A number of startups are targeting the gut microbiome as a way to potentially treat disease, but identifying specific microbes at the root of illness is a challenge. Although software that analyzes troves of biological data helps, the trillions of gut microbes make the research like looking for a needle in a haystack, says James Rosen, CEO of Artizan Biosciences.
“What our technology does is make that haystack smaller,” he says.
Artizan aims to turn its research about disease-causing microbes into a pipeline of new microbiome drugs. On Monday, the New Haven, CT, company announced it completed a Series A round of financing, bringing its total venture capital haul to $12 million. Rosen says his company could start human testing within two years.
The Artizan technology identifies problem microbes by searching for immunoglobulin A. This antibody, which plays a role in immune response, is found in mucus. It also coats some microbes in the gut—microbes that cause some gastrointestinal disorders, according to Artizan’s research.
The Artizan technology comes from Yale University, where it was developed in the laboratory of Richard Flavell, a professor of immunobiology and the former chief scientific officer of Biogen (NASDAQ: BIIB). In 2016, the Yale research reached a point where it could become the basis for a company, Rosen says. Hatteras Venture Partners, the Durham, NC, venture capital firm where Flavell is also a member of the scientific advisory board, assembled the investor group that backed Artizan with an initial $5 million and brought on Rosen, a veteran venture capitalist, as CEO. The Yale technology is available for research purposes, but Rosen says Artizan holds an exclusive license to use it to develop drugs.
Artizan’s first disease target is inflammatory bowel disease (IBD), a disorder characterized by chronic inflammation of the digestive tract. IBD affects an estimated 3 million US adults, according to the Centers for Disease Control and Prevention. Current treatments include anti-inflammatory drugs, immune system suppressors, and antibiotics. When drugs and changes to lifestyle and diet don’t work, some patients choose surgery.
Other companies have researched microbiome drugs for IBD. In 2014, South San Francisco-based Second Genome started out targeting Crohn’s disease, a form of IBD that can occur anywhere along the digestive tract. The company later shifted its lead drug’s focus to ulcerative colitis, a form of IBD affecting the colon. The drug is now being tested as a potential treatment for nonalcoholic steatohepatitis (NASH), a liver disorder.
Second Genome’s experimental drug is a small molecule. Several other microbiome startups are developing formulations of microbes that come from healthy human donors. These “bugs as drugs” are intended to restore a patient’s gut microbiome to a healthy balance. One company taking this approach is Whole Biome, which formulates capsules containing microbes lacking in patients with type 2 diabetes. However, the San Francisco company’s product is a “medical food,” not a drug.
Seres Therapeutics (NASDAQ: MCRB) of Cambridge, MA, has advanced its experimental treatment for ulcerative colitis to mid-stage testing. But the industry and regulators still lack experience with bugs as drugs, and that has led to setbacks. Three years ago, Seres drug SER-109 failed a Phase 2 study in Clostridium difficile infection, a type of gut infection. Although the FDA later gave the company the go-ahead to try again with another study, that drug has yet to be submitted to the FDA for review. Vedanta Biosciences, another Cambridge biotech that researches microbiome therapies made from live bacteria, has advanced its experimental C. diff drug to mid-stage testing.
Rosen says it’s too early to say what type of drug an Artizan IBD therapy will be, but he notes that the company is steering clear of the bugs as drugs approach. Instead, he says Artizan plans to develop small molecules, antibodies, and vaccines—drugs that have well-established regulatory pathways that should ideally avoid setbacks, such as the Seres clinical trial failure.
If Artizan’s approach works, the company will need more than one drug to treat IBD. The gut microbiome varies from one person to another, and it can change depending on factors that include environment and diet. Rosen says Artizan’s research so far has identified bacteria that are consistently causing IBD in 20 percent of patients. By continuing to identify bacteria that cause IBD, Rosen says he hopes Artizan can develop treatments for a greater percentage of IBD patients. He adds that the company’s technology has the potential to apply to other gastrointestinal diseases, as well as disorders affecting nearby organs, such as the liver.
With the close of the latest financing, Artizan has relocated its headquarters from Durham to New Haven’s Science Park. Besides Hatteras, Artizan’s investors include Malin, Johnson & Johnson Innovation, Osage University Partners, and Elm Street Ventures. The startup also has a partnership with Brii Biosciences, a Durham, NC, company that is developing therapies for the Chinese market. The partnership, which encompasses up to three programs stemming from Aritzan’s research, gives Brii an equity stake in Artizan.