Development of a DIVI platform for issue resolution in pre-clinical drug development.



 DESCRIPTION (provided by applicant): Drug-induced vascular injury (DIVI) is a common phenomenon in pre-clinical animal studies and is typically characterized by hemorrhage, vascular endothelial and smooth muscle cell necrosis, medial blood cell infiltration and inflammation. Mechanisms underlying DIVI are not well understood for several reasons. A DIVI result in a preclinical GLP animal study can interrupt or stop the progression of a promising drug to the clinic. In addition, GLP safety studies in non-human primates required to de-risk early DIVI findings in lower species are costly. HemoShear, LLC is a biotechnology research company that utilizes patented methodologies (US 7,811,782) to restore in vivo biology to animal and human primary cells in co-culture in vitro. The HemoShear vascular system exposes primary endothelial cells to vascular region-specific hemodynamics in co-culture with primary smooth muscle cells. In this system, vascular cells are rescued from a non-physiological "state" as indicated by restoration of region-specific in vivo morphology and function. Importantly, cells in the HemoShear system demonstrate an efficacious or toxic response to drugs at concentrations that approximate in vivo animal or human exposure levels, which are often 1 to 2 orders of magnitude different from standard 2D static cell culture systems. HemoShear's preliminary data with known DIVI compounds show that our science can predict unforeseen DIVI in vitro and prior to pre-clinical GLP studies. In 2014, HemoShear received the Tibbetts SBIR Award from the Small Business Administration for commercialization of innovation. The purpose of this SBIR is to further validate the HemoShear DIVI platform for routine commercial application and prospective decision-making in pre-clinical drug discovery and development.