The FDA has acknowledged the need for more precise and meaningful electrocardiographic markers than the QTc interval prolongation - currently the surrogate marker for arrhythmia liability by ICH E14 regulatory guidance. Current Thorough QT (TQT) studies that are based on this biomarker have several shortcomings that increase time and cost of drug development and lead to false-positives and false negatives in cardiac safety studies. Specifically, the limitations of the current QTc marker are the following:

• Limited precision due to reliance on consistent identification of the end of T-wave;
• High cost due to the need for manual adjustment of the end of T-wave measurement by cardiologists;
• Poor performance of the marker (i.e., high rate of false-positives and lower but not insignificant rate of false-negatives) for drugs that affect the autonomic state;
• Inability to distinguish among genetic and phenotypic differences that may predispose subjects to arrhythmias.

iCardiac develops and implements advanced ECG biomarkers that enable a comprehensive evaluation of repolarization morphology and dynamics, bringing greater clarity to a drug’s cardiac safety profile. Unlike the current QTc prolongation measurement, iCardiac’s repolarization biomarkers enable measurement of the subtle differences in ECG signals that may indicate arrhythmia predisposition. iCardiac’s Beyond QT morphologic biomarkers offer:

• Identification of drug-induced repolarization abnormalities with dramatically fewer false positives and false negatives.
• Characterization of a drug’s effect on specific ion channels in the heart based on ECG data;
• Greater automation (No need for measuring the end of the T-wave);
• Dramatically lower cost of analysis;
• Advanced testing and research tools for analyzing repolarization in animal, clinical phase I and II studies, and large phase III and IV clinical trials.

The effectiveness of these biomarkers for cardiac safety evaluation has been demonstrated in several validation studies.

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