STIFEL 2026 HEALTHCARE CONFERENCE - PYXIS ONCOLOGY INC

Financial Performance:

• Executed two strategic fundraisings in 2026, securing sufficient capital to extend the cash runway into the first half of 2028.
• Current funding provides ample liquidity to support enrollment of the pivotal "Headliner" trial and subsequent operations.
• No specific revenue, profit margins, or debt figures disclosed as the company remains in the clinical development phase.

Guidance and Future Outlook:

• Aiming to dose the first patient in the pivotal Phase 3 "Headliner" trial in mid-2027.
• Guiding to an update on Overall Survival (OS) data from the ongoing Phase 1/2 study in the first half of 2028.
• Plans to present new data at the Triple-A (TRIPLE) meeting in Barcelona; final details remain under embargo.
• Objective is to advance to a full Phase 3 registration path, with the primary goal of establishing MCFO as the standard of care in second-line head and neck cancer.

Business Segments and Product Lines:

• Lead Asset (MCFO): A first-in-class Antibody-Drug Conjugate (ADC) targeting EDBFN in the extracellular matrix, a target present in nearly all solid tumors but absent in normal tissue.
• Secondary Pipeline: Exploring combination therapies, including MCFO with pembrolizumab in the frontline setting, and potential expansion into neoadjuvant/adjuvant settings.
• Dosing Strategy: Implemented a weight-based dose cap (addressing toxicity in high-body-weight patients) which reduced discontinuation rates due to peripheral neuropathy by nearly 50%.
• Trial Portfolio:
  • Monotherapy: Phase 1/2 dose-expansion in second-line head and neck (HPV-positive and negative) showing 36% response rate and 94% disease control rate.
  • Combination: Ongoing dose-escalation with pembrolizumab in frontline head and neck (20+ patients dosed at 3.6mg and 4.4mg).

Market and Competitive Landscape:

• Target Population: Estimated 30,000 new cases annually in head and neck cancer; approximately 20,000-21,000 patients are expected to require second-line therapy (projected 70% progression rate from frontline).
• Competitive Moat: Second-line options for HPV-unrelated patients are limited; competitors' EGFR bispecifics are anticipated to move into frontline treatment by 2028, potentially increasing the unmet need for second-line options.
• Market Dynamics: The introduction of EGFR bispecifics and checkpoint inhibitors in the frontline setting is expected to create a larger pool of patients progressing to the second-line space where MCFO is positioned.
• Differentiation: MCFO demonstrated rapid and deep responses (>50% tumor reduction in >50% of patients within 6 weeks), addressing critical quality of life issues (eating, speaking) in head and neck cancer.

Risks and Challenges:

• Toxicity Management: Historical limiting toxicity in high-body-weight patients managed via dose capping; ongoing monitoring of neuropathy, ocular, and cutaneous adverse events.
• Data Maturity: Overall Survival (OS) data is currently early (6 events at cut-off), requiring further observation to validate durability and long-term trends.
• Trial Execution: Need to secure a control arm (docetaxel, methotrexate, or cetuximab) in a landscape where frontline standards of care are rapidly evolving.
• Regulatory Path: Requires successful completion of "Project Optimus" dose optimization meetings with the FDA to finalize the Phase 3 design.

Management Commentary and Tone:

• Tone is highly confident and optimistic, emphasizing that MCFO represents a "first-in-concept" breakthrough with a clear benefit-risk profile.
• Management expressed strong conviction that the 5.4 mg/kg dose with the weight cap is the optimal dosing strategy, noting the safety profile is manageable and expected for prolonged otistatin exposure.
• CEO Tom Sivick highlighted the "small but mighty" team's progress and the strategic alignment of the trial design with future market trends (EGFR bispecifics moving to frontline).
• Management emphasized the "tailwind" effect of evolving frontline therapies increasing the second-line patient pool.

Analyst Questions and Answers:

• Q: Efficacy discrepancy post-EGFR inhibition?
  • A: Management attributed the delta to line of therapy rather than biological resistance; noted that 45% of patients in pure second-line setting responded vs. 35% in third-line, despite prior EGFR exposure.
• Q: Impact of AMI (Amivantamab) approval on survival analysis?
  • A: Believed to have negligible impact on the pivotal trial design or survival curves given the timeline gap between AMI commercialization and the trial's expected completion.
• Q: Confidence in OS durability?
  • A: High confidence based on converging data points (Response Rate, Disease Control Rate, PFS), though acknowledged OS data requires time to mature.
• Q: Future tumor indications?
  • A: Confirmed MCFO is not limited to head and neck; will explore other solid tumors based on clinical activity and market size once the primary indication is validated.
• Q: Frontline combination data update?
  • A: Expected to release response and safety data for >20 patients (HPV+ and HPV-) by year-end 2027, with durability data expected in H2 2028.

Other Key Points:

• The "Headliner" Phase 3 trial will be a global, randomized 1:1 study comparing MCFO to investigator's choice of docetaxel, methotrexate, or cetuximab.
• Enrollment criteria will stratify for HPV status and prior EGFR inhibitor exposure to accommodate global variations in standard of care.
• Management confirmed that the dose expansion data showed efficacy regardless of HPV status, a critical factor for the target population.
• The company is leveraging a unique "basket study" approach that identified head and neck cancer as the lead indication due to the strongest clinical signal and unmet need.