bomedemstat (MK-3543) / Merck (MSD) - LARVOL DELTA

Closing the disease modification gap: Emerging therapies in myelofibrosis beyond JAK inhibition. (PubMed, Semin Hematol) - "We discuss BET inhibitors (pelabresib), PIM kinase inhibitors (TP-3654), telomerase inhibition (imetelstat), nuclear export inhibition (selinexor), LSD1 inhibition (bomedemstat), MDM2 antagonism (navtemadlin), mutant CALR-directed immunotherapies, and activin receptor ligand traps (elritercept). Strategies such as high-molecular-risk mutation profiling and variant allele frequency monitoring to assess disease progression and clonal burden will also be discussed. As the focus of MPN management shifts towards curative nontransplant options, a combination of improved access to clinical trials and accounting for patient-reported outcomes will be vital if we are to realize the promise of these next-generation therapies."

IO biomarker • Journal • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Transplantation • CALR

Brief Communication: LSD1 Inhibition Enhances Susceptibility of Primary AML Cells for NK Cell-Mediated Killing. (PubMed, J Immunother) - "Interestingly, we observed that treatment with the LSD1 inhibitors, bomedemstat and GSK-LSD1, led to the upregulation of multiple stress ligands known to activate NK cells. Importantly, this increased stress ligand expression was associated with enhanced NK cell-mediated cytotoxicity, suggesting the potential for both therapies to be used synergistically. To our knowledge, this is the first study to assess the combination of LSD1 inhibition and exNK cells in AML."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Bomedemstat (IMG-7289), an LSD1 Inhibitor, Manages the Signs and Symptoms of Essential Thrombocythemia (ET) While Reducing the Burden of Cells Homozygous for Driver Mutations (ASH 2023) - P2 | "All current treatments - hydroxyurea, interferon, or anagrelide - have their limitations and do not substantially affect the natural history of ET. Furthermore, this study shows that sequencing germline+granulocyte DNA provides a reliable qualitative view of the impact of treatment on the genotypic distribution among CD34+ cells as revealed by scDNA genotyping. Finally, bomedemstat showed activity reducing stem/progenitor cells homozygous for mutations in JAK2, CALR, and MPL."

Cardiovascular • CNS Disorders • Constipation • Essential Thrombocythemia • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Infectious Disease • Musculoskeletal Pain • Myeloproliferative Neoplasm • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia • Thrombocytosis • CALR • CD14 • CD34 • JAK2

Efficacy and safety of the LSD1 inhibitor bomedemstat in participants with polycythemia vera (PV) resistant or intolerant to cytoreductive therapy: The Phase 2 shorespan-004 study (ASH 2025) - P2 | "Bomedemstat had manageable safety and clinically relevant activity in pts with previouslytreated PV. Half of all pts had a reduction in hematocrit to <45% by wk 52 that lasted ≥12 wk withoutphlebotomy; 85% had a hematocrit reduction to <45%, 90% had a platelet reduction to ≤450 x 109/L, and85% had a WBC reduction to <10 x 109/L at any time. A clinically significant reduction in MFSAF total scorewas observed."

Clinical • P2 data • Acute Myelogenous Leukemia • Cerebral Hemorrhage • Essential Thrombocythemia • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytopenia • Thrombocytosis • Thrombosis • JAK2

A Clinical Trial of Bomedemstat in Participants With Polycythemia Vera (MK-3543-025) (clinicaltrials.gov) - P2/3 | N=380 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2/3 trial • Polycythemia Vera

Bomedemstat vs Hydroxyurea for Essential Thrombocythemia (MK-3543-007) (clinicaltrials.gov) - P3 | N=300 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Essential Thrombocythemia • Hematological Disorders • Myeloproliferative Neoplasm • Thrombocytosis

A Study of Bomedemstat (IMG-7289/MK-3543) Compared to Best Available Therapy (BAT) in Participants With Essential Thrombocythemia and an Inadequate Response or Intolerance of Hydroxyurea (MK-3543-006) (clinicaltrials.gov) - P3 | N=340 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Essential Thrombocythemia • Hematological Disorders • Myeloproliferative Neoplasm • Thrombocytosis

Bomedemstat Demonstrates Long-Term Safety in Patients With MPNs (Hematology Advisor) - "Results were presented at the EHA 2026 Congress...Any-grade AEs were reported in 35 of the 40 (88%) patients with ET. The most common AEs of any grade occurring in at least 2 participants with ET included diarrhea (23%), contusion (13%), abdominal pain (10%), upper respiratory tract infection (10%), anemia (8%), arthralgia (8%), fall (8%), and others...Among patients with MF, any-grade AEs were reported in 12 patients (75%), with grade 3 or 4 AEs reported in 6 patients (38%), and with no grade 5 AEs. In patients with MF, dose modifications due to an AE occurred in 9 patients (56%), and 2 patients discontinued treatment due to AEs of either spleen disorder or spontaneous splenic rupture. Serious AEs were reported in 3 patients (19%) with MF."

