ATX-559

ATX-559 is a first-in-class, potent, and selective oral small molecule inhibitor of DHX9, a novel and previously undrugged RNA and DNA/RNA helicase. DEAH-box helicase 9 (DHX9) plays critical roles in replication, transcription, translation, RNA splicing and processing, as well as maintenance of genomic stability. Inhibition of DHX9 exploits tumor vulnerabilities—particularly in cancers with high levels of replication stress or deficiencies in DNA repair mechanisms (such as BRCA1/2-deficient tumors) or hyper-mutated states (such as MSI-H/dMMR). Preclinical studies have shown robust anti-tumor activity across various solid tumor models including breast cancer (especially BRCA1/2-deficient), ovarian cancer, colorectal cancer (especially MSI-H/dMMR), endometrial cancer, gastric cancer, and others. ATX-559 is being developed by Accent Therapeutics for the treatment of advanced or metastatic solid tumors with molecularly defined vulnerabilities to DHX9 inhibition. The drug is currently being evaluated in a Phase 1/2 clinical trial to assess safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD), and preliminary efficacy[1][2][3][4][5][6][7].