icovamenib (BMF-219) / Biomea Fusion - LARVOL DELTA

Icovamenib and semaglutide combination therapy enhances body weight loss and glycaemic control while preserving lean mass in a type 2 diabetes animal model (EASD 2025) - P2 | "Icovamenib enhanced the effects of semaglutide in ZDF rats, demonstrating improved glycemic control, enhanced weight loss and complete preservation of lean mass. Assessment of this novel combination in persons with T2D and obesity is warranted, as it may provide greater glycemic and weight loss effects."

Combination therapy • Preclinical • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Therapeutic Implications of Menin Inhibitors in the Treatment of Acute Leukemia: A Critical Review. (PubMed, Diseases) - "Currently, six menin inhibitors are in clinical evaluation as monotherapy or in combination regimens: revumenib, ziftomenib, bleximenib (previously JNJ-75276617), enzomenib (previously DSP-5336), DS-1594, and BMF-219. We discuss their efficacy, safety profiles, and potential roles within the current treatment algorithm. The continued clinical evaluation of menin inhibitors may redefine treatment paradigms for NPM1m and KMT2Ar AML and other acute leukemia with the aberrant MEIS1-HOXA axis, offering new hope for patients with limited therapeutic options."

Journal • Review • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • KMT2A • MEIS1 • NPM1

BF-MNN-112: Phase 2 Trial of BMF-219 in Participants With Type 1 Diabetes Mellitus (clinicaltrials.gov) - P2 | N=37 | Active, not recruiting | Sponsor: Biomea Fusion Inc. | N=190 ➔ 37 | Trial primary completion date: Aug 2025 ➔ May 2025

Enrollment change • Trial primary completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

COVALENT-101: Study of BMF-219, a Covalent Menin Inhibitor, in Adult Patients With AML, ALL (With KMT2A/ MLL1r, NPM1 Mutations), DLBCL, MM, and CLL/SLL (clinicaltrials.gov) - P1 | N=55 | Terminated | Sponsor: Biomea Fusion Inc. | Active, not recruiting ➔ Terminated; Biomea Fusion, Inc., is no longer pursuing oncology indications for BMF-219. No safety concerns or efficacy observations led to this study closure.

Trial termination • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Icovamenib Rescues Human Myotube Atrophy Ex Vivo and Displays Complete Lean Mass Preservation in a Type 2 Diabetes Rat Model (ADA 2025) - "The direct impact of icovamenib on myotube recovery and lean mass preservation was investigated. Ex-vivo derived 3D-engineered healthy human myotubes were cultured with icovamenib or garetosmab for 16 days, beginning one day prior to atrophy induction with Activin A or dexamethasone (dex), and myotube morphology was assessed. Icovamenib enhanced healthy myotube morphology and promoted recovery from drug-induced atrophy ex vivo. In ZDF rats, combination of icovamenib and low dose sem induced greater body weight reduction with protected lean mass. Collectively, these results support combination of icovamenib with GLP-1RA based therapies as a promising strategy to enhance body weight reduction with preservation of muscle homeostasis."

Late-breaking abstract • Preclinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

COVALENT-111: 26-Week Efficacy and Safety after 8 and 12 Weeks of Daily Oral Icovamenib in Patients with Poorly Controlled Type 2 Diabetes (ADA 2025) - "Icovamenib for 8 or 12 wks resulted in significant improvements in A1C at 26 wks in poorly controlled T2D. As expected, based on icovamenib's mechanism of action, this effect was most pronounced in insulin-deficient T2D. These results support icovamenib as a potential first-in-class menin inhibitor for the management of T2D."

Clinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Combination Therapy of Icovamenib and Semaglutide Enhances Body Weight Loss and Glycemic Control While Increasing Lean Mass in a Type 2 Diabetes Animal Model (ADA 2025) - "Icovamenib enhanced the effects of semaglutide in ZDF rats, demonstrating improved glycemic control, weight loss and lean mass. Assessment of this novel combination in persons with T2D and obesity is warranted, as it may provide greater glycemic and weight loss efficacy while potentially improving the overall side effect profile."

Combination therapy • Preclinical • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Design, synthesis, and evaluation of Menin-targeting compounds for the treatment of acute Myelocytic leukemia (AML). (PubMed, Eur J Med Chem) - P1 | "BMF-219, a promising inhibitor in Phase 2 clinical trials (NCT05153330), forms a stable and irreversible covalent bond with Menin...Finally, in vivo activity evaluation demonstrated that MJ-26 hydrochloride also displayed anti-tumor efficacy in the MV-4-11 mouse xenograft model. These findings may offer valuable insights and guidance for the development of Menin-targeting compounds for the treatment of hematologic malignancies."

