Biotech venture group Flagship Ventures is doubling down on the microbiome. The Cambridge, MA-based firm, which specializes in building new therapeutics companies in stealth mode, today launched Evelo Therapeutics, its second microbiome-based startup, with $35 million in funding to develop cancer treatments fashioned from mixes of bacteria found in nature.
The effect of bacteria on cancer has been known for more than a century, ever since New York doctor William Coley in the late 1800s 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.
CEO Simba Gill of Evelo, pronounced “eh-VEL-oh,” acknowledges his company is piggybacking on “a foundation of deep scientific knowledge.”
“We’re building on old observations that bacteria have potent effects on cancer, with strong activation of the innate and adaptive immune system,” he says.
There is, in fact, already a bacterial therapy for cancer: a modified version of bacillus Calmette-Guerrin, or BCG, used for decades to treat early-stage bladder cancer.
And other groups have more recently made progress with modified bacteria as weapons against cancer. But Gill says Evelo wants to do something novel: create mixtures of naturally occurring, unmodified bacteria as cancer therapies.
The crux of that work stems from a database of bacteria that have been isolated from human cancer tissue and have had their properties characterized. It is work that Flagship began within its skunkworks-like group called VentureLabs.
“Other academics and organizations have looked at modified bacteria as single products, and there’s already a bacterial therapy on the market,” Gill says, “but nobody is systematically looking to understand the biology.”
So far, bacteria-based therapies derived from the huge wave of microbiome research the past several years have focused on diseases of the gut. For example, Seres Therapeutics is developing a bacterial mix that, when swallowed, would help fight infection from the bug Clostridium difficile, which invades the bowels of people whose healthy bacterial mix has been wiped out by antibiotics or chemotherapy. C. difficile infected an estimated 500,000 people in the U.S. alone in 2011, according to the Centers for Disease Control, and killed nearly 30,000 of them within 30 days of infection.
Rebiotix of Roseville, MN, and the nonprofit stool bank OpenBiome of Medford, MA, are also pursuing bacterial C. difficle treatments. Others such as Vedanta Biosciences and Second Genome are using microbiome insights to tackle more complicated gastrointestinal diseases.
Flagship also launched Seres—then as Seres Health—in 2011. Gill said that Evelo is not a spinout of Seres and does not derive any of its intellectual property from that company. “Our IP is all coming from Flagship’s VentureLabs,” he says.
Evelo is working on preclinical product candidates, but Gill declined to say when the first one might reach clinical trials. Bacteria in the therapeutic mix will be selected to navigate to tumors and the immediate surrounding tissue, known as the tumor microenvironment, which includes blood vessels, immune cells, and more. There is a complex interplay between the cells of a tumor and the normal cells just beyond, and Gill says there are “multiple opportunities” for bacteria to have an effect, such as directly killing tumor cells or disrupting tumor metabolic processes.
Those developing modified bacteria to treat cancer say Evelo’s work could mark a new approach.
“We are not aware of efforts to develop bacterial mixes as therapies,” says David Chao, the president and CEO of BioMed Valley Discoveries, a Kansas City, MO-based company running a Phase 1 trial with a modified bacterium, Clostridium novyi-NT. That effort grabbed attention last year when researchers at Johns Hopkins University, BioMed Valley—a for-profit offshoot of Kansas City’s Stowers Institute for Medical Research—and others published a paper on preclinical results.
The microbiome is the trillions of bacteria and other microbes living in and on our bodies, most prevalently in the gastrointestinal tract, respiratory tract, and on the skin. But bacteria are found everywhere in our bodies, and Evelo CEO Gill says his company won’t limit its R&D to tumors that grow in the GI tract and other places where the bulk of microbiome research has focused. “The lung, prostate, breast, they are all areas where cancer-associated bacteria have been found,” Gill says.
Gill is a veteran of San Francisco Bay Area biotech. He worked with Draper Prize-winning chemist Willem “Pim” Stemmer at Maxygen and various spinouts. (Stemmer passed away in 2013.)
Evelo’s entire $35 million fundraise came from Flagship, Gill says.
