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 1.5 million patients in the United States. It is a disease of high unmet medical need, currently treatable with only one of several approved immunosuppressive therapies, often leading to toxic side effects. Symbiotix Biotherapies, Inc. is a startup biotechnology company developing a first-in-class therapeutic agent for IBD and other immune-mediated diseases based on discoveries recently emerging from the human microbiome. Our scientific founders have identified a specific gut commensal organism, Bacteroides fragilis that induces interleukin (IL)-10-secreting regulatory T cells (Treg) that are able to dampen the pro-inflammatory activities of Th1, Th2 and Th17 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 mouse colitis models. Our objective for this Phase 1 STTR project is to conduct key translational studies that will be essential for advancing PSA towards an IND filing as a safe and efficacious oral first-in-class treatment for IBD. The project consists of 3 Specific Aims:
In Specific Aim 1, we will expand on initial in vivo efficacy studies of oral PSA in a murine colitis model to evaluate the effect of PSA in dose-escalating efficacy studies.
In Specific Aim 2, we will radiolabel PSA and carry out PK/biodistribution studies of orally-administered PSA.
In Specific Aim 3, we will carry out HLA haplotype restriction studies to evaluate the ability of PSA to modulate human cells of the major HLA haplotypes. Successful completion of this Phase 1 STTR project will generate the preclinical efficacy data, biodistribution data and HLA haplotype restriction data necessary to justify a rapid push towards IND filing that will take PSA into human clinical trials with the support of follow-on Phase II STTR funding. As our company works to translate these groundbreaking academic studies that have resulted in the first therapeutic molecule to emerge from the human microbiome, Phase 1 STTR support will not only lay the groundwork for the development of a revolutionary treatment option for IBD, but may also pave the way for application of PSA to other immune- mediated diseases such as multiple sclerosis, asthma, psoriasis and / or rheumatoid arthritis.
Inflammatory bowel disease (IBD) is a chronic and progressive gastrointestinal disease characterized by uncontrolled activation of the intestinal immune system, affecting over 1.5 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 that is responsible for the protective effect. Symbiotix Biotherapies, Inc. is a startup biotechnology company formed to bring this new therapy to patients as an orally administered, safe and effective treatment for IBD, and the Phase 1 STTR project will enable crucial studies that will give us safety and efficacy information needed to take this therapy into human clinical trials.