Pyxis Oncology (PYXS) Investor presentation summary

Differentiated ADC platform and technology

• MICVO is a first-in-concept antibody-drug conjugate (ADC) targeting the extracellular matrix protein EDB+FN, a splice variant of fibronectin, which is abundant in tumor ECM but negligible in normal tissue.

• The ADC is engineered for optimized stability, potency, and permeability, using site-specific conjugation and a uniform drug-antibody ratio to maximize tumor killing and minimize off-target effects.

• MICVO’s three-pronged mechanism of action includes direct tumor cell killing, bystander effect, and induction of immunogenic cell death, potentially enhancing immune response.

• Preclinical and translational data support MICVO’s activity in both immunologically 'hot' and 'cold' tumors, with strong binding and minimal off-target toxicity.

Clinical development and efficacy in R/M HNSCC

• Phase 1 dose escalation and expansion studies in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) identified 5.4 mg/kg as the optimal monotherapy dose.

• Confirmed overall response rate (ORR) of 46% and disease control rate (DCR) of 92% were observed in 2L+ R/M HNSCC patients at this dose, with rapid and deep responses.

• Combination with KEYTRUDA® (pembrolizumab) showed a 71% confirmed ORR and 100% DCR in preliminary data, with no overlapping toxicities.

• MICVO demonstrated efficacy in heavily pre-treated patients, including those with HPV-unrelated disease, and responses were seen across multiple tumor types.

Safety, dosing, and patient tolerability

• No grade 4 or 5 treatment-related adverse events (TRAEs) were observed at the 5.4 mg/kg dose; most TRAEs were grade 1/2, with manageable grade 3 events.

• Discontinuations were linked to overexposure in high body weight patients, prompting a shift to modified weight-based dosing (dose capping and adjusted ideal body weight, AIBW).

• PK modeling and external ADC precedents support that modified dosing mitigates overexposure and improves tolerability without sacrificing efficacy.