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Still Years From Clinic, Navitor Gets $33M And More Pharma Friends

Xconomy Boston — 

These are early days for Navitor Pharmaceuticals. It’ll be a few years before the Cambridge, MA-based startup can even test its idea, to hit a well-known disease target with drugs in a new way, in human volunteers. But a number of large pharma companies are paying millions of dollars to keep a close eye on Navitor’s progress.

Navitor said today that venture groups associated with multinational firm Sanofi and EMS, Brazil’s largest pharma, are part of its new $33 million Series B round.

Navitor already had GlaxoSmithKline’s SROne and Johnson & Johnson Development Corp. among its backers, meaning four pharma companies in the U.S., England, and South America now have stakes in the startup.

“That reflects the interest that pharma companies have in what we’re doing,” says Navitor president and CEO George Vlasuk.

Vlasuk emphasizes, however, that these companies are “just strategic investors.” They don’t have any special rights associated with their investments, just an inside look at Navitor and an equity stake.

Navitor is developing small molecule drugs that can interfere with a molecular target called mTORC1, which Vlasuk refers to as a “master regulator of cellular metabolism and growth.” mTORC1 gets thrown out of whack in a variety of diseases, so tweaking it in different ways with a drug could have an impact on a host of metabolic and neurodegenerative diseases and other maladies.

Vlasuk points out, for instance, that mTORC1 might play a role in what’s known as tuberous sclerosis, a genetic disease that causes non-malignant tumors to form in the body.

Some early data from Navitor suggest that targeting mTORC1 might be useful in treating neurological diseases like Huntington’s or Parkinson’s, or perhaps even activating T cells, the body’s attack dogs.

“It’s probably the most important signaling pathway in a cell,” Vlasuk says.

As such, figuring out the right direction to go with this is taking time. Vlasuk estimates that Navitor should have its first drug in clinical testing by early 2018, more than two years from now. The new cash will help Navitor reach those first critical experiments in humans.

Boston venture firm Polaris Partners seeded Navitor six years ago, originally as Calorics Pharmaceuticals, but the company’s name changed when Polaris scooped up core intellectual property based on the work of Whitehead Institute professor David Sabatini.

Sabatini is widely known for discovering a kinase two decades ago called mTOR, or “mammalian target of rapamycin.” It’s become a popular target for a number of cancer drugs like Novartis’ everolimus (Afinitor) and Pfizer’s temsirolimus (Tosirel), which work by blocking mTOR as a standalone target. (mTor is one of hundreds of kinases, signaling molecules that regulate a wide range of cellular activities.)

Navitor, however, is trying to prove that drugging mTOR itself is too narrow an approach. It’s a key actor in two larger complexes of proteins—mTORC1 and mTORC2—which can each cause a variety of different biological effects when dialed up or down.

Navitor aims to develop small molecule drugs that bind to certain protein targets on mTORC1 because, as Vlasuk told Xconomy in 2014, it’s the “primary complex that senses changes to the environment,” like the availability of nutrients outside a cell. Activating or suppressing mTORC1, while leaving mTORC2 untouched, could have an impact on a range of diseases. (Check out these recent publications, for instance, which highlight mTORC1’s role in cellular metabolism, cancer growth, and Huntington’s.)

The company announced a $23.5 million Series A in June 2014. Since then, Vlasuk says there have been important breakthroughs in understanding how mTORC1 responds to the environment around it. For instance, Sabatini co-authored a paper in Science two months ago identifying specific proteins called sestrins that help regulate mTORC1 by sensing the presence of the amino acid leucine, which is critical for muscle growth. These types of discoveries are important to help learn what exactly to target when drugging mTORC1. Vlasuk, for instance, says the family of sestrin proteins are of “significant interest” to Navitor as a potential drug target.

One decision Navitor must make is whether to treat common or rare diseases. Going after rare diseases means smaller clinical trials and lower costs. Developing drugs for common diseases would likely require financial help from a partner—perhaps one of the companies in Navitor’s investor group.

“We’re still pretty early in the game,” Vlasuk says. “There are a lot of great possibilities out there for us to consider.”

Remeditex Ventures and an unspecified institutional investor joined Sanofi-Genzyme BioVentures and EMS’s Brace Pharma Capital fund for the new round. Founding backer Polaris and fellow Boston area VC firm Atlas Venture also participated. Brace Pharma president and CEO Vinzenz Ploerer and Remeditex chief operating officer Barry Burgdorf have joined Navitor’s board.