ORIC-259

ORIC-259 is a potent, selective, and orally bioavailable small molecule mRNA degrader (splice-modifier) targeting Cancerous Inhibitor of PP2A (CIP2A). Developed by ORIC Pharmaceuticals, it is designed to modify mRNA splicing to incorporate a premature stop codon, leading to mRNA degradation and loss of CIP2A protein. CIP2A is a protein involved in protein phosphorylation, mitosis, and DNA damage response that contributes to the development and progression of many cancer types. ORIC-259 is being developed primarily for cancers with homologous recombination deficiency (HRD). Preclinical data show robust antitumor activity in both PARP inhibitor-sensitive and PARP inhibitor-resistant settings. In October 2026, ORIC Pharmaceuticals announced a collaboration with Cancer Research UK (CRUK), under which CRUK's Centre for Drug Development will fully fund, sponsor, design, and execute CTA-enabling studies and Phase 1/2 clinical trials, with ORIC retaining an exclusive option to reacquire rights following Phase 1/2 data.