Schrödinger and Centessa Pharmaceuticals plc, together with subsidiary Orexia Therapeutics, have entered into an exclusive collaboration focused on the discovery of novel therapeutics targeting the orexin-2 receptor (OX2R), which is known to play a role in a broad spectrum of sleep disorders, including narcolepsy. The collaboration provides Orexia with substantial access to Schrödinger’s entire computational platform as well as Schrödinger’s expertise in large-scale deployment of its technology.

Orexia will leverage Schrödinger’s computational platform, including LiveDesign and Free Energy Perturbation (FEP+), which facilitates calculations for drug discovery to enable accurate prediction of potency at the target of interest. The collaboration will be enabled by Orexia’s structural biology capabilities, including the stabilized OX2R StaR protein exclusively licensed from Sosei Heptares, and high-resolution crystal structures in agonist conformation. The collaboration represents the first time Schrödinger’s technology will be applied in an orexin agonist setting at scale.

“While prevailing treatment approaches only address the symptoms associated with narcolepsy type 1 (NT1), we believe orexin agonists offer a disruptive approach, with the capacity to address the underlying pathology of the disorder. Orexia’s utilization of OX2R stabilized receptors (StaR technology) provides the foundation for R&D which could significantly benefit patients with NT1. We look forward to partnering with Schrödinger to complement the discovery and development work we are conducting at Orexia,” says Saurabh Saha, MD, PhD, Centessa CEO, in a release.

“Orexia’s asset-centric approach enables us to pick the best technology partners for discovery and development. While we expect to enter IND enabling studies with our lead molecule next year, we are also delighted to work with Schrödinger to enable the acceleration of our discovery efforts for molecules with potentially differentiated clinical profiles. Indeed, the therapeutic possibilities of orexin agonists extend well beyond NT1 into other rare primary hypersomnia disorders, such as narcolepsy type 2 and idiopathic hypersomnia, and into a broad range of additional indications characterized by excessive daytime sleepiness. We are committed to exploring the full potential of orexin agonists to help patients across a wide range of indications,” says Mario Alberto Accardi, PhD, Orexia CEO, in a release.

“Our research collaboration with Orexia is illustrative of a new approach to help support discovery efforts at biotech companies, where we apply our technology at scale on behalf of our collaborator,” says Ramy Farid, PhD, president and CEO of Schrödinger, in a release. “The Orexia team brings deep experience in orexin biology and structure-based drug design, and we’re excited to provide Orexia with large-scale access to our leading computational approaches and expertise to accelerate the discovery of novel therapeutics targeting orexin biology.”

Under the terms of the agreement, Orexia will be responsible for preclinical research activities, clinical development, and commercialization of future product candidates discovered under the collaboration. Schrödinger will receive an upfront software access payment and may become eligible to receive certain preclinical, development, regulatory and commercial milestone payments, as well as low single digit royalties on global net sales.

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