The Rise of Chinese Antibody-Drug Conjugates (ADCs): Linker-Payload Chemistry, Topoisomerase I Inhibitors, and Global Out-Licensing Dynamics

• Chinese ADC developers have secured over $35 billion in out-licensing deals since 2023, with DualityBio, Kelun-Biotech, and MediLink leading in deal value. • Topoisomerase I inhibitor payloads (exatecan derivatives) with DAR 8 and hydrophilic linkers achieve superior bystander killing and reduced aggregation, as demonstrated by DS-8201a's success. • Hydrophilic cleavable linkers (valine-citrulline, GGFG) show >90% stability in human plasma, minimizing premature payload release and off-target toxicity. • Clinical benchmarks: Trastuzumab deruxtecan (Enhertu) shows ORR 79.7% in HER2-mutant NSCLC; Chinese ADCs like RC48 and SHR-A1811 are closing the gap with comparable efficacy in earlier lines. • Interstitial lung disease (ILD) remains a key safety concern, with incidence rates of 10-15% for DXd-based ADCs, necessitating rigorous monitoring protocols.