On June 13, 2025 Biomea Fusion, Inc. ("Biomea" or the "Company") (Nasdaq: BMEA), a clinical-stage diabetes and obesity medicines company, reported 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") (Press release, Biomea Fusion, JUN 13, 2025, View Source [SID1234653874]). The results will be presented in a poster presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) ("EHA") 2025 Congress in Milan, Italy.

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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 (Free EHA Whitepaper) 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
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 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.