Centessa Receives FDA Clearance for Phase 1 Clinical Trial of Promising Narcolepsy Treatment

Centessa Pharmaceuticals plc 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 (OX2R) agonist designed to directly target the underlying pathophysiology of orexin neuron loss in narcolepsy type 1 (NT1), with potential applicability to narcolepsy type 2 (NT2), idiopathic hypersomnia (IH), and other sleep-wake disorders with normal orexin levels.

The Phase 1 study will evaluate the safety, tolerability and pharmacokinetics of single-ascending doses (SAD) and multiple-ascending doses (MAD) of ORX750 in healthy adult subjects. In parallel to the SAD, a cross-over pharmacodynamic (PD) assessment will be performed utilizing the Maintenance of Wakefulness Test (MWT) and Karolinska Sleepiness Scale (KSS) 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.

The Phase 1 study design of ORX750 includes SAD combined with PoC cohorts to assess PD effects of ORX750 by measuring sleep latency with the MWT and subjective sleepiness with the KSS in acutely sleep-deprived healthy subjects.

“This is a significant milestone for the development of our potential best-in-class OX2R agonist, ORX750, for the treatment of narcolepsy and other sleep-wake disorders,” said Saurabh Saha MD PhD, Chief Executive Officer of Centessa. “We are excited to begin executing what we believe is an elegant, adaptive Phase 1 study aimed at generating early proof-of-concept data for ORX750 in acutely sleep-deprived healthy volunteers in the second half of this year. We expect this study to enable dose selection for planned studies evaluating ORX750 in patients with NT1 and in patient populations with normal orexin levels, including NT2 and IH.”

Source: Centessa Pharmaceuticals