camibirstat (FHD-286) / Foghorn Therap, Montefiore Medical Center - LARVOL DELTA

Synergistic targeting of mSWI/SNF and UTX reveals a novel combination therapy in T-cell acute lymphoblastic leukemia (AACR 2026) - "A synergistic effect emerged when T-ALL cells or patient-derived xenografts (PDXs) were co-treated with GSK-J4, a histone demethylase inhibitor, and FHD-286. Transcriptomic analyses indicated that genes promoting ribosomal and mitochondrial function were substantially downregulated in UTX KO T-ALL cells treated with FHD-286 but not in similarly treated WT cells, suggesting a previously unrecognized role of UTX in gene regulation. Overall, these findings demonstrate that simultaneously targeting the mSWI/SNF complex and UTX may represent an innovative combinatorial strategy for T-ALL treatment."

Combination therapy • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • NOTCH1 • RUNX1 • SMARCA2

Neuroblastoma phenotypic switching is blocked by FHD-286, a small molecule inhibitor of the SWI/SNF ATPases SMARCA2/4 (AACR 2026) - "Abstract is embargoed at this time."

Late-breaking abstract • Neuroblastoma • Oncology • Solid Tumor • SMARCA2

FHD-286 With Low-Dose Weekly Decitabine/Venetoclax in Patients With Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=33 | Recruiting | Sponsor: Montefiore Medical Center | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Overcoming Menin inhibitor resistance in AML cells with combinations including BET proteins and dual BRG1/BRM inhibitor. (PubMed, Blood) - "Compared to each drug alone, co-treatment with SNDX-5613 (revumenib) and FHD-286 or OTX015 and FHD-286 significantly reduced the in vivo AML burden and improved survival of the immune depleted mice, without inducing significant toxicity, in the xenograft models of MITR and MI-resistant PD MLL1-r AML cells. These findings highlight novel, targeted, drug combinations that overcome MI resistance in AML cells with MLL1-r or mtNPM1."

Journal • Acute Myelogenous Leukemia • BRD4 • CREBBP • HOXA9 • MEIS1 • NPM1 • SMARCA2 • SMARCA4

Yatiri Bio Accurately Predicts AML Drug Response in Blinded Study Using Foghorn’s FHD-286 (GlobeNewswire) - "Yatiri Bio correctly identified patients who achieved complete or partial responses (CR/PR) and accurately classified patients who experienced stable disease or treatment failure. All predictions were generated exclusively from pre-dose peripheral blood samples, without access to additional patient information, including mutational status, dosing, trial arm assignment, or clinical outcomes....As a result of this work, Yatiri Bio and Foghorn Therapeutics have now signed a collaboration agreement for Foghorn to supply material for the further clinical development of FHD-286....The terms of the agreement include clinical, and sales milestones valued at >$40M."

Licensing / partnership • P1 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

Distinct 3D chromatin organisation underlies neuroendocrine plasticity in prostate cancer (LCC 2026) - "Furthermore, pharmacological inhibition of chromatin remodelling using the SWI/SNF inhibitor FHD-286 disrupted NE-associated gene expression and suppressed cell proliferation in vitro. Taken together, our findings establish 3D chromatin remodelling as a key driver of luminal-to-neuroendocrine plasticity in prostate cancer and highlight promising therapeutic strategies to mitigate the NEPC state."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FOXA1 • FOXA2 • HOXB13

A Phase 1 Study of FHD-286, a Dual BRG1/BRM (SMARCA4/SMARCA2) Inhibitor, in Patients With Advanced Myeloid Malignancies. (PubMed, Clin Cancer Res) - P1 | "DS was the most frequent serious TRAE. While antileukemic activity was observed, no objective responses were achieved and disease progression frequently occurred within 1-2 treatment cycles. Blast reductions were reported across cytogenetic and mutational profiles, coupled with myeloid differentiation via BRG1/BRM inhibition. This novel mechanism warrants further investigation of FHD-286 in combination with other agents in myeloid malignancies."

Journal • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Hepatology • Leukemia • Myelodysplastic Syndrome • Oncology • Xerostomia • SMARCA2 • SMARCA4

A phase I dose escalation and expansion study of FHD-286, a novel BRG1/BRM (SMARCA4/SMARCA2) inhibitor, for the treatment of metastatic uveal melanoma (ESMO 2023) - P1 | "The RP2D(s) has not yet been established. Updated dosing, safety, tolerability, PK and anti-tumor activity data will be shared at the meeting."

