HER3 and MET were co-expressed in various tumor types, and their signaling plays a key role in EGFR TKI drug resistance. HER3×MET bsAbs generated from the RenLite® platform contain a full human heavy chain variable domain with a common human kappa light chain, demonstrating cross-species reactivity to human and cynomolgus monkey antigens. HER3×MET bsAbs bound to a variety of HER3/MET co-expressing tumor lines, including NSCLC, gastric, liver, and colorectal cancers, and have enhanced internalization activity in the NUGC-4 cell line. Both BCG022-vcMMAE and BCG022-BLD1102 bsADCs showed superior or comparable anti-tumor activity to the benchmark ADCs in CDX and PDX models.