Abstract 4365373: An Innovative Human iPSC Cardiomyocyte Platform to Accelerate Cardiac Drug Discovery and Target Validation

Background: Effective treatment of cardiac diseases requires a deep understanding of disease-relevant cellular mechanisms that drive pathology in the human heart. Traditional cell lines often lack the complexity and genetic context necessary to capture these mechanisms. Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes provide a physiologically relevant and genetically diverse platform to model human cardiac disease biology. Evotec’s iPSC platform enables detailed study of disease processes critical for identifying therapeutic targets and developing novel treatments. Methods&Results: We developed a robust, scalable human iPSC-based cardiomyocyte platform integrating a genetically diverse bank of well-characterized iPSC lines and optimized cardiac differentiation protocols. The platform enables the generation of multiple human-relevant cardiac cell types and model systems, including cardiomyocytes, cardiac fibroblasts, 2D co-cultures of these cell types, 3D cardiac spheroids, and engineered heart tissue (EHT). Genome editing technologies, including CRISPR/Cas9 and RNA interference, are routinely applied at both iPSC and cardiomyocyte stages. These tools enable the introduction of disease-relevant mutations to model specific cardiac pathologies, as well as the validation and exploration of novel target gene functions within a human cellular context. To assess disease mechanisms and potential target effects, we use multi-electrode arrays (MEA) for electrophysiology, xCELLigence and FlexCyte for contractility, and calcium transient assays. This enables high-throughput, quantitative, and physiologically relevant phenotyping. Pharmacological testing with well-characterized compounds confirms the platform’s sensitivity to cardiac functional changes. Conclusion: Evotec’s iPSC cardiomyocyte platform, combined with the Evotec Heart Atlas, offers a human-relevant system for cardiac disease modeling, drug target validation, and mechanistic insights. Together, these platforms accelerate cardiovascular therapy discovery and increase clinical success through improved human and disease relevance.