Eli Lilly and Co. plans to buy Centessa Pharmaceuticals plc for $6.3 billion in up-front cash and another potential $1.5 billion through contingent value rights, gaining access to a pipeline of orexin receptor 2 agonists for sleep disorders. The Indianapolis-based pharma is re-entering a field that has multibillion-dollar potential and one that could emulate the success seen with its obesity program. Centessa, of Boston and London, has a lead candidate, cleminorexton (formerly ORX-750), with positive phase IIa data in narcolepsy types 1 and 2 and idiopathic hypersomnia.
After reaching their peaks in late November, both the BioWorld Drug Developers Index and the Nasdaq Biotechnology Index finished the year slightly down from those highs.
The pricier offer by Lundbeck A/S for Avadel Pharmaceuticals plc – which follows last month’s agreement for a takeover by Alkermes plc – had Wall Street buzzing as pundits weighed the odds for each suitor.
Alkermes plc’s placebo-controlled phase II study of alixorexton in treating narcolepsy type 2 (NT2) hit its dual primary endpoints, producing statistically significant and clinically meaningful improvement in wakefulness and excessive daytime sleepiness. Alkermes said alixorexton is the first oral orexin 2 receptor agonist that has shown efficacy in a large phase II clinical trial in those with NT2.
Centessa Pharmaceuticals plc’s unremarkable third-quarter 2025 earnings report was greatly overshadowed by an early readout from its orexin receptor 2 (OX2R) agonist program in narcolepsy, particularly promising phase IIa data demonstrating ORX-750’s efficacy across a group of sleep disorders, though investors seek further data to differentiate Centessa’s program from potential competitors such as Takeda Pharmaceutical Co. Ltd.’s oveporexton and Alkermes plc’s alixorexton.
Having reached peace with Jazz Pharmaceuticals plc over litigation related to its U.S. FDA-approved drug, Lumryz (sodium oxybate), Avadel Pharmaceuticals plc agreed to a cash takeover by Alkermes plc valued at about $2.1 billion, a deal Alkermes CEO Richard Pops said “puts us in the sleep market immediately on closing,” which is expected in the first quarter of 2026. All three players are based in Dublin.
Losing nearly 60% of its value, Mural Oncology plc backed away from its lead interleukin-2 (IL-2) drug, nemvaleukin alfa, in platinum-resistant ovarian cancer based on interim results showing it failed to reach significance in the overall survival primary endpoint.
Evercore ISI analyst Umer Raffat recently called orexin a “red hot neuropsychiatry target,” and the recent Sleep 2024 meeting in Houston bolstered such a view. Also known as hypocretin, the neuropeptide orexin is known to play a crucial role in regulating wakefulness, arousal, and appetite. It’s made in the hypothalamus, and was discovered in the late 1990s. Investigators found that people with narcolepsy can show a deficiency of orexin due to the loss of neurons.
A year after Alkermes plc announced it would divide its oncology and neuroscience efforts into two separate businesses, the Dublin-based company spun out Mural Oncology plc with $275 million in funding and the lead solid tumor candidate nemvaleukin alfa. Shares of Mural (NASDAQ:MURA) will begin trading Nov. 16. “We’re very excited,” Mural’s CEO Caroline Loew told BioWorld. “We’ve got two major clinical datapoints in the next 18 months.”
