Foghorn Therapeutics Doses First Patient with Oral SMARCA2 Inhibitor FHD-909 in Phase 1 Trial for SMARCA4 Mutated Tumors

Foghorn Therapeutics Inc., a clinical-stage biotechnology firm, announced the commencement of dosing the initial patient in their Phase 1 trial of FHD-909 (LY4050784). This trial targets individuals with SMARCA4 (BRG1) mutated cancers, specifically non-small cell lung cancer (NSCLC). FHD-909 is a pioneering oral and highly potent compound that shows exceptional selectivity for SMARCA2 (BRM) over SMARCA4, which is a closely related protein.

Adrian Gottschalk, President and CEO of Foghorn, emphasized the significance of this milestone, highlighting that FHD-909 is the first SMARCA2 selective inhibitor to enter the clinical phase. He pointed out that dosing the first patient signifies an important step forward for the program and their ongoing partnership with Lilly. Gottschalk explained that FHD-909's high selectivity for SMARCA2 over SMARCA4 provides a promising synthetic lethality strategy, particularly for prevalent SMARCA4 mutations and their sensitivity to SMARCA2 inhibition in NSCLC and other solid tumors. He expressed optimism about the continued progress of FHD-909 in collaboration with Lilly.

The Phase 1 trial is open-label and multicenter, designed to evaluate the safety, tolerability, and initial efficacy of FHD-909 in patients with locally advanced or metastatic solid tumors that possess a SMARCA4 alteration. Preclinical studies have shown that FHD-909 is a potent and selective SMARCA2 inhibitor with strong anti-tumor activity as a monotherapy. In vivo studies have demonstrated that FHD-909 has favorable tolerability and dose-dependent modulation of SMARCA2 target genes, as well as significant tumor growth inhibition and regression in SMARCA2 mutant xenograft mouse models.

Back in December 2021, Foghorn announced a strategic collaboration with Lilly to develop novel oncology medicines. This collaboration includes an agreement for the co-development and co-commercialization of Foghorn’s Selective SMARCA2 oncology program in the U.S., as well as an additional undisclosed oncology target. The partnership also involves three discovery programs utilizing Foghorn’s proprietary Gene Traffic Control® platform.

FHD-909 is a potent, first-in-class, allosteric, and orally available small molecule that selectively inhibits the ATPase activity of SMARCA2 (BRM) over SMARCA4 (BRG1). These proteins are the catalytic engines across all forms of the BAF complex, a crucial regulator of the chromatin regulatory system. Preclinical studies indicate that tumors with SMARCA4 mutations depend on SMARCA2 for BAF function, and FHD-909 has demonstrated significant anti-tumor activity across multiple SMARCA4 mutant lung tumor models.

Foghorn Therapeutics is focused on discovering and developing a novel class of medicines that target genetically determined dependencies within the chromatin regulatory system. Utilizing its scalable Gene Traffic Control® platform, Foghorn is systematically studying, identifying, and validating potential drug targets within this system. The company is in the process of developing multiple product candidates in the field of oncology.