Foghorn Therapeutics (FHTX) Jefferies Global Healthcare Conference 2025 summary

Platform and scientific focus

• Focused on the chromatin regulatory system, particularly the BAF complex, which is implicated in about 20% of all cancers and up to 50% when including related proteins.

• Developed a platform with advanced biochemical, biophysical, and functional assays, enabling the study of difficult protein targets with high selectivity.

• Emphasizes novel targets over commonly pursued ones, with clinical-stage programs targeting SMARCA2, CBP, EP300, and ARID1B.

Pipeline progress and clinical development

• Phase 1 trial for selective SMARCA2 inhibitor (FHD-909) is underway in collaboration with Eli Lilly, enrolling patients with SMARCA4 mutations across multiple tumor types.

• Dose escalation includes all histologies with SMARCA4 mutations; backfill cohorts will focus on non-small cell lung cancer (NSCLC) with loss-of-function mutations.

• Approximately 10% of NSCLC patients have SMARCA4 mutations, with 60-70% of those being loss-of-function; these patients have poorer prognosis, especially with concomitant KRAS mutations.

• Efficacy bar for refractory patients is set at a 10-20%+ response rate with duration past two to three months.

Key challenges and learnings

• Major challenge is achieving selectivity due to high similarity between protein paralogs (e.g., SMARCA2/4, CBP/EP300).

• Protein production and biochemistry expertise are critical for screening and developing selective chemical matter.

• Sustained target coverage is essential for efficacy, whether using inhibitors or degraders.

• Toxicity profile for selective SMARCA2 inhibition appears manageable, with a wider therapeutic window than dual inhibition.