Deal would represent major comeback for gene therapy developer
Pfizer explores licensing deal with Voyager
Pfizer is interested in exploring the use of Voyager Therapeutics' newest gene therapy technology, agreeing Wednesday to pay $30 million for a chance to license from the biotech two of the viral shells developers use to shuttle genetic information into the body's cells.
As Voyager ‘s website explained, “Adeno-associated virus (AAV) has emerged as a highly promising and attractive approach to gene therapy. AAV is a common, naturally occurring virus that has been shown to be a well-tolerated and effective gene therapy delivery vehicle in clinical trials. Advances in AAV vector design and related dosing techniques that enable widespread gene delivery in the brain and spinal cord have made AAV particularly well-suited for the treatment of neurological diseases. Since the targeted cells in the central nervous system (CNS) are long-lived, non-dividing neurons, treatments delivered in a single dose could generate long-lasting, or even lifelong, benefits.”
Voyager believes that improvements in related technology and approaches have made AAV production more easily scalable and efficient to meet clinical and commercial requirements. Voyager selects and optimizes AAV vectors that are best suited for each program. The company invests to advance the science and technology around the three key elements of AAV vectors: capsid, promoter and transgene. It also systematically develops and optimizes delivery techniques that are best suited for a particular disease.
Under the deal terms, Pfizer has a year to decide whether it likes what it sees. If the pharma chooses to exercise its options, Voyager would receive up to another $20 million for both and could earn another $580 more should development hit certain milestones. The agreement limits Pfizer's use of Voyager's viral shells, called capsids, to unspecified neurological and cardiovascular diseases, according to Jonathan Gardner, senior reporter at BioPharma Dive.
Voyager is one of many gene therapy specialists that have faced clinical or regulatory setbacks over the past two years. The company's deal with Pfizer is the first since it discontinued its leading drug candidates. Months earlier, its CEO and top physician departed. While shares in Voyager have recently traded at or near record lows, they jumped 50 percent as a result of news of the Pfizer deal.
Voyager's first generation of gene therapies for ALS, Parkinson's and Huntington's disease depended on a direct infusion into brain tissue, an invasive procedure. With those products discontinued, the company believes that its new technology, named TRACER, is more cell- and tissue-specific and can penetrate the blood-brain barrier. Thus ,it could be infused through a less invasive intravenous procedure.
Pfizer is interested in that technology. The drug giant has clinical-stage gene therapy programs in Duchenne muscular dystrophy and hemophilia. However, some mutation-driven neurologic diseases have been more challenging to target because the frequently used adeno-associated virus, or AAV, vectors aren't as tissue-specific as researchers would like.
"We are impressed with Voyager's results to date and are enthusiastic about the potential to utilize these novel capsids to help accelerate the development of new therapeutic options for patients living with certain neurologic and cardiovascular diseases," said Seng Cheng, chief scientific officer of Pfizer's rare disease research unit.
For Voyager, TRACER and the Pfizer deal are somewhat of a lifeline. The company's leadership decided to replace on an interim basis the former CEO with board chair Michael Higgins and the former research chief with director Glenn Pierce. The executive reshuffle preceded a strategic shift to increase investment in the TRACER technology and focus on second-generation TRACER-based AAV gene therapies in neurologic and muscular disease. That added years to Voyager's clinical development timelines, prompting Cantor Fitzgerald analyst Charles Duncan to cut his rating on the company's stock on August 12. With $149 million in cash and quarterly expenditures of $30 million, Duncan then estimated that Voyager had enough resources to fund itself through early 2023 and the pre-clinical studies necessary to seek regulatory permission to begin human testing. The Pfizer deal offers that cash balance and provides a sign to investors that the new gene therapy technology has promise.
In June Andre Turenne, Voyager's CEO and president for 3 years, stepped down from those roles and was succeeded on an interim basis by Michael Higgins, the company's board chairman. Also departing was Omar Khwaja, chief medical officer and head of research and development. Board director Glenn Pierce assumed the role of interim chief scientific officer. Maria Lopez-Bresnahan, head of translational medicine and clinical development, continued to lead clinical programs.
The executive shake-ups come as Voyager prepares to begin human testing for one of its most advanced gene therapies, which targets Huntington's disease. Voyager recently found in preclinical tests that its technology was able to make more potent gene therapies for hard-to-reach areas of the body, like the brain and spinal cord. The company said Wednesday it plans further investment in this technology, with the potential to use it in strategic partnerships or licensing deals.
Third Rock Ventures launched Voyager in 2014. Shortly afterwards, the company entered a research and development deal with pharma giant Sanofi. By the end of 2015, Voyager raised almost $81 million by going public. In the ensuing years since, Voyager has been involved with other drugmakers, including AbbVie and Neurocrine.
Still, Voyager's mission to use gene therapy to fight diseases of the brain and central nervous system could be viewed as somewhat of a longshot. Neurological illnesses are very hard to treat. Gene therapy keeps posing challenges for even the largest and wealthiest drug companies. Late in 2020, Voyager’s Huntington's program was set back when the FDA said that human testing could not begin without more information on how the gene therapy is manufactured.
There were also problems with Voyager's partnerships. The arrangement with AbbVie terminated last summer. The Sanofi collaboration has been completely revised to focus on Voyager's capsid technology that creates outer coatings for gene therapies to help them get to desired tissues.
Voyager is now focused on an early-stage study of the Hungtinton's gene therapy, while also advancing other programs. The company sees more opportunities for its capsid technology, especially after non-human primate testing showed that one of its novel capsids resulted in 1,000-fold or higher transgene expression in the brain, and 100-fold higher transgene expression in the spinal cord.