RegulationFast Track (US), Orphan Drug (US), Orphan Drug (EU), Priority Review (CN), Orphan Drug (KR), Orphan Drug (AU), Overseas New Drugs Urgently Needed in Clinical Settings (CN), Priority Review (AU), Conditional marketing approval (CN)

Structure/Sequence

Molecular FormulaC62H92N16O10

InChIKeyUJOUWHLYTQFUCU-WXXKFALUSA-N

CAS Registry1254053-84-3

Clinical Trials associated with Gilteritinib Fumarate

NCT06667973

/ Not yet recruitingPhase 2IIT

A Phase 2, Open-label, Multicentre Study Investigating Tolerability and Efficacy of Gilteritinib in Combination With Fludarabine, Cytarabine and Idarubicin (FLAI) as Induction Therapy of Newly Diagnosed Non-M3 FLT3-positive Acute Myeloid Leukemia

The goal of this clinical trial is to evaluate the efficacy of gilteritinib as induction therapy in FLT3-positive adult acute myeloid leukemia patients. The main question it aims to answer is:
Is gilteritinib in combination to chemotherapy able to improve the complete remission rate of FLT3-positive AML?
Participants will receive up to 2 induction cycles with gilteritinib in combination with FLAI (fludarabine, cytarabine, idarubicine) and up to 3 consolidation cycles with gilteritinib and high-dose cytarabine.

Start Date01 Mar 2025

Sponsor / Collaborator

Gruppo Italiano Malattie EMatologiche dell'Adulto

NCT06696183

/ Not yet recruitingPhase 2

Sequential Gilteritinib in Combination with Venetoclax and Azacitidine for Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) and FLT3 Mutations Ineligible for Intensive Treatment

Explore the best tolerable and efficacious dose of Gilteritinib when combined with standard treatment with Venetoclax and Azacitidine in AML patients with FLT3 mutations which are ineligible for intensive chemotherapy

Start Date01 Jan 2025

Sponsor / Collaborator

Dresden University of Technology

NCT06734585

/ Not yet recruitingNot Applicable

A Comparison Between Gilteritinib in Phase 3 Trials Versus Real-World External Comparator Cohort of Relapsed/Refractory (R/R) FLT3m+ Acute Myeloid Leukemia (AML) Patients After Hematopoietic Stem Cell Transplantation (HSCT)

People with acute myeloid leukemia (AML) are usually treated with chemotherapy. When the cancer comes back (relapse) the next treatment is usually a stem cell transplant. Some people with AML have a changed FLT3 gene which causes leukemia cells to grow faster. This means their cancer may come back more quickly after treatment.
Gilteritinib is approved in many countries to treat people with AML with the changed FLT3 gene whose cancer has come back or have not responded to previous treatment. In some countries, more studies are needed to approve gilteritinib for use.
This study is about people with AML with the changed FLT3 gene. The main aim was to learn if gilteritinib improves how long people stay cancer-free (in remission) after a stem cell transplant. To do this, 2 groups were compared. 1 group were given gilteritinib after a stem cell transplant. This happened in previous studies called the ADMIRAL study and COMMODORE study. The other group received standard of care after their stem cell transplant. They did not receive gilteritinib after their stem cell transplant.
In this study, information about the people who received standard of care after their stem cell transplant will be collected. This study is about collecting information only. The study sponsor (Astellas) will not provide any treatment.
Information will be collected from the people's medical records between 01 Jan 2015 and 31 Dec 2022. The study doctors will collect information from the first relapse, during and after the stem cell transplant. Then, they will record when any of the following happened after the stem cell transplant: the person passed away, their cancer came back, they decided to leave the study or could not be contacted.

Start Date31 Dec 2024

Sponsor / Collaborator

Astellas Pharma Singapore Pte Ltd.

