FHD-609 / Foghorn Therap - LARVOL DELTA

A Phase I Study of FHD-609, a Heterobifunctional Degrader of Bromodomain-Containing Protein 9, in Patients with Advanced Synovial Sarcoma or SMARCB1-Deficient Tumors (Clin Cancer Res) - P1 | N=55 | NCT04965753 | Sponsor: Foghorn Therapeutics Inc. | "Fifty-five patients received FHD-609 for a median of 43 days. The maximum tolerated doses were 40 mg twice weekly and the equivalent weekly dose, 80 mg once weekly....FHD-609 showed dose-dependent increases in pharmacokinetic exposure, with no substantial accumulation. Extensive BRD9 degradation in tumor tissue corresponded to the downregulation of cancer cell proliferation gene sets. One (2%) patient achieved a partial response; eight (15%) patients achieved stable disease, which lasted longer than 6 months in two patients."

P1 data • Synovial Sarcoma

A Phase 1 Study of FHD-609, a Heterobifunctional Degrader of Bromodomain-Containing Protein 9, in Patients With Advanced Synovial Sarcoma or SMARCB1-Deficient Tumors. (PubMed, Clin Cancer Res) - P1 | "FHD-609 showed dose-dependent increases in systemic FHD-609 exposure and pharmacodynamic response profiles. The MTDs were identified (40 mg BIW/80 mg QW) and preliminary clinical activity was observed. Future studies of BRD9 degraders will require strict cardiac monitoring given the QTc prolongation observed in this study."

Journal • Metastases • P1 data • Fatigue • Hematological Disorders • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • Xerostomia • SMARCB1

FHD-609-C-001: FHD-609 in Subjects With Advanced Synovial Sarcoma or Advanced SMARCB1-Loss Tumors (clinicaltrials.gov) - P1 | N=55 | Terminated | Sponsor: Foghorn Therapeutics Inc. | N=104 ➔ 55 | Trial completion date: May 2025 ➔ Dec 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2024 ➔ Dec 2023; Sponsor decision

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • SMARCB1 • SS18

Long acting injectable FHD-609 micro-suspension: A potent BRD9 degrader with comparable efficacy, reduced frequency of dosing in preclinical models (AACR 2024) - "The long acting FHD-609 injectable formulation has the potential to offer better patient compliance and acceptance in clinical settings than IV dosing. The long acting injectable formulation provides a promising and effective drug delivery option for various protein degraders that are not orally bioavailable."

Preclinical • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • SS18

Discovery of FHD-609: A potent and selective heterobifunctional degrader of BRD9 (ACS-Sp 2024) - "In preclinical studies, FHD-609 has been shown to selectively degrade bromodomain-containing protein 9 (BRD9), taking advantage of a synthetic lethal relationship with the SS18-SSX translocation. The discovery and optimization of this first-in-class clinical compound will be described."

Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • SS18

Foghorn Therapeutics Provides Financial Update for 2023 and 2024 Strategic Outlook (GlobeNewswire) - "Research and development expenses were $109.7 million for the year ended December 31, 2023, compared to $105.6 million for the year ended December 31, 2022. This increase was primarily due to costs associated with continued investment in R&D personnel, platform, and other early-stage research, partially offset by a decrease in spend on FHD-286 and FHD-609."

Commercial • 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

PHARMACODYNAMICS AND MECHANISTIC IMPACTS OF FHD-609, A BROMODOMAIN-CONTAINING PROTEIN 9 DEGRADER, IN A PHASE 1 STUDY IN PATIENTS WITH ADVANCED SYNOVIAL SARCOMA OR SMARCB1-LOSS TUMORS (CTOS 2023) - "In this Phase 1 dose escalation study, treatment with FHD-609 drove robust degradation of BRD9 in synovial sarcoma patient tumors. Complete degradation was observed in samples from QW and BIW cohorts, including several collected multiple days post-dose. BRD9 degradation was associated with histological treatment effects, and decreased markers of proliferation."

Clinical • Metastases • P1 data • PK/PD data • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • MYC • SMARCB1 • SS18

PRELIMINARY RESULTS FROM A PHASE 1 STUDY OF FHD-609, A BROMODOMAIN-CONTAINING PROTEIN 9 DEGRADER, IN PATIENTS WITH ADVANCED SYNOVIAL SARCOMA OR SMARCB1-LOSS TUMORS (CTOS 2023) - No abstract available

Clinical • Metastases • P1 data • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • SMARCB1

Foghorn Therapeutics to Present Clinical and Pre-Clinical Data from Multiple Programs Across Its Diverse Pipeline at AACR-NCI-EORTC International Conference (GlobeNewswire) - "Foghorn® Therapeutics...announced that...pre-clinical data for its selective EP300 program, and pre-clinical data for its BRD9 degrader FHD-609, will be presented at the AACR-NCI-EORTC International Conference....The Company will present data from its selective EP300 program, including in vitro selective degradation and antiproliferation in AR+ prostate and DLBCL cell lines....In addition, the Company will present results from next-generation-sequencing (NGS) analyses exploring the mechanism by which degradation of BRD9 may lead to proliferation defects in synovial sarcoma, as well as results from in vitro and in vivo studies demonstrating the anti-tumor efficacy of FHD-609, a BRD9 degrader, in a sub-type of AML."

