Foghorn Therapeutics and Lilly will not advance FHD-909 after a Phase 1 review found insufficient clinical efficacy, shifting focus to proprietary programs.
Written By: Saniya Katakdhond, PharmD
Reviewed By: Pharmacally Editorial Team
Foghorn Therapeutics announced on October 1, 2026, that it and Lilly will not advance FHD-909 (LY4050784) into the clinical development expansion phase following a review of clinical data from the Phase 1 dose-escalation trial.
The companies also decided not to advance their selective SMARCA2 degrader program under the collaboration and do not anticipate further collaboration activities. Foghorn will instead prioritize financial and development resources toward its wholly owned portfolio programs.
The decision followed an assessment of the clinical data generated during the Phase 1 program. According to Foghorn, FHD-909 demonstrated selective activity against the SMARCA2 target and maintained a favorable safety profile at exposures exceeding preclinical targets. However, the company said the underlying SMARCA2/4 synthetic-lethality relationship did not translate into the level of clinical efficacy required to support further development.
Foghorn did not disclose numerical efficacy results in its October 1 announcement.
FHD-909 Was Designed to Selectively Target SMARCA2
FHD-909, also known as LY4050784, is a potent, first-in-class, allosteric and orally available small molecule that selectively inhibits the ATPase activity of SMARCA2, also known as BRM, over its closely related paralog SMARCA4, or BRG1.
SMARCA2 and SMARCA4 are catalytic components of the BAF complex, an important regulator of the chromatin regulatory system. FHD-909 was developed to exploit dependencies associated with SMARCA2 and SMARCA4 by selectively inhibiting SMARCA2 while sparing SMARCA4.
Before the October decision, Foghorn had been developing FHD-909 in collaboration with Lilly for cancers carrying SMARCA4 alterations, with non-small cell lung cancer (NSCLC) as a primary target population in the Phase 1 program. The company had reported in March and August 2026 that the trial was progressing through dose escalation.
The October update indicates that the program achieved the intended target selectivity and favorable safety profile, but the biological hypothesis did not generate sufficient clinical efficacy to justify expansion into further clinical development.
Company Redirects Resources to Wholly Owned Programs
Following the FHD-909 decision, Foghorn is prioritizing its financial and development resources toward proprietary programs that the company considers important to its future pipeline.
The programs and platforms specifically highlighted by Foghorn include its selective EP300 degrader program, novel oral immunology and inflammation program, selective CBP degrader program and induced proximity platform. The company’s broader preclinical portfolio also includes a selective ARID1B degrader program and other preclinical candidates.
These programs reflect Foghorn’s continued focus on targeting genetically determined dependencies within the chromatin regulatory system, while expanding its development efforts into immunology and inflammation.
Organizational Changes Include Approximately 40% Workforce Reduction
Foghorn also announced organizational changes intended to align its operating structure with the revised pipeline priorities.
As part of these changes, the company expects to reduce its workforce by approximately 40%. Foghorn said the workforce reduction, pipeline prioritization and operating changes are expected to extend its cash runway into the second half of 2029.
The company has identified its proprietary EP300 and CBP degrader programs, novel oral immunology and inflammation program and induced proximity platform as central areas for continued investment.
Gene Traffic Control Platform Supports Development Strategy
Foghorn Therapeutics is focused on discovering and developing medicines targeting genetically determined dependencies within the chromatin regulatory system.
Its proprietary Gene Traffic Control platform is designed to systematically study, identify and validate potential drug targets within chromatin regulation. The company is developing product candidates in oncology as well as immunology and inflammation.
The discontinuation of further development of FHD-909 therefore marks a shift in near-term resource allocation rather than a change in the company’s broader focus on chromatin biology.
Reference
Foghorn Therapeutics Provides Update on FHD-909 and Strategic Priorities, Foghorn Therapeutics, 01 October 2026
A Study of LY4050784 in Participants with Advanced or Metastatic Solid Tumors, ClinicalTrials.gov ID NCT06561685
About the Writer
Saniya Sanjay Katakdhond (Linkedin) is a Doctor of Pharmacy professional with hands-on experience in patient case review, clinical documentation, medical record analysis, and patient care.
Her hospital experience has strengthened her understanding of clinical conditions, treatment approaches, and multidisciplinary healthcare practices.
With ICH-GCP certification and a research-oriented approach, she brings clinical insight and attention to detail to healthcare content development.
As a healthcare writer, Saniya focuses on translating clinical knowledge and patient-care experience into clear, accurate, and evidence-informed medical content.