Metastases • P1 data • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • SMARCA2 • SMARCA4

Highly effective combination of BRG1/BRM inhibitor with BET inhibitor or decitabine for high-risk MECOM-rearranged AML. (PubMed, Hemasphere) - "In AML with 3q26.2 rearrangements (r) the distal GATA2 hematopoietic enhancer becomes aberrantly relocated leading to activation of EVI1 expression. In patient-derived xenograft (PDX) models of AML with MECOM-r, compared to each drug alone, co-treatment with FHD-286 and BETi OTX015 significantly reduced AML burden and improved survival, without inducing significant toxicity. These findings highlight the FHD-286-based combinations as promising therapy of AML with chromosome 3q26.2 rearrangement and EVI1 overexpression."

Journal • Acute Myelogenous Leukemia • CDK4 • GATA2 • MECOM • MYC • SMARCA2 • SMARCA4

FHD-286 With Low-Dose Weekly Decitabine/Venetoclax in Patients With Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=33 | Not yet recruiting | Sponsor: Montefiore Medical Center

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Machine learning-powered integration of global proteomics and ex vivo sensitivity unveils a protein signature predictive of treatment success to AML therapy: Validation in patients treated with FHD-286, a SMARCA2/4 dual inhibitor (ASH 2025) - P1 | "Patients had received a median 3 prior lines of therapy (range 1-7),including venetoclax and hypomethylating agents (100%), high-dose chemotherapy (71%), and stem celltransplant (57%). A clinical trial prospectively assigning patients tospecific treatment arms based on our proteomics signature will launch in 2025. This result highlights theutility of Yatiri Bio's deep learning model to guide AML treatment decisions and improve outcomes andsupports the development of a mass spectrometry-based clinical assay for patient selection in clinicaltrials."

Machine learning • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • SMARCA2 • TP53

BRM/BRG1 is a novel therapeutic target in ZNF384-rearranged mixed phenotype acute leukemia (ASH 2025) - "At the chromatin level, FHD-286 not only results in loss of BRG1 binding but also,interestingly, in loss of ZNF384 binding, suggesting that inhibiton of BRM/BRG1 may specifically affect theZNF384 fusion protein. We have established cell line-derived and patient-derived xenograft models ofZNF384-r MPAL and will confirm our findings in vivo in pre-clinical studies."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Targeted Protein Degradation • CCNB1 • CDK1 • CDK6 • EP300 • SMARCA4 • ZNF384

Genomic and phenotypic impact of FHD-286–induced inhibition of SMARCA4/2 in patients with relapsed/refractory myeloid malignancies (ASH 2025) - P1 | "FHD-286 monotherapy induced myeloiddifferentiation in patients (pts) with relapsed/refractory (R/R) acute myeloid leukemia (AML) ormyelodysplastic syndrome (MDS), and the addition of decitabine (DAC) produced objective responses.In a multicenter, open-label, Phase 1 dose escalation study (NCT04891757), pts with R/R AML, MDS, orchronic myelomonocytic leukemia received FHD-286 monotherapy or in combination with DAC. FHD-286 induced broad immunophenotypic and transcriptional changes in leukemic blasts, consistentwith decreased stemness and increased myeloid differentiation. In the combination therapy cohort,responders exhibited stronger transcriptional impacts than nonresponders or monotherapy-treated pts.Additional studies will be needed to understand the context in which FHD-286+DAC leads to greaterefficacy, and may support pt enrichment strategies."

Clinical • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD34 • ITGAM • KIT • SMARCA4

Preclinical evaluation of SWI/SNF targeting agents in multiple myeloma including t(4; 14) subtypes (ASH 2025) - "AU-24118 log2 IC₅₀ values correlatedwith those of FHD-286 (r=0.62, p=0.0002) and with pomalidomide (r=0.61, p=0.0002), suggesting a sharedbiology. Broad PRISM profiling confirms lineage-specific vulnerability of MM to SWI/SNF inhibition,with in vitro and in vivo validation supporting selective efficacy in high-risk t(4; 14)-positive subtypes. FHD-286, AU-15330, and AU-24118 demonstrated strong in vitro activity, particularly in t(4; 14)-positive HMCLs.This activity was due, in part, to chromatin compaction and decommissioning of lineage and oncogenicenhancers as well as eviction of IKZF1/3 off chromatin. AU-24118 showed high selectivity, with picomolarrange IC₅₀ in sensitive HMCLs."

Preclinical • Hematological Malignancies • Multiple Myeloma • Plasmacytoma • Targeted Protein Degradation • ANXA5 • CRBN • DUSP22 • IKZF1 • IRF4 • NSD2 • POU2AF1 • SMARCA2 • USP22

Notable Efficacy of Co-Treatment with FHD-286, a Dual BRG1/BRM ATP-Ase Inhibitor, and Menin or BET Inhibitor, Decitabine or Venetoclax Against AML with MLL-r or Mutant NPM1 (ASH 2023) - "BRG1 (SMARCA4) and BRM (SMARCA2) are the core ATPase within the multi-protein, ATP-dependent, chromatin remodeling BAF complexes that regulate gene transcription. Finally, co-treatment with FHD-286 and OTX015 or SNDX-5613 (oral gavage) was significantly more effective than each drug alone in reducing the AML burden and overall survival of mice engrafted with a separate PDX model of AML cells with mtNPM1 and FLT3-ITD, without significant toxicity. These findings demonstrate the pre-clinical efficacy of FHD-286-based rational combinations and underscore their promise against AML with MLL1r or mtNPM1."

