Epithelial barriers are essential for organism’s homeostasis and survival. Defects in resistance of body barrier epithelial tissues and their repair are thought to underlie a range of diseases, which affect millions. Antonio Jacinto’s group has discovered that Septate/Tight Junctions are essential for epithelial repair. These cell-cell junctions can be potentially targeted by candidate compounds that have been identified by Thelial, a Start-Up that will collaborate in this project. In EMODI we will complete preclinical proof of concept of the potential therapeutic activity of two selected compounds, relying on scientific results and technologies developed under ERC starting grant awarded to Dr. Antonio Jacinto. Regarding clinical application, we will focus on rare (orphan) diseases which have been associated to impaired epithelial repair in the gastro-intestinal track for which there are very limited treatment options: Sjoergen Syndrome (SjS) and Eosinophilic Esophagitis (EoE). The plan of activities involves the following steps: 1) Biological efficacy testing of the-1 and the-2 in a zebrafish Tight Junction model and in mouse models of the diseases under focus; 2) Development of IPR based on the biological testing; 3) Consolidate outcomes of steps 1 and 2 into a business plan; 4) Present the business plan to VC funds to seek for extra round of funding. The long-term aim is clinical development of our candidates not only in the context of SjS and EoE but also towards a range of o diseases where impaired epithelial barrier function is impaired and a cause of morbidity.