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Alnylam and Regeneron sign big RNAi deal
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The $800 million partnership will test RNAi drugs on eye and central nervous system diseases Alnylam Pharmaceuticals, the first company to bring an RNA interference (RNAi) drug to market, has struck an $800 million–plus deal with Regeneron Pharmaceuticals to develop RNAi therapies for eye and central nervous system diseases. Alnylam CEO John Maraganore says
Alnylam CEO John Maraganore the partnership “positions us for the next phase of growth.” The partnership will also be an important test for the RNAi field, which has thus far struggled to make the technology work in organs besides the liver. In the first phase of the collaboration, Regeneron and Alnylam will seek to develop RNAi therapies that knock down, or silence, 30 disease-causing genes. Regeneron will pay Alnylam $400 million up front, buy $400 million worth of its stock, and offer up to $200 million in milestone payments. Alnylam began developing RNAi therapies when it was founded in 2002. But crafting the right lipid nanoparticle to safely and effectively deliver RNAi drugs was a major hurdle. And since most lipid nanoparticles congregate in the liver, the company has focused on using RNAi drugs to treat liver diseases or block the production of proteins that are made by liver cells. For the new realms of the eye and central nervous system, Alnylam will likely have to inject its drugs directly into the organs.
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C&EN | CEN.ACS.ORG | APRIL 15, 2019
A class of gene-blocking drugs called antisense oligonucleotides—similar, older cousins to RNAi therapies—offers a precedent. These drugs have been safely injected into the gel-like vitreous fluid of the eye to treat viral infections and into the spinal fluid to treat a childhood neurodegenerative disease. In addition to lipid nanoparticles, RNAi therapies for the liver need a liver-homing chemical tag called N-acetylgalactosamine. The tag is appended to the RNAi molecules and recognized by receptors on specific kinds of liver cells, which then engulf the drugs so they can exert their gene-silencing powers inside cells. Alnylam’s plans for getting RNA drugs into the brain may rely on a similar mechanism. A presentation at a Cold Spring Harbor Laboratory conference last month indicated that the company is using a ligand to help get its therapies into the brain cells of rodents and monkeys, but it didn’t provide any clues to the ligand’s molecular makeup. The preliminary results indicated RNAi’s potential for knocking down a gene linked to amyotrophic lateral sclerosis (ALS). Alnylam suggested that the same gene-silencing trick could be applied to other brain conditions, including Alzheimer’s, Parkinson’s, and Huntington’s. Regeneron and Alnylam aren’t disclosing any targets for their eye and brain programs yet, but Alnylam predicts it will be filing investigational new drug applications for one to two eye or nervous system conditions every year beginning in 2020. Separately, Sanofi says it is wrapping up a rare-disease research agreement it struck with Alnylam when it made a $700 million investment in the company in 2014. The more than 10.5 million shares of Alnylam stock that Sanofi owns are now valued at roughly $1 billion. The two firms will continue developing two RNAi drugs: fitusiran for hemophilia and vutrisiran for transthyretin-mediated amyloidosis. They will also advance an undisclosed rare-disease program.—RYAN CROSS
Versum accepts new deal from Merck KGaA Five dollars per share more did the trick. Merck KGaA, the German drug and chemical conglomerate, has increased its offer to acquire Versum Materials by that amount, and Versum has accepted. The agreement likely marks the end of a takeover battle that began in late January when Versum and Entegris announced that they were merging to become a $3 billion-peryear supplier of high-purity materials for making computer chips. A few weeks later, Merck stepped in with an offer to acquire Versum for $48 per share in cash, or about $6 billion including Versum’s debt. Merck contended that its offer—a 52% premium over Versum’s stock price before the Entegris deal was announced—was superior because it provided shareholders more certainty than the merger with Entegris did. Versum produces deposition materials, specialty gases, and chemical-mechanical planarization slurries; it had sales last year of about $1.4 billion. Both deals would make it part of a larger supplier of materials for semiconductor fabrication. Versum initially resisted Merck’s overture, saying the merger with Entegris had more upside potential over the long term. Versum urged shareholders to vote for the Entegris deal, but it also acknowledged that it would talk with Merck. Merck CEO Stefan Oschmann and Versum chair Seifi Ghasemi held a meeting on April 6 in Munich at which Oschmann raised Merck’s offer to $53 per share. The next day, Versum informed Entegris that it had received what it considered a superior proposal. Entegris says it has no plans to revise its deal. But it does have one small consolation: Versum is obligated to pay Entegris a $140 million breakup fee.—MICHAEL MCCOY
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