BMF-500, a novel 3rd generation oral covalent inhibitor of FMS-like tyrosine kinase 3 (FLT3), is the second product candidate discovered and developed by Biomea’s proprietary FUSION™ System to enter the clinic

  • Phase I study (COVALENT-103) of BMF-500 will examine monotherapy safety and efficacy in adult patients with relapsed or refractory acute leukemia with FLT3 wild-type and FLT3 mutations, including those with co-occurring MLL1r / NPM1 mutations
  • BMF-500 was designed to be highly selective for FLT3 and to avoid inhibition of closely related receptors, such as cKIT that can cause myelosuppression and is thought to limit the safety and efficacy of other FLT3 inhibitors
  • Preclinical studies of BMF-500 have shown promising activity against all known FLT3 activating and resistance conferring mutations

REDWOOD CITY, CA, USA I October 17, 2023 I 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 that the first patient has been dosed in COVALENT-103, the company’s Phase I trial of BMF-500, an investigational covalent FLT3 inhibitor developed using the proprietary FUSIONTM System, in adult patients with relapsed or refractory acute leukemia.

“Despite several late stage and approved therapies targeting FLT3, the majority of patients with AML harboring FLT3 mutations have not achieved durable remissions. We believe that BMF-500, which is designed to have key attributes of covalency, potency, and selectivity, has the capacity to fully extinguish FLT3-driven disease and the potential to combine with other targeted therapies and standard-of-care agents,” said Steve Morris, MD, Biomea’s Chief Development Officer.

“Today, we have taken another important step to bring novel covalent drug candidates into the clinic by exploring the potential of BMF-500, an investigational covalent FLT3 inhibitor, in treating adult patients with relapsed or refractory acute leukemia. BMF-500 is designed to be a potent molecule and is the second covalent inhibitor we have developed in-house, demonstrating the potential of the FUSIONTM platform and our team in bringing novel assets to the clinic. Beyond single agent studies of BMF-500 we are planning combination studies with various approved therapies and therapy candidates, including BMF-219, to explore the potential of this powerful dual-mechanistic approach to provide deeper and more durable treatment responses,” said Thomas Butler, Biomea’s CEO and Chairman of the Board.

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. 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 BMF-219, 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 (ASH) 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 than the commercially available non-covalent FLT3 inhibitor gilteritinib. These data also showed complete tumor regression in mouse models of FLT3-ITD AML, with no tumor regrowth even after treatment cessation.

Data presented at the 2023 American Association for Cancer Research (AACR) Annual Meeting exhibited the potential utility of combination strategies to achieve higher antileukemic cell killing with reduced concentrations of BMF-500 and BMF-219. Additionally, Biomea has shown the potential of combinatorial approaches of BMF-500 and BMF-219 with MEK and BCL2 blockade in other preclinical studies. These data provide preclinical evidence for combining pathway-specific inhibitors as a promising 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 30% of AML patients have a FLT3 mutation, representing more than 6,000 incident patients in the U.S. each year. In addition, academic literature suggests that >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 covalent small molecules to treat patients with genetically defined cancers and metabolic diseases. 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 with various cancers and metabolic diseases, including diabetes. 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, Twitter and Facebook.

SOURCE: Biomea Fusion