ALX Oncology Holdings Inc. announced the initiation of a Phase 2 investigator-sponsored trial ("IST") of neoadjuvant radiation and evorpacept, a next-generation CD47 blocker, in combination KEYTRUDA®? (pembrolizumab) in patients with previously untreated and early-stage locally advanced, resectable, humanapillomavirus-mediated oropharyngeal cancer ("HPVOC"). This multi-center, single-arm, open-label Phase 2 IST is being led by Joseph A. Califano III, M.D., Director of the Hanna and Mark Gleiberman Head and Neck Cancer Center at the University of California, San Diego (NCT05787639).

Radadiotherapy induces the release of tumor-associated antigens and upregulates PD-L1 expression by tumor cells. Blocking the CD47/SIRPa axis may yield a synergistic anti-tumor effect when combined with radiotherapy and immunotherapy. The Company's pipeline of therapeutic candidates with standard-of-care agents include: Anti-cancer antibodies (the "don't eat me" signal): evorpacept enables Fc-mediated antibody-dependent phagocytosis by macrophages in combination with anti-cancer antibodies (e.g., Herceptin®?) with an active Fc domain, which is otherwise impaired by CD47 expression on cancer cells binding to SIRP alpha on macrophages.

This same mechanism of action applies to ADCs. PD-1/PD-L1 immune checkpoint inhibitors (the "don't activate T-cells" signal): evor pacept enables T-cell activation by dendritic cells that are constitutively inhibited by CD47 expression on cancer cell binding to SIRP alpha On dendritic cells. Activated dendritic cells present neoantigens to T-cells that once activated will kill cancer cells when the PD-1/PD- L1 inhibitory interaction is blocked by T-cell checkpoint inhibitors.