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KHN928 is a novel bispecific, dual-payload antibody-drug conjugate (ADC) designed for the treatment of neuroendocrine cancers, particularly small cell lung cancer (SCLC). Developed by Keymed Biosciences, the molecule simultaneously targets Delta-like ligand 3 (DLL3) and B7-homologue 3 (B7-H3). It is engineered with a DLL3-targeting nanobody and a humanized B7-H3 antibody, site-specifically conjugated to two distinct cytotoxic payloads: exatecan (a topoisomerase I inhibitor) and triptolide (an RNA polymerase II inhibitor). This dual-targeting strategy is intended to enhance tumor selectivity and binding avidity, while the dual-payload mechanism concurrently induces DNA double-strand breaks and disrupts RNA synthesis. Preclinical studies have demonstrated that KHN928 exhibits potent antitumor activity across multiple SCLC cell lines and patient-derived xenograft (PDX) models, including those resistant to monospecific ADCs, with a favorable safety profile in non-human primates.
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