ORX750 / Centessa - LARVOL DELTA

Understanding idiopathic hypersomnia: diagnosis, pathophysiology, and management. (PubMed, Curr Opin Pulm Med) - "Growing insights into the pathophysiology and clinical features of idiopathic hypersomnia have led to improved diagnostic clarity and therapeutic innovation. These developments carry significant implications for clinical practice, offering hope for better symptom control and quality of life in affected individuals. Ongoing research is crucial for refining treatment strategies and deepening our understanding of this complex condition."

Journal • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Development of a Novel, Oral Orexin Receptor 2 Agonist, ORX750 for Treatment of Patients with Narcolepsy (type 1 and 2) and Idiopathic Hypersomnia (WSS 2025) - "ORX750 showed a favorable safety profile and clinically meaningful and statistically significant improvements on wakefulness in the phase 1 study in acutely sleep-deprived healthy volunteers. ORX750 was well tolerated, and normative wakefulness (>30 mins on the MWT) was achieved at the doses ≥ 2.5mg. The phase 1 study, ORX750-0201 and ORX750-202 are open, and results will inform future clinical development."

Clinical • Cataplexy • Cognitive Disorders • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

A Long-term Extension Study of ORX750 in Participants With Narcolepsy and Idiopathic Hypersomnia (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Centessa Pharmaceuticals (UK) Limited | Not yet recruiting ➔ Recruiting

Enrollment open • Narcolepsy • Sleep Disorder

A Long-term Extension Study of ORX750 in Participants With Narcolepsy and Idiopathic Hypersomnia (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: Centessa Pharmaceuticals (UK) Limited

New P2 trial • Narcolepsy • Sleep Disorder

Centessa Pharmaceuticals Reports Business Highlights and Financial Results for the Fourth Quarter and Full-Year 2024 (GlobeNewswire) - "ORX750: Phase 2a CRYSTAL-1 study ongoing in participants with NT1, NT2 and IH. The Company expects to share Phase 2a data across all three indications in 2025. In addition, data from the Phase 1 study will be presented in a poster session at the AAN Annual Meeting on April 5, 2025."

P1 data • P2a data • Narcolepsy • Sleep Disorder

Phase 1 Clinical Data with Orexin Receptor 2 (OX2R) Agonist, ORX750, in Acutely Sleep-Deprived Healthy Participants (AAN 2025) - "Results support that ORX750 was well tolerated across the evaluated dose range, and clinically meaningful and statistically significant improvements in wakefulness were observed in acutely sleep-deprived healthy participants. Doses ≥2.5 mg produced MWT mean sleep latencies >30 minutes. These results support continued evaluation of ORX750 for the potential treatment of narcolepsy and idiopathic hypersomnia."

Clinical data • P1 data • Narcolepsy • Sleep Disorder

Centessa Pharmaceuticals Announces Poster Presentation of Phase 1 Clinical Data for ORX750, a novel orexin receptor 2 (OX2R) agonist, at the American Academy of Neurology (AAN) 2025 Annual Meeting (GlobeNewswire) - "Centessa Pharmaceuticals...announced that data from the Phase 1 clinical trial of ORX750, an investigational novel highly potent and selective OX2R agonist being progressed for the treatment of narcolepsy type 1 (NT1), narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH), will be presented in a poster session at the American Academy of Neurology (AAN) 2025 Annual Meeting....Details of the poster presentation are as follows: Title: Phase 1 Clinical Data with Orexin Receptor 2 (OX2R) Agonist, ORX750, in Acutely Sleep-Deprived Healthy Participants; Abstract Number: 2277."

P1 data • Narcolepsy • Sleep Disorder

CRYSTAL-1: A Study of ORX750 in Participants with Narcolepsy and Idiopathic Hypersomnia (clinicaltrials.gov) - P2 | N=78 | Recruiting | Sponsor: Centessa Pharmaceuticals (UK) Limited

New P2 trial • Narcolepsy • Sleep Disorder

ORX750, an oral selective orexin receptor 2 agonist, promotes wakefulness and reduces cataplexy in the orexin/ataxin-3 mouse (WSS 2023) - "Electrophysiological recordings were performed on slices of the ventral tuberomammillary nucleus (TMN) from mouse hypothalamus; effects on membrane potential were measured in the presence of 1 micromolar tetrodotoxin to block neuron firing. ORX750 is an oral, highly potent, and selective OX2R agonist with the potential to treat patients with primary symptoms of NT1, as well as reduce excessive sleepiness in those presenting sleep/wake disorders with normal orexin levels."

Preclinical • Cataplexy • CNS Disorders • Narcolepsy • Sleep Disorder • Sleep Wake Cycle Disorder • ATXN3

Centessa Pharmaceuticals to Present Preclinical Data for Novel Orexin Receptor 2 (OX2R) Agonist at World Sleep Congress (GlobeNewswire) - "Centessa Pharmaceuticals plc...announced that preclinical data for ORX750, its first orexin agonist development candidate, will be featured in an oral presentation at the World Sleep Congress being held on October 20-25, 2023, in Rio de Janeiro, Brazil....Oral presentation to include preclinical profile for ORX750, Centessa’s first orexin agonist development candidate for the treatment of narcolepsy and other sleep disorders."

Preclinical • CNS Disorders • Narcolepsy • Sleep Disorder

Centessa Pharmaceuticals Announces Third Quarter 2021 Financial Results and Business Updates (GlobeNewswire) - "Orexia Therapeutics’ oral orexin receptor agonist for Narcolepsy Type 1 ('NT1'), and other neurological disorders characterized by excessive daytime sleepiness: The Company is on track to select a candidate for its oral program and commence IND enabling activities in 2022."

Preclinical • CNS Disorders • Narcolepsy • Sleep Disorder