Neurocrine Gets Rights to GBA1 Gene Therapy Work for Parkinson’s
Collaboration with Voyager Therapeutics to extend through Phase 1 clinical trial
Neurocrine Biosciences has acquired rights to Voyager Therapeutics’ experimental gene therapy program for Parkinson’s disease associated with mutations in the GBA1 gene and for other GBA1-mediated diseases.
The collaboration agreement also includes three gene therapy programs for rare diseases of the central nervous system (CNS; the brain and spinal cord). All are based on Voyager’s proprietary TRACER platform to identify improved viral carriers, called capsids, for gene therapy.
In exchange for worldwide rights to these programs, Neurocrine will pay Voyager $175 million upfront, including $39 million in equity investments, the company announced in a press release.
GBA1 mutations linked with earlier onset and fast progressing Parkinson’s
Neurocrine will fund the development of the GBA1 program through the completion of a first Phase 1 trial. After results are out, Voyager may elect to either co-develop and co-commercialize the program with Neurocrine, or to be eligible for more than $900 million in developmental milestone payments as well as potential payments related to commercial milestones and royalties.
“We believe GBA1 gene therapy has the potential to play a transformational role in the future treatment of Parkinson’s disease and other serious neurological diseases,” said Jude Onyia, PhD, chief scientific officer of Neurocrine.
“This new collaboration with Voyager … complements our existing collaboration around Friedreich’s Ataxia and other CNS targets, establishing the foundation for a strong franchise of next-generation gene therapies utilizing Voyager’s TRACER capsids to treat serious neurological diseases,” added Onyia, who will join Voyager’s board of directors once the deal is closed.
The GBA1 gene provides instructions for producing beta-glucocerebrosidase (GCase), an enzyme that’s important for the function of cellular compartments called lysosomes. Lysosomes work to clear cellular waste, and problems with GCase cause molecules that should have been recycled to build to toxic levels inside cells.
Mutations in the GBA1 gene, observed in about 10% of Parkinson’s patients, are one of the most common risk factors for the neurodegenerative disease, raising the risk by up to about 20 times. Patients with GBA1 mutations also often have an earlier disease onset and faster progression.
GBA1 mutations also cause Gaucher’s disease, a rare condition marked by the buildup of fatty molecules in organs and tissues.
Voyager’s experimental GBA1 gene therapy is designed to provide patients who have a GBA1 mutation with a working copy of the gene, enabling the body to produce more of its own GCase enzyme.
Gene therapies typically are packaged into modified and harmless adeno-associated viruses (AAVs) that help to deliver them to target cells. But these AAVs don’t easily cross the blood-brain barrier (BBB), a highly selective membrane that prevents potentially harmful agents circulating in the blood from reaching the CNS.
To enable enough of the therapy to reach the CNS via the bloodstream, high systemic doses are required, which can affect other cells than those targeted and have side effects, Neurocrine noted in its website. An alternative is direct injection into the CNS, but this is a more invasive and risky procedure.
Voyager working on more effective and safer gene therapy viral carriers
Voyager’s TRACER screening platform helps to select and engineer viral carriers expected to be more successful at reaching the target tissue while minimizing off-target effects.
One such capsid was found to increase BBB penetrance by about 50 times when injected directly into the bloodstream of non-human primates or mice compared with a standard AAV vector.
Notably, a single dose of the GBA1 gene therapy, delivered using a CNS-penetrant vector, resulted in therapeutically relevant levels of the GCase enzyme throughout the brain in a mouse model of GBA1 deficiency, the company reported.
Neurocrine and Voyager have a long-standing collaboration in the development of gene therapies.
The two companies previously joined in work to develop VY-AADC, another of Voyager’s gene therapy candidates for Parkinson’s. Neurocrine announced that it was ending this collaboration in 2021, but it would continue to work with Voyager on other gene therapy programs.
“We look forward to expanding our engagement with Neurocrine Biosciences, with whom we already enjoy a strong relationship,” said Alfred W. Sandrock, Jr., MD, PhD, CEO of Voyager.
“We anticipate that the opportunities enabled by this collaboration will allow us to continue to invest in our platform and pipeline programs, as well as to advance cutting-edge research initiatives,” Sandrock added.