Nearly a year to the day after bursting on the scene with a $45 million series A financing, Voyager Therapeutics Inc. landed a potential $845 million deal with Genzyme, a unit of Sanofi SA, of Paris, to discover, develop and commercialize gene therapies for severe central nervous system (CNS) disorders.

Both partners expressed excitement about efforts to combine Voyager's adeno-associated virus (AAV) approach in CNS disorders with Genzyme's scientific prowess in gene therapy, with the goal of developing breakthrough therapies in a range of indications, including programs for Parkinson's disease (PD), Friedreich's ataxia, Huntington's disease (HD) and other CNS disorders.

The collaboration is designed to combine programs and intellectual property from both companies.

Voyager, of Cambridge, Mass., will be in the driver's seat for research and development. Genzyme will have the option to license ex-U.S. rights for several programs following completion of initial proof-of-concept human trials. Voyager will retain U.S. rights to its lead programs in PD (VY-AADC01) and Friedreich's ataxia (VY-FXN01) and will split U.S. profits with Genzyme for an HD program (VY-HTT01).

Voyager retained global rights to its lead program in amyotrophic lateral sclerosis (ALS) (VY-SOD101), which is excluded from the collaboration.

Voyager is set to receive $100 million up front, parceled out as $65 million in cash, a $30 million equity investment and additional in-kind contributions. The company also is eligible for development and sales milestone payments of up to $745 million plus tiered royalties on product sales.

Terms of the deal spoke to pharma's growing interest in gene therapy, according to Steven Paul, Voyager's president and CEO and a venture partner at Third Rock Ventures.

"It's still early days, but I think there are some fairly compelling reasons why people should believe that this is going to result in some new therapies and some new medicines," Paul told BioWorld Today.

'WE'RE SEEING A LOT OF ENTHUSIASM IN THE SPACE'

Formed several years ago by Third Rock, Voyager uses gene replacement or gene knockdown techniques, depending on the disease, to increase or decrease production of relevant proteins at targeted CNS sites. Its series A was designed to fuel the company's business platform for three years. (See BioWorld Today, Feb. 12, 2014.)

At the time, Third Rock entrepreneur-in-residence Jim Geraghty, who served as Voyager's interim chief business officer, told BioWorld Today that pharma and big biotech prospects had expressed a "high level of inbound interest" in collaborating in different areas, with "room for so-called non-dilutive financing" as an option to widen capabilities and add partners.

"There was some excitement around potential partners," Paul said, confirming a competitive process for the deal. "But we were well aware of Genzyme's track record in rare genetic diseases and in gene therapy, and we knew their scientists."

When the Voyager team compared notes about prospective partners, "it became apparent to both companies that there was a lot of overlap in both the disease indications and in the approaches or strategies we would take," Paul said. "Working together, we could create synergies and could be more productive and effective than working separately."

In the end, Voyager's leadership "recognized and appreciated" that Genzyme was a natural fit, both for its commitment to gene therapy and for the strength and quality of its science, he added.

It didn't hurt that Genzyme and parent Sanofi enjoy longstanding relationships with Third Rock.

"We're interested in gene therapy," acknowledged Mark Barrett, Genzyme's vice president for strategy and business development in rare diseases. "Third Rock is thinking about a gene therapy. Steve was involved in the discussion. These were great starting points, from our view, for putting together a highly credentialed and experienced team to work in the space. The discussions grew from there."

The PD program, currently in a phase Ib study and Voyager's only asset in the clinic, will be the first to benefit from the Genzyme collaboration.

"We are attempting and I think we will be successful in optimizing both the delivery of the vector – the gene – as well as the dose to provide a transformative therapy for patients who are no longer responding to their medicine," Paul said. How quickly that program progresses will depend on data that emerge over the next six to 18 months, he added.

Although the HD and Friedreich's ataxia programs are preclinical, "given what I know about our program as well as the efforts at Genzyme, we're fairly far along," Paul said. "I wouldn't anticipate that having a clinical candidate in hand to pursue the preclinical work needed to get an [investigational new drug application] and begin dosing patients would take too long." Whether that time frame is one year, two or longer, the Genzyme partnership "can accelerate this to the greatest extent possible," he pointed out.

Barrett noted that the confluence of the company's resources in Boston will provide solid support for Voyager.

"Sitting here in Cambridge at Genzyme, and with our Boston hub with Sanofi, we're in this very strong and dynamic biotech ecosystem," he told BioWorld Today. "We're thrilled to have the chance to partner with a great organization like Voyager. We try to be flexible and creative in the way that we partner, and we think this relationship is an example of that."

Sanofi spokeswoman Erin Pascal confirmed reports that surfaced Wednesday afternoon of a "reorganization of Sanofi R&D" in the Boston biotech hub, considered a strategic asset in the gene therapy deal. Without elaborating, Pascal said the changes "will have no effect Genzyme's collaboration with Voyager."

Whatever the local fallout for Sanofi, Voyager now is nicely financed to advance its pipeline of gene therapies, including its unpartnered ALS asset.

Ensuring momentum for the gene therapy field "boils down to some relatively simple ingredients," Paul maintained, characterizing these as demonstrated efficacy "that's therapeutically, clinically and commercially meaningful" in combination with "a background of relative safety." Those elements are beginning to emerge in programs targeting eye diseases, hemophilia and rare inborn errors of metabolism, he said, citing some of the promising early approaches.

"We're seeing a lot of enthusiasm in the space," Paul said, but the take-home message for Voyager is the need to reflect similar success in its own programs.

"Genzyme taught the world that you could go after rare diseases and make a huge difference for patients, first and foremost," in turn, creating value for the company and shareholders, he pointed out. "That story, over many years, has facilitated where the field of gene therapy is right now."