100 Clinical Results associated with Gilteritinib Fumarate

100 Translational Medicine associated with Gilteritinib Fumarate

100 Patents (Medical) associated with Gilteritinib Fumarate

410

Literatures (Medical) associated with Gilteritinib Fumarate

01 Feb 2025·CANCER LETTERS

FLT3 inhibitors induce p53 instability, driven by STAT5/MDM2/p53 competitive interactions in acute myeloid leukemia

Article

Author: Chen, Yun ; Pei, Han Zhong ; Zhao, Yuming ; Zhou, Jingfeng ; Zhao, Zhizhuang Joe ; Chen, Chun ; Zhang, Dengyang ; Guo, Yao ; Baek, Suk-Hwan ; Chang, Zhiguang

FLT3 mutations are present in one third of patients with Acute myeloid leukemia (AML) and stand as an attractive therapeutic target. Although FLT3 inhibitors demonstrate clinical efficacy, the drug resistance remains challenging attributed to multiple mechanisms. In this study, we found that tyrosine kinase inhibitors (TKIs) targeting FLT3 prompt p53 degradation in AML cells with FLT3-ITD through ubiquitination. STAT5 phosphorylation facilitates its nuclear localization, leading to competitive interactions among STAT5, MDM2, and p53. TKIs blocked STAT5 nuclear entry, amplifying MDM2/p53 binding and subsequent p53 degradation. Additionally, STAT5 overexpression inhibited MDM2-mediated p53 ubiquitination, whereas knock-down of STAT5 destabilizes p53. Co-administration of MDM2 inhibitors stabilizes p53 ubiquitination induced by TKIs, enhancing pro-apoptotic effects on AML cells. Moreover, in mice engrafted with AML cells, gilteritinib treatment results in decreased p53 protein levels and the transcriptional repression of downstream genes in leukemia cells, which are mitigated by the co-administration of MDM2 inhibitors. In conclusion, our study shows that FLT3 TKIs impede STAT5 nuclear translocation, strengthening p53/MDM2 interaction and consequent p53 degradation. This finding reveals a novel mechanism of TKIs resistance and indicates a combination of MDM2 inhibitors with TKIs for AML therapy, offering new insights into effective treatment strategies.

01 Jan 2025·AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS

Maintenance Therapy in Acute Myeloid Leukemia

Review

Author: Sabakhtarishvili, Giorgi ; Ansari, Amir ; Tabbara, Imad A.

Acute myeloid leukemia (AML) poses significant challenges due to its high relapse rates despite initial successful induction chemotherapy. Maintenance therapy aims to prevent disease recurrence, particularly in high-risk patients. This review explores current maintenance treatments, their impacts on patient outcomes, and ongoing studies shaping the treatment landscape for AML. Hypomethylating agents like azacitidine and decitabine have shown promise in improving relapse-free and overall survival, particularly in older patients with AML ineligible for transplantation. Combination regimens involving azacitidine and venetoclax have demonstrated encouraging outcomes post–hematopoietic stem cell transplantation. Targeted therapies, particularly FLT3 inhibitors like midostaurin and quizartinib, have shown significant benefits in improving survival outcomes, especially in FLT3-mutated AML cases. Gilteritinib and sorafenib also exhibit the potential to reduce relapse rates post-transplant. Isocitrate dehydrogenase inhibitors, including ivosidenib and enasidenib, present novel options for postchemotherapy and posttransplantation maintenance. Immunotherapies, such as Wilms tumor 1 peptide-based vaccines and checkpoint inhibitors, are being explored, although results vary. Despite ongoing research, the role of maintenance chemotherapy remains uncertain, with inconsistent outcomes across trials. The approval of oral azacitidine represents a significant advancement, emphasizing the need for further investigation into personalized maintenance approaches. In conclusion, the evolving landscape of maintenance therapy and integrating targeted therapies in AML offers promising avenues for improving patient outcomes.

01 Jan 2025·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Identification of inhibitors targeting the FLT3-ITD mutation through 4D-QSAR, in vitro, and in silico

Article

Author: Yan, Hong ; Zhong, Qidi ; Chu, Dongchen ; Zhang, Xiaokun ; Zhang, Yu ; Ji, CuiCui ; Wei, Chaochun ; Wang, Juan

The FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation is a key target for acute myeloid leukemia (AML) treatment. The second-generation inhibitors such as Gilteritinib still present off-target effects and associated side effects. Therefore, identifying novel FLT3-ITD inhibitors has become a promising strategy for AML treatment. In this study, a 4D-QSAR model was developed based on Gilteritinib and its analogues, and it was found that introducing hydrophobic bulky groups at the piperazine or piperidine of Gilteritinib would enhance the binding affinity to FLT3-ITD. So, three series of targeted compounds (A1-A5, B1-B5 and C1-C5) were designed and synthesized. The antiproliferative activity against MOLM-13 cells was evaluated in vitro. Compound A1 (IC₅₀ = 25.65 nM), with a cubane group at the piperazine position; Compounds B2 (IC₅₀ = 63.38 nM) and C2 (IC₅₀ = 54.96 nM), with a norbornene group at the piperidine position, showed the strongest inhibition in their series. Their IC₅₀ values were comparable to that of the positive control Gilteritinib (IC₅₀ = 22.37 nM). FLT3-ITD was confirmed as the degradation target through a kinase inhibition assay, where the IC₅₀ values were 2.12 nM (Compound A1), 1.29 nM (Compound B2), and 3.06 nM (Compound C2), which were comparable to that of Gilteritinib (IC₅₀ = 0.43 nM). Additionally, molecular docking and molecular dynamics (MD) simulations showed that Compounds A1, B2, and C2 had similar binding modes to that of Gilteritinib with more stable affinities. Overall, these results demonstrated that Compounds A1, B2, and C2 were promising inhibitors for targeting AML with FLT3-ITD mutation.

119

News (Medical) associated with Gilteritinib Fumarate

13 Jan 2025

·www.globenewswire.com

ORYZON Announces First Patient Dosed in NCI-Sponsored Iadademstat in Combination With Venetoclax and Azacitidine Clinical Trial in First Line Acute Myeloid Leukemia

