FHD-909

FHD-909 is a first-in-class, orally available small molecule that acts as a highly potent and selective allosteric inhibitor of SMARCA2 (also known as BRM), with high selectivity over its closely related paralog SMARCA4 (BRG1). Both SMARCA2 and SMARCA4 are catalytic subunits of the BAF chromatin remodeling complex, which regulates gene expression. In cancers with mutations in SMARCA4—such as certain non-small cell lung cancers—tumor cells become dependent on SMARCA2 for survival. By selectively inhibiting the ATPase activity of SMARCA2, FHD-909 exploits this synthetic lethality to induce tumor cell death while sparing normal cells. Preclinical studies have shown robust anti-tumor activity in models of BRG1/SMARCA4-mutant lung cancer. The drug is being developed through a collaboration between Foghorn Therapeutics and Eli Lilly[1][2][3][5][6][7].