rebecsinib

Rebecsinib is a novel, first-in-class small molecule inhibitor of splicing-mediated activation of the enzyme ADAR1 (adenosine deaminase acting on RNA 1), specifically targeting the p150 isoform. It is derived by modification of the natural product Pladienolide B. Rebecsinib selectively eradicates therapy-resistant cancer stem cells in blood cancers by inhibiting ADAR1-driven RNA editing and splice isoform switching, which are implicated in immune evasion, metastasis, and therapeutic resistance across at least 20 cancer types. The drug has demonstrated efficacy in preclinical models for secondary acute myeloid leukemia (sAML) and high-risk myelofibrosis (MF), sparing normal hematopoietic stem cells while impairing leukemia stem cell self-renewal. Rebecsinib is currently under development for relapsed/refractory sAML and high-risk MF, with IND-enabling studies completed and Phase 1 clinical trials planned or initiated as of 2025[2][4][7][8].