A group of former executives of AveXis, the developer of the gene therapy Zolgensma, is behind a new startup launching publicly on Thursday with plans to push genetic medicine in new directions.
The startup, called Jaguar Gene Therapy, has been quietly building out its research pipeline and team for more than a year, backed by just over $40 million in funding from Deerfield Management, an early AveXis investor.
Jaguar's research programs are still preclinical, but they stand out for the diseases they target. One, aimed at an inherited metabolic disorder called galactosemia, is the type of condition gene therapy developers often go after: rare, triggered by mutations in specific genes and with disease symptoms caused by the disruption in DNA.
But Jaguar also aims to develop treatments for two more complex diseases, autism spectrum disorder and Type 1 diabetes, by targeting genes it says are associated the disorders but won't reveal just yet.
"We're trying to do what's bold," said Sean Nolan, a former AveXis CEO who will serve as executive chairman of Jaguar. "We're thinking bigger in terms of size of patient populations, and going where gene therapy hasn't gone before."
While autism may be a less obvious choice for gene therapy, a number of companies have for years studied conditions linked to the developmental disorder, like Rett, Angelman and Fragile X syndromes. And last summer, Novartis agreed to a research collaboration with Sangamo Therapeutics to study gene therapies for neurological conditions, including autism.
Jaguar estimates about 30,000 people in the U.S. are affected by the genetically associated autism it's targeting, compared to the roughly 4,500 who are thought to have severe galactosemia. Type 1 diabetes is much more prevalent, but Jaguar said it's still evaluating the "appropriate clinically relevant patients" who could possibly be treated with a gene therapy.
"In all candor, Type 1 is a bit more 'to be determined,'" said Nolan, acknowledging the higher technical difficulty a disease like diabetes presents. "Based on what we've seen — and it's early — but it looks like the gene we're targeting has a major effect."
Nolan is joined at Jaguar by Joe Nolan (unrelated), a general manager at AveXis who will serve as chief executive of the new startup. Four other former AveXis executives will round out Jaguar's leadership team, including Suku Nagendran as head of research and development.
In an interview, Sean Nolan pitched the team's collective experience in gene therapy as a strength, citing R&D lessons that have become more apparent amid both progress and setbacks in the field.
"There are still only two gene therapies approved in the U.S. and there's significant more road that we need to pave," he said, referring to the spinal muscular atrophy treatment Zolgensma, now owned by Novartis after a 2018 buyout of AveXis, and Roche's blindness treatment Luxturna.
Jaguar will use some of the same technology favored by AveXis, relying on a type of inactivated virus known as adeno-associated virus serotype 9, or AAV9, to deliver its gene therapies into the body. Many other gene therapy biotechs use AAVs as well, particularly for diseases affecting the liver and muscles.
A recently diagnosed case of liver cancer in a study of a gene therapy developed by Dutch drugmaker UniQure, however, has renewed questions about AAV's long-term safety and cancer risk. UniQure uses a different AAV type, serotype 5, and hasn't yet reported any direct link between its treatment and the cancer diagnosis.
"For now, AAV really is the most studied, the most well understood and gave us the most comfort with the diseases were are looking at to go forward with," said Nolan.
The fourth disease Jaguar plans to study will be targeted by a majority-owned subsidiary that's also launching Thursday.
Axovia Therapeutics will carry forward the work of Philip Beales, a professor at University College London who's spent decades researching a condition called Bardet-Biedl syndrome. Axovia will target a life-threatening form called BBS1 that leads to early-onset retinal blindness, diabetes, kidney failure, endocrine abnormalities and intellectual disability.
Deerfield Management funded Axovia, too, along with the UCL Technology Fund.
"When we were talking through formation of Jaguar, [Axovia] was already on its path and was going to be a standalone company," said Nolan. Deerfield helped set up the subsidiary structure, which will allow Axovia to tap Jaguar's help in manufacturing, clinical and regulatory aspects of its research.
Editor's note: This story has been updated to include mention of research into other genetic disorders associated with autism spectrum disorder.