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With $19M, Axial Becomes Latest Startup to Target Gut-Brain Connection

Xconomy Boston — 

We’re still a long way from understanding how the trillions of bacteria that live in and on our bodies, known collectively as the human microbiome, affect our health and well-being. Despite those unknowns, a steady drip of companies have launched in recent years to explore those links and make drugs for a range of diseases.

Axial Biotherapeutics is the latest to enter the fray. The Boston company, based on research by California Institute of Technology microbiology professor Sarkis Mazmanian (pictured), is emerging this morning with $19 million in Series A financing. David Donabedian, a former deal maker at AbbVie and GlaxoSmithKline and most recently a venture partner at Longwood Fund, is the CEO.

Axial aims to delve into what’s known as the “gut-brain axis,” a kind of information superhighway that conducts signals between the microbes in our guts and our central nervous system. Tweaking those signals with a therapeutic might impact a variety of diseases. The startup isn’t alone in that pursuit.

New York-based Kallyope formed last year from research at Columbia University to examine the gut-brain axis as well. It hasn’t disclosed which diseases it intends to pursue. And various industry and academic groups have been exploring how the gut and the brain communicate, and how that impacts human health. That work has started to illuminate the relationship between the gut and other aspects of human physiology, such as metabolism, anxiety, and depression. As Kallyope CEO and Merck veteran Nancy Thornberry told Xconomy last year, “gut biology relative to other areas is in its infancy.”

“It is difficult to differentiate us from Kallyope as their focus is not really clear,” Donabedian says. “Targeting the gut-brain axis is a broad field.” (To see just how broad, check out this July feature from The Scientific American for a look at some of this research and how it’s being applied to drug making.)

Caltech’s Mazmanian is a pioneer in the space and is a co-founder of Axial. The firm aims to develop drugs for neurological diseases based on his recent work. In 2013, for instance, Mazmanian co-authored a paper published in the journal Cell examining the link between a certain type of gut bacteria, B. fragilis, and autism. Autism and Parkinson’s disease—two notoriously difficult neurological diseases to treat—are among the first potential targets of Axial’s drugs.

What form will these drugs take? Kallyope has said it wants to develop small-molecule drugs or nutritional products to cross up the signals gut microbes send to the brain. Other companies like Seres Therapeutics (NASDAQ: MCRB) develop cocktails of bacteria to balance the good and bad bacteria in our guts. But the first big test of a microbiome-based drug—a Phase 2 trial of Seres’s experimental SER-109—came up woefully short, highlighting how little we know about the relationship between the microbiome and human disease.

Donabedian says Axial’s range of products could be “quite diverse” depending on the disease and regulatory strategy. The company could develop therapeutic bacteria, or it might try to tweak the microbiome in other ways. The company has developed screening tools to help unearth drugs that can target “both microbes and microbial entities,” Donabedian says.

Depending on which way Axial decides to go, it could bring its first drug candidate into clinical testing within 18 to 24 months, he says.

Domain Associates and Longwood Fund led the financing round. Kairos Ventures, Heritage Medical Systems, and some unnamed high net worth individuals in Southern California also participated. Mazmanian, Longwood partner (and former OvaScience CEO) Michelle Dipp, and Domain partner James Blair are on Axial’s board.