Rare Daily Staff

Alnylam Pharmaceuticals and Regeneron Pharmaceuticals said they have entered into a collaboration to discover, develop, and commercialize new RNA interference therapeutics for the eye and central nervous system worth up to $1 billion.

Under the terms of the agreement, Regeneron will make a $400 million upfront payment to Alnylam and purchase 4.4 million shares of Alnylam stock at a price $90 per share for a totalling an additional $400 million. Alnylam is eligible to receive up to an additional $200 million in milestone payments upon achievement of certain criteria during early clinical development for the eye and CNS programs.

The companies said they plan to advance programs directed to 30 targets and introduce many into clinical development during the initial five-year discovery period, which includes an option to extend. For each program, Regeneron will provide Alnylam with $2.5 million in funding at program initiation and an additional $2.5 million at lead candidate identification, translating to the potential for approximately $30 million in annual discovery funding to Alnylam as the alliance reaches steady state.

Alnylam will work exclusively with Regeneron to discover RNAi therapeutics for eye and CNS diseases. Regeneron will lead development and commercialization for all programs targeting eye diseases, with Alnylam entitled to potential milestone and royalty payments. The companies will jointly advance and alternate leadership on CNS programs, with the lead party retaining global development and commercial responsibility. For CNS programs, both companies will have the option at candidate selection to participate equally in potential future profits of programs led by the other party.

The collaboration will leverage Alnylam’s technology, which in recent preclinical data showed potent and highly durable delivery of RNAi therapeutics to achieve target gene silencing in the eye and CNS. It will also benefit from Regeneron’s suite of antibody technologies and capabilities from the Regeneron Genetics Center.

“This collaboration couples proven and emerging RNAi technology, which holds important promise in many diseases, with Regeneron’s world-leading genetics research and target discovery engine,” said George Yancopoulos, president and chief scientific officer of Regeneron. “This collaboration enables us to reach targets inside the cell complementing our expertise in antibodies, which are ideal for extracellular targets and those on the cell surface.”

The collaboration also includes a select number of RNAi therapeutic programs designed to target genes expressed in the liver, which can influence a wide variety of diseases throughout the body. These programs include a planned joint effort evaluating anti-C5 antibody-siRNA combinations for C5 complement-mediated diseases including evaluating the combination of Regeneron’s pozelimab (REGN3918), currently in phase 1 development, with Alnylam’s cemdisiran, currently in phase 2 development.

Alnylam will retain control of cemdisiran monotherapy development, and Regeneron will lead combination development. The parties will equally share investment and potential future profits on the monotherapy program, and Alnylam will receive royalties on any potential combination product sales. For all other alliance liver programs, the parties will alternate leadership and participate equally in potential profits.

The two companies will continue their previously-announced collaboration to identify RNAi therapeutics for the chronic liver disease nonalcoholic steatohepatitis (NASH) based on novel findings from the
Regeneron Genetics Center. Alnylam retains broad global rights to all of its other unpartnered liver-directed clinical and preclinical pipeline programs.

“This new industry-leading alliance is aimed at realizing what we believe to be a significant opportunity for RNAi therapeutics as potentially transformative medicines for ocular and CNS diseases,” said John Maraganore, CEO of Alnylam. “Importantly, the alliance structure enables Alnylam to continue to build its industry-leading pipeline of RNAi therapeutics while retaining significant product rights.”

Photo: John Maraganore, CEO of Alnylam