iCardioTox Profiler Developing a Novel In Vitro Assay to Assess Cardiotoxicity Using a Panel of Patient derived Cardiomyocytes

Abstract This proposed NIH SBIR Phase I Project by Stem Cell Theranostics SCT is aimed at developing a novel in vitro pre clinical screening platform to predict drug induced cardiotoxicity Cardiotoxicity is the most serious adverse drug reaction in clinical development and a leading cause of late stage drug failures The pharmaceutical industry is under growing pressure to correct declining productivity which is increasingly driven by the high level of late stage drug failures It is now estimated that the average cost to bring a new drug to market is more than $ billion dollars To reduce high attrition rates and increased costs drug developers need to be able to identify potential safety issues as early as possible during the drug discovery process Doing so would enable more attention to be focused on programs with optimal chances of progressing through end stage clinical trials rather than on costly failures The overall focus of this proposal is to develop a screening assay using a panel of patient derived cardiomyocytes and standardized methods to rapidly assess cardiotoxicity Our patient and disease specific human induced pluripotent stem cell derived cardiomyocytes iPSC CM models address an urgent need a means for investigators to perform in vitro toxicity testing of their compounds on human cells before in vivo testing These preclinical models enable faster critical decisions by prioritizing drug candidates and dramatically reduce development costs by predicting clinical outcomes Using patient derived iPSC CMs as translational models holds the promise of revolutionizing drug discovery and development The streamlined drug toxicity testing made possible by this innovation has the potential to bridge the Valley of Death created by phenomenal drug attrition and catalyze a shift to a new drug development paradigm where life threatening hazards to human health are predicted early in development Successful completion of this project will lead to improved detection of cardiotoxicity early in the drug discovery process Importantly this project will pave the path for using cardiac disease models to improve toxicity testing and will set precedence for using precision methods and disease models to inform drug discovery Our goal is to enable the development of safer drugs and dramatically reduce development costs NIH Project Narrative Cardiotoxicity is the most serious adverse drug reaction in clinical development and a leading cause of late stage drug failures Here our start up company Stem Cell Theranostics proposes to develop a robust in vitro screening platform to predict drug induced cardiotoxicity Our approach is to assemble a diverse panel of patient derived cardiomyocytes and using standardized methods screen drug candidates to rapidly assess cardiotoxicity early in development Our goal is to enable the development of safer drugs dramatically reduce development costs and reduce life threatening risks