The first generation of microbiome therapeutics is hitting its first approvals. Savita Bernal, chief business officer at the French biotech MaaT Pharma outlines the firm’s efforts to blaze a trail in clinical testing and manufacturing in the new field.
The microbiome world recently made a regulatory step forward as Australia greenlit a stool transplant developed by the company BiomeBank for the treatment of debilitating gut infections by Clostridioides difficile (CDI). By seeding a patient’s gut with microbiota from a healthy donor, the so-called fecal microbiotica transplant (FMT) is designed to provide an alternative to harsh antibiotics and prevent infections from recurring.
However, FMTs are just the start for the microbiome space. FMTs are typically produced in hospital pharmacies, and, while thoroughly screened to be safe, their precise composition can vary depending on the donor.
To advance microbiome-based therapies, a wave of companies is developing industrially processed, controlled and enriched versions of FMTs. The U.S. company Rebiotix is one of the closest to the market; in September 2022, the U.S. Food and Drug Administration (FDA) gave a positive vote to Rebiotix’s therapeutic for the treatment of recurrent CDI, and a final market approval decision is pending.
Alongside Rebiotix, the French microbiome player MaaT Pharma is one of the most advanced companies developing microbiome therapeutics. The firm’s lead candidate — an industrially produced enema of gut microbiota taken from healthy donors — is in a phase 3 trial for the treatment of graft-versus-host-disease (GvHD).
While Rebiotix’s FDA vote is promising, Savita Bernal, chief business officer at MaaT Pharma, commented that the event itself isn’t the most significant for the space. “What would change something is if they do get the approval, which I think would be an important milestone for the microbiome industry,” she added.
Regulators are catching up with microbiome therapeutics
The multiple microbiome therapies in clinical development and close to the commercial stage is a sign that the regulatory agencies have come a long way in the last decade. For a while, European regulators had difficulty categorizing industrially processed microbiome therapeutics.
“We don’t consider ourselves as doing FMT because what we do is microbiome system therapies, which is a step further in terms of standardization, and in terms of composition,” said Bernal.
However, the path ahead is clearer for microbiome players like MaaT Pharma, which are in late-stage clinical trials.
“The regulatory authorities are more than catching up,” added Bernal. “They’re putting together standards and they’re working on it. But I think it’s a cohesive effort between the industry and the regulatory authorities because this is a new field.”
The microbiome manufacturing scale up
In addition to its product development activities, MaaT Pharma is also building a manufacturing plant in Lyon that can produce its microbiome therapies at a commercial scale. As part of the project, the contract development and manufacturing organization (CDMO) Sky Pharma is providing the workfloor space, while MaaT Pharma is filling up that space with its manufacturing equipment and staff.
Once complete, the plant should set up MaaT Pharma for the next 10 years of manufacturing and R&D activities in newer forms of microbiome therapeutics.
Historically, the newness of microbiome therapeutics has meant that most manufacturing is done in-house. According to Bernal, CDMOs have been slowly catching up to the technology.
“It’s already better than it used to be a few years ago. You could not talk about bacteria to CDMOs except if you were talking about insulin,” remarked Bernal. “The industry is growing so other services related to that industry will grow accordingly.”
Pushing the boundaries of microbiome therapies
In addition to its lead candidate, MaaT Pharma has other forms of microbiome treatments in the works. The firm’s second asset is an oral formulation of the same substance as its lead program, and is in phase 1b development to treat complications of bone marrow transplants in patients with cancer.
The steps to manufacture an oral microbiome therapeutic differ strongly from preparing for delivery via enema. For example, while the lead program must be stored frozen at -70 degrees centigrade, the oral method involves freeze drying the medicine.
Another mission for MaaT Pharma is to boost the number of patients with cancer that respond to treatment with immunotherapies called checkpoint inhibitors. The company is aiming to achieve this with a preclinical-stage microbiome treatment that isn’t derived directly from donor samples.
Instead, the company profiles the microbiomes of patients that do or don’t respond to checkpoint inhibitors, and uses artificial intelligence to tease out patterns. Based on these analyses, the company then co-cultures hundreds of bacterial species that, when delivered orally, can condition the gut microbiome to boost the immune system against tumors. The approach is easier to scale up than traditional FMTs and other donor-based treatments.
“We are definitely very differentiated from consortium companies, the ones that only target a few strains,” noted Bernal. “These few strains don’t operate alone: they operate within the network. If you remove that network, most likely you will remove part of the ability of this strain.”
Microbiome therapeutic approvals to come
MaaT Pharma’s lead candidate is expected to provide its first interim phase 3 readout in early 2023, and, if promising, the next few years could see it reaching the market. Fellow microbiome players Rebiotix and Seres Therapeutics likely have similar plans. As long as these big players can keep their push funded in difficult market conditions, then the maturing microbiome field could be well on the way to the mainstream.
“There is a consolidation I think of the regulatory approaches in different countries and I think it’s also a good thing,” said Bernal. “Hopefully it’ll get to that stage where we can actually start seeing the translatability of those approaches in real life.”