The gastrointestinal system is often viewed as a barrier to drugs. Conditions ideal for breaking down food also break down drugs in ways that can limit how well they work. Interaction with the gut microbiome can also diminish a drug’s efficacy or boost its toxicity.
Paul-Peter Tak, a former GlaxoSmithKline (NYSE: GSK) executive who is now the CEO of Cambridge, MA-based Kintai Therapeutics, contends that the gut and its microflora can also open up new ways to treat an array of diseases throughout the body. Research is showing how the gut connects to the immune system, the nervous system, and more. As a nexus for various systems of the body, Tak (pictured above) says the gut can also be place where the human body interfaces with the external world—much more so than the skin. Those connections are key to treating diseases beyond the gut.
“We look at the gut’s biology in a region specific way,” Tak says. “All areas are relevant—and different.”
Kintai has been quietly researching its approach to “gut science” for two years. On Tuesday, the startup is coming out of stealth with a pipeline of 10 programs spanning a range of therapeutic areas. The two most advanced programs are expected to begin tests in humans next year. Kintai joins a growing number of startups developing drugs that interact with the human microbiome. But Tak says his company is not a microbiome drug company.
The research that forms the basis for Kintai began in the labs of venture capital firm Flagship Pioneering. David Berry, a general partner at the firm and a Kintai co-founder, says there has been a progression in medical understanding about the gut as an interconnected ecosystem. Scientists have already found ways that the gut can be an indicator of health. The signs and symptoms of Parkinson’s disease, for example, can be preceded by changes in the gut. In cancer, a patient’s response to a type of immunotherapy called a checkpoint inhibitor can depend on its interaction with microbes in the gut.
The gut is the place where the immune system, the human microbiome, and the enteric nervous system—the neurons and cells of the gastrointestinal tract—all interconnect. Berry says Kintai is developing drugs that use the biology of the gut to treat disease locally in the gut or systemically throughout the body.
“This integrated biology concept that’s at the core of this, this is actually a theme we’ve been thinking about at Flagship going back about a decade,” Berry says.
The Flagship portfolio includes companies developing drugs targeting the gut microbiome in various ways. Compounds now in clinical testing from Seres Therapeutics (NASDAQ: MCRB) and Evelo Biosciences (NASDAQ: EVLO) consist of microbes intended to treat disease. Kaleido Biosciences (NASDAQ: KLDO) is taking a different approach, developing small molecules whose therapeutic benefit is meant to come from the drug’s effect on the metabolism of the microbiome.
Kintai’s experimental drugs are small molecules, not microbes or other biological compounds, Tak says. He adds that Kintai’s research on the gut microbiome has identified more than 44,000 new genes and hundreds of new metabolites, which are substances produced as a byproduct of metabolism. That research helped the company understand how different regions of the gut connect to different systems in the body.
Kintai isn’t the only company aiming to tap gut connections to treat disease. Axial Biotherapeutics and Kallyope are two biotechs researching the signaling that occurs between the gut and the brain. The goal is to tap into these signals to treat neurological conditions.
Tak says a Kintai drug could activate natural metabolites or immune cells that circulate in the body. With that approach, he says the effects of a Kintai medicine could reach the liver to treat nonalcoholic steatohepatitis, or the brain to treat neurological disorders. Tak says one benefit of Kintai’s approach is the potential to treat neurological conditions without needing to cross the blood-brain barrier, the membrane that makes it hard for some drugs to reach the brain.
Ulcerative colitis and metabolic syndrome are Kintai’s two lead disease targets. Tak says that the work on these drugs is based on biology that is well understood, which makes them more likely to be successful. Those programs are expected to begin clinical testing next year.
Tak, whose roles at GSK included serving as head of immunoinflammation research as well as chief immunology officer, says he was attracted to Kintai because of his long academic and professional interest in the workings of the immune system. He declined to say how much money has been pumped into Kintai’s research so far, other than to say that Flagship is providing the company with enough support to reach the clinic. But he says the company may also consider working with partners to develop some of its programs. Tak says the reason Kintai waited until now to talk about its work is that it first needed to secure the intellectual property protecting its discoveries.
Photo by Kintai Therapeutics