ES004 is a potentially best-in-class antibody targeting pan-allele signal-regulatory protein alpha (SIRPα). SIRPα is an inhibitory receptor expressed only on myeloid cells and dendritic cells. Binding of CD47 to SIRPα delivers a “don’t eat me” signal to suppress phagocytosis. Tumor cells frequently overexpress CD47 to evade macrophage-mediated destruction. To overcome this issue, ES004 stimulates potent macrophage-mediated phagocytosis against multiple tumor cells by blocking SIRPα. Unlike agents targeting CD47, targeting SIRPα is designed to avoid anemia and thrombocytopenia and improve the therapeutic window.
In preclinical studies, no severe hemolytic anemia and thrombocytopenia were observed in ES004 treated hCD47/hSIRPα double knock-in mice, suggesting a potential lower safety risk.