BMF-500 / Biomea Fusion - LARVOL DELTA

MODULE 3: Role of FLT3 Inhibitors in AML Management (ASH 2024) - "This program is supported by educational grants from AbbVie Inc, Astellas, and Daiichi Sankyo Inc.Pharmacologic similarities and differences among available FLT3 inhibitors for AML; implications for potency, activity and tolerability Principal findings from the Phase III QuANTUM-First study evaluating the addition of quizartinib to chemotherapy and its continuation as a single agent for patients with newly diagnosed AML with a FLT3-ITD mutation FDA approval of quizartinib for previously untreated AML with a FLT3-ITD mutation; clinical role Long-term outcomes reported with gilteritinib versus salvage chemotherapy for patients with relapsed/refractory (R/R) AML with a FLT3 mutation; optimal integration into routine practice Early data with gilteritinib combined with standard intensive chemotherapy or venetoclax-based therapy for AML with a FLT3 mutation Available data with and ongoing investigations of other novel FLT3 inhibitors, such as crenolanib and BMF-500, for AML..."

Acute Myelogenous Leukemia • FLT3

Covalent-103: A Phase 1, Open-Label, Dose-Escalation, and Dose-Expansion Study of Bmf-500, an Oral Covalent FLT3 Inhibitor, in Adults with Acute Leukemia (AL) (ASH 2023) - P1 | "Endpoints include best overall response rate (ORR), complete remission (CRc), duration of response (DOR), relapse-free survival (RFS) and overall survival (OS). The study was initiated in July 2023 and will enroll ~110 participants at approximately 30 sites."

Clinical • P1 data • Bone Marrow Transplantation • CNS Disorders • Hematological Malignancies • Leukemia • Oncology • FLT3

COVALENT-103: A Phase 1 Study of BMF-500 in Adults With Acute Leukemia (clinicaltrials.gov) - P1 | N=35 | Active, not recruiting | Sponsor: Biomea Fusion Inc. | Recruiting ➔ Active, not recruiting | N=84 ➔ 35 | Trial primary completion date: Jul 2025 ➔ Jan 2026

Enrollment change • Enrollment closed • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • NPM1

Biomea Fusion Reports Second Quarter 2025 Financial Results and Corporate Highlights (GlobeNewswire) - "BMF-500 (Oral Small Molecule FLT3 Inhibitor in Acute Myeloid Leukemia (AML)):...The Company concluded its oncology efforts and is now exploring strategic partnerships for BMF-500."

Pipeline update • Acute Myelogenous Leukemia

COVALENT FLT3 INHIBITOR BMF-500 IN RELAPSED OR REFRACTORY (R/R) ACUTE LEUKEMIA (AL): PRELIMINARY PHASE 1 DATA FROM THE COVALENT-103 STUDY (NCT05918692) (EHA 2025) - P1 | "Background: R/R FLT3m AL post-failure with gilteritinib (gilt) has a poor prognosis...Baseline features: 8 (33.3%) females, 5 (20.8%) non-whites, mean 57 yrs (23,80), median therapies 4 (1,10), HSCT 10 (41.7%), 24 (100%) with prior venetoclax (ven)...Nine (81.8%) pts showed clinical activity: decreased BM blasts (77.8%; 1 normalized blasts, 1 >50% reduction, 5 50% reduction), 4 decreased hydroxyurea use, 4 decreased transfusions... BMF-500 was well-tolerated. The majority of efficacy-evaluable pts showed reduced BM blasts, with 1 pt achieving CRi. mOS of the efficacy-evaluable FLT3m pts has not yet been reached."

P1 data • Bone Marrow Transplantation • Dermatology • Endocrine Disorders • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hypotension • Leukemia • Neutropenia • Oncology • Pain • Pulmonary Disease • Respiratory Diseases • FLT3

Biomea Fusion Presents Updated Preliminary Clinical Data for Covalent FLT3 Inhibitor BMF-500 in Relapsed or Refractory Acute Leukemia at EHA 2025 (GlobeNewswire) - P1 | N=84 | COVALENT-103 (NCT05918692) | Sponsor: Biomea Fusion Inc. | "27 patients were enrolled across two study arms, Arm A (no CYP3A4 inhibitor; n=10) and Arm B (CYP3A4 inhibitor; n=17)....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....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."

