Cytokinetics Presents Data From Heart Failure Program

Presentation Supports Advancement of CK-1827452 Towards Clinical Development

South San Francisco, CA - July 27, 2005

Cytokinetics, Incorporated (Nasdaq: CYTK) announced that the company presented a scientific poster related to its congestive heart failure program yesterday at the 2nd Annual Symposium of the American Heart Association Council on Basic Cardiovascular Sciences – Targeting Heart Failure: New Science, New Tools, New Strategies which is currently being held at the Keystone Conference Center in Keystone, Colorado.

The poster titled, “Direct Activation of Cardiac Myosin, A Novel Mechanism for Improving Cardiac Function” [Poster Abstract Presentation #P136] was presented on Tuesday, July 26, 2005 at 5:00 pm Mountain Time. This presentation covered experiments that characterized the mechanism of action of CK-1213296, a small molecule activator of cardiac myosin discovered by Cytokinetics. The objective of this research was to discover and optimize molecules that improve cardiac function in a manner consistent with the therapeutic hypothesis, specifically that improving cardiac contractility by directly activating cardiac myosin can potentially address the liabilities of current inotropic drugs. The data demonstrated that CK-1213296 activated cardiac myosin by accelerating actin-dependent phosphate release. In cardiac myocytes, CK-1213296 increased contractility without changes in intracellular calcium, a finding consistent with its mechanism of action. In addition, CK-1213296 demonstrated an increase in cardiac contractility and stroke volume in a dog model of heart failure in a manner that supports the therapeutic hypothesis.

The presentation provided non-clinical support for the Company’s novel therapeutic approach of directly activating the cardiac myosin motor protein as a potential next-generation approach to managing acute and chronic congestive heart failure. In addition, the findings support the hypothesis that drug candidates arising from this research program may address certain clinical liabilities associated with existing pharmaceuticals. In prior presentations, Cytokinetics scientists have demonstrated that cardiac myosin activators increase cardiac contractility without stimulating beta-adrenergic receptors or inhibiting phosphodiesterase activity to increase intracellular calcium, which may be arrhythmogenic and has been associated with adverse clinical effects. Cytokinetics is planning to advance another cardiac myosin activator, CK-1827452, designated for development earlier this year, into Phase I human clinical trials for congestive heart failure in the second half of 2005.

“We are very pleased to have the opportunity to present these research findings which further characterize the mechanism of action for compounds arising from this program” stated David Morgans, Jr., Ph.D., Senior Vice President of Drug Discovery and Development. “Building on the data we presented at the Scientific Sessions of the American Heart Association in November 2004 and at the American Society of Cell Biology in December 2004, this presentation further demonstrates the breadth and depth of our knowledge related to our cardiac myosin activators, by extending validation of the therapeutic hypothesis through pharmacologic models.”

“We are pleased with the progress of this program and look forward to moving our lead drug candidate from our cardiac myosin program, CK-1827452, into human clinical trials this year,” stated James Sabry, M.D., Ph.D., President and Chief Executive Officer. “Cardiac myosin activators represent a novel class of drug candidates that may improve the treatment of congestive heart failure, without the liabilities associated with current inotropes. We are excited about testing this therapeutic hypothesis in humans.”

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, the fundamental unit of muscle contraction in the heart that is a highly ordered cytoskeletal structure composed of cardiac myosin, actin and a set of regulatory proteins. 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 congestive 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 to increase intracellular calcium, which may be associated with adverse clinical effects in heart failure patients. Existing drugs that seek to improve cardiac cell contractility increase the concentration of intracellular calcium, which indirectly activates cardiac myosin, but this effect on calcium levels also has been 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. Cytokinetics expects to enter human clinical trials in 2005 with a novel small molecule cardiac myosin activator, CK-1827452, for the treatment of heart failure. 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 expected timing, scope and results of our clinical development and research programs and statements regarding the potential benefits of our drug candidates and potential drug candidates and the enabling capabilities 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, testing, regulatory approval, production and marketing of Cytokinetics’ drug candidates that could slow or prevent clinical development, product approval or market acceptance (including the risks related to uncertainty of patent protection for Cytokinetics’ intellectual property or trade secrets, Cytokinetics’ ability to obtain additional financing if necessary and unanticipated research and development and other costs). For further information regarding these and other risks related to Cytokinetics’ business, investors should consult Cytokinetics’ filings with the Securities and Exchange Commission.