Foghorn Therapeutics (FHTX) AACR Annual Meeting 2025 summary

FHD909 program and clinical progress

• FHD909 is a highly selective oral SMARCA2 inhibitor targeting SMARCA4-mutated cancers, with strong preclinical anti-tumor activity and tumor regressions in multiple models, especially NSCLC, and demonstrates synergy in combination with chemotherapy, KRAS inhibitors, and pembrolizumab.

• Phase 1 clinical trial is ongoing with dose escalation and expansion in advanced solid tumors harboring SMARCA4 alterations, focusing on NSCLC, in collaboration with Lilly.

• Patient selection uses both NGS panels and immunohistochemistry for SMARCA4 loss; backfill cohorts can be enriched for specific mutations.

• Communication of clinical progress will align with partner Lilly, with major updates expected at the end of dose escalation or upon key study transitions.

• FHD909 demonstrates high selectivity for SMARCA2 over SMARCA4, with strong in vivo efficacy and tolerability in preclinical models.

Pipeline programs and preclinical data

• Advancing selective CBP, EP300, and ARID1B degrader programs, each targeting synthetic-lethal relationships in chromatin regulation, with promising preclinical data and a program update for ARID1B expected in 2025.

• CBP degrader shows strong single-agent and combination activity in lung, bladder, gastric, and ER-positive breast cancer models, with long-acting injectable formulations and no platelet toxicity.

• EP300 degrader demonstrates complete tumor regression in multiple myeloma models and spares platelets compared to dual inhibitors.

• ARID1B degrader program has achieved selective degradation, targeting cancers with ARID1A mutations; further updates expected later this year.

• Foghorn's platform targets chromatin regulatory system genes, implicated across a wide range of cancers, using proprietary assays to engineer highly selective compounds.

Strategic partnerships and financial outlook

• Collaboration with Lilly on FHD909 is one of the largest preclinical deals in the industry, including $300M upfront, $80M in equity, a 50/50 US economic split, tiered ex-US royalties, and up to $1.3B in milestones for additional programs.

• Additional strategic partnerships for pipeline assets are anticipated over the next 6–24 months, but no immediate plans to partner CBP, EP300, or ARID1B programs.

• Cash position of $243 million as of December 2024 provides runway into 2027, supporting continued pipeline advancement and value creation.

• Significant financial and strategic support from Lilly underpins continued R&D and potential future collaborations.

• The company is leveraging its Gene Traffic Control Platform to develop additional candidates and expand target populations.