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Recent research demonstrating how important the human microbiome is for maintaining good health has led to the founding of many biotech companies hoping to create microbiome-based therapeutics. These five biotech companies all have candidates in clinical trials and are primed to be among the first to receive market approval.

The human microbiome, consisting of all the “friendly” non-pathogenic micro-organisms living in and on the human body, plays an important role in keeping us healthy. Research on the gut microbiome shows that the microbes living in our gut help their host in many ways—for example, by fermenting dietary fiber into short-chain fatty acids, which can then be absorbed by the body, or by producing beneficial vitamin B and K.

The possibilities of harnessing the microbiome, in particular the gut microbiome, for therapeutic purposes came into the spotlight with the discovery of how effective a fecal transplant of “healthy” gut bacteria could be for the treatment of recurrent Clostridium difficile infection. A paper published in 2009 concluded that it was a simple, effective, and inexpensive procedure and it has since been proved 85-90% effective at resolving hard-to-treat C. difficile infections, although no FDA approved fecal transplant or other microbiome-based products are yet on the market.

Woman researcher performing examination of bacterial culture plate
Credit: Manjurul / Getty Images

Over the last decade, many biotech companies have been established to try and develop therapeutics that target or utilize the beneficial properties of microbial communities, such as the gut and skin microbiomes. These companies plan to develop therapeutics to treat a range of diseases, infections and chronic conditions including inflammatory bowel disease, diabetes, cancer, and depression.

Although the road to the clinic has not been smooth, with a number of trial failures and regulatory holds placed by the FDA, the first official microbiome-based therapeutic—produced by big pharma Ferring, which acquired Rebiotix in 2018—is predicted to be approved in the short term, after an FDA committee recommended approval of its C. difficile treatment in September.

While Ferring is likely to be first to achieve approval, the following five companies are hot on its heels and are also hoping to reach the market very soon.

Seres Therapeutics logo

Seres Therapeutics: Founded: 2012
Headquarters: Cambridge, Massachusetts

Founded by serial entrepreneur David Berry and launched by Flagship Pioneering in 2012, Seres Therapeutics listed on the Nasdaq in 2015, raising $134M, and now has a market cap of $730.8M.

It is hot on Rebiotix/Ferring’s heels to get a microbiome therapeutic approved. It’s lead candidate, SER-109, which it developed in collaboration with Nestlé Health Sciences, is an oral capsule containing live, purified Firmicutes bacterial spores to treat recurrent C. difficile infection.

The therapeutic bacteria in the capsule compete with C. difficile for essential nutrients and help the gut become more resistant to being colonized by the pathogen bacteria. In a recent phase III trial, SER-109 reduced the relative risk of recurrent C. difficile infection by 59–76% (depending on age and antibiotic use) compared with placebo. After reporting good follow-up results in June, the company is hoping for FDA approval later this year and has already submitted its application to the FDA.

The phase III success of SER-109 comes after a rocky initial road for Seres, with phase II failures for both SER-109 and last year its second most advanced candidate to treat ulcerative colitis SER-287. The company also has another program, currently in phase I trials, to treat graft versus host disease in patients receiving bone marrow transplants. This therapy includes a selection of gut bacteria designed to stop proliferation of antibiotic-resistant bacteria and dampen unwanted immune activity in the gut.

Finch Therapeutics logo

Finch Therapeutics: Founded: 2014
Headquarters: Somerville, Massachusetts

Finch Therapeutics was founded in 2014 and listed on the Nasdaq last year raising $128M in an upsized IPO. It also has a treatment for recurrent C. difficile infection in late-stage development, consisting of freeze-dried gut bacteria from healthy donors.

In an extended phase II trial reported last year, the therapy reached a “sustained cure” rate of around 80% for up to 24 weeks and a good safety profile. However, a hold on further research was issued by the FDA due to concerns about whether the donors were being adequately screened for SARS-CoV-2 infection. This hold was lifted in April, clearing the company to start phase III trials after manufacturing and quality system updates. Finch also has early-stage candidate treatments for ulcerative colitis (FIN-524), Crohn’s disease (FIN-525) and autism spectrum disorder in development. Phase I trials of the autism candidate are expected to start soon.

The company market cap, currently $83.5M, took a hit recently when long-time big-pharma collaborator Takeda pulled out of a partnership to develop the two inflammatory bowel disease therapeutics (FIN-524 and FIN-525) citing “pipeline reprioritization” as the reason. Finch is now looking for new partners to help fund further development of these assets.

