Centessa Pharmaceuticals Announces Preclinical Data Supporting ORX750’s Potential as a Best-in-Class Oral OX2R Agonist for the Treatment of Narcolepsy and Other Sleep-Wake Disorders

- Preclinical data demonstrated significant activity at low doses of ORX750 in highly predictive translational models of Narcolepsy Type 1 (NT1)

- ORX750 advancing in IND-enabling studies; Clinical proof of concept data planned for 2024

BOSTON and LONDON, Oct. 25, 2023 (GLOBE NEWSWIRE) -- Centessa Pharmaceuticals plc (Nasdaq: CNTA), a clinical-stage pharmaceutical company that aims to discover and develop medicines that are transformational for patients, today announced a robust set of new preclinical data from in vivo and in vitro studies of its investigational, novel orexin receptor 2 (OX2R) agonist, ORX750, that support its potential best-in-class profile for the treatment of narcolepsy and other sleep-wake disorders.

The preclinical data will be featured today in an oral presentation by Sarah Wurts Black PhD, Head of Biology for Centessa’s Orexin Agonist Program, entitled, “ORX750, an Oral Selective Orexin Receptor 2 Agonist, Promotes Wakefulness and Reduces Cataplexy in the Orexin/Ataxin-3 Mouse,” at the World Sleep Congress in Rio De Janeiro, Brazil.

“We are very excited to share this robust preclinical dataset, which we believe shows the significant activity of low doses of ORX750 in highly predictive, translational models of narcolepsy type 1 (NT1),” said Mario Alberto Accardi PhD, President of Centessa’s Orexin Agonist Program. “The preclinical data showed ORX750 achieved maximal wake times and suppressed cataplexy at 0.1 mg/kg, the lowest oral dose tested in the DTA mouse model. Notably, this activity was observed in both the DTA and Atax mouse models that recapitulate NT1 symptoms in humans. The data also showed ORX750 significantly increased wake time in healthy wild type mice at 1 mg/kg, the lowest oral dose tested, supporting the potential for expansion into broader sleep-wake disorders with normal orexin tone, including narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH). We believe these data highlight the breadth of ORX750’s potential as a novel treatment for individuals living with narcolepsy and other sleep-wake disorders.”

“ORX750 is a highly potent and selective novel orexin agonist that closely mimics the function of the endogenous peptide,” said Saurabh Saha MD PhD, Chief Executive Officer of Centessa. “These preclinical data showed that ORX750 has the potential to address the underlying pathophysiology of orexin neuron loss in NT1 and promote wakefulness during the day and suppress cataplexy, including at levels that correspond to very low predicted human doses. In addition, the preclinical pharmacokinetic (PK) profile of ORX750, informed by PK testing in multiple species, including non-human primates, suggests the potential for ORX750 to have high, early and sustained brain exposure. We believe these data provide a strong translational foundation for clinical development. We are focused on rapidly moving ORX750 through IND-enabling studies, obtaining IND clearance and initiating clinical development of ORX750 with the goal of sharing clinical proof of concept data in 2024. We look forward to providing further updates in the coming months.”