Improve efficiency, reduce late-stage failures, and align with regulatory standards by assessing the proarrhythmic liability of your compounds early.
Metrion’s human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte assay is an advanced tool, providing key advantages for early cardiac derisking in drug discovery.
Our clinically translatable cardiomyocyte model offers early decision-making data on the potential cardiac risks of novel early-stage discovery compounds, significantly reducing the reliance on costly animal studies.
This high-throughput model:
Provides comprehensive safety pharmacology and toxicology data from acute and chronic (24 h or greater) exposure of compounds.
Is a cost efficient 96-well plate-based assay, assesses changes in action potential morphology.
Aligns with current ICH S7B guidelines and adheres to the principles of the FDA Modernization Act 2.0.
Figure 1. Representative traces showing the impact on hiPSC-derived action potential morphology of selective ion channel or hERG trafficking block. Metrion’s hiPSC-derived cardiomyocyte assay is a powerful tool for early cardiac derisking, contributing to safer and more efficient drug development processes.
Peter Kilfoil, Shuyun Lily Feng, Asser Bassyouni, Tiffany Lee, Derek Leishman, Dingzhou Li, David J. MacEwan, Parveen Sharma, Eric D. Watt, Stephen Jenkinson, Characterization of a high throughput human stem cell cardiomyocyte assay to predict drug-induced changes in clinical electrocardiogram parameters, European Journal of Pharmacology, Volume 912, 2021.
Our reliable and reproducible translational human cardiovascular assays demonstrate the cardiac safety of your therapeutic compounds in line with current and future CiPA and FDA guidelines.
QTc and QRS liabilities are a serious concern when developing novel clinical compounds. Assessment of ion channel activity provides a robust method to highlight potential risks, however it may not be sufficient to capture all potential mechanisms that could induce QTc, QRS or arrhythmia issues. In such cases an integrated system such as the hiPSC-derived cardiomyocyte (hiPSC-CM) model can be a valuable model.
We can assess compounds for such liabilities in hiPSC-CMs in a higher throughput 96-well plate-based format. Using a voltage sensitive fluorescent dye, we can simultaneously measure action potential waveforms with high fidelity across all wells using the Lumencor VOLTA high frequency (10kHz) plate reader. This allows us to accurately capture endpoints such as action potential duration (e.g. APD90), rise time and beat rate. Moreover, this system allows for the assessment of compounds over extended time periods (up to 72h) in serum free conditions.
A key aspect of this model is its ability predict a compounds propensity to generate a prolongation in the clinical QTc interval. Moreover, that assay can help predict the free clinical exposure of a novel compound that would be associated with a 10 ms change in clinical QTc. Similarly, this model can also define the probability of a QRS clinical liability.
Further reading: Characterization of a high throughput human stem cell cardiomyocyte assay to predict drug-induced changes in clinical electrocardiogram parameters, European Journal of Pharmacology, Volume 912, 2021.
Figure 2. Assessing the effect of compounds on the ventricular action potential waveform in a high-throughput human stem cell cardiomyocyte model.
The assay provides a more human-relevant model compared to animal studies, potentially improving the predictability of human responses in clinical trials.
The use of hiPSC-derived cardiomyocytes reduces the need for animal testing, aligning with the principles of the 3Rs (Replacement, Reduction, Refinement) in animal research and the FDA Modernization Act 2.0.
By identifying cardiotoxic compounds early in the drug development process, Metrion’s VOLTA hiPSC-derived cardiomyocyte assay helps to avoid late-stage failures, saving time and resources.
These assays can be used in conjunction with various types of cardiac assessments, including electrophysiological studies, contractility assays, biochemical analyses and even in vivo studies.
Improve efficiency, reduce late-stage failures, and align with regulatory standards by assessing the proarrhythmic liability of your compounds early.
"The data is always correct and is in a format that imports directly into our systems, making it so quick and easy for our team to review the data across individual projects."