Undisclosed masked antibodies

In normal tissues, the SAFEbody masking moiety is expected to shield ADG153 from binding to CD47; however, in the presence of highly upregulated CD47 in protease-rich tumor microenvironment (TME), the masked antibody can engage dynamically with highly expressed CD47 and can be cleaved, enabling efficient binding to CD47, blocking CD47/SIRPα signaling, and triggering strong anti-tumor activities in solid tumors. The in vivo anti-tumor efficacy of ADG153 or magrolimab analog (magrolimab) was assessed across several solid tumor xenograft models. ADG153 demonstrates significantly reduced antigen sink liabilities and favorable CD47 engagement in the TME, which are highly differentiated from other anti-CD47 agents. ADG153 is locally enriched and efficiently cleaved in tumors, engages its target, and elicits potent anti-tumor activities in multiple solid tumor xenograft models. These results indicate that the ADG153 SAFEbody is a novel anti-CD47 IgG1 antibody prodrug with strong ADCC and ADCP capacities and substantially reduced liabilities, supporting its advancement into clinical development.