BMF-500

New clinical results show sustained CRi, deep bone marrow responses, and encouraging survival in FLT3-mutant AML patients, including those previously treated with gilteritinib REDWOOD CITY, Calif., June 13, 2025 (GLOBE NEWSWIRE) -- Biomea Fusion, Inc. (“Biomea” or the “Company”) (Nasdaq: BMEA), a clinical-stage diabetes and obesity medicines company, today announced updated preliminary clinical data from the ongoing Phase I COVALENT-103 trial of BMF-500 in adults with relapsed or refractory (“R/R”) acute leukemia (“AL”). The results will be presented in a poster presentation at the European Hematology Association (“EHA”) 2025 Congress in Milan, Italy. The presentation by Dr. Farhad Ravandi of The University of Texas MD Anderson Cancer Center will highlight emerging safety, pharmacokinetics/pharmacodynamics, and early clinical activity data for BMF-500, a highly selective covalent FMS-like tyrosine kinase 3 (“FLT3”) inhibitor, in heavily pretreated patients with R/R AL. Key Results from the EHA 2025 Poster Presentation 27 patients were enrolled across two study arms, Arm A (no CYP3A4 inhibitor; n=10) and Arm B (CYP3A4 inhibitor; n=17). All patients had R/R AL, with a median of 4 prior lines of therapy. 18 of the 27 patients were FLT3 mutations (“FLT3m”) while the other 9 patients had FLT3 wild-type AL. Frequent co-mutations included WT1, TP53, IDH1/2, and NRAS. All 18 FLT3m patients had failed gilteritinib in the R/R setting and 9 of the 18 had received at least two FLT3 inhibitors prior to study entry. 26 of 27 (96%) enrolled patients had also received and failed the BCL2 inhibitor venetoclax. Key findings include: Clinical Activity Observed : 9 of 11 efficacy-evaluable FLT3m patients, defined as all patients enrolled who received at least one dose and had at least one disease assessment, showed bone marrow (BM) blast reduction; 5 of 11 achieved >50% BM blast reduction. 1 FLT3m patient achieved complete remission with incomplete hematologic recovery (CRi), sustained for 6 cycles. 1 FLT3m patient achieved morphologic leukemia-free state (MLFS); response is ongoing. 1 FLT3m patient met all criteria for partial response (PR) except platelet recovery; categorized as near PR. 2 of 4 efficacy-evaluable FLT3 wild-type patients achieved durable disease control ≥120 days, with treatment ongoing for one patient. Additional clinical improvements include reductions in peripheral blasts, transfusion dependency, and frequency of hydroxyurea use. Pharmacokinetics/Pharmacodynamics : FLT3 inhibition correlated with BMF-500 systemic exposures. Bone marrow and plasma concentrations of BMF-500 and its metabolites were comparable, suggesting good compartmental penetration. Survival: Median overall survival (mOS) among all treated FLT3m patients (n=18) was 3.8 months (Arm A) and 3.5 months (Arm B) during dose escalation. For the efficacy-evaluable FLT3m patients (n=12), the mOS for Arms A and B was 3.8 and 3.6 months, respectively during dose escalation. These survival durations compare favorably to historical mOS of 2.1 months in patients with R/R FLT3m acute myeloid leukemia (“AML”) post-failure with both gilteritinib and venetoclax. 1 Ongoing Dose Escalation : Dose escalation continues at 200 mg BID (Arm A) and 75 mg BID (Arm B). Based on observed activity and tolerability, further evaluation is underway to determine optimal biologic dose (“OBD”) and recommended Phase II dose (“RP2D”). Safety and Tolerability BMF-500 was generally well-tolerated across dose levels. No dose-limiting toxicities (DLTs), QT prolongation, or discontinuations due to treatment-related adverse events were reported. Escalation is ongoing without safety restrictions. “The updated COVALENT-103 results continue to support the potential of BMF-500 as a selective, covalent FLT3 inhibitor,” said Mick Hitchcock, Ph.D., Interim Chief Executive Officer of Biomea Fusion. “We are encouraged by the depth of bone marrow responses, the achievement of MLFS and CRi, and the early survival benefit in heavily pretreated patients with FLT3 mutations who had progressed following prior FLT3 inhibitor therapy. These data speak to BMF-500’s potential to meaningfully improve outcomes in a high-risk AML population with no currently available treatment options.” Following completion of the COVALENT-103 dose escalation phase in R/R AL patients with FLT3m, Biomea plans to conclude its internal development of BMF-500 in oncology and is actively exploring strategic partnerships to advance the program. Poster Presentation Details Date/Time: Saturday, June 14 (18:30-19:30 CEST) Title: Covalent FLT3 Inhibitor BMF-500 