Centessa Pharmaceuticals Subsidiary, Orexia Therapeutics, and Schrödinger Announce Collaboration to Discover Novel Orexin Receptor Agonists

Discovery efforts will focus on small molecules with differentiated clinical profiles to harness the broad potential of orexin agonism across different indications

First time Schrödinger is applying its computational platform in an orexin agonist setting enabled by Orexia’s structural biology capabilities

Schrödinger (Nasdaq:SDGR) and Centessa Pharmaceuticals plc (“Centessa”) (Nasdaq:CNTA), together with subsidiary Orexia Therapeutics (“Orexia”), today announced 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 extensive expertise in ultra-large-scale deployment of its technology.

Orexia will leverage Schrödinger’s computational platform, including LiveDesign and Free Energy Perturbation (FEP+), which facilitates high-performance 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,” said Saurabh Saha, M.D., Ph.D., chief executive officer of Centessa.

“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,” said Mario Alberto Accardi, Ph.D., chief executive officer of Orexia.

“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,” stated Ramy Farid, Ph.D., president and chief executive officer of Schrödinger. “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.

About Schrödinger

Schrödinger is transforming the way therapeutics and materials are discovered. Schrödinger has pioneered a physics-based software platform that enables discovery of high-quality, novel molecules for drug development and materials applications more rapidly and at lower cost compared to traditional methods. The software platform is used by biopharmaceutical and industrial companies, academic institutions, and government laboratories around the world. Schrödinger’s multidisciplinary drug discovery team also leverages the software platform to advance collaborative programs and its own pipeline of novel therapeutics to address unmet medical needs.

Founded in 1990, Schrödinger has over 500 employees and is engaged with customers and collaborators in more than 70 countries. To learn more, visit www.schrodinger.com and follow us on LinkedIn and Twitter.

About Centessa Pharmaceuticals

Centessa Pharmaceuticals plc aims to bring impactful new medicines to patients by combining the strengths of an asset-centric model with the benefits of scale and diversification typical of larger R&D organizations. The asset-centric model refers to a highly specialized, singular-focused company that is led by a team of well-recognized subject matter experts. Centessa’s asset-centric companies’ programs range from discovery-stage to late-stage development and include diverse therapeutic areas such as oncology, hematology, immunology/inflammation, neuroscience, hepatology, pulmonology and nephrology. For more information, visit www.centessa.com.

About Orexia Therapeutics

Orexia was founded by venture capital firm Medicxi in collaboration with Heptares Therapeutics Limited, a wholly owned subsidiary of Sosei Group Corporation (Sosei Heptares), and leverages Sosei Heptares’ GPCR StaR^® technology to develop oral and intranasal orexin receptor agonists using structure-based drug design approaches. These agonists target the treatment of narcolepsy type 1, with the aim to directly address the underlying pathology of orexin loss, as well as other neurological disorders characterized by excessive daytime sleepiness. For more information, visit www.orexiatherapeutics.com.

Schrödinger Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 including, but not limited to those regarding our expectations about the speed and capacity of our computational platform, the ability for our platform to be applied in an orexin agonist setting, the potential of our collaboration with Orexia to develop new therapies, our ability to realize potential milestones, royalties or other payments under the collaboration and the risk that we may not realize the expected benefits of the collaboration. Statements including words such as "anticipate," "believe," "contemplate," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," "would" and statements in the future tense are forward-looking statements. These forward-looking statements reflect our current views about our plans, intentions, expectations, strategies, and prospects, which are based on the information currently available to us and on assumptions we have made. Actual results may differ materially from those described in these forward-looking statements and are subject to a variety of assumptions, uncertainties, risks and factors that are beyond our control, including our reliance upon third-party providers of cloud-based infrastructure to host our software solutions, our reliance on Orexia to perform its obligations to develop and commercialize any development candidates discovered under the collaboration, the uncertainties inherent in drug development and commercialization, uncertainties associated with the regulatory review of clinical trials and applications for marketing approvals, the potential impact of the COVID-19 pandemic on our operations or the operations of third parties we rely on, as well as the other risks and uncertainties identified under the caption "Risk Factors" and elsewhere in our Securities and Exchange Commission filings and reports, including the Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on August 12, 2021, as well as future filings and reports by us. Any forward-looking statements contained in this press release speak only as of the date hereof. Except as required by law, we undertake no duty or obligation to update any forward-looking statements contained in this press release as a result of new information, future events, changes in expectations or otherwise.

Centessa Forward-Looking Statement

This press release contains forward-looking statements. These statements may be identified by words such as "believe," "anticipate," "plan," "expect," "intend," "will," "may," "goal," "project," "estimate," "potential," and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. These statements include discussions relating to discovery of novel therapeutics targeting the orexin-2 receptor (OX2R); plans for continued research and development; our expectations with respect to the treatment paradigm for narcolepsy type 1 (NT1) and our belief that orexin agonists offer a disruptive approach to NT1 treatment and has the capacity to address the underlying pathology of the disorder; our ability to deliver impactful medicines to patients; the ability of our key executives to drive execution of our portfolio of programs; our asset-centric business model and the intended advantages and benefits thereof; research and clinical development plans; the scope, progress, results and costs of developing our product candidates or any other future product candidates; strategy; regulatory matters, including the timing and likelihood of success of obtaining approvals to initiate or continue clinical trials or market any products; market size and opportunity; and our ability to complete certain milestones.

Any forward-looking statements in this press release are based on our current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, our ability to discover novel therapeutics targeting OX2R; foreign regulatory agencies may not agree with our regulatory approval strategies, components of our filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted; risks inherent in developing products and technologies; risks related to our ability to protect and maintain our intellectual property position; business, regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about the company; our ability to obtain adequate financing to fund our research and development plans and other expenses; trends in the industry; the legal and regulatory framework for the industry; future expenditures risks related to our asset-centric corporate model; the risk that any one or more of our product candidates will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies; and risks related to the COVID-19 pandemic including the effects of the Delta variant. These and other risks concerning our programs and operations are described in additional detail in our most recent Form 10-Q, which is on file with the SEC and available on the SEC’s website at www.sec.gov. We operate in a very competitive environment in which new risks emerge from time to time. These forward-looking statements are based on our current expectations, and speak only as of the date hereof. We explicitly disclaim any obligation to update any forward-looking statements except to the extent required by law.

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