BMS-986405

BMS-986405 (also known as JSMD194) is an investigational small molecule gamma-secretase inhibitor (GSI) developed by Bristol Myers Squibb (formerly Celgene) for the treatment of relapsed or refractory multiple myeloma. In the context of myeloma therapy, BMS-986405 is primarily used as an adjunct to BCMA-targeted therapies, such as the CAR-T cell therapy idecabtagene vicleucel (ide-cel). Gamma-secretase is an enzyme complex responsible for the proteolytic cleavage and "shedding" of B-cell maturation antigen (BCMA) from the surface of plasma cells into the systemic circulation as soluble BCMA (sBCMA). By inhibiting this process, BMS-986405 increases the density of BCMA on the surface of malignant plasma cells and reduces the levels of sBCMA, which can otherwise act as a decoy receptor and impede the efficacy of BCMA-directed treatments. BMS-986405 is currently being evaluated in clinical trials, such as the Phase 1/2 KarMMa-7 study, to determine its safety and ability to enhance the clinical activity of ide-cel.

Other names

JSMD194JSMD-194JSMD 194gamma-secretase inhibitor BMS-986405