Pyxis Oncology (PYXS) Status Update summary

Key clinical findings and development strategy

• PYX-201, a novel ADC targeting EDB+FN, demonstrated strong safety and efficacy in heavily pretreated, late-stage cancer populations, especially in head and neck cancer, with a 50% objective response rate and durable responses across both HPV-positive and negative patients.

• The agent showed promising early activity in five additional tumor types: lung, ovarian, HR-positive breast, triple-negative breast, and sarcoma, with evidence of tumor regression and durable disease control.

• Safety profile was favorable, with low rates of discontinuation (3% due to TRAEs), minimal neuropathy and ocular toxicity, and manageable cutaneous and neutropenia side effects.

• Most TRAEs were Grade 1/2, with Grade 3/4 events infrequent and reversible; no treatment-related deaths were reported.

• A new clinical trial collaboration with Merck will evaluate PYX-201 in combination with KEYTRUDA, with three head and neck studies and exploratory work in other tumor types launching in the first quarter.

Mechanism of action and innovation

• PYX-201 is a first-in-concept ADC targeting the extracellular domain B (EDB) of fibronectin, a non-cellular extracellular matrix component overexpressed in solid tumors.

• Releases its payload extracellularly, enabling direct tumor killing, bystander effect, and immunogenic cell death.

• Site-specific conjugation and optimized auristatin payload improve stability, reduce off-target effects, and result in lower free payload in circulation and longer half-life compared to traditional ADCs.

• Designed for broad applicability across multiple cancer types.

• Mechanism supports potential for use in combination regimens and as a radiosensitizer.

Clinical trial design and patient population

• Phase 1 dose escalation study enrolled 80 patients with 10 solid tumor types across 18 global sites, with no biomarker selection and a median of 4 prior therapy lines.

• Doses ranged from 0.3 to 8 mg/kg, with 3.6–5.4 mg/kg identified as the effective range; 52% of patients were in the 5.4 mg/kg group.

• Median age was 65 years, and 71% had ECOG performance status 1.