Going after neurodegenerative diseases where lysosomal dysfunction is an underlying cause, Prevail Therapeutics Inc. announced a $75 million series A round to fund development of its gene therapies.

The New York-based company is still largely in stealth mode; the only information on its website are emails for general contact and another for potential employees to send resumes to human resources. Nevertheless, founder and CEO Asa Abeliovich was willing to share some details with BioWorld.

Prevail got its start last year through a relationship between Abeliovich, who was a faculty member at Colombia University for 17 years, and venture capital firm Orbimed. A few years earlier, Orbimed helped fund the series A round for Alector LLC, a San Francisco-based company focused on harnessing the immune system to treat neurodegeneration diseases and cancer, which Abeliovich helped found. (See BioWorld Today, Nov. 1, 2013.)

Orbimed's general partner and co-head of global private equity, Jonathan Silverstein, had recently started the Silverstein Foundation for Parkinson's with GBA after being diagnosed with Parkinson's disease. Given Abeliovich's background in neurodegeneration and his desire to translate that work, Orbimed and the Silverstein Foundation put up the seed funding, and Abeliovich was off and running, hiring about a dozen employees while being incubated at Orbimed until it moved into lab and office space in the Alexandria Center for Life Sciences in New York.

Alexandria, through its Alexandria Venture Investments, was one of the investors in the series A round, which also included Orbimed, Pontifax Fund, RA Capital Management, Ecor1 Capital, Omega Funds, BVF Partners LP, Boxer Capital LLC and Adage Capital Management LP.

Prevail's lead program, PR-001, will express an undisclosed gene to help a subset of Parkinson's disease patients with an underlying genetic mutation and potentially other mechanistically related disorders.

While the exact mechanism that leads to Parkinson's disease isn't fully understood, it's clear that mutations in certain genes, such as glucocerebrosidase (GBA), contribute to the development of the disease. Mutations in GBA lead to dysfunction of lysosomes, the organelles in cells that contain enzymes responsible for breaking down macromolecules, including nucleic acids, proteins and polysaccharides.

"When you get older, when a lot of the cells don't turn over, it's essential to have proper recycling and disposal," Abeliovich explained.

About 10 percent of the 1 million Americans with Parkinson's have a mutation in GBA – from which the Silverstein Foundation for Parkinson's with GBA gets its full moniker – suggesting GBA might be a good protein to express, but Abeliovich wasn't willing to elaborate. "We're not in a position to disclose what gene we're delivering," he told BioWorld.

The secrecy likely comes from potential competition from other companies developing gene therapies for Parkinson's disease.

While not a going after the same mechanism, last year, Voyager Therapeutics Inc., of Cambridge, Mass., reported promising data from its phase Ib Parkinson's disease trial testing adeno-associated virus 2 (AAV2) gene therapy VY-AADC-01, which expresses AADC, an enzyme that catalyzes the conversion of levodopa to dopamine that's lacking in Parkinson's disease patients. In January, Voyager said its IND using its new manufacturing process cleared the FDA, allowing it to start a phase II/III program that's scheduled to treat the first patient in the second quarter of 2018. (See BioWorld, Sept. 7, 2017.)

Prevail is using a NAV AAV9 vector that it licensed from Regenxbio Inc., of Rockville, Md. "It has shown remarkable safety in humans thus far," Abeliovich said, noting that it has good distribution allowing it to target the brain.

Abeliovich wasn't willing to give a timeline for when he thought PR-001would enter the clinic, only noting that the company is "going as quickly as possible."

The goal is to use the rather large series A round to get two to three gene therapy programs designed to correct lysosomal dysfunction into the clinic before needing to raise more capital. Additional potential neurodegenerative diseases that Prevail might target include Alzheimer's disease and amyotrophic lateral sclerosis.