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.

Financial Data and Key Metrics Changes - The company reported a strong cash position of $243 million as of December 2024, providing a cash runway into 2027 [42] Business Line Data and Key Metrics Changes - FHD-909 is highlighted as a highly selective oral inhibitor of SMARCA2, with multibillion-dollar potential, particularly targeting SMARCA4 mutated non-small cell lung cancer [5][6] - The collaboration with Eli Lilly, initiated in December 2021, is noted as one of the largest deals for preclinical programs in the industry, with significant upfront payment and downstream participation for the company [7] Market Data and Key Metrics Changes - SMARCA4 mutations are found in approximately 5% of all human cancers, with non-small cell lung cancer showing about 10% prevalence of these mutations [11] - The median overall survival for patients with SMARCA4 mutations in metastatic non-small cell lung cancer is reported at 8 months, compared to 15 months for wild-type counterparts [12] Company Strategy and Development Direction - The company aims to develop FHD-909 as a standard frontline therapy for patients with non-small cell lung cancer harboring SMARCA4 mutations, addressing a significant unmet medical need [28][29] - The strategy includes defining the potential added benefit of FHD-909 in combination with leading therapies such as pembrolizumab and platinum-based combinations [19][20] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of FHD-909 to change the treatment landscape for patients with SMARCA4 mutations, emphasizing the urgent need for novel agents in this area [29] - The company is focused on advancing its proprietary pipeline programs, including selective CBP and EP300 degraders, which are expected to enhance its position in oncology [31][32] Other Important Information - The company is currently enrolling patients in the monotherapy dose-finding portion of the FHD-909 study, with plans for combination studies in anticipation of successful dose escalation [29] - The proprietary pipeline includes three additional programs that are advancing toward the clinic, showcasing the company's commitment to innovative cancer therapies [31] Q&A Session Summary Question: Can you enrich the backfill cohorts for specific characteristics? - Yes, the company can select specific doses and backfill those levels with specific indications and SMARCA4 alterations [45] Question: How will trial progress be communicated? - The company intends to align with Eli Lilly on clinical data disclosure, aiming to communicate results at the end of dose escalation [46] Question: Are SMARCA4 alterations detectable through standard panels? - Yes, SMARCA4 alterations can be detected using conventional FDA-approved NGS panels and immunohistochemistry [61] Question: What is the therapeutic index for FHD-909? - The dosing holidays at the higher dose were due to accumulation in rodents, not a lack of tolerability, indicating a favorable therapeutic window [62] Question: What is the potential for the ARED1B degrader program? - The company is excited about the selective degradation of ARED1B and is waiting for a complete story before disclosing further updates [74] Question: Will there be partnerships for the proprietary pipeline? - The company is not in a rush to partner but anticipates that strategic partnerships will be beneficial as they progress their proprietary pipeline [76]