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    DRUG CLASS:

    Menin-MLL inhibitor

    Related drugs:
    3d
    Targeting the Menin-KMT2A Interface: Medicinal Chemistry Rules Governing Reversible, Covalent, and Degrader Inhibitors. (PubMed, Chem Biol Drug Des)
    The menin-lysine methyltransferase 2A acute leukemia (KMT2A) protein-protein interaction has emerged as a clinically validated epigenetic target in acute leukemia, following the approval of the reversible menin inhibitor Revumenib for KMT2A-rearranged and nucleophosmin 1 (NPM1)-mutant disease...Across all chemical classes, sustained target engagement-rather than equilibrium affinity alone-emerges as the dominant determinant of antileukemic efficacy. By integrating structure-activity relationship (SAR), resistance mechanisms, safety considerations, and translational scope across oncology and metabolic indications, this review provides a roadmap for the rational design of next-generation menin inhibitors and establishes menin as a model system for modern epigenetic drug discovery.
    Review • Journal
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    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
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    NPM1 mutation
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    Revuforj (revumenib)
    7d
    Phase 2 Trial of Icovamenib in Participants With Type 2 Diabetes Mellitus Who Are Not Achieving Glycemic Targets While Using GLP-1-Based Therapy (clinicaltrials.gov)
    P2, N=60, Recruiting, Biomea Fusion Inc.
    New P2 trial
    |
    icovamenib (BMF-219)
    7d
    Phase 2 Trial of Icovamenib in Participants With Type 2 Diabetes Who Are Not Achieving Glycemic Targets (clinicaltrials.gov)
    P2, N=60, Recruiting, Biomea Fusion Inc.
    New P2 trial
    |
    icovamenib (BMF-219)
    10d
    A Study to Find the Highest Dose of SNDX-5613 (Revumenib) as a Treatment Option After Hematopoietic Stem Cell Transplant in Children With Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, and Mixed Phenotype Acute Leukemia (clinicaltrials.gov)
    P1, N=29, Not yet recruiting, Children's Oncology Group
    New P1 trial
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    KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CD4 (CD4 Molecule)
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    KMT2A rearrangement
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    cytarabine • methotrexate • Revuforj (revumenib) • Starasid (cytarabine ocfosfate)
    12d
    Сlinical Study Aiming to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of ZE63-0302 in Healthy Volunteers (clinicaltrials.gov)
    P1, N=82, Completed, Eilean Therapeutics | Recruiting --> Completed
    Trial completion • First-in-human
    |
    itraconazole
    13d
    Revumenib in Combination With 7+3 + Midostaurin in AML (clinicaltrials.gov)
    P1, N=22, Recruiting, Richard Stone, MD | Trial completion date: Mar 2027 --> Mar 2028 | Trial primary completion date: Mar 2026 --> Mar 2027
    Trial completion date • Trial primary completion date
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    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • SRSF2 (Serine and arginine rich splicing factor 2) • CREBBP (CREB binding protein) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • KAT6A (Lysine Acetyltransferase 6A) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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    TP53 mutation • FLT3-ITD mutation • NPM1 mutation • Chr del(5q)
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    midostaurin • daunorubicin • Revuforj (revumenib)
    13d
    REVEAL-ND NPM1: Study of Revumenib in Combination With Intensive Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia (AML) With a NPM1 Mutation (clinicaltrials.gov)
    P3, N=468, Recruiting, Syndax Pharmaceuticals
    Trial initiation date
    |
    NPM1 (Nucleophosmin 1)
    |
    NPM1 mutation
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    cytarabine • Revuforj (revumenib)
    14d
    DSP-5336-101: A Phase 1/2 Study of Enzomenib (DSP-5336) in Patients With Acute Leukemia (Horizen-1) (clinicaltrials.gov)
    P1/2, N=606, Recruiting, Sumitomo Pharma America, Inc. | N=362 --> 606
    Enrollment change
    |
    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    FLT3-ITD mutation • FLT3 mutation • NPM1 mutation
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    Venclexta (venetoclax) • Xospata (gilteritinib) • azacitidine • enzomenib (DSP-5336)
    19d
    Discovery and preclinical activity of the menin-KMT2A inhibitor ziftomenib in acute leukemia models. (PubMed, Blood)
    We next assessed ziftomenib against four MEN1 (gene encoding menin) mutants (T349M, M327I, G331R, G331D) associated with clinical resistance to another menin inhibitor revumenib. The crystal structures of ziftomenib in complex with menin wild-type, T349M or G331R mutants revealed a similar binding mode of ziftomenib to these menin variants, rationalizing potent inhibitory activity towards these mutants. Ziftomenib has recently received FDA approval for adult patients with NPM1-mutated acute myeloid leukemia and continues to be evaluated clinically in leukemias with NPM1 or KMT2A alterations, both as monotherapy and in combinations.
    Preclinical • Journal
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    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • HOXA9 (Homeobox A9) • MEIS1 (Meis Homeobox 1) • MEN1 (Menin 1) • HOXB2 (Homeobox B2)
    |
    NPM1 mutation • KMT2A rearrangement
    |
    Revuforj (revumenib) • Komzifti (ziftomenib)
    20d
    AUGMENT-101: A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation (clinicaltrials.gov)
    P1/2, N=447, Recruiting, Syndax Pharmaceuticals | N=67 --> 447
    Enrollment change
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2)
    |
    NPM1 mutation • KMT2A rearrangement
    |
    Revuforj (revumenib) • Tybost (cobicistat)
    25d
    KOMET-017: Studies to Assess Ziftomenib in Combination With Ven+Aza or 7+3 in Patients With Untreated NPM1-m or KMT2A-r AML (clinicaltrials.gov)
    P3, N=1300, Recruiting, Kura Oncology, Inc. | N=719 --> 1300
    Enrollment change • Trial initiation date
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    Venclexta (venetoclax) • cytarabine • azacitidine • daunorubicin • Komzifti (ziftomenib)
    25d
    OSU-23199: SNDX-5613 and Gilteritinib for the Treatment of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia and Concurrent MLL-Rearrangement or NPM1 Mutation (clinicaltrials.gov)
    P1, N=30, Recruiting, Uma Borate | Trial completion date: Dec 2025 --> Feb 2027 | Trial primary completion date: Dec 2025 --> Jan 2027
    Trial completion date • Trial primary completion date
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • MEIS1 (Meis Homeobox 1)
    |
    FLT3 mutation • NPM1 mutation • MLL mutation
    |
    Xospata (gilteritinib) • Revuforj (revumenib)