Study conducted under the CRADA agreement between NCI and Oryzon MADRID, Spain and CAMBRIDGE, Mass., Jan. 13, 2025 (GLOBE NEWSWIRE) -- Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, announced today that the first patient has been dosed in a Phase I dose-finding clinical trial of iadademstat, Oryzon’s potent and selective LSD1 inhibitor, in combination with venetoclax and azacitidine in newly diagnosed acute myeloid leukemia (AML), sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health. The trial (NCT06514261), titled “Phase 1 Trial of Iadademstat in Combination With Venetoclax and Azacitidine in Patients With Treatment Naive AML”, will evaluate the safety, tolerability, and optimal dose of iadademstat when administered together with the standard-of-care venetoclax and azacitidine in treatment-naïve AML patients. Preliminary efficacy of the triple combination will also be evaluated. This Phase I study will be conducted and sponsored by the NCI, and will be led by Principal Investigator, Dr. Natalie Galanina, from the University of Pittsburgh Cancer Institute. The trial plans to enroll 45 patients and is carried out under a Cooperative Research and Development Agreement (CRADA) that Oryzon has in place with the NCI. Dr. Carlos Buesa, Oryzon’s CEO, added: “We are excited to have the first patient dosed in this study. The trial expands on the findings from our ALICE trial, where combining iadademstat with azacitidine demonstrated robust antileukemic effects in first-line AML, producing deep and durable responses along with a manageable safety profile, including in patients with high-risk prognostic factors that respond poorly to venetoclax plus azacitidine.” In AML, iadademstat is also being evaluated in combination with venetoclax and azacitidine in newly diagnosed AML patients in an investigator-initiated Phase I clinical trial at Oregon Health & Science University (OHSU) Knight Cancer Institute (NCT06357182), and in a company-sponsored Phase Ib clinical trial in combination with gilteritinib in patients with relapsed/refractory AML harboring a FMS-like tyrosine kinase mutation (FLT3mut+) (NCT05546580). About OryzonFounded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. Oryzon’s team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston, and San Diego. Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS (Phase III-ready) and iadademstat in oncology (Phase II). The company has other pipeline assets directed against other epigenetic targets like HDAC-6 where a clinical candidate ORY-4001, has been nominated for its possible development in CMT and ALS. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. For more information, visit www.oryzon.com About IadademstatIadademstat (ORY-1001) is a small oral molecule, which acts as a highly selective inhibitor of the epigenetic enzyme LSD1 and has a powerful differentiating effect in hematologic cancers (see Maes et al., Cancer Cell 2018 Mar 12; 33 (3): 495-511.e12.doi: 10.1016 / j.ccell.2018.02.002.). A FiM Phase I/IIa clinical trial with iadademstat in R/R AML patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi (see Salamero et al, J Clin Oncol, 2020, 38(36): 4260-4273. doi: 10.1200/JCO.19.03250). Iadademstat has shown encouraging safety and strong clinical activity in combination with azacitidine in a Phase IIa trial in elder 1L AML patients (ALICE trial) (see Salamero et al., ASH 2022 oral presentation & The Lancet Haematology, 2024, 11(7):e487-e498). Iadademstat is currently being evaluated in combination with gilteritinib in the ongoing Phase Ib FRIDA trial in patients with relapsed/refractory AML with FLT3 mutations, and in combination with azacitidine and venetoclax in 1L AML in an investigator-initiated study led by OHSU and in a trial under the Cooperative Research and Development Agreement (CRADA) signed with the U.S. National Cancer Institute (NCI) to collaborate on further clinical development of iadademstat in different types of hematologic and solid cancers. Beyond hematological cancers, the inhibition of LSD1 has been proposed as a valid therapeutic approach in some solid tumors such as small cell lung cancer (SCLC), neuroendocrine tumors (NET), medulloblastoma and others. In a Phase IIa trial in combination with platinum/etoposide in second line ED-SCLC patients (CLEPSIDRA trial), preliminary activity and safety results have been reported (see Navarro et al., ESMO 2018 poster). Iadademstat is in a collaborative Phase II trial with the Fox Chase Cancer Center (FCCC) in combination with paclitaxel in R/R neuroendocrine carcinomas, and in a Phase I/II randomized trial in 1L ED-SCLC in combination with ICI sponsored by NCI and led by the Memorial Sloan Kettering Cancer Center (IND approved). Oryzon is further expanding the clinical development of iadademstat through additional investigator-initiated studies. Iadademstat has orphan drug designation for SCLC in the US and for AML in the US and EU. FORWARD-LOOKING STATEMENTS This communication contains, or may contain, forward-looking information and statements about Oryzon, including financial projections and estimates and their underlying assumptions, statements regarding plans, objectives, and expectations with respect to future operations, capital expenditures, synergies, products and services, and statements regarding future performance. Forward-looking statements are statements that are not historical facts and are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates” and similar expressions. Although Oryzon believes that the expectations reflected in such forward-looking statements are reasonable, investors and holders of Oryzon shares are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Oryzon that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the documents sent by Oryzon to the Spanish Comisión Nacional del Mercado de Valores (CNMV), which are accessible to the public. Forward-looking statements are not guarantees of future performance and have not been reviewed by the auditors of Oryzon. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date they were made. All subsequent oral or written forward-looking statements attributable to Oryzon or any of its members, directors, officers, employees, or any persons acting on its behalf are expressly qualified in their entirety by the cautionary statement above. All forward-looking statements included herein are based on information available to Oryzon on the date hereof. Except as required by applicable law, Oryzon does not undertake any obligation to publicly update or revise any forward‐looking statements, whether as a result of new information, future events, or otherwise. This press release is not an offer of securities for sale in the United States or any other jurisdiction. Oryzon’s securities may not be offered or sold in the United States absent registration or an exemption from registration. Any public offering of Oryzon’s securities to be made in the United States will be made by means of a prospectus that may be obtained from Oryzon or the selling security holder, as applicable, that will contain detailed information about Oryzon and management, as well as financial statements. SpainOryzonIR & Media, Europe & US Patricia Cobo/Mario CorderaEmili TorrellSandya von der Weid AtreviaChief Business OfficerLifeSci Advisors, LLC +34 91 564 07 25 +34 673 33 97 65+34 93 515 1313+41 78 680 05 38 pcobo@atrevia.com mcordera@atrevia.cometorrell@oryzon.comsvonderweid@lifesciadvisors.com

Phase 1Phase 2Orphan DrugClinical Result

12 Dec 2024

·www.globenewswire.com

Aptose Announces Publication of Preclinical Data in AACR Journal Demonstrating Tuspetinib’s Unique Mechanism of Action and Synthetic Lethality on AML Cells When Combined with Venetoclax

