Synlogic Nabs $40M, Prepares To Put Modified Microbes Into Patients

Xconomy Boston — 

Synlogic just inked its first partnership, with AbbVie, last week. Today the Cambridge, MA-based startup got the cash needed to get to another first: tests of its genetically altered microbes in human patients.

Synlogic has raised a $40 million Series B round led by new investor Orbimed HealthCare Fund Management. The company—founded in 2014 by Atlas Venture and New Enterprise Associates, which also participated in the round—has now raised about $70 million since inception.

Synlogic will use the cash to get its first two programs into clinical testing. Both aim to treat rare metabolic diseases: phenylketonuria, which causes the amino acid phenylalanine to build up in the body, and urea cycle disorders, in which the body’s waste-disposal system malfunctions.

Those studies should begin early next year, according to Synlogic CEO Jose-Carlos Gutierrez Ramos.

Synlogic is based on the work of MIT professor and synthetic biology pioneer Jim Collins and his protégé Timothy Lu. The concept they came up with sits at the nexus of two fields: the human microbiome, the trillions of bacteria that colonize our bodies; and synthetic biology, in which the genes of living organisms are modified to change what those organisms do.

The result is what Synlogic calls “synthetic biotics,” engineered microbes that could serve as living drugs. These microbes 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 are equipped with various fail-safes to make sure they stop when their job is done. Then they’re packed into a pill that the patient swallows.

Collins initially thought to use the technology to develop diagnostics or treatments for infectious diseases like cholera.  But as he told Xconomy last year, Synlogic’s venture backers steered the company toward rare genetic metabolic disorders, where the microbes could be used to, for instance, break down a toxic protein that is harming the patient (like phenylalanine in the case of PKU patients). Microbes, like any other single cell, make proteins; Synlogic wants to harness that power and reprogram them, effectively turning the microbes into little controllable drugmaking factories.

These diseases could prove a good initial testing ground for the technology, because the medical need is high, and the trials Synlogic would have to run are small and inexpensive.

Synlogic brought in Gutierrez-Ramos—a former Pfizer executive—last May to run the company.

The cash raise comes just days after Synlogic inked its first partnership, a collaboration with pharma firm AbbVie to develop drugs for inflammatory bowel disease. The deal is likely a small bet by AbbVie—financial terms weren’t disclosed—to find a successor to its wildly successful adalimumab (Humira), which is approved for autoimmune disorders, among them Crohn’s disease and ulcerative colitis, the two types of inflammatory bowel disease.

For Synlogic, the AbbVie deal fits thestrategy Gutierrez-Ramos is trying to institute: A focus on rare diseases in-house but with big-company partnerships for diseases that require large, expensive clinical trials. Should any drug candidates come out of the AbbVie deal, for instance, AbbVie will pay for clinical development, and get worldwide rights to those drugs. Gutierrez-Ramos says Synlogic is exploring the technology’s potential use in autoimmune diseases like lupus, arthritis, or multiple sclerosis, and metabolic conditions like diabetes, with additional AbbVie-like partnerships in mind.

Synlogic is banking that its two lead candidates, for urea cycle disorders and phenylketonuria, will require smaller trials that take less cash to complete than studies in more common diseases. Gutierrez-Ramos says that Synlogic can get a signal that its drug is working in PKU, for instance, if it’s tested in a sample size of 30 to 40 patients. In IBD, that would take a few hundred, he says.

But first Synlogic has to reach those studies, a more difficult challenge than it would be with yet another small molecule or antibody drug. Synlogic has to convince regulators that it’s safe for people to ingest genetically engineered bacteria before it can begin testing them in people. “Clearly [these drugs] will have a different type of regulatory scrutiny—and they should,” Gutierrez-Ramos says.

Synlogic has already taken a few steps to address potential problems. For instance, it is using probiotic bacteria that are already part of the human microbiome—in other words, bacteria that our bodies already recognize and theoretically won’t trigger unintended consequences. Synlogic is wiring those bacteria with genetic circuits that come either from human genes or those of other bacteria in the microbiome. It’ll also use bacteria that survive for a short time, rather than colonize the gut.

“This is the armamentarium that we will take in [to discussions with regulators],” Gutierrez-Ramos says, noting that the outcome of those meetings will be a “very important milestone” for the company.

Should Synlogic get the green light to start human testing, would success in these initial studies propel the company towards an IPO?  Flash back to just a year ago and a round like this, which includes a “crossover” investor, Deerfield Management, was all but a guarantee that an IPO was on the way. But biotech has tumbled, and the IPO market has become shaky ever since. Synlogic is taking its time.

“I don’t want us to get distracted by things we can’t control,” says Gutierrez Ramos, speaking of the public market for biotechs. “If we get a significant signal [that our drugs work in humans] as I hope we will, then we’ll see what the market is and what the next step is.”

OrbiMed private equity partner Chau Khuong joined Synlogic’s board as part of the funding.