Benzinga | Oct 29, 2021 07:37AM EDT

Cytokinetics Announces Preclinical Data Relating To CK-3828136 Presented At 2021 Medicinal Chemistry Gordon Research Conference

Cytokinetics, Incorporated (NASDAQ:CYTK) today announced that preclinical data relating to the discovery and optimization of CK-3828136 (CK-136) were presented at the 2021 Medicinal Chemistry Gordon Research Conference in West Dover, VT. CK-136 is a novel, selective cardiac troponin activator in development for the potential treatment of diseases associated with impaired cardiac contractility, such as heart failure with reduced ejection fraction (HFrEF), right ventricular heart failure, and others.



"There is substantial evidence showing that activating cardiac myosin augments cardiac contractility and improves the clinical outcomes of patients, suggesting that activating the cardiac sarcomere is a viable approach to treat heart failure. We are developing an activator of cardiac troponin that also selectively increases cardiac function without increasing intracellular myocyte calcium concentrations," said Brad Morgan, Ph.D., Cytokinetics' Senior Vice President, Research and Non-Clinical Development. "CK-136 appears to have a favorable pharmacodynamic window that may provide for meaningful increases in cardiac function supportive of further clinical research to investigate its mechanism of action in diseases characterized by reduced cardiac function."

Data presented today describe the primary research objectives related to CK-136 including the identification of initial hit compounds and subsequent chemical optimization as well as preclinical characterization in biochemical assays, cardiac myocytes, and in vivo models of cardiac function. An initial cardiac troponin activator identified in screening was shown in a reconstituted sarcomere assay to selectively activate the cardiac troponin complex. Importantly, it did not inhibit phosphodiesterase 3 (PDE-3) IC50, and showed no effect on the cardiomyocyte calcium transient, indicating its selectivity. The optimization of the initial hit compound that led to CK-136 focused to maximizing the therapeutic window and its pharmacokinetic profile as could result in favorable increases in cardiac function. Preclinical studies demonstrated that the pharmacodynamic range for CK-136 was larger than that associated with omecamtiv mecarbil in similar preclinical models. Additionally, CK-136 demonstrated a pharmacokinetic profile and a projected human half-life that should enable once or twice daily dosing.

These preclinical data suggest that CK-136 is a selective cardiac troponin activator with a favorable pharmacodynamic window associated with substantial increases in cardiac contractility, representing a potential approach to augmenting cardiac contractility in diseases characterized by reduced cardiac function.