A number of groups are commercialising bacteria and fecal microbiota products for the marketplace including artificial and human poop capsules. These products are in various stages of development and testing, with some being trialled in laboratories and others in patients.
Openbiome, a non-profit, provides hospitals with screened, filtered, and frozen fecal transplant material ready for clinical use to treat C difficile. The organization prepares processed, frozen human stool from donors that have been carefully selected and screened for multiple infectious diseases at least twice, at a cost that’s about 1/6 the price of testing one donor. This service eliminates the time, staff, protocols, and facilities needed to screen and prepare material from new donors for each treatment.
A new non-profit private bank has been established in the USA with an aim to provide online loans to doctors and hospitals in the USA. Advancing Lending is located on the West Coast in Sacramento, California, USA. According to the organizations’ website, it has a history in dealing with financial products, and refers to their operation of USWTA, an organization providing loans in the USA since 1948.
Note that doctors in the USA can only perform FMT for c. difficile. In addition, the company will not sell fecal microbiota to patients directly, and only sell to doctors or hospitals. This product is not for sale to non-clinicians.
The organization is currently able to provide pre-screened, ready-to-administer microbiota preparations to clinicians performing FMTs for adult, recurrent C. difficile patients within the United States. This product is not for sale to non-clinicians.
Rebiotix Inc. is a biotechnology company founded to revolutionize the treatment of challenging gastrointestinal diseases by harnessing the power of the human microbiome. The company has developed a unique biopharmaceutical platform called Microbiota Restoration Therapy (MRT) to restore healthy gut flora through the transplantation of live human-derived microorganisms. With a goal of furthering evidence-based knowledge of MRT through a structured clinical research program, Rebiotix recently completed enrollment in the PUNCH™ CD study, designed to assess the safety of RBX2660 (microbiota suspension) for the treatment of recurrent C diff infection. Delivered via enema, RBX2660, is streamlining delivery of the therapy for both patients and physicians. The company’s goal is to make this therapy widely available and as easy to use as a flu vaccine. RBX2660 is currently (January 2015) in Stage 2 trials at various centres throughout North America.
GT Biologics (owned by 4D Pharma PLC)
GT Biologics is developing microbiome based drugs, with two entering clinical trials in Q2 2015. These two drug candidates are Blautix and Thetanix – biotherapeutics using live bacteria. Blautix is a treatment for irritable bowel syndrome (IBS), while Thetanix is intended to treat Paediatric Crohn’s Disease (PCD). Both products are “live biotherapeutics”, which use live bacteria as the active agent. In addition, in Fall 2014, the FDA awarded an ‘orphan’ designation for Rosburix, which is used in the treatment of paediatric ulcerative colitis.
Department of Defense – Defense Advanced Research Projects Agency (DARPA)
The Defense Advanced Research Projects Agency (DARPA) has given the Wyss Institute $4.7 (June 2015) million to develop a squadron of genetically engineered bacteria that will be able to identify, report on and attack harmful bugs in our gastrointestinal tracts. Researchers at the institute, an alliance between various Harvard schools, plus other universities and medical centers, will be using the funds to create synthetic bacteria that will be able to detect inflammation in the gastrointestinal tract. The bacteria will be taken in pill form.
Symbiotic Health, Inc.
According to this article published in the US publication, “The Atlantic” on December 2, 2013, a biotechnology start up, Symbiotic Health, is working towards developing FMT capsules.
Symbiotic Health Inc is a New York-based biotechnology company focused on the development of novel microbiome therapies for C. difficile. According to the company website “Our pipeline includes a capsule microbiome therapeutic designed to cure Cdiff by restoring a community of protective bacteria. The potential of microbiome restoration as a treatment for gastrointestinal infection has been recognized for decades, but has never been commercialized due to fundamental technological limitations. Our proprietary technology addresses key challenges for the development and production of microbiome-based therapies.”
Pureflora is a medical device company with a unique solution to intestinal infections. This company sponsored an engineering team at Dartmouth College, NH, USA, with the resulting invention, “Microflora Refinement System’, winning first place in the 2013 US National Institute of Health (NIH) sponsored competition, DEBUT (Design by Biomedical Undergraduate Teams) in the ‘Therapeutic Devices Category’. The ‘Microflora Refinement System’ automizes the preparation of donor feces, making the process faster and more standardized. The invention prepares both enema style FMT for colonic delivery and encapsulated FMT for oral delivery. Read about it here and here. Further information and articles can be found by internet searching under the term ‘Microflora Refinement System Dartmouth’.
There is not a company website, however, the invention does have a patent number, WO2013090825, described under the patent title ‘Device for the collection, refinement, and administration of gastrointestinal microflora’. Information included in the patent can be found here and here.
