Regeneron Invests $800 Million in Alnylam to Advance Nobel Prize-Winning RNAi Therapeutics for Ocular, CNS, and Liver Diseases

Regeneron Pharmaceuticals and Alnylam Pharmaceuticals, an industry-leading RNAi therapeutics company, announced a collaboration agreement aimed at discovering, developing, and commercializing RNAi therapies for the treatment of ophthalmic diseases, central nervous system disorders, and several targets expressed in the liver.

Under the terms of the agreement, Regeneron will pay Alnylam $400 million and acquire an additional $400 million in equity at a price of $90 per share, or 4.44 million ordinary shares, for a total investment of $800 million. During the early clinical development of the ophthalmology and CNS programs, Alnylam will be eligible for an additional $200 million in milestone payments, bringing the total value of the collaboration agreement to $1 billion.

Alnylam plans to collaborate with Regeneron to discover RNAi therapies for two major indications: ophthalmic and central nervous system (CNS) diseases. Regeneron will lead the development and commercialization of RNAi therapies for ophthalmic indications, while Alnylam will be eligible for milestone payments and royalties. The two companies will jointly advance and alternately lead the CNS development programs, with the leading party assuming global development and commercial responsibilities.

RNA interference (RNAi) is a technique that silences genes before they produce harmful proteins, and it has gradually matured after years of ups and downs. Since 2002, Alnylam, the largest company in the RNAi field, has attempted to develop drugs using this approach. After experiencing a series of fluctuations and clinical setbacks, it finally obtained approval in 2018 for its first RNAi therapeutic, Onpattro (patisiran), for the treatment of hereditary transthyretin-mediated amyloidosis (hATTR), a rare genetic disorder.

It took scientists years to figure out how to safely and effectively deliver large RNA molecules into cells, a process in which many pharmaceutical companies became mired. However, Alnylam survived, largely because early partners provided sufficient cash to weather the storm. Furthermore, the key to Alnylam’s success lay in customizing its method for delivering RNAi therapeutics to the liver, a large organ capable of absorbing macromolecules from the bloodstream. This deal also reflects the recognition by major pharmaceutical companies of Alnylam’s progress in the field of RNAi therapeutics.

After burning through nearly $2.4 billion, Alnylam has finally seen its RNAi therapeutic reach the market. Patisiran generated $12.1 million in sales during the final months of 2018, but RNAi drugs from other companies are also on the horizon. In March, Alnylam announced plans to seek approval for a drug targeting acute hepatic porphyria, a rare liver disorder, while its pipeline candidates for hemophilia and hypercholesterolemia are undergoing late-stage clinical trials.

Alnylam and Regeneron believe that “there is significant opportunity for RNAi therapeutics as a potentially transformative approach to treating serious neurological and ocular diseases,” said John Maraganore, CEO of Alnylam. “This transaction will help Alnylam significantly accelerate the advancement of these drug candidates.”

The agreement also includes a smaller third component: a commitment to jointly develop RNAi therapeutics for certain liver diseases. This includes plans to test combinations of RNAi and antibody drugs, with antibody therapeutics being Regeneron’s area of expertise. One such combination involves Alnylam’s cemdisiran and Regeneron’s pozelimab, both targeting C5 complement inhibition for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). Regeneron recognizes that certain diseases can be better addressed through combination therapies, thereby improving upon existing treatment options.

References:

https://www.biospace.com/article/regeneron-and-alnylam-ink-1-billion-eye-and-central-nervous-system-r-and-d-deal/

https://www.statnews.com/2019/04/08/regeneron-to-invest-800-million-in-alnylam-betting-on-drug-making-technique-enabled-by-a-nobel-prize-winning-discovery/