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Iadademstat + ASTX727 is an investigational, orally administered combination regimen consisting of iadademstat (ORY-1001) and ASTX727. Iadademstat is a small-molecule, covalent inhibitor of the epigenetic enzyme lysine-specific demethylase 1 (LSD1/KDM1A). ASTX727 is a fixed-dose combination of decitabine, a DNA methyltransferase inhibitor (DNMTi) that acts as a hypomethylating agent, and cedazuridine, a cytidine deaminase inhibitor that prevents decitabine degradation to allow oral bioavailability. Developed through a collaboration between Oryzon Genomics and Astex Pharmaceuticals (a subsidiary of Otsuka Pharmaceutical), this combination is being evaluated in the Phase II clinical trial NCT06661915 for the treatment of accelerated or blast-phase Philadelphia chromosome-negative myeloproliferative neoplasms (MPN-AP/BP) and myelodysplastic/myeloproliferative neoplasms. The therapeutic rationale is based on the synergistic epigenetic modulation of LSD1 inhibition combined with DNA hypomethylation, which promotes cellular differentiation and suppresses tumor growth in hematologic malignancies.
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