Peer-reviewed publication details unique TUS mechanism of action TUS+VEN combination synthetic lethality overcomes resistance to VEN Tuspetinib prolongs survival in multiple AML models resistant to other drugs Findings suggest TUS will demonstrate broad antileukemic activity across AML patients TUS+VEN+AZA Triplet Frontline Therapy in Newly Diagnosed AML Patients Now Enrolling SAN DIEGO and TORONTO, Dec. 12, 2024 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. (“Aptose” or the “Company”) (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated targeted agents to treat hematologic malignancies, today announced the publication of preclinical data for Aptose’s lead hematology compound tuspetinib (TUS) in Cancer Research Communications, a journal of the American Association for Cancer Research (AACR), available online now (link). The publication, entitled “Preclinical development of tuspetinib for the treatment of acute myeloid leukemia,” is the first preclinical profiling of tuspetinib, a well-tolerated, once daily, oral kinase inhibitor currently in clinical development for treatment of acute myeloid leukemia (AML). The publication defines TUS activities on select oncogenic signaling targets, demonstrates enhanced activity and safety of TUS when combined with other agents, and illustrates synthetic lethality when combined with venetoclax (VEN). Pharmacokinetic and toxicology studies revealed that TUS is readily absorbed and achieves plasma concentrations sufficient to inhibit the target kinases, it has a plasma half-life that supports once daily dosing, and it demonstrates a favorable safety profile. Aptose is now enrolling newly diagnosed AML patients in a Phase 1/2 clinical study to receive the tuspetinib + venetoclax + azacitidine (TUS+VEN+AZA) triplet combination (NCT03850574). Clinical studies in patients with relapsed or refractory AML receiving TUS single agent or the TUS+VEN combination have been completed. “The non-clinical findings presented in the publication suggest that TUS will demonstrate favorable safety and a breadth of antileukemic activity across AML patient populations with a diversity of adverse mutations, and the initial clinical data is bearing that out,” said William G. Rice, Chairman, President and Chief Executive Officer. “We are eager for the next set of data in our triplet combination trial of TUS+VEN+AZA.” Key findings: Tuspetinib inhibits a defined cluster of oncogenic signaling kinases operative in AML TUS inhibits SYK, JAK1/2, RSK2, mutant KIT, and wild type and mutant forms of FLT3TUS potently killed AML lines (GI50 = 1.3 to 5.2 nM) and Ba/F3 cells expressing wildtype (GI50 = 9.1 nM) or various mutant forms of FLT3 (GI50 = 2.5 – 56 nM)TUS dampens stroma-induced activation of FLT3-ITD signaling in AML cells TUS prolongs survival in multiple AML models Oral TUS markedly extended survival in subcutaneously and orthotopically inoculated xenograft models of FLT3 mutant human AML, was well tolerated, and delivered enhanced activity when combined with venetoclax or 5-azacytidine TUS combines effectively with other classes of agents to kill AML cells with mutations in RAS and other difficult-to-treat adverse mutationsTUS was 2.1-15-fold and a 4.5-13-fold more potent than gilteritinib at blocking fibrinogen and immunoglobulin-mediated activation of SYK in KG-1a cellsThe most notable observation was the marked and unexpected synthetic lethal vulnerability to venetoclax and two MCL1 inhibitors in the TUS-resistant cells About Aptose Aptose Biosciences is a clinical-stage biotechnology company committed to developing precision medicines addressing unmet medical needs in oncology, with an initial focus on hematology. The Company's small molecule cancer therapeutics pipeline includes products designed to provide single agent efficacy and to enhance the efficacy of other anti-cancer therapies and regimens without overlapping toxicities. The Company’s lead clinical-stage, oral kinase inhibitor tuspetinib (TUS) has demonstrated activity as a monotherapy and in combination therapy in patients with relapsed or refractory acute myeloid leukemia (AML) and is being developed as a frontline triplet therapy in newly diagnosed AML. For more information, please visit www.aptose.com. Forward Looking Statements This press release may contain forward-looking statements within the meaning of Canadian and U.S. securities laws, including, but not limited to, statements relating to the therapeutic potential of tuspetinib, its clinical development and safety profile, including that it combines effectively with other classes of agents and will demonstrate a favorable safety profile and a breadth of antileukemic activity across an AML patient population with a diversity of adverse mutations, as well as statements relating to the Company’s plans, objectives, expectations and intentions and other statements including words such as “continue”, “expect”, “intend”, “will”, “should”, “would”, “may”, and other similar expressions. Such statements reflect our current views with respect to future events and are subject to risks and uncertainties and are necessarily based upon a number of estimates and assumptions that, while considered reasonable by us are inherently subject to significant business, economic, competitive, political and social uncertainties and contingencies. Many factors could cause our actual results, performance or achievements to be materially different from any future results, performance or achievements described in this press release. Such factors could include, among others: our ability to obtain the capital required for research and operations and to continue as a going concern; the inherent risks in early stage drug development including demonstrating efficacy; development time/cost and the regulatory approval process; the progress of our clinical trials; our ability to find and enter into agreements with potential partners; our ability to attract and retain key personnel; changing market conditions; inability of new manufacturers to produce acceptable batches of GMP in sufficient quantities; unexpected manufacturing defects; and other risks detailed from time-to-time in our ongoing quarterly filings, annual information forms, annual reports and annual filings with Canadian securities regulators and the United States Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should the assumptions set out in the section entitled “Risk Factors” in our filings with Canadian securities regulators and the United States Securities and Exchange Commission underlying those forward-looking statements prove incorrect, actual results may vary materially from those described herein. These forward-looking statements are made as of the date of this press release and we do not intend, and do not assume any obligation, to update these forward-looking statements, except as required by law. We cannot assure you that such statements will prove to be accurate as actual results and future events could differ materially from those anticipated in such statements. Investors are cautioned that forward-looking statements are not guarantees of future performance and accordingly investors are cautioned not to put undue reliance on forward-looking statements due to the inherent uncertainty therein. For further information, please contact: Aptose Biosciences Inc.Susan PietropaoloCorporate Communications & Investor Relations201-923-2049spietropaolo@aptose.com

