FHD-909 / Foghorn Therap, Eli Lilly - LARVOL DELTA

A first-in-human phase 1 study of LY4050784, an oral, potent, and selective SMARCA2 inhibitor, in patients with advanced solid tumors with SMARCA4 alterations (Trial in Progress) (AACR 2025) - P1 | "4Lee JY, et al. Poster presented at AACR 2024."

Clinical • First-in-human • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • SMARCA2 • SMARCA4

Program Overview and Upcoming Milestones (Investing News Network (INN)) - "Phase 1 trial on track. Enrollment in the first-in-human Phase 1 multi-center trial of FHD-909 is progressing well. The trial in patients with NSCLC as the primary target population is on track...Pending successful Phase 1 dose escalation results, Foghorn and Lilly anticipate evaluating FHD-909 in combination studies in NSCLC with pembrolizumab....The collaboration, the research term of which will expire in December 2026, also includes three discovery programs from Foghorn's proprietary Gene Traffic Control platform."

First-in-human • Licensing / partnership • New P1 trial • Trial status • Non Small Cell Lung Cancer

J5M-OX-JOXA: A Study of LY4050784 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=340 | Recruiting | Sponsor: Eli Lilly and Company | N=160 ➔ 340 | Trial completion date: Oct 2027 ➔ May 2028

Enrollment change • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Phase 1 trial on track. (The Manila Times) - "Enrollment in the first-in-human Phase 1 multi-center trial of FHD-909 is progressing well."

Enrollment status • Non Small Cell Lung Cancer

LY4050784, a selective inhibitor of SMARCA2, demonstrates synergistic activity in combinations with pembrolizumab or KRAS inhibitors (AACR 2025) - P1 | "LY4050784 demonstrated robust activity in vitro and in vivo when combined with standard lung cancer chemotherapies (paclitaxel, cisplatin, and pemetrexed)...Finally, we explored the activity of LY4050784 in combination with both mutant-selective KRAS G12C and G12D inhibitors (olomorasib and LY3962673, respectively) and the isoform-selective pan-KRAS inhibitor LY4066434...These results demonstrate that LY4050784 exhibits robust antitumor activity in combination with chemotherapy, pembrolizumab, and multiple KRAS inhibitors in preclinical models of SMARCA4-mutant cancers. Investigation of these combinations clinically is warranted"

IO biomarker • Colon Cancer • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • SMARCA2 • SMARCA4

Title: Leveraging paralog relationships for targeting chromatin modulators in cancer: ARID1B and SMARCA2 (FHD-909) (GlobeNewswire) - "Foghorn Therapeutics presents new preclinical data...at the 2026 AACR Annual Meeting....Complete regression in pre-clinical syngeneic efficacy models of FHD-909 in combination with an anti-PD1 antibody, with tumors failing to regrow after dosing halted. Tumor rejection upon rechallenge, where attempts to implant fresh tumor on the opposite flank of previously treated animals with FHD-909 plus an anti-PD1 antibody were not successful, suggesting an immune memory effect....Robust degradation achieved with cereblon-based selective ARID1B degraders with potential for oral bioavailability."

Preclinical • Solid Tumor

Foghorn Therapeutics to Present New Preclinical Data for Selective SMARCA2 Inhibitor FHD-909 and Selective CBP, EP300 and ARID1B Degrader Programs at the 2026 AACR Annual Meeting (GlobeNewswire) - "Poster presentations will also highlight additional preclinical data characterizing our wholly owned Selective CBP, Selective EP300, and Selective ARID1B degrader programs."

Preclinical • Diffuse Large B Cell Lymphoma • Estrogen Receptor Positive Breast Cancer • Follicular Lymphoma • Multiple Myeloma • Non Small Cell Lung Cancer

Program Overview and Upcoming Milestones: FHD-909 (LY4050784) (GlobeNewswire) - "(i) Phase 1 trial on track: Enrollment in the first-in-human Phase 1 multi-center trial of FHD-909 is progressing well...; (ii) Preclinical data support enhanced anti-tumor activity of FHD-909 in combination with standard-of-care (SoC) chemotherapies, anti-PD-1 pembrolizumab and several novel KRAS inhibitors in NSCLC animal models. Pending successful Phase 1 dose escalation results, Foghorn and Lilly anticipate evaluating FHD-909 in combination studies in the front-line setting of NSCLC."

Enrollment status • Preclinical • Non Small Cell Lung Cancer

J5M-OX-JOXA: A Study of LY4050784 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrialsregister.eu) - P1 | N=112 | Recruiting | Sponsor: Eli Lilly & Co.

New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Jefferies initiates Foghorn Therapeutics stock with buy rating (Investing.com) - "Jefferies initiated coverage on Foghorn Therapeutics Inc...with a Buy rating and set a price target of $12.00, down from $14.00....The firm expects the company’s key 2026 catalyst to arrive mid-year, when Foghorn is expected to report limited topline phase I dose-escalation results for FHD-909, a SMARCA2 inhibitor. The company will then decide on dose expansion."

P1 data • Stock price • Non Small Cell Lung Cancer • Solid Tumor

Foghorn’s lead, Lilly‑partnered SMARCA2 program began global Phase 1 dosing around October 2024 with favorable safety to date (no MTD reached), escalation and backfilling underway, and a mid‑year decision expected on progressing to dose expansion in NSCLC patients with SMARCA4 loss‑of‑function mutations… (Yahoo Finance)

Trial status • Non Small Cell Lung Cancer • Solid Tumor

Phase 1 dose-escalation trial of FHD-909 (LY4050784) advancing as planned, targeting SMARCA4 (BRG1)-mutant cancers with a focus on non-small cell lung cancer (NSCLC) (GlobeNewswire) - "Selective CBP degrader program with potential in ER+ breast cancer on track to be IND-ready in 2026; Selective EP300 degrader program shows preclinical superior anti-tumor efficacy and tolerability over dual CBP/EP300; EP300 degrader program – IND-enabling studies expected in 2026, with a focus in MM and DLBCL....Pending successful Phase 1 dose escalation results, Foghorn and Lilly anticipate evaluating FHD-909 in combination studies in the front-line setting of NSCLC."