Adverse events • P3 data • Serious adverse event • Essential Thrombocythemia • Myelofibrosis • Myeloproliferative Neoplasm

PHASE 2 STUDY TO ASSESS THE SAFETY AND EFFICACY OF BOMEDEMSTAT (IMG-7289) IN COMBINATION WITH MOMELOTINIB IN PATIENTS WITH MYELOFIBROSIS (EHA 2026) - "Enrollment expected to start in September 2026. ISRCTN98283910"

Clinical • Combination therapy • P2 data • Chronic Eosinophilic Leukemia • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytosis • ACVR1 • JAK1 • JAK2

SHORESPAN-017: A PHASE 3 EXTENSION STUDY EVALUATING THE SAFETY OF CONTINUED BOMEDEMSTAT IN PARTICIPANTS WITH ESSENTIAL THROMBOCYTHEMIA (EHA 2026) - P3 | "One serious treatment-related AE of grade 2 constipation was reported. Summary/Conclusion Results of this analysis show that continued treatment with bomedemstat had manageable safety in participants with essential thrombocythemia who had achieved a clinical benefit with bomedemstat in their feeder study."

Clinical • P3 data • Cardiovascular • Constipation • Essential Thrombocythemia • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hematological Malignancies • Infectious Disease • Myeloproliferative Neoplasm • Respiratory Diseases • Thrombocytosis

CHIP-ASSOCIATED MUTATIONS ARE LINKED TO POOR SURVIVAL IN SOLID MALIGNANCIES AND DRIVE PRO-TUMORIGENIC MACROPHAGE CROSSTALK (EHA 2026) - "Notably, treatment with JAK1/2i ruxolitinib or LSD1i bomedemstat selectively reduced Jak2-V617F macrophage abundance without affecting WT macrophages and consequently decreased R254 cell proliferation by 72.0% (ruxolitinib) and 50.0% (bomedemstat). Summary/Conclusion CHIP-associated mutations are linked to inferior OS in patients with advanced malignancies and, in a murine model, promote tumor cell expansion via Jak2-V617F -driven macrophage-tumor interactions. These data suggest that CHIP can shape a pro-tumorigenic immune microenvironment and may represent a therapeutically actionable vulnerability, where targeting mutant immune cells complements tumor-directed therapies."

Breast Cancer • Colorectal Cancer • Hematological Malignancies • Lung Adenocarcinoma • Lung Cancer • Microsatellite Instability • Non Small Cell Lung Cancer • Pancreatic Adenocarcinoma • Pancreatic Cancer • Sarcoma • Solid Tumor • CSF1 • HRD • JAK1 • JAK2 • KRAS • MSI • TP53

A phase 2 study to assess the safety and efficacy of bomedemstat (IMG-7289) in combination with momelotinib in patients with myelofibrosis. (ASCO 2026) - "The study will run in 5 Countries (UK, France, Spain, Dubai, USA), for a total of 20 Sites. Enrollment expected to start in September 2026."

Clinical • Combination therapy • P2 data • Chronic Eosinophilic Leukemia • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Polycythemia Vera • Thrombocytosis • ACVR1 • JAK1 • JAK2

Human Ductal Carcinoma In Situ: Role of Spatial Niches in Invasive and Metastatic Progression (ASBrS 2026) - "Transcriptional drivers were functionally validated using Lysine-Specific Demethylase 1(LSD1) inhibitors (ORY-1001 and bomedemstat) in HER2+ DCIS cell lines and xenograft models (BCM 3613, BCM 3963). Spatial niches enriched with FOXA1-driven, stem-like luminal hormone-responsive cells play a key role in the underlying invasive and metastatic potential of DCIS, particularly in HER2+ subtypes. These niches are characterized by distinct ligand-receptor signaling (e.g., CEACAM6–EGFR) and epigenetic regulation. Targeting transcriptional regulators of stemness, like FOXA1, along with their microenvironmental signals, offers a promising strategy to prevent progression in high-risk DCIS."

Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CEACAM6 • EGFR • FOXA1 • HER-2

The lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat in myelofibrosis: results from a phase 1/2 study. (PubMed, Blood Adv) - P1/2 | "Bomedemstat has manageable safety and clinical activity in participants with MF in need of an alternative therapy. This trial was registered at www.cinicaltrials.gov as #NCT03136185."

Journal • P1/2 data • Fatigue • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Thrombocytopenia • CALR • JAK2

Phase 2 study of the lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat for essential thrombocythemia. (PubMed, Blood Adv) - P2 | "Bomedemstat had clinically relevant activity and manageable safety in participants with ET. Registration: NCT04254978 (Study of Bomedemstat in Participants With Essential Thrombocythemia [IMG-7289-CTP-201/MK-3543-003])."

