Centessa presents preclinical Data for ORX142 in excessive daytime sleepiness

Centessa Pharmaceuticals shared new preclinical data from non-human primate – NHP – studies of ORX142, an investigational, novel, orexin receptor 2, or OX2R, agonist being advanced for the treatment of excessive daytime sleepiness – EDS – in select neurological, neurodegenerative and psychiatric disorders. ORX142 is the second drug candidate from the company’s growing pipeline of OX2R agonists and is in IND-enabling studies. The preclinical data were featured in a late-breaking poster presentation at the 27th Congress of the European Sleep Research Society in Seville. ORX142 potently activated the human OX2R with an EC50 of 0.069 nM and greater than 13,000-fold selective over the human orexin receptor. Oral administration of ORX142 showed significant activity at the lowest dose tested, which was 0.03 mg/kg. ORX142 induced sustained increases in wakefulness that suppressed NREM and REM sleep at the lowest dose tested. Wakefulness induced by ORX142 was associated with normal physiological arousal and EEG power spectra signatures of enhanced alertness and attention. No significant pharmacological activity was observed in GPCR selectivity and in vitro safety panels.