Cytokinetics Announces the Initiation of a Phase I Clinical Trial of CK-1827452 for the Treatment of Acute Heart Failure

Cardiac Myosin Activator Extends Validation of Cytoskeletal Platform

South San Francisco, CA - September 6, 2005

Cytokinetics, Incorporated (Nasdaq: CYTK) announced the initiation of a Phase I clinical trial with CK-1827452, a novel, small-molecule activator of cardiac myosin, for the treatment of patients with heart failure. CK-1827452 is the first clinical drug candidate to arise from the company’s cardiac myosin activator program which leverages Cytokinetics’ expertise in cytoskeletal pharmacology and muscle contractility.

This first-in-humans Phase I clinical trial is a double-blind, randomized, placebo-controlled trial being conducted to investigate the safety, tolerability, pharmacokinetic, and pharmacodynamic profile of CK-1827452 in normal healthy volunteers. This dose-escalation trial is designed to identify the maximally tolerated dose of a 6-hour intravenous infusion of CK-1827452. The effect of CK-1827452 on the left ventricular function of these healthy volunteers will be evaluated using serial echocardiograms. Importantly, because of the cross-over design of this clinical trial, the volunteers will be acting as their own controls to compare the effects of escalating doses of CK-1827452 to those of placebo. The study is being conducted under a Clinical Trial Application at a clinical center in the United Kingdom.

“Based on non-clinical data in normal animals and also animals with heart failure, we believe this drug candidate may increase the indices of left ventricular systolic function, such as stroke volume and ejection fraction, in healthy volunteers,” stated Andrew Wolff, M.D., F.A.C.C., Senior Vice President, Clinical Research and Development and Chief Medical Officer. “The echocardiographic data may help to corroborate the novel mechanism of the drug and may inform the translation of this novel approach to the treatment of acute and chronic heart failure. We believe that the novel mechanism of cardiac myosin activators may improve the treatment of acute and chronic heart failure by potentially increasing the contractile function of the heart while avoiding some of the unwanted side effects of currently available drugs.”

Cardiac myosin activators directly activate the cardiac myosin motor protein and are a potential next-generation treatment for acute and chronic heart failure. Cytokinetics has presented non-clinical data relating to this novel therapeutic approach. Cytokinetics’ scientists have demonstrated in animal models that cardiac myosin activators increase cardiac contractility without stimulating beta-adrenergic receptors or inhibiting phosphodiesterase activity, and consequently, without increasing cardiac myocyte intracellular calcium, which may be arrhythmogenic and has been associated with other adverse clinical effects. Those findings supported the hypothesis that CK-1827452 and other similar cardiac myosin activators may address certain clinical liabilities associated with existing pharmaceuticals. Furthermore, CK-1827452 has been demonstrated to be orally bioavailable in animals, which raises the prospect of its development for chronic oral administration in the long-term treatment of heart failure. Additional non-clinical results relating specifically to CK-1827452 will be presented at the Heart Failure Society of America Annual Meeting in Boca Raton, Florida on September 19, 2005.

“We are excited about achieving this important milestone for this program and about the potential of CK-1827452 as a novel approach to addressing the central problem in most cases of heart failure; that is, impaired left ventricular function,” stated James Sabry, M.D., Ph.D., President and Chief Executive Officer. “CK-1827452 is the third drug candidate to emerge from our internal research activities and further validates the importance of our focus on cell biology and cytoskeletal pharmacology.”

Background on Cardiac Contractility and Cardiac Myosin Activators

Cardiac myosin is the cytoskeletal motor protein in the cardiac muscle cell that is directly responsible for converting chemical energy into mechanical force, resulting in cardiac contraction. Cardiac contractility is driven by the cardiac sarcomere, a highly ordered cytoskeletal structure composed of cardiac myosin, actin and a set of regulatory proteins, that is the fundamental unit of muscle contraction in the heart. The sarcomere represents one of the most thoroughly characterized protein machines in human biology.

Cytokinetics’ heart failure program is focused towards the discovery and development of small molecule cardiac myosin activators in order to create next-generation treatments to manage acute and chronic heart failure. Cytokinetics’ program is based on the hypothesis that activators of cardiac myosin may address certain mechanistic liabilities of existing pharmaceuticals by increasing cardiac contractility without stimulating beta-adrenergic receptors or inhibiting phosphodiesterase activity, and consequently, without increasing cardiac myocyte intracellular calcium, which has been associated with adverse clinical effects in heart failure patients. Existing drugs improve cardiac cell contractility by increasing the concentration of intracellular calcium, which indirectly activates cardiac myosin, but this effect on calcium levels may also be linked to potentially life threatening arrhythmias. In contrast, cardiac myosin activators have been shown to work by a novel mechanism that directly stimulates the activity of the cardiac myosin motor protein by accelerating the rate-limiting step of the myosin enzymatic cycle, thereby shifting the enzymatic cycle in favor of the force producing state.

About Cytokinetics

Cytokinetics is a leading biopharmaceutical company focused on the discovery, development and commercialization of novel small molecule drugs that specifically target the cytoskeleton. The cytoskeleton is a complex biological infrastructure that plays a fundamental role within every human cell. Cytokinetics’ focus on the cytoskeleton enables it to develop novel and potentially safer and more effective classes of drugs directed at treatments for cancer, cardiovascular disease and other diseases. Cytokinetics has developed a cell biology driven approach and proprietary technologies to evaluate the function of many interacting proteins in the complex environment of the intact human cell. Cytokinetics employs the PUMA™ system and Cytometrix™ technologies to enable early identification and automated prioritization of compounds that are highly selective for their intended protein targets without other cellular effects, and may therefore be less likely to give rise to clinical side effects. Cytokinetics and GlaxoSmithKline have entered into a strategic alliance to discover, develop and commercialize small molecule therapeutics targeting human mitotic kinesins for applications in the treatment of cancer and other diseases. GlaxoSmithKline is conducting Phase II and Phase Ib clinical trials for ispinesib (SB-715992) and a Phase I clinical trial for SB-743921, each a drug candidate that has emerged from the strategic alliance. Cytokinetics’ heart failure program is the second program to leverage the company’s expertise in cytoskeletal pharmacology. Additional information about Cytokinetics can be obtained at www.cytokinetics.com.

This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Cytokinetics disclaims any intent or obligation to update these forward-looking statements, and claims the protection of the Safe Harbor for forward-looking statements contained in the Act. Examples of such statements include, but are not limited to, statements relating to the potential development of CK-1827452 as an improved treatment of acute and chronic heart failure while avoiding unwanted side effects, the expected clinical development of this compound, statements about upcoming presentations of results from these developmental efforts and statements regarding the potential benefits of our drug candidates and potential drug candidates and the enabling capabilities and utility of our proprietary technologies and biological focus. Such statements are based on management’s current expectations, but actual results may differ materially due to various factors. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to difficulties or delays in development, and conducting clinical trials, unexpected toxicities or lack of demonstrated efficacy in such clinical trials, uncertainties in receiving regulatory approval, or market. For further information regarding these and other risks related to Cytokinetics’ business, investors should consult Cytokinetics’ filings with the Securities and Exchange Commission.