Foghorn Therapeutics (Nasdaq: FHTX) and Lilly have decided not to advance FHD-909 (LY4050784), a selective SMARCA2 ATPase inhibitor, into the clinical development expansion phase following a review of Phase I dose-escalation data. The two firms will also not advance Foghorn's selective SMARCA2 degrader program, with no further collaboration anticipated. Consequently, Foghorn said it is reducing its workforce by approximately 40% and realigning its operating structure as part of a pipeline prioritization.
Foghorn describes FHD-909 as a potent, allosteric, orally available small molecule whose therapeutic rationale rests on SMARCA2/SMARCA4 synthetic lethality. CEO Adrian Gottschalk said the drug was selective, demonstrated a favorable safety profile, and reached exposures above preclinical targets, but that "the biology of the SMARCA2/4 synthetic lethality relationship has not translated into the level of efficacy required to further advance the program."
The collaboration originated in December 2021, when Loxo Oncology at Lilly and Foghorn announced a partnership using Foghorn's Gene Traffic Control chromatin-biology platform. The deal included USD 300 million upfront, an USD 80 million equity investment, and up to USD 1.3 billion in milestones tied to three additional discovery programs. Foghorn retained a 50/50 US economic split on the SMARCA2 program and one other undisclosed target.