Food gurus tout the benefits of eating spinach and kale, but some people are better off leaving them on the plate. A molecule in these leafy greens contributes to hyperoxaluria, a condition characterized by kidney stones at first and serious organ damage later.
Novome Biotechnologies is developing a gut microbiome treatment for hyperoxaluria. The company is engineering bacteria intended to populate the gut and then break down the key molecule before it causes problems. South San Francisco-based Novome now has $33 million in Series A financing to continue its research, which is expected to lead to tests in humans in about a year.
The problem molecule leading to hyperoxaluria is called oxalate. The term hyperoxaluria literally means high levels of oxalate in urine, says Will DeLoache, co-founder and chief scientific officer of Novome. Some people lack the enzyme to break oxalate down, a genetic condition called primary hyperoxaluria. Secondary hyperoxaluria is caused by eating too much oxalate-containing food. In both forms, kidney stones are an early sign of the disease. Urinary tract infections, chronic kidney disease, and end-stage renal disease can follow. There are no FDA-approved treatments for hyperoxaluria, which is typically managed by drinking more fluids to flush out oxalate as well as avoiding certain foods.
Novome aims to develop a treatment for secondary hyperoxaluria. The startup works with Bacteroides, bacteria that are prevalent in the gut and have a symbiotic relationship with humans. These bacteria help break down food and produce nutrients for the body.
The first genetic modifiation the company does to the bacteria is intended to get them to colonize the gut. CEO Blake Wise says it’s hard to achieve high levels of a therapeutic bacteria with an oral formulation, which is why some experimental microbiome treatments must be taken daily. Novome aims to overcome that hurdle by engineering its bacteria to feed on a particular carbohydrate given with the therapy. Other bacteria in the gut don’t eat it, so they aren’t affected, Wise says.
“We really don’t have a detectable impact on the community [of bacteria],” Wise says. “ We’re just adding our therapeutic strain at a high level.”
The Novome bacteria are also engineered to break down oxalate. If a patient or clinician wants to stop the treatment, all that’s needed is to stop ingestion of the carbohydrate that the bacteria eat, Wise says. The bacterial strains then wash out of the gut, leaving the rest of the microbiome intact. DeLoache says Novome’s approach should have minimal effect on other bacteria in a person’s gut compared to some experimental treatments such as fecal transplantion, which introduces an entirely new microbial community and comes with potential risks.
The gut microbiome has drawn scientific and investor interest in recent years for its potential to address a range of disorders in the gastrointestinal tract and beyond. Seres Therapeutics (NASDAQ: MCRB), founded in 2010, was one of the first microbiome companies. The Cambridge, MA, company’s pipeline includes clinical-stage programs for Clostridum difficile infection and ulcerative colitis. New York-based Kallyope aims to treat central nervous system disorders by targeting a signaling network called the “gut brain axis.” Pendulum, a San Francisco startup formerly known as Whole Biome, has developed a microbial product for diabetes that is classified as a medical food, not a drug. None of these companies engineer their microbes.
Wise says Novome’s bacteria-tweaking approach, which is based on research licensed from Stanford University, could be used to develop treatments for diseases that are now being pursued by other microbiome companies. Hyperoxaluria is the startup’s first target because it’s a straightforward disease with a clear connection to the gut microbiome, he explains. After validating the technology in hyperoxaluria, Novome plans to move on to other diseases. The company’s pipeline includes a program for irritable bowel syndrome.
Novome has tested its experimental hyperoxaluria therapy in rodents and pigs. Wise says that the new financing will support additional preclinical work and a Phase 1 test he hopes will start next year. DCVD Bio led the latest investment in Novome. Also participating were seed investor 5AM Ventures, Alta Partners, Alexandria Venture Investments, and Mayo Clinic.
Photo by Ben Romano