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

Icovamenib, an investigational oral small molecule for the treatment of diabetes, activates mechanisms that support metabolic health (EASD 2026) - "Icovamenib-induced GLP-1 expression, myogenesis and protection from atrophy, align with menin's negative regulation of these events. Results additionally reveal icovamenib's potential to promote adipose tissue metabolism. Overall findings help shed mechanistic insights on the icovamenib-induced enhancements in glycemic control, fat reduction and lean mass preservation during combination treatment with low dose semaglutide in ZDF rats, and support icovamenib's potential for treating obesity in addition to diabetes."

Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Phase 2 Trial of Icovamenib in Participants With Type 2 Diabetes Who Are Not Achieving Glycemic Targets (clinicaltrials.gov) - P2 | N=64 | Active, not recruiting | Sponsor: Biomea Fusion Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

BF-MNN-112: Phase 2 Trial of BMF-219 in Participants With Type 1 Diabetes Mellitus (clinicaltrials.gov) - P2 | N=37 | Completed | Sponsor: Biomea Fusion Inc. | Terminated ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Biomea Fusion Announces First Patient Dosed in OPAL Study Evaluating Icovamenib in Combination with Semaglutide in Obesity (GlobeNewswire) - "The newly activated experimental OPAL study arm will evaluate the effects of Biomea’s investigational small molecule, icovamenib (100mg, QD for 12 weeks) in combination with low-dose semaglutide (for 24 weeks) versus low dose semaglutide alone (for 24 weeks) in individuals without type 2 diabetes that are either overweight (with one or more weight-related complications) or obese. This randomized double-blind study-arm, is designed to enroll 64 participants..."

Trial status • Obesity

Phase 2 Trial of Icovamenib in Participants With Type 2 Diabetes Who Are Not Achieving Glycemic Targets (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Biomea Fusion Inc. | Trial primary completion date: Jun 2027 ➔ Mar 2027

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

Biomea Fusion Announces Research Collaboration with University of Leicester to Evaluate Icovamenib in Combination with Semaglutide in Obesity (Investing News Network (INN)) - "The collaborative study will be activated within OPAL and will evaluate Biomea's investigational menin inhibitor, icovamenib, in combination with semaglutide in order to assess if adding icovamenib to the GLP-1 therapy will enhance the body weight lowering effects of semaglutide...The newly activated experimental arm will evaluate the effects of icovamenib (100 mg, QD for 12 weeks) in combination with low-dose semaglutide (for 24 weeks) versus low-dose semaglutide alone (for 24 weeks) in individuals without type 2 diabetes that are either overweight (with 1 or more weight-related complications) or obese. This randomized and double blinded study will begin enrollment in the third quarter and will assess the combination therapy with the primary outcome assessment to be performed at Week 24....Biomea will also present late-breaking preclinical findings at the 86th American Diabetes Association (ADA) Scientific Sessions..."

Licensing / partnership • Preclinical • Trial status • Obesity • Type 2 Diabetes Mellitus

Cascade-responsive HA-decorated liposome/mesoporous silica nanoplatform co-delivering BMF-219 and 5-FU enhances gastric cancer chemotherapy through Menin- and p53-associated apoptotic signaling. (PubMed, J Exp Clin Cancer Res) - "HLM@BF integrates Menin inhibition with 5-FU chemotherapy and enhances antitumor efficacy through Menin- and p53-associated apoptotic signaling, providing a targeted nanomedicine strategy for gastric cancer."

Journal • Gastric Cancer • Oncology • Solid Tumor

Icovamenib, a Menin Inhibitor, Improves Endogenous Insulin Secretion in Type 1 Diabetes: Results from the COVALENT-112 Study (ADA 2026) - "Icovamenib treatment in individuals with T1D appeared to slow the decline in endogenous insulin secretion observed in natural history studies, with a dose-response trend. Despite the small sample size, these findings suggest menin inhibition may enhance residual beta-cell function."

Late-breaking abstract • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Menin Inhibitor Icovamenib Activates Mechanisms That Support Metabolic Health (ADA 2026) - "Icovamenib-induced GLP-1 expression, myogenesis and protection from atrophy, align with menin's negative regulation of these events. Results additionally reveal icovamenib's potential to promote adipose tissue metabolism. Overall findings help provide mechanistic insights on the icovamenib-induced enhancements in glycemic control, fat reduction and lean mass preservation during combination treatment with low dose semaglutide in ZDF rats, and support icovamenib's potential for treating obesity in addition to diabetes."

