Summary of Foghorn Therapeutics FY Conference Call Company Overview - Foghorn Therapeutics is a clinical stage biotech company focused on precision oncology, particularly in chromatin regulation, which is relevant to approximately 50% of cancers [2][3] Core Programs and Partnerships - The company is developing various programs, including classical enzymatic inhibitors and protein degradation approaches [2] - The 909 study, in partnership with Eli Lilly, targets the SMARC-II program and is expected to make a decision on expansion in the first half of next year [3][4] Data Disclosure and Development Plans - Foghorn plans to disclose material data regarding the 909 program, especially if Lilly decides to proceed with expansion [4][5] - The intent is to move quickly into front-line settings, particularly in combination with pembrolizumab and chemotherapy for metastatic non-small cell lung cancer [5][6] Competitive Landscape - Prelude's recent decision to halt their SMARC-II program is not seen as a negative indicator for Foghorn's target, as Foghorn believes their approach has better target coverage [6][9] - Foghorn emphasizes the importance of achieving high levels of target inhibition (IC90 or DC90) for effective treatment responses [7][10] Clinical Trial Progress - Enrollment in the 909 study has been strong, with 15 sites in the U.S. and additional sites opening in Japan and Europe [11][12] - The company is now backfilling cohorts with patients who have specific SMARCA4 mutations, focusing on those with significant loss of function [12][16] Patient Characteristics and Market Opportunity - The target patient population includes third and fourth-line non-small cell lung cancer patients, who have poor prognosis and limited treatment options [17][18] - Foghorn aims to demonstrate better response rates and overall survival compared to existing treatments, with a focus on achieving a duration of response of four months or more [18][21] Future Directions and Pipeline - Foghorn is also developing programs targeting ARID1B and CBP EP300, with plans for in vivo proof of concept and IND submissions in the coming year [25][26][27] - The company is optimistic about its unique approach to targeting these areas, which have not been extensively explored in the clinical setting [26][27] Conclusion - Foghorn Therapeutics is positioned to make significant advancements in the oncology space, particularly with its 909 program in collaboration with Eli Lilly, and has a promising pipeline of additional therapeutic targets [28]

Summary of Foghorn Therapeutics FY Conference Call Company Overview - **Company**: Foghorn Therapeutics (NasdaqGM:FHTX) - **Focus**: Targeting the chromatin regulatory system and the BAF complex, primarily in oncology [2][3] Industry Insights - **Oncology Relevance**: Approximately 50% of cancers have dependencies or mutations related to chromatin regulation, highlighting the importance of this area in cancer biology [2] - **Targeting Challenges**: The similarity between proteins in the BAF complex (e.g., SMARCA2 and SMARCA4) complicates selective targeting due to their 90%-95% similarity [3][4] Key Programs and Developments SMARCA2 Program - **Scientific Rationale**: SMARCA2 is targeted due to its synthetic-lethal relationship with SMARCA4, where loss of SMARCA4 increases dependency on SMARCA2 in cancer cells [6][7] - **Clinical Data**: Patients with SMARCA4 mutations show significantly worse prognosis in non-small cell lung cancer, with response rates dropping from approximately 40% to 20% [7] - **Market Opportunity**: In the U.S., about 22,000 non-small cell lung cancer patients have SMARCA4 mutations, with an estimated 11,000-17,000 potentially having loss of function [8] Clinical Trials - **Current Status**: The SMARCA2 inhibitor FHD-909 is in phase one trials, with ongoing dose escalation and no maximum tolerated dose reached yet [16][17] - **Study Design**: The trial includes various cancer histologies with a focus on non-small cell lung cancer patients with SMARCA4 mutations [15] - **Expected Outcomes**: Anticipation of a go/no-go decision for dose expansion in the first half of 2026 [16] CBP and EP300 Programs - **Mechanism**: CBP and EP300 are sister proteins involved in histone acetylation, with challenges in dual inhibition leading to myelosuppressive effects [21][22] - **Commercial Opportunity**: Targeting CBP could address approximately 20,000-25,000 patients with specific mutations, while EP300 shows potential in hematological malignancies [23][24] ARID1B Program - **Target Validation**: ARID1B is a highly mutated target in cancer, with Foghorn being the only company to develop selective binders for this target [27][28] - **Development Status**: The program is in hit-to-lead stage, with in vivo proof of concept expected in 2026 [29] Additional Insights - **Combination Studies**: The company recognizes the importance of combination therapies in oncology and plans to explore both monotherapy and combination regimens in future studies [18][19] - **Clinical Risks**: Acknowledgment of the risks associated with being first to market, particularly in the context of the SMARCA2 program [9][10] Conclusion Foghorn Therapeutics is positioned in a promising niche within oncology, focusing on challenging targets related to chromatin regulation. The company is advancing several innovative programs, particularly in SMARCA2, CBP, and EP300, with significant market opportunities and ongoing clinical trials that could lead to impactful treatments for cancer patients.

Core Insights - Foghorn Therapeutics is advancing its clinical programs, particularly FHD-909, a first-in-class oral SMARCA2 selective inhibitor, in a Phase 1 trial targeting SMARCA4-mutated cancers, primarily non-small cell lung cancer (NSCLC) [1][2][3] - The company is developing several selective degrader programs, including Selective CBP, EP300, and ARID1B degraders, with promising preclinical data indicating robust anti-tumor activity and favorable tolerability [2][6][7][8] - Foghorn has a strong financial position with $180.3 million in cash and equivalents as of September 30, 2025, providing a cash runway into 2028 [1][19] FHD-909 Program - FHD-909 is designed to selectively inhibit SMARCA2, showing significant anti-tumor activity in preclinical models of SMARCA4-mutant lung tumors [3][14] - The ongoing Phase 1 trial is progressing well, with enrollment on track and preclinical data supporting its combination with standard therapies [4][2] Selective Degrader Programs - The Selective CBP degrader is entering non-GLP toxicology studies with potential applications in EP300-mutant cancers and ER+ breast cancer, aiming for IND readiness in 2026 [1][12] - The Selective EP300 degrader is showing broad efficacy across hematological malignancies, with IND-enabling studies expected in 2026 [1][7][12] - The Selective ARID1B degrader is advancing towards in vivo proof of concept in 2026, targeting ARID1A-mutated cancers, which represent up to 5% of solid tumors [1][8][13] Financial Performance - Collaboration revenue increased to $8.2 million for Q3 2025, up from $7.8 million in Q3 2024, driven by advancements in programs under the Lilly collaboration [19] - Research and development expenses decreased to $20.0 million in Q3 2025 from $24.7 million in Q3 2024, attributed to reduced costs in various areas [19] - The net loss for Q3 2025 was $15.8 million, an improvement from a net loss of $19.1 million in the same quarter of the previous year [19][22] Leadership Update - The Chief Financial Officer, Kristian Humer, will be leaving the company, with a search for a successor already underway [10]