AACR

06 Dec 2024

·www.globenewswire.com

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

REDWOOD CITY, Calif., Dec. 06, 2024 (GLOBE NEWSWIRE) -- Biomea Fusion, Inc. (“Biomea”) (Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to discovering and developing oral covalent small molecules to treat and improve the lives of patients with diabetes, obesity, and genetically defined cancers, today 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. Conference Call and Webcast DetailsWebcast of Biomea’s investor update on Monday, December 9, 2024 at 4:30 pm EST will be available to registered attendees under the Investors and Media section of the company’s website at https://investors.biomeafusion.com/news-events/events. A replay of the presentation will be archived on Biomea’s site following the event. About COVALENT-103COVALENT-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 relapsed or refractory acute leukemia with FMS-like tyrosine kinase 3 (FLT3) wild-type and FLT3 mutations. Additional information about the Phase I clinical trial of BMF-500 can be found at ClinicalTrials.gov using the identifier, NCT05918692. About BMF-500BMF-500, an investigational, 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 has demonstrated encouraging potential based on extensive preclinical studies. The kinase inhibitory profile of BMF-500 showed high target selectivity, suggesting the potential for reduced off-target liabilities. BMF-500 was designed to have a therapeutic profile to allow for combinations with standard of care and/or novel targeted agents like icovamenib, Biomea’s investigational covalent menin inhibitor currently in clinical development for solid and liquid tumors as well as diabetes. Previous data presented at the 2022 American Society of Hematology Annual Meeting showed BMF-500’s picomolar affinity for inhibition of activating FLT3 mutations, including FLT3-ITD and various tyrosine kinase domain (TKD) mutations. BMF-500 demonstrated multi-fold higher potency and increased cytotoxicity than the commercially available non-covalent FLT3 inhibitor gilteritinib. These data also showed complete tumor regression in mouse models of FLT3-ITD acute myeloid leukemia (AML), with no tumor regrowth even after treatment cessation. Data presented at the 2023 American Association for Cancer Research (AACR) Annual Meeting exhibited the potential utility of combination strategies to achieve higher antileukemic cell killing with reduced concentrations of BMF-500 and icovamenib. Additionally, Biomea has shown the potential of combinatorial approaches of BMF-500 and icovamenib with MEK and BCL2 blockade in other preclinical studies. These data provide preclinical evidence for combining pathway-specific inhibitors as a promising therapeutic strategy for further investigation in acute leukemia. About FLT3 in AMLFLT3 is a receptor tyrosine kinase (RTK) that plays a central role in the survival, proliferation, and differentiation of immature blood cells. 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 7,000 incident patients in the U.S. each year. In addition, academic literature suggests that more than 50% of AML patients with an NPM1 mutation also harbor a FLT3 mutation. 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. About Biomea FusionBiomea Fusion is a clinical-stage biopharmaceutical company focused on the discovery and development of oral covalent small molecules to improve the lives of patients with diabetes, obesity, and genetically defined cancers. A covalent small molecule is a synthetic compound that forms a permanent bond to its target protein and offers a number of potential advantages over conventional non-covalent drugs, including greater target selectivity, lower drug exposure, and the ability to drive a deeper, more durable response. We are utilizing our proprietary FUSION™ System to discover, design, and develop a pipeline of next-generation covalent-binding small-molecule medicines designed to maximize clinical benefit for patients. We aim to have an outsized impact on the treatment of disease for the patients we serve. We aim to cure. Visit us at biomeafusion.com and follow us on LinkedIn, X, and Facebook. Forward-Looking StatementsStatements we make in this press release may include statements which are not historical facts and are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact, including statements regarding the clinical and therapeutic potential of our product candidates and development programs, may be deemed to be forward-looking statements. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. Any forward-looking statements in this press release are based on our current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including the risk that we may encounter delays in preclinical or clinical development, patient enrollment and in the initiation, conduct and completion of our ongoing and planned clinical trials and other research and development activities. These risks concerning Biomea Fusion’s business and operations are described in additional detail in its periodic filings with the U.S. Securities and Exchange Commission (the “SEC”), including its most recent periodic report filed with the SEC and subsequent filings thereafter. Biomea Fusion explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law. Contact:Investor and Media Relations:Ramses ErdtmannCOO & President of Biomea Fusionre@biomeafusion.com

