Pyxis Oncology (PYXS) Study Update summary

Preliminary efficacy and safety results

• Monotherapy with MICVO at 5.4 mg/kg in recurrent/metastatic HNSCC showed a 46% confirmed objective response rate and 92% disease control rate, with rapid and deep tumor regression observed.

• Combination with pembrolizumab (KEYTRUDA®) at 3.6 and 4.4 mg/kg demonstrated a 71% confirmed objective response rate and 100% disease control rate, with rapid and durable responses across HPV status and prior therapies.

• Responses were observed across HPV-positive and HPV-negative tumors, various prior therapies (including taxanes, platinum, checkpoint inhibitors, and EGFRs), and a range of tumor sizes and PD(L)-1 CPS scores.

• No Grade 4/5 ADC payload-related adverse events were observed in monotherapy or combination arms; most treatment-related adverse events were Grade 1/2, with Grade 3 events more common in high bodyweight patients.

• Adjusted Ideal Body Weight (AIBW) dosing is being implemented to optimize safety, particularly for overweight and underweight patients, and is expected to further reduce adverse events.

Study design, enrollment, and regulatory plans

• Monotherapy study includes two arms: post-platinum/PD-1 and post-EGFR/PD-1, with more heavily pretreated patients in the latter.

• Combination study is a basket design, currently enrolling at 5.4 mg/kg, with global site expansion to diversify patient demographics.

• Target enrollment for the next data update is approximately 20 patients per arm in monotherapy and 20 in combination, with mature data expected mid-2025 for mono and late 2025 for combo; further updates expected in 2026.

• FDA alignment has been achieved for a randomized pivotal monotherapy study in second-line plus, using a control arm of cetuximab, methotrexate, or docetaxel, and incorporating AIBW dosing.

• Project Optimus principles will guide dose optimization in future registrational studies.

Mechanism of action and market positioning

• MICVO is a first-in-concept ADC targeting extradomain-B of fibronectin (EDB+FN), a noncellular tumor matrix component minimally expressed in normal tissue, with a three-pronged mechanism: direct tumor cell killing, bystander effect, and immunogenic cell death.

• Tumor microenvironment factors (pH, proteases, stromal architecture) influence response, with head and neck tumors showing favorable matrix organization for MICVO activity.

• MICVO's construct is optimized for stability, potency, and permeability in the tumor ECM.

• Market analysis highlights significant unmet need in second/third-line and certain frontline segments (HPV-positive, low CPS), with MICVO positioned to address these gaps.

• MICVO's mechanism is orthogonal to next-gen EGFRs, allowing potential for combination or sequential use, and applicability to other tumor types with similar microenvironmental features.