Summary of Foghorn Therapeutics Conference Call Company Overview - **Company**: Foghorn Therapeutics (NasdaqGM:FHTX) - **Industry**: Clinical-stage oncology focused on chromatin biology - **Key Focus**: Regulating gene expression through drug discovery targeting previously undrugged proteins [3][4] Core Programs and Partnerships - **Main Compound**: Partnership with Eli Lilly focusing on SMARCA2, established with a deal worth approximately $300 million upfront and $80 million in equity [4][9] - **Current Status**: In a 50/50 cost-sharing phase for the SMARCA2 program, with a decision on dose expansion expected in the first half of 2026 [9][13] - **Other Proprietary Programs**: Targets include CBP, EP300, and ARID, with ongoing development towards IND submissions over the next 12-18 months [4][10] Drug Discovery and Development - **Unique Platform**: Foghorn has developed a platform to study large protein assemblies, enabling selective drugging of challenging targets like SMARCA2 and SMARCA4 [6][8] - **Challenges**: Historically, finding selective drugs for SMARCA2 and SMARCA4 has been difficult due to their high similarity (90% identical) [8][10] - **Efficacy Benchmarks**: For SMARCA4 mutant non-small cell lung cancer, the response rate is significantly lower (20%) compared to wild-type patients (40+%) [15][16] Clinical Insights - **Current Trials**: The SMARCA2 inhibitor (FHD-909) is in a phase one dose escalation study targeting patients with SMARCA4 mutations [12][13] - **Expected Outcomes**: Aiming for a response rate of at least 15% in the fourth-line setting, with plans to move into frontline settings based on preclinical data [17][20] Competitive Landscape - **Resistance Mechanisms**: No known resistance mechanisms for SMARCA2 inhibitors or degraders have been identified yet [21] - **Screening Process**: SMARCA4 mutations are routinely screened in major cancer centers, facilitating patient enrollment in clinical trials [23] Future Directions - **Combination Therapies**: Plans to explore combinations with pembrolizumab and chemotherapy for enhanced efficacy in SMARCA4 mutant patients [24][25] - **Pipeline Development**: Focus on multiple myeloma for EP300 degraders, with IND-enabling studies expected by late 2026 [29][30] Financial Position - **Cash Reserves**: As of Q3, Foghorn has $180 million, projected to last into early 2028, covering ongoing programs and potential future financing needs [39] Strategic Partnerships - **Partnership Philosophy**: Foghorn is open to partnerships for proprietary programs, emphasizing the need for strategic capabilities that small biotechs may lack [36][37] Conclusion - **Outlook**: Foghorn Therapeutics is positioned for significant developments in oncology, particularly with its innovative approach to chromatin biology and strategic partnerships, while maintaining a solid financial foundation for future growth [39][40]

Summary of Foghorn Therapeutics (FHTX) Conference Call Company Overview - **Company**: Foghorn Therapeutics (FHTX) - **Event**: Jefferies Global Healthcare Conference - **Date**: June 05, 2025 Industry Focus - **Industry**: Biotechnology, specifically targeting chromatin regulatory systems and cancer therapies Key Points and Arguments Chromatin Regulatory System and BAF Complex - Foghorn Therapeutics focuses on the chromatin regulatory system, which is crucial for gene expression, likening it to an architect (regulatory system) and blueprints (genes) [3][4] - Approximately **20% of all cancers** have mutations in the BAF complex, and about **50% of cancers** relate to chromatin biology [4] Clinical Pipeline - The company is currently in clinical stages with a **Phase 1 trial** for a selective SMARCA2 inhibitor (FHD-909) in collaboration with Eli Lilly [6] - The next **12 to 18 months** are expected to be significant for the company with potential data releases [6][7] Challenges in Drug Development - Developing drugs targeting the chromatin system is challenging due to the complexity of proteins and their paralogs, which often share high sequence similarity [10][11] - Issues include purification difficulties and the intrinsic disorder of some proteins, making it hard to find selective chemical matter [12] Patient Enrollment and Selection Criteria - The Phase 1 trial includes patients with various tumor types, specifically those with **SMARCA4 mutations** [15] - Approximately **10% of non-small cell lung cancer (NSCLC)** patients have SMARCA4 mutations, with **60-70%** of those being loss-of-function mutations [19][20] Efficacy Expectations - The company aims for a response rate of **10-20%** in refractory patients, which would be considered promising compared to existing treatments [25][26] - Patients with SMARCA4 mutations have a worse prognosis and lower response rates to existing therapies [20][21][22] Combination Therapy Potential - There is interest in exploring combination therapies with KRAS inhibitors and immune checkpoint inhibitors, pending monotherapy efficacy results [39][40] - The timeline for potential combination studies is expected around **2026**, depending on the results of the ongoing trials [41] CBP and EP300 Programs - Foghorn is developing selective degraders for CBP and EP300, with potential applications in various cancers, including gastric and bladder cancers [44][48] - The CBP program is set to begin IND-enabling studies in the second half of 2025, with EP300 following closely behind [47][48] Upcoming Milestones - Key milestones include updates on the FHD-909 program, CBP, and EP300, with potential IND submissions in the next year [54][58] - The company anticipates significant data releases in the **October timeframe** related to ongoing studies [57] Additional Important Information - The company emphasizes the importance of a homogeneous patient population for clinical trials to avoid confusion in data interpretation [31] - Foghorn aims to avoid interim data releases to provide clearer insights into trial outcomes [32] - The therapeutic window for their compounds appears promising based on preclinical data, suggesting better tolerability compared to previous dual inhibitors [35][36] This summary encapsulates the critical insights from the conference call, highlighting the company's strategic focus, clinical developments, and future expectations in the biotechnology sector.