Metrion provides cardiac safety screening services using clinically translatable human induced pluripotent stem cell (hiPSC) -derived cardiomyocyte assays to identify cardiac liabilities early in drug discovery. Our cardiac safety experts generate actionable data on QTc prolongation, QRS widening, proarrhythmic risk and cardiotoxicity, enabling informed project decisions before compounds enter expensive preclinical and clinical development stages.
Our cardiac safety screening services include:
Our clinically translatable cardiomyocyte model delivers early decision-making data regarding the potential cardiac risks associated with new compounds. By utilising a hiPSC-derived cardiomyocyte assay, researchers can obtain predictive data on how a compound might affect cardiac function in humans before it enters clinical trials. This data can ultimately prevent late-stage drug development failures and avoid the substantial costs associated with such failures.
In addition to providing valuable information about drug-induced cardiac effects, this advanced model can improve the overall efficiency of the drug discovery process. By detecting potential safety issues early, researchers can make informed decisions about whether to proceed with a compound or pursue other options.
Integrating a clinically translatable assay into your preclinical strategy allows you to protect your development investment, maximise speed to market, and ensure every pound of R&D spend is strategically deployed.
Reduce the risk of costly late-stage failure
Allocate capital towards candidates with the highest probability of success
Accelerate time-to-decision and reach key milestones faster
Protect shareholder value and avoid expensive rework
Strengthen your approach to risk management and due diligence
Fully aligned with regulatory expectations and new approach methodologies
High-throughput, reliable detection of compound-induced effects such as QTc prolongation and arrhythmogenic risk, well before in vivo or clinical studies
Suitable for a range of compound modalities, including those with complex ion channel pharmacology
Seamless integration with cardiac ion channel profiling and toxicity testing
Detect and contextualise risk earlier, including effects missed by acute ion channel studies
Streamline workflow with expert support at every stage
Metrion’s hiPSC-derived cardiomyocyte assay is a higher-throughput, 96-well plate-based system designed to assess changes in action potential morphology, which is a key indicator of cardiac function. The assay can be used to evaluate both acute and chronic exposure to compounds, providing comprehensive safety pharmacology and toxicology data over a range of exposure durations (24 hours or greater). This is especially important for detecting chronic toxicities that may not be apparent during short-term testing.
The 96-well plate format makes the assay highly cost-efficient and suitable for higher-throughput screening.
The assay is aligned with current International Council for Harmonisation (ICH) S7B guidelines for non-clinical cardiac safety testing and adheres to the principles outlined in the FDA Modernization Act 2.0. These guidelines are designed to ensure that drugs are evaluated in ways that are relevant to human health, improving the overall safety and efficacy of new therapeutics. Read about the need to embrace the future of preclinical drug discovery safety.
A critical feature of Metrion’s hiPSC-derived cardiomyocyte assay is its ability to assess the impact of compounds on action potential morphology. Changes in the shape and duration of the cardiac action potential are key indicators of potential toxicity or arrhythmia risk. By examining how compounds affect ion channel activity and their interactions with critical cardiac proteins such as hERG, researchers can gain insight into whether a compound might cause harmful effects on the heart.
Recordings using voltage-sensitive dye (VSD) with quality equivalent to patch-clamp are valuable for assessing cardiovascular risk in drug discovery. They provide a high-fidelity, high-throughput alternative to traditional electrophysiology techniques.
VSD-based recordings offer:
Figure 1. Representative traces from the assay clearly demonstrate how selective ion channel blockers or hERG trafficking block agents influence the action potential morphology of hiPSC-derived cardiomyocytes. This enables detailed analysis of how different compounds might cause changes in the duration and characteristics of the action potential, providing a clearer understanding of their potential risks before clinical testing. 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.
A significant challenge in drug development is the potential for novel compounds to cause QTc prolongation or QRS interval widening, both of which are associated with a higher risk of arrhythmias and sudden cardiac events. Accurate prediction of these issues is essential for identifying and mitigating cardiac risks early in the development process.
Metrion’s hiPSC-derived cardiomyocyte assay:
Figure 2. Metrion’s hiPSC cardiomyocyte assay highlights QRS risk. An ROC analysis of 22 QRS positive and 12 QRS negative compounds clearly defines the ability of the assay to define the free clinical exposure associated with QRS with high accuracy.
Another significant advantage of Metrion’s hiPSC-derived cardiomyocyte assay is its ability to assess compounds over extended periods, up to 48 hours, in serum-free conditions. This allows for the evaluation of chronic toxicities and other long-term effects that might not be detectable in shorter, serum-containing assays. Extended testing durations are critical for assessing the full impact of drugs that may require prolonged exposure to cause adverse effects.
