On December 12, 2022 Biomea Fusion, Inc. (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, reported preclinical data today for BMF-500, an investigational covalent FLT3 inhibitor, at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Biomea Fusion, DEC 12, 2022, View Source [SID1234625087]). The preclinical poster can be viewed at Biomea’s website at View Source
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BMF-500, a 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 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. The company is on track to submit an investigational new drug (IND) application for BMF-500 in the first half of 2023 and, subject to successful IND clearance, plans to initiate clinical trials evaluating BMF-500 as a single agent and in novel combinations shortly thereafter.
"The majority of late-stage and approved FLT3 inhibitors fall short of providing sufficient and sustained inhibition of FLT3 signaling required for maximal benefit. We believe the exquisite potency, selectivity and durability of BMF-500, all of which are possible through the design of this novel covalent molecule with our proprietary FUSION system, have the potential to translate to deep and durable remissions in patients with FLT3-mutant AML, representing nearly a third of all AML patients," said Steve Morris, M.D., Biomea’s Chief Medical Officer. "We look forward to advancing BMF-500 toward the clinic in 2023, which will mark our second clinical-stage novel covalent small molecule program for cancer and further solidify our position as a leader in next-generation covalent medicines."
"The impressive profile of BMF-500 speaks to the bench strength of our Discovery Team and to our ability to design and deliver novel therapeutics. We believe that targeting FLT3 with a covalent inhibitor, as we did with menin, represents another significant opportunity to improve the outcomes that reversible inhibition provide. BMF-500 has the potential to be an effective option as a monotherapy as well as in combination," said Thomas Butler, Biomea’s Chief Executive Officer and Chairman of the Board.
The data presented at the ASH (Free ASH Whitepaper) conference today showed that in FLT3-driven AML cell lines, three-hour exposure to BMF-500 produced complete phospho-FLT3 inhibition, which was maintained following washout of the compound. The commercially available reversible (i.e., non-covalent) FLT3 inhibitor gilteritinib required 16 times higher concentration than BMF-500 and continuous exposure for 96 hours to produce the same effect. The covalent small molecule inhibitor BMF-500 exhibited potent inhibition of FLT3 receptor kinase and marked cell killing in FLT3-ITD AML cell lines, as demonstrated by IC90s at physiologically relevant doses. In addition, the kinase profile of BMF-500 revealed high target selectivity and selective cytotoxicity profile against a panel of non-target cancer cell lines suggesting the potential for minimal off-target liabilities. As part of the poster presentation, Biomea also presented the results of two preclinical animal xenograft models in which BMF-500 demonstrated antitumor activity with sustained tumor regression and improved survival while being well tolerated, with body weight maintenance across treatment groups.
About BMF-500
BMF-500 is a novel orally bioavailable, highly potent and selective covalent small molecule inhibitor of FLT3 in preclinical development, which has been shown to exhibit favorable durability, selectivity and tolerability in preclinical studies in comparison to commercially available FLT3 inhibitor gilteritinib. BMF-500 was discovered and developed in-house by Biomea using its proprietary FUSION System and designed to have a therapeutic profile to allow for combinations with standard of care and novel targeted agents like BMF-219, Biomea’s investigational covalent menin inhibitor. The kinase profile of BMF-500 showed high target selectivity, suggesting the potential for minimal off-target liabilities.
About FLT3 (fms-like tyrosine kinase 3)
FLT3 is a receptor tyrosine kinase (RTK) that plays a central role in the survival, proliferation, and differentiation of immature blood cells. Notably, 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 United States each year. 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.