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

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

Icovamenib and Semaglutide Combination Enhances Weight Loss While Preserving Lean Mass in ZDF Rats (OBESITY WEEK 2025) - "Icovamenib enhanced the effectiveness of low dose semaglutide in ZDF rats, promoting enhanced weight loss and complete preservation of lean mass together with improved glycemic control. Assessment of this novel combination in persons with obesity is warranted, as it may provide improved glycemic and weight loss effects."

Preclinical • Genetic Disorders • Obesity

Title: Icovamenib and Semaglutide Combination Enhances Weight Loss While Preserving Lean Mass in ZDF Rats (GlobeNewswire) - "Biomea Fusion Showcases Preclinical Advances for...Icovamenib with Low Dose Semaglutide at ObesityWeek 2025....Key Findings: Combination treatment was superior to low dose semaglutide; 60% lower fasting blood glucose vs semaglutide alone; 50% lower glucose area under the curve during oral glucose tolerance test....In the fourth quarter of 2025, Biomea plans to begin clinical evaluation of icovamenib added to the treatment of T2D patients who are currently on GLP-1 based treatment and not achieving glycemic targets. The first patient is expected to be dosed in the first quarter of 2026."

New trial • Preclinical • Obesity • Type 2 Diabetes Mellitus

Biomea Fusion to Present Poster Presentations at ObesityWeek 2025 (GlobeNewswire) - "The presentations will highlight preclinical data for BMF-650, Biomea’s next-generation oral small molecule glucagon-like peptide-1 ('GLP-1') receptor agonist ('RA'), and combination data for icovamenib, the company’s first-in-class covalent menin inhibitor, with semaglutide, a GLP-1 based therapy."

Preclinical • Obesity

Menin Inhibitors in KMT2A-Rearranged and NPM1-Mutated Acute Leukemia: A Scoping Review of Safety and Efficacy (SOHO 2025) - " Thirteen clinical trials evaluating six menin inhibitors—revumenib (SNDX-5613), ziftomenib (KO-539), bleximenib (KO-2806), enzomenib (DS-1594), BMF-219, and JNJ-75276617—were analyzed. These findings demonstrate the potent efficacy of menin inhibitors in genetically defined subsets of leukemia. However, their clinical application requires careful management of toxicity profiles, including QTc prolongation and differentiation syndrome. Additionally, menin inhibitors exhibit synergistic effects with agents like venetoclax and FLT3 inhibitors, enhancing therapeutic efficacy and potentially improving outcomes in KMT2A-rearranged and NPM1-mutated AML."

Clinical • Review • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • KMT2A • NPM1

Biomea Fusion Presents Data Demonstrating Enhanced Preclinical Activity of Icovamenib in Combination with Semaglutide in Type 2 Diabetes (T2D) Animal Model at the 61st EASD Annual Meeting… (GlobeNewswire) - "60% lower fasting blood glucose; 50% lower glucose AUC during OGTT; Greater reduction in HbA1c; >1% by Day 28 and >2% by Day 39; Greater improvement in insulin sensitivity; 75% lower HOMA-IR....~10% greater reduction in body weight, driven by fat loss with full preservation of lean mass...Biomea plans to advance clinical evaluation of icovamenib in combination with GLP-1 therapies, with a Phase II study expected to begin in the second half of 2025."

New P2 trial • Preclinical • Obesity • 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 | Terminated | Sponsor: Biomea Fusion Inc. | Active, not recruiting ➔ Terminated; Sponsor made a business decision to terminate the study based on prioritization of portfolio.

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

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

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=443 | Completed | Sponsor: Biomea Fusion Inc. | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • 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