With Bugs As Drugs, Evelo CEO Plans Immune, Cancer Trials in 2017

Xconomy Boston — 

While the Obama administration wants to dedicate a tiny sliver of the federal budget to microbiome research, a growing number of startups—often with the backing of international corporations—are racing to turn microbiome research into health products.

The Cambridge, MA-based firm Evelo Biosciences wants to harness live bacteria as cancer and immune-disease treatments. Evelo, which launched last year with a cancer-fighting agenda, is expanding into immune and inflammatory disease, the company announced today. Evelo is absorbing the work of stealthy Epiva Therapeutics, which, like Evelo, began inside a skunkworks-like group called VentureLabs, which is part of the Cambridge biotech investment firm Flagship Ventures.

The combined company, which will keep the Evelo name, aims to get at least one cancer treatment and one immune-related treatment into clinical trials next year, said Evelo CEO Simba Gill. He declined to specify which diseases might be first in line.

If that comes to pass, Evelo would join Seres Therapeutics, Rebiotix, Second Genome, and OpenBiome with microbiome-related medicines being tested on humans. Some of those products are mixes of bacteria—that’s also Evelo’s aim—and some are more conventional drugs that aim to change the way microbes interact with their human hosts. Major drug and nutrition companies such as Nestle, Danone, and Johnson & Johnson have partnered with some of the smaller companies to gain a window into the new field or grab partial rights to the first wave of products.

Evelo and Epiva began as sister projects, the former to explore the role of bacteria in cancer, the latter the role of bacteria in autoimmune and inflammatory diseases. Both wholly funded by Flagship, they were building separate banks of bacteria and separate laboratory facilities to screen the bacteria in oxygen-free conditions that mimic life inside the body. Only in recent months, the companies’ management realized the efforts were duplicative. “They were mirror images,” said Gill. “But it wasn’t clear two and a half years ago that we’d need a common technology base. We were working through many different ideas.”

The notion of bacteria fighting cancer stems from the work of New York doctor William Coley in the late 1800s, who noted how cancer patients recovered more rapidly when they also came down with a bacterial infection. He then injected his patients with the bacterium S. pyogenes and reported good results—the birth of immunotherapy—but the practice faded with his death in the 1930s, replaced by chemotherapy and radiation.

In the age of rapid genome sequencing, the DNA of the trillions of microbes that live in and on us is coming to light, as are the connections between those bugs and human health, and the subtle conditions in which “bad” bugs might play a good role and vice versa. Evelo’s aim is to figure out which bacteria stimulate an immune response that might fight different types of cancer, and under which conditions. Epiva’s role is to discern which bacteria might suppress the immune system and tamp down inflammation or immune-related diseases.

The ideas Evelo has settled on are offered only in outline form. Gill said it will first seek to deliver unmodified bacteria into specific parts of the gut that act as immune surveillance, or perhaps deliver them systemically right into a tumor site. The company’s exact methods are a secret, said Gill. But he says the idea of having patients swallow a dose of live bacteria that have a therapeutic benefit outside the stomach, elsewhere in the body, is particularly intriguing.

Even if Evelo is successful getting bacteria, either as a single species or as a mix of species, to the right spot, many questions remain.

It’s relatively straightforward to deliver a cocktail of bacteria into the gut to fight a gastrointestinal infection; the bacteria themselves are replenishing a natural but barren defense against an invasive bug. (That’s the goal of Seres (NASDAQ: MCRB), also a Flagship company, whose experimental treatment for the deadly Clostridium difficile (pictured) is inspired by the success of fecal microbiota transplant and could produce important clinical data this summer. OpenBiome, a nonprofit in Medford, MA, also distributes low-cost fecal transplant capsules.)

It’s more complicated, however, to help bacteria survive the teeming gut and stimulate an immune response in another part of the body; or make their way through the bloodstream to a tumor or inflammation site. To treat cancer, for example, would the bacteria need to remain in their target niche and grow to provoke an immune response? If so, Evelo must ensure that they don’t grow out of control, said William Phelps, director of the preclinical and translational cancer research program at the American Cancer Society in Atlanta. Phelps is not connected with the company.

Another problem, noted Phelps, is that a heightened immune response could also wipe out the bacteria, which could make sustained growth difficult. It could also render a second dose, if needed, ineffective. “The immune system would be educated,” said Phelps, “meaning you have a ‘one and done’ response.”

Gill said Evelo would address these obstacles, but he was spare on details. “Dose and formulation are important,” he said, and to help medicinal bugs navigate the gut, some “clearing” of other bacteria in advance might be necessary.

Flagship launched Evelo last year and pledged $35 million in funding. It has also sunk $5 million in Epiva. The funding should last 12 to 18 months into the start of clinical trials, said Gill. And the cash, combined with the hundreds of millions of dollars that Seres and other firms have raised privately and on the public markets, dwarfs the $121 million the Obama administration pledged earlier this year when it announced its national microbiome initiative.

Image of Clostridium difficile courtesy of the U.S. Centers for Disease Control.