Ontorpacept (TTI-621) is a soluble fusion protein comprising the N-terminal (1-118) of human SIRPα fused to the Fc region of human IgG1. This N-terminal (1-118) segment serves as the binding domain for CD47, an inhibitor of macrophage-mediated phagocytosis. As a checkpoint inhibitor that blocks CD47, ontorpacept exhibits antitumor activity [1].

Ontorpacept, at concentrations ranging from 0.001 to 1000 nmol/L administered over 2 hours, dose-dependently enhances macrophage phagocytosis of tumor cells in samples from patients with acute myeloid leukemia, myelodysplastic syndromes, multiple myeloma, B-cell acute lymphoblastic leukemia, and T-cell acute lymphoblastic leukemia, with an average EC50 of 10 nmol/L [1].

Ontorpacept, at a dose of 8 mg/kg administered intraperitoneally thrice weekly for four weeks, demonstrated antitumor activity in an acute myeloid leukemia xenograft model in SCID mice [1].