ALX Oncology (ALXO) Jefferies London Healthcare Conference 2025 summary

Strategic focus and program overview

• Company has pivoted to focus on two high-value clinical programs: a differentiated CD47 inhibitor (evorpacept) and a novel EGFR-targeted ADC (ALX2004).

• Evorpacept leverages a 'dead Fc' design, avoiding toxicity seen in other CD47 approaches and showing strong clinical results in HER2-positive gastric and breast cancers.

• ALX2004, developed after acquiring a specialized ADC team, features a unique linker payload and epitope, aiming to minimize toxicity and maximize efficacy.

• Both programs are now the primary focus, with ongoing clinical trials and recent data releases guiding future development.

Clinical data insights and biomarker strategy

• Evorpacept demonstrated compelling efficacy in HER2-positive, CD47-high gastric cancer, with similar promise in breast cancer.

• Response rates were robust across multiple CD47 expression cutoffs, supporting the mechanism's strength and broad applicability.

• Ongoing studies are validating the CD47 biomarker in additional cancers, including collaborations in breast cancer and multiple myeloma.

• Interim phase II data in HER2-positive breast cancer is expected in Q3 next year, with a 35%+ response rate in double-positive patients seen as a key benchmark.

• The company is working with the FDA on assay validation and pivotal trial design, aiming for a seamless transition to registration studies.

EGFR ADC program development

• ALX2004 uses a Topo-I payload (DAR-8) and a unique epitope to reduce on-target skin toxicity and avoid ILD, differentiating it from prior EGFR ADCs.

• Preclinical work showed strong activity and safety, with no need for masking technology due to optimized design.

• Phase I dose escalation began at 1 mg/kg, with no DLTs observed; the study is now dosing at 2 mg/kg.

• Early clinical focus is on tumors with high EGFR expression, including lung, CRC, head and neck, and esophageal cancers.

• Safety data is expected in the first half of next year, with rapid indication selection planned based on early efficacy signals.