SEZ6 and B7H3 have emerged as promising therapeutic targets for ADCs in SCLC. We developed a bsADC targeting SEZ6 and B7H3, derived generated from RenLite. The bsAb exhibited high affinity for both human and monkey antigens and effectively bound to various SCLC cell lines, demonstrating enhanced internalization compared to the parental mAbs. In proof-of-concept studies, the bsADC also showed significant efficacy in SEZ6-negative and SEZ6-low PDX models. These findings suggest that the bsADC has the potential to extend patient benefits. Further studies utilizing a TOPO1i linker-payload are currently underway.