Resistance to ADC Enhertu (DS-8201) therapy presents a significant clinical challenge for patients with HER2-positive cancers. To address this unmet need, we have developed a novel dual-payload ADC (CAN016), conjugating both MMAE and exatecan to a HER2 antibody, based on our proprietary StarLinkerTM multi-payload technology. This dual payload ADC has demonstrated great in vitro and in vivo efficacy against Enhertu-resistant cell lines, including Enhertu resistant CDX and PDX tumor models. Furthermore, CAN016 has exhibited excellent DMPK and safety profiles in non-human primates with a high HNSTD in the GLP tox study. The CMC manufacturing process has been successfully established and validated. CAN016 is at a stage of IND filling (US & China).