Monarch Laboratories and BTER (Biotherapeutics, Education and Research Foundation)
Monarch laboratories is developing two FMT products. The first product is a current good manufacturing (CGMP) processing and banking service for autologous FMT transplantation. This is the process of preparing an individuals’ fecal matter prior to that individual undergoing antibiotic treatment. The fecal matter would be used after the antibiotics to re-populate the gut with the pre-antibiotic fecal matter.
The second product is Medical Microbiota(TM) a FMT product screened for major pathogens and CGMP processed for allograft transplantation. This product would be used in clinical settings to treat patients.
CIPAC Therapeutics, a division of CIPAC Limited, is developing Full-Spectrum MicrobiotaTM (FSM) as an FDA-approved therapeutic derived from the human gut microbiome. FSM is a lyophilized powder that can be reconstituted for rectal infusion (enema or colonoscopy) or encapsulated for short-term or long-term oral use. The lyophilized product will facilitate easy administration for a variety of therapeutic indications and potentially can be used for routine restoration of healthy gastrointestinal microbiota in current and future indications.
CIPAC Limited is based in Australia with subsidiaries in California, USA.
Repoopulate is an artificial fecal product that includes 33 species of the bacteria in the colon. It was developed at the University of Guelph, located in Ontario, Canada. It is not yet commercially available and has been used twice to treat C. difficile. The treatment was successful in both patients treated.
Read more here and here.
Wellcome Trust Sanger Institute
Per the MRC Centenary Awards website, which is providing the funding: “Our aim is to create a treatment where doctors transplant a handful of known bacteria that have been cultured in the lab to treat C difficile. We’ve already done this in mice — in research published in PLoS Pathogens we showed that six species of bacteria taken from the guts of healthy mice cured C. difficile infections in the animals. Now we want to do that in humans. With our Centenary Award we intend to continue looking at bacteria from healthy people’s guts to identify those that might be best for treatment. We’ve become pretty good at culturing bacteria from mice in the lab and now we’re extending that to bacteria from human guts. Once we’ve defined the human bacteria to use, they could then be tested in patients by encapsulating the bacteria in a pill form and asking the patients to swallow them.”
This company was created by Puretech Ventures, a venture capital company. According to the company website, the mission of the company is “Vedanta Biosciences mission is to develop a novel class of therapies that modulate pathways of interaction between the human microbiome and the host immune system. Vedanta was co-founded by Puretech Ventures and a group of renowned experts in immunology and microbiology.”
Vedanta has created its first drug, VE-202. VE-202 is essentially a mixture of different strains of live bacteria packed into a pill that would be ingested and make its way into the gut, where the bacteria would colonize the intestine, and stimulate the immune system in a specific way. Vedanta’s plan is to initially test that drug as a treatment for inflammatory bowel disease, where Olle (Dr. Bernat Olle is one of Puretech Ventures principals) says there is the strongest amount of evidence that shows alterations in the microbiome lead to disease symptoms. Read more here and here.
In June 2013, Johnson & Johnson’s venture unit backed Vedanta Biosciences. Read about it here and here.
This organization proposes to treat C Difficile using a modified faecal bacteriotherapy (MFB), employing autologous samples collected from the patients prior to their treatment in a hospital. The samples will be homogenised with saline and filtered. The filtrate will be freeze-dried, placed in enteric coated capsules and used to treat the patient’s C Difficile, should the patient contract it while in hospital. RFID tags will be employed to associate capsules with the patient and assist with sample inventory.
Interestingly, a hospital in Toronto, Ontario, Canada, began a “stool banking” service in November 2013. This service is for patients undergoing surgery; if the patient should contract c. difficile, their own specimen will be used in a FMT. Read about it here.
Seres Health is a clinical stage biotherapeutic company focused on discovering and developing Ecobiotic™ therapeutic products to treat important diseases by targeting the underlying biology of the human microbiome. Seres Healths’ lead Ecobiotic, SER-109, is currently in the clinic for the treatment of Clostridium difficile infection (CDI). An early stage clinical trial has shown efficacy of SER-109 for the treatment of CDI. Seres Health is developing Ecobiotics across a range of other therapeutic areas including metabolic and inflammatory conditions. In June 2015, Seres Therapeutics, Inc., announced that SER-109 (Firmacute Eubacterial Spores, Purified Suspension, Encapsulated), its lead product candidate under investigation for the prevention of recurrent C. diff in adults, has been granted breakthrough therapy designation by the U.S. FDA. Breakthrough therapy designation is intended to expedite the development and review of therapeutics for serious or life-threatening conditions where preliminary clinical evidence indicates that the product may demonstrate a substantial improvement over existing therapies on one or more clinically significant endpoints. This designation allows for more intensive FDA guidance on an efficient drug development program, an organizational commitment involving senior managers, and eligibility for rolling review and priority review.
