Abstract: We have been constructing multi-organ human-on-a-chip systems for safety and efficacy with up to 5 organs and have demonstrated long-term (>28 days) evaluation of drugs and compounds, that have shown similar response to results seen from clinical data or reports in the literature. These models utilize a pumpless platform with serum free recirculating medium, which is a low volume system that can evaluate parent compounds as well as metabolites, if the liver is included. Specific embodiments of this technology are the creation of a functional human NMJ system to understand ALS and a long-term potentiation (LTP) for AD utilizing clinically relevant functional readouts. Sanofi has used efficacy data from our conduction velocity model to file an IND for CIDP that has enabled a clinical trial (#NCT04658472) and is described in our recent joint publication utilizing 15 patient sera samples, and has now progressed to a two-armed Phase III (NCT06290141 and NCT06290128). Numerous other INDs for phenotypic models based on data from 2-3 mutant iPSC derived organs have also been filed. Therapeutic index determination has also been shown for cancer and malaria applications as well as the construction of digital twins. For safety we believe the bar will be similar for augmentation of animal studies but would be significantly higher to replace a particular animal regulatory requirement. We have already demonstrated augmentation of a large animal model with Vanda Therapeutics.

Bio:  James J. Hickman is the Chief Scientist and Co-founder of Hesperos Inc. that is focusing on cell-based systems for drug discovery and toxicity as well as the founding Director of the NanoScience Technology Center and a Professor of Nanoscience Technology, Chemistry, Biomolecular Science, Material Science and Electrical Engineering at UCF and has a Ph.D. from MIT in Chemistry. While in industry, he established one of the first bioelectronics labs in the country that focused on cell-based sensors and their integration with electronic devices and MEMS devices. He has been constructing multi-organ human-on-a-chip or body-on-a-chip systems for toxicology and efficacy with up to 6 organs and has demonstrated long-term (>28 days) evaluation of drugs and compounds. He has also pioneered the development of functional platforms for CNS and PNS neurodegenerative disease. He has 185 publications, 20 book chapters and over 250 presentations, in addition he has over 40 pending and issued patents. He is a Fellow of AIMBE (2004), AVS (2007) and the National Academy of Inventors (2020). He is currently the President of the International Microphysiological Systems Society (IMPSS).