Preclinical • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Prostate Cancer • Synovial Sarcoma

Investigation of FHD-609, a potent degrader of BRD9, in preclinical models of acute myeloid leukemia (AML). (AACR-NCI-EORTC 2023) - No abstract available

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

FHD-609-C-001: FHD-609 in Subjects With Advanced Synovial Sarcoma or Advanced SMARCB1-Loss Tumors (clinicaltrials.gov) - P1 | N=104 | Active, not recruiting | Sponsor: Foghorn Therapeutics Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • SMARCB1 • SS18

"And now $FHTX FHD-609 goes on hold after a grade 4 QTc prolongation event @ highest dose https://t.co/34Z1TwSlbW" (@JacobPlieth)

Foghorn Therapeutics Provides an Update on FHD-609 (GlobeNewswire) - "Foghorn^® Therapeutics Inc...announced an update on the FHD-609 program in synovial sarcoma and SMARCB1-deleted tumors. Foghorn is pausing enrollment in the FHD-609 study in synovial sarcoma and SMARCB1-deleted tumors due to a grade 4 QTc prolongation event in a synovial sarcoma patient at the second highest dose. Enrollment of the dose escalation portion of the study has been completed and a maximum tolerated dose has been identified....The Company promptly communicated the enrollment pause and risk mitigation actions to the FDA and European regulatory authorities. Consequently, the FDA placed the study on partial clinical hold in the United States, while allowing patients currently enrolled and benefiting from therapy to continue dosing and to remain on FHD-609. The Company is not at this time planning to pursue a dose expansion study independently."

Trial suspension • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma

Foghorn Therapeutics to Highlight Transcription Factor and Protein Degradation Capabilities at the 18th Annual Drug Discovery Chemistry Meeting (GlobeNewswire) - "Foghorn® Therapeutics Inc...announced upcoming oral presentations highlighting its transcription factor and protein degradation capabilities at the 18th Annual Drug Discovery Chemistry Meeting. The hybrid meeting will be held April 10–13, 2023, at the Hilton Bayfront in San Diego, CA, and virtually. The company will present preclinical data on FHD-609, a potent and selective heterobifunctional protein degrader of BRD9, a protein that synovial sarcoma cells rely on for survival. The presentation will also describe the discovery and optimization of this first-in-class clinical compound....In addition, Foghorn will present preclinical data showcasing its platform focused on the discovery of new medicines that target the disruption of transcription factors."

Preclinical • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Foghorn Therapeutics Highlights Recent Clinical and Research Progress and Provides Strategic Objectives for 2023 (GlobeNewswire) - "FHD-609 Update. Patient enrollment is continuing in the Phase 1 dose escalation clinical study of FHD-609, a potent and selective heterobifunctional protein degrader of BRD9, being developed for the treatment of synovial sarcoma and SMARCB1-loss tumors, with initial efficacy and safety data expected in mid-2023....Pipeline Advancement. Foghorn continues to expand its platform and pipeline. The Company anticipates at least six potential new molecular investigational new drug applications (INDs) in the next four years. The Company continues to progress programs for multiple targets which include chromatin remodeling complexes, transcription factors, helicases, and chromatin binding proteins. High-value targets include Selective BRM, CBP, and ARID1B as well as other undisclosed targets."

P1 data • Pipeline update • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma

Foghorn Therapeutics to Present at Connective Tissue Oncology Society Annual Meeting (GlobeNewswire) - "Foghorn^® Therapeutics Inc...announced the Company will share preclinical data for FHD-609, a first-in-class, highly potent and selective degrader of BRD9, at the 2022 Connective Tissue Oncology Society (CTOS) Annual Meeting. The meeting will be held November 16–19, 2022, at the Vancouver Convention Centre in Vancouver, BC, Canada."

Preclinical • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Foghorn Therapeutics Announces New Data Demonstrating BRD9 Degradation in Patient Tumor Biopsies and Discloses New Selective CBP Program (GlobeNewswire) - P1 | N=104 | NCT04965753 | Sponsor: Foghorn Therapeutics Inc. | "Foghorn Therapeutics Inc....today will present new data across its protein degradation platform at Hanson Wade’s 5th Annual Targeted Protein Degradation Summit....Preclinical data from...EP300 mutated cancers reinforce Foghorn’s significant advancement across its protein degradation platform and pipeline....Initial clinical data that will be presented today, from two patients in the study with metastatic synovial sarcoma treated with the same low dose of FHD-609 from the ongoing Phase 1 dose escalation study, show degradation of BRD9 in on-treatment metastatic tumor biopsies. Preclinical data also show exquisite selectivity with FHD-609, potentially avoiding the adverse effects associated with unwanted off-target degradation....'Presenting the initial safety and efficacy data from the ongoing FHD-609 Phase 1 dose escalation trial in synovial sarcoma in 2023.'"