Synthetic Biologics Inc
Synthetic Biologics Inc (SYN) a clinical-stage company focused on developing therapeutics to protect the microbiome while targeting pathogen-specific diseases, announced in May 2015, that the company dosed the first participant in a second Phase 2a clinical trial of SYN-004. This trial will evaluate the gastrointestinal (GI) antibiotic-degrading effects and the safety of SYN-004, in the presence of the proton pump inhibitor (PPI), esomeprazole. SYN-004 is the Company’s candidate therapy designed to degrade certain intravenous (IV) beta-lactam antibiotics within the GI tract and maintain the natural balance of the gut microbiome for the prevention of C. difficile infection, antibiotic-associated diarrhea (AAD) and secondary antibiotic-resistant infections.
ViThera Pharmaceuticals is an early stage biotech company located in Cambridge, MA. ViThera scientists harness the synthetic potential of bacteria to produce therapeutic molecules within the body to develop a revolutionary new treatment for Inflammatory Bowel Disease. ViTheras’ research combines the natural benefits of probiotics with the power of synthetic biology to create game-changing, novel therapeutics for chronic diseases.
Osel Inc. is a biopharmaceutical company with a proprietary technology platform to develop next-generation probiotics as pharmaceutical products to address major gastrointestinal (“GI”), infectious diseases and women’s health indications.
Osel has two naturally occurring bacterial strains in clinical development. LACTIN-V is a vaginal product that contains a human vaginal strain of Lactobacillus (L. crispatus CTV-05) and is being developed for the treatment of recurrent urinary tract infections (RUTI) and bacterial vaginosis (BV). MIYA-BM is an oral product containing the probiotic bacterium Clostridium butyricum MIYAIRI 588 (CBM 588) that is under development for antibiotic-associated diarrhea (AAD), particularly AAD caused by Clostridium difficile infection (CDI).
This Belgium company is developing proprietary drugs based on single strain bacterium. The company is developing the next class of probiotics, which will be pharmaceutical grade. Three products are in the pipeline and are at different phases in drug development. The three products are AG013 for Oral Mucositis, AG014 for IBD, and AG015 for IBD.
An interesting side note is that technology has been developed by Actogenix, which may eventually prove useful in developing freeze dried FT. Actogenix developed a GMP-compliant process to manufacture freeze-dried single strain drug product with nearly 100% viability and reported stability up to three years.
MicroBiome Therapeutics (formerly known as Nume health) is developing medical food and pharmaceutical products that improve health status by interacting with the human microbiome in specific ways. MT is developing evidence-based microbiome modulators–products designed to alter bacterial populations and their environment in the gastrointestinal (GI) tract to prevent or treat serious health conditions.
MicroBiome Therapeutics’ (MBT) initial products are microbiome modulators that are specifically designed to modify the bacterial populations and the environment in the GI tract to produce measurable improvements in health status in individuals with prediabetes, diabetes and other metabolic diseases. MBT has one product that is in clinical development. NM504, a microbiome modulator, is intended to be a prescription product for treatment of prediabetes and diabetes.
Second Genome is a pioneer in the development of microbiome modulators, which are bioactive therapeutics that benefit human health by altering the composition and activities of the microbial communities in the body to regulate host pathways. Second Genome’s focus is on microbiome modulators that impact infection, immunity and metabolic disease. The company is currently pursuing three preclinical programs and additional discovery efforts.
In June 2013, Second Genome secured funding from Johnson & Johnson. Read about it here and here.
This company is developing a microbiome product to treat lactose intolerance. The company has developed a technology termed ‘colonic adaption’. Colonic Adaptation is based on selectively colonizing microbiota in the colon by increasing the number of specific beneficial bacteria, and thus changing the colon’s microbial composition. The process has been shown to stimulate the growth of endogenous bifidobacteria and lactobacilli which after a short feeding period, become predominant in the colon resulting in reduced inflammation and improved digestion, thereby reducing digestive symptoms. Particularly for lactose intolerance both these bacterial species are lactose metabolizing, thereby minimizing or eliminating the digestive problems associated lactose intolerance. The company has one main compound, RP-G28, to treat lactose intolerance. RP-G28 has completed Phase 2 testing.
Per the company website “Omnibiome is focused on developing diagnostic, therapeutic, and medical device products for pregnancy-associated and pediatric conditions or diseases where there is a documented or substantive putative link with microbiome dysbiosis (disruption or imbalance).” The founders of OmniBiome have filed multiple U.S. patent applications for apparently novel inventions, including microbiome modulation/transplants.
