Foghorn Therapeutics FY Conference Call Summary Company Overview - **Company**: Foghorn Therapeutics (NasdaqGM:FHTX) - **Date of Call**: October 30, 2025 - **Focus**: Updates on proprietary programs including selective ARID1B, CBP, and EP300 degraders [1][2][3] Key Industry Insights - **Chromatin Regulatory System**: Foghorn Therapeutics targets the chromatin regulatory system, which is implicated in cancer, with mutations found in up to 50% of tumors [4][5] - **Market Opportunity**: Successful drugs targeting this biology represent multi-billion-dollar opportunities [5] Core Programs and Developments 1. **FHD-909** - **Description**: First-in-class selective oral small molecule inhibitor of SMARCA2, targeting tumors with SMARCA4 mutations [7] - **Clinical Trial**: Currently enrolling patients in a phase 1 dose escalation trial in the US and Japan, focusing on non-small cell lung cancer patients with SMARCA4 mutations [8] - **Timeline**: Anticipated decision on dose expansion by Lilly in the first half of 2026 [8] 2. **Selective ARID1B Degrader** - **Significance**: First to publicly demonstrate robust degradation of ARID1B, targeting a population with ARID1A mutations found in approximately 5% of solid tumors [9][10] - **Clinical Context**: ARID1A mutations accelerate tumor genesis and promote metastases, indicating a high unmet medical need [17] - **Progress**: Achieved 80% degradation in preclinical models, with in vivo proof of concept expected in 2026 [19][20] 3. **Selective CBP Degrader** - **Target Population**: Potential in EP300 mutated cancers and ER-positive breast cancer, with over 200,000 cases diagnosed annually in the US [24][25] - **Mechanism**: Selective degradation of CBP could provide a wider therapeutic window than dual CBP/EP300 inhibitors, avoiding hematological toxicities [24][27] - **Development Status**: Pre-development candidate CBP degrader (CPPD171) is on track for IND readiness in 2026 [10][28] 4. **Selective EP300 Degrader** - **Target Indications**: Significant potential in hematological malignancies, particularly multiple myeloma, with approximately 100,000 patients in the US potentially benefiting [31][32] - **Clinical Validation**: Previous dual CBP/EP300 inhibitors have shown compelling results in multiple myeloma, supporting the approach [34] - **Development Timeline**: Tracking towards IND-enabling studies in 2026 [38] Additional Insights - **Mechanistic Understanding**: Foghorn emphasizes a biology-first approach, focusing on novel biology and targets, with a deep mechanistic understanding of the chromatin regulatory system [5][6] - **Partnership Strategy**: The company is considering partnerships for larger tumor types, particularly in breast cancer and multiple myeloma, to leverage resources for clinical studies [80][81] - **Feedback from Conferences**: Positive feedback received on the selective degradation of ARID1B, indicating significant interest and curiosity from industry peers [83] Conclusion Foghorn Therapeutics is advancing a robust pipeline of selective degraders targeting critical components of the chromatin regulatory system, with significant potential to address unmet medical needs in various cancers. The company is on track for key milestones in 2026, including IND readiness for multiple programs.

Core Insights - Foghorn Therapeutics Inc. is advancing its Selective ARID1B, Selective CBP, and Selective EP300 degrader programs, showcasing significant progress in addressing challenging cancer targets [1][2] Selective ARID1B Degrader Program - The Selective ARID1B degrader targets a dependency found in up to 5% of solid tumors, including endometrial, gastric, gastroesophageal junction, bladder, and non-small cell lung cancer [3][5] - The program is advancing towards in vivo proof of concept expected in 2026, with recent data presented at the TPD and Induced Proximity Summit [4][5] Selective CBP Degrader Program - The Selective CBP degrader is on track for non-GLP toxicology studies in Q4 2025, with potential applications in EP300-mutant cancers and ER+ breast cancer, aiming for IND readiness in 2026 [5][8] - The program is designed to overcome challenges associated with dual inhibition of CBP and EP300, which have shown dose-limiting toxicities [7][9] Selective EP300 Degrader Program - The Selective EP300 degrader is focused on hematological malignancies such as multiple myeloma and diffuse large b-cell lymphoma, with IND-enabling studies planned for 2026 [9][10] - This program demonstrates encouraging anti-tumor efficacy and favorable tolerability in preclinical studies, differentiating itself from dual CBP/EP300 approaches [5][10] Company Overview - Foghorn Therapeutics is developing a novel class of medicines targeting genetically determined dependencies within the chromatin regulatory system, utilizing its Gene Traffic Control platform [11]

