[Updated, 1:15 pm ET] Few companies have stuck around in gene therapy as long as Genzyme. Despite the ups and downs—and never winning approval of a product—the Sanofi unit, unlike so many of its peers, never abandoned the field.
So perhaps it’s no surprise that with the field in a full-on renaissance, it’s Genzyme that today is making another big gene therapy bet: a broad collaboration with Cambridge, MA-based startup Voyager Therapeutics to develop gene therapies for a bunch of neurological diseases.
Genzyme is paying Voyager $100 million up front—and potentially as much as $845 million overall—for rights to a group of gene therapies for brain diseases like Parkinson’s, Friedreich’s Ataxia, and Huntington’s Disease.
Specifically, Genzyme is paying $65 million in cash, making a $30 million equity investment in Voyager, and adding other (unspecified) “in-kind contributions.” Voyager could get an additional $745 million in various development and sales milestones, with royalties attached should any of these products ever reach the market.
In return, Genzyme has grabbed international rights to Voyager’s experimental gene therapies for Parkinson’s and Friedreich’s (Voyager is keeping U.S. rights to these programs), and can split any U.S. profits from Voyager’s Huntington’s program if that therapy is approved. Genzyme will also have the option to license a number of programs that come out of the collaboration after proof-of-concept studies in humans.
The Parkinson’s candidate is currently in Phase 1b testing. According to Voyager CEO Steven Paul, the Friedreich’s and Huntington’s candidates are two to three years away from clinical studies.
The deal doesn’t include a gene therapy Voyager is developing for amyotrophic lateral sclerosis (ALS); the startup is keeping full rights to that program.
The pact is a big validating move for Voyager, which was started up just a year ago with a $45 million Series A round by Third Rock Ventures. The big idea behind Voyager is to use gene therapy, and to a certain extent, micro RNA tools, to either cure or significantly reverse the effects of a broad range of neurological disorders. Part of that plan was to build a proprietary in-house library of adeno-associated virus (AAV) vectors—a tool for gene therapy delivery—that the company could use to either make its own therapies, or form deals with others. Paul, Eli Lilly’s former R&D chief, left his post as a Third Rock venture partner in July to lead the company.
[Updated with comments from Genzyme] The alliance also has a familiar feel for Genzyme and its parent company, Sanofi. As it has in the past with Alnylam Pharmaceuticals (NASDAQ: ALNY) and Regeneron Pharmaceuticals (NASDAQ: REGN), the larger company is taking a stake in a smaller company, and they’re working together to develop a group of drugs and share in their successes—all while allowing the little guy to stay independent, and preserve some upside for itself. For Voyager, that means partial rights to several gene therapy programs and full ownership of its ALS candidate.
“For both of us to succeed here…[Voyager] has to succeed beyond the bounds of our collaboration and have the opportunity to create and retain value for itself. That’s why we [made] an equity investment as part of the deal,” says Genzyme’s VP of business development, Mark Barrett. “It makes for a strong relationship [and] a strong partner.”
The deal is also the last example of how far gene therapy has come over the past few years. The field began tantalizing scientists in the early 90s with the potential of reaching diseases conventional therapies couldn’t get to, and potentially curing them with a single procedure. The idea, in simple terms, is to use modified viruses to carry copies of healthy genes into cells, where they can replace the missing or defective ones that are thought to be causing a disease.
Hordes of companies piled into the field, among them Genzyme. The big firm started working on gene therapy in 1991, and has since poured hundreds of millions of dollars into it, chasing therapies in cystic fibrosis, Parkinson’s, and peripheral artery disease, among others. Those efforts have never led to an approved product, however, and a PAH trial Genzyme completed in 2009—one of the largest gene therapy studies ever—failed to produce a positive result.
While Genzyme was toiling away on this work, safety issues derailed gene therapy, and many companies left the field altogether. It wasn’t until fairly recently that sentiment shifted, catalyzed by better delivery technologies and encouraging early clinical data. There is one gene therapy, from UniQure, that is approved in Europe. BlueBird Bio (NASDAQ: BLUE) has become a Wall Street darling over the past year because of indications a gene therapy it’s developing might help reverse a devastating blood disorder, beta-thalassemia (Genzyme, incidentally, helped Bluebird along when it contributed to a $35 million financing for the company when it was known as Genetix Pharmaceuticals).
Startups like Voyager, Spark Therapeutics, Audentes Therapeutics, and others have emerged. Large companies like Pfizer, Bayer, Celgene, and Biogen Idec are placing bets with startups and research institutions in the space.
None of those companies, however, have been making broad gene therapy bets in neuroscience. Genzyme is changing that with its deal today. It’s a risky one, for sure: Diseases like Parkinson’s have frustrated scientists for decades, because there is so much that is still unknown about the underlying biology. No gene therapy for a neurological disorder has ever even made it to a Phase 3 trial. Voyager aims to effectively deliver these therapies by injecting them directly either into the spine or brain; Safety issues are always a risk.
[Updated with comments from Paul] But the two companies believe they can make it work. Paul says Voyager has seen positive signs in preclinical studies in large animals that it can deliver these genes “up and down the spinal cord” to the motor neurons that are involved in many of the diseases it’s targeting.
Paul also points to a few potential advantages of delivering gene therapies into the spine or brain. First, he says those sites are “immunologically privileged,” which means gene therapies delivered there might be less likely to provoke an immune system attack. Secondly, Paul says, nerve cells don’t divide and grow, so an AAV gene therapy delivered to them could last as long as the cell lives. By comparison, a gene therapy delivered with an AAV to cells that grow and divide might wear off sooner. That’s the kind of thing that can lower the value proposition of gene therapy.
“We don’t think we have that problem, at least based on animal and some limited clinical data,” Paul says.
That’ll have to be proven in trials, of course. But Paul is optimistic.
“I don’t want to trivialize the challenges; there are going to be challenges here,” he says. “[But] we think if we can get the gene to the right place, we should have a therapeutic effect.”
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