P1 data • Acute Myelogenous Leukemia

Biomea Fusion’s BMF-500 Selected for Poster Presentation at EHA 2025 Highlighting Phase I Data in Relapsed/Refractory Acute Leukemia (GlobeNewswire) - P1 | N=84 | COVALENT-103 (NCT05918692) | Sponsor: Biomea Fusion Inc. | "Median treatment duration was 48 d (1,170). Eleven (45.8%) pts had at least one disease assessment and were efficacy evaluable. Nine (81.8%) pts showed clinical activity: decreased BM blasts (77.8%; 1 normalized blasts, 1 >50% reduction, 5 50% reduction), 4 decreased hydroxyurea use, 4 decreased transfusions. Objective response (ELN 2017) occurred as early as end of C1, and best response as CRi by end of C2. At 100 mg BID/DL2 (Arm A), 1 of 2 FLT3m pts achieved CRi and completed six cycles; the other achieved >60% reduced BM blasts. mOS for the 23 pts is 3.48 mos (3.25, NE; 95% CI; see figure) whereas mOS for the 7 efficacy evaluable FLT3m pts has not been reached (not shown); 9 pts continue in survival follow up. The historical mOS for pts R/R to gilt/ven is 2.1 mos."

P1 data • Acute Myelogenous Leukemia

Biomea Fusion Reports First Quarter 2025 Financial Results and Corporate Highlights (GlobeNewswire) - "Key Anticipated 2025 Milestones:...BMF-500 (Oral Small Molecule FLT3 Inhibitor in Acute Leukemia): (i) Survival data from the dose escalation study in relapsed/refractory acute leukemia expected in the second quarter of 2025; (ii) The Company concludes its oncology efforts with BMF-500 and is exploring strategic partnerships."

P1 data • Pipeline update • Acute Myelogenous Leukemia

COVALENT-103: A Phase 1, Study of BMF-500 in Adults With Acute Leukemia (clinicaltrials.gov) - P1 | N=84 | Recruiting | Sponsor: Biomea Fusion Inc. | Trial completion date: Jul 2026 ➔ Dec 2025

Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • NPM1

Biomea Fusion Announces Preliminary Data from Ongoing COVALENT-103 Study of Investigational Covalent FLT3 Inhibitor BMF-500 in Relapsed or Refractory Acute Leukemia (GlobeNewswire) - P1 | N=110 | NCT05918692 | Sponsor: Biomea Fusion Inc. | "As of the data cut off, November 20, 2024, 20 patients with R/R acute leukemia had been enrolled in the dose-escalation portion of the study, all of whom received at least one dose of BMF-500....Preliminary data supports BMF-500’s potential as a transformative therapy for patients with FLT3 mutated R/R acute leukemia. During dose escalation, BMF-500 achieved a first CRi at the end of Cycle 2, in 1 of 2 (50%) FLT3 mutated patients dosed at 100 mg twice daily (BID), while the other patient experienced a clearance of peripheral blasts, greater than 50% reduction in bone marrow blasts and reduced transfusion frequency....Other evidence of clinical activity such as: clearance or reduction of peripheral blasts, reduction of transfusion frequency, reduction in use of hydroxyurea were observed."

P1 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia

Biomea Fusion to Host Conference Call to Present initial Clinical Data from Phase I COVALENT-103 Study of BMF-500, a Covalent FLT3 Inhibitor, in Relapsed or Refractory Acute Leukemia (GlobeNewswire) - "Biomea Fusion, Inc....announced that it will host a conference call and webcast on Monday, December 9, 2024 at 4:30 pm EST to present data from COVALENT-103, the company’s Phase I trial of BMF-500, an investigational covalent FLT3 inhibitor developed using the proprietary FUSION System, in adult patients with relapsed or refractory acute leukemia."

