effectively work as tiny drug-making factories. These microbes, Mahadevia says, can be manipulated to identify and react to specific things—like molecules tied to a disease process, or a physiological environment that’s too acidic or basic—and then shut down and literally “blow themselves up” when they’ve done their job.
That means that, in theory, Synlogic could engineer a microbe that could sense an infection going on in the gastrointestinal system, secrete a therapeutic molecule (an antimicrobial peptide, for instance) to hit it directly, and then stop when the infection is eradicated and self-destruct while still in the gut. Mahadevia adds that Synlogic can tune the microbe’s response up or down depending on what’s needed, and that these bacteria can be loaded up with a number of potential functions—like a complex computer program.
“That requires exquisite integration amongst those circuits—it’s something we can do that’s not trivial,” Mahadevia says. “You can just do the permutations, and the opportunity to produce things that are missing in the GI system, or process things that shouldn’t be there, or create a therapeutic where it’s relevant, or not when it’s not, is pretty cool.”
Indeed, the potential advantage here over some other drugs designed to treat gastrointestinal diseases, for example, is specificity. Mahadevia says that a number of the side effects tied to drugs for GI diseases arise because those drugs run through the bloodstream and impact healthy cells. They don’t just get to the gut, find the problem, and attack it while leaving other tissue unscathed.
“You think about some of the GI disorders that we treat with systemic therapies—you could treat them locally in this case,” Mahadevia says, though he declined to name the ones Synlogic is eyeing specifically.
That potential is what brought Atlas to the table to seed the company last year, and led NEA to join up. Now the challenge is to move Synlogic past the successful lab experiments, and turn it into a real company.
The Series A funding is designed to get Synlogic to the doorstep of its first clinical trial, and as the size of the round shows—it’s much larger than some of Atlas’s recent early deals in biotech—it’s likely to be a capital-intensive operation. Mahadevia notes that a company like Synlogic is “best served as having bricks and mortar scientific facilities,” rather than being an exclusively virtual operation.
Mahadevia acknowledges the challenges ahead, like choosing the right potential applications, and of course making sure the bacteria do their job effectively and then stop when they should, when they’re finally given to humans.
The company is essentially hoping to advance as many programs as it feasibly can, and Mahadevia says Synlogic is in talks with potential partners that have different ideas than Atlas and NEA have had about how to use Synlogic’s platform, hoping to cut some deals. The company may add a few strategic investors to its Series A round “relatively soon,” according to Mahadevia.
“It’s incumbent on us to make sure we push the envelope, think of the breadth of the platform, and find like-minded folks who can help us take it forward,” he says.
