CBPd-171 / Foghorn Therap - LARVOL DELTA

Foghorn is advancing a Selective CBP degrader, on track to be Investigational New Drug (IND)-ready in 2026. Key updates include: (Foghorn Press Release) - "Highly potent and selective lead candidate CBPd-171 advancing to dose range finding toxicology studies in Q4 2025; Anti-tumor activity in EP300-mutant solid tumors and in CBP-dependent cancers, including promising potential in ER+ breast cancer; No significant impact on platelet counts and megakaryocytes spared with CBPd-171 dosing"

New trial • Preclinical • Estrogen Receptor Positive Breast Cancer

Program Overview and Upcoming Milestones (GlobeNewswire) - "Continued progress on Selective EP300 degrader and Selective ARID1B degrader, with program updates expected in Q4 2025...Selective CBP degrader program....On track for IND-enabling studies, targeting an IND in 2026."

IND • Preclinical • Diffuse Large B Cell Lymphoma • Estrogen Receptor Positive Breast Cancer • Hematological Malignancies • Multiple Myeloma • Solid Tumor

Foghorn Therapeutics Provides First Quarter 2025 Financial and Corporate Update (GlobeNewswire) - "Selective CBP degrader on track for IND-enabling studies, targeting IND in 2026; Continued progress on Selective EP300 degrader and Selective ARID1B degrader with program updates expected in H2 2025."

IND • Preclinical • Oncology

Establishing rational combination strategies with selective CBP degraders in solid tumor indications (AACR 2025) - "Through a large-scale in vitro combination screen, we show that CBP degrader treatment synergizes with multiple standard-of-care chemotherapies, including paclitaxel, as well as targeted agents, including CDK4/6 inhibitors. Furthermore, by genome-wide CRISPR knockout screening across four cell line models of different solid tumor types, we establish genetic determinants of resistance and sensitivity to CBP degradation in an EP300-mutant background, providing further mechanistic insight into combination therapy approaches. Collectively, we have defined cellular processes that present therapeutic vulnerabilities that can be leveraged for rational combination strategies with selective CBP degraders in solid tumor indications."

Oncology • Solid Tumor • CREBBP • EP300

Poster Presentation Title: Establishing Rational Combination Strategies with Selective CBP Degraders in Solid Tumor Indications (GlobeNewswire) - "Foghorn Therapeutics...announced new preclinical data for potential first-in-class medicines...at the 2025 American Association for Cancer Research (AACR) Annual Meeting....Synergistic combination activity demonstrated, including with paclitaxel and CDK4/6 inhibitor abemaciclib in ER+ breast cancer. Findings support combination opportunities for selective CBP degraders in solid tumors beyond EP300-mutant cancers."

Preclinical • Solid Tumor

Foghorn Therapeutics to Host Virtual Investor Event to Review Pipeline Updates in Conjunction with 2025 AACR Annual Meeting (GlobeNewswire) - "Company to share new preclinical combination data for FHD-909 (LY4050784), a potential first-in-class selective SMARCA2 inhibitor, with non-small cell lung cancer (NSCLC) as the primary target population; Additional updates include new preclinical data for Selective CBP degrader program in combination with chemotherapy and targeted agents and for Selective EP300 degrader program in hematological malignancies."

Preclinical • Non Small Cell Lung Cancer

Foghorn Therapeutics Announces New Preclinical Data for Selective SMARCA2 Inhibitor FHD-909 and Selective CBP and EP300 Degrader Programs at 2025 AACR Meeting (GlobeNewswire) - "Poster presentations on the Phase 1 trial design for FHD-909 and on preclinical data for the Selective CBP program and the Selective EP300 degrader program will also be presented."

Clinical protocol • Preclinical • Hematological Malignancies • Solid Tumor

Foghorn Therapeutics Provides Financial Update for 2024 and 2025 Strategic Outlook (GlobeNewswire) - "Ongoing first-in-human Phase 1a/b open-label, multicenter trial design for FHD-909 will be presented at the AACR Annual Meeting (April 25-30, 2025)...In 2025, preclinical data for the Selective CBP degrader program, in combination with approved chemotherapeutics and targeted agents, will be presented at the AACR Annual Meeting (April 25-30, 2025)...In 2025, preclinical data for the Selective EP300 degrader program demonstrating biological activity in hematological malignancies will be presented at the AACR Annual Meeting (April 25-30, 2025)."

P1 data • Preclinical • Bladder Cancer • Endometrial Cancer • Gastric Cancer • Hematological Malignancies • Prostate Cancer • Solid Tumor

Foghorn Therapeutics Highlights Program Progress and Strategic Objectives for 2025 (GlobeNewswire) - "Selective CBP degrader program: Identified potent and selective CBP protein degraders. Pharmacodynamic and pharmacokinetic preclinical data demonstrate: Deep and sustained CBP degradation significantly inhibited tumor growth in mouse xenograft solid tumor models; Robust monotherapy preclinical anti-tumor activity that was not associated with significant body weight loss, thrombocytopenia or anemia; Long-acting injection formulation that resulted in tumor regression from a single dose in a mouse xenograft efficacy study."

