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Cytokinetics Presents Research Data from Heart Failure Program; Additional Presentations at the American Society of Cell Biology Meeting Span Multiple Therapeutic Areas.


SOUTH SAN FRANCISCO South San Francisco, city (1990 pop. 54,312), San Mateo co., W Calif.; inc. 1908. South San Francisco has several industrial parks; its manufactures include medical supplies and equipment, foods, paint, paper products, consumer goods, and clothing. , Calif. -- Cytokinetics, Inc. (Nasdaq: CYTK) announced today that four of the eleven poster presentations that the company made this week at the 44th Annual American Society of Cell Biology (ASCB ASCB American Society for Cell Biology
ASCB Avionics Standard Communication Bus
ASCB Address Space Control Block (MVS)
ASCB Arbitrarily-Shaped Conducting Body
) Meeting in Washington, DC relate to its congestive heart failure congestive heart failure, inability of the heart to expel sufficient blood to keep pace with the metabolic demands of the body. In the healthy individual the heart can tolerate large increases of workload for a considerable length of time.  program. The heart failure program presentations provide further preclinical support for the novel mechanism of directly stimulating the activity of the cardiac myosin myosin (mī`əsĭn), one of the two major protein constituents responsible for contraction of muscle. In muscle cells myosin is arranged in long filaments called thick filaments that lie parallel to the microfilaments of actin.  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 mechanistic liabilities of existing pharmaceuticals by increasing cardiac contractility contractility /con·trac·til·i·ty/ (kon?trak-til´i-te) capacity for becoming shorter in response to a suitable stimulus.

contractility

a capacity for becoming short in response to suitable stimulus.
 without increasing intracellular calcium or inhibiting phosphodiesterase phosphodiesterase /phos·pho·di·es·ter·ase/ (-di-es´ter-as) any of a group of enzymes that catalyze the hydrolytic cleavage of an ester linkage in a phosphoric acid compound containing two such ester linkages.  activity, each of which may be associated with adverse clinical effects. Cytokinetics is currently planning to move a compound from this program into Phase I human clinical trials for congestive heart failure in 2005.

The presentations related to the company's congestive heart failure program were as follows:

--"Activation of Cardiac Sarcomere sarcomere /sar·co·mere/ (sahr´ko-mer) the contractile unit of a myofibril; sarcomeres are repeating units, delimited by the Z bands, along the length of the myofibril.

sar·co·mere
n.
 ATPase by CK-1122534, a Small Molecule Agent that Specifically Targets Cardiac Myosin," was presented on Sunday, December 5, 2004. This presentation covered experiments that characterized the mechanism of action of CK-1122534, a small molecule activator of cardiac myosin discovered at Cytokinetics, in a series of steady-state and transient kinetic biochemical assays. This presentation concluded that this experimental compound can activate the ATPase of cardiac myosin in various reconstituted systems and in skinned cardiac myofibrils, that this activation is specific for cardiac myosin and that it involves an acceleration of actin-dependent phosphate release.

--"The Cardiac Myosin Activator, CK-1122534, Overcomes the Myosin II Inhibitors 2, 3-Butanedione-2-Monoxime and (-)-S-Blebbistatin without Affecting the Ca(2+) Transient in Ventricular Myocytes," was presented on Tuesday, December 7, 2004. This presentation summarized work in cardiac myocytes designed to further characterize the mechanism of action of CK-1122534 indicating that the cardiac myosin activator can overcome the inhibition of ventricular myocyte contractility by the myosin inhibitors, blebbistatin and 2, 3-Butanedione-2-Monoxime (BDM BDM Black Divorced Male
BDM Business Development Manager
BDM Background Debug(ger) Mode
BDM Bund Deutscher Mädel (League of German Girls during the Third Reich, akin to Hitler Youth) 
).

--"The Cardiac Myosin Activator, CK-1122534, Increases Contractility in Adult Cardiac Myocytes without Altering the Calcium Transient," was presented on Tuesday, December 7, 2004. This presentation concluded that CK-1122534 increases the fractional shortening in ventricular myocytes (a measure of cardiac contractility) in a dose-dependent manner, does not increase the calcium transient, does not inhibit phosphodiesterase (PDE PDE Pennsylvania Department of Education
PDE Plug-In Development Environment
PDE Partial Differential Equation
PDE Phosphodiesterases
PDE Personal Digital Entertainment
PDE Pulse Detonation Engine
PDE Product Data Exchange
PDE Present-Day English
) activity and is active in the presence of a beta-adrenergic blocker Betablocker (beta-adrenergic blocker)
A class of drugs that bind beta-adrenergic receptors and thereby decrease the ability of the body's own natural epinephrine to bind to those receptors, leading to inhibition of various processes in the body's sympathetic
.

--"Cellular Responses of the Myosin Activator CK-0689705 in Normal and Heart Failure Models," was presented on Tuesday, December 7, 2004. This presentation concluded that the cardiac myosin activator, CK-0689705, increases the fractional shortening in ventricular myocytes in a dose-dependent manner, does not increase the calcium transient and increases contractility in ventricular myocytes from rats with defined heart failure.

