Public Funding for Xenogesis Limited

The Caco-2 cell line is the gold standard for the prediction of drug absorption and permeability in vitro by mimicking the small intestine. However, this model lacks the dynamic motion which represents one of the physiological functions of the small intestine (peristalsis). In our research, we investigate the possibility the similarity between the static Caco-2 cell model and the dynamic intestine by creating a dynamic in vitro environment using MICA technology. Our results to date have shown that MICA’ technology improves the absorption of the selected drugs, and their permeability is more similar to that found in the human intestine. Our data suggests that MICA’ technology applied to Caco-2 drug permeability assay could be used to a better predict, using in vitro assays, the in vivo human drug absorption rates. This feasibility study will enable us to test rigorously against the gold standards and generate a new assay for the pharmaceutical market. Our research will lead ultimately to a reduction in animal research and more drugs coming through the pipeline to applications in healthcare.

Non-alcoholic fatty liver disease (NAFLD) encompasses a range of conditions from fatty liver (steatosis) to non-alcoholic steatohepatitis (NASH). NAFLD is a condition affecting around 30 % of the general population and 70 % of obese and diabetic patients. The prevalence of NAFLD is set to rise as the obesity and diabetic pandemic escalates. It is therefore important that there are tools available to investigate this disorder, however current in vitro models for NAFLD research are limited. To address this we aim to create models to study NAFLD using CN Bio's proprietary 3D in vitro primary human hepatocyte culture system, LiverChip. The goals of this project are to generate and characterise commercially viable models for NAFLD research, which will then be exploited for xenobiotic studies. This project will be a collaborative work between CN Bio and Xenogesis.

Inhalation is an increasingly important delivery approach of therapeutic agents to the lung. There remains an unmet medical, commercial and practical need for 'once-a-day' treatment in various therapeutic areas and this is lacking for some current therapies. Once daily treatment is possible in some cases, but this approach can involve over-dosing to give the required duration of action. A negative issue is often side-effects due to initial higher than desired drug exposure. The proposed project involves chemically modifying current drugs via a pro-drug approach. The active drug will be released in a controlled manner at the target site, so the duration of pharmacological effect will be significantly longer than the traditional approach. The concept will be tested pre-clinically with the iterative design and synthesis of various test agents and drug metabolism tests in vitro and in vivo to prove that the required extension of duration is realised.