ALX Oncology Holdings (ALXO) Earnings Call Presentation

ALX2004 Program Overview - ALX2004 is an EGFR-targeted ADC with a DAR of 8, utilizing a topoisomerase I inhibitor (Top1i) payload, with IND cleared in April 2025[13, 98] - ALX2004 is designed to maximize the therapeutic window and overcome toxicity challenges, with a focus on EGFR-expressing solid tumors[14, 99] - ALX2004's Phase 1a dose escalation trial is planned to start in mid-2025, targeting NSCLC, CRC, HNSCC, and ESCC[14, 99] ALX2004 Design and Preclinical Data - ALX2004's EGFR antibody binding epitope is selected to minimize off-tumor skin toxicities, and its affinity is tuned to maximize the therapeutic window[20] - The linker-payload is designed for lysosomal cleavage, similar to deruxtecan ADCs, with improved linker-antibody stability to minimize off-tumor payload release[20] - Preclinical data demonstrates dose-dependent activity across a range of tumors and EGFR expression levels, with a differentiated safety profile in NHP toxicity studies, showing no EGFR-related skin toxicity at clinically relevant doses[24] - In preclinical studies, ALX2004 demonstrated superior anti-tumor activity compared to DXd ADCs in CDX mouse models, showing improved bystander effect[47, 49] Clinical Development Plan - The Phase 1 trial is rationally designed around tumor types with established sensitivity to EGFR-directed therapies, including HNSCC, CRC, NSCLC, and ESCC, representing over 250,000 patient prevalence in the US[87] - The Phase 1 clinical development plan includes dose escalation (Phase 1a, up to 40 patients), dose exploration (up to 50 patients), and dose expansion (Phase 1b, up to 80 patients)[89, 90, 91] - ALX Oncology anticipates initial safety data for ALX2004 in EGFR-expressing solid tumors in the first half of 2026[101]