Antibiotics are one of the most common medicines in the world, with about 236 million prescriptions in the U.S. in 2022 alone, according to the Centers for Disease Control and Prevention. These drugs are great for clearing out bacterial infections but also have an unintended side effect: They wreak havoc on the healthy microbes that call our guts home.
“There's a lot of research and clinical data that shows that the disruption of the beneficial microbes in your gut actually is a high risk factor for many diseases,” Andrés Cubillos-Ruiz, Ph.D., a microbiologist and synthetic biologist at the Wyss Institute for Biologically Inspired Engineering at Harvard University, told Fierce Biotech in an interview. “This is a huge problem that is still a highly unmet need.”
Florey Biosciences, a company spun out of Cubillos-Ruiz’s work in the MIT and Wyss Institute lab of James Collins, Ph.D., seeks to fill this unmet need with genetically modified microbes and a unique regulatory approach. The company launched Oct. 1 with pre-seed funding from Seerave Ventures, the investment arm of the microbiome-focused Seerave Foundation, according to a release. The team hopes to close out a seed funding round by mid-2025, Cubillos-Ruiz said.
In addition to Cubillos-Ruiz, who is CEO, and Collins, Raphaël Gayet, Ph.D., is also a co-founder. Collins is a synthetic biologist known for his entrepreneurial spirit; he’s a co-founder of the Flagship Pioneering-launched Cellarity as well as the publicly traded Synlogic Therapeutics and Senti Biosciences, among others.
Florey’s lead program is a genetically modified yeast called FLR-101. This yeast produces an enzyme that breaks down beta-lactam antibiotics, which make up about 50% of all antibiotics used, Cubillos-Ruiz said. Because the yeast is localized to the gut, its anti-antibiotic activity shields the microbiome there while the antibiotic is still able to clear an infection elsewhere in the body. The team first tested this approach using modified bacteria in a 2022 paper, and has now improved upon the method.
“We have technologies that prevent these genes from jumping into bacteria,” Cubillos-Ruiz said, so that the yeast’s antibiotic-destroying power can’t be picked up by other microbes.
When it came to forming a strategy for Florey, Cubillos-Ruiz learned from predecessors like Seres Therapeutics and Rebiotix (acquired by Ferring Pharma) about the perils of developing drugs for the microbiome. “You were going to incur huge development costs, and then you're going to create a product that doesn't have the market access and the market opportunity,” he said.
To avoid those pitfalls, Florey is aiming to get FLR-101 into the world as a medical food instead of as a drug.
Medical foods are products that are meant to be taken orally for the management of a disease or condition under the supervision of a physician but that don’t require a prescription. While drugs require studies of safety and efficacy, reporting of side effects and a thorough label review before hitting the market, medical foods do not.
There is no formal stamp of approval that the FDA gives to medical foods, but the agency does provide guidelines for the products. Once FLR-101 is recognized as safe to consume, it could be put on the market right away along with the countless other probiotics that claim to support gut health.
However, in order to market the modified yeast as being able to manage the microbiome dysfunction that comes from antibiotic use, Florey plans to run human trials to test whether FLR-101 paired with antibiotics leads to less microbiome damage than antibiotics alone.
If successful, Florey would be able to add that information to FLR-101’s label and distinguish it from the other probiotics alongside it on the shelf.
To bolster FLR-101’s chances of successfully navigating the medical foods regulatory pathway, Florey is adding Peter Hutt, former chief counsel of the FDA, to its board of directors, the company said in the release. At the FDA, Hutt helped craft the medical food regulatory framework, and he also played a pivotal role in the creation of nutrition labels, according to the release.
“We have all the pieces of the puzzle to have a biotech product that, in its core, its technology is highly advanced, but we can put it in the market using different ways,” Cubillos-Ruiz said.
Putting out products as consumer goods rather than prescription drugs presents a marketing challenge: How do you make sure patients, physicians and pharmacists know about your product? Cubillos-Ruiz sees an opportunity in FLR-101’s partner, antibiotics.
“There is a big push from government agencies and within medical societies to be better antibiotic stewards,” he said. Hospitals don’t want readmissions of patients who develop health problems due to antibiotic-weakened gut microbiomes, and antibiotics tend to have slim profit margins. Pairing the drugs with a proven probiotic could be a way to boost revenues, Cubillos-Ruiz suggested.
The company is currently preparing in vivo safety studies in preparation for human trials, Florey said in the release. If all goes well, Florey hopes to launch its flagship product in three years, Cubillos-Ruiz said.
First-time biotech CEO Cubillos-Ruiz thinks that in 10 years, we’ll all look back and wonder how we could let antibiotics run roughshod over our gut microbes for so long. It will be like “going to a beach day and not using sunscreen to protect yourself from the sun,” he said.