease concentration and tumor matrix characteristics are considered [47] - **Exploration of Other Tumor Types**: Ongoing studies in combination therapy may inform potential applications in other cancers beyond head and neck [48]

Summary of Pyxis Oncology FY Conference Call Company Overview - **Company**: Pyxis Oncology (NasdaqGS:PYXS) - **Lead Asset**: MICVO, an antibody-drug conjugate (ADC) targeting the extracellular domain B (EDB) in solid tumors [4][5] Key Points and Arguments Development Focus - **Target Indication**: Focus on head and neck cancers, with two ongoing programs: monotherapy for second and third line, and combination therapy with Pembrolizumab (Pembro) [5][18] - **Mechanism of Action**: MICVO utilizes a three-pronged mechanism involving direct tumor killing, bystander effect, and immunogenic cell death, allowing for broad applications across various solid tumors [4][12] Clinical Trial Insights - **Phase I Study**: Conducted as a basket dose escalation trial with 80 patients across 10 tumor types, identifying an efficacious dose range of 3.6-5.4 mg/kg [6][7] - **Efficacy Results**: Confirmed response rate of 50% in head and neck cancer patients, with tumor regression observed in six different tumor types [8][15] - **Safety Profile**: Minimal grade three adverse events reported, indicating broad tolerability, particularly in heavily pretreated end-of-life patients [7][10] Competitive Landscape - **Market Positioning**: Aiming to establish a foothold in the head and neck cancer market, competing against other therapies with a focus on both current and emerging treatment lines [16][22] - **Efficacy Expectations**: Minimum expected overall response rate (ORR) of 35% to be considered a credible competitor in the second and third line settings [22][23] Future Development Plans - **Data Updates**: Upcoming data disclosure will include preliminary results from both monotherapy arms and the combination therapy, aimed at shaping the understanding of the competitive landscape [19][20] - **Broader Applications**: While currently focused on head and neck cancers, the mechanism of MICVO suggests potential applications in other solid tumors over time [35][36] Translational Biology Work - **Supporting Mechanism**: Recent translational biology work has validated the mechanism of MICVO, including the identification of key proteases in the tumor microenvironment and T cell activation [12][13][14] Strategic Considerations - **Market Segmentation**: Plans to provide insights on market segmentation and competitive positioning in future updates, considering factors like HPV status and prior treatment history [33][34] Additional Important Insights - **Combination Therapy**: Ongoing combination therapy program with Keytruda, currently in dose escalation phase [18] - **Patient Cohorts**: Distinction between cohorts based on prior treatments (platinum and PD-1 vs. EGFR and PD-1) to assess the agent's efficacy in different treatment lines [16][17] This summary encapsulates the critical aspects of Pyxis Oncology's conference call, highlighting the company's strategic focus, clinical insights, and future development plans in the oncology space.

Core Insights - Pyxis Oncology, Inc. is a clinical-stage biopharmaceutical company focused on developing therapeutics for difficult-to-treat cancers [2] - The company will participate in two upcoming investor conferences in November 2025, including the Guggenheim 2 Annual Healthcare Innovation Conference and the Stifel 2025 Healthcare Conference [1][3] Company Overview - Pyxis Oncology's lead candidate, micvotabart pelidotin (MICVO), is a first-in-concept antibody drug conjugate (ADC) targeting extradomain-B of fibronectin (EDB+FN), which is overexpressed in various solid tumors [2] - MICVO aims to treat solid tumors through a mechanism involving direct tumor cell killing, bystander effect, and immunogenic cell death [2] - The drug is currently in Phase 1 clinical studies for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) and other solid tumors, both as a monotherapy and in combination with Merck's KEYTRUDA® [2]

