Treating autism through the gut? Axial Therapeutics refuels on its exploration of the gut-brain axis
If Stewart Campbell had said five years ago that you could treat conditions of the brain through the gut, you probably would have thought he was crazy — or at least that’s what he likes to say.
Since then, a crop of biotechs exploring the gut-brain axis has gotten the attention of some well-known investors. Campbell’s Axial Therapeutics is now the latest, unveiling a $37.25 million Series C round on Wednesday morning that brings the company’s total raise to just over $90 million.
The extra cash will be used to conduct a Phase II trial of the company’s lead program, a gut-restricted molecular therapy for irritability in children with autism called AB-2004.
Axial’s science traces back to a platform that professor Sarkis Mazmanian had brewing in his lab several years ago at Caltech. His team published research from animal studies that established a link between the population of tiny microbes in your body and the course of autism spectrum disorders. In 2016, he and the Longwood Fund’s David Donabedian spun that research into a company, which Donabedian ran until handing the reins to Campbell earlier this year.
AB-2004’s mechanism of action begins with microbes in the gut that digest protein down to their component amino acids, which are further digested into something called small molecule metabolites. A certain class of these metabolites are then absorbed by the blood and can travel to the brain, Campbell explained. There, scientists have shown that the metabolites can alter the development of certain brain cells — in particular, cells that produce myelin.
If you think of an electrical wire, there’s usually a plastic coating to insulate the wire and keep it from short-circuiting, Campbell said. That’s what myelin is for neurons. When cells that produce myelin are prevented from maturing properly, Axial believes behavior is affected, like danger sensing or fear conditioning.
“That’s the way we connect all those dots from the gut microbes all the way to behavior,” he said.
AB-2004 is designed to pass through the gut, picking up metabolites almost like a sponge, then pass through the stool, lowering metabolite levels in the gut, and therefore in the brain. It’s an oral medication that would need to be taken three times per day with food (though Campbell says they’re working on formulations that could be taken twice or even once per day). The company recently read out Phase Ia/IIb data that showed the candidate was safe, and that it reduced several key GI neuroactive microbial metabolites in the plasma and urine.
“We think it has got a strong safety profile, because we don’t need to get it in the body or into the brain at all in order for it to work,” Campbell said.
Axial is planning on launching a Phase II trial soon, which should read out in 2023, Campbell said. They’ve also got preclinical programs in Parkinson’s disease and oncology in the works.
When asked if an IPO is in the future, Campbell responded with a chuckle: “No idea.”
“We’re so focused right now on just getting this execution toward our milestones and (moving) our programs ahead,” he added.
Australian VC firm OneVentures led Axial’s latest round along with the University of Tokyo Innovation Platform Company. The Autism Impact Fund, Corundum Systems Biology, the Longwood Fund, Seventure Partners, Taiho Ventures, and Domain Associates also chimed in.
Axial is one of several microbiome companies exploring the gut-brain axis, including Kallyope, which landed a $112 million Series C round last year. Novo Nordisk has dipped its feet, inking a partnership with Kallyope in obesity and diabetes back in 2018.
“Autism and Parkinson’s are the tip of the iceberg for us,” Campbell said. “This is a very different way and we hope this is really like a phase shift in how we think about neurological disorders.”