Orexin agonists have the potential to address a broad range of neuroscience indications. At Centessa, we are building a pipeline of potential best-in-class orexin receptor 2 (OX2R) agonists designed to deliver transformative treatment options for people living with sleep-wake disorders—including narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH)—as well as select neurological, neurodegenerative, and neuropsychiatric disorders. We also believe that our OX2R agonists may have broader applicability in addressing impaired attention, cognitive deficits, fatigue and other related symptoms.

Despite the significant therapeutic promise of OX2R agonists, there has been a substantial gap in their clinical development given their complex medicinal chemistry. We aim to overcome this obstacle by leveraging structural biology and structure-based drug design to inform the development of small molecule orexin agonists.