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 in combination with antibody-drug conjugates (ADCs) like enfortumab vedotin (PADCEV), and has shown robust clinical activity and a favorable safety profile in other solid tumors.

• Combining evorpacept with ADCs is supported by strong scientific rationale and preclinical data, showing enhanced anti-tumor activity and phagocytosis.

• The ASPEN-07 study is the first to evaluate CD47 blockade with an ADC in advanced bladder cancer, targeting patients who progressed after platinum chemotherapy and PD-1/PD-L1 inhibitors.

• 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 mechanism leverages both innate and adaptive immunity by blocking CD47 and activating macrophages and dendritic cells.

Study design and patient characteristics

• Phase 1, open-label, dose-escalation study enrolled 28 patients with advanced/metastatic urothelial carcinoma, all previously treated with platinum chemotherapy and PD-1/PD-L1 inhibitors.

• Patients received evorpacept at 20 or 30 mg/kg every two weeks plus standard PADCEV dosing.

• Median age was 71 years; 93% had metastatic disease, with common sites including lymph nodes, lung, and liver.

• The population was heavily pretreated, with 61% in second line and 29% in third line or beyond, and a higher proportion of liver metastases compared to historical controls.

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

Safety and tolerability

• Evorpacept plus PADCEV was generally well tolerated, with no dose-limiting toxicities or treatment-related deaths observed; maximum tolerated dose was not reached at 30 mg/kg.

• Most common adverse events included low-grade fatigue, nausea, dysgeusia, diarrhea, and hyperglycemia.

• Two cases of grade 4 neutropenia occurred without febrile neutropenia.

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

• The regimen was generally well tolerated, allowing patients to remain on therapy longer.