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    DRUG CLASS:

    LSD1 inhibitor

    Related drugs:
    1m
    ALICE: Iadademstat in Combination With Azacitidine and Venetoclax in Treating Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=30, Recruiting, OHSU Knight Cancer Institute | Trial completion date: May 2026 --> May 2028 | Trial primary completion date: Mar 2026 --> Mar 2027
    Trial completion date • Trial primary completion date
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    ABL1 (ABL proto-oncogene 1)
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    ABL1 fusion
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    Venclexta (venetoclax) • azacitidine • iadademstat (ORY-1001)
    1m
    Am80 (tamibarotene) and ATRA induce highly similar molecular responses and myeloid differentiation in non-APL AML, enhanced by LSD1/GCN5 inhibition and increased RARA expression. (PubMed, BMC Cancer)
    The study provides evidence that ATRA can be substituted by the more stable Am80 in retinoid-based AML therapies. It also identifies elevated RARA expression as a potential marker for sensitivity to combination therapy with retinoids and epigenetic inhibitors in AML.
    Journal
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    RARG (Retinoic Acid Receptor Gamma)
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    Amnolake (tamibarotene)
    2ms
    A Study of Bomedemstat (IMG-7289/MK-3543) Compared to Best Available Therapy (BAT) in Participants With Essential Thrombocythemia and an Inadequate Response or Intolerance of Hydroxyurea (MK-3543-006) (clinicaltrials.gov)
    P3, N=340, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting
    Enrollment closed
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    Jakafi (ruxolitinib) • hydroxyurea • busulfan • bomedemstat (MK-3543)
    2ms
    A Randomized Study of ASTX727 With or Without Iadademstat in Advanced Myeloproliferative Neoplasms (MPNs) (clinicaltrials.gov)
    P2, N=62, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
    Trial suspension
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    Inqovi (decitabine/cedazuridine) • iadademstat (ORY-1001)
    3ms
    Dual Targeting of EZH2 and LSD1 Suppresses Hepatocellular Carcinoma via Disruption of Sonic Hedgehog Signaling. (PubMed, Int J Mol Sci)
    Functionally, dual pharmacological inhibition of EZH2 (GSK126) and LSD1 (SP2509) suppressed HCC cell proliferation, induced G1-phase arrest, and enhanced apoptosis, as evidenced by increased caspase-3/7 activity and decreased pro-caspase levels. Chromatin immunoprecipitation revealed reduced EZH2, LSD1, and STAT3 occupancy at the GLI1 promoter following dual inhibition, leading to the repression of GLI1 and its downstream targets. Collectively, these findings demonstrate that EZH2 and LSD1 cooperatively sustain GLI1-dependent SHH signaling in HCC, and that dual epigenetic inhibition represents a mechanistically defined therapeutic strategy.
    Journal
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    EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • STAT3 (Signal Transducer And Activator Of Transcription 3) • GLI1 (GLI Family Zinc Finger 1) • KDM1A (Lysine Demethylase 1A) • CASP3 (Caspase 3) • CASP7 (Caspase 7)
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    GSK2816126 • SP-2509
    3ms
    CL12-ORY-2001: A PHASE 1, OPEN-LABEL STUDY TO ASSESS THE ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION, INCLUDING THE MASS BALANCE, OF A SINGLE ORAL DOSE OF [14C]-VAFIDEMSTAT IN HEALTHY MALE PARTICIPANTS (2025-524832-20-00)
    P1, N=8, Not yet recruiting, Oryzon Genomics S.A.
    New P1 trial
    3ms
    CL09-ORY-2001: A Clinical trial to evaluate the efficacy of vafidemstat in negative symptoms and cognitive impairment associated with schizophrenia. (EVOLUTION study) (2023-507372-42-00)
    P1/2, N=239, Recruiting, Oryzon Genomics S.A. | N=84 --> 239
    Enrollment change
    3ms
    The lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat in myelofibrosis: results from a phase 1/2 study. (PubMed, Blood Adv)
    Bomedemstat has manageable safety and clinical activity in participants with MF in need of an alternative therapy. This trial was registered at www.cinicaltrials.gov as #NCT03136185.
    P1/2 data • Journal
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    JAK2 (Janus kinase 2) • CALR (Calreticulin)
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    bomedemstat (MK-3543)
    4ms
    Dose Determining Study of EXS74539 (REC-4539) in Participants With Select Solid Tumors (clinicaltrials.gov)
    P1, N=40, Recruiting, Exscientia AI Ltd., a wholly owned subsidiary of Recursion Pharmaceuticals, Inc.
    New P1 trial
    4ms
    Iadademstat With Hypomethylating Agent in Patients With Myelodysplastic Syndrome (clinicaltrials.gov)
    P1, N=12, Recruiting, Medical College of Wisconsin | Trial completion date: Oct 2027 --> Dec 2027 | Trial primary completion date: Oct 2026 --> Dec 2026
    Trial completion date • Trial primary completion date
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    iadademstat (ORY-1001)
    4ms
    NCI-2020-14163: Seclidemstat and Azacitidine for the Treatment of Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia (clinicaltrials.gov)
    P1/2, N=24, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=44 --> 24
    Enrollment closed • Enrollment change
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    TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SETBP1 (SET Binding Protein 1)
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    TP53 mutation • NRAS mutation • ASXL1 mutation
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    azacitidine • seclidemstat (SP2577)
    4ms
    Uncovering BAP1 deubiquitination landscape enhances mechanism elucidation and therapeutic precision for BAP1-deficient pancancers. (PubMed, Sci Transl Med)
    Combined inhibition of LSD1 and PARP1, using SP2509/SP2577 and olaparib, respectively, synergistically hinders NER, induces apoptosis, reduces tumor burden, and prolongs the survival of multiple BAP1-deficient pancancer in vitro models and in vivo xenografts. In conclusion, our results provide a deubiquitination landscape of BAP1; elucidate the mechanisms of action of BAP1, LSD1, and PARP1 in pancancers; and describe a promising combination therapeutic strategy applicable across multiple cancers with BAP1 mutations.
    Journal • BRCA Biomarker • PARP Biomarker • Pan tumor
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    BAP1 (BRCA1 Associated Protein 1) • DDB1 (Damage Specific DNA Binding Protein 1) • RAD23B (RAD23 Homolog B)
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    BRCA1 mutation
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    Lynparza (olaparib) • seclidemstat (SP2577) • SP-2509