Phase 1Clinical ResultAACRASH

100 Deals associated with Gilteritinib Fumarate

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	L01XE54	DB12141

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Acute Myeloid Leukemia	CA	Astellas Pharma Canada, Inc.	23 Dec 2019
FLT3 positive Acute Myeloid Leukemia	JP	Astellas Pharma, Inc.	21 Sep 2018

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Anemia, Refractory, With Excess of Blasts	Phase 3	AU	Astellas Pharma Global Development, Inc.	20 Dec 2019
Anemia, Refractory, With Excess of Blasts	Phase 3	AT	Astellas Pharma Global Development, Inc.	20 Dec 2019
Anemia, Refractory, With Excess of Blasts	Phase 3	BE	Astellas Pharma Global Development, Inc.	20 Dec 2019
Anemia, Refractory, With Excess of Blasts	Phase 3	FI	Astellas Pharma Global Development, Inc.	20 Dec 2019
Anemia, Refractory, With Excess of Blasts	Phase 3	FR	Astellas Pharma Global Development, Inc.	20 Dec 2019
Anemia, Refractory, With Excess of Blasts	Phase 3	DE	Astellas Pharma Global Development, Inc.	20 Dec 2019
Anemia, Refractory, With Excess of Blasts	Phase 3	IE	Astellas Pharma Global Development, Inc.	20 Dec 2019
Anemia, Refractory, With Excess of Blasts	Phase 3	LT	Astellas Pharma Global Development, Inc.	20 Dec 2019
Anemia, Refractory, With Excess of Blasts	Phase 3	NL	Astellas Pharma Global Development, Inc.	20 Dec 2019
Anemia, Refractory, With Excess of Blasts	Phase 3	NO	Astellas Pharma Global Development, Inc.	20 Dec 2019

