Core Insights - Centessa Pharmaceuticals is advancing a potential best-in-class orexin receptor 2 (OX2R) agonist pipeline, with key data readouts expected in 2025 [2][3] - The company aims to redefine the standard of care for sleep-wake disorders and related comorbidities through its innovative drug candidates [2][3] Pipeline and Milestones - ORX750 is in an adaptive Phase 2a study for narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH), with data expected this year [6][7] - ORX142 has initiated a Phase 1 clinical trial, with results from acutely sleep-deprived healthy volunteers anticipated in 2025 [6][7] - ORX489 is currently in IND-enabling studies targeting neuropsychiatric disorders [6][7] Financial Performance - As of June 30, 2025, the company reported cash, cash equivalents, and investments totaling $404.1 million, expected to fund operations into mid-2027 [12] - Research and Development (R&D) expenses for Q2 2025 were $42.7 million, up from $32.8 million in Q2 2024 [12] - The net loss for Q2 2025 was $50.3 million, compared to a net loss of $43.8 million in Q2 2024 [12][14]

Core Viewpoint - Centessa Pharmaceuticals has received FDA clearance to initiate a Phase 1 clinical study of ORX142, a novel OX2R agonist aimed at treating neurological and neurodegenerative disorders, marking a significant milestone in the company's drug development pipeline [1][2]. Group 1: Clinical Development - The Phase 1 study will assess the safety, tolerability, and pharmacokinetics of ORX142 in healthy volunteers, including single-ascending doses (SAD) and multiple-ascending doses (MAD) [2]. - A placebo-controlled crossover pharmacodynamic assessment will be conducted using the Maintenance of Wakefulness Test (MWT) and Karolinska Sleepiness Scale (KSS) in acutely sleep-deprived subjects [2]. - Clinical data from the Phase 1 study is expected to be available within the year, which will aid in dose selection for future studies involving patients [2]. Group 2: OX2R Agonist Program - Centessa's OX2R agonist program includes multiple candidates: ORX750, ORX142, and ORX489, targeting various sleep-wake disorders and neuropsychiatric conditions [3]. - ORX750 is currently in a Phase 2a study for narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) [3]. - The orexin pathway is being targeted to address excessive daytime sleepiness (EDS), cognitive deficits, and fatigue associated with a range of neurological and neurodegenerative disorders [3]. Group 3: Company Overview - Centessa Pharmaceuticals is a clinical-stage pharmaceutical company focused on developing transformational medicines, particularly in the area of OX2R agonists [4]. - The company is also exploring an early-stage immuno-oncology program utilizing its novel LockBody technology platform [4].