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Audentes, Loaded With $30M, Pursues Gene Therapy for Rare Diseases

Five years ago, hardly anybody would invest in a startup focused on gene therapies for ultra-rare diseases. But gene therapy has been on the comeback trail, and a San Francisco startup called Audentes Therapeutics has corralled $30 million to see if it can overcome some of the obstacles that have tripped up others in this field over the past 20 years.

Audentes announced last week that it raised the hefty sum of $30 million in a Series A venture financing from a trio of well-known healthcare investors—OrbiMed Advisors, Versant Ventures, and 5AM Ventures. That will be enough money to run the company for the next several years, to see if it can come up with promising data from clinical trials for a couple of rare diseases called X-linked myotubular myopathy and Pompe disease.

Gene therapy has tantalized biologists for a couple decades, and frustrated biotech and pharmaceutical companies. The idea, for those unfamiliar, is about modifying viruses to carry copies of genes into cells, where they can replace missing or faulty genes at the root cause of certain diseases. Billions of dollars were invested in companies large and small throughout the 90s and early 2000s, and after a series of safety concerns, there are still no FDA-approved gene therapy products. But Netherlands-based UniQure broke through in November with the first gene therapy approved in Europe, and growing scientific enthusiasm around a series of technical improvements helped propel Cambridge, MA-based Bluebird Bio (NASDAQ: BLUE) to one of the most successful biotech IPOs of the year.

While looking around for opportunities last year as an entrepreneur-in-residence at OrbiMed in New York, Matthew Patterson saw enough improvement in the underlying technology of gene therapy to give it a chance in rare muscle disorders.

“It became clear to me there’s been tremendous scientific advances in field,” Patterson says.

Still, tremendous scientific advancement doesn’t guarantee the next steps will be clear or obvious. The company name, which Patterson came up with, is derived from the Latin term for “one who has courage or boldness.” Some readers probably know the phrase “audentes fortuna juvat,” which translates to “fortune favors the bold.” He knows there is still plenty of skepticism in the industry of gene therapy, largely from veterans who have seen failure after failure.

“The theme of courage is very appropriate when we think about the patients we’re trying to serve,” he says. “I like the boldness, the effort it will take from everyone involved.”

Patterson is a veteran of the rare disease field, with past experience at Amicus Therapeutics (NASDAQ: FOLD), BioMarin Pharmaceuticals (NASDAQ: BMRN), and Genzyme. During his time at OrbiMed, he connected with a couple of key scientific advisors—Martin “Casey” Childers at the University of Washington and Barry Byrne at the University of Florida—to put together the plan for Audentes.

The idea is to use tiny modified viruses known as adeno-associated viruses (AAVs) to deliver genes to fix underlying genetic problems for patients with X-linked myotubular myopathy and Pompe disease. AAVs have long been attractive to gene therapy researchers because they have a virus’s natural ability to efficiently get inside cells. They’re also thought to be safer than other viruses, like retroviruses or adenoviruses. The newest generations of AAVs have shown good safety profiles in humans, an ability to be efficiently distributed throughout tissues in the body, and can even be modified to be delivered to specific tissue types if desired, Patterson says.

The first disease, X-linked myotubular myopathy, is a good candidate for gene therapy because it’s a single gene defect in newborns that is deadly after a couple years, and currently has no effective therapy, Patterson says. About one in 50,000 newborn males worldwide are thought to have this condition, according to the National Institutes of Health.

The second program at Audentes, for Pompe disease, is different in that there are already a couple of enzyme-replacement therapies available—Sanofi/Genzyme’s alglucosidase alfa (sold as Myozyme and Lumizyme)—although those treatments have limited effectiveness, Patterson says. Audentes is hopeful that by making a gene therapy for Pompe, it might be able to penetrate skeletal muscle tissues, and motor neurons, which could address some of the muscle weakness and respiratory problems that patients often struggle with while on the existing therapies, Patterson says. An estimated one out of every 40,000 children is born with Pompe.

Audentes doesn’t have any data yet from clinical trials, but it has gotten its venture investment based on promising animal studies, Patterson says. In Florida, Byrne is running a clinical trial with an older version of an AAV delivery vector in clinical trials for Pompe, which could help pave the way for Audentes to move ahead with a newer version, Patterson says.

With the financing in hand, Audentes is moving ahead to flesh out its management team by making 10-20 hires, Patterson says. He’s looking for people with experience in the science of AAV vectors, manufacturing them, and for clinical development types with experience in rare diseases. Although Patterson has personally lived and worked in both Boston and San Francisco in the past—both great biotech hubs—he picked the Bay Area as the place for Audentes largely to tap into its talent pool. He says he’s gotten more than a few inquiries from potential hires since the Series A financing announcement, and he’s eager to get a few of those folks on staff to help him and the company’s scientific advisors. “[Job] offers are going out the door,” Patterson says.