Clinical • IO biomarker • Acute Myelogenous Leukemia • BCL2 • BRD4 • CASP3 • CD123 • CD33 • CD99 • CDK4 • CDKN1A • CEBPA • CLEC12A • FLT3 • HEXIM1 • IL3RA • ITGAM • MCL1 • MEF2C • MYC • NPM1 • PBX3 • PLK1 • SMARCA2 • SMARCA4

Preliminary Results from a Phase 1 Dose Escalation Study of FHD-286, a Novel BRG1/BRM (SMARCA4/SMARCA2) Inhibitor, Administered As an Oral Monotherapy in Patients with Advanced Hematologic Malignancies (ASH 2023) - P1 | "Enrollment into the single-agent dose escalation phase of the study is complete. Based on nonclinical, translational, and single-agent clinical data, FHD-286 in combination with decitabine or low-dose cytarabine is being evaluated in the combination dose escalation phase of the study."

Clinical • Metastases • Monotherapy • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Dental Disorders • Endocrine Disorders • Hematological Malignancies • Hepatology • Leukemia • Myelodysplastic Syndrome • Oncology • Stomatitis • Transplantation • Xerostomia • KMT2A • MECOM • SMARCA2 • SMARCA4

Identifying 'Druggable' Targets and Preclinically Overcoming Non-Genetic/Adaptive Resistance to Menin Inhibitors in AML with MLL1r or mtNPM1 (ASH 2024) - "These MITR cells exhibited cross-resistance to other MIs, including ziftomenib and DS1594b...Notably, in a luciferized MLL1r MITR AML PDX model, compared to treatment with each agent alone, co-treatment with FHD-286 and SNDX-5613 or OTX015 for 8-weeks yielded significantly superior survival of the NSG mice (p < 0.05). These findings demonstrate that co-treatment with FHD-286 overcomes in vitro and in vivo MI-resistance, while significantly improving in vivo efficacy of BETi in the cell-line xenograft and PDX models of MITR AML cells. They also show that combinations of epigenetically targeted agents may be effective in MI-sensitive or -resistant AML with MLL1r or mtNPM1."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • BRD4 • CDK6 • CLEC12A • CREBBP • EP300 • FLT3 • HOXA9 • IGF2BP2 • MEF2C • MEIS1 • NPM1 • PBX3 • SMARCA4

Leveraging SMARCA4 Dependency of Mantle Cell Lymphomas to Overcome BTK Inhibitor Resistance (ASH 2024) - "Covalent Bruton tyrosine kinase inhibitors (cBTKi), such as ibrutinib, zanubrutinib, and acalabrutinib, are mainstays of treatment relapsed MCL, and their use is emerging in the front-line setting...We found that pharmacological inhibition of SMARCA4 by FHD-286, an allosteric SMARCA2/4 ATPase inhibitor, which is a clinical stage asset owned by Foghorn Therapeutics and currently under investigation in AML in combination with decitabine and cytarabine, potently induced cytotoxicity in MCL cells at low nanomolar ranges...Consistently, combining FHD-286 with pirtobrutinib led to a substantial synergistic cytotoxic effect in MCL cell lines and primary MCL cells. Altogether, our findings suggest that SMARCA4 plays a tumor maintenance role in MCL. Targeting SMARCA4 can be further exploited as a therapeutic strategy in cBTKi-resistant MCL and may be even more effective in SMARCA4-mutated MCL."

Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CARD11 • CD79A • NR4A1 • RAC2 • SMARCA2 • SMARCA4 • SYK • TP53

Targeting the SWI/SNF Chromatin Remodeling Complex Subunit SMARCA4 in ALL (ASH 2024) - "Validating our hypothesis, pharmacologic SMARCA4 inhibition using two recently developed inhibitors (BRM014 and FHD-286) showed that Ph-like B-ALL was significantly more sensitive to SMARCA4 inhibition compared to KMT2A-R ALL...Furthermore, we demonstrate a direct correlation between high SMARCA4 expression and poor patient outcomes, as well as a clear dependency of Ph-like B-ALL on SMARCA4. Based on our data, applying a SMARCA4 inhibitor-based therapy may specifically benefit patients with Ph-like B-ALL."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • T Acute Lymphoblastic Leukemia • CD34 • KMT2A • SMARCA4

