Cleminorexton

Eli Lilly may not have discovered orexins, but the pharma’s latest acquisition marks increasing momentum for a drug class that’s maturing after years of fine-tuning. The big question on the minds of Wall Street is whether orexins’ potential is fully known. Lilly announced last week that it was buying Centessa Pharmaceuticals for $6.3 billion upfront, its largest acquisition since it bought Loxo Oncology in 2019, should the deal close. The move gives Lilly access to a pipeline of orexin receptor 2 agonists, primarily in development to treat sleep disorders like narcolepsy. But what if narcolepsy is just scratching the surface? Interviews with Wall Street analysts suggest that’s a possibility, and with Lilly in control, a lot more money could be poured into widening the drugs’ development scope — specifically, testing whether they broadly help with focus or fatigue. “It’s not a small, little number that they’re paying for this. And clearly Lilly believes there’s something here,” Leerink Partners senior managing director Marc Goodman said. Goodman laid out an all-too-familiar potential circumstance for those who closely watched the development of the diabetes and weight loss drugs. Novo Nordisk, a cardiometabolic powerhouse, was first to market with Ozempic, then Wegovy. But Lilly has since snagged a majority of the injectable market share, and with it a dominant position atop the largest current drug market and possibly the largest ever. Does history dare repeat itself? The orexin race is currently led by Takeda, which had its new drug application accepted by the FDA in February and is expecting a decision in the third quarter. Alkermes has a candidate in Phase 3, followed by Centessa in Phase 2. But those assets are focused on narcolepsy or idiopathic hypersomnia, a condition marked by excessive daytime sleepiness. “Now to me, all of a sudden, the Centessa asset, or I should say, the second asset, and the third asset … I think those are strategically advantaged versus the Alkermes ones big-time because of Lilly acquiring them,” Goodman said. Behind Centessa’s lead asset ORX750 are two others: Phase 1-stage ORX142, which is broadly aimed at neurodegenerative and neurological conditions; and ORX489 for neuropsychiatric conditions. The latter is still in preclinical development. Alkermes is shining a light on where these drugs might go next. Its two follow-up orexin candidates, both in the clinic, are aimed at neurodegenerative disease-related fatigue and attention deficit hyperactivity disorder. Paul Matteis, managing director and head of therapeutics research at the investment bank Stifel, said Lilly could ultimately end up being a tailwind for the whole class as more proof-of-concept data are generated across a host of additional conditions. “It’s going to increase the breadth of use for the whole class, even if there might be some molecules that are first here, first there,” Matteis told Endpoints News . The final pillar of the drug market that Lilly could capitalize on is how these drugs actually make it to patients. The Indianapolis pharma has been building its direct-to-consumer infrastructure on the back of its GLP-1 portfolio , and that may be a potential distribution stream for future orexin drugs. Matteis and Goodman both said it’s a worthwhile consideration, but that it would be unlikely to impact the sleep disorder market, given they expect the price of these drugs to cost hundreds of thousands of dollars. “I think that’s something that you could see with a next-generation drug, but I don’t think it would be with these first generations,” Matteis said.

Welcome back to Endpoints Weekly! They say March comes in like a lion and out like a lamb, but two pharma giants made a roar this week with megadeals worth more than $5 billion upfront. If the pharma industry keeps it up, it could outpace last year’s already-strong M&A figures. Our team also tracked developments this week on Eli Lilly’s obesity pill and President Donald Trump’s plans for pharmaceutical tariffs. You can read Anna Brown’s story here for the details on Trump’s executive order. — Nicole DeFeudis 🤝 Several pharma companies have inked deals in the last couple weeks, including two $5 billion-plus upfront deals that were disclosed on Tuesday morning alone. Here’s what you need to know: Eli Lilly said it would pay $6.3 billion upfront and up to $1.5 billion in contingent value rights to acquire Centessa Pharmaceuticals and its orexin receptor 2 agonists. It’s Lilly’s third acquisition of the year, but its largest since the $8 billion takeover of Loxo Oncology in 2019. Centessa’s lead drug, called cleminorexton (ORX750), is in Phase 2a testing for narcolepsy type 1, narcolepsy type 2 and idiopathic hypersomnia. That same day, Biogen unveiled a $5.6 billion deal to acquire Apellis Pharmaceuticals. The deal comes with two approved drugs, most notably a rare blood disorder drug called Empaveli, which was also approved last year for a rare kidney disease — and Biogen execs think this could be its next big market. Across March, biopharmas lined up 10 acquisitions worth up to $31.5 billion, according to an Endpoints tally. If the pace continues, 2026 could surpass 2025, which was already a standout year for M&A, Kyle LaHucik wrote in this analysis . Jon Norris, a healthcare banker at HSBC, told Endpoints that he thinks the M&A pace will remain, “though maybe not at the frenzy we saw in Q1.” 💰Blackstone this week announced it had raised $6.3 billion for its latest life sciences vehicle, Blackstone Life Sciences VI — the industry’s largest-ever private investment fund . It’s equal to more than half the value of new investment funds raised all of last year, according to a year-end report from William Blair. Blackstone has already deployed about $2 billion from the fund over the past 12 months, and could continue investing at a pace of about $1.5 billion to $2 billion a year, Nick Galakatos, global head of Blackstone Life Sciences, told Endpoints. The fund lands as the biotech industry pulls out of a yearslong slump , but Blackstone is also taking a different strategy than most. Instead of high-risk, early-stage bets, Blackstone tends to back late-stage development programs. Read more from Kyle LaHucik here . 🥜 The surge in food allergies transformed how many American children grow up. But a combination of better biological understanding, and a new use of an old drug, has cracked open a potentially huge market in biopharma — and effective treatments for patients. We took a comprehensive look at how Roche and Novartis’ Xolair, a 23-year-old asthma medicine, found renewed life as a blockbuster after it won expanded approval in 2024 to treat food allergies. Big pharma is ready to engage, too. GSK and Novartis both snapped up allergy biotechs this year. A crop of biotechs has also raised more than $240 million in the last 12 months (including the one Novartis acquired). The resurgence suggests a clear and eager demand among patients and families for new treatments. Read more from Max Gelman here . 💊A new competition is brewing, as Eli Lilly brings its obesity pill to market. The FDA announced on Wednesday that it approved orforglipron under its new Commissioner’s National Priority Voucher program. Lilly plans to market the pill as Foundayo, but as with the obesity shots Novo and Lilly have both brought to market, the Indianapolis drugmaker will be second to reach patients. Lilly suggested that Foundayo might have an edge over the Wegovy pill in its relative ease of use. It plans to start selling Foundayo on its direct-to-consumer platform LillyDirect, with shipping beginning April 6. Get more details here.