P1 data • Hematological Malignancies • Leukemia • Oncology

Biomea Fusion Reports Second Quarter 2024 Financial Results and Corporate Highlights (GlobeNewswire) - "COVALENT-103 (BMF-500 for Acute Leukemias): Complete dose escalation portion of COVALENT-103 expected by year end 2024."

Trial status • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Covalent-103: A phase 1, open-label, dose-escalation and expansion study of BMF-500, an oral covalent FLT3 inhibitor, in adults with acute leukemia (AL). (ASCO 2024) - P1 | "Secondary objectives include characterization of the PK/PD of BMF-500, and assessment of its antitumor activity per modified Cheson (2003) criteria or NCCN Clinical Practice Guidelines (ALL Version 1.2022) as determined by the investigator. The study was initiated in July 2023, is currently in dose escalation, and we plan to enroll approximately 110 patients total."

Clinical • P1 data • Bone Marrow Transplantation • Cardiovascular • CNS Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation • FLT3

Biomea Fusion Reports First Quarter 2024 Financial Results and Corporate Highlights (GlobeNewswire) - "ONCOLOGY: (i) COVALENT-101 (BMF-219 for Liquid Tumors) - Anticipated 2024 Milestones: On track to complete dose escalation portion of COVALENT-101 and establish recommended Phase 2 dose (RP2D); (ii) COVALENT-102 (BMF-219 for Solid Tumors) - Anticipated 2024 Milestones: On track to complete dose escalation portion of COVALENT-102 and establish RP2D; (iii) COVALENT-103 (BMF-500 for Acute Leukemias) - Anticipated 2024 Milestones: On track to complete dose escalation portion of COVALENT-103 and establish RP2D."

Trial status • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Colorectal Cancer • Diffuse Large B Cell Lymphoma • Multiple Myeloma • Non Small Cell Lung Cancer • Pancreatic Cancer

Biomea Fusion Reports Fourth Quarter and Full Year 2023 Financial Results and Corporate Highlights (GlobeNewswire) - "Anticipated 2024 Milestones: On track to complete dose escalation portion of COVALENT-102 in solid tumors and establish RP2D; On track to complete dose escalation portion of COVALENT-103 and establish RP2D."

Trial status • Acute Myelogenous Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

COVALENT-103: investigating BMF-500, an oral covalent FLT3 inhibitor, in acute leukemias (YouTube) - "Marcello Rotta, MD...introduces the COVALENT-103 trial (NCT05918692), a Phase I, open-label, dose escalation and expansion study that will investigate the safety, tolerability, and efficacy of BMF-500, a novel oral FLT3 inhibitor, in patients with relapsed/refractory (R/R) acute leukemias. This will include acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and mixed-phenotype acute leukemia (MPAL). This interview took place at the 65th ASH Annual Meeting and Exposition, held in San Diego, CA."

Interview • Video

Biomea Fusion Announces Two Poster Presentations at Upcoming ASH Annual Meeting 2023 (GlobeNewswire) - "First presentation of clinical data from ongoing COVALENT-101 trial of covalent menin inhibitor BMF-219 as a treatment for patients with liquid tumors; Trial in progress presentation featuring study design of ongoing COVALENT-103 trial of covalent FLT3 inhibitor BMF-500."

Clinical protocol • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

Biomea Fusion Announces First Patient Dosed with Covalent FLT3 Inhibitor BMF-500 in Relapsed or Refractory Acute Leukemia in Phase I Clinical Trial (COVALENT-103) (GlobeNewswire) - "Biomea Fusion, Inc...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 FUSION^TM System, in adult patients with relapsed or refractory acute leukemia."

Trial status • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

NI-0501-04: A Phase 1, Study of BMF-500 in Adults With Acute Leukemia (clinicaltrials.gov) - P1 | N=110 | Recruiting | Sponsor: Biomea Fusion Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • NPM1

NI-0501-04: A Phase 1, Study of BMF-500 in Adults With Acute Leukemia (clinicaltrials.gov) - P1 | N=110 | Not yet recruiting | Sponsor: Biomea Fusion Inc.

