Centessa Pharmaceuticals Receives IND Clearance From FDA For Investigational Orexin Receptor 2 Agonist ORX142

Centessa Pharmaceuticals plc, a clinical-stage pharmaceutical company, has received clearance from the U.S. Food and Drug Administration (FDA) to begin a Phase 1 clinical trial for ORX142, an investigational OX2R agonist. ORX142 is the second drug candidate to emerge from Centessa’s orexin development program, which is focused on addressing neurological and neurodegenerative conditions.

ORX142 is a novel compound designed to selectively and potently activate the orexin-2 receptor (OX2R), a target believed to play a key role in regulating wakefulness and cognitive function. The upcoming Phase 1 trial will assess the safety, tolerability, and pharmacokinetics of the drug in healthy volunteers. The study will involve both single-ascending dose (SAD) and multiple-ascending dose (MAD) evaluations.

Saurabh Saha MD PhD, Chief Executive Officer of Centessa, said in a statement, “The clearance of our IND to initiate clinical studies of ORX142 represents a significant milestone, signaling the beginning of an exciting new phase in the clinical development of our OX2R agonist pipeline for indications beyond rare hypersomnias. With our most advanced OX2R agonist, ORX750, advancing in the Phase 2a CRYSTAL-1 study for the treatment of narcolepsy type 1 (NT1), narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH), we are eager to leverage our insights from this new drug class and explore ORX142’s potential to treat a broad range of neurological and neurodegenerative disorders with significant unmet needs. We are excited to begin executing our ORX142 Phase 1 clinical study in acutely sleep-deprived healthy volunteers which is aimed at generating early proof-of-concept data for ORX142 this year which we expect to enable a dose selection for planned studies evaluating ORX142 in patients.”

In addition to these standard assessments, the study will include a placebo-controlled crossover pharmacodynamic (PD) component. This portion will use the Maintenance of Wakefulness Test (MWT) and the Karolinska Sleepiness Scale (KSS) to measure the effects of ORX142 on alertness in healthy adults subjected to acute sleep deprivation. Centessa plans to initiate the first-in-human trial in the near future, with initial clinical data expected later this year. The advancement of ORX142 reinforces the company's commitment to its orexin-based research and its potential to provide new treatment options for disorders that impact the brain and nervous system.