Over the past year, Sanofi and Alnylam have been retooling their 2014 R&D pact around Alnylam's RNA tech; today, the pair signaled its end, and former Sanofi partner Regeneron has stepped in.
First up, let's look at the original deal: The French pharma-U.S. biotech team first signed this pact five years ago, with the pharma paying a hefty premium to buy up a 12% stake in the biotech while investing $700 million and greatly expanding its rights to Alnylam's lead drug along with a portfolio of therapies.
But a lot has happened to Sanofi since 2014, with a new leadership team and a refocus on cancer, changes which have seen it tweak and cull old research pacts. At the same time, Alnylam has been looking to take more control over R&D and launch of its programs.
Last January, the beginnings of changes within the pact began, when the pair retooled that 2014 deal, seeing Alnylam stepping up its commitment to pioneering RNAi drug patisiran by adjusting its agreement with Sanofi.
The revised deal returned full global control of the ATTR amyloidosis drug to Alnylam and saw Sanofi obtain worldwide rights to hemophilia candidate fitusiran, a drug that was briefly held up by an FDA clinical hold in 2017.
Patisiran was soon approved by the FDA as Onpattro, the first-ever RNAi drug to reach the U.S. market, and focuses on a method cells use to silence a gene before it makes a damaging protein.
The partnership between the pair on this drug is now mostly divided up by asset, not geography: Alnylam, having previously ceded control to Onpattro outside of North America and Western Europe, is now in charge of bringing the drug to market around the world. In return, Alnylam is giving Sanofi full control of fitusiran.
Alnylam and Sanofi also replaced the split and codevelopment rights with royalties. Sanofi takes home royalties of up to 25% on sales of Onpattro in the markets it used to own. And Alnylam gets tiered royalties of up to 30% on global sales of fitusiran.
Then, two months later, more changes came when Sanofi in March 2018 turned down the chance to opt into Alnylam’s primary hyperoxaluria type 1 (PH1) drug lumasiran. The French pharma’s decision gave Alnylam control of a phase 3-ready rare disease drug with an FDA breakthrough therapy designation.
Alnylam originally granted Sanofi the option to pick up rights to its rare genetic disease programs outside of North America and Western Europe in 2014. The provision, and option to take the global rights for one program, survived the first restructuring of the deal. But Sanofi quickly opted to stay on the sidelines after assessing the phase 1/2 data Alnylam presented in late 2017 for lumasiran.
A year down the line, and both companies said they have now “agreed to conclude the research and option phase of the companies’ 2014 RNAi therapeutics alliance in rare genetic diseases,” adding the “material collaboration terms” for patisiran, vutrisiran (currently in a phase 3 for ATTR amyloidosis) and fitusiran will “continue unchanged."
“Our landmark 2014 rare disease alliance with Sanofi resulted in the advancement of three phase 3 programs—patisiran, vutrisiran and fitusiran—and the global launch of Onpattro, the world’s first RNAi therapeutic. We’re pleased to now conclude the research and product option phase of the collaboration, allowing Alnylam to focus on future continued growth of its rare disease pipeline,” said Yvonne Greenstreet, chief operating officer of Alnylam.
“We couldn’t be more pleased with the success of this alliance over the last five years, advancing RNAi therapeutics to patients afflicted with rare diseases around the world, and we look forward to our continued collaboration with Sanofi on our alliance programs.”
As the pact ends, Alnylam gets to “advance a selected investigational asset” in a rare genetic disease, the target of which the biotech is staying mum on, through the end of IND-enabling studies. For its part, Sanofi will be responsible for any potential further development or sale of this asset. If this product is approved, Alnylam is in line for biobucks related to net sales.
The pair have also penned a change to “certain terms of the companies’ equity agreement,” which will see Sanofi obtaining a release of its lock-up of Alnylam stock holdings.
Then today, another twist: Regeneron has stepped in and signed a new RNA pact with Alnylam, months after it and Sanofi rejigged their own immuno-oncology deal, as the Big Biotech looks to take a new track in its R&D work.
Under this pact, Alnylam will work exclusively with Regeneron to discover RNAi meds specifically for eye and CNS diseases. Regeneron will lead development and sales for all programs targeting eye diseases, with Alnylam entitled to potential milestone and royalty payments.
The collaboration also includes a number of RNAi programs designed to target genes expressed in the liver, including a planned joint effort evaluating anti-C5 antibody-siRNA combinations for C5 complement-mediated diseases, and a combo of Regeneron’s pozelimab, currently in phase 1, with Alnylam’s cemdisiran, currently in phase 2.
“At Regeneron we believe the best use of our resources is to invest in potentially game-changing science that will yield innovative medicines for patients with serious diseases. 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, M.D., Ph.D., president and chief scientific officer of Regeneron.Regeneron will pay $400 million upfront, $400 million in equity and add $200 million in biobucks for the buy-in. The companies are plotting a series of programs directed to 30 targets during the initial five-year discovery period, which includes an option to extend. On top of this, Regeneron will also hand over $2.5 million to Alnylam when it starts a new program and an additional $2.5 million at lead candidate identification.