ORX142 Promotes Wakefulness at Very Low Doses, Preclinical Data Shows
Centessa Pharmaceuticals has presented preclinical data on ORX142, an investigational orexin receptor 2 (OX2R) agonist, during the 27th Congress of the European Sleep Research Society. ORX142 demonstrated significant wake-promoting effects in non-human primates at very low doses, showing its potential for treating excessive daytime sleepiness in certain neurological, neurodegenerative, and psychiatric disorders. The data was highlighted in a presentation by Sarah Wurts Black, PhD, and is part of Centessa’s broader pipeline of OX2R agonists, which includes ORX750 currently in phase 1 clinical trials.
Key Takeaways:
Ø Low-Dose Efficacy: ORX142 promoted wakefulness in non-human primates at a low dose (0.03 mg/kg), showing significant increases in wake times with minimal pharmacological side effects.
Ø Targeted Treatment: ORX142 is being developed to treat excessive daytime sleepiness in select neurological and psychiatric disorders, expanding Centessa’s pipeline of orexin receptor 2 agonists alongside ORX750, which is currently in clinical trials.
Ø Scientific Validation: The preclinical data, presented at Sleep Europe 2024, supports the potential of ORX142 as a promising therapeutic for sleep-wake disorders, with its activity rooted in advanced structural chemistry techniques.
Clinical-stage pharmaceutical company Centessa Pharmaceuticals plc shared new preclinical data from non-human primate studies of ORX142, an investigational, novel, orexin receptor 2 (OX2R) agonist being advanced for the treatment of excessive daytime sleepiness in select neurological, neurodegenerative and psychiatric disorders.
ORX142 is the second drug candidate from the company’s pipeline of OX2R agonists and is in Investigational New Drug-enabling studies.
The preclinical data were featured in a late-breaking poster presentation by Sarah Wurts Black, PhD, head of biology for Centessa’s orexin agonist program, at the 27th Congress of the European Sleep Research Society (Sleep Europe 2024) in Seville, Spain.
“ORX142 has shown significant activity in promoting wakefulness at very low doses in highly predictive and translational preclinical models,” says Saurabh Saha, MD, PhD, chief executive officer of Centessa, in a release. “More specifically, the preclinical data showed ORX142 achieved significant increases in wake times at 0.03 mg/kg, the lowest oral dose tested in the [non-human primate] model”
Centessa is developing a pipeline of potential best-in-class OX2R agonists, including ORX750 for the treatment of sleep-wake disorders, including narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia, and ORX142 for the treatment of excessive daytime sleepiness in select neurological, neurodegenerative, and psychiatric disorders.
ORX750 is in a phase 1 clinical study. ORX750 and ORX142 have not been approved by the US Food and Drug Administration or any other regulatory authority.