Journal • P2 data • Cardiovascular • Essential Thrombocythemia • Hematological Disorders • Myeloproliferative Neoplasm • Thrombocytosis • CALR • JAK2

MK-3453-023: A Study of Bomedemstat (MK-3543) in Participants With Mild or Moderate Hepatic Impairment (MK-3543-023) (clinicaltrials.gov) - P1 | N=9 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed | N=24 ➔ 9

Enrollment change • Trial completion • Hepatitis C • Hepatology • Liver Failure

Bomedemstat (IMG-7289) in Combination With Momelotinib in Patients With Myelofibrosis (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: United Lincolnshire Hospitals NHS Trust

New P2 trial • Myelofibrosis

Therapeutic advances in acute myeloid leukemia: from LSD1 blockade to PROTAC-based strategies. (PubMed, Ann Med Surg (Lond)) - "Several PROTAC therapies are now in AML trials. LSD1-targeted degradation is promising, but further research is needed to confirm its safety, overcome resistance, and identify optimal drug combinations for AML treatment."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Targeted Protein Degradation • KDM1A

MK-3453-023: A Study of Bomedemstat (MK-3543) in Participants With Mild or Moderate Hepatic Impairment (MK-3543-023) (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatitis C • Hepatology • Liver Failure

VenBom: Venetoclax and Bomedemstat in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Terrence J Bradley, MD | Suspended ➔ Recruiting | Trial completion date: Nov 2025 ➔ Nov 2026 | Trial primary completion date: Nov 2025 ➔ Nov 2026

Enrollment open • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

IMG-7289 in Patients With Essential Thrombocythemia (ET) or Polycythemia Vera (PV) (clinicaltrials.gov) - P2 | N=4 | Active, not recruiting | Sponsor: Terrence J Bradley, MD | Trial completion date: Oct 2026 ➔ Oct 2027 | Trial primary completion date: Oct 2025 ➔ Oct 2026

Trial completion date • Trial primary completion date • Essential Thrombocythemia • Hematological Disorders • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytosis

Combined inhibition of lysine-specific demethylase 1 and kinase signaling as a preclinical treatment strategy in glioblastoma. (PubMed, Neurooncol Adv) - "Glioblastoma stem cell (GSC) lines and normal human astrocytes (NHAs) were treated with catalytic LSD1 inhibitors, NCD38 and bomedemstat, and the LSD1 scaffolding inhibitor, seclidemstat alone and in combination with kinase inhibitors, including osimertinib, afatinib, and ulixertinib. Combined treatment with NCD38 and osimertinib in glioblastoma-bearing mice delayed tumor growth and improved survival outcomes. These findings provide a rationale for further investigation of combination therapies of catalytic inhibitors of LSD1 and EGFR and dual-targeted inhibitors to overcome resistance and improve outcomes."

Journal • Preclinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • EGFR • KDM1A

Elucidating Stemness-Associated Regulatory Pathways to Guide Personalized Treatment for Ductal Carcinoma in Situ (SABCS 2025) - "To target FOXA1, we employed bomedemstat, an inhibitor of lysine-specific demethylase 1 (LSD1)... Cellular stemness may serve as a predictor of DCIS with a future risk for invasive progression. By targeting the key biological drivers of cellular stemness, our goal is to distinguish aggressive from indolent disease, ultimately reducing overtreatment and improving outcomes for patients with high-risk DCIS."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • CEACAM6 • EGFR • FOXA1 • HER-2

LSD1 inhibition enhances venetoclax efficacy in Acute Myeloid Leukemia via metabolic rewiring (ASH 2025) - "Supporting this, combiningbomedemstat with OxPhos inhibitors (IACS-010759, rotenone, antimycin, oligomycin) synergisticallyreduced cell proliferation, and Rho-zero MOLM-13 cells, lacking mitochondrial DNA, were more sensitiveto bomedemstat than wild-type cells.Consistent with its metabolic effects, bomedemstat increased expression (P = 0.0002) and activation (P =0.02) of the energy stress sensor AMPK, as shown by western blotting. Bomedemstat and venetoclax co-treatment showed synergistic anti-leukemic effects in AMLmodels in vitro and in vivo. Our findings suggest that LSD1 inhibition primes AML cells to venetoclax viadifferentiation-induced metabolic rewiring and activation of AMPK-mediated stress responses, providingthe basis for a planned clinical trial."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • ANXA5 • DNMT3A • FLT3 • HOXA9 • IDH2 • MEIS1 • NPM1 • PTPRC • WT1

Shorespan-017: Phase 3 extension study for safety of bomedemstat in participants with essential thrombocythemia who received bomedemstat from a prior clinical study (ASH 2025) - P3 | "Bomedemstat had a manageable safety profile in participants with essentialthrombocythemia who were currently receiving bomedemstat for longer duration in this extension studyand achieved a clinical benefit."

Clinical • P3 data • Cardiovascular • Constipation • Essential Thrombocythemia • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Infectious Disease • Musculoskeletal Pain • Myelofibrosis • Myeloproliferative Neoplasm • Neutropenia • Respiratory Diseases • Thrombocytosis