CGT4859

CGT4859 is a reversible, selective small molecule inhibitor targeting fibroblast growth factor receptor 2 (FGFR2) and fibroblast growth factor receptor 3 (FGFR3). It is being developed by Cogent Biosciences for the treatment of cholangiocarcinoma and other advanced solid tumors harboring FGFR2 and/or FGFR3 genetic alterations. The drug demonstrates high selectivity for FGFR2 over FGFR1, aiming to avoid the dose-limiting toxicities associated with pan-FGFR inhibitors, such as hyperphosphatemia. Preclinical studies show that CGT4859 has low nanomolar potency against wild-type and mutant forms of FGFR2, retains activity across resistance mutations including C491S, exhibits favorable pharmacokinetics with high oral bioavailability, and induces dose-responsive tumor regression in animal models. Clinical development is ongoing in phase 1/2 trials for patients with intrahepatic cholangiocarcinoma or other advanced solid tumors with relevant genetic alterations[1][5][6][7].