ONR-001

**ONR-001** is a first-in-class small molecule developed by Oniria Therapeutics that allosterically activates TET2 (ten-eleven translocation 2), a master epigenetic enzyme responsible for DNA demethylation. By over-activating TET2 beyond physiological levels, it converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), reactivating tumor suppressor genes, antitumor genes, and those involved in cell cycle inhibition, DNA repair, apoptosis, immune activation, and tumor metabolism without reactivating oncogenes. This induces cell cycle arrest, dormancy, and apoptosis specifically in persistent tumor cells, including those resistant to chemotherapy or immunotherapy. Administered orally, it demonstrates efficacy in preclinical models of melanoma (BRAF wild-type, NRAS wild-type), acute myeloid leukemia (AML), and colorectal cancer, with favorable PK/PD, safety, and tumor penetration.[1][3][5][11]