• DM005 is a novel bsADC that targets EGFR and MET with a novel DNA topoisomerase I inhibitor payload. EGFR and MET are co-expressed in a broad spectrum of tumor types, including EGFRwt and EGFRmut NSCLC, making them excellent targets for bsADC. • The unconjugated DM005 bsAb showed enhanced tumor cell binding and internalization activity in EGFR/MET co-expressing tumor cells. • EGFRxMET bsADCs (DM005 and its prototype DM005-vcMMAE) showed potent and stronger anti-tumor activity in multiple CDX and PDX models than their parental mAb ADCs and benchmark ADCs. • DM005 inhibited both EGFRwt and EGFRmut NSCLC PDX models. • Preclinical development of DM005 is ongoing.