SMP-656: A self-catalyzed ring-opening hydrolysis linker-based ADC with enhanced stability and antitumor efficacy. (PubMed, Eur J Med Chem) - Oct 3, 2026 - "Incorporation of SuperHydra into the HER2-targeting ADC SMP-656, comprising the antibody Inetetamab and the microtubule inhibitor Eribulin, resulted in markedly enhanced plasma stability while preserving HER2 binding, internalization, Fc-mediated effector function, and bystander killing. SMP-656 exhibited potent antigen-dependent cytotoxicity, retained activity in DS-8201a-resistant tumor models, and achieved durable antitumor efficacy in multiple HER2-positive xenograft models. In cynomolgus monkeys, SMP-656 demonstrated favorable pharmacokinetic properties and an acceptable safety profile. Collectively, these findings establish SMP-656 as a promising HER2-targeting ADC, support its ongoing clinical evaluation in HER2-expressing solid tumors, and highlight the potential of the SuperHydra linker as a versatile platform for improving the stability and overall performance of maleimide-based ADCs."
Journal • Oncology • Solid Tumor • HER-2
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Chaoyang Feng; Chenglong Wu; Ding Luo; Jiahao Geng; Jinkun Huang; Shouping Wang; Tingting Yang; Xiaojie Heng; Xiaoli Li
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