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

Menin Inhibitors in KMT2A-Rearranged and NPM1-Mutated Acute Leukemia: A Scoping Review of Safety and Efficacy. (PubMed, Crit Rev Oncol Hematol) - "Menin inhibitors demonstrate promising clinical activity in molecularly defined leukemias, with Revumenib establishing proof-of-concept for this therapeutic approach. However, challenges remain, including resistance development, optimal timing of therapy initiation, and determination of effective combination strategies. Larger randomized trials with extended follow-up are needed to establish long-term efficacy and safety profiles. The rapid clinical development of multiple agents in this class suggests an expanding role for Menin inhibitors in leukemia treatment paradigms."

Journal • Review • Hematological Malignancies • Leukemia • Oncology • KMT2A • MEN1 • NPM1

Biomea Fusion Reports First Quarter 2025 Financial Results and Corporate Highlights (GlobeNewswire) - "Key Anticipated 2025 Milestones: Icovamenib (Oral Small Molecule Menin Inhibitor for Type 2 and Type 1 Diabetes): (i) 52-week data from the Phase II COVALENT-111 study in type 2 diabetes expected in the second half of 2025; (ii) Type-C meeting planned with FDA in the second half of 2025 to discuss a Phase IIb trial design and the requirements to advance icovamenib into later stage clinical development; (iii) Initiation of Phase II study of icovamenib in T2D patients currently uncontrolled on a GLP-1 based therapy in the second half of 2025; (iv) Preliminary data from the Phase II COVALENT-112 study in type 1 diabetes anticipated in the second half of 2025."

FDA event • New P2 trial • P2 data • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Icovamenib Treatment in Patients with Severe Insulin-Deficient Diabetes Led to a Significant Improvement in Pancreatic Beta-cell Function with a 53% Mean Increase in C-peptide Levels 3 Months After Last Dose (GlobeNewswire) - P=NA | N=NA | "Preclinical in vivo experiments indicated that icovamenib enhanced the responsiveness of human islets to GLP-1-based medicines, consistent with the increase in expression levels (transcript and protein) of both the GLP-1 receptor and intracellular insulin...ATTD 2025 Conference Highlights...The data represents the first large-scale assessment of C-peptide levels in icovamenib-treated patients, providing robust evidence supporting its proposed mechanism of action. C-peptide, a key biomarker of endogenous insulin production, demonstrated significant increases, indicating improved pancreatic beta-cell function over 3 months after the final dose of icovamenib...Patients with insulin deficient diabetes (n=45) experienced a mean increase in C-peptide index levels....Insulin deficient patients who received icovamenib (n=45) demonstrated a persistent increase in C-peptide levels beyond the active treatment period, over 3 months after the final dose of icovamenib..."

Clinical data • Preclinical • Type 2 Diabetes Mellitus

COMBINATION OF ICOVAMENIB AND GLP-1-BASED THERAPEUTIC AGENTS IMPROVES BETA CELL FUNCTION AND INSULIN SECRETION (ATTD 2025) - "Following the treatment, islets were tested for glucose stimulated insulin secretion in the presence of semaglutide (GLP-1 receptor agonist) or tirzepatide (GLP-1/GIP dual receptor agonist).Results Icovamenib induced a dose-dependent enhancement in insulin secretion potentiated by semaglutide or tirzepatide. Details into the mechanism will be presented.Conclusions These results highlight the complementary mechanisms of action: icovamenib increases beta-cell mass and function, while GLP-1-based therapies improve nutrient-stimulated insulin secretion and peripheral insulin sensitivity. Administering these agents as part of a combination regimen has the potential to provide a synergistic response, thereby enhancing the therapeutic window of GLP-1-based therapies."

Diabetes • Metabolic Disorders

Icovamenib: A Novel Approach to Diabetes Management (ATTD 2025) - "Sponsored by Biomea Fusion"

Diabetes • Metabolic Disorders

COVALENT-111: EVALUATING LONG-TERM EFFICACY AND SAFETY OF SHORT-TERM ICOVAMENIB TREATMENT IN PERSONS WITH TYPE 2 DIABETES (ATTD 2025) - P1/2 | "Conclusions Icovamenib addresses the root cause of T2D, beta-cell dysfunction, with a novel mechanism of action. COVALENT-111 aims to evaluate the long-term efficacy and safety of short-term icovamenib therapy, potentially addressing a significant unmet need in T2D management."

Clinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

COVALENT-111: EXPLORING ICOVAMENIB IN PERSONS WITH POORLY CONTROLLED SEVERE INSULIN-DEFICIENT (SIDD) TYPE 2 DIABETES (ATTD 2025) - P1/2 | "These exploratory patient-level data suggest menin-inhibition may be particularly effective in a presumed insulin-deficient subgroup of patients. This finding points to potential benefits of targeted treatment strategies in type 2 diabetes management, warranting further investigation in larger trials."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

1150 - PARALLEL INDUSTRY SYMPOSIUM 12 (INDUSTRY SESSION NOT INCLUDED IN THE MAIN EVENT CME/CPD CREDIT): Fusion Harnessing Menin Inhibition: Exploring Icovamenib as a Potential First-in-Class Medicine for Precision Diabetes Care - Industry Symposium (ATTD 2025) - "Sponsored by Biomea Fusion"

CME • Diabetes • Metabolic Disorders

Biomea Fusion to Unveil New Icovamenib Data at the 18th International Conference on Advanced Technologies & Treatments for Diabetes (GlobeNewswire) - "Biomea Fusion, Inc...today announced that it will feature two oral presentations, one poster presentation, and chair a symposium at the 18th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD 2025)...Biomea’s presentations at ATTD 2025 will showcase preclinical data evaluating the combination of icovamenib with GLP-1 receptor agonists, as well as new clinical findings from the Expansion Phase of the COVALENT-111 study."

P1/2 data • Preclinical • Type 2 Diabetes Mellitus

COVALENT-101: Study of BMF-219, a Covalent Menin Inhibitor, in Adult Patients With AML, ALL (With KMT2A/ MLL1r, NPM1 Mutations), DLBCL, MM, and CLL/SLL (clinicaltrials.gov) - P1 | N=55 | Active, not recruiting | Sponsor: Biomea Fusion Inc. | Recruiting ➔ Active, not recruiting | N=177 ➔ 55

Enrollment change • Enrollment closed • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

COVALENT-102: Study of Covalent Menin Inhibitor BMF-219 in Adult Patients With KRAS Driven Non-Small Cell Lung Cancer, Pancreatic Cancer, and Colorectal Cancer (clinicaltrials.gov) - P1 | N=13 | Terminated | Sponsor: Biomea Fusion Inc. | N=90 ➔ 13 | Trial completion date: Oct 2026 ➔ Jan 2025 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2025 ➔ Jan 2025; Biomea Fusion, Inc., is no longer pursuing oncology indications for BMF-219. No safety concerns or efficacy observations led to this study closure.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Colorectal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS • ROS1

Biomea Fusion Reports New Preclinical Data on Icovamenib-Semaglutide Combination Study (GlobeNewswire) - "Highlights of the Study: Superior Glycemic Control: A 60% reduction in fasting blood glucose level was observed with combination therapy compared to semaglutide alone; A 50% reduction in area under the curve (AUC) was observed during the Oral Glucose Tolerance Test (OGTT) with combination therapy versus semaglutide alone, indicating improved glucose metabolism (p1%) compared to semaglutide alone (p<0.05)...Combination therapy reduced body weight by 11.5% and fat mass by 29.5% compared to semaglutide alone; A 43% increase in lean mass compared to semaglutide alone was also observed with combination therapy....Icovamenib in combination with semaglutide was well tolerated across multiple time points."

Preclinical • Type 2 Diabetes Mellitus

Biomea Fusion to Host Conference Call to Announce Topline Results from Phase II COVALENT-111 Study in Patients with Type 2 Diabetes (T2D) (GlobeNewswire) - "Biomea Fusion...announced that it will host a conference call and webcast on Tuesday, December 17, 2024 at 8:00 am EST to present topline results from COVALENT-111, the company’s Phase II trial of icovamenib in patients with type 2 diabetes."

P2 data • Type 2 Diabetes Mellitus

Complete remission of NUP98 fusion-positive acute myeloid leukemia with the covalent menin inhibitor BMF-219, icovamenib. (PubMed, Haematologica) - "Not available."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • NUP98

COVALENT-111: Study of BMF-219 in Healthy Adult Subjects and in Adult Subjects With Type 2 Diabetes Mellitus (T2D) (clinicaltrials.gov) - P1/2 | N=414 | Active, not recruiting | Sponsor: Biomea Fusion Inc. | Suspended ➔ Active, not recruiting | Trial primary completion date: Jul 2024 ➔ Nov 2024

Enrollment closed • Trial primary completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Biomea Fusion Announces Approval of “icovamenib” as International Nonproprietary Name for BMF-219 (GlobeNewswire) - "Biomea Fusion...announced that the World Health Organization (WHO) has approved 'icovamenib' as the International Nonproprietary Name (INN) for its lead product candidate BMF-219, and that the United States Adopted Name Council has adopted 'icovamenib' as the United States Adopted Name (USAN) for BMF-219....Biomea will use 'icovamenib' in upcoming presentations, publications and public statements as the company advances the clinical development of the product candidate."

Commercial • Hematological Malignancies • Solid Tumor

BF-MNN-112: Phase 2 Trial of BMF-219 in Participants with Type 1 Diabetes Mellitus (clinicaltrials.gov) - P2 | N=190 | Active, not recruiting | Sponsor: Biomea Fusion Inc. | Suspended ➔ Active, not recruiting

Enrollment closed • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus