Pyxis Oncology (PYXS) Study Update summary

Clinical study design and background

• MICVO (MCVO) is a first-in-concept ADC targeting extradomain-B of fibronectin (EDB+FN), a splice variant highly expressed in tumors but not normal tissue, optimized for stability, potency, and tumor ECM permeability.

• The Phase 1 program includes monotherapy and combination studies with pembrolizumab (Keytruda) in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), with global expansion and transition to specialist sites.

• Monotherapy focuses on a 5.4 mg/kg dose in two arms: post-platinum/PD-1 and post-EGFR/PD-1 patients.

• Combination studies are in dose escalation, currently enrolling at 5.4 mg/kg, with prior doses of 3.6 and 4.4 mg/kg cleared.

• Ongoing studies are enrolling additional patients and expanding to other tumor types.

Efficacy results

• Monotherapy at 5.4 mg/kg showed a 46% confirmed ORR and 92% DCR in 13 patients, with rapid, deep, and durable responses.

• Arm one (post-platinum/PD-1) had a 60% confirmed ORR; arm two (post-EGFR/PD-1) had a 25% confirmed ORR, both exceeding efficacy benchmarks.

• Combination with pembrolizumab at 3.6 and 4.4 mg/kg demonstrated a 71% confirmed ORR and 100% DCR in seven patients, with rapid and durable responses.

• Responses were observed regardless of HPV status, CPS score, or number of prior therapies, including patients with prior checkpoint inhibitor progression.

• Tumor regression or control was seen in nearly all evaluable patients in both monotherapy and combination arms.

Safety and dosing strategy

• No Grade 4 or 5 ADC payload-related adverse events observed in monotherapy or combination arms.

• Most treatment-related adverse events were Grade 1/2; Grade 3 events were more common in high bodyweight patients, with 28% discontinuation in monotherapy due to AEs, all in high bodyweight patients.

• Adjusted Ideal Body Weight (AIBW) dosing is being implemented to optimize exposure and reduce AEs, especially in overweight and underweight patients.

• Combination therapy at lower doses (3.6 and 4.4 mg/kg) showed only Grade 1 and 2 AEs, with no Grade 3 or higher events or discontinuations due to toxicity.

• Dose reductions, delays, and prophylactic measures (e.g., eye drops) are being used to further manage AEs.