Eli Lilly has gone big in the name of neuroscience, paying $6.3 billion in a front-loaded deal for Centessa Pharmaceuticals and its sleep disorder pipeline.
In recent years, U.K.-based Centessa has been focused on a portfolio of orexin receptor 2 (OX2R) agonists, which the biotech has been targeting at conditions related to the sleep-wake cycle. Centessa’s lead program is cleminorexton, formerly known as ORX750, which is undergoing a phase 2 study for two types of narcolepsy as well as idiopathic hypersomnia (IH).
Last year, the biotech touted phase 2 data for cleminorexton that it said showed “statistically significant, clinically meaningful and dose-dependent results” across key measures of wakefulness, sleepiness and cataplexy—a symptom of narcolepsy that involves a sudden, temporary loss of muscle tone.
Centessa had been aiming for cleminorexton to become the first OX2R agonist to treat narcolepsy type 2 (NT2) and IH. In this morning’s deal announcement, Lilly agreed that cleminorexton had “demonstrated a potential best-in-class profile” in the mid-stage study.
Behind cleminorexton, Centessa also has another candidate in the clinic in the form of ORX142. Last year, the biotech reported that the drug had achieved statistically significant and dose-dependent improvements in mean sleep latency in a phase 1 study of healthy adults. There is also a third asset, dubbed ORX489, in preclinical development for neuropsychiatric disorders.
“Orexin receptor biology represents one of the most compelling mechanistic opportunities in neuroscience as a direct intervention on the master switch of the sleep-wake cycle,” Carole Ho, the head of Lilly Neuroscience, said in the March 31 release.
“Centessa has assembled a portfolio with the breadth and depth to improve wakefulness across a broad array of indications,” Ho added.
To get its hands on this portfolio, Lilly is shelling out $38 per share of Centessa—a 27% markup on the biotech’s Monday closing price of $27.58. The deal also includes a non-transferrable contingent value right (CVR) that entitles Centessa shareholders to a total of an additional $9 per share related to approval milestones for cleminorexton and ORX142 in the next several years.
On top of the $6.3 billion upfront payment, the CVR means Lilly could also pay out an additional $1.5 billion within the next five years.
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Lilly said this morning’s deal “expands [its] neuroscience portfolio.” As well as the company’s approved Alzheimer’s disease med Kisunla, its clinical-stage portfolio includes the likes of mevidalen, a dopamine D1 receptor positive allosteric modulator being developed for various neurodegenerative disorders, and a GBA1 gene therapy for Parkinson’s disease.
Centessa only fully focused its attention on its OX2R franchise in late 2024, having slowly shed various hemophilia B, alpha-1 antitrypsin deficiency and autosomal dominant polycystic kidney disease prospects over previous years.
“Centessa is at the forefront of orexin science, and we’ve built a potential best-in-class portfolio of OX2R agonists with a level of depth and breadth that could help redefine what’s possible in neuroscience,” CEO Mario Alberto Accardi, Ph.D., said in this morning’s release.
Accardi, who founded Centessa’s orexin program, took on the CEO role at the end of last year as part of a strategic decision to focus the company on the OX2R pipeline.
