Centessa Signals Strategic Shift with Leadership Change
Centessa Pharmaceuticals is making a pivotal move by appointing Dr. Mario Alberto Accardi, President and founder of the company’s orexin program, as the new CEO, effective January 1, 2026. This transition follows the decision by current CEO Dr. Saurabh Saha to step down, transitioning into an advisory role as the company enters its next phase.
This leadership update is more than a management shuffle—it represents Centessa’s sharpened focus on advancing its orexin receptor 2 (OX2R) agonist portfolio, targeting multiple neurological and neuropsychiatric disorders. The company, once an early-stage R&D startup, is doubling down on what it sees as its strongest opportunity: pioneering new treatments for sleep-wake and neurodegenerative diseases using orexin pathway therapeutics.
Centessa’s Pipeline Is Centered Around OX2R Agonist Innovation
At the heart of this transition is a strategy anchored in scientific expertise. Dr. Accardi, previously the founder and CEO of Orexia Therapeutics (acquired by Centessa in 2021), has built a team with deep orexin biology expertise and a vision to unlock orexin’s full clinical potential. Centessa’s leading candidate, ORX750, is currently in a Phase 2a trial (CRYSTAL-1) and will initiate a registrational program in early 2026 for narcolepsy and idiopathic hypersomnia—indications where a clear need for more effective therapies exists.
The pipeline extends beyond ORX750. Additional candidates, such as ORX142 and ORX489, are set to enter development for broader neurological, neurodegenerative, and neuropsychiatric disorders with key clinical milestones expected next year.
| Program | Lead Compound | Indications | Clinical Stage | Key Milestones (Expected 2026) |
|---|---|---|---|---|
| OX2R Agonist | ORX750 | Narcolepsy, Idiopathic Hypersomnia | Phase 2a (CRYSTAL-1) | Start registrational trial Q1 2026 |
| OX2R Agonist | ORX142 | Neurodegenerative Disorders | Preclinical | Development milestone in 2026 |
| OX2R Agonist | ORX489 | Neuropsychiatric Disorders | Preclinical | Development milestone in 2026 |
Specialized Leadership Signals Clear Strategic Direction
The Board’s choice to elevate Dr. Accardi aligns Centessa’s operational focus with its orexin science leadership. Chair of the Board, Dr. Francesco De Rubertis, stated this move ensures the right expertise is in place to maximize the pipeline’s potential, as Centessa evolves from a multi-asset early-stage player into a pure-play leader in orexin-based neuroscience.
For investors and industry watchers, this shift means that upcoming clinical readouts, regulatory developments, and the initiation of late-stage studies could define Centessa’s near-term value creation—and spotlight the therapeutic potential of OX2R agonists in addressing a broad range of sleep-wake and cognitive disorders.
What Should Stakeholders Watch for in 2026?
Centessa has set expectations for multiple key milestones next year: a registrational program for ORX750 in narcolepsy and idiopathic hypersomnia, alongside progress in bringing ORX142 and ORX489 forward in broader neuroscience indications. With these programs advancing, Centessa could emerge as a critical player in next-generation therapies for neurological disorders.
The focus for current and prospective stakeholders? Monitor the clinical trial updates on ORX750 (especially via the CRYSTAL-1 study, NCT06752668 and NCT07096674 on ClinicalTrials.gov) and stay tuned for pipeline milestones in 2026 as the new leadership seeks to turn scientific expertise into commercial and patient impact.
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