Key Takeaways: 

  • Centessa Pharmaceuticals reported progress in its orexin agonist program, spotlighting the potential of ORX750 to treat narcolepsy and other sleep-wake disorders based on promising preclinical data.
  • ORX750 demonstrated effectiveness in reducing cataplexy and increasing wake times at low doses in narcolepsy models, indicating its potential as a best-in-class treatment for a range of sleep-wake disorders.
  • The company is on schedule to share clinical proof-of-concept data for ORX750 in sleep-deprived healthy volunteers in 2024, marking a critical step forward in its development program.

Centessa Pharmaceuticals plc, a clinical-stage pharmaceutical company, reported recent business highlights and financial results for Q4 and the full year of 2023, spotlighting progress in its orexin agonist program aimed at treating narcolepsy and sleep-wake disorders.

In October 2023, the company announced preclinical data from in vivo and in vitro studies of its investigational, novel orexin receptor 2 (OX2R) agonist, ORX750, that it believes supports a potential best-in-class profile.

The preclinical data showed ORX750 achieved maximal wake times and suppressed cataplexy at 0.1 mg/kg, the lowest oral dose tested in a DTA mouse model. Notably, this activity was observed in both DTA and Atax mouse models that recapitulate narcolepsy type 1 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 and idiopathic hypersomnia.

“This is an exciting and pivotal time for Centessa,” says Saurabh Saha, MD, PhD, chief executive officer of Centessa, in a release. “We are laser-focused on….advancing our orexin receptor 2 agonist development program into the clinic for the treatment of narcolepsy and other sleep-wake disorders.”

The company remains on track with its goal to share clinical proof-of-concept data for ORX750 in sleep-deprived healthy volunteers this year.

Anticipated upcoming program milestone:

  • Orexin agonist program – Upon Investigational New Drug clearance, the company plans to rapidly advance ORX750 into clinical development with the goal of sharing clinical proof-of-concept data in sleep-deprived healthy volunteers in 2024.

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