Foghorn Therapeutics (FHTX) Jefferies London Healthcare Conference 2024 summary

Strategic focus and scientific platform

• Focuses on chromatin regulatory system as a novel area for cancer therapeutics, targeting chromatin remodeling complexes and transcription factors.

• Developed a platform integrating biology, advanced assays, and chemistry to drug difficult protein targets, including SMARCA2, CBP, EP300, and ARID1B.

• Achieved external validation through a $380 million deal with Lilly for five targets, including a selective SMARCA2 program.

• Pipeline includes about 10 programs, with several in clinical or preclinical stages and data readouts expected within 12-18 months.

• Prioritizes targets with significant patient populations and commercial potential.

SMARCA2/4 programs and clinical development

• SMARCA2/4 dual inhibitor (FHD-286) is in clinical development for AML in combination with decitabine, with top-line data expected before year-end.

• Selective SMARCA2 inhibitor (909) in collaboration with Lilly began dosing in a Phase I trial, enrolling patients with SMARCA4 mutations across tumor types.

• Phase I design includes dose escalation with plans for expansion cohorts in non-small cell lung cancer and other relevant tumors.

• SMARCA2 degrader program is advancing serially behind the inhibitor, with clinical entry anticipated in the coming years.

• Both inhibitor and degrader offer potential for sequencing or combination to address resistance, with selectivity and tolerability profiles under evaluation.

Market landscape, indications, and combination strategies

• SMARCA4 mutations occur in about 5% of solid tumors, with non-small cell lung cancer being a primary focus due to high prevalence.

• Other relevant tumor types include cutaneous melanoma, esophageal cancer, and cancers of unknown origin.

• SMARCA4 mutation screening is established at major centers and is associated with poor response to immune checkpoint inhibitors.

• Combination strategies under consideration include pairing with PD-1 inhibitors, chemotherapy, and agents targeting KRAS.

• Recent competitor data validate the SMARCA2 target, showing partial responses in difficult-to-treat cancers.