in Relapsed or Refractory (R/R) Acute Leukemia (AL): Preliminary Phase 1 Data from the COVALENT-103 Study (NCT05918692) Poster Number: PS1520 Presenter: Farhad Ravandi, M.D., University of Texas MD Anderson Cancer Center A bout COVALENT-103 COVALENT-103 is a multicenter, open-label, non-randomized trial seeking to evaluate the safety and efficacy of BMF-500, a twice daily oral treatment, in adult patients with R/R AL with FLT3 wild-type or FLT3m. The Phase I COVALENT-103 study aims to evaluate the safety and tolerability of BMF-500, determine the optimal biologic dose and recommended Phase II dose, and identify initial efficacy signals. Additional information about the Phase I clinical trial of BMF-500 can be found at ClinicalTrials.gov using the identifier, NCT05918692. About BMF-500 BMF-500 is an investigational, orally bioavailable, covalent small molecule inhibitor of FLT3, discovered in-house using Biomea’s proprietary FUSION™ System. Designed to be highly potent and selective, BMF-500 has demonstrated encouraging potential in extensive preclinical studies. Its kinase inhibitory profile indicates strong target selectivity, which may translate to a reduced risk of off-target effects. About Biomea Fusion Biomea Fusion is a clinical-stage diabetes and obesity medicines company focused on the development of its oral small molecules, icovamenib and BMF-650, both designed to significantly improve the lives of patients with diabetes, obesity, and other metabolic diseases. We aim to cure. Visit us at biomeafusion.com and follow us on LinkedIn , X , and Facebook . Forward-Looking Statements Statements we make in this press release may include statements which are not historical facts and are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact, including statements regarding the clinical and therapeutic potential of our product candidates and development programs, including BMF-500, the potential of BMF-500 as a treatment for patients with FLT3m R/R AL, our research, development, partnership and regulatory plans, and the timing of such events may be deemed to be forward-looking statements. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. Any forward-looking statements in this press release are based on our current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including the risk that preliminary or interim results of preclinical studies or clinical trials may not be predictive of future or final results in connection with future clinical trials and the risk that we may encounter delays in preclinical or clinical development, patient enrollment and in the initiation, conduct and completion of our ongoing and planned clinical trials and other research and development activities. These risks concerning Biomea’s business and operations are described in additional detail in its periodic filings with the U.S. Securities and Exchange Commission (SEC), including its most recent periodic report filed with the SEC and subsequent filings thereafter. Biomea Fusion explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law. Reference: 1. Corley et al. (P1798) HemaSphere 2024;8(S1), 3339-3340. Contact : Meichiel Jennifer Weiss Sr. Director, Investor Relations and Corporate Development IR@biomeafusion.com Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

Preliminary data supports BMF-500’s potential as a transformative therapy for patients with FLT3 mutated relapsed or refractory (R/R) acute leukemiaBMF-500 showed a favorable safety and tolerability profile, with no dose-limiting toxicities observed across all dose levelsPharmacokinetic and pharmacodynamic data confirmed on-target FMS-like tyrosine kinase 3 (FLT3) inhibition, demonstrating dose-proportional activity and good compartmental penetrationPreliminary Phase I data for BMF-500 in R/R acute leukemia patients with FLT3 gene mutations having failed gilteritinib indicated clinical activity with evidence of responses, including a first complete response with incomplete hematologic recovery (CRi) and reductions in bone marrow blasts in 5 of 6 of the evaluable FLT3 mutated patients REDWOOD CITY, Calif., Dec. 09, 2024 (GLOBE NEWSWIRE) -- Biomea Fusion, Inc. (“Biomea” or “the company”) (Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to discovering and developing novel covalent small molecules to treat and improve the lives of patients with genetically defined cancers and metabolic diseases, today announced preliminary data from the ongoing Phase I COVALENT-103 study evaluating BMF-500, the company’s investigational covalent FLT3 inhibitor developed using the proprietary FUSION™ System. “These