New collaboration aims to discover novel orexin receptor agonists for narcolepsy and other sleep disorders


Sleep Treatments | Sleep Review

Schrödinger and Centessa Pharmaceuticals plc, along 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 be used in a wide spectrum of insomnia plays a role. including narcolepsy. The collaboration gives Orexia extensive access to Schrödinger’s entire computing platform and to Schrödinger’s expertise in the large-scale use of its technology.

Orexia will leverage Schrödinger’s computing platform, including LiveDesign and Free Energy Perturbation (FEP +), to facilitate drug discovery calculations to enable accurate prediction of efficacy at the target of interest. The collaboration is made possible 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 marks the first time that Schrödinger’s technology has been applied on a large scale in an orexin agonist setting.

“While the prevailing treatment approaches only treat the symptoms associated with narcolepsy type 1 (NT1), we believe that orexin agonists offer a disruptive approach with the ability to address the underlying pathology of the disease. Orexia’s use of OX2R Stabilized Receptors (StaR technology) provides the foundation for research and development that could benefit patients with NT1 significantly. We look forward to partnering with Schrödinger to complement the research and development work we do at Orexia, ”said Saurabh Saha, MD, PhD, Centessa CEO, in a press release.

“Orexia’s plant-centric approach enables us to select the best technology partners for discovery and development. We expect to enter IND-enabling studies with our lead molecule next year, but we look forward to working with Schrödinger to accelerate our research efforts for molecules with potentially differentiated clinical profiles. Indeed, the therapeutic possibilities of orexin agonists extend well beyond NT1 to other rare primary hypersomnia disorders such as narcolepsy type 2 and idiopathic hypersomnia, as well as a wide range of additional indications characterized by excessive daytime sleepiness. We are committed to exploring the full potential of orexin agonists to help patients in a wide variety of indications, ”said Mario Alberto Accardi, PhD, CEO of Orexia, in a press release.

“Our research collaboration with Orexia illustrates a new approach to support the research efforts of biotech companies where we apply our technology on a large scale on behalf of our employees,” said Ramy Farid, PhD, President and CEO of Schrödinger, in a press release. “The Orexia team brings extensive experience in orexin biology and structure-based drug design, and we are pleased to provide Orexia with extensive access to our leading computational approaches and expertise to help discover novel therapeutics for orexin biology to accelerate.”

Under the terms of the agreement, Orexia will be responsible for the preclinical research activities, clinical development and commercialization of future product candidates identified as part of the collaboration. Schrödinger is pre-paid for software access and may be eligible for certain preclinical, development, regulatory, and commercial milestone payments, as well as low single-digit royalty payments on global net sales.

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