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SERES THERAPEUTICS, INC. filed this Form 10-K on 03/16/2017
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Compared to the baseline data developed by the HMP, numerous scientific studies are emerging in both animals and humans, suggesting that many human diseases can be correlated with dysbiosis of the microbiome. These include infections, such as CDI or vancomycin-resistant Enterococcus, or VRE; metabolic disorders, such as early-stage, non-insulin dependent diabetes, obesity and non-alcoholic fatty liver disease, or NAFLD/NASH; allergies; autoimmune disease; inflammatory diseases, such as UC, Crohn’s disease and pouchitis; and cancer, including immune-oncology related applications. Examples of some studies include:

 

A study published in PLOS Pathogens in 2012 suggested that a mixture of six different bacteria found naturally in the gastrointestinal system of mice, when isolated from stool and reintroduced into the infected mice, was effective at suppressing CDI (Lawley et al., PLOS Pathogens, 2012). Researchers in the study found that a single treatment of the bacteria was sufficient and that the suppression lasted for months.

 

A placebo-controlled, randomized, blinded clinical study published in Gastroenterology in 2015 showed that repetitive fecal microbiota transplant, or FMT, delivered via enema weekly for 6 weeks could induce clinical remissions in patients with active UC (Moayyedi et al., Gastroenterology, 2015).   This study used an established measure of colonic mucosal healing to assess the efficacy of FMT compared to placebo, thus demonstrating the role of the microbiome in treating active UC. A subsequent randomized, placebo controlled, blinded study of FMT delivered 5 days per week for 8 weeks demonstrated similar clinical and endoscopic response rates (Paramsothy et al., Lancet, 2017).

 

Data from cancer patients undergoing allo-HSCT show the influence of the microbiome on patient survival. An observational study of allo-HSCT patients following allo-HSCT demonstrated that 3-year survival in patients with a low diversity microbiome was 36% whereas survival in patients with a medium to high diversity microbiome was ≥60%. Excess mortality in the low diversity subset was driven by deaths due to infection and GvHD, not the underlying cancer itself (Taur et al, Blood, 2014).  A follow up from the same researchers looked at allo-HSCT patients receiving transplants who are at highest risk of GvHD and showed a greater than 5-fold increase in mortality was correlated with microbiome composition. (Jenq et al., Biol of Blood and Marrow Transplant, 2015).  

 

A placebo-controlled, randomized, blinded clinical study published in Gastroenterology in 2012 showed that administration of FMT derived from lean donors to obese subjects with metabolic syndrome could transiently increase insulin sensitivity (Vrieze et al, Gastro, 2012).  This study furthermore identified changes in the microbiome of the small intestine that might have caused the effect.

 

Two studies in mouse cancer models, both published in Science in 2015, demonstrated that the anti-tumor response to immunological checkpoint inhibitors could be enhanced by altering the microbiome (Velizou et al., Science 2015; Slvan et al., Science 2015).  In addition, a prospective study in melanoma patients receiving anti-CTLA4 therapy for their cancer showed that a difference in the microbiome prior to treatment correlated with the subsequent development of colitis, a major side-effect of anti-CTLA4 treatment (Dubin et al., Nature, 2016). Most recently, researchers at MD Anderson Cancer Center have reported that the diversity and content of the microbiome may determine the efficacy of treatment with checkpoint inhibitors (Gopalakrishnan, et al., 2017 ASCO-SITC Clinical Immuno-Oncology Symposium).  Taken together, these results suggest that microbiome therapies might improve the safety and efficacy of checkpoint inhibitors in immuno-oncology treatments.

 

A study published in the Journal of Clinical Investigation in 2015 demonstrated that the microbiome of mice could be engineered to treat hyperammonemia, a clinical consequence of a set of rare genetic diseases known as Urea Cycle Disorders (Shen et al., JCI, 2015).  In this preclinical model, gut microbes that lack a functional urease gene were able to alter ammonia balance in the blood, suggesting a new route to novel therapeutics.

There are currently no microbiome therapeutics approved by the FDA. We believe that the ability to develop drugs that are able to modulate the microbiome and return a dysbiotic microbiome to its healthy state presents a significant opportunity to improve human health.

Our Microbiome Therapeutics Platform

We are developing a new approach to restoring health in settings of microbiome dysbiosis by using our microbiome therapeutics platform to develop Ecobiotic microbiome therapeutics. Our microbiome therapeutics platform is premised on the hypothesis that the proximal cause or significant contributor to multifactorial diseases is a dysbiosis of the colonic microbiome. We believe this represents a paradigm shift in approaching the way the underlying disease is defined and can be treated. Our microbiome therapeutics are a novel class of biological drugs designed to treat disease by restoring a dysbiotic microbiome to a state of health. They represent rationally defined ecological compositions, consisting of discrete combinations of beneficial microorganisms with designed functional properties that provide the ability to re-establish keystone features of a functional microbiome in settings of disease.

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