Foghorn Therapeutics (FHTX) AACR Annual Meeting 2025 summary

Key program updates and scientific insights

• FHD909, a highly selective oral SMARCA2 inhibitor, demonstrated significant anti-tumor activity and tumor regression in SMARCA4-mutated cancer models, especially NSCLC, as monotherapy and in combination with chemotherapies, KRAS inhibitors, and pembrolizumab.

• Combination studies revealed synergy between FHD909 and KRAS inhibitors in lung, pancreas, and colon cancer models, and profound tumor regression when combined with pembrolizumab in humanized NSCLC models.

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

• The ongoing Phase 1 clinical trial, in collaboration with Lilly, is enrolling patients with SMARCA4-altered solid tumors, with expansion cohorts focusing on NSCLC and other advanced tumors.

• Patient selection for trials uses NGS panels and immunohistochemistry for SMARCA4 loss, with backfill cohorts to enrich for specific mutations.

Pipeline and strategic development

• Advanced programs include selective degraders for CBP, EP300, and ARID1B, all targeting chromatin regulatory dependencies in cancer, with promising preclinical data and an ARID1B update expected in 2025.

• CBP degrader shows high selectivity and efficacy in lung, bladder, and gastric cancer models, with long-acting injectable formulations enabling flexible dosing.

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

• Achieved selective degradation of ARID1B, addressing unmet needs in ARID1A-mutant cancers; further updates expected later this year.

• Strategic partnerships, notably with Lilly, include $300M upfront, $80M in equity, a 50/50 US economic split, tiered ex-US royalties, and up to $1.3B in milestones, underpinning continued R&D and future collaborations.

Financial and operational outlook

• Well-capitalized with $243 million in cash as of December 2024, providing runway into 2027.

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

• Positioned to deliver significant value with differentiated, high-impact medicines in 2025 and beyond.