Late-breaking abstract • Diabetes • Metabolic Disorders • Obesity

Emerging drug profile: menin inhibitors in NPM1-mutated and KM2A-rearranged acute myeloid leukemia. (PubMed, Leuk Lymphoma) - "Currently, several small-molecule menin inhibitors are being tested in combination with conventional therapies. This publication reviews the recent progress in investigating the clinical evidence of menin inhibitors (revumenib, ziftomenib, bleximenib, enzomenib, BMF-219, emilumenib) toward aggressive leukemias, guides future study and optimal treatment for patients with this type of leukemia."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • KMT2A • NPM1

Glycemic Improvements with Icovamenib in T2D on Background GLP-1 Therapy: COVALENT-111 Subgroup Analysis (ADA 2026) - "In adults with T2D receiving background GLP-1 RA therapy, icovamenib showed clinically meaningful reductions in HbA1c vs placebo, with the benefit continuing at 52 weeks. These findings suggest icovamenib may provide additive glycemic benefit alongside GLP-1-based therapy and support further evaluation of menin inhibition for T2D."

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

Molecular profiling of covalent menin inhibitor, BMF-219, in KRAS-mutated solid tumors (AACR 2024) - P1 | "Collectively, these data suggest that the functional pathway alterations induced by BMF-219 in solid tumor cells are likely pan-KRAS and are similar across different solid tumor indications. This provides further support for advancing the clinical investigation of BMF-219 in KRAS-driven solid tumors."

Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • KMT2A • KRAS • MYC

Targeting the Menin-KMT2A Axis in Acute Leukemia: From Epigenetic Dependency to Clinical Translation. (PubMed, Eur J Haematol) - "We critically evaluate the preclinical and clinical development of menin inhibitors, including revumenib, ziftomenib, bleximinib, and icovamenib, summarizing efficacy signals in relapsed/refractory disease, safety profiles, and emerging resistance mechanisms. Special attention is given to combination strategies with venetoclax, FLT3 inhibitors, chemotherapy, and epigenetic agents, which aim to enhance response durability and mitigate resistance. Finally, we discuss ongoing clinical trials, unresolved challenges in patient selection and sequencing, and future directions for integrating menin inhibition into precision-based treatment paradigms for acute leukemia."

Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • KMT2A • MEIS1 • NPM1 • NUP98

Phase 2 Trial of Icovamenib in Participants With Type 2 Diabetes Mellitus Who Are Not Achieving Glycemic Targets While Using GLP-1-Based Therapy (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Biomea Fusion Inc.

New P2 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Phase 2 Trial of Icovamenib in Participants With Type 2 Diabetes Who Are Not Achieving Glycemic Targets (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Biomea Fusion Inc.

New P2 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

COVALENT-111: 52-WEEK EFFICACY AND SAFETY OF ICOVAMENIB IN INSULIN-DEFICIENT TYPE 2 DIABETES (ATTD 2026) - "Short-term icovamenib treatment led to clinically significant improvements in glycemia, especially in insulin-deficient T2D patients. Reductions in HbA1c improved over time, and were durable through Week 52, nine months after icovamenib was stopped. These findings further support menin inhibition as a promising targeted strategy for T2D management."

Clinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Clinical Integration of Menin Inhibitors in AML: Evolving Data and Therapeutic Perspectives. (PubMed, Oncol Res) - "This manuscript reviews the molecular rationale of menin inhibition for aberrant homeobox/myeloid ectopic insertion site 1 (HOX/MEIS1)-driven gene expression and leukemogenesis, clinical trial outcomes, and safety data for menin inhibitors, with a focus on recently FDA-approved revumenib and several other agents in development, ziftomenib (KO-539), bleximenib (JNJ-75276617), and icovamenib (BMF-219). We also focused our discussion on future directions to include resistance mechanisms, biomarker identification and monitoring strategies, and combination therapies. Menin inhibition is now being clinically integrated into relapsed/refractory and frontline treatment settings."

Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • KMT2A • MEIS1 • NPM1

Food Effect Study in Healthy Volunteers (clinicaltrials.gov) - P1 | N=60 | Completed | Sponsor: Biomea Fusion Inc. | Active, not recruiting ➔ Completed

Trial completion

Menin-MLL inhibitors as a new therapeutic target for middle ear cholesteatoma. (PubMed, Sci Rep) - "In our previous study, we demonstrated that histone modifications are involved in the pathogenesis of cholesteatoma and that keratinocyte growth factor (KGF)-induced murine cholesteatoma is suppressed by administration of MI-503, a menin-MLL inhibitor. Among the menin-MLL inhibitors, BMF-219 (50 µM), a covalent menin inhibitor, showed the strongest inhibitory effect against cholesteatoma, with a 70.75 ± 8.92% rate of residual lesion. These findings show promising results for the therapeutic use of menin-MLL inhibitors in the non-surgical management of cholesteatoma."

Journal • Otorhinolaryngology

Biomea’s anticipated 2026 milestones include (GlobeNewswire) - "Anticipate completion of additional preclinical studies in relevant diabetes models to further evaluate the potential of icovamenib and BMF-650 across selected diabetes and obesity subpopulations."

Preclinical • Obesity • Type 2 Diabetes Mellitus

Food Effect Study in Healthy Volunteers (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: Biomea Fusion Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed

The promise of menin inhibitors: from approval to triplet regimens. (PubMed, Hematology Am Soc Hematol Educ Program) - "Next-generation agents (ziftomenib, bleximenib, enzomenib, BMF-219) have displayed similar composite complete remission rates (20-35%) and overall response rates (45-65%) in heavily pretreated KMT2Ar and NPM1m acute myeloid leukemia (AML) with measurable residual disease (MRD) negativity and prolonged overall survival (5-7 months)...Acquired mutations in the menin gene described in 39% of post-revumenib relapses have not been identified following other inhibitors (ziftomenib, bleximenib), prompting new questions about resistance mechanisms. These promising results swiftly led to the launch of multiple trials of menin inhibitors combined with intensive (cytarabine and anthracycline) and nonintensive (venetoclax and hypomethylating) chemotherapy backbones...Ongoing/pending phase 3 trials will clarify whether menin blockade should be incorporated into frontline and maintenance regimens for all patients with KMT2A rearranged or NPM1 mutant disease. In the current era, menin..."

Journal • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • KMT2A • NPM1

Food Effect Study in Healthy Volunteers (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Biomea Fusion Inc.

New P1 trial

Covalent Menin Inhibitor Bmf-219 in Patients with Relapsed or Refractory (R/R) Acute Leukemia (AL): Preliminary Phase 1 Data from the Covalent-101 Study (ASH 2023) - P1 | "Patient B: 70/F, NPM1m, ECOG=1, 125 mg QD, Arm B, 1 prior line of treatment with decitabine and an investigational agent. BMF-219 is generally well tolerated with no DLT observed (and able to be taken with and without CYP3A4 inhibitors) with no pts discontinuing therapy due to toxicity. BMF-219 dose escalation is ongoing and approaching target exposure. BMF-219 demonstrates early signs of clinical activity in different genomic subgroups."

Clinical • P1 data • Bone Marrow Transplantation • Chronic Lymphocytic Leukemia • Diabetes • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Metabolic Disorders • Oncology • Solid Tumor • CEBPA • KMT2A • NPM1 • NSD1 • NUP214 • NUP98 • SETBP1

MODULE 5: Potential Role of Menin Inhibitors and Other Novel Agents in the Treatment of AML (ASH 2024) - "This program is supported by educational grants from AbbVie Inc, Astellas, and Daiichi Sankyo Inc.Mechanism of action of menin inhibitors and rationale for their activity in AML with KMT2 rearrangements and NPM1 mutations Pharmacologic similarities and differences among various menin inhibitors under investigation for AML, such as revumenib, ziftomenib and BMF-219 Early efficacy and safety data with novel menin inhibitors for R/R AML Design, eligibility criteria and available efficacy and safety findings from the pivotal Phase II AUGMENT-101 trial evaluating revumenib for patients with R/R leukemias; efficacy of revumenib for AML with a KMT2 rearrangement FDA breakthrough therapy designation of revumenib; potential role in clinical practice Rationale for targeting CD123 in AML; structural components and mechanism of action of the anti-CD123 antibody-drug conjugate pivekimab sunirine Available data with, ongoing evaluation of and potential clinical role of pivekimab..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123 • IL3RA • NPM1