AvidBiotics has two product platforms. The first, Avidocin™ proteins, represent a new class of highly specific, targeted bactericidal agents for use in the treatment or prevention of bacterial infections. Because they are so specific, Avidocin proteins also have potential for use in manipulating bacterial populations in a targeted fashion – killing only the desired microbes while leaving untargeted, beneficial organisms untouched, a capability unmatched by antibiotics. The company’s second platform, Micacide™ proteins, specifically flag virus-infected or cancer cells for enhanced destruction by the Natural Kill and T cells of the potent innate immunity system.
AvidBiotics is developing human therapeutic applications of its technologies, both on its own and in partnership with governmental agencies and research institutions.
Note: The products under development are considered to be FT derived products, since bacteriocins (R-type) are secreted by bacteria and act against other bacteria.
Enterome is developing diagnostic tests related to the microbiome (i.e. testing intestinal bacteria). From the company website:
“Enterome is advancing an internal pipeline of biomarkers in chronic serious diseases like metabolic diseases (NASH, obesity, type-2 diabetes); inflammatory bowel diseases (Crohn’s disease and ulcerative colitis); and central nervous system diseases (depression, multiple sclerosis, Parkinson, autism).”
In May 2015, Genomic services contract research organization Genewiz and Hy Laboratories announced a partnership to develop diagnostic panels to characterize the gut microbiome in patients with obesity and diabetes.
Metabogen, a Swedish start up, is developing diagnostic tests related to the microbiome. Metabogen (Gothenburg) has applied existing metagenomic tools to discover a microbial gene signature in stool samples that identifies type 2 diabetes patients as well as patients at high risk of stroke.
Per the company website: “Micropharma Limited discovers and develops theraputics, diagnostics and devices based on the emerging science of the human microbiome. The Company uses its proprietary discovery and development platform ProSelect to screen and select bacteria capable of expressing phenotypic traits that can effectively target metabolic pathways recognized as having therapeutic potential. Micropharma then uses its novel fermentation and optimization techniques to induce over-expression of these traits.”
The company is developing an ‘ingestible gastrointestinal sampling technology ‘, a pill that can sample GI matter throughout the intestine, including the small intestine.
Micropharma has three products – Cardioviva, to treat high cholesterol, LRC, or Lactobacillus reuteri NCIMB 30242, also used for high cholesterol, and Glucoviva, used to maintain normal blood glucose levels.
Optibiotix Health PLC
Per the company website: “Optibiotix is creating a range of products designed to prevent or manage many of the chronic and debilitating illnesses associated with ‘lifestyle’ and ageing. Products will be natural (i.e. not genetically modified) food ingredients, compounds, and formulations which will work by seeding and/or modifying the human microbiome (the microbes in and on the body) to produce health benefits.”
Aobiome, a biotechnology company, is pioneering microbiome treatments for the skin. The company has developed a product, stabilized Ammonia Oxidizing Bacteria (AOB), which restores the skin’s microbiome. Read more about it here.
Arizona State University – Medical Device to isolate good intestinal bacteria from bad
Arizona State University scientists have developed a microfluidic chip that can sort good intestinal germs from bad.
Read about it here and here.
Other – Patents
Patent – Probiotic recolonisation therapy:
Professor Thomas Borody of the Centre for Digestive Diseases in Sydney, Australia is the father of FMT in its modern form. He has lodged a patent for a poop capsule that makes very interesting reading.
In essence, this patent includes compositions that comprise viable non-pathogenic or attenuated pathogenic Clostridia, with other microbiota. The concept is that colonization is more likely to be achieved with the addition of Clostridia to the microbiota.
Patent – Encapsulated intestinal flora (freeze dried):
A patent has been granted to an individual, William John Martin, in Great Britain under the terms “(WO2011033310) ENCAPSULATED INTESTINAL FLORA EXTRACTED FROM FECES”
Description of the product:
Freeze dried capsules of fecal matter to be used to treat gastrointestinal diseases. Other than the link below, no other information related to this patent or individual were found.
Patent – Composition comprising anaerobically cultivated human intestinal microbiota:
A patent titled “Composition comprising anaerobically cultivated human intestinal microbiota” was issued to Quantum Pharmaceuticals Sa, a Swiss company. Description of the patent: “The present invention relates to an anaerobic micro-ecological system comprising anaerobically cultivated human intestinal microbiota. The present invention also relates to a composition of anaerobically cultivated microbiota that constitutes a functional seeding culture for re-establishing normality of a disturbed human microbiome and gastrointestinal functions.” The company, Quantum Pharmaceuticals Sa, has a website, but the site makes no mention of any products in the pipeline and does not include any information on R&D activities.
The Gut Microbiota as a Target for Innovative Drug Development
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