TAK-164

TAK-164 is a second-generation antibody–drug conjugate (ADC) designed for the treatment of gastrointestinal cancers expressing guanylyl cyclase C (GCC). It consists of a fully human immunoglobulin G1 (IgG1) monoclonal antibody that specifically targets the extracellular domain of GCC, which is highly expressed in various gastrointestinal malignancies, including colorectal, stomach, pancreatic, and esophageal cancers. The antibody is conjugated via a peptide linker to a novel DNA alkylating agent from the mono-indolinobenzodiazepine pseudodimer (IGN) class. Upon binding to GCC-expressing tumor cells, TAK-164 is internalized and releases its cytotoxic payload intracellularly, leading to DNA damage and cell death. Preclinical studies demonstrated selective binding and cytotoxicity in GCC-positive cells as well as antitumor activity in xenograft models. Clinical development included phase I trials evaluating safety and pharmacokinetics; however, further development was discontinued due to insufficient clinical benefit at recommended dosing[1][2][4][5][6].