Pyxis Oncology (PYXS) investor relations material

Differentiated ADC platform and target

• MICVO is a first-in-concept antibody-drug conjugate (ADC) targeting EDB+FN, a splice variant of fibronectin abundant in tumor extracellular matrix (ECM) and minimally expressed in normal tissue.

• The ADC is engineered for optimized stability, potency, and permeability, using site-specific conjugation and a uniform drug-antibody ratio of 4.

• MICVO’s mechanism involves extracellular linker cleavage, payload diffusion, bystander killing, and immunogenic cell death, potentially amplifying immune response.

• Preclinical and translational data support activity in both immunologically 'cold' and 'hot' tumors, with minimal off-target effects.

Clinical efficacy and safety in R/M HNSCC

• Phase 1 studies in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) showed a 46% confirmed objective response rate (ORR) and 92% disease control rate (DCR) at 5.4 mg/kg.

• Strong monotherapy signals were observed in heavily pre-treated patients, with rapid and deep responses and emerging durability.

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

• Safety profile at 5.4 mg/kg showed no grade 4/5 ADC payload-related adverse events; most discontinuations were linked to overexposure in high body weight patients.

Addressing dosing and tolerability

• Overexposure and related adverse events in high body weight patients led to the implementation of dose capping and adjusted ideal body weight (AIBW) dosing.

• PK modeling and external ADC precedents support modified weight-based dosing to mitigate toxicity without sacrificing efficacy.

• All treatment-related discontinuations occurred in patients above AIBW, with no such events in those at or below AIBW.