Orexin agonists have the potential to address the underlying cause of narcolepsy type 1 (NT1) and treat excessive daytime sleepiness (EDS) across multiple disorders. At Centessa, we are building a pipeline of potential best-in-class orexin receptor 2 (OX2R) agonists to bring potentially transformative treatment options to enhance the lives of individuals living with sleep-wake disorders, including NT1, narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH), as well as EDS in select neurological, neurodegenerative, and psychiatric disorders. We also anticipate that our OX2R agonists may have utility in treating impaired attention, cognitive deficits, fatigue and other symptoms.

Although OX2R agonists have significant therapeutic potential, there has been a substantial gap in the development of orexin agonists, attributed to their complex medicinal chemistry. We aim to overcome this obstacle by leveraging structural biology techniques and structure-based drug design to help guide the design of small molecule orexin agonists.