For close to a year, Navitor Pharmaceuticals has been quietly working behind the scenes with scientists at the Whitehead Institute on an approach to hit a well-known disease target in a novel way. Now the Cambridge, MA-based startup is stepping out of the shadows to unveil its plan with a big round of financing.
Today, Navitor is announcing it has closed a $23.5 million Series A round from a group of big-name investors—Polaris Partners, Atlas Venture, Johnson & Johnson Development Corp. (the VC arm of Johnson & Johnson), SR One (the venture unit of GlaxoSmithKline), and the Longevity Fund. The cash will help bankroll Navitor’s plan to ultimately whip up drugs that are meant to restore balance to a well-known cellular signaling pathway called mTORC1, which tends to get thrown out of whack in a variety of diseases. If successful, Navitor believes that approach gives it the capability to treat a whole host of autoimmune, metabolic, musculoskeletal, and even rare disorders.
“What’s unique about what we’re trying to do, and what I think is going to be attractive to a number of people, including potential partners and others, is the fact that what we’re focusing on is a very critical central pathway that cells basically use to adjust to changes in their environment,” says CEO George Vlasuk, the former head of Sirtris Pharmaceuticals, and an executive at Wyeth before that.
Navitor was originally seeded by Polaris in late 2009 as Calorics Pharmaceuticals, but the company changed its name after a search for a core of intellectual property led Polaris to the work David Sabatini, a professor and cell biologist at the Whitehead Institute, has been doing regarding a well-known cellular network revolving around a kinase called mTOR.
mTOR is an acronym for “mammalian target of rapamycin,” named as such because it was discovered in studies into the mechanism of action of the immunosuppressive drug rapamycin. It’s a kinase that Sabatini discovered when he was a grad student at Johns Hopkins; two decades later, several companies have successfully developed drugs that block mTOR to treat cancer, like Novartis’ everolimus (Afinitor) and Pfizer’s temsirolimus (Tosirel).
Those drugs work by blocking mTOR as a standalone target. The kinase is also the central actor, however, in two larger complexes of proteins called mTORC1 and mTORC2, and Navitor wants to develop drugs that hit targets in just one of those complexes—mTORC1. The company has homed in on mTORC1, Vlasuk says, because it is the “primary complex that senses changes to the environment,” such as the availability of amino acids and other nutrients. When mTORC1 is in disarray, a number of different diseases can occur. Vlasuk says too much activity in the pathway, for instance, can result in the reduction of insulin production. By contrast, mTORC1 activity is suppressed in certain skeletal muscle diseases.
This is where Navitor aims to come in. The company intends to use small molecules to selectively bind to certain protein targets (Vlasuk wouldn’t say which ones) in the mTORC1 complex so that its activity is either dialed up or down, depending on the need and the disease. The company was renamed Navitor to reflect the idea of navigating the mTORC1 pathway.
That selectivity is ultra important, because messing with mTORC2 as well—while necessary in certain types of cancer to create a bigger drug effect, according to Vlasuk—can lead to serious side effects. Chronic use of rapamycin, for instance, is linked to diabetes because its effect on mTORC2 can cause insulin resistance. So Navitor is hoping to prove its drugs can get to certain targets on mTORC1, while leaving mTORC2 untouched.
Vlasuk says he isn’t aware of any other company specifically targeting mTORC1, and that working with scientists out of the Sabatini lab gives Navitor a leg up on “any” competition because it’s working with the people that are discovering these biological pathways in the first place.
“That’s the basis of our proprietary know-how,” he says. “David and his group [are] at the forefront of this particular pathway.”
Still, this is all very early-stage work. Navitor is only at the discovery stage at this point, and is basically looking at various sets of chemical compounds, trying to unearth small molecules that have a chance to become a drug. Navitor isn’t saying which types of diseases specifically it plans to target first, but then again, it doesn’t know where the science will lead it yet. Navitor hopes to identify its first development candidate within the next two years.
“That’s an important next step for us and I think that’s going to be critical to how we go forward from there,” Vlasuk says.
Sabatini, meanwhile, is chairing a six-member scientific advisory board that also includes Brian Hubbard (the Broad Institute); Tom Hughes (CEO of Zafgen); Brendan Manning (Havard School of Public Health); Blake Rasmussen (University of Texas); and James Tobin (J&J Innovation).