Core Viewpoint - Nurix Therapeutics, Inc. successfully closed an underwritten registered offering of 24,485,799 shares at $10.21 per share, raising gross proceeds of $250 million to fund clinical development and research activities [1][4]. Group 1: Offering Details - The offering included participation from both new and existing investors, highlighting strong support for the company's mission [2]. - J.P. Morgan Securities LLC, Jefferies LLC, and Stifel, Nicolaus & Company acted as joint book-running managers for the offering [3]. - The securities were offered under a shelf registration statement previously filed with the SEC [5]. Group 2: Use of Proceeds - The net proceeds will primarily fund the clinical development of bexobrutideg (NX-5948) for chronic lymphocytic leukemia (CLL) and explore potential autoimmune indications [4]. - Additional funds will support research and development activities to expand the pipeline and cover working capital and general corporate purposes [4]. Group 3: Company Overview - Nurix Therapeutics focuses on targeted protein degradation medicines for oncology and autoimmune diseases, with a pipeline that includes degraders of Bruton's tyrosine kinase (BTK) [8][9]. - The company is advancing multiple potentially first-in-class or best-in-class drug candidates and has collaborations with major pharmaceutical companies like Sanofi and Gilead [8][9].

Core Insights - Nurix Therapeutics, Inc. (NASDAQ:NRIX) is recognized as a small-cap stock with significant upside potential, particularly noted by billionaire Steve Cohen [1] - H.C. Wainwright has lowered its price target for Nurix from $34.00 to $33.00 while maintaining a Buy rating following the company's Q3 2025 earnings report [1][2] - The company reported a net loss of $1.03 per share, which was wider than the expected loss of $0.68, and generated revenue of $7.9 million, significantly below the projected $30 million [1][2] Financial Performance - Operating expenses exceeded expectations, with research and development (R&D) costs amounting to $86.1 million [2] - Despite the earnings miss, Nurix ended the quarter with $428.8 million in cash, which is projected to fund operations into early 2027 [2] Business Overview - Nurix Therapeutics is a biopharmaceutical company focused on discovering and developing targeted protein degradation (TPD) medicines aimed at treating cancer and immune disorders by modulating specific protein levels within cells [3]

Core Insights - Arvinas, Inc. announced preclinical data for ARV-806, a PROTAC KRAS G12D degrader, demonstrating significant tumor growth inhibition in models of pancreatic, colorectal, and lung cancer, highlighting its best-in-class potential for KRAS G12D mutated cancers [1][2][5] Group 1: Drug Development and Efficacy - ARV-806 showed robust and durable KRAS G12D degradation, leading to significant tumor growth inhibition in various cancer models [1] - The drug targets both ON and OFF forms of KRAS G12D, which is the most common mutation of the KRAS protein, addressing high unmet needs in solid tumors [1][5] - In vitro studies indicated that ARV-806 degraded KRAS G12D with picomolar potency across multiple cancer cell lines without affecting wild-type and other mutant RAS isoforms [6] - Following a single intravenous dose, ARV-806 achieved over 90% degradation of KRAS G12D for seven days, with sustained effects on c-MYC suppression and BIM induction for at least five days [6] Group 2: Clinical Trials and Future Potential - Arvinas is currently evaluating ARV-806 in a Phase 1 clinical trial for patients with KRAS G12D–mutated advanced solid tumors [3] - The data suggest that ARV-806's sustained pharmacodynamic activity supports intermittent clinical dosing, indicating a potential for effective treatment regimens [3][8] - The drug demonstrated over 25-fold greater potency in reducing cancer cell proliferation and over 40-fold higher potency in degrading KRAS G12D protein compared to other clinical-stage G12D degraders [6] Group 3: Company Overview - Arvinas is a clinical-stage biotechnology company focused on developing protein degradation therapies through its PROTAC platform, targeting various diseases including cancers with KRAS mutations [7] - The company is advancing multiple investigational drugs, including ARV-806 for KRAS G12D, vepdegestrant for ER+/HER2- breast cancer, and ARV-393 for non-Hodgkin lymphoma [7]

Bexobrutideg Investor Update Investor Presentation October 2025 Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company's own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any infor ...

Core Viewpoint - Nurix Therapeutics, Inc. has announced the pricing of its underwritten registered offering of 24,485,799 shares at $10.21 per share, aiming to raise approximately $250 million for clinical development and research activities [1][4]. Group 1: Offering Details - The offering consists of 24,485,799 shares priced at $10.21 each, with expected gross proceeds of $250 million before expenses [1]. - The offering is set to close on or about October 23, 2025, pending customary closing conditions [1]. - Participation in the offering includes both new and existing investors such as General Atlantic and Redmile Group [2]. Group 2: Use of Proceeds - Nurix intends to use the net proceeds primarily for clinical development of drug candidates, including bexobrutideg (NX-5948) for chronic lymphocytic leukemia (CLL) and potential autoimmune indications [4]. - Additional uses include funding research and development to expand the pipeline, as well as for working capital and general corporate purposes [4]. Group 3: Management and Registration - J.P. Morgan Securities LLC, Jefferies LLC, and Stifel, Nicolaus & Company are acting as joint book-running managers for the offering [3]. - The offering is made under a shelf registration statement previously filed with the SEC, which was declared effective on June 11, 2024 [5].

