Pyxis Oncology (PYXS) Study update summary

Study Background and Rationale

• MICVO is a first-in-concept antibody-drug conjugate (ADC) targeting the extra domain B of fibronectin in the tumor extracellular matrix, offering a novel, non-cellular targeting mechanism with potential advantages over conventional ADCs.

• The construct is engineered for high binding avidity, uniform drug-to-antibody ratio, optimized auristatin E payload, and enhanced permeability for efficient bystander killing and tolerability.

• MICVO induces direct tumor cell killing, bystander effect, immunogenic cell death, reduces matrix density, inhibits angiogenesis, and mobilizes immune response.

• Initial focus is on 2L+ recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) due to high unmet need and robust EDB+ FN expression.

• MICVO received Fast Track Designation from the FDA for R/M HNSCC post-platinum and anti-PD-(L)1 therapy.

Clinical Study Design and Patient Population

• Phase I study included dose escalation and expansion in 2L+ R/M HNSCC, focusing on patients who progressed after platinum and anti-PD-(L)1, or EGFR-targeted therapy.

• Dose cap was implemented at 80 kg for males and 70 kg for females to mitigate toxicity, with 35 patients in the dose cap subgroup forming the primary analysis set.

• Median age was 65 years, 83% male, 83% white; all patients had prior platinum and anti-PD-(L)1 therapy, 57% had prior EGFR inhibitor exposure, and median prior systemic therapy lines was three.

• HPV-positive and HPV-unrelated subgroups were nearly equally represented; most common primary cancer site was oropharynx (63%).

• Data cutoff for analysis was August 18, 2026.

Efficacy Results

• Confirmed overall response rate (ORR) was 36%, with 75% of responders achieving response at first scan and 83% experiencing >50% tumor reduction.

• Disease control rate reached 94%, and median progression-free survival (PFS) was 6.2 months; 12-month overall survival probability was 79%.

• Efficacy was consistent across subgroups, including HPV status, prior EGFR inhibitor, and prior taxane exposure.

• Patients previously treated with novel EGFR inhibitors also showed tumor regression and a 40% response rate.

• MICVO outperformed historical controls (KEYNOTE-040, CheckMate-141) in ORR, mPFS, and OS.