Acquisition of Centessa by Lilly Approved by the High Court of Justice of England and Wales

High Court Approves Lilly's Acquisition of Centessa

Centessa Pharmaceuticals plc announced that the High Court of Justice of England and Wales has approved its proposed acquisition by Eli Lilly and Company. The transaction, valued at approximately $7.8 billion, involves Lilly acquiring Centessa for $38.00 in cash per share plus one non-transferable contingent value right (CVR) entitling holders to receive up to an aggregate of $9.00 based on three milestones. The acquisition is being implemented via a Court-sanctioned scheme of arrangement under English law. The Court Order was issued on June 22, 2026, with the transaction expected to close and become effective on June 24, 2026. Trading of Centessa ADSs on Nasdaq is anticipated to halt before market opening on June 24, 2026, with June 23, 2026, being the last trading day.

• The High Court of Justice of England and Wales officially sanctioned the acquisition of Centessa by Eli Lilly and Company on June 22, 2026. This approval facilitates the transaction, which is structured as a Court-sanctioned scheme of arrangement under English law, ensuring a legally robust framework for the acquisition.
• The total transaction is valued at approximately $7.8 billion. Centessa shareholders will receive $38.00 in cash per share, along with a non-transferable contingent value right (CVR). This CVR offers potential additional payments of up to $9.00 per share, contingent upon the achievement of three specific milestones.
• Following the Court's approval, the transaction is expected to close and become effective on June 24, 2026, upon delivery of the Court Order to the Registrar of Companies. Consequently, the last day for trading Centessa American Depositary Shares (ADSs) on Nasdaq is projected to be June 23, 2026, with trading halting before the market opens on the effective date.

Lilly's Strategic Play: The Broad Potential of OX2R Agonists

Beyond excessive daytime sleepiness and neurological indications, OX2R agonists are being investigated across a broader therapeutic landscape — most notably in sleep-disordered breathing and perioperative respiratory management. The emerging clinical data suggest that orexin system modulation may offer meaningful utility wherever arousal state, ventilatory drive, or sleep architecture is therapeutically relevant.

• Obstructive Sleep Apnea Syndrome (OSAS): Orexin agonists are under investigation as pharmacological interventions for OSAS, a condition affecting 13–33% of males and 6–9% of females globally. Trials are evaluating improvements in primary respiratory and symptomatic endpoints, including the apnea-hypopnea index (AHI) and the Epworth Sleepiness Scale (ESS), with findings suggesting enhanced sleep quality and symptom management — particularly relevant given the well-documented challenges of poor adherence to Continuous Positive Airway Pressure (CPAP) therapy and residual excessive sleepiness (RES).

• Opioid-Induced Respiratory Depression (OIRD): TAK-925 (danavorexton), a selective OX2R agonist, has been evaluated in a single-center, double-blind, placebo-controlled, two-way crossover Phase 1 trial in perioperative settings (2025). Thirteen healthy men were randomized (1:1) to receive danavorexton (low-dose 11 mg, then high-dose 19 mg) or placebo under remifentanil infusion, titrated under isohypercapnic conditions to achieve an approximately 30–40% reduction in minute ventilation, across two occasions separated by a ≥36-hour washout period.

• Ventilatory Outcomes in the OIRD Trial: Both low- and high-dose danavorexton produced statistically significant increases in minute volume (+8.2 L/min and +13.0 L/min, respectively), tidal volume (+312 mL and +483 mL), and respiratory rate (+3.8 and +5.2 breaths/min; all P < 0.001 vs. placebo), with respiratory improvements persisting beyond completion of the infusion period.

• Sedation Reversal and Analgesic Neutrality: High-dose danavorexton significantly reduced sedation as measured by visual analog scale (−29.7 mm; P < 0.001) and the Richmond Agitation Sedation Scale (+0.4; P < 0.001) versus placebo. Notably, no significant differences in pain tolerance were observed between danavorexton and placebo at either dose (low dose P = 0.491; high dose P = 0.140), suggesting the agent does not antagonize opioid analgesia — a clinically meaningful distinction for perioperative utility.

• Safety Profile in the OIRD Trial: Treatment-emergent adverse events (TEAEs) occurred in 30.8% of danavorexton-treated participants versus 8.3% in the placebo arm; all events were mild in severity. One participant experienced insomnia lasting one day, considered related to danavorexton — consistent with the pro-arousal pharmacology of OX2R agonism.

Navigating the Competitive Landscape for OX2R Agonists

The OX2R agonist space is increasingly competitive, with multiple compounds advancing through preclinical and early clinical development across overlapping indications. Two agents — TAK-925 (danavorexton) and OX-201 — represent the most clearly characterized OX2R-selective programs, each with distinct intervention models and therapeutic targets.

Addressing Unmet Needs in Neurological Sleep Disorders

Current treatment approaches for excessive daytime sleepiness (EDS) in neurological conditions face a complex array of pharmacological, diagnostic, and disease-specific limitations. Effectively managing EDS requires not only identifying and addressing the primary underlying disorder, but also navigating significant variability in treatment response, tolerability, and long-term safety across patient populations.

• Wake-promoting agents are not a substitute for sleep: Agents such as amphetamines, methylphenidate, pemoline, and modafinil are effective but cannot replace adequate sleep, and their utility is further constrained by inadequate efficacy, poor tolerability, or adverse effects in a subset of patients.

• Non-hypocretin-related hypersomnia syndromes present particular therapeutic challenges: These conditions are diagnoses of exclusion — only confirmed after eliminating sleep deprivation, sleep apnea, disturbed nocturnal sleep, and psychiatric comorbidities — and lack the codified treatment frameworks that exist for narcolepsy/hypocretin deficiency, often necessitating empirical, case-by-case approaches including high-dose stimulants or sodium oxybate.

• Tolerance, addiction risk, and diagnostic drift complicate long-term management: In conditions where etiology and disease evolution remain poorly understood, ongoing reassessment of both diagnosis and therapy is essential, with particular vigilance for stimulant tolerance and the development of dependence.

• EDS in Parkinson's disease is multifactorial and difficult to target precisely: Contributing factors include interrupted nocturnal sleep, intrinsic PD pathology, and dopaminergic medications — particularly dopamine agonists — meaning that treatment must be individualized, and stimulants such as modafinil may offer only modest benefit.

• Validated, disease-specific treatment guidelines are largely absent: Few specific guidelines exist for EDS in Parkinson's disease, controlled trial data for REM sleep behavior disorder pharmacotherapy are lacking, and a dedicated expert consensus on the clinical application of wake-promoting agents across neurological conditions has yet to be fully established.

• Kleine-Levin Syndrome remains largely without effective intervention: This condition is generally best left untreated, with lithium considered only in severe cases with frequent episodes, reflecting the broader gap in evidence-based options for rare hypersomnia syndromes.

• Accurate diagnosis is a prerequisite for effective treatment: Determining whether sleepiness is attributable to voluntary sleep loss, occupational or social factors, medication effects, or an intrinsic sleep or neurological disorder is the essential first step — requiring comprehensive patient and bed partner interviews, and referral to a sleep specialist for quantitative evaluation including polysomnography.