10P DS-6000a, a novel CDH6-targeting antibody-drug conjugate with a novel DNA topoisomerase I inhibitor DXd, demonstrates potent antitumor activity in preclinical models

Abstract

Human Cadherin 6 (CDH6) is a single transmembrane protein consisting of 790 amino acids classified into the type 2 cadherin family. Human CDH6 is specifically expressed in the brain and kidneys during the development phase and has been reported to systemically decrease CDH6 expression in the adult body. CDH6 expression is increased specifically in renal cell carcinoma (RCC) and ovarian cancer (OVC). Therefore, CDH6 could be an attractive target for cancer therapy. We created DS-6000a, a CDH6-targeting antibody-drug conjugate (ADC) using an enzymatically cleavable tetrapeptide-based linker, and a high drug-to-antibody ratio (DAR 7 to 8) with a novel DNA topoisomerase I inhibitor (DXd).