Centessa Pharmaceuticals Announces CEO Transition as Company Advances Strategy to Extend Orexin Leadership into Multiple Neuroscience Indications 

Rhea-AI Summary

Centessa Pharmaceuticals (Nasdaq: CNTA) announced a CEO transition effective January 1, 2026, appointing Mario Alberto Accardi PhD, president and founder of Centessa’s Orexin Program, as CEO and board member; outgoing CEO Saurabh Saha MD PhD will step down and serve as advisor.

The company is refocusing from a diversified early-stage pipeline to a pure-play orexin portfolio. Key program milestones: a registrational program for ORX750 is expected to start in Q1 2026, and clinical progress on ORX142 and ORX489 targets neurodegenerative and neuropsychiatric indications with milestones planned in 2026. Dr. Accardi previously led Orexia Therapeutics, raising €40M Series A and leading its acquisition by Centessa in 2021.

Positive

• CEO appointment effective Jan 1, 2026
• Registrational program for ORX750 expected Q1 2026
• Additional OX2R assets (ORX142, ORX489) with milestones in 2026
• CEO has prior €40M Series A fundraising and acquisition experience

Negative

• Outgoing CEO Saurabh Saha to step down Jan 1, 2026
• Company shifts to a pure‑play orexin strategy, narrowing pipeline diversification

Key Figures

CEO transition effective date January 1, 2026 Effective date for new CEO appointment

Registrational start Q1 2026 Expected start of ORX750 registrational program

Key milestones year 2026 Multiple orexin program milestones expected

Series A raise €40M Capital raised by Orexia Therapeutics under Dr. Accardi

Acquisition year 2021 Year Orexia Therapeutics was acquired by Centessa

Market Reality Check

$26.51 Last Close

Volume Volume 953,803 is below the 20-day average of 1,986,877, suggesting a moderate reaction to the CEO transition. low

Technical Shares at $29.57 are trading above the $17.86 200-day MA and sit 3.3% below the $30.58 52-week high.

Peers on Argus 1 Down

CNTA gained 3.39% alongside multiple biotech peers also up, including IMVT (+3.97%) and TLX (+4.53%), indicating broader strength in related neuroscience/biotech names rather than an isolated move.

Common Catalyst Same-day peer news includes an IMVT equity financing, pointing to active capital markets in the biotech space.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Nov 11	Equity offering priced	Negative	+0.9%	Underwritten ADS offering raising about <b>$250M</b> at <b>$21.50</b> per ADS.
Nov 11	Equity offering proposed	Negative	+0.9%	Announcement of proposed ADS offering with 30-day overallotment option.
Nov 07	Investor conferences	Neutral	-3.1%	Planned participation in multiple healthcare investor conferences in late 2025.
Nov 05	Earnings & pipeline	Positive	-5.1%	Q3 2025 results plus positive ORX750 and ORX142 clinical data and timelines.
Sep 03	Conference participation	Neutral	-7.9%	Announcement of attendance at Morgan Stanley Global Healthcare Conference.

Pattern Detected

Recent financings and earnings with positive clinical data often saw mixed or negative price reactions, indicating a tendency toward divergence on ostensibly constructive news.

Recent Company History

Over the last few months, Centessa executed multiple capital-raising steps, including a public ADS offering priced at $21.50 for gross proceeds of $250M, and reported Q3 2025 results with $349.0M in cash funding operations into mid-2027. Conference participation has been frequent, and orexin data updates highlighted potential best-in-class OX2R agonists. Against this backdrop, the CEO transition continues the shift toward a focused orexin-driven neuroscience strategy.

Market Pulse Summary

The stock moved -8.1% in the session following this news. A negative reaction despite the leadership change would fit a pattern where prior constructive news, including positive orexin data and financings, sometimes saw weak price follow-through. The appointment of the orexin program’s founder as CEO emphasized scientific continuity, but recent capital raises and insider net selling in November might have weighed on sentiment and introduced concerns about dilution or profit-taking after a strong move toward the 52-week high.

Key Terms

orexin medical

"extend Orexin leadership into multiple neuroscience indications"

Orexin is a naturally occurring brain chemical that helps regulate wakefulness, alertness and appetite, acting like a thermostat that keeps the body awake and cues hunger. Investors watch orexin closely because drugs that boost or block its activity can treat sleep disorders, insomnia or metabolic conditions, which can create large markets, regulatory scrutiny and binary clinical trial outcomes that move stock prices.

OX2R agonists medical

"pipeline of potential best-in-class OX2R agonists for a broad range"

Ox2r agonists are drugs that activate the orexin type‑2 receptor, a brain protein that responds to the wakefulness‑promoting chemical orexin. By turning on this receptor they can help keep people awake and stabilize sleep‑wake cycles, so investors watch them as potential treatments for narcolepsy, excessive daytime sleepiness and related disorders; successful clinical results can create new prescription markets and regulatory value.

neurodegenerative medical

"targeting neurodegenerative and neuropsychiatric indications with key milestones"

Neurodegenerative describes diseases where nerve cells in the brain or spinal cord progressively lose function and die, causing worsening movement, memory or other mental abilities over time. For investors this matters because such conditions create large, long-term needs for therapies and caregiving; developing treatments often requires lengthy, expensive research and regulatory testing but can lead to substantial, sustained market opportunities if a therapy proves effective — like fixing the wiring in a whole neighborhood rather than a single house.

neuropsychiatric medical

"targeting neurodegenerative and neuropsychiatric indications with key milestones"

Conditions or symptoms that involve both the brain’s biology and a person’s mood, thinking or behavior; they sit at the intersection of neurology and psychiatry. Investors care because neuropsychiatric issues often require specialized drugs, devices or diagnostics, carry distinct regulatory and safety risks, and can affect patient populations and market size — think of them as disorders where hardware (brain circuitry) and software (behavior) problems overlap.

narcolepsy medical

"profile for narcolepsy and idiopathic hypersomnia, with a registrational program"

A chronic neurological condition that causes sudden, uncontrollable episodes of deep sleep and extreme daytime drowsiness, like a phone that unexpectedly shuts off during the day. It matters to investors because it defines the market need for treatments, influences clinical trial results and regulatory decisions, and can drive revenue or risk for companies developing medications, devices, or diagnostics tied to sleep disorders.

idiopathic hypersomnia medical

"profile for narcolepsy and idiopathic hypersomnia, with a registrational"

A chronic sleep disorder that causes extreme daytime sleepiness and prolonged, unrefreshing sleep despite adequate night sleep, with no identifiable medical or neurological cause. Think of it like a phone battery that won’t hold charge: sufferers remain tired and less productive even after long rest. For investors, idiopathic hypersomnia matters because it creates demand for treatments, diagnostics and supportive services, influencing market opportunities and regulatory pathways in sleep medicine.

AI-generated analysis. Not financial advice.

Mario Alberto Accardi PhD, President and founder of Centessa’s Orexin Program, appointed Chief Executive Officer and member of the Board of Directors

BOSTON and LONDON, Dec. 11, 2025 (GLOBE NEWSWIRE) -- Centessa Pharmaceuticals plc (Nasdaq: CNTA), a clinical-stage pharmaceutical company, today announced that its Board of Directors has appointed Mario Alberto Accardi PhD, President and founder of Centessa’s Orexin Program, as Chief Executive Officer (CEO) and member of the Board, effective January 1, 2026. Dr. Accardi will succeed Saurabh Saha MD PhD, who will step down from his position as CEO and a member of the Board, effective January 1, 2026. Dr. Saha will be appointed advisor to the CEO.

“This leadership transition underscores Centessa’s strategic evolution from an R&D driven start-up with a diversified early-stage pipeline to an organization focused on advancing a pure-play orexin portfolio positioned at the forefront of this rapidly emerging therapeutic class,” said Francesco De Rubertis PhD, Chair of Centessa’s Board. “This strategic focus has enabled a robust pipeline of potential best-in-class OX2R agonists for a broad range of neurological, neurodegenerative and neuropsychiatric disorders, as well as earlier-stage efforts targeting differentiated orexin pharmacology. As Centessa advances its pipeline into multiple neuroscience indications with significant milestones planned for 2026, the Board is committed to ensuring the Company has the specialized leadership needed to unlock its full potential. In close alignment with Saurabh, we determined that Mario is best positioned to lead the Company into this next chapter, bringing a deep understanding of orexin biology and a long-standing vision that underpins our strategy. The Board thanks Saurabh for his outstanding and vital contributions in building Centessa’s strong foundation. His leadership in guiding the Company from its inception through critical development milestones, shaping strategic portfolio priorities, and assembling a top-tier neuroscience team has enabled Centessa to concentrate its resources on orexin therapeutics, one of the most promising areas in neuroscience.”

“Leading Centessa from start-up through its transformation to an orexin-focused company has been a privilege,” said Dr. Saha. “Together, we built what we believe is a world class organization with an industry leading orexin franchise. With Centessa well-positioned for its next chapter, I believe now is the appropriate time for a transition in leadership. Along with the Board, I am confident that Mario, the principal architect of our OX2R agonist program, is the right leader to further advance Centessa’s pipeline and strategy, and I look forward to working with him to ensure a smooth transition.”

“OX2R agonists represent one of the most compelling growth opportunities in neuroscience, and Centessa’s leading orexin franchise is well-positioned to capitalize on this potential,” said Dr. Accardi. “ORX750, our most advanced OX2R agonist, has already demonstrated a potential best-in-class profile for narcolepsy and idiopathic hypersomnia, with a registrational program expected to initiate in Q1 2026. In parallel, we are advancing additional, novel OX2R agonists, including ORX142 and ORX489, targeting neurodegenerative and neuropsychiatric indications with key milestones expected in 2026. I’m thrilled to step into the CEO role and join Centessa’s Board at this exciting time. Together with the team, I look forward to advancing our multi-asset orexin strategy aimed at extending our orexin leadership beyond the rare hypersomnias and into multiple high-value neuroscience indications and unlocking the full potential of our pipeline for patients and all our stakeholders.”

As President of Centessa’s Orexin Program, Dr. Accardi has been responsible for leading the advancement of the orexin pipeline, which has become the full focus of the Company. Prior to Centessa, he was founder and CEO of Orexia Therapeutics, a neuroscience company harnessing advanced structural biology technologies to discover and develop orexin agonists for narcolepsy and other sleep-wake disorders. At Orexia, he successfully raised a €40M Series A, established multiple strategic partnerships, and led the company through its successful acquisition by Centessa in 2021. Dr. Accardi holds a Postgraduate in Genomic Medicine, a PhD in Biomedical Engineering and a First-Class Honours MEng Degree in Mechanical Engineering from Imperial College London.

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 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), and ORX142 and ORX489 for the treatment of select neurological, neurodegenerative and neuropsychiatric disorders. ORX750 is being evaluated in the Phase 2a CRYSTAL-1 study. Information about the trial can also be found at ClinicalTrials.gov (NCT06752668 and NCT07096674). 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 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.

Forward Looking Statements
This press release contains forward-looking statements. These statements may be identified by words such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” “aim,” “seek,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements, including statements related to the Company’s ability to discover and develop transformational medicines for patients; its expectations for executing on the Company's pipeline; its expectations on its anticipated cash runway; the timing of commencement of new studies or clinical trials or clinical and preclinical data related to ORX750, ORX142, ORX489 and other OX2R agonist molecules; its ability to identify, screen, recruit and maintain a sufficient number of or any subjects in its existing and anticipated studies or clinical trials of ORX750, ORX142, ORX489 and other OX2R agonist molecules; its expectations on executing its research and clinical development plans and the timing thereof; its expectations as to the potential results and impact of each of its clinical programs and trials; the Company’s ability to differentiate ORX750, ORX142, ORX489 and other OX2R agonist molecules from other treatment options, including those being developed by competitors; the development, design and therapeutic potential of ORX750, ORX142, ORX489 and other OX2R agonist molecules, including the potential for ORX750 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; and regulatory matters, including the timing and likelihood of success of obtaining regulatory clearance, obtaining authorizations to initiate or continue clinical trials. Any forward-looking statements in this press release are based on our current expectations, estimates, assumptions and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, risks related to the safety and tolerability profile of our product candidates; our ability to identify, screen and recruit a sufficient number of or any subjects in our existing and anticipated new studies or clinical trials of ORX750, ORX142, ORX489 or within anticipated timelines; our expectations relating to the clinical trials of ORX750 and ORX142, including the predicted timing of enrollment, the predicted efficacious doses of ORX750 and ORX142 and our ability to successfully conduct our clinical development of ORX750 and ORX142, our ability to protect and maintain our intellectual property position; business (including commercial viability), regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about the Company; risks inherent in developing product candidates and technologies; future results from our ongoing and planned clinical trials; our ability to obtain adequate financing, including through our financing facility with Oxford Finance, to fund our planned clinical trials and other expenses; trends in the industry; the legal and regulatory framework for the industry, including the receipt and maintenance of clearances to conduct or continue clinical testing; our operating costs and use of cash, including cash runway, cost of development activities and conducting clinical trials, future expenditures risks; the risk that any one or more of our product candidates will not be successfully developed and/or commercialized; the risk that the historical results of preclinical studies or clinical studies will not be predictive of future results in ongoing or future studies; economic risks to the United States and United Kingdom banking systems; and geo-political risks such as the Russia-Ukraine war or the Middle East conflicts or trade wars and impact of imposition of tariffs. These and other risks concerning our programs and operations are described in additional detail in our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and our other reports, which are on file with the U.S. Securities and Exchange Commission (SEC). We explicitly disclaim any obligation to update any forward-looking statements except to the extent required by law.

Contact:

Kristen K. Sheppard, Esq.
SVP of Investor Relations
investors@centessa.com

FAQ

When does Centessa (CNTA) make the CEO change effective?

The CEO transition is effective January 1, 2026.

Who is the new Centessa CEO and what is his role in orexin programs?

Mario Alberto Accardi PhD, founder of Centessa’s Orexin Program, is appointed CEO and board member and led the company’s OX2R agonist efforts.

What is the timeline for Centessa’s ORX750 registrational program (CNTA)?

Centessa expects to initiate the ORX750 registrational program in Q1 2026.

Which additional orexin assets does Centessa (CNTA) plan to advance in 2026?

Centessa is advancing ORX142 and ORX489 with key milestones expected in 2026.

What change in company strategy did Centessa announce alongside the CEO transition?

The company is shifting from a diversified early‑stage pipeline to a pure‑play orexin portfolio focused on OX2R agonists.