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

Icovamenib Rescues Human Myotube Atrophy Ex Vivo and Displays Complete Lean Mass Preservation in a Type 2 Diabetes Rat Model (ADA 2025) - "Available on Friday, June 13, 2025 at 08:00am CDT."

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) - "Available on Friday, June 13, 2025 at 08:00am CDT."

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) - "Available on Friday, June 13, 2025 at 08:00am CDT."

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

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

Biomea Fusion Presents Preclinical Data Showing Icovamenib (BMF-219) Enhanced Effectiveness of GLP-1-Based Therapies... (GlobeNewswire) - "Preclinical studies evaluated insulin secretion by GLP-1-based therapies (tirzepatide and semaglutide) using human islets cultured ex vivo under hyperglycemic conditions, with and without icovamenib treatment; We hypothesized that menin inhibition would enhance the effectiveness of GLP-1-based therapies and showcased functional data, indicating stronger insulin responses with both tirzepatide and semaglutide when combined with icovamenib treatment. Further studies with orforglipron also indicated that icovamenib pretreatment improved insulin secretion, approximately doubling the effect-size depending on the dose....The initiation of a Phase II study, COVALENT-211, to evaluate the combination of icovamenib with a GLP-1-based therapy, is planned for 2025."

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

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

Biomea Fusion Reports Second Quarter 2024 Financial Results and Corporate Highlights (GlobeNewswire) - "Anticipated Milestones: Complete dose escalation portion of COVALENT-101 expected by year end 2024 (Two cohorts, CLL and DLBCL of COVALENT-101 have been discontinued due to insufficient enrollment.); Complete dose escalation portion of COVALENT-102 expected by year end 2024."

Trial status • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lung Cancer • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

COVALENT 112—A Clinical Trial Assessing BMF-219, an Oral Covalent Menin Inhibitor in Type 1 Diabetes (ADA 2024) - P2 | "BMF-219 is a novel oral covalent menin inhibitor. In preclinical studies, it has demonstrated beta cell proliferation. COVALENT-112 assesses the efficacy and safety of 12-week QD BMF-219 in Stage 3 T1D, potentially addressing an important unmet need in this patient population."

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

BF-MNN-112: Phase 2 Trial of BMF-219 in Participants With Type 1 Diabetes Mellitus (clinicaltrials.gov) - P2 | N=190 | Suspended | Sponsor: Biomea Fusion Inc. | Recruiting ➔ Suspended

Trial suspension • Diabetes • Metabolic Disorders • Type 1 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=414 | Suspended | Sponsor: Biomea Fusion Inc. | Recruiting ➔ Suspended

Trial suspension • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus