Axial Biotherapeutics

Axial is working to treat CNS disorders in a three-pronged approach through the gut-brain connection.
Fierce 15

This biopharmaceutical company is targeting the gut to heal the brain.

CEO: David Donabedian
Founded: 2016
Based: Boston
Clinical focus: Diseases and disorders of the central nervous system

The scoop: Axial is working to treat CNS disorders in a new way—one that doesn’t involve the blood-brain barrier. Instead, the biotech has a three-pronged approach to treat disease through the gut-brain connection. This includes small-molecule and biologic treatments, as well as bacteria-based therapies to modify the gut microbiome and affect changes in the brain.

What makes Axial Fierce: A number of diseases and disorders fall under the CNS umbrella, ranging from mood disorders and neurodegenerative diseases such as Alzheimer’s and Parkinson’s to conditions caused by infection or trauma.

The blood-brain barrier protects the brain from infection but also stops nearly all small and large molecules from entering the organ, which has hindered efforts to develop neurotherapeutic drugs. The gut, says Axial CEO and co-founder David Donabedian, is a more receptive tissue, which can help reduce off-target effects that can come when drugs target the blood-brain barrier.

“It is a totally disruptive approach to target the gut and not the brain for CNS disorders,” Donabedian said. “Localized therapy in the gut has never been done before in diseases believed to be of CNS origin.”

Axial started out last fall with a $19 million investment and the global rights to the work of co-founder Sarkis Mazmanian, a professor of microbiology at Caltech. The biotech’s lead programs are in Parkinson’s and autism spectrum disorder.

In December, Mazmanian’s lab published the first study that suggests changes in the gut microbiome could have a hand in the onset and severity of Parkinson’s disease. The study used mice that overexpressed alpha-synuclein, a protein believed to affect the progression of the neurodegenerative disorder.

“When we transplanted the microbiome from Parkinson’s patients into mice, we found that symptoms like motor deficits and neuroinflammation were more severe compared to mice harboring gut bacteria from healthy controls,” Mazmanian said at the time. “This suggests there is a fundamental relationship between bacteria in the gut and the disease processes involved in Parkinson’s.” Mazmanian is now working to identify the specific bacteria involved.

As for autism, many children with autism spectrum disorder also have gastrointestinal distress, and a subset of these patients doesn’t have a particular species of gut bacteria, Donabedian said. When Mazmanian added this bacterium back into mouse models of autism, it addressed behavioral symptoms and solved GI problems.

While the gut is a promising route to the brain, for Axial, targeting the gut microbiome isn’t just about finding new targets and creating new drugs. It also offers new ways to measure drug efficacy. Looking at bacterial biomarkers in the gut could help drug developers objectively assess whether a treatment is actually working.

“We can look at biomarkers to change disease and not just at behavioral or motor symptoms, which can be subjective,” Donabedian said. And that’s not all. Further on, patients could even be stratified for treatment based on their level—or lack—of a particular microbe or metabolite.

Axial is currently working on a bacteria-based intervention, a biological intervention and a small-molecule therapy for Parkinson’s, and is “rapidly advancing” a small-molecule and biological approach for autism spectrum disorder. It expects to move treatments into the clinic within the next 12 months.

To that end, Axial has secured office space in Boston, built out its team—which included poaching Srinivas Rao from Depomed to be its chief medical officer—and established a clinical/scientific advisory board around autism spectrum disorders. Soon, the company plans to announce “a top-tier group” in neurology, Parkinson’s, GI and the microbiome, Donabedian said.

Investors: Longwood Fund, Domain Associates, Kairos Ventures, Heritage Medical Systems and a group of “high net worth individuals.”

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Axial Biotherapeutics