DISCLAIMER AND FORWARD LOOKING STATEMENTS This presentation has been prepared by Centessa Pharmaceuticals plc (the "Company") for informational purposes only and not for any other purpose. This presentation does not contain all the information that is or may be material to investors or potential investors and should not be considered as advice or a recommendation to investors or potential investors in respect of the holding, purchasing or selling of securities or other financial instruments and does not tak ...

BOSTON and LONDON, June 16, 2025 (GLOBE NEWSWIRE) -- Centessa Pharmaceuticals plc (Nasdaq: CNTA), a clinical-stage pharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has cleared the IND to initiate a Phase 1 clinical study of ORX142 in healthy volunteers. ORX142 is an investigational, novel, highly potent and selective OX2R agonist being developed for the treatment of select neurological and neurodegenerative disorders. ORX142 is the second drug candidate from the Compa ...

Summary of Centessa Pharmaceuticals (CNTA) Conference Call Company Overview - **Company**: Centessa Pharmaceuticals (CNTA) - **Focus**: Orexin program, specifically ORX750, an orexin agonist for treating narcolepsy and idiopathic hypersomnia Key Insights on Orexin Space - **Exciting Year Ahead**: Centessa anticipates a data-rich year with multiple catalyst events, including Phase II data disclosures for narcolepsy type one, type two, and idiopathic hypersomnia with ORX750, which is considered the most potent and selective orexin agonist in clinical development [2][4] - **First in Class Opportunity**: The company aims for a first-in-class opportunity in narcolepsy type two and idiopathic hypersomnia, with a best-in-class profile characterized by rapid onset of action, potential for QT dosing, linear pharmacokinetics (PK), and flexible dosing [2][4] Phase II Study Design - **Innovative Design**: The Phase II study allows for dose selection during the study based on real-time data, enabling optimal dosing and flexibility for patients [2][3] - **Efficacy Data**: Preliminary data from sleep-deprived healthy volunteers showed significant efficacy, with patients on ORX750 maintaining wakefulness significantly longer than those on placebo [7][8] Safety and Tolerability - **High Tolerability**: The drug class is reported to be extremely well tolerated, with minimal on-target adverse events (AEs) such as insomnia and polyuria [15][16] - **Liver Toxicity Concerns**: Centessa emphasizes that liver toxicity is molecule-specific and not an on-target effect, focusing on developing molecules with a favorable metabolic profile to mitigate risks [20] Market Opportunity - **Large Patient Population**: The company has revised epidemiological numbers, identifying approximately 50,000 diagnosed and treated narcolepsy type one patients, 100,000 in type two, and 120,000 in idiopathic hypersomnia, indicating a substantial market opportunity [24][25] - **Potential for Multiple Agonists**: There is potential for more than one orexin agonist in the market, given the large patient population and unmet clinical needs [25] Future Directions - **Expansion into Other Indications**: Centessa plans to explore orexin agonists in neurodegenerative and psychiatric disorders, such as Parkinson's disease and major depressive disorder, where excessive daytime sleepiness is prevalent [36][37] - **Partnership Opportunities**: While currently fully financed to execute clinical development plans, the company remains open to partnerships for indication expansion in the future [38] Conclusion - **Transformational Potential**: The orexin agonist class, particularly ORX750, is positioned to significantly impact the treatment landscape for narcolepsy and other disorders characterized by excessive daytime sleepiness, with a strong focus on patient needs and flexible dosing strategies [36][37]

Group 1 - Centessa Pharmaceuticals announced the presentation of Phase 1 clinical trial data for ORX750, a novel OX2R agonist aimed at treating narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) at the AAN 2025 Annual Meeting [1] - The ongoing Phase 2a clinical trial (CRYSTAL-1) is evaluating ORX750 in participants with NT1, NT2, and IH [1] - The poster presentation will take place on April 5, 2025, with details including the title, abstract number, and presenter provided [2] Group 2 - Centessa Pharmaceuticals is focused on developing best-in-class OX2R agonists for sleep-wake disorders and anticipates potential applications in treating cognitive deficits and excessive daytime sleepiness [3] - The company is also advancing an earlier stage pipeline in immuno-oncology utilizing its proprietary LockBody® technology platform [3]

Centessa Pharmaceuticals (CNTA) Conference February 06, 2025 01:00 PM ET Company Participants Debjit Chattopadhyay - Managing DirectorMario Accardi - President of the Orexin Program Debjit Chattopadhyay Good afternoon, and thank you for joining Guggenheim's second, Smithcap conference. I am Devchit, and joining me from Syntesa is Mario Carty, the president of the Orexin program. Did I get that right? Mario Accardi You did. Yes, Doug. Hi. Great to be here with you. Debjit Chattopadhyay Well, it's been a very ...