"We are pleased to have the opportunity to present these research findings," stated David Morgans, Jr., Ph.D., Cytokinetics' Senior Vice President of Drug Discovery and Development. "Building on the data we recently presented at the 2004 Scientific Sessions of the American Heart Association American Heart Association (AHA),
n.pr a national voluntary health agency that has the goal of increasing public and medical awareness of cardiovascular diseases and stroke, and thereby reducing the number of associated deaths and disabilities.
 (AHA) in November, these presentations add to the breadth and depth of the mechanistic profile of cardiac myosin activators, spanning elegant enzymological characterization through studies using myocytes from an animal model of heart failure. We are pleased with the progress of this program in optimizing and advancing multiple lead candidates and look forward to moving a drug candidate into human clinical trials in 2005."

Other Presentations

Cytokinetics also announced the presentation of seven additional poster presentations at the ASCB conference. Cumulatively, these presentations are indicative of the company's progress derived from fruitful research across multiple classes of protein families in the cytoskeleton cytoskeleton

System of microscopic filaments or fibres, present in the cytoplasm of eukaryotic cells (see eukaryote), that organizes other cell components, maintains cell shape, and is responsible for cell locomotion and for movement of the organelles within it.
 that further elucidates the identity, roles and regulation of potential cytoskeletal cy`to`skel´e`tal   

a. 1. (Cell Biology) Of or pertaining to the cytoskeleton; as, cytoskeletal microtubules s>.
 targets involved in actin dynamics and microtubule microtubule

Tubular structure enclosed by a membrane found within animal and plant cells. Of varying length, they have several functions. They help give shape to many cells and are major components of cilia and flagella, participate in the formation of the spindle during
 dynamics in the pathogenic yeast, Candida albicans Candida albicans,
n a pathogenic yeast, which is the causal agent of thrush, vaginal infections, and systemic candidiasis.

Candida albicans 
, the malarial parasite, Plasmodium falciparum Plasmodium fal·cip·a·rum
n.
A protozoan that causes falciparum malaria.
, and mammalian cells. These presentations covered a broad variety of areas that could provide valuable insight to advance research and drug discovery across multiple therapeutic areas including cancer, cardiovascular diseases, fungal infections and malaria.

"These poster presentations are the result of our focus on research in the cytoskeleton," stated James Sabry, M.D., Ph.D., President and Chief Executive Officer at Cytokinetics. "When we started the company over six years ago, we knew that the cytoskeleton would provide a rich area for potential next-generation pharmaceuticals. We are very excited about the maturation of the company programs having leveraged this expertise in cytoskeletal biology and pharmacology into clinical programs in oncology and cardiovascular disease and a strong research pipeline."

Background on the Cytoskeleton

The cytoskeleton is a diverse, multicomponent framework upon which the cell interior is ordered. As such it plays a fundamental role in all aspects of cell mechanics including cell division, intracellular transport, cell motility and the establishment and regulation of cell polarity and organization. In many ways, this framework can be considered to be analogous to a highly organized city plan, where cellular activities are regulated in systematized locations connected by highways upon which components are transported by motor cars. However, in the case of cells, the cytoskeletal highways are protein structures called microtubules Microtubules
Slender, elongated anatomical channels in worms.

Mentioned in: Antihelminthic Drugs
 and microfilaments microfilaments,
n.pl any of the submicroscopic cellular filaments, such as the tonofibrils, found in the cytoplasm of most cells, that function primarily as a supportive system.
 and the motor cars are enzymes, termed molecular motors, which more recently have been discovered to generate the mechanical forces critical to cellular function. The cytoskeleton has been implicated im·pli·cate  
tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates
1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot.

2.
 in a variety of disease pathologies, ranging from cancer to cardiovascular diseases to infectious diseases.

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, fungal diseases 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(TM) system and Cytometrix(TM) technologies to enable early identification and automated prioritization of compounds that are highly selective for their intended protein targets without other cellular effects, and are thereby 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 mitotic

pertaining to mitosis.


mitotic activity
degree to which a cell population is proliferating; used as an index of tumor aggression.
 kinesins for applications in the treatment of cancer and other diseases. GlaxoSmithKline is conducting Phase II and Phase Ib clinical trials for SB-715992 and a Phase I clinical trial Noun 1. phase I clinical trial - a clinical trial on a few persons to determine the safety of a new drug or invasive medical device; for drugs, dosage or toxicity limits should be obtained
phase I
 for SB-743921, each a drug candidate that has emerged from the strategic alliance. 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 The Private Securities Litigation Reform Act of 1995 (PSLRA) implemented several significant substantive changes affecting certain cases brought under the federal securities laws, including changes related to pleading, discovery, liability, class representation and awards fees and  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. 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.
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Geographic Code:1USA
Date:Dec 8, 2004
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