Biomea Fusion (BMEA) Study Update summary

Study background and rationale

• BMF-500 is a novel, highly potent, selective covalent FLT3 inhibitor developed for relapsed/refractory acute leukemia, particularly AML with FLT3 mutations, and is orally bioavailable.

• FLT3 mutations are present in up to 37% of AML and ~5% of ALL, associated with poor prognosis, high relapse risk, and limited treatment options after gilteritinib failure.

• Existing FLT3 inhibitors have limited efficacy, with low durable response rates and significant side effects, highlighting the need for more effective therapies.

• BMF-500 was designed for high selectivity, minimal off-target effects, and potential for combination therapy, avoiding cKIT inhibition.

• Preclinical studies showed BMF-500 is ~24-fold more potent than gilteritinib, induces sustained tumor regression, and is effective against resistance mutations.

Study design and patient characteristics

• COVALENT-103 is a multicenter, open-label, non-randomized Phase 1 trial evaluating BMF-500 in adults with relapsed/refractory acute leukemia, including both FLT3 wild-type and FLT3 mutations.

• The study uses dose escalation with accelerated titration and 3+3 design, with parallel arms for patients with/without CYP3A4 inhibitors.

• As of November 2024, 20 patients were enrolled, median age 55.2 years, median of 4 prior therapies, most had prior intensive therapy, stem cell transplant, and venetoclax regimens.

• 65% of patients were FLT3-mutant, all of whom had failed prior FLT3 inhibitors, including gilteritinib; some had received two or more FLT3 inhibitors.

• The population is heavily pretreated and high-risk, with 90% having received venetoclax regimens.

Safety and tolerability findings

• BMF-500 demonstrated a favorable safety profile with no dose-limiting toxicities, no dose reductions, and no treatment-related cytopenias.

• No QT prolongation or differentiation syndrome observed to date.

• Most common adverse events were mild and manageable; anemia, febrile neutropenia, hypocalcemia, hypokalemia, and peripheral edema occurred in ≥20% of patients.

• Lack of c-KIT inhibition suggests low risk for myelosuppression and cytopenias, supporting combination potential.

• No dose reductions or significant adverse events were observed as of the data cut-off.