ES004 is a potential best-in-class antibody targeting pan-allele signal-regulatory protein alpha (SIRPα). SIRPα is an inhibitory receptor expressed mainly 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, thrombocytopenia and antigen sink and improve the therapeutic window.  


In preclinical studies, ES004 demonstrated excellent safety profile in cynomolgus monkeys with no hematology adverse effects, suggesting a potential lower safety risk to humans.