Non-clinical data of CK-2017357 presented by Cytokinetics

Cytokinetics, Incorporated (NASDAQ: CYTK) announced today that both a poster and an oral presentation summarizing non-clinical data regarding CK-2017357, a novel fast skeletal troponin activator, were presented at the 5th Cachexia Conference, organized by the Society on Cachexia and Wasting Disorders, being held December 5-8, 2009 in Barcelona, Spain. CK-2017357 is currently the subject of two ongoing Phase I clinical trials.

"As a result of our focused R&D activities directed to the biology of muscle contractility, we have been able to identify and characterize compounds that activate the skeletal muscle sarcomere, such as CK-2017357, which may have treatment applications in syndromes such as cachexia, as well as other diseases and medical conditions associated with aging, muscle wasting or fatigue and neuromuscular dysfunction," stated Fady Malik, MD, PhD, FACC, Cytokinetics' Vice President of Biology and Therapeutics. "We are pleased to have had an opportunity to share these encouraging data at this leading scientific forum on cachexia and look forward to our planned advancement of CK-2017357 into Evidence of Effect studies in disease populations in 2010."

Oral Presentation at 5th Cachexia Conference

An oral presentation titled "Direct Activation of the Skeletal Sarcomere by the Troponin Activator, CK-2017357, a Novel Approach to Improving Skeletal Muscle Function" was presented by Fady Malik, MD, PhD, FACC, Vice President, Biology and Therapeutics, Cytokinetics, Inc., South San Francisco, California on December 7, 2009. The presentation highlighted the therapeutic hypothesis underlying Cytokinetics' skeletal muscle contractility drug discovery and development program. Following a description of the mechanism of action of CK-2017357, namely activation of the fast skeletal muscle troponin complex resulting in sensitization of the sarcomere to calcium, the presentation described three basic pharmacological consequences of this mechanism of action. The presentation highlighted that in non-clinical studies, CK-2017357 and related skeletal troponin activators amplified the response to motor neuron input, increased muscle power and slowed the development of muscle fatigue. In addition, the presentation summarized non-clinical data indicating that CK-2071357 delayed the onset of muscle fatigue in a model of vascular insufficiency and increase muscle performance in a model of muscle endurance. Finally, the presentation reviewed the current development plan for CK-2017357 including a discussion of the two ongoing Phase I clinical trials of CK-2017357 in healthy volunteers designed to assess the safety, tolerability and pharmacokinetics of single doses and multiple doses, respectively, as well as planned Phase II Evidence of Effect clinical trials in patients with neuromuscular disease or medical conditions associated with muscle wasting or fatigue, several of which are expected to be conducted in 2010.

Poster Presentation at 5th Cachexia Conference

A poster presentation titled "The Fast Skeletal Troponin Activator, CK-2017357, Increases Skeletal Muscle Force in-vitro and in-situ" was presented on December 6, 2009 - December 7, 2009 at the 5th Cachexia Conference. The objective of the study was to evaluate whether CK-2017357 changes force development in native skeletal muscle preparations in vitro, using skinned and living skeletal muscle fibers, and in situ, where nerve and blood supply are left intact. The authors demonstrated that CK-2017357 increased sub-maximal force development of skinned fast skeletal muscle in vitro. Similar findings were observed in human skinned fast skeletal muscle fibers. In addition, compound specificity for fast skeletal muscle fibers was demonstrated, as skinned slow skeletal muscle fibers were approximately ten-fold less responsive to CK-2017357 than skinned fast skeletal muscle fibers. CK-2017357 did not appear to activate cardiac muscle fibers. CK-2017357 increased the force development in living muscle fibers at sub-maximal stimulation frequencies. In situ, CK-2017357 increased sub-maximal force development in a predominantly fast skeletal fiber muscle (extensor digitorum longus). Finally, CK-2017357 was shown to reduce isometric fatigue in living skeletal muscle in vitro. This effect is hypothesized to be linked to the reduced stimulation frequency required to elicit the same starting force in treated muscle.

The authors concluded that these data support a proposed mechanism of action of CK-2017357 through calcium sensitization of the fast skeletal muscle troponin complex. In skinned muscle fibers, CK-2017357 increased the sensitivity of skeletal muscle to exogenously added calcium. In living muscle fibers, CK-2017357 increased the sensitivity of skeletal muscle to the frequency of electrical stimulation which results in calcium release within the muscle. In each case, the result was an increase in muscle force development at sub-maximal muscle activation, where muscle normally operates. The ability to generate the same force at lower frequencies of nerve input may result in a resistance to fatigue. These findings may translate into functional improvements in skeletal muscle performance and efficiency in conditions marked by muscle weakness by improving the extent of muscle fiber recruitment during physical activity and reducing the rate at which muscle fibers fatigue.

Development Status of CK-2017357

In June 2009, Cytokinetics announced that it had initiated a first-time-in-humans Phase I clinical trial of CK-2017357 in healthy male volunteers. The ongoing first part, or "Part A," of this trial is designed to assess the safety, tolerability, and pharmacokinetic profile of this drug candidate and to determine its maximum tolerated dose and plasma concentration. In November 2009, Cytokinetics announced that the company had initiated the second part, or "Part B," of this clinical trial. Part B is designed to evaluate the pharmacodynamic effect of single doses that have been tolerated to date in Part A of this trial. In November 2009, the company also announced the initiation of a second Phase I clinical trial to investigate the safety, tolerability and pharmacokinetic profile of CK-2017357 after multiple oral doses to steady state in healthy male volunteers.