early findings from the COVALENT-103 study announced today highlight the potential of BMF-500 to deliver meaningful clinical benefits for patients with acute leukemia harboring a FLT3 mutation. BMF-500 is an exceptionally potent molecule and the second covalent inhibitor we have developed in-house and advanced to the clinic and has shown high target selectivity and inhibition,” said Thomas Butler, CEO of Biomea Fusion. “Our early results are particularly exciting as FLT3 gene mutations are common in AML patients and are associated with a very poor prognosis. Patients with such mutations who have failed gilteritinib have a median overall survival of less than 2 months. We hope to provide a significant improvement in the outcome for these patients with BMF-500. Given the safety profile demonstrated to date, and the lack of myelosuppression, we think BMF-500 could be an excellent combination partner used in standard of care.” As of the data cut off, November 20, 2024, 20 patients with R/R acute leukemia had been enrolled in the dose-escalation portion of the study, all of whom received at least one dose of BMF-500. Among these, the study enrolled 13 patients with confirmed FLT3-mutations, of which 10 harbored FLT3-ITD mutations and 3 had FLT3-TKD mutations. All patients with FLT3-mutations had progressed following treatment with gilteritinib, and 5 had received at least 2 prior FLT3 inhibitors. The study enrolled 5 patients with wild-type FLT3 and 2 patients with an unknown FLT3 mutation status. The median number of prior lines of therapies among the enrolled patients was 4. No QT prolongations or related cytopenias were observed and no dose-limiting toxicities (DLTs) were reported as of the data cut off. BMF-500 was generally well tolerated, and dose escalation is continuing per protocol. Pharmacokinetic/pharmacodynamic data confirmed on-target FLT3 inhibition, as BMF-500 and its metabolites showed bone marrow penetration and near complete FLT3 inhibition as early as Day 1 of dosing, as well as dose-proportional FLT3 inhibition. Preliminary data supports BMF-500’s potential as a transformative therapy for patients with FLT3 mutated R/R acute leukemia. During dose escalation, BMF-500 achieved a first CRi at the end of Cycle 2, in 1 of 2 (50%) FLT3 mutated patients dosed at 100 mg twice daily (BID), while the other patient experienced a clearance of peripheral blasts, greater than 50% reduction in bone marrow blasts and reduced transfusion frequency. The majority (5 of 6) of efficacy evaluable FLT3-mutated patients experienced a reduction of their bone marrow blasts. Other evidence of clinical activity such as: clearance or reduction of peripheral blasts, reduction of transfusion frequency, reduction in use of hydroxyurea were observed. Case Study Highlights of Patient with Complete Response (CRi) 61-year-old patient with R/R AML, post allogenic transplant, with six co-occurring mutations (FLT3-ITD, ASXL1, IDH2, PHF6, RUNX1, SRSF2)4 prior treatment regimens including venetoclax and gilteritinibConfirmed CRi at 100 mg BID dosingProgressive improvement in normal white blood cells, neutrophils, and monocytes despite ongoing transfusion needs Webcast and Conference Call Details Biomea Fusion will host a webcast and conference call today, Monday, December 9 at 4:30 pm EST. Interested parties will be able to join the webcast and view the related presentation under the Investors and Media section of the company’s website at https://investors.biomeafusion.com/news-events/events. A replay of the webcast and conference call will be archived on Biomea’s website following the event. About COVALENT-103 COVALENT-103 is a multicenter, open-label, non-randomized trial seeking to evaluate the safety and efficacy of BMF-500, a twice daily oral treatment, in adult patients with relapsed or refractory acute leukemia with FMS-like tyrosine kinase 3 (FLT3) wild-type and FLT3 mutations. The Phase I COVALENT-103 study aims to evaluate the safety and tolerability of BMF-500, determine the optimal biologic dose and recommended Phase II dose. Additional information about the Phase I clinical trial of BMF-500 can be found at ClinicalTrials.gov using the identifier, NCT05918692. About BMF-500 BMF-500, an investigational, novel, orally bioavailable, highly potent and selective covalent small molecule inhibitor of FLT3, was discovered and developed in-house at Biomea using the company’s proprietary FUSION™ System and has demonstrated encouraging potential based on extensive preclinical studies. The kinase inhibitory profile of BMF-500 showed high target selectivity, suggesting the