Metrion combines expertise in ion channel pharmacology, cardiac electrophysiology and translational safety pharmacology to provide scientifically robust cardiac safety screening services that support decision-making throughout drug discovery and preclinical development.
Early cardiac derisking helps identify potential cardiac liabilities, such as QTc prolongation, arrhythmias and other cardiotoxic effects, before compounds enter expensive preclinical and clinical development stages. Detecting these risks early enables drug discovery teams to make informed candidate selection decisions, reduce the likelihood of costly late-stage failures, improve patient safety and minimise reliance on animal testing. Metrion's hiPSC-derived cardiomyocyte assays provide clinically translatable data that support early assessment of cardiac risk and more confident progression of drug candidates.
Cardiac safety screening is most valuable during hit-to-lead, lead optimisation and candidate selection, enabling potential liabilities to be identified before significant development investment.
Yes. Metrion can integrate ion channel profiling and hiPSC cardiomyocyte screening to provide a more comprehensive assessment of cardiac safety risk.
Metrion’s hiPSC-derived cardiomyocyte assay is designed to be reliable, reproducible, and highly translatable to human clinical data. This is particularly important as drug developers are under increasing pressure to ensure that their preclinical studies are predictive of human clinical outcomes. The use of hiPSC-derived cardiomyocytes provides a more accurate representation of human cardiac function compared to traditional animal models, which can often have species-specific differences in ion channel expression and drug response.
Our assays demonstrate the cardiac safety of therapeutic compounds in accordance with current regulatory guidelines, including those set forth within ICH S7B.
Figure 3. Assessing the effect of compounds on the ventricular action potential waveform in a plate-based human stem cell cardiomyocyte model.
The hiPSC-derived cardiomyocyte model offers several key advantages, making it an essential tool for early cardiac derisking in drug discovery:
Human relevant cardiac safety model
The assay provides a human-relevant model that better reflects the response of human hearts to therapeutic compounds, which is critical for improving the predictability of drug safety in clinical trials. Traditional animal models, such as those using rats or dogs, do not always replicate human cardiac physiology accurately.
Reduction of animal testing in drug discovery
The use of hiPSC-derived cardiomyocytes significantly reduces the need for animal testing, which aligns with the ethical principles of the 3Rs (Replacement, Reduction, Refinement) in animal research. This reduction in animal testing not only improves the ethical standards of drug development but also reduces costs and enhances the sustainability of the drug discovery process.
Early detection of cardiotoxicity in preclinical drug discovery
By identifying cardiotoxic compounds early in the drug development process, Metrion’s hiPSC-derived cardiomyocyte assay helps to avoid late-stage failures that can be costly and time-consuming. Early detection of cardiac risks allows for more informed decision-making and resource allocation, ultimately saving time and money in the long run.
Versatile assay for comprehensive cardiac safety assessment
This assay can be used in conjunction with other types of cardiac assessments, such as electrophysiological studies, contractility assays, biochemical analyses, and even in vivo studies. Its flexibility makes it an invaluable tool that can complement other experimental systems and provide a comprehensive view of a compound’s cardiac safety profile.
As the FDA embraces non-animal testing methods, Metrion’s hiPSC cardiomyocyte assay offers a human-relevant, clinically translatable solution for early cardiac safety assessment in drug development. Using hiPSC-derived cardiomyocytes and high-frequency optical recording, this assay reliably predicts key cardiac risk markers like QTc prolongation, aligning with FDA-endorsed New Approach Methodologies (NAMs) and the CiPA framework. Scalable, reproducible, and validated, it provides an ethical and efficient alternative to animal models, helping sponsors reduce costs, accelerate timelines, and meet evolving regulatory expectations in a post-animal testing era.
The VOLTA scanner is produced by Lumencor, a developer of advanced illumination and imaging technologies for life science research. At Metrion, the VOLTA platform supports high-content optical electrophysiology studies, enabling efficient assessment of compound effects in human-relevant cellular models used in drug discovery and safety pharmacology programmes.
Optical voltage imaging of human iPSC-derived cardiomyocytes was used to assess electrophysiological effects of compounds beyond hERG inhibition. Action potential waveform analysis revealed compound-specific and concentration-dependent changes, enabling mechanistic differentiation of multichannel activity and demonstrating a human-relevant approach for translational cardiac safety assessment.
Action Potential Waveform Analysis in Human IPSC-Cardiomyocytes Enables Mechanistic Assessment of Multichannel Cardiac Effects