IND • Preclinical • Trial status • Diffuse Large B Cell Lymphoma • Estrogen Receptor Positive Breast Cancer • Multiple Myeloma • Non Small Cell Lung Cancer

J5M-OX-JOXA: A Study of LY4050784 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=340 | Recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Dec 2028 ➔ Oct 2027 | Trial primary completion date: Dec 2028 ➔ Oct 2027

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

J5M-OX-JOXA: A Study of LY4050784 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=340 | Recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Oct 2027 ➔ Dec 2028 | Trial primary completion date: Oct 2027 ➔ Dec 2028

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Phase 1 trial enrolling well. Enrollment in the first-in-human Phase 1 multi-center trial of FHD-909, with NSCLC as the primary target population, is progressing well and the study remains on track. (GlobeNewswire)

Trial status • Non Small Cell Lung Cancer

Foghorn Therapeutics Provides Second Quarter 2025 Financial and Corporate Update (GlobeNewswire) - "FHD-909 (LY4050784) Phase 1 dose escalation trial in SMARCA4 (BRG1) mutated cancers, with non-small cell lung cancer (NSCLC) as the primary target population....Phase 1 trial enrolling well and remains on track. Enrollment in the first-in-human Phase 1 multi-center trial of FHD-909 is progressing well."

Trial status • Non Small Cell Lung Cancer

J5M-OX-JOXA: A Study of LY4050784 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=340 | Recruiting | Sponsor: Eli Lilly and Company | Trial completion date: May 2028 ➔ Oct 2027

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Poster Presentation Title: A First-in-human Phase 1 Study of LY4050784, an Oral, Potent, and Selective SMARCA2 Inhibitor, in Patients with Advanced Solid Tumors with SMARCA4 Alterations (Trial in Progress) (GlobeNewswire) - "Foghorn Therapeutics...announced new...data for potential first-in-class medicines...at the 2025 American Association for Cancer Research (AACR) Annual Meeting....First-in-human trial of FHD-909 will evaluate patients with SMARCA4 mutated locally advanced or metastatic solid tumors who have exhausted standard treatment options. Upon completion of the dose escalation part of the study, two separate expansion cohorts will enroll either patients with NSCLC or with other advanced solid tumors harboring eligible SMARCA4 alteration(s)."

Clinical protocol • Solid Tumor

Oral Presentation Title: LY4050784, a Selective Inhibitor of SMARCA2, Demonstrates Synergistic Activity in Combinations with Pembrolizumab or KRAS Inhibitors (GlobeNewswire) - "Foghorn Therapeutics...announced new preclinical data for potential first-in-class medicines...at the 2025 American Association for Cancer Research (AACR) Annual Meeting....FHD-909 monotherapy selectively inhibits SMARCA4 mutant cancer cells in vitro, is well tolerated, and demonstrates robust anti-tumor efficacy in SMARCA4 mutant NSCLC xenograft models. FHD-909 shows additive activity with standard-of-care chemotherapies (platinum, paclitaxel, pemetrexed, gemcitabine and docetaxel) and synergistic activity in multiple combinations including KRAS G12C, KRAS G12D, and pan-KRAS inhibitors, as well as anti-PD-1 pembrolizumab."

Preclinical • Non Small Cell Lung Cancer

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

Lilly announces details of presentations at 2025 American Association for Cancer Research (AACR) Annual Meeting (PRNewswire) - "In an oral presentation, Lilly, in collaboration with Foghorn Therapeutics, will present new preclinical data for LY4050784, a selective inhibitor of SMARCA2, in combination with chemotherapy, pembrolizumab, and KRAS inhibitors in preclinical models of SMARCA4 mutant cancers. Preclinical data for LY4066434, a pan-KRAS inhibitor that is highly selective over HRAS and NRAS, will also be presented."

Preclinical • 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) - "First-in-class oral selective SMARCA2 (BRM) inhibitor, FHD-909 (LY4050784), advancing in Phase 1 trial for SMARCA4 mutated cancers, with non-small cell lung cancer (NSCLC) as the primary target patient population; FHD-909 preclinical combination data with pembrolizumab and KRAS inhibitors to be presented at the AACR Annual Meeting (April 25-30, 2025)."

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

Foghorn Therapeutics Provides Update on FHD-286 Clinical Development Program and Strategic Priorities (GlobeNewswire) - "Foghorn Therapeutics Inc...announced today that it has made the decision to discontinue the independent development of FHD-286 in combination with decitabine in patients with relapsed and/or refractory acute myeloid leukemia (AML)....The Company will prioritize its proprietary pipeline and Lilly collaboration programs, including the clinical-stage selective SMARCA2 (BRM) inhibitor FHD-909 (LY4050784)....In the Phase 1 dose escalation trial of FHD-286 in combination with decitabine in relapsed and/or refractory AML, objective clinical responses were observed by standard response criteria. However, the observed response rate did not meet the Company’s threshold to continue development by Foghorn alone. Foghorn expects to report the results at a medical conference in 2025."

Discontinued • P1 data • Pipeline update • Acute Myelogenous Leukemia