ALX Oncology (ALXO) Jefferies Global Healthcare Conference 2025 summary

Pipeline overview and clinical progress

• Two main clinical programs: Evorpacept (anti-CD47) and a novel EGFR-targeted ADC, both showing promise in early studies.

• Evorpacept has demonstrated differentiation by avoiding on-target toxicity seen in the CD47 class, supported by five positive clinical studies.

• Ongoing and upcoming studies include randomized phase II in post-HER2 breast cancer and a single-arm study in second-line colorectal cancer.

• The EGFR ADC program, developed in-house, aims to be first and best in class, with IND cleared and clinical trials starting mid-year.

• Additional collaborations include a multiple myeloma program with Sanofi and ongoing ADC combination studies.

Key clinical study details

• The breast cancer phase II study will randomize 120 post-HER2 patients to standard of care (Herceptin + chemo) vs. the same plus Evorpacept, with interim data expected in the second half of 2026.

• Patient selection leverages ctDNA as a surrogate for HER2 positivity, building on learnings from gastric studies.

• The colorectal study combines Evorpacept with Cetuximab and FOLFIRI in patients without prior exposure to these agents, with early safety and efficacy data expected in the first half of 2026.

• ADC combination studies, including with I-SPY, are ongoing, but the main focus is on antibody and ADC monotherapy programs.

• All three main studies are open-label, providing flexibility for interim analyses and data-driven decisions.

EGFR ADC innovation and differentiation

• The EGFR ADC uses a Topo1-based payload, a novel linker, and a unique epitope to minimize on-target skin toxicity, a key challenge in prior EGFR ADCs.

• Preclinical primate studies showed dosing up to 10 mg/kg without significant skin toxicity.

• The phase I trial will enroll late-line patients with EGFR-dependent tumors (head and neck, NSCLC, colorectal, esophageal), with dose escalation and expansion planned.

• The design aims to optimize dosing and select tumor types for phase II based on early safety and efficacy signals.

• The program was kept confidential until IND clearance to maintain competitive advantage.