Bold up-fronts and even bigger milestones defined ambitious neurology deals Abbvie Inc. struck with Voyager Therapeutics Inc. in 2018 and 2019. With vectorized antibodies, they planned to target multiple indications tied to excess aggregations of tau and tragic synucleinopathies. Considerable progress was made, said Omar Khwaja, Voyager's chief medical officer. But despite millions of dollars invested in the programs, Abbvie has now decided to quit the venture, leaving Voyager to either go it alone or find a new partner in its work on the challenging indications.
In explaining the dissolution of their marriage, an affair headlined by talk of its multibillion-dollar potential, Abbvie "exercised its right to terminate for convenience," according to a regulatory filing. What that means is unclear, as the North Chicago-based company declined to expound.
Whatever the case, Voyager was not left empty-handed. On the most basic level, it laid claim to non-refundable up-front payments of $69 million in the tau agreement and a further $65 million in the alpha-synuclein deal. But it was also left with a gift that could be equally valuable: "substantially advanced" know-how and IP around delivering higher levels of antibodies to the brain through its vectorization technology.
Voyager’s gene therapy platform is built on adeno-associated virus (AAV) technology. In January 2017, scientists from Voyager and Weill Cornell Medical College published a paper in the Journal of Neuroscience describing reduced tau pathology, including neurofibrillary tangles and neurodegeneration, following treatment with a single dose of an AAV vector designed to administer the tau monoclonal antibody (MAb) PHF1 to the hippocampus of mutant tau transgenic mice. The findings showed that, by placing a MAb directed against tau into an AAV vector, it could achieve higher brain levels of the antibody, which has been one of the rate-limiting aspects of immunotherapy for Alzheimer's disease.
During the course of its partnership with Abbvie, Voyager’s team was able to demonstrate an ability to deliver "significantly higher levels of antibodies to the brain compared to passive immunization," the company's president and CEO, Andre Turenne, told BioWorld. Furthermore, it also "developed significant proprietary knowledge focused on optimal transgene expression, and on the engineered components of vectorized antibodies, as well as selective promoter and other regulatory elements that drive cell type specificity for antibody production in specific cell types in the brain," he said.
The company also regained full clinical and commercial rights to the candidates developed in the tau program, leaving it free to pursue those and any alpha-synuclein programs on its own or with a partner.
It's not unfamiliar territory for the Cambridge, Mass.-based company. In June 2019, a joint termination of the company's agreement with Sanofi SA's Genzyme unit saw Voyager regain full rights to its Huntington disease gene therapy program, VY-HTT01, now the lead wholly owned asset in the company's broader pipeline alongside its Neurocrine Biosciences Inc.-partnered Parkinson's program.
Less Abbvie work could leave new bandwidth for the Neurocrine-partnered program, VY-AAD, which appears poised to ramp up in the months ahead. Trial sites for the phase II Restore-1 trial had temporarily suspended patient screening and enrollment activity in response to the COVID-19 pandemic and the implementation of previously disclosed protocol amendments. Now, they'll likely need support as patient screening for the study resumes in the second half of this year. Furthermore, the phase III Restore-2 trial lies ahead. That trial, which could potentially form the basis for submission of a BLA in PD, is expected to start in the first half of 2021.
For now, Voyager said it remains funded into mid-2022 with $250.9 million in cash and marketable debt securities on hand and additional funds expected to flow from its partner, Neurocrine.
Voyager's shares (NASDAQ:VYGR) fell 8.6% following Tuesday's news, closing at $10.35.