FHD-909 Discontinued: Foghorn and Lilly End SMARCA2 Program

FHD-909 discontinued: Foghorn Therapeutics and Eli Lilly have decided not to advance FHD-909 (LY4050784), an experimental oral SMARCA2 inhibitor for SMARCA4-mutated cancers, after reviewing Phase 1 dose-escalation data, Foghorn said on October 1, 2026. The companies will also not advance their selective SMARCA2 degrader program, and Foghorn is cutting about 40% of its workforce.

Foghorn said FHD-909 selectively hit its target with a favorable safety profile, but the SMARCA2/SMARCA4 synthetic-lethality strategy did not deliver enough clinical efficacy to justify further development. Foghorn shares fell about 49% to $1.84, Parameter reported.

Key Takeaways: FHD-909 Discontinued

• Foghorn and Lilly will not move FHD-909 from Phase 1 dose escalation into the expansion phase, and they will not advance the selective SMARCA2 degrader program.
• Foghorn said the drug engaged SMARCA2 selectively with a favorable safety profile, but the biology did not translate into the efficacy needed to continue.
• Foghorn is reducing its workforce by about 40%, with the cuts expected to be substantially complete in the fourth quarter of 2026.
• The company says the restructuring extends its cash runway into the second half of 2029.
• No response-rate data were included in the announcement, and no further collaboration activity with Lilly is expected.

What Is FHD-909?

FHD-909 (LY4050784) is a first-in-class, allosteric, orally available small molecule that selectively inhibits the ATPase activity of SMARCA2, also called BRM, over its close relative SMARCA4, also called BRG1. Both proteins are catalytic engines of the BAF chromatin-remodeling complex. The idea behind it is synthetic lethality: tumors that have lost SMARCA4 may depend on SMARCA2, so blocking SMARCA2 could kill those cancer cells while sparing healthy ones.

Why Foghorn and Lilly Stopped the FHD-909 Program

In its announcement, Foghorn said the Phase 1 data showed the drug hit SMARCA2 selectively at exposures that exceeded its preclinical targets, with a favorable safety profile. Chief Executive Adrian Gottschalk said the company was disappointed because the SMARCA2/SMARCA4 synthetic-lethality biology had not translated into the level of efficacy required to advance the program.

According to a Foghorn filing with the SEC, the companies made the decision on September 25, 2026 after reviewing the data, and Foghorn’s board approved the restructuring on September 30. The first-in-human trial enrolled patients with SMARCA4-mutated cancers, with non-small cell lung cancer (NSCLC) as the primary target population. Combination studies with pembrolizumab had been planned only if dose escalation succeeded, so those plans fall away.

FHD-909 Timeline

Foghorn’s Restructuring and Cash Runway

Foghorn said it will reduce its workforce by approximately 40% and align its operating structure to focus on proprietary programs. In its filing, the company listed a selective EP300 degrader, an immunology and inflammation asset, a selective CBP degrader, its induced proximity platform and other proprietary programs as priorities. It said the changes should fund those programs into the second half of 2029, compared with the first half of 2028 it had guided to earlier this year, according to its January update.

The setback follows an earlier one. AllSci reported that Foghorn discontinued its wholly owned clinical-stage asset FHD-286 in late 2024 after it failed in a leukemia trial, leaving FHD-909 as the primary clinical program. Foghorn had also retained a 50/50 U.S. economic split with Lilly on the SMARCA2 program and one other undisclosed target.

What the FHD-909 Setback Means for SMARCA2 Synthetic Lethality

SMARCA4 is mutated in up to about 10% of NSCLC and in up to 5% of solid tumors, according to Foghorn’s investor materials, so the target population is meaningful and outcomes in SMARCA4-mutated lung cancer are poor. That is why the result matters beyond one company.

In our assessment, this is a significant setback for the SMARCA2 selective-inhibitor approach, because a drug that engaged its target safely at planned exposures still did not produce enough benefit. The decision to drop the degrader program as well suggests the companies did not see a path forward with that modality either. The announcement did not publish response data, so it is not yet clear how deep or how common the responses were, and other molecules or combinations were not addressed.

What the Decision Means for Patients and Trial Participants

FHD-909 was never available outside clinical trials. People with SMARCA4-mutated cancers who are interested in clinical research can discuss options with their oncologist or search ClinicalTrials.gov, and anyone currently enrolled in the FHD-909 study should follow the guidance of their study team. For related coverage of drug development and regulation, read our reports on the FDA’s expedited IND pilot, Pharming’s positive Phase II leniolisib results and the FDA approval of Mirum’s Atebrioz, or browse our pharmaceutical news.

Frequently Asked Questions About FHD-909

Why was FHD-909 discontinued?

Foghorn and Lilly reviewed Phase 1 dose-escalation data and concluded that the SMARCA2/SMARCA4 synthetic-lethality approach did not translate into the efficacy needed to advance FHD-909, even though the drug hit its target selectively with a favorable safety profile.

What is FHD-909 (LY4050784)?

It is an oral, allosteric, first-in-class SMARCA2 inhibitor that was being tested in patients with SMARCA4-mutated cancers, mainly non-small cell lung cancer.

How many jobs is Foghorn cutting?

Foghorn is reducing its workforce by approximately 40%, with the reduction expected to be substantially complete in the fourth quarter of 2026.

What will Foghorn focus on now?

Foghorn says it will prioritize its selective EP300 degrader, an immunology and inflammation program, a selective CBP degrader, its induced proximity platform and other proprietary programs, with cash expected to last into the second half of 2029.

Does this end the Lilly collaboration?

The companies said they do not anticipate further collaboration activities after deciding not to advance FHD-909 or the selective SMARCA2 degrader program.

How we reported this: this article is based on Foghorn’s announcement and SEC filings, plus trade coverage linked above. Foghorn has not published the Phase 1 efficacy data. Last updated October 2, 2026. It is for information only and is not medical or investment advice.