BSI-730

BSI-730 is a first-in-class HER2 x PD-L1 bispecific antibody-drug conjugate (ADC) engineered specifically to address the critical clinical vacuum in the post-Enhertu® (T-DXd) setting, where HER2 downregulation and payload efflux are potential mechanisms of resistance. Designed with a knob-in-hole heterodimer backbone comprising a Trastuzumab and proprietary PD-L1 sequence, BSI-730 is site-specifically conjugated to an exatecan payload at a highly stable Drug-to-Antibody Ratio (DAR) of 4. This unique architecture circumvents ABCC1 efflux pumps and drives a synergistic dual-mechanism: it enforces robust cellular internalization and targeted immunogenic cell death even in low-antigen-density environments, while simultaneously blocking the PD-1/PD-L1 signaling axis to reverse adaptive immune resistance and turn "cold" tumors "hot". BSI-730 has demonstrated structural de-risking and exceptional potency, outperforming a DAR 8 T-DXd analog by achieving superior tumor growth inhibition in HER2-low xenograft models using 50% less payload. Currently advancing through IND-enabling studies, BSI-730 offers prospective partners exclusive global rights to a "pipeline-in-a-product" capable of capturing the multi-billion dollar HER2-low and post-Enhertu market across breast, gastric, and NSCLC indications.