JSKN-003: A Comprehensive Clinical and Scientific Dossier

Executive Summary

JSKN-003 is an investigational, next-generation antibody-drug conjugate (ADC) engineered to target the human epidermal growth factor receptor 2 (HER2). Developed by Alphamab Oncology, it represents a significant evolution in ADC technology, integrating multiple proprietary innovations to enhance efficacy and broaden the therapeutic window.[1] The core structure of JSKN-003 is built upon KN026, a biparatopic antibody that uniquely binds to two distinct epitopes on the HER2 receptor. This antibody is site-specifically conjugated to a potent topoisomerase I inhibitor payload using a proprietary glycan-specific platform, resulting in a highly stable and homogenous therapeutic agent with a powerful bystander effect.[1]

The clinical development program for JSKN-003 has yielded compelling data across multiple heavily pretreated solid tumor indications, most notably in platinum-resistant ovarian cancer (PROC) and HER2-positive breast cancer. In a pooled analysis of patients with PROC, JSKN-003 demonstrated a transformative objective response rate (ORR) of 64.4% and a median progression-free survival (PFS) of 7.1 months, far exceeding historical benchmarks for standard-of-care chemotherapy.[3] A landmark finding from these studies is the drug's profound activity in patients with HER2-negative (immunohistochemistry [IHC] 0) tumors, challenging the conventional biomarker-driven paradigm for HER2-targeted agents and suggesting a potential HER2-agnostic role in this setting.