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10-K
SERES THERAPEUTICS, INC. filed this Form 10-K on 03/06/2019
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Our proprietary strain library of over 35,000 bacterial isolates from healthy donors and patients enables us to translate computational insights into defined compositions.  It includes the majority of the HMP’s “most wanted” and many novel species not described in other databases or the scientific literature.  Using proprietary assays and full-genome sequences, we characterize the functional capabilities of the bacteria in our strain library, based on both metabolomics and how the bacteria interact with human colonic epithelial cells and human immune cells.  We also seek to understand how these microbes improve the health of barrier cells in the gut and how this may impact immune responses.

We select bacteria from our library with specific predicted properties using novel algorithms for functional design and grow the compositions in the lab to be tested both in vitro and in vivo animal models.  Our animal models include conventional mice, germ-free mice, and “humanized” mice that possess only bacteria derived from humans, which we developed to minimize confounding variables presented by murine microbes.  Data from our in vitro and in vivo screens are analyzed and used to optimize compositional designs; introducing new bacterial strains and optimizing existing strains until we identify a lead composition suitable for clinical testing.  

Finally, we manufacture the bacterial composition under current Good Manufacturing Practices, or cGMP, which are required by FDA and European regulators. We believe our unique manufacturing capacities position us to exploit the insights of our proprietary human data and the novel biology of species and strains that have not previously been used for therapeutics. We have optimized fermentation conditions to generate spores and enhance bacterial yields in anaerobic fermentation and have in-house capabilities to formulate both spores and live non-spore bacteria.  Our manufacturing facility in Cambridge, Massachusetts was designed to be fit-for-purpose and is highly differentiated compared to the offerings of commercial contract research organizations.  We address quality control requirements for our Ecobiotic microbiome therapeutic candidates using proprietary microbiological and sequence-based testing schemes, including high-throughput quantitative analytics to assess the identity, potency and purity of the final product. These methods have been qualified to meet regulatory standards for live biotherapeutic products.

Taken together, we believe our platform, spanning drug discovery, preclinical translation, and novel manufacturing and quality control approaches, has enabled a field leading pipeline across a range of therapeutics areas.

Disease Overview and Our Product Pipeline

We believe our Ecobiotic microbiome therapeutic candidates represent a novel approach with potential application across a broad range of human diseases.  SER-287 is under development for the treatment of active mild-to-moderate UC and has completed a Phase 1b study in the United States. SER-287 has been designated an Orphan Drug for pediatric UC by the FDA. We are designing SER-301, a rationally-designed, fermented Ecobiotic microbiome therapeutic candidate, for the treatment of IBD.  Our most advanced drug development program, SER-109, focuses on recurrent CDI. SER-109 has been designated as a Breakthrough Therapy and an Orphan Drug by the FDA. Based on feedback received from the FDA, we have initiated a Phase 3 SER-109 clinical study in approximately 320 patients with multiply recurrent CDI. We are designing SER-401 for combination therapy with immune CPIs in cancer. We have also conducted early stage research on potential Ecobiotic microbiome therapeutic candidates for the treatment of metabolic disorders, such as early-stage, non-insulin dependent diabetes, NASH, and metabolic syndrome. Research in these indications is focused on developing Ecobiotic drugs that address specific functional defects in the microbiome, including the specific metabolic products made by the microbes.  We believe this approach may enable pursuit of a range of disorders including various forms of liver disease and rare genetic diseases of metabolism. 

Ulcerative Colitis, SER-287 and SER-301

UC is a relapsing-remitting chronic inflammatory disorder affecting the mucosal surface of the colon, leading to episodes of bloody diarrhea, urgency and mucosal inflammation (Danese and Fiocchi, 2011), which generally begins in young adulthood and endures for life. As the disease mostly affects young and middle-aged individuals, a time of peak reproductive and economic productivity, the disease leads to decreased quality of life in those affected by the condition, high morbidity, and significant health economic burden. (Ghosh and Mitchell, 2007; Kappelman et al., 2008; Rubin et al., 2014; Theede et al., 2015) The incidence of UC is rising worldwide and the prevalence of the disease is highest in the United States, Canada, and Europe. In the United States alone, the prevalence of UC in adults is estimated to be 263 per 100,000, while in the pediatric population (age <20 years), prevalence of the disease is estimated to be 33.9 per 100,000. (Kappelman et al., 2013)

UC is characterized by recurring episodes of inflammation limited to the mucosal layer of the colon. The severity of symptoms, diarrhea associated with blood and abdominal pain, may range from mild disease to severe disease with more than 10 stools per day with severe cramps and continuous bleeding. The severity, extent, and duration of disease are also risk factors for developing colon cancer, which occurs at a rate as high as 0.5-1.0% per year, an important complication given the young age at which the disease strikes. Patients with UC also experience increased risk of CDI and primary sclerosing cholangitis, compared to the general population.

The pathogenesis of UC is unclear but thought to arise from an aberrant immune response to a change in the colonic luminal environment in a genetically susceptible individual. The key features of UC include diffuse mucosal inflammation in a continuous pattern starting distally in the rectum to more proximal disease in the left colon to pancolitis.

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