Scientists at microbiome therapy developers often talk about the importance of community, how the bugs in our gut act in concert in addition to their individual roles. That’s important for microbiome health and for microbe-based therapies, says Emily Drabant Conley, CEO of startup Federation Bio.
Conley’s company is developing therapies that build on the understanding of the microbiome community. It’s also going a step further by engineering some bacteria to take on new roles fighting disease. The biotech now has $50 million to advance its most advanced program toward human testing for a rare metabolic disorder.
South San Francisco-based Federation Bio is developing two microbiome technologies. The first is a platform that curates naturally occurring gut bacteria to form a large and diverse community of microbes. The second technology enables the company to engineer certain microbes with the ability to interact with the immune system. Both technologies could have become separate companies, Conley says. But Venrock, which provided Federation Bio’s intial funding nearly two years ago, saw the potential for overlapping the technologies to develop different types of microbiome treatments: a community of microbes, a single engineered strain, or a combination of the two. The startup’s lead therapeutic program takes the community approach with a curated community of different microbes that work together to make an effective and durable treatment.
“We believe that in order to have complete metabolic function, you need this high diversity,” Conley says. “Diversity here is the key.”
The therapy is a potential treatment for secondary hyperoxaluria, a condition in which oxalate from food builds up in the body. Oxalate is found in leafy greens such as spinach and kale, but it’s not needed by humans so the body gets rid of it in waste. However, some people have problems excreting it. The condition can also develop as a complication of gastric bypass surgery. In addition to reducing how much food and nutrients are absorbed, the surgery also diminishes the small intestine’s ability to absorb oxalate and pass it from the body in urine. Consequently, patients can develop kidney stones and renal failure.
The Federation Bio therapy is comprised of microbes from healthy human fecal donors. The company has analyzed the bacteria to understand their roles and functions. It has identified bacteria in this community whose sole source of food is oxalate. But Conley says it’s not enough to have a therapy comprised of oxalate-eating bacteria. Federation Bio surrounds its experimental therapy with other bacteria from the community.
The community is why patients won’t excrete the therapy each time they answer nature’s call. The Federation Bio approach is based on findings from early fecal microbiota transplant research, Conley says. Patients were treated with antibiotics to clear out their gut microbiomes, then transplanted with a single dose of fecal matter from healthy donors. Three to five years later, most of those patients still had the transplanted microbiome in their guts. Federation Bio aims to see if the same thing happens with its microbiome therapy.
“The theory is the space was made for [the community of new bacteria] to take up residence, and they can coexist, stay there long term,” Conley says. “This is something we need to study in humans and we’re not there yet.”
There are other companies developing treatments for secondary hyperoxaluria. Newton, MA-based Allena Pharmaceuticals (NASDAQ: ALNA) has advanced to late-stage testing with reloxialiase, an enzyme-based therapy that degrades oxalate in the gastrointestinal tract. Another South San Francisco-based biotech, Novome Biotechnologies, is developing a microbe-based therapy for the disorder. Unlike the approach taken by Federation Bio, Novome is taking a bacterium found in the gut and engineering it to colonize the GI tract and break down oxalate.
Federation Bio isn’t yet disclosing much about its engineered bacteria, but Conley says that this approach has the potential to address cancer and autoimmune disorders. Research shows that the microbiome is in constant communication with the immune system. By engineering bacteria with capabilities to interact with immune cells, she says her company’s therapies can influence whether a cell divides, changes from one type of cell to another, or dies.
“Certain strains of bacteria can actually induce T cell fate,” Conley says. “Federation Bio is building on that by applying an engineering approach to drive the immune system up or down.”
Conley declined to specify what Federation Bio is engineering its bacteria to do to immune cells. She only says that while other microbiome companies are leveraging bacteria as they are found naturally, taking a broader approach to activating T cells, Federation Bio is engineering bacteria that “drive the immune system in a more specific way.”
Federation Bio was founded in 2019 by Stanford University professors Michael Fischbach and Dylan Dodd, with initial funding from Venrock. Conley says the new cash enables the startup to continue developing its drug pipeline; the secondary hyperoxaluria candidate is expected to reach clinical testing in 2022. Federation Bio could also advance another drug to the clinic that same year. Conley says that besides cancer and autoimmune disorders, other diseases that the company is researching include multiple sclerosis and primary sclerosing cholangitis, which is a progressive disorder that leads to scarring of the bile ducts.
The Series A round of financing announced Tuesday was led by Horizons Ventures, with participation from earlier investors Venrock and Altitude. Stanford, Seventure Partners, and Health for Life Capital, which is a Seventure fund, also joined in the investment round. Along with the new financing, the company also announced that Conley had succeeded Racquel Bracken as CEO. Bracken is a Venrock partner and a co-founder of Federation Bio.
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