Camibirstat

Foghorn Therapeutics is laying off 40% of its workforce after a long-running collaboration with Eli Lilly collapsed over disappointing phase 1 data. The Indianapolis Big Pharma first tapped up Foghorn back in 2021, handing $300 million in upfront cash and making an $80 million equity investment in the Massachusetts biotech to work together on Foghorn's BRM-selective program, as well as another undisclosed cancer target and three discovery programs. The collaboration eventually produced FHD-909, also known as LY4050784, a SMARCA2 inhibitor designed to selectively inhibit the ATPase activity of BRM. FHD-909 entered a phase 1 trial in 2024 for patients with non-small cell lung cancer featuring SMARCA4 (BRG1) mutations. But the partners revealed this morning that they had decided not to advance FHD-909 any further after reviewing data from the dose-escalation cohort of the phase 1 study. In fact, the companies are parting ways for good, abandoning work on a SMARCA2 degrader program as well as an additional undisclosed oncology target they had been working on. “While we are disappointed with the clinical results, we and Lilly developed a drug in FHD-909 that selectively hits the SMARCA2 target with a favorable safety profile at exposures that exceeded our preclinical targets,” Foghorn CEO Adrian Gottschalk explained in an Oct. 1 release. “Unfortunately, the biology of the SMARCA2/4 synthetic lethality relationship has not translated into the level of efficacy required to further advance the program,” Gottschalk added. The SMARCA4 mutation is linked to more aggressive forms of cancer and is found in 10% of all non-small cell lung cancers and 5% of all cancers in general. Lilly and Foghorn aren’t the only companies that have struggled with this target—Prelude Therapeutics paused work on its SMARCA2 degraders months after one candidate underperformed in a phase 1 trial. As Foghorn digested the end of the Lilly partnership, the biotech said it was laying off 40% of its workforce, while “further aligning its operating structure resulting in cash to fund Foghorn’s priority programs into the second half of 2029.” The company expects to be left with 65 full-time employees following the restructuring, compared to the 106 staffers with whom it entered the year . As of June, the biotech still had $167.6 million in the bank. The company will now focus on its preclinical pipeline, including a selective EP300 degrader program being developed for hematological malignancies and prostate cancer. Foghorn had previously pointed to preclinical data that suggested the program’s potential to treat multiple myeloma and had been hoping to secure permission next year to take the therapy into phase 1. That’s the same timeframe that the company has said it's hoping to advance its oral small molecule in the immunology and inflammation space. There’s also a program aimed at degrading CBP, an acetyltransferase closely related to EP300. EP300-mutated cancers can include endometrial, cervical, ovarian, bladder, and colorectal cancer, and Foghorn has previously said that its lead asset from this CBP program, dubbed CBPd-171, had shown “strong therapeutic potential” in ER+ breast cancer. However, Foghorn recently had to push back the development timeline for CBPd-171 due to “an unexpected operational issue at a third-party contract research organization supporting the in vivo animal models.” “We built Foghorn based on a demonstrated capability in designing drugs for challenging molecular targets, and we have leveraged this capability to build a proprietary pipeline,” Gottschalk said in this morning's release. “Today, we are committed to focusing our financial and developmental resources to advance these programs toward the clinic.” It’s not the first time Foghorn has pivoted its pipeline. In late 2024, the biotech abandoned work on FHD-286, an enzymatic inhibitor of BRG1 and BRM, which was the company’s only solely owned clinical-stage candidate. Foghorn made the call after the troubled cancer drug came up short in a phase 1 study in patients with acute myeloid leukemia.