Centessa Pharmaceuticals has initiated a Phase II trial of ORX750, an investigational, orally administered, highly potent and selective orexin receptor 2 (OX2R) agonist for the treatment of narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia. 

ORX750 was designed using Nxera Pharma technology to directly target the underlying pathophysiology of orexin neuron loss in NT1, with potential applicability to NT2, idiopathic hypersomnia, and other sleep-wake disorders with normal orexin levels. 

The ORX750 programme originated from a strategic co-investment between Nxera and Medicxi, the life sciences investment firm, in 2019, which subsequently resulted in Nxera owning 929,353 shares in Centessa (currently valued at approximately US$15 million).  

“The totality of data across our OX2R agonist programme continues to reinforce the strength of our discovery engine and the therapeutic potential of these assets across a broad spectrum of disorders,” said Saurabh Saha, Chief Executive Officer of Centessa. “The Phase I interim data for ORX750, now updated to include over 70 subjects dosed with ORX750, continue to support its best-in-class potential in NT1, NT2 and IH. Based on the strength of these interim data, we recently initiated a Phase IIa clinical study of ORX750 in patients with NT1, NT2 and IH. Similar to our Phase I study, which enabled a move from IND clearance to clinical data in the course of a few months, we expect our Phase IIa study design to generate clinical data for all three indications in 2025 and enable dose selection for future pivotal studies with the potential to be first-in-class in NT2 and IH.” 

Dr Saha continued, “In addition to ORX750, we are advancing a growing pipeline of OX2R agonists targeting excessive daytime sleepiness (EDS) in neurological, neurodegenerative, and psychiatric disorders, as well as other potential symptoms including impaired attention, cognitive deficits, and fatigue. ORX142 is currently in IND-enabling studies, and subject to IND clearance, we expect to initiate clinical development and share clinical data in acutely sleep-deprived healthy volunteers in 2025. We’re also pleased to be kicking off our next wave of candidates with ORX489, our most potent OX2R agonist to date based on preclinical data, which is entering IND-enabling studies.”