Product Development - Pyxis Oncology's product candidate micvotabart pelidotin (MICVO) targets EDB+FN, a component of the tumor extracellular matrix, aiming to destabilize tumor support while directly killing tumor cells[90]. - In the Phase 1 dose escalation study, micvotabart pelidotin achieved a 50% objective response rate (ORR) in six patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) at a dose range of 3.6 mg/kg – 5.4 mg/kg IV Q3W[96]. - The study also reported a disease control rate (DCR) of 100% among the six heavily pre-treated R/M HNSCC patients[96]. - Across six solid tumor types of interest, micvotabart pelidotin achieved a 26% ORR (n=31) at the same dose range[97]. - The FDA granted Fast Track Designation to micvotabart pelidotin for the treatment of adult patients with R/M HNSCC whose disease has progressed after platinum-based chemotherapy and anti-PD-(L)1 therapy[103]. - Pyxis Oncology plans to prioritize resources to further develop micvotabart pelidotin based on the promising efficacy signals observed in R/M HNSCC[104]. - A clinical trial collaboration with Merck has been established to study micvotabart pelidotin in combination with KEYTRUDA®[108]. - The company initiated a Phase 1/2 combination study with KEYTRUDA® to evaluate the safety and preliminary efficacy of micvotabart pelidotin in advanced solid tumors[109]. - Preliminary data from the ongoing studies are expected to be disclosed in the fourth quarter of 2025[111]. - The company is actively recruiting patients for two monotherapy expansion cohorts in the R/M HNSCC study, each expecting to enroll approximately 20 patients at the 5.4 mg/kg IV Q3W dose[111]. Financial Performance - For the nine months ended September 30, 2025, the company reported a net loss of $61.5 million, compared to a net loss of $41.8 million for the same period in 2024, representing an increase in losses of $19.8 million[115]. - Research and development expenses for the nine months ended September 30, 2025, increased by $7.3 million to $52.0 million, up from $44.7 million in the same period in 2024[136]. - The company recognized $2.8 million in milestone revenue related to regulatory approval of Suvemcitug in China during the nine months ended September 30, 2025, compared to $16.1 million in total revenues for the same period in 2024[133]. - The accumulated deficit as of September 30, 2025, was $425.1 million, with net equity of $68.8 million and cash and cash equivalents totaling $77.7 million[115]. - Research and development expenses for the three months ended September 30, 2025, were $17.8 million, a slight increase of $0.1 million from $17.7 million in the same period in 2024[126]. - The company expects to continue incurring significant operating losses and expenses in the foreseeable future, primarily due to ongoing clinical and preclinical activities[115]. - General and administrative expenses decreased by $0.4 million to $5.6 million for the three months ended September 30, 2025, compared to $6.0 million in the same period in 2024[130]. - Micvotabart pelidotin program-specific research and development costs increased by $2.0 million, primarily due to increased contract manufacturing and clinical trial expenses[127]. - The company has not generated any revenues from product sales and does not expect to do so in the foreseeable future[116]. - Other income, net for the three months ended September 30, 2025, was $1.4 million, down from $2.5 million in the same period in 2024, primarily due to decreased interest and investment income[131]. - Micvotabart pelidotin program-specific R&D costs increased by $9.1 million, driven by a $5.0 million rise in contract manufacturing costs and a $3.9 million increase in clinical trial expenses[137]. - PYX-106 program-specific R&D costs decreased by $3.9 million due to the pause in clinical development[138]. - General and administrative expenses decreased by $3.4 million, from $20.3 million in 2024 to $16.9 million in 2025, primarily due to lower stock-based compensation and professional fees[139]. - Other income decreased from $7.6 million in 2024 to $4.9 million in 2025, mainly due to reduced interest and investment income[140]. - As of September 30, 2025, the company had cash and short-term investments totaling $77.7 million, with net losses of $61.5 million for the nine months ended September 30, 2025[141]. - The company expects substantial increases in expenses related to ongoing clinical trials and may finance operations through equity offerings and collaborations[143]. - Net cash used in operating activities was $53.1 million for the nine months ended September 30, 2025, compared to $38.4 million in 2024[146][148]. - Net cash provided by investing activities was $42.6 million in 2025, primarily from the redemption of marketable debt securities[149]. - The company had $106.2 million of remaining capacity available under its ATM facility as of September 30, 2025[142]. - The company raised substantial doubt about its ability to continue as a going concern for the next 12 months due to insufficient cash resources[154].