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 30-40% of AML and up to 5% of ALL cases, associated with poor prognosis and high relapse risk, especially after gilteritinib failure.

• Existing FLT3 inhibitors face challenges such as resistance, adverse effects, and limited efficacy, especially post-gilteritinib failure.

• BMF-500 was designed for high selectivity, minimal off-target effects, and compatibility with combination therapies, avoiding c-KIT 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 in the U.S. at 21 sites, enrolling 20 patients as of November 2024.

• Dose escalation uses accelerated titration and 3+3 design, with parallel arms for patients with/without CYP3A4 inhibitors; Arm A (150 mg), Arm B (50 mg).

• Patients are heavily pretreated, median of 4 prior therapies; 65% had FLT3 mutations, all post-gilteritinib failure, some with two or more prior FLT3 inhibitors.

• Median age was 55.2 years; 45% had prior HSCT and 90% had prior venetoclax regimens.

• Both FLT3-mutant and wild-type relapsed/refractory acute leukemia patients included.

Safety and tolerability findings

• BMF-500 demonstrated a generally well-tolerated safety profile across all dose levels, with no dose-limiting toxicities, dose reductions, or QT prolongation.

• Most common adverse events (≥20%) included anemia, febrile neutropenia, hypocalcemia, hypokalemia, and peripheral edema; most were mild and manageable.

• No treatment-related cytopenias or QT prolongation observed as of data cut-off.

• Lack of c-KIT inhibition suggests low risk of myelosuppression and cytopenias.

• One case of grade 2 hypertension resolved without discontinuation.