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Advancing a broad, potential best-in-class orexin receptor 2 (OX2R) agonist franchise, with key data readouts expected this year

• ORX750 Phase 2a CRYSTAL-1 study for the treatment of narcolepsy type 1 (NT1), narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) on track with data expected in all three indications this year with first-in-class potential in NT2 and IH
• ORX142 Phase 1 clinical trial for the treatment of select neurological and neurodegenerative disorders underway with data in acutely sleep-deprived healthy volunteers expected this year
• ORX489 in IND-enabling studies for the treatment of neuropsychiatric disorders

BOSTON and LONDON, Aug. 12, 2025-- Centessa Pharmaceuticals plc (Nasdaq: CNTA), a clinical-stage pharmaceutical company, today reported financial results and business highlights for the second quarter ended June 30, 2025.

“As clinical validation of the orexin agonist class continues to grow, we believe Centessa is well positioned with a novel potential best-in-class OX2R agonist pipeline aimed at redefining the standard of care. This includes not only restoring normal wakefulness to meet the real-world needs of individuals with sleep-wake disorders, but also potentially addressing comorbidities such as excessive daytime sleepiness, impaired attention, cognitive deficits and fatigue across a range of neurological, neurodegenerative and neuropsychiatric conditions where there is unmet need,” said Saurabh Saha MD PhD, Chief Executive Officer of Centessa.

Dr. Saha continued, “ORX750, our most advanced OX2R agonist drug candidate, is progressing in an adaptive Phase 2a study that incorporates real-time drug development strategies aimed at optimizing dosing and best positioning ORX750 for planned registrational studies. This innovative approach continues to build our confidence in ORX750’s potential to be a best-in-class OX2R agonist for the treatment of NT1, NT2 and IH, and potentially the first OX2R agonist to treat NT2 and IH. Our top priority remains the successful execution of the Phase 2a study, and we look forward to sharing data for ORX750 in all three indications this year.”

“In parallel, we recently initiated clinical development of ORX142, our second OX2R agonist drug candidate, with data in acutely sleep-deprived healthy volunteers also expected this year. With two programs advancing toward key clinical milestones and a broad pipeline of potentially transformative orexin therapies, we believe Centessa is positioned to become a long-term leader in the orexin space,” concluded Dr. Saha.

Recent Highlights

• Following clearance of the Investigational New Drug application (IND) from the U.S. Food and Drug Administration (FDA) in June 2025, the Company initiated a Phase 1 first-in-human clinical trial of ORX142, with data in acutely sleep-deprived healthy volunteers expected this year.
• In April 2025, additional data from the Phase 1 study of ORX750 were presented in a poster session at the American Academy of Neurology (AAN) Annual Meeting. Along with previously disclosed Phase 1 data, the poster highlighted time-course curves for both the Maintenance of Wakefulness Test (MWT) and the Karolinska Sleepiness Scale (KSS) from the 5.0 mg dose cohort. At this dose, sustained effects were observed across the full 8-hour post-dose observation period, with mean sleep latency exceeding 30 minutes on the MWT and improvements in KSS scores compared to placebo.
• An abstract highlighting the adaptive design of the Company’s Phase 2a CRYSTAL-1 study for ORX750, including an open-label long-term extension (LTE), has been accepted as a poster presentation at the World Sleep 2025 Congress being held on September 5–10, 2025, in Singapore. The abstract, Development of a Novel, Oral Orexin Receptor 2 Agonist, ORX750 for Treatment of Patients with Narcolepsy (type 1 and 2) and Idiopathic Hypersomnia, is available on the conference website. A copy of the poster will be available on the Centessa website at https://investors.centessa.com/events-presentations at the time of the poster presentation.

OX2R Agonist Pipeline and Anticipated Upcoming Milestones 

• ORX750: The Phase 2a CRYSTAL-1 study is ongoing with data in NT1, NT2 and IH expected in 2025.
• ORX142: The Phase 1 first-in-human study of ORX142 is ongoing with data in acutely sleep-deprived healthy volunteers expected in 2025.
• ORX489: Currently in IND-enabling studies.

Second Quarter 2025 Financial Results

• Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments totaled $404.1 million as of June 30, 2025. The Company expects its cash, cash equivalents and investments as of June 30, 2025 will fund operations into mid-2027.
• Research & Development (R&D) Expenses: R&D expenses were $42.7 million for the second quarter ended June 30, 2025, compared to $32.8 million for the second quarter ended June 30, 2024.
• General & Administrative (G&A) Expenses: G&A expenses were $11.9 million for the second quarter ended June 30, 2025, compared to $11.2 million for the second quarter ended June 30, 2024.
• Net Loss: Net loss was $50.3 million for the second quarter ended June 30, 2025, compared to $43.8 million for the second quarter ended June 30, 2024.

About Centessa’s Orexin Receptor 2 (OX2R) Agonist Program

Orexin is a neuropeptide that regulates the sleep-wake cycle, leading to arousal and promoting wakefulness. Targeting the orexin pathway with novel orexin receptor 2 (OX2R) agonists represents a potential promising approach to address excessive daytime sleepiness (EDS), impaired attention, cognitive deficits and fatigue associated with a broad range of neurological, neurodegenerative and neuropsychiatric disorders. Centessa is developing a pipeline of potential best-in-class OX2R agonists, including ORX750 for the treatment of sleep-wake disorders including narcolepsy type 1 (NT1), narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH), ORX142 for the treatment of select neurological and neurodegenerative disorders, and ORX489 for the treatment of neuropsychiatric disorders. ORX750 is being evaluated in the Phase 2a CRYSTAL-1 study. For more information, visit https://clinicaltrials.gov/study/NCT06752668. ORX750, ORX142 and ORX489 are investigational candidates and have not been approved by the FDA or any other regulatory authority.

About Centessa Pharmaceuticals

Centessa Pharmaceuticals, plc is a clinical-stage pharmaceutical company with a mission to discover, develop and ultimately deliver medicines that are transformational for patients. We are pioneering a new class of potential therapies within our orexin receptor 2 (OX2R) agonist program for the treatment of EDS, impaired attention, cognitive deficits and fatigue across neurological, neurodegenerative and neuropsychiatric disorders. For more information, visit www.centessa.com, which does not form part of this release.