Biotech companies are closer than ever to harnessing the healing power of poop. Three Boston firms are racing to develop pills based on a medical procedure called fecal microbiota transplant, in which feces from a healthy individual — teeming with good gut bacteria — are collected, processed, and given to a sick person via colonoscopy, enema, or pill.
Fecal transplants are being tested in numerous diseases with the aim of healing a person’s gut microbiome, the trillions of microscopic denizens that live in our digestive tracts. The procedure has made the biggest strides in treating recurring infections of a deadly bacterium called Clostridioides difficile, or C. diff. But exactly how the transplants work has remained somewhat of a mystery.
Vedanta Biosciences chief executive Bernat Olle said his firm wants to move microbiome therapies “beyond the black box that is fecal transplantation.” Or to put it another way, Vedanta wants to take the poop out of poop pills.
Vedanta has opened a new manufacturing plant alongside its existing labs in Cambridge to grow eight strains of bacteria that it believes are responsible for the curative properties of fecal transplants. By growing these bacteria in-house, freeze-drying them, and packaging them in pills, Vedanta could offer a fecal-free alternative for patients with C. diff.
In contrast, the firm’s three biggest competitors — Seres Therapeutics in Cambridge, Finch Therapeutics in Somerville, and Rebiotix in Roseville, Minn., — all rely on stool donations to make their treatments for C. diff.
All of these therapies are still experimental, but Seres is closest to the finish line with its pill of bacterial spores purified from stool. The company is expected to finish submitting its therapy for C. diff to the Food and Drug Administration this summer. It could become the first microbiome-based therapy approved by the FDA next year. Finch expects to begin its advanced clinical trial of its pill of stool-derived bacteria later this year.
Although Vedanta is further behind, experts are excited by the firm’s approach. Its scientists and engineers will stay busy through the rest of the year making the pills for its advanced clinical trial, which could start early next year, Olle said. That study will mark the first time a microbiome therapy based on a carefully selected group of lab-grown bacteria reaches the advanced stages of testing.
“It speaks volumes to the progress of this field,” said Jeffrey Heiser, a vice president at Arranta Bio, a contract manufacturing firm in Watertown that specializes in microbiome therapies.
Although ribbon-cutting ceremonies for new labs are a dime-a-dozen in Boston, several experts said that Vedanta’s new manufacturing suite is a sign that the microbiome industry is maturing and moving away from fecal-derived products.
“It is really a milestone for the field,” said Dr. Majdi Osman, chief medical officer of OpenBiome, the Somerville nonprofit that collects and distributes stool donations to doctors treating patients with C. diff. “Being able to do high- quality manufacturing is so important.”
An observational study led by Osman and published in April found that about 80 percent of people who received a fecal transplant were subsequently cured of their C. diff infection. But despite those results, OpenBiome has begun winding down its C. diff operations in anticipation that one or more companies will begin selling an FDA-approved therapy in the next year or two.
“We have always considered this to be a stopgap measure until a therapy is able to get through the FDA approval process,” Osman said.
So far the results of the newer therapies look promising. About 88 percent of patients who took the Seres pill remained free from C. diff eight weeks after treatment, compared to 60 percent of patients who received a placebo, in the company’s Phase 3 study. Vedanta’s intermediate Phase 2 study reported similar results. About 86 percent of patients who got the pill recovered, compared to 54.5 percent of those who got a placebo.
“I think the field has always viewed fecal transplants as a great proof of concept and a blunt tool that we can definitely improve upon,” said Stephanie Culler, cofounder and chief executive of the microbiome startup Persephone Biosciences in San Diego. “It’s imminent that we’re going to get an approval in the space.”
Vedanta says that one of the biggest advantages to its approach is safety. Stool donations used in fecal transplants must be extensively screened to avoid unintentionally spreading harmful pathogens, but sometimes a bad bug slips through. In 2019, a 73-year-old man died at Mass General Hospital after receiving a fecal transplant that contained an antibiotic resistant strain of E. coli. And during the pandemic, fecal transplant work slowed because of concerns about spreading SARS-CoV-2 through feces.
The death at MGH and the pandemic “highlighted that there are probably many unknown organisms transmitted that we weren’t really testing for or controlling,” said Dr. Alan Moss, a gastroenterologist at Boston Medical Center and a professor of medicine at Boston University. Growing the bacteria in the lab could be “a far safer approach for patients,” he added.
Dr. Elizabeth L. Hohmann, an infectious disease doctor at MGH, agreed that Vedanta’s lab-grown bacteria and Seres’s purified bacterial spores should be safer than transplanting the whole ecosystem of microbes, as is done in a fecal transplant. “But with any of these things there are inherent risks,” she added, and that risk can vary between people.
Not everyone who received the E. coli-infected stool at MGH died, she said. “Many other people who received that particular donor’s materials did swimmingly well, including other cancer patients,” Hohmann added.
In addition to being potentially safer, Vedanta hopes that its pills will lead to more consistent benefits than fecal transplants, which have varying compositions of bacteria. Each of Vedanta’s pills will have equal amounts of the eight bacteria selected for their ability to overcome C. diff. The firm has the capacity to make about a million pills per year.
Seres once had a program for C. diff based on lab-grown bacteria, but the company decided to move forward with purified spores, since it was “the fastest path” toward a commercial therapy, said chief technology officer David Ege.
But his company is testing a therapy for ulcerative colitis, a form of inflammatory bowel disease, based on lab-grown bacteria.
Vedanta has earlier stage programs focused on identifying specific combinations of bacteria that could be used to quell inflammatory bowel disease, suppress food allergies, or even improve the effectiveness of cancer immunotherapies. Olle said that the firm’s new manufacturing facility will help them make pills for those programs and others.