P1 data • Preclinical • Oncology • Sarcoma • Synovial Sarcoma

FHD-609-C-001: FHD-609 in Subjects With Advanced Synovial Sarcoma or Advanced SMARCB1-Loss Tumors (clinicaltrials.gov) - P1 | N=104 | Recruiting | Sponsor: Foghorn Therapeutics Inc. | N=70 ➔ 104

Enrollment change • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • SMARCB1 • SS18

PRECLINICAL VALIDATION OF TARGET ENGAGEMENT ASSAYS AND INVESTIGATION OF MECHANISTIC IMPACTS OF FHD-609, A CLINICAL-STAGE BRD9 DEGRADER BEING DEVELOPED FOR THE TREATMENT OF SYNOVIAL SARCOMA (CTOS 2022) - "Here we report the first use of IHC and flow cytometry to measure target engagement with a BRD9 protein degrader in clinically relevant tissues. Using these methods, we found that higher doses of FHD-609 led to more prolonged suppression of BRD9 in tumors and PBMCs. Our results also suggest that certain PBMC populations are effective surrogates for tumor PD, which may enable longitudinal assessment of target engagement through serial blood collection in the clinic."

Preclinical • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • SS18

Foghorn Therapeutics Provides Second Quarter 2022 Financial and Corporate Update (GlobeNewswire) - "FHD-609 Update. Patient enrollment is continuing in the Phase 1 dose escalation clinical study of FHD-609, a potent and selective heterobifunctional protein degrader of BRD9, initially being developed for the treatment of synovial sarcoma with initial data expected in 2023."

P1 data • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Targeted Therapy for Adrenocortical Carcinoma: A Genomic-Based Search for Available and Emerging Options. (PubMed, Cancers (Basel)) - "We identified TP53-modulating drugs to be possibly effective in 20-26% of patients, followed by the Wnt signaling pathway inhibitors (15%), Telomelysin and INO5401 (13%), FHD-609 (13%), etc. According to our data, 67% of ACC patients exhibited genomic alterations that might be targeted by FDA-approved drugs or drugs being tested in current clinical trials. Although there are not many current therapy options directly targeting reported ACC alterations, this study identifies emerging options that could be tested in clinical trials."

Journal • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Rare Diseases • Solid Tumor • CDK4 • CTNNB1 • FLT4 • TP53

Foghorn Therapeutics Provides Full Year 2021 Corporate Update and 2022 Outlook (GlobeNewswire) - "Foghorn expects to provide initial Phase 1 clinical data for FHD-286...in metastatic uveal melanoma (mUM), relapsed and/or refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), in the first half of 2022; Foghorn anticipates providing initial Phase 1 clinical data for FHD-609...for the treatment of synovial sarcoma, as early as the first half of 2022...Foghorn is advancing its BRM-selective program in collaboration with Loxo Oncology at Lilly..."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Melanoma • Myelodysplastic Syndrome • Oncology • Sarcoma • Synovial Sarcoma • Uveal Melanoma

DISCOVERY OF A POTENT AND SELECTIVE BRD9 DEGRADER FHD-609 FOR THE TREATMENT OF SYNOVIAL SARCOMA AND OTHER CANCERS WITH DYSREGULATION OF CHROMATIN REMODELER COMPLEXES (CTOS 2021) - "BRD9 degradation induced by FHD-609 is UPS-dependent, as including the proteasome inhibitor, Bortezomib, largely abrogated the BRD9 degradation activity. We have discovered and advanced to the clinic a potent, selective, and efficient BRD9 degrader, FHD-609. This drug candidate possesses suitable drug like properties and potently degrades BRD9, which translates into strong anti-tumor activity in synovial sarcoma cell lines. FHD-609 has a durable PD profile and shows strong efficacy as mono-agent therapy in synovial sarcoma xenograft models with an intermittent (BIW) administration and compares favorably to standard-of-cares, such as ifosfamide or pazopanib, that were tested in the same models."

Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma • Targeted Protein Degradation • BRD4 • CRBN • SMARCA4 • SS18

Foghorn Therapeutics Provides Third Quarter 2021 Corporate Update (GlobeNewswire) - "Key Upcoming Milestones: FHD-286 data. Foghorn expects to have initial data from the Company’s phase 1 studies of FHD-286 in both metastatic uveal melanoma and relapsed/refractory AML and MDS as early as the fourth quarter of 2021; FHD-609 data. Foghorn expects to have initial data from the Company’s phase 1 study in synovial sarcoma as early as the first half of 2022."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Melanoma • Myelodysplastic Syndrome • Oncology • Sarcoma • Uveal Melanoma