ES004 is a potentially best-in-class antibody targeting pan-allele signal-regulatory protein alpha (SIRPα).
SIRPα is an inhibitory receptor expressed on myeloid cells and dendritic cells. Ligation of CD47 to SIRPα delivers a “don’t eat me” signal to suppress phagocytosis. Tumor cells frequently overexpress CD47 to evade macrophage-mediated destruction.
Although SIRPα targeting antibodies are being developed by multinational companies to block “don’t eat me” signal, they weakly stimulate or fail to stimulate potent macrophage-mediated phagocytosis, thus resulting in insufficient anti-tumor efficacy. On the other hand, ES004 alone is sufficient to stimulate potent macrophage mediated phagocytosis against multiple tumor cells by blocking CD47/SIRPα signaling axis. Additionally, unlike agents targeting CD47, no severe hemolytic anemia and thrombocytopenia were observed in ES004 treated hCD47/hSIRPα double knock-in mice, suggesting a low safety risk in vivo.
We are currently advancing the development of ES004 into a clinical candidate.