Foghorn Therapeutics Inc. and Eli Lilly and Company decided not to advance Fhd-909 (Ly4050784) into the clinical development expansion phase, following a review of data from the drug's Phase I dose escalation trial.

As part of the decision, the companies will also discontinue the broader selective SMARCA2 degrader program under their collaboration, with both companies not anticipating further joint activities moving forward.¹

"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. Unfortunately, the biology of the SMARCA2/4 synthetic lethality relationship has not translated into the level of efficacy required to further advance the program," said Adrian Gottschalk, president and chief executive officer of Foghorn Therapeutics.

The decision closes out a multi-year partnership between Foghorn and Lilly's Loxo Oncology research and development group, and also triggers a significant restructuring at Foghorn.^1, The company is reducing its workforce by approximately 40% and further aligning its operating structure, a move it says will fund its priority pipeline programs into the second half of 2029.²

Foghorn and Lilly's decision to stop Fhd-909 before it reached the expansion phase reflects a broader shift in how the industry is managing pipeline risk. In a discussion with Pharmaceutical Executive, Dan Chancellor, vice president of thought leadership at Norstella, touched on how companies are increasingly choosing to cut weak programs at the earliest possible stage rather than carrying them into costlier late-stage trials.

"Trials aren't failing more often overall, they're failing earlier," Chancellor said. "38% of all disclosed failures now happen in Phase I, up from 32% in 2020, while failures at the approval stage have dropped to under 1%.”

What is Fhd-909?

Fhd-909 is a potent, first-in-class, allosteric and orally available small molecule that selectively inhibits the ATPase activity of SMARCA2 (BRM) over its closely related paralog SMARCA4 (BRG1).¹ The two proteins are the catalytic engines across all forms of the BAF complex, one of the key regulators of the chromatin regulatory system, the biological rationale that originally drew Foghorn and Lilly into the program.¹

What is Foghorn doing with its pipeline now?

"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. Today, we are committed to focusing our financial and developmental resources to advance these programs toward the clinic," Gottschalk said.

With the workforce reduction and operating realignment, Foghorn is directing its cash toward four proprietary programs, its EP300 degrader program, a novel oral immunology and inflammation program, a CBP degrader program, and its induced proximity platform.¹ The company says the resulting cash position is expected to fund these priority programs into the second half of 2029.¹

Gottschalk also thanked Foghorn's former partner for its role in the now-closed collaboration. "I would like to thank our partner Lilly for their support, as well as the patients, caregivers, investigators, study site staff, and all others who participated in and contributed to the Fhd-909 clinical trial," he said.

What was the original Lilly collaboration built on?

Loxo Oncology at Lilly and Foghorn entered their strategic collaboration in 2021 to create novel oncology medicines by applying Foghorn's proprietary Gene Traffic Control platform.³ The agreement included a co-development and co-commercialization deal covering Foghorn's selective BRM oncology program, the effort that produced Fhd-909, along with an additional undisclosed oncology target, plus three further discovery programs built on the Gene Traffic Control platform.³

Under the original terms, Foghorn received upfront consideration of $300 million in cash along with an $80 million equity investment from Lilly in Foghorn common shares at $20 per share. Foghorn led discovery and early research on the BRM-selective and undisclosed target programs, while Lilly led development and commercialization, with the two companies splitting U.S. economics 50/50 and Foghorn eligible for royalties on ex-U.S. sales starting in the low double digits and escalating into the twenties based on revenue levels.³

Sources

1. Foghorn Therapeutics Provides Update on FHD-909 and Strategic Priorities Foghorn October 1, 2026, https://www.globenewswire.com/news-release/2026/10/01/3372741/0/en/foghorn-therapeutics-provides-update-on-fhd-909-and-strategic-priorities.html
2. Foghorn to cut 40% of workforce after scrapping Lilly-partnered cancer drug Reuters October 1, 2026, https://www.reuters.com/legal/litigation/foghorn-cut-40-workforce-after-scrapping-lilly-partnered-cancer-drug-2026-10-01/
3. Lilly and Foghorn Announce Strategic Collaboration for Novel Oncology Targets Using Foghorn's Proprietary Gene Traffic Control® Platform Eli Lilly and Company December 13, 2021, https://investor.lilly.com/news-releases/news-release-details/lilly-and-foghorn-announce-strategic-collaboration-novel