Cytokinetics, Incorporated (NASDAQ: CYTK) announced today that three abstracts summarizing non-clinical data regarding its smooth muscle contractility program were presented at the 2009 Scientific Sessions of the American Heart Association in Orlando, Florida.
"Our smooth muscle contractility program leverages our expertise in the contractile apparatus of muscle systems, which has generated clinical stage drug candidates in both our cardiac and skeletal muscle programs," stated David J. Morgans, PhD Cytokinetics' Executive Vice President of Preclinical Research and Development. "We are pleased to share these three presentations relating to our novel mechanism approach for modulation of smooth muscle contractility. We believe that these data demonstrate the potential of smooth muscle myosin inhibitors for the treatment of patients with diseases that may cause significant morbidity, such as refractory systemic hypertension and pulmonary arterial hypertension."
Oral Presentations
An oral presentation titled "Inhibition of Smooth Muscle Myosin, a Novel Anti-Hypertensive Strategy" was presented on Monday, November 16, 2009 by Fady Malik, MD, PhD, FACC, Vice President, Biology and Therapeutics, Cytokinetics, Inc., South San Francisco, California. This presentation summarized non-clinical research evaluating smooth muscle myosin inhibitors in models of hypertension. The authors concluded that smooth muscle myosin inhibition reduced vascular resistance and lowered blood pressure in a canine model of hypertension. In addition, the pattern of regional vasodilation is different for a specific smooth muscle myosin inhibitor, CK-2018448, as compared to the calcium channel blocker, amlodipine. For CK-2018448, blood flow to the kidney increased without change in blood flow to the limb. In contrast, for amlodipine, the largest increases in blood flow were found in the limb. The authors concluded that the smooth muscle myosin inhibitor and the calcium channel blocker elicited different patterns of regional vasodilation. In addition, the renal vasodilation induced by smooth muscle myosin inhibition could have salutary effects in conditions accompanied by renal insufficiency such as hypertension, acute heart failure, and acute renal failure due to an interruption of adequate blood flow to the kidney.
An oral presentation titled "A Direct Inhibitor of Smooth Muscle Myosin as a Novel Therapeutic Approach for the Treatment of Pulmonary Artery Hypertension" was presented on Tuesday, November 17, 2009 by Malarvannan Pannirselvam, M.V.Sc., Ph.D., Scientist, Cytokinetics, Inc., South San Francisco, California. This presentation summarized a non-clinical study designed to test the hypothesis that direct inhibition of smooth muscle myosin should provide a novel and effective means of relaxing vascular smooth muscle. In this study, the authors concluded that CK-2018571, a smooth muscle myosin inhibitor, selectively inhibited the ATPase activity of smooth muscle myosin and relaxed contracted arteriovascular tissue rings as a consequence of direct inhibition of smooth muscle myosin. In addition, CK-2018571 relaxed pulmonary arterial rings from MCT-PAH rats suggesting its potential use as a vasodilator in pulmonary arterial hypertension. Finally, an active pro-drug of CK-2018571, CK-2019165, decreased the elevated right ventricular systolic pressure in two animal models of pulmonary arterial hypertension. The authors concluded that these data together support the hypothesis that direct inhibition of smooth muscle myosin could be a novel therapeutic approach for the treatment of pulmonary arterial hypertension.
Poster Presentation
A poster presentation titled "Inhibition of Smooth Muscle Myosin, a Novel Therapeutic Approach for Pulmonary Hypertension" was presented on Tuesday, November 17, 2009 by David Ho, MD, CV Dynamics and the Department of Cell Biology and Molecular Medicine and Cardiovascular Research Institute, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ from 9:30 AM - 11:00 AM Eastern Time. This poster summarized a non-clinical study designed to establish a porcine model of acute pulmonary arterial hypertension, by either hypoxia or administration of a thromboxane analog, and to examine the extent to which the inhibition of smooth muscle myosin by CK-2019165 administered either intravenously or by inhalation is able to ameliorate pulmonary hypertension in chronically instrumented pigs. The authors concluded that CK-2019165, delivered intravenously at a dose of 4 mg/kg, reduced (p < 0.01) the increased pulmonary vascular resistance in both hypoxia and thromboxane models, respectively. Mean arterial pressure fell modestly and heart rate rose slightly in the conscious state. In addition, in the hypoxia model, CK-2019165 was delivered via inhalation and the increased pulmonary vascular resistance fell similarly while mean arterial pressure and heart rate were unchanged. The maximum extent of vasodilation was similar to that produced with sodium nitroprusside. The authors concluded that inhibition of smooth muscle myosin may be a novel therapeutic approach to the treatment of pulmonary arterial hypertension.
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