Alnylam and Regeneron join on RNAi therapeutics

Companies focus on ocular and CNS, and advance select programs with targets expressed in the liver

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CAMBRIDGE, Mass. & TARRYTOWN, N.Y.—In April, Alnylam Pharmaceuticals Inc. and Regeneron Pharmaceuticals Inc. announced a collaboration to discover, develop and commercialize new RNA interference (RNAi) therapeutics by addressing disease targets expressed in the eye and central nervous system (CNS), in addition to a select number of targets expressed in the liver.
The collaboration will use both companies’ scientific and technological expertise and build on Alnylam’s recent preclinical data showing potent and durable delivery of RNAi therapeutics to achieve target gene silencing in the eye and CNS. The companies will also benefit from Regeneron’s industry-leading VelociSuite technologies and capabilities from the Regeneron Genetics Center (RGC).
“This collaboration couples proven and emerging RNAi technology, which holds important promise in many diseases… [and] 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,” said Dr. George D. Yancopoulos, president and chief scientific officer of Regeneron. “Through the RGC and our other research groups, we are already identifying additional targets that may be well suited for RNAi-based drug development, particularly in the eye and CNS.”
Under the terms of the alliance, Alnylam will work exclusively with Regeneron to discover RNAi therapeutics for eye and CNS diseases. Regeneron will lead development and commercialization for 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 agreement also includes a select number of RNAi therapeutic programs designed to target genes expressed in the liver. 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 share investment and potential future profits on the monotherapy program, and Alnylam will receive royalties on potential combination product sales.
For all other liver programs, the parties will alternate leadership and participate equally in potential profits. The companies plan to continue their previously announced collaboration to identify RNAi therapeutics for the chronic liver disease nonalcoholic steatohepatitis (NASH), based on novel RGC findings. Alnylam retains broad global rights to all of its unpartnered liver-directed clinical and preclinical programs.
“We are thrilled to collaborate with Regeneron, a like-minded science-based organization, to significantly accelerate our efforts to bring RNAi therapeutics to patients. Importantly, the alliance structure enables Alnylam to continue to build its industry-leading pipeline of RNAi therapeutics while retaining significant product rights. In addition, the near-term payments under this new agreement will strengthen Alnylam’s balance sheet with over $2 billion in pro-forma cash upon closing of the transaction,” added Dr. John Maraganore, CEO of Alnylam.
Regeneron agreed to make a $400 million upfront payment to Alnylam and purchase $400 million of Alnylam equity at a price per share of $90.00. Alnylam is eligible to receive up to $200 million in additional milestone payments, upon achievement of certain criteria during early clinical development for eye and CNS programs.
The companies plan to advance programs directed to 30 targets and introduce many into clinical development during the initial five-year discovery period, which includes an extension option. 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, This holds the potential for approximately $30 million in annual discovery funding to Alnylam.
In other eye news, Regeneron received approval in May from the U.S. Food and Drug Administration (FDA) of Eylea (aflibercept) Injection to treat all stages of diabetic retinopathy (DR) and reduce the risk of blindness. Eylea is a VEGF inhibitor eye injection designed to block the growth of new blood vessels and decrease vascular permeability in the eye by blocking VEGF-A and placental growth factor.
“With [the] FDA approval, Eylea has once again set a high bar for the treatment of diabetic eye diseases. The PANORAMA trial showed that by one year, 20 percent of untreated patients developed proliferative diabetic eye disease, and Eylea reduced this risk by 85 percent to 88 percent when administered using an every 16-week or eight-week dosing regimen, respectively,” said Yancopoulos. “In fact, 80 percent of patients who received the Eylea eight-week dosing regimen had significant improvement in their diabetic retinopathy.”
Eylea is approved with two dosing options. In DR, Eylea may be dosed every eight weeks following five initial monthly injections, or every four weeks.
Canaccord Genuity biotechnology analyst Dr. John Newman noted that “FDA approves Eylea for diabetic retinopathy, but the upside is limited in our opinion. As expected, FDA approved Eylea for treatment of all forms of diabetic retinopathy, but we do not expect much usage here. Eylea was already approved for treatment of diabetic macular edema (DME), which is a complication of diabetic retinopathy that causes vision loss and requires treatment. Non-proliferative diabetic retinopathy (NPDR), on the other hand is generally less symptomatic, with patients simply being observed. We currently estimate ~$261M in U.S. sales for Eylea in the diabetic retinopathy indication by 2025.”

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