Synthetic biology has become something of a biotech buzz-phrase—lots of lab experiments and hype, yet little tangible impact on patients to show for it.
Still, new ideas keep coming out of the startup world to finally harness the potential that comes with genetically engineering biological parts and systems, with the promise of making a huge difference in healthcare. Today, one of those ambitious ideas is taking shape in a Cambridge, MA-based startup called Synlogic, which aims to whip up a line of custom-made bacteria that double as little drug-making factories.
Synlogic today is coming out of stealth mode with a $29.4 million Series A commitment led by founding investor Atlas Venture and New Enterprise Associates. Synlogic isn’t getting all that cash up front, of course—it’ll come in tranches tied to the company’s progress—but the big sum will help the startup embark on a difficult, yet high-reward scientific quest: perfecting a method of manufacturing microbes that are programmed to sense a specific disease or infection, secrete a drug to treat it, and then self-destruct when they’re done.
The idea of packing bacteria into a pill isn’t new, of course. You can buy probiotic supplements at your local GNC, and the evolving scientific understanding of the human microbiome—the trillions of good and bad bugs that live in our bodies—has led to new startups like Seres Health and Vedanta Biosciences, among others.
Synlogic, however, is taking cues from both microbiome research and synthetic biology. The result is a company that Synlogic co-founder and Atlas venture partner Ankit Mahadevia says owns a “next generation” synthetic biology technology: one that can be used to micromanage and “tune”—up or down, very specifically—the activities of genetically-engineered bacteria.
“We’re taking a concept that I think has been long recognized as therapeutically viable, but has been difficult to execute because of the limitation of tools out there,” Mahadevia says. “Now we have a set of tools that really opens up the landscape widely for what we can do.”
Still, it’ll be some time before Synlogic will be able to prove its method can safely and effectively treat human disease. Right now, Mahadevia says the company is sifting through several potential applications for the platform and choosing which ones to pursue. He estimates that the company is “a couple years off” from filing its first papers with the FDA seeking permission to begin a clinical trial.
Synlogic doesn’t have a management team yet—although Mahadevia says those names should be announced “relatively soon”—and is in the process of setting up an office in the Kendall Square area. The company’s board currently consists of Mahadevia, Atlas partner Peter Barrett, and NEA partner Ed Mathers. Dean Falb, formerly of Millennium Pharmaceuticals, is running the company’s scientific operations so far. Alison Silva, a former executive at Cequent Pharmaceuticals (now owned by Marina Biotech), is Synlogic’s chief operating officer.
Mahadevia has been involved in two other Atlas seed projects that have gone on to become full-fledged startups in the past few months: neurology startup Rodin Therapeutics (Mahadevia is the company’s chief business officer), and antibiotics developer Spero Therapeutics (where he’s acting president and chief business officer). As it turns out, Mahadevia’s experience with Spero directly led to the creation of Synlogic.
As Mahadevia was helping to build out Spero, Boston University professor James Collins, one of the pioneers in synthetic biology and understanding how antibiotics work, came aboard as an advisor. During that time, Collins introduced the Atlas team to some other work he and a former postdoc, MIT professor Timothy Lu, were doing.
Collins and Lu, according to Mahadevia, have been developing and getting patents for a platform to genetically engineer microbes that 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.