ASTX295 + olaparib

ASTX295 + olaparib (MOS101) is an investigational combination therapy being developed by Mosaic Therapeutics for the treatment of biomarker-selected solid tumors, specifically those harboring BRCA2 mutations and wild-type TP53. The combination consists of ASTX295, a potent and highly selective small-molecule MDM2 antagonist, and olaparib, an approved small-molecule PARP inhibitor. ASTX295 was designed with a short half-life (approximately 4–6 hours) to enable transient, pulsatile activation of the p53 pathway, thereby minimizing the prolonged myelosuppression and hematologic toxicities typically associated with first-generation MDM2 inhibitors. Olaparib inhibits PARP1 and PARP2, leading to the accumulation of unresolved DNA single-strand breaks that convert to double-strand breaks during replication. In BRCA2-mutant cells, which are deficient in homologous recombination repair, this genotoxic stress combined with ASTX295-mediated p53 stabilization synergistically triggers cell cycle arrest and apoptosis. Mosaic Therapeutics in-licensed ASTX295 from Astex Pharmaceuticals in April 2025 and is preparing a Phase 1b/2a clinical trial to evaluate the combination.

Other names

ASTX295 and olaparibASTX-295 and olaparibASTX 295 and olaparibASTX295 in combination with olaparibASTX-295 in combination with olaparibASTX 295 in combination with olaparib