SYMBIOTIX BIOTHERAPIES, INC. — Department of Health and Human Services STTR Phase II: 300

Description

PROJECT SUMMARY ABSTRACT Interactions between the gut microbiome and the immune system have been linked to inflammatory bowel disease IBD IBD is a chronic and progressive gastrointestinal disease characterized by uncontrolled activation of the intestinal immune system resulting in severe medical complications affecting over million patients in the United States It is a disease of high unmet medical need currently treatable with only one of twelve approved immunosuppressive therapies often leading to toxic side effects Symbiotix Biotherapies Inc is an early stage biotechnology company developing a first in class therapeutic agent for IBD and other immune mediated diseases based on recent discoveries emerging from the human microbiome Our scientific founders have identified a specific gut commensal organism Bacteroides fragilis that induces interleukin IL secreting regulatory T cells Tregs that are able to dampen the pro inflammatory activities of Th Th and Th subsets of T cells We have furthermore identified a specific capsular polysaccharide PSA from this organism responsible for the protective effect shown that PSA works through a novel mechanism of Treg activation to expand anti inflammatory T cell populations in mice and shown that oral administration of purified PSA is protective in multiple models of mouse colitis Our objective for this Phase STTR project is to conduct key translational activities that will be essential for advancing PSA towards an IND filing as a safe and efficacious oral first in class treatment for human inflammatory bowel disease The project consists of Specific Aims In Specific Aim we will expand on initial human in vitro efficacy studies that demonstrate the capacity of PSA to convert na ve T cells into Treg cells in culture that secrete anti inflammatory IL to evaluate the effect of PSA on PBMCs and gut tissue taken from patients with inflammatory bowel disease In Specific Aim we will work with a biopharmaceutical contract manufacturer to scale up the manufacturing process that we have optimized to enable production of L batches that can support IND enabling GLP toxicology studies In Specific Aim we will carry out analytical method development to support scaleup and production of larger quantities of material necessary for tox studies and clinical trials These Specific Aims will lay the essential groundwork allowing PSA to move to IND filing and Phase I clinical trial As our company works to translate the groundbreaking academic studies that have resulted in the first therapeutic molecule to emerge from the human microbiome Phase STTR support will advance this revolutionary treatment option for IBD to the brink of human clinical trials and will pave the way for application of PSA to other immune mediated diseases such as multiple sclerosis asthma and rheumatoid arthritis PROJECT NARRATIVE Inflammatory bowel disease IBD is a chronic and progressive gastrointestinal disease characterized by uncontrolled activation of the intestinal immune system affecting over million patients in the United States Recent work emerging from the human microbiome the collection of microbial species that live on and in the human body has identified a specific beneficial bacterial species that resides in the human gut as crucial to maintaining a healthy immune system and protecting against immune mediated diseases such as IBD The scientific founders of our company have extensively studied this microbe Bacteroides fragilis and have identified the single molecule Polysaccharide A that is responsible for the protective effect This Phase STTR project will enable crucial translational studies that will help advance this first in class oral drug to the brink of human clinical trials