Centessa announces open IND for ORX750

Centessa Pharmaceuticals announced that the U.S. Food and Drug Administration, FDA, has cleared the Investigational New Drug application, IND, to initiate a Phase 1 first-in-human, clinical trial of ORX750 for the treatment of narcolepsy. ORX750 is an investigational, orally administered, highly potent and selective orexin receptor 2 agonist designed to directly target the underlying pathophysiology of orexin neuron loss in narcolepsy type 1, with potential applicability to narcolepsy type 2, idiopathic hypersomnia, and other sleep-wake disorders with normal orexin levels. The Phase 1 study will evaluate the safety, tolerability and pharmacokinetics of single-ascending doses and multiple-ascending doses of ORX750 in healthy adult subjects. In parallel to the SAD, a cross-over pharmacodynamic assessment will be performed utilizing the Maintenance of Wakefulness Test and Karolinska Sleepiness Scale in acutely sleep-deprived healthy adult subjects which is intended to provide proof-of-concept data to enable dose selection for NT1, NT2 and IH indications. The study has a maximum exposure limit specified by the FDA which the Company believes significantly exceeds the predicted efficacious doses of ORX750 in indications associated with or without orexin loss; therefore, the Company does not expect this limit to affect any of the planned clinical development activities for ORX750. The Company expects to commence dosing of the Phase 1 study in healthy volunteers imminently, and proof-of-concept data are anticipated in the second half of 2024.