Drug intelligence / Profile preview

KHN928

Development stage
Preclinical
Lead developer
Keymed Biosciences
Modality
Bispecific Antibodies → Multispecific Antibodies → Engineered Antibody Formats → Antibody-Based Therapeutics, Nanobodies (VHH) → Antibody Fragments → Engineered Antibody Formats → Antibody-Based Therapeutics, Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics
Administration
Intravenous
01

Overview

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.

Other names
DLL3 x B7-H3 bispecific dual-payload ADCDLL-3 x B7-H3 bispecific dual-payload ADCDLL 3 x B7-H3 bispecific dual-payload ADC
02

Targets

Pol II (RNA polymerase II elongation factors)DLL3 (Delta-like ligand 3)B7-H3TOP1 (DNA Topoisomerase I)

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