Non-invasive exfoliome platform to accelerate treatment for gastrointestinal disorders

SUMMARY Inflammatory Bowel Disease (IBD), composed of Crohn’s disease (CD) and ulcerative colitis (UC), is the most common chronic inflammatory condition of the gastrointestinal (GI) tract. Over the last decade, the prevalence of IBD has increased two to three-fold, with incidences as high as 1.3% in US adults, and significant efforts have been devoted to profiling IBD using multi-omics approaches to understand molecular drivers of disease, however, there remains major knowledge gaps in the temporal processes regulating inflammatory states in the gut at disease onset and during flare-ups. In addition, top pharmaceutical companies collectively spent ~$7B on R&D in 2022 allocated to GI-related diseases but over a third of patients are regularly failing to respond to first line therapeutic modalities. Therefore, there is a continued demand for novel interventions that are better tailored to the patient. The GI lining is constantly renewed, as ~1010 intestinal epithelial cells are shed into the digesta daily, and end up into the stool, with the host cells’ DNA and RNA contents. The exfoliome, i.e. the RNA content exfoliated from host cells, is a valuable tool to gather insights into the gene expression patterns, cellular signatures, and biological processes occurring in the gastrointestinal tract, making it potentially useful for understanding IBD., and providing a non-invasive means to longitudinally profile dynamic processes occurring within the GI tract. However, numerous technical obstacles prevent direct exfoliome analysis from stool. Foli Bio Inc. has developed an innovative technology, called Exfo-seq, to sequence fecal exfoliome in a highly sensitive and quantitative manner. Exfo-seq is based on a proprietary signal amplification approach and enables to precisely and robustly quantify the expression level of several thousand of host genes directly from stool RNA. In this proposed project, Foli Bio aims to validate the functional utility of Exfo-seq using samples collected from IBD clinical trial. The overarching goal of this project is to generate unprecedented knowledge regarding the human GI exfoliome at baseline and over time, and examine the local gut immune profile, evaluate heterogeneity in inflammatory states between individuals, identify early biomarkers, and predict therapeutic response. More importantly, Foli Bio believes this technology holds great potential as a non-invasive method to transform future GI drug development and will substantially benefit pharmaceutical companies as well as the larger population of IBD patients who remain underserved by the current treatment paradigms in IBD.