potential for reduced off-target liabilities. BMF-500 was designed to have a therapeutic profile to allow for combinations with standard of care and/or novel targeted agents like icovamenib, Biomea’s investigational covalent menin inhibitor currently in clinical development for solid and liquid tumors as well as diabetes. Previous data presented at the 2022 American Society of Hematology Annual Meeting showed BMF-500’s picomolar affinity for inhibition of activating FLT3 mutations, including FLT3-ITD and various tyrosine kinase domain (TKD) mutations. BMF-500 demonstrated multi-fold higher potency and increased cytotoxicity as compared to the commercially available non-covalent FLT3 inhibitor gilteritinib. These data also showed complete tumor regression in mouse models of FLT3-ITD acute myeloid leukemia (AML), with no tumor regrowth even after treatment cessation. Data presented at the 2023 American Association for Cancer Research (AACR) Annual Meeting demonstrated the potential utility of combination strategies to achieve higher antileukemic cell killing with reduced concentrations of BMF-500 and icovamenib. Additionally, Biomea has shown the potential of combinatorial approaches of BMF-500 and icovamenib with MEK and BCL2 blockade in other preclinical studies. These data provide preclinical evidence for combining pathway-specific inhibitors as a potential therapeutic strategy for further investigation in acute leukemia. About FLT3 in AML FLT3 is a receptor tyrosine kinase (RTK) that plays a central role in the survival, proliferation, and differentiation of immature blood cells. FLT3 gene mutations are common in patients with AML and are associated with a poor prognosis. Nearly 40% of AML patients have a FLT3 mutation, representing more than 7,000 incident patients in the U.S. each year. Once failing the only approved agent in the R/R setting, gilteritinib, patients typically have a poor prognosis and very short survival (median overall survival ~1.8 months). Academic literature suggests that up to 50% of AML patients with an NPM1 mutation also harbor a FLT3 mutation. While FLT3-specific and pan-tyrosine kinase inhibitors are approved by the FDA across various lines of therapy in AML, these agents have produced relatively low rates of durable responses and overall survival remains an unmet need. About Biomea Fusion Biomea Fusion is a clinical-stage biopharmaceutical company focused on the discovery and development of oral covalent small molecules to improve the lives of patients with diabetes, obesity, and genetically defined cancers. A covalent small molecule is a synthetic compound that forms a permanent bond to its target protein and offers a number of potential advantages over conventional non-covalent drugs, including greater target selectivity, lower drug exposure, and the ability to drive a deeper, more durable response. We are utilizing our proprietary FUSION™ System to discover, design, and develop a pipeline of next-generation covalent-binding small-molecule medicines designed to maximize clinical benefit for patients. We aim to have an outsized impact on the treatment of disease for the patients we serve. We aim to cure. Visit us at biomeafusion.com and follow us on LinkedIn, X, and Facebook. Forward-Looking Statements Statements we make in this press release may include statements which are not historical facts and are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact, including statements regarding the clinical and therapeutic potential of our product candidates and development programs, may be deemed to be forward-looking statements. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. Any forward-looking statements in this press release are based on our current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including the risk that we may encounter delays in preclinical or clinical development, patient enrollment and in the initiation, conduct and completion of our ongoing and planned clinical trials and other research and development activities, and the risk that preliminary or interim data from our clinical trials will not be predictive of future results of such trials. These risks concerning Biomea Fusion’s business and operations are described in additional detail in its periodic filings with the U.S. Securities and Exchange Commission (the “SEC”), including its most recent periodic report filed with the SEC and subsequent filings thereafter. Biomea Fusion explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law. Contact:Investor and Media Relations:Ramses ErdtmannCOO & President of Biomea Fusionre@biomeafusion.com