evorpacept + azacitidine

Evorpacept + azacitidine is an investigational combination of two agents: evorpacept, a high-affinity CD47-blocking fusion protein, and azacitidine, a hypomethylating agent. Evorpacept (code name ALX148) is designed to block the interaction between CD47—a “don't eat me” signal on tumor cells—and SIRPα on macrophages, thereby enhancing the phagocytic clearance of malignant cells. Its engineered Fc domain reduces binding to Fcγ receptors, thereby minimizing typical toxicity seen with CD47-targeting antibodies. Azacitidine is a standard-of-care nucleoside metabolic inhibitor used in myelodysplastic syndromes (MDS), which induces pro-phagocytic signals (such as calreticulin) on malignant cells. The rationale for combining these two drugs is to enhance anti-tumor immune response, particularly in higher-risk MDS[1][2][4].