Clinical Result

Indication

Phase

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03182244 (COMMODORE, CTgov)	Phase 3	Relapsing acute myeloid leukemia \| Acute Myeloid Leukemia with FLT3/ITD Mutation \| Refractory acute myeloid leukemia	276	Gilteritinib (Gilteritinib)	hjcjrrvylt(mtrnevttga) = kietldfkng pungetpvnv (jlhiiuheki, tlvwrzrrpa - adrlutvlzu) View more	-	14 Jan 2025
				Etoposide+Fludarabine+Mitoxantrone+Cytarabine+G-CSF (Salvage Chemotherapy)	hjcjrrvylt(mtrnevttga) = hovmhjnlmv pungetpvnv (jlhiiuheki, ubookkhjfm - pkdusjgeal) View more
NCT05010772 (4277, ASH2024)	Phase 1	Acute Myeloid Leukemia complex cytogenetics \| antecedent MDS/MPN \| therapy-related AML ... View more	31	ASTX727 alone	bezdwpqykf(xeqiwbrrke) = mgwtsknddc vxxnlqgvrx (yefsduamve ) View more	Positive	09 Dec 2024
				ASTX727 plus venetoclax	bezdwpqykf(xeqiwbrrke) = dcozhnbjhr vxxnlqgvrx (yefsduamve ) View more
ASH2024	Not Applicable	-	-	Gilteritinib (GILT) monotherapy	csythllawm(mckgmquciy) = nieytlkcxr ybcbdsbqmj (claibxxvvg ) View more	-	08 Dec 2024
				Salvage chemotherapy	csythllawm(mckgmquciy) = bxoghofnqb ybcbdsbqmj (claibxxvvg ) View more
ASH2024	Not Applicable	-	-	Gilteritinib	jtrueeipqb(ysiggowchl) = grade >=3 TRAE was reported in 73%G vs 70% M during induction and 79%G vs 73%M pts during consolidation emnknywvgv (dnguvnmadt )	-	07 Dec 2024
				Midostaurin
NCT02310321 (CTgov)	Phase 1/2	Acute Myeloid Leukemia with FLT3/ITD Mutation	97	Cytarabine+Idarubicin+Gilteritinib (Phase 1: Dose Evaluation (DEv))	uuwdzhwkju(qercxuwpiv) = pjmtpwelbc duqcoautqk (mcjimgfgtt, rajuhyazkb - ytcoahsdns) View more	-	16 Oct 2024
				Cytarabine+Idarubicin+Gilteritinib (Phase 1: Dose Expansion (DEx))	dsmjbzohgx(frejgvkldm) = rktjgzkjlq kztoeoeuap (nalmyeiaze, cajogqqvip - iylrtwkltk) View more
NCT02997202 (ADMIRAL, CTgov)	Phase 3	Acute Myeloid Leukemia with FLT3/ITD Mutation	356	gilteritinib (Gilteritinib)	jmscluisqw(rtbbztfkbq) = mdtybhgrro hukvfhthde (sbskdaiets, sqdiggkwvf - kxjzdcoikl) View more	-	19 Sep 2024
				Placebo (Placebo)	jmscluisqw(rtbbztfkbq) = zpjpydhwcy hukvfhthde (sbskdaiets, ttxinijzgy - ccewdolydm) View more
SOHO2024	Not Applicable	Acute Myeloid Leukemia	-	Gilteritinib monotherapy	vmmsdtfeac(tpdnacbnwq) = ddqycephqo rbpqtoclfg (gsmyasbdge ) View more	-	04 Sep 2024
				Gilteritinib + Venetoclax	vmmsdtfeac(tpdnacbnwq) = iljwdgwwqx rbpqtoclfg (gsmyasbdge ) View more
NCT03182244 (COMMODORE, EHA2024) Manual	Phase 3	Acute Myeloid Leukemia with FLT3/ITD Mutation Second line FLT3 Mutation	234	Gilteritinib 120 mg/day	xqyhliwczf(pzfijuhrnz) = cyolwndlxc yfytjnixqm (qsvvhofyar ) View more	Positive	14 May 2024
				Salvage Chemotherapy (SC)	xqyhliwczf(pzfijuhrnz) = rqdvzlloel yfytjnixqm (qsvvhofyar ) View more
EHA2024	Not Applicable	Relapsing acute myeloid leukemia FLT3 mutations	59	Gilteritinib monotherapy	ufzbtgjbhw(mtiwtknlxp) = etkehivvun ueksywydho (qefmauverx ) View more	Positive	14 May 2024
				Venetoclax-based regimen	cglahhluba(ptmbjcvxsu) = dtjjkctuuw qsrfripacb (ltwutqjcqs, 3.42 - NA)
NCT02997202 \| NCT02421939 (ADMIRAL, EHA2024)	Phase 3	Acute Myeloid Leukemia with FLT3/ITD Mutation	25	Gilteritinib 80 mg/d	hwgfutnaai(hngwkamotn) = 50% (8/16) cqkckbadqi (htmxqenpra )	Positive	14 May 2024
				Gilteritinib 120 mg/d

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