Centessa Pharmaceuticals Announces Poster Presentation Featuring Novel Orexin Receptor 2 (OX2R) Agonist Discovery Pipeline at the 26th Conference of the European Sleep Research Society (Sleep Europe 2022)

– Data demonstrate potent efficacy of small-molecule OX2R agonists in a non-clinical model of narcolepsy type 1 (NT1) –
– Company recognizes World Narcolepsy Day on September 22^nd –

BOSTON and LONDON, Sept. 20, 2022 (GLOBE NEWSWIRE) — Centessa Pharmaceuticals plc (Nasdaq: CNTA), today announced that non-clinical data from its oral orexin receptor 2 (OX2R) agonist discovery pipeline have been accepted for poster presentation at the 26th Conference of the European Sleep Research Society meeting (Sleep Europe 2022) being held on September 27-30, 2022, in Athens, Greece. Centessa’s OX2R agonists are designed to directly target the underlying pathophysiology of orexin neuron loss in narcolepsy type 1 (NT1), with potential expansion into narcolepsy type 2 (NT2), and other sleep disorders.

The poster presentation will feature the non-clinical activity profiles of small-molecule OX2R agonists from multiple lead chemical series developed using structure-based drug design with an OX2R protein stabilized in the agonist conformation (Sosei Heptares’ Stabilized Receptor Technology (StaR^®)), together with CryoEM (cryogenic electron microscopy) and high-resolution protein crystallography. These novel OX2R agonist compounds showed high potency in activating recombinant human and endogenous mouse OX2Rs, with more than a thousand-fold selectivity for OX2R compared to OX1R. The OX2R agonists also showed efficacy in promoting wakefulness and in reducing cataplexy events in NT1 model mice, and increased wakefulness in healthy mice.

“Over the past year, we have made significant advances building a deep pipeline of novel, potent and selective OX2R agonists,” said Saurabh Saha, MD, PhD, Chief Executive Officer of Centessa. “Centessa’s orexin program is led by some of the most experienced and insightful scientists in this field. Our innovative pipeline is both a testament to their expertise and strong validation of our approach to structure-based drug design. We are encouraged by the non-clinical data and are rapidly progressing several potentially best-in-class oral small-molecule OX2R agonists through our discovery pipeline.”

“We are excited to showcase some of our small-molecule OX2R agonist discovery pipeline and share these data at Sleep Europe 2022,” said Mario Alberto Accardi, PhD, Head, Centessa Orexin Program. “Additionally, as part of our ongoing commitment to patients, we look forward to joining the entire narcolepsy community in recognizing World Narcolepsy Day on September 22^nd to reinforce the critical need for broader disease awareness and additional treatment options for narcolepsy and other sleep disorders.”

Details of the poster are as follows:
Title: Novel Orexin Receptor-2 Agonists Developed Using Structure-based Drug Design: Prototype Compounds Promote Wakefulness and Reduce Cataplexy in Orexin/Ataxin-3 and WT Mice
Abstract number: 401 Poster code: P001
Presenters: Sarah Wurts Black, Karl Gibson, Deborah S. Hartman
Session name: Late Breaking Abstracts
Session details: September 29, 2022, at 12:15 PM (local time)

The abstract and additional meeting information can be found on the Sleep Europe 2022 website at https://esrs.eu/sleep-congress/. The poster will also be available on the Centessa website at https://investors.centessa.com/events-presentations after the conference concludes.

About Centessa Pharmaceuticals
Centessa Pharmaceuticals plc is a clinical-stage pharmaceutical company with a Research & Development (“R&D”) innovation engine that aims to discover, develop and ultimately deliver impactful medicines to patients. Our programs span discovery-stage to late-stage development and cover a range of high-value indications in rare diseases and immuno-oncology. We are led by a management team with extensive R&D experience, providing direct guidance to our program teams to rapidly advance our candidates from research through all stages of development. For more information, visit www.centessa.com, which does not form part of this release.

Forward Looking Statements
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Contact:

Kristen K. Sheppard, Esq.
SVP of Investor Relations
investors@centessa.com