ORX142

ORX142 is an investigational, orally administered, highly potent and selective small molecule agonist of orexin receptor 2 (OX2R). Developed by Centessa Pharmaceuticals, it is designed to promote wakefulness and is being advanced for the treatment of excessive daytime sleepiness (EDS) in select neurological, neurodegenerative, and psychiatric disorders. Preclinical studies in non-human primates demonstrated that ORX142 induces sustained increases in wakefulness at very low doses (as low as 0.03 mg/kg), with significant selectivity for OX2R (>13,000-fold over OX1R) and minimal off-target activity. The drug’s mechanism leverages high-resolution crystallography and cryo-EM structural chemistry to achieve its potency and selectivity. As of June 2025, the FDA has cleared an IND application for Phase 1 clinical trials in healthy volunteers[1][2][4][5][6].

Other names

ORX142ORX-142ORX 142