ALX Oncology (ALXO) Study Update summary

Study background and rationale

• Evorpacept is a differentiated CD47 blocker with an inactive Fc, designed to enhance anti-tumor immune response when combined with antibody-drug conjugates (ADCs) like enfortumab vedotin (Padcev), and has shown robust clinical activity and a favorable safety profile in other solid tumors.

• The combination targets both innate and adaptive immunity by promoting macrophage phagocytosis and dendritic cell activation, leading to enhanced tumor antigen presentation.

• Preclinical data show enhanced anti-tumor activity and phagocytosis when evorpacept is combined with ADCs compared to either agent alone.

• Advanced bladder cancer represents a significant unmet need, with over 80,000 new US cases annually and limited options for patients progressing after first-line therapy.

• The ASPEN-07 study is the first to report on CD47 blockade combined with an ADC in this patient population.

Study design and patient characteristics

• Phase 1, open-label, dose-escalation study enrolled patients with advanced or metastatic urothelial carcinoma who had progressed after platinum-based chemotherapy and PD-1/PD-L1 inhibitors.

• Patients received evorpacept at 20 or 30 mg/kg every two weeks plus standard dosing of enfortumab vedotin (Padcev).

• 28 patients enrolled as of April 2024, median age 71, 93% with metastatic disease, and common sites including lymph nodes, lung, and liver.

• The study population was heavily pretreated, with 61% in second line, 29% in third line or beyond, and a notable proportion having liver metastases.

• No patients had prior exposure to enfortumab vedotin, aligning the cohort with the EV-301 trial population.

Safety and tolerability

• Evorpacept plus enfortumab vedotin (Padcev) was generally well tolerated, with no dose-limiting toxicities or treatment-related deaths observed, and the maximum tolerated dose was not reached at 30 mg/kg.

• Most evorpacept-related adverse events were low-grade, including fatigue, nausea, dysgeusia, diarrhea, and hyperglycemia.

• Grade 4 events included neutropenia (without fever), thrombocytopenia, and anemia.

• Evorpacept showed dose-proportional pharmacokinetics consistent with prior studies.

• The regimen was considered tolerable, allowing patients to remain on therapy and potentially benefit from prolonged treatment.