Five Takeaways From “Boston’s Life Science Disruptors”

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idea for engineered microbes that could serve as living drugs or diagnostics. Mahadevia’s response: “We really want to do something with you guys, we just don’t know what.”

A month later, Atlas decided no to the tools, and yes to the living drugs. But how to use them? Collins’s preference—wiping out infectious diseases, like a cholera infection. Mahadevia’s response: “We still want to do something with you guys, we just don’t know what.”

It took a suggestion from Atlas entrepreneur-in-residence Dean Falb to figure out what to do. He showed Collins a list of 12 rare genetic metabolic disorders, all of which Collins had never heard of. The microbes made sense here—they could either make a metabolite that is missing, or break down a toxic one. The medical need is significant, and Synlogic could run small, inexpensive clinical trials for it.

“I thought this was brilliant,” Collins said. Synlogic is now targeting phenylketonuria and urea cycle disorders.

How to make living drugs less risky. The idea of living drugs that can switch on and off inside your body sounds great—and risky. Engineered bacteria, Gutierrrez-Ramos said, are going to pose a challenge for regulators. So Synlogic has decided to do a few things to minimize that risk. First, it’s going to use probiotic bacteria that are already part of the human microbiome—the trillions of bacteria that colonize our bodies. Second, the components of the  “genetic circuits” engineered into these bacteria are coming either from human genes, or those of other bacteria in the microbiome. And lastly, Synlogic decided to use bacteria that don’t colonize in the gut, but instead would be taken as a pill every day and survive just 18 or so hours.

“We’re going to make sure that patients, payers, and regulators feel very comfortable,” Gutierrez-Ramos says. The first trials of Synlogic’s drugs should begin next year.

Building Seres: A long, sometimes smelly journey. When Flagship Ventures began looking into the idea of starting a company based on the microbiome in the late aughts, it did so with little if any technology available to capitalize on. What it did know, Afeyan said, was that the sequencing of the microbiome was revealing a “lot of interesting insights,” like that bacteria in our bodies were making chemicals that had a lot of influence many of our systems. So Flagship started several “proto-companies” to see if it was worth taking a stab at the field, and this led them to fecal transplants—which are exactly what they sound like, and are often used, quite effectively, to stop a bacterial infection known as Clostridium difficile. “What we found out probably earlier than anybody, is that [doctors] all did it differently, and they got the same result,” Afeyan said. “Any time you see that happen, you’re over-specifying the solution.”

So Flagship identified a group of microbes it believed to be wiping out C. diff in these fecal transplants, set up a lab, found what it was looking for, and Seres emerged. Last year, the drug to emerge from that work, SER-109, produced data that were good enough to support a roughly $140 million IPO.

“We just followed the data that was being generated opportunistically,” Afeyan said.

Unimpressed with your CEO candidates? Just hire yourself. Pomerantz left a high-profile position at Merck a few years ago and promised his wife he wouldn’t take another role in company operations. He’d just join boards, and “have a nice life,” he said. Then Seres came along and that changed everything. He started with a board seat, was pushed by Afeyan to be chairman, and then in that role began interviewing candidates for CEO.

The problem: Pomerantz wasn’t satisfied. The candidate had to have a background in infectious diseases, drug development, and business. It’s pretty uncommon for someone to have experience doing all three, Afeyan said, and Pomerantz “kept telling me all the things that were wrong with the candidates.” That left Seres with few options. Well, actually just one: “I pulled a Dick Cheney and thought about hiring myself,” Pomerantz said.

He was named CEO in June 2014.

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