Foghorn Therapeutics is cutting 40% of its workforce after its long-running partnership with Eli Lilly came to an end following less-than-stellar Phase 1 results for their lead oncology program.
Lilly began working with the Massachusetts-based biotech in 2021, providing $300 million in upfront funding and purchasing $80 million worth of equity. The collaboration covered Foghorn’s BRM-selective program, an additional undisclosed cancer target and three discovery-stage programs.
The partnership ultimately gave birth to FHD-909, also known as LY4050784, a SMARCA2 inhibitor engineered to selectively block the ATPase activity of BRM. The drug entered a Phase 1 study in 2024 involving patients with non-small cell lung cancer carrying SMARCA4, or BRG1, mutations.
After reviewing results from the dose-escalation portion of the Phase 1 trial, the companies decided not to take FHD-909 into further development. Their relationship is also ending entirely, with the partners discontinuing development of a SMARCA2 degrader program and another undisclosed oncology target.
Foghorn CEO Adrian Gottschalk said the company was disappointed by the clinical outcome but noted that the collaboration had successfully produced a molecule that selectively engaged SMARCA2 while maintaining a favorable safety profile at drug exposures above the levels predicted during preclinical testing.
He explained that the expected synthetic-lethal interaction between SMARCA2 and SMARCA4 did not produce the degree of antitumor activity needed to justify continuing the program.
SMARCA4 mutations are associated with more aggressive cancers and occur in approximately 10% of non-small cell lung cancers and around 5% of cancers overall. Other developers have also encountered challenges with SMARCA2. Prelude Therapeutics, for example, suspended development of its SMARCA2 degraders several months after one of its candidates produced disappointing results in a Phase 1 study.
Following the termination of the Lilly partnership, Foghorn said its restructuring would eliminate 40% of its workforce and reshape operations around its remaining programs. The company expects the changes to leave it with enough cash to fund its priority pipeline through the second half of 2029.
The restructuring is expected to leave Foghorn with 65 full-time employees, down from the 106 people employed at the beginning of the year. The biotech reported nearly $168 million in cash as of the end of June.
Foghorn will now concentrate on its preclinical pipeline, including a selective EP300 degrader program targeting hematologic cancers and prostate cancer. Earlier preclinical findings had suggested potential activity in multiple myeloma, and the company has been targeting next year for regulatory clearance to begin a Phase 1 study.
The same general timeline applies to Foghorn’s oral small-molecule program in immunology and inflammation, which the company also hopes to move into clinical development.
Another program is focused on CBP, an acetyltransferase closely related to EP300. Cancers associated with EP300 mutations can include colorectal, bladder, ovarian, cervical and endometrial tumors.
Foghorn has previously reported that its lead CBP degrader, CBPd-171, demonstrated strong therapeutic potential in estrogen receptor-positive breast cancer, providing another potential avenue for the company as it redirects resources toward its internally controlled pipeline.
Foghorn Therapeutics is reducing its workforce by approximately 40% after ending a major cancer drug collaboration with Eli Lilly following disappointing early clinical results. The restructuring is part of a broader effort to conserve cash and concentrate resources on the company’s proprietary pipeline.
Foghorn and Lilly End Cancer Development Programs
The decision follows a review of Phase 1 dose-escalation data for FHD-909, also known as LY4050784. Foghorn and Lilly decided not to move the program into its clinical development expansion phase. The companies also decided not to advance a selective SMARCA2 degrader program and said they do not anticipate additional collaboration activities.
The collaboration originally began in 2021 and was designed to develop oncology medicines using Foghorn’s Gene Traffic Control platform. The agreement included $300 million in upfront cash and an $80 million equity investment from Lilly.