Core Insights - Nurix Therapeutics has initiated the DAYBreak clinical trial for bexobrutideg, a pivotal Phase 2 study targeting relapsed or refractory chronic lymphocytic leukemia (r/r CLL) [1][4] - The 600 mg once-daily dose of bexobrutideg has been cleared by global regulators, including the FDA and EMA, following data analysis from a Phase 1b study [2][4] - The company plans to conduct a Phase 3 confirmatory trial in the first half of 2026, comparing bexobrutideg to other treatment options for r/r CLL patients [5][6] Company Developments - Nurix is transitioning to a pivotal-stage company with the initiation of the DAYBreak study, marking a significant milestone for bexobrutideg [4] - The DAYBreak study will enroll patients who have progressed after treatment with various BTK inhibitors, aiming to address unmet medical needs [4][6] - The company has generated substantial data supporting bexobrutideg's potential as a best-in-class BTK degrader [7][8] Clinical Trial Details - The DAYBreak trial is a single-arm Phase 2 study evaluating the efficacy of bexobrutideg in patients with r/r CLL [1][4] - A randomized Phase 3 trial is planned to compare bexobrutideg monotherapy against other treatment regimens in patients whose disease has progressed on prior therapies [5][6] - The favorable safety profile of the 600 mg dose is expected to optimize therapeutic effects for patients [6] Investor Engagement - Nurix will host an investor webcast to provide updates on the program and discuss new preclinical data supporting bexobrutideg [3][9] - The webcast will include highlights of unpublished data demonstrating superior degradation potency and selectivity of bexobrutideg [8][10]

Core Insights - NX-1607 is a first-in-class oral inhibitor of CBL-B, demonstrating on-target peripheral immune activation and anti-tumor activity in heavily pretreated patients with advanced solid tumors [1][2][4] - The clinical data presented at ESMO 2025 supports the initiation of expansion cohorts for further evaluation of NX-1607 as a monotherapy or in combination therapies [1][2] Company Overview - Nurix Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on targeted protein degradation medicines, aiming to improve treatment options for cancer and inflammatory diseases [7] - The company is advancing multiple clinical and preclinical programs, including NX-1607 and bexobrutideg, an oral BTK degrader [7] Clinical Data Summary - In a Phase 1a study, 82 patients with various solid tumors were treated with NX-1607 across different dosing regimens, showing a disease control rate (DCR) of 49.3% [2][3] - Notable clinical activity included reductions in tumor-specific biomarkers, long-term stable disease, and a confirmed partial response in a patient with micro-satellite stable colorectal cancer [2][3] - The most significant reductions in prostate-specific antigen (PSA) were observed in patients receiving BID dosing, with 6 out of 13 patients achieving PSA reductions of ≥50% [2] Safety Profile - NX-1607 exhibited a tolerable safety profile, comparable to approved immuno-oncology agents, with most adverse events being Grade 2 or less [3] - Immune-related adverse events were observed in 6 patients, indicating on-target immune activation similar to PD-1/PD-L1 therapies [3] Future Development - The company plans to further explore the therapeutic potential of NX-1607, particularly in indications where current immunotherapies have shown limited efficacy, such as MSS colorectal cancer and metastatic prostate cancer [4]

Core Insights - NX-1607 is a first-in-class oral inhibitor of CBL-B, demonstrating on-target peripheral immune activation and anti-tumor activity in heavily pretreated patients with advanced solid tumors [1][2][4] - The clinical data presented at ESMO 2025 supports the initiation of expansion cohorts for further evaluation of NX-1607 as a monotherapy or in combination therapies [1][2] Company Overview - Nurix Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on targeted protein degradation medicines, aiming to improve treatment options for cancer and inflammatory diseases [7] - The company is advancing multiple clinical and preclinical programs, including NX-1607 and bexobrutideg, an oral BTK degrader [7] Clinical Data Summary - In a Phase 1a study, 82 patients with various solid tumors were treated with NX-1607 across different dosing regimens, showing dose-dependent exposure and clinical activity [2][3] - The disease control rate (DCR) was reported at 49.3%, with notable reductions in tumor-specific biomarkers such as PSA and CEA [2][3] - The treatment was well-tolerated, with most adverse events being Grade 2 or less, and immune-related adverse events indicating on-target immune activation [3][4] Therapeutic Potential - NX-1607 targets a previously unaddressed pathway in immune regulation, affecting multiple immune cell types, which may enhance its efficacy in treating solid tumors [2][6] - The results are particularly promising for tumor types like micro-satellite stable colorectal cancer and metastatic prostate cancer, where current immunotherapies have shown limited efficacy [4]