Preclinical • Bladder Cancer • Endometrial Cancer • Gastric Cancer • Oncology • Solid Tumor

Foghorn Therapeutics Provides Third Quarter 2024 Financial and Corporate Update (GlobeNewswire) - "Program Overview and Upcoming Milestones: (i) FHD-286:...AML Phase 1 trial:...Topline safety, tolerability, initial efficacy, and PK/PD data expected by year-end 2024....(ii) Selective CBP degrader program:...Investigational New Drug (IND)-enabling studies are on track to initiate by the fourth quarter of 2024."

P1 data • Preclinical • Acute Myelogenous Leukemia • Solid Tumor

Foghorn Therapeutics Provides Second Quarter 2024 Financial and Corporate Update (GlobeNewswire) - "FHD-909: Dosing of the first patient in the Phase 1 trial for FHD-909 is planned to begin in the second half of 2024; Selective CBP degrader program: IND-enabling studies on track to initiate by the fourth quarter of 2024."

Preclinical • Trial status • Non Small Cell Lung Cancer • Oncology

Identification of selective CBP degraders with robust preclinical PK, PD, efficacy and safety across solid tumor indications (AACR 2024) - "This anti-tumor activity was not associated with significant body weight loss or hematopoietic toxicity. Our CBP-selective protein degraders have the potential to be a first-in-class therapeutic option for patients with tumors harboring EP300 mutations."

Preclinical • Oncology • Solid Tumor • CREBBP • EP300

Foghorn Therapeutics Presents New Preclinical Data on Potential First-in-Class BRM Selective Inhibitor FHD-909 and Selective CBP and Selective EP300 Degrader Oncology Programs (GlobeNewswire) - "Poster 6067 / 26: Identification of selective CBP degraders with robust preclinical PK, PD, efficacy, and safety across solid tumor indications - Preclinical pharmacodynamic and pharmacokinetic data presented at AACR support the identification of potent and selective CBP degraders with anti-tumor activity across various EP300 mutant cell lines from multiple indications: Deep and sustained CBP degradation leading to significant tumor growth inhibition in mouse xenograft solid tumor models....Long-acting CBP-selective protein degrader formulations with first-in-class potential for patients with tumors harboring EP300 mutations."

Preclinical • Solid Tumor

Foghorn Therapeutics Provides Financial Update for 2023 and 2024 Strategic Outlook (GlobeNewswire) - "Foghorn is presenting new preclinical data for its CBP and EP300 selective degrader programs at the 2024 AACR Annual Meeting...CBP selective degraders have shown significant tumor growth inhibition in a colorectal cancer in vivo model. Antiproliferative effects were also observed for numerous cancer cell lines, including colorectal, gastric and bladder cancers; EP300 selective degraders have shown potent cellular antiproliferation and in vivo tumor growth inhibition in an AR+ enzalutamide prostate in vivo model."

Preclinical • Colorectal Cancer • Prostate Cancer • Solid Tumor

Foghorn Therapeutics to Present New Preclinical Data at 2024 AACR Annual Meeting, Reflecting Advances with Multiple Potential First-in-Class Medicines, including the Selective Inhibitor of BRM, FHD-909 (GlobeNewswire) - "Poster presentation of FHD-909, a first-in-class oral BRM selective inhibitor, highlighting preclinical efficacy and safety in multiple mouse models of NSCLC....IND filing planned in Q2 2024; Oral presentation demonstrating preclinical efficacy and tolerability data for Selective CBP and Selective EP300 degraders; Significant anti-tumor activity observed, with no thrombocytopenia as historically observed with dual CBP/EP300 inhibitors; Additional poster presentation demonstrating long-acting degrader capabilities confirming up to once-a-month dosing for protein degrader programs."

IND • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Foghorn Therapeutics Highlights Clinical Program Updates and Research Progress and Provides Strategic Objectives for 2024 (GlobeNewswire) - "Selective EP300 and Selective CBP programs: At preclinical efficacious doses, neither the EP300 nor the CBP selective degraders caused thrombocytopenia, a commonly observed safety liability for dual CBP/EP300 inhibitors. Additional preclinical data will be presented in the first half of 2024."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Foghorn Therapeutics to Present at Upcoming Conferences Including New Preclinical Data from EP300 and CBP Selective Degrader Programs (GlobeNewswire) - "Foghorn® Therapeutics Inc...today announced that the Company will present new data from multiple preclinical and clinical programs at the 6th Annual Targeted Protein Degradation (TPD) Summit and the Connective Tissue Oncology Society (CTOS) Annual Meeting....Foghorn will participate in multiple sessions, including a keynote presentation by Steve Bellon, Foghorn’s Chief Scientific Officer, where data from its selective EP300 and CBP degrader programs will be presented."

Clinical data • Preclinical • Oncology

Discovery and characterization of potent, selective CBP degraders (AACR 2023) - "Due to the high homology between CBP and p300, identification of selective chemical matter that specifically and directly targets CBP has proven challenging. Here, we describe a potent, highly selective CBP heterobifunctional degrader with selective biological activity in CBP dependent cancer lines."

Oncology • CREBBP

Selective CBP degradation shows superior potency and differentiated biological activity compared to small molecule inhibitors (AACR 2023) - "Small molecule inhibitors (SMIs) targeting the HAT or bromodomain of CBP/p300 have been developed, however these agents are not selective for either paralog and inhibit both proteins equally, potentially limiting their clinical application. Herein, we describe the biological activity of selective, potent CBP degraders and show differentiation from SMIs."

Oncology • CREBBP