New P1 trial • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • NPM1

Biomea Fusion Announces FDA Clearance of Investigational New Drug (IND) Application for Covalent FLT3 Inhibitor BMF-500 in Relapsed or Refractory Acute Leukemia (GlobeNewswire) - "Biomea Fusion...announced that the U.S. Food and Drug Administration (FDA) has cleared the company's Investigational New Drug (IND) application to begin a Phase I trial (COVALENT-103) of BMF-500, an investigational covalent FLT3 inhibitor, in adult patients with relapsed or refractory acute leukemia....Phase I study (COVALENT-103) of BMF-500 will examine its safety and efficacy in patients with relapsed or refractory acute leukemia with FLT3 wild-type and FLT3 mutations, including those with MLLr / NPM1 mutations."

IND • New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Combinatorial approach using covalent menin inhibitor, BMF-219, and/or covalent FLT3 inhibitor, BMF-500, with MEK or BCL2 blockade potentiates therapeutic use in AML (AACR 2023) - "Repeated experiments revealed patterns of increased cell killing is achieved when trametinib, MEK inhibitor, and venetoclax, BCL2 inhibitor, are combined with BMF-219 treatment.Collectively, our studies demonstrate the utility of combination strategies to achieve higher antileukemic cell killing with reduced concentrations of menin and FLT3 covalent inhibitors. Collectively, our studies demonstrate the utility of combination strategies to achieve higher antileukemic cell killing with reduced concentrations of menin and FLT3 covalent inhibitors. Additionally, we show benefit of combinatorial approaches of menin and FLT3 covalent inhibitors with MEK and BCL2 blockade. These data provide initial pre-clinical evidence for combining pathway specific inhibitors as a promising therapeutic strategy for further investigation in acute leukemia."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • FLT3 • KMT2A • NPM1 • NRAS

Biomea Fusion To Present Two Preclinical Posters at the 114th AACR Annual Meeting (GlobeNewswire) - "Biomea Fusion...announced the upcoming presentation of two preclinical abstracts at the American Association for Cancer Research (AACR) Annual Meeting....Abstract 473 highlights the dose dependent reduction of menin target genes in ex vivo chronic lymphocytic leukemia (CLL) patient samples treated with BMF-219, an investigational covalent inhibitor. BMF-219 showed greater potency and ability to achieve >98% growth inhibition in these CLL patient samples in comparison with reversible BTK inhibitor, pirtobrutinib, and irreversible BTK inhibitor, ibrutinib. Abstract 4939 demonstrates the potential utility of combining a covalent menin inhibitor, BMF-219, and a FLT3 covalent inhibitor, BMF-500, to achieve higher cell killing at lower concentrations in preclinical acute myeloid leukemia (AML) models."

Preclinical • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Biomea Fusion to Present at 41st Annual J.P. Morgan Healthcare Conference and Highlight 2023 Corporate Milestones (GlobeNewswire) - "COVALENT-101 (BMF-219)...On track to present initial clinical data of AML/ALL patients (including those with MLL rearrangement and NPM1 mutation) dosed in the COVALENT-101 study in the first half of 2023. COVALENT-102 (BMF-219)...On track to dose first patient in COVALENT-102 study in January 2023. COVALENT-103 (BMF-500)...On track to file IND for BMF-500 in the first half of 2023 to initiate COVALENT-103 study of the covalent FLT3 inhibitor in patients with acute leukemia."

IND • P1 data • Trial status • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Bmf-500: An Orally Bioavailable Covalent Inhibitor of FLT3 with High Selectivity and Potent Antileukemic Activity in FLT3-Mutated AML (ASH 2022) - "BMF-500 is a picomolar inhibitor with markedly improved potency over gilteritinib, a reversible inhibitor of FLT3. Study results including efficacy and PD response will be presented. Collectively these data demonstrate BMF-500 to be a novel FLT3 inhibitor with best-in-class potential, given its efficacy, durability, and selectivity in comparison to existing FLT3 inhibitors."

Acute Myelogenous Leukemia • Oncology • FLT3 • STAT5