Foghorn Therapeutics (FHTX) Guggenheim Securities 2nd Annual Healthcare Innovation Conference summary

Scientific rationale and target selection

• Chromatin regulation is implicated in about 50% of cancers, making it a significant therapeutic target.

• Selectivity is challenging due to high similarity among protein paralogs in chromatin complexes.

• SMARCA2 and SMARCA4 are highly similar enzymes; targeting SMARCA2 exploits a synthetic-lethal relationship in cancers with SMARCA4 loss.

• Preclinical models show that selective inhibition of SMARCA2 can kill tumors with SMARCA4 loss.

• SMARCA4 mutations are associated with poor prognosis in non-small cell lung cancer, highlighting unmet need.

Clinical development and program updates

• The SMARCA2 inhibitor FHD-909 is in phase 1, enrolling patients with SMARCA4 mutations or deletions across multiple countries.

• Dose escalation is ongoing, with no maximum tolerated dose reached; expansion decision expected in first half of 2026.

• Enrollment has been robust, with no issues in patient recruitment.

• Adverse events to monitor include fatigue and muscle weakness, based on prior dual SMARCA2/4 program experience.

• Monotherapy efficacy is expected, but combination regimens are planned for future development.

Pipeline and commercial opportunities

• CBP and EP300 are advanced in-house programs, with selective degraders developed to minimize myelosuppressive effects.

• CBP targets cancers with EP300 mutations and ER-positive breast cancer, representing 20,000–25,000 US patients.

• EP300 shows promise in hematological malignancies like multiple myeloma and diffuse large B-cell lymphoma.

• Selective degraders are expected to improve tolerability and enable combination therapies.

• ARID1B is a novel, intractable target; selective binders and degraders have been developed, with in vivo proof of concept targeted for 2026.