Discovery of novel SMARCA2 small molecule inhibitors with best-in-class potency and selectivity for the treatment of SMARCA4-mutant cancers (AACR-NCI-EORTC 2025) - "Multiple Phase 1 clinical trials exploring the SMARCA4/2 dual inhibitor FHD-286 in different indications were discontinued, flagging safety concerns...Here, we identified unique SMARCA2 selective inhibitor series with a best-in-class potency and selectivity profile. Thorough characterization and optimization efforts are ongoing to identify clinical development candidates with the ultimate goal of achieving greater efficacy along with enhanced safety, providing meaningful benefits to patients diagnosed with SMARCA4 deficient cancer."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • KRT80 • SMARCA2 • SMARCA4

Pan-RAS Inhibitor RMC-6236 Suppresses Myeloma Growth and Shows Enhanced Efficacy with SWI/SNF Inhibition (IMS 2025) - " We evaluated the anti-myeloma activity of novel pan-RAS inhibitors, RMC-6236 and RMC-7977, across a broad panel of over 50 MM cell lines. Our findings demonstrate that RMC-6236 shows broad and potent anti-tumor activity in RAS- and FGFR3-driven MM by suppressing MAPK and mTORC1 signaling. Its therapeutic efficacy is significantly enhanced in combination with SWI/SNF inhibitor FHD-286. These findings represent a promising therapeutic strategy that supports further clinical investigation in RAS-dependent MM."

Clinical • Hematological Malignancies • Multiple Myeloma • EIF4EBP1 • FGFR3 • KRAS • MAPK1 • NRAS • RPS6 • RPS6KA3 • SLC3A2

Superior Preclinical Efficacy of BRG1/BRM Inhibitor Combined With BET Inhibitor or Decitabine Against MECOM-rearranged (MECOM-r) Acute Myeloid Leukemia (AML) (SOHO 2025) - "Taken together, these findings highlight the promise of FHD-286– based rational combinations, especially with BETi, navitoclax, or decitabine, in exerting significant anti-AML efficacy against cellular models of MECOM-r AML."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • CD93 • CDK4 • GATA2 • ITGAM • KIT • MECOM • MYC • PLK1 • SMARCA4

Selective Sensitivity of Ph-like B-ALL to BRG1 Inhibition Reveals a Novel Targeted Therapy Strategy. (PubMed, bioRxiv) - "The pharmacologic inhibition of BRG1 using two selective inhibitors, BRM014 and FHD-286, revealed marked sensitivity in Ph-like B-ALL cell lines, whereas KMT2A -R B-ALL was resistant...These results support the advancement of BRG1-directed strategies as a viable treatment approach for patients with Ph-like B-ALL, with the potential to improve outcomes in this high-risk population. Higher levels of BRG1 correlate to poor clinical outcomes in Ph-like but KMT2A -R B-ALL Inhibition of BRG1 induces cell cycle arrest in Ph-like cells in vitro and extends the survival of mice in pre-clinical in vivo studies."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • CCND3 • CDK4 • CDK6 • CDKN1B • E2F1 • KMT2A • SMARCA4

PRELIMINARY SAFETY, PHARMACOKINETIC, AND CLINICAL ACTIVITY RESULTS WITH FHD-286, A BRG1/BRM INHIBITOR, PLUS DECITABINE IN A PHASE 1 STUDY IN PATIENTS WITH RELAPSED OR REFRACTORY MYELOID MALIGNANCIES (EHA 2025) - P1 | "The median number of prior therapies was 3 (range 1-9), including hypomethylating agents (93%), venetoclax (91%), cytarabine-based regimens (64%), and hematopoietic stem cell transplant (27%). In summary, preliminary data suggest FHD-286+DAC is better tolerated among pts not receiving strong CYP3A4 inhibitors as they increase FHD-286 exposure. FHD-286+DAC is clinically active in pts with R/R AML or MDS."

Clinical • P1 data • PK/PD data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myelomonocytic Leukemia • CNS Disorders • Diabetes • Fatigue • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia • CD34 • ITGAM • SMARCA4

IN VIVO EPIGENETIC CRISPR SCREENING IDENTIFIES SMARCA4 AS A CRITICAL TARGET FOR AUTOIMMUNE BONE MARROW FAILURE (EHA 2025) - "In vitro drug experiments using SWI/SNF small molecule inhibitors FHD-286 and FHT-1015 significantly decreased the cytotoxicity of CD8+ T cells without impairing long-term T cell expansion... This study successfully identified Smarca4 as a critical target for autoimmune bone marrow failure through in vivo epigenetic CRISPR-Cas9 screening, providing novel therapeutic targets and strategies for AA management."

Preclinical • Anemia • Aplastic Anemia • Hematological Disorders • Immunology • CD8 • JAK2 • SMARCA4