Enterome logo

Enterome: Founded: 2012
Headquarters: Paris, France

Enterome was established in 2012 and has raised around $112 Million in private funding and loans. It is focused on developing unique microbiome-inspired therapies to treat cancer and immune diseases.

OncoMimics are peptides derived from gut bacteria that mimic tumor-associated antigens or markers in different types of cancer. The company has a database of more than 20 Million gut microbiome proteins and it is using this tool to develop new targets and drug candidates.

The company’s lead OncoMimic candidate, EO2401, currently being tested in phase I/II trials combined with the checkpoint inhibitor nivolumab, comprises three bacterial peptides that strongly resemble three important human tumor antigens found in glioblastoma and adrenal tumors. Earlier stage candidates are targeting non-Hodgkin lymphomas and colorectal cancer.

In addition to cancer, Enterome is also developing oral bioactives to treat conditions such as inflammatory bowel disease called EndoMimics, which act like human hormones or cytokines. In July, the Parisian company signed a deal with Nestlé Health Science to co-develop EndoMimics and AllerMimics aimed at treating food allergies and inflammatory bowel disease. Enterome received $38.7M as an upfront payment and is eligible for further milestone, sales and royalty payments should co-developed candidates reach the market.

MaaT Pharma: logo

MaaT Pharma: Founded: 2014
Headquarters: Lyon, France

MaaT Pharma, which stands for Microbiota as a Therapy, was founded in 2014. Its lead candidate, MaaT013, is designed to treat graft versus host disease following stem cell transplantation, and is also being trialled as a possible treatment for melanoma. Another candidate therapy, MaaT033, aims to improve outcomes after allogeneic hematopoietic stem cell transplantation for leukemia patients.

The company launched a phase III trial of MaaT013 in Europe in March, for patients with acute graft versus host disease, following good phase II trial results. The candidate consists of fecal bacteria from healthy donors, which has been screened and processed. The treatment calms inflammation in the gut and aims to reduce or stop future immune flare ups.

Progressing MaaT013 in the U.S. has proved difficult. MaaT submitted an investigational new drug application in June 2021, with a view to starting a phase III, open-label, single-arm study of MaaT013 in the U.S., but in August 2021 the FDA issued a clinical hold, citing questions about safety and efficacy. Despite sending a detailed response to the FDA’s questions, the hold continues to date while the FDA assesses additional information on how MaaT013 was developed.

MaaT launched on the Euronext Paris stock exchange with an IPO of approximately $30.4M late last year and has a current market cap of $79.2M.

Vedanta Biosciences logo

Vedanta Biosciences: Founded: 2010
Headquarters: Cambridge, Massachusetts

Vedanta Biosciences was launched in 2010 by PureTech Health and microbiome experts Dan Littman, Kenya Honda, and others. It has built what it believes to be the world’s biggest library of bacteria derived from the human microbiome.

Similar to Finch and Seres, its lead candidate aims to treat high-risk C. difficile infection. VE303 comprises eight types of human commensal gut bacteria strains able to provide colonization resistance to C. difficile. In a phase II trial, completed and published last year, the treatment achieved a greater than 80% reduction in recurrence risk compared with placebo.

The company is currently preparing to start a phase III trial of its lead therapy in the next few months and recently announced the opening of a new large-scale Current Good Manufacturing Practice (CGMP) facility to produce multiple drug candidates compliant with global regulatory standards. Vedanta’s earlier stage candidates are aimed at inflammatory bowel disease, solid tumors, gram negative infections, hepatic encephalopathy and food allergies.

In 2020, Vedanta was awarded up to $76.9M of federal funds from the Biomedical Advanced Research and Development Authority, to partially fund the development of VE303. In addition, last year, the company announced the closing of a $68 million Series D financing round.

 

Helen Albert is senior editor at Inside Precision Medicine and a freelance science journalist. Prior to going freelance, she was editor-in-chief at Labiotech, an English-language, digital publication based in Berlin focusing on the European biotech industry. Before moving to Germany, she worked at a range of different science and health-focused publications in London. She was editor of The Biochemist magazine and blog, but also worked as a senior reporter at Springer Nature’s medwireNews for a number of years, as well as freelancing for various international publications. She has written for New Scientist, Chemistry World, Biodesigned, The BMJ, Forbes, Science Business, Cosmos magazine, and GEN. Helen has academic degrees in genetics and anthropology, and also spent some time early in her career working at the Sanger Institute in Cambridge before deciding to move into journalism.

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