Cytokinetics Announces The Initiation Of A First-Time-in-Humans, Phase I Clinical Trial Of CK-2017357

Cytokinetics, Incorporated (NASDAQ: CYTK) announced that the company has initiated a first-time-in-humans, Phase I clinical trial of CK-2017357 in healthy male volunteers. CK-2017357 is a fast skeletal muscle troponin activator and is the lead drug candidate that has emerged from the company's skeletal sarcomere activator program. CK-2017357 selectively activates the troponin complex and increases its sensitivity to calcium, subsequently leading to an increase in skeletal muscle force. This mechanism of action has demonstrated encouraging pharmacological activity in preclinical models that may relate to the potential treatment of diseases associated with aging, muscle wasting, and neuromuscular dysfunction.


This Phase I clinical trial is a double-blind, randomized, placebo-controlled, single ascending dose study designed to evaluate CK-2017357 in healthy male volunteers. Each volunteer will participate in two dosing sessions separated by an adequate washout period. Subjects will be randomized (3:1) at the start of each dosing period to receive active study drug or placebo. The primary objective of this clinical trial is to determine the safety, tolerability and maximum tolerated dose (MTD) of CK-2017357 administered orally. The secondary objective is to evaluate the pharmacokinetic profile of CK-2017357. Following determination of the MTD and the pharmacokinetic profile of CK-2017357, further evaluation of the drug candidate's pharmacodynamic effects on skeletal muscle function in healthy volunteers may be undertaken in a second stage of this clinical trial.


"This first-time-in-humans clinical trial of CK-2017357 builds on our expertise in the biology of muscle function, initially demonstrated with our cardiac muscle myosin activator program and now translated to our skeletal sarcomere activator program," stated Fady Malik, MD, PhD, Cytokinetics' Vice President, Biology and Therapeutics. "This novel drug candidate may represent an important approach to treating skeletal muscle weakness that is a consequence of a wide array of diseases associated with muscle wasting or primary neuromuscular dysfunction."


"The initiation of this Phase I clinical trial is further demonstration of Cytokinetics' expertise in building a portfolio of novel drug candidates that leverage our expertise in the cytoskeletal pharmacology and biology of muscle contractility," stated Robert I. Blum, Cytokinetics' President and CEO. "This drug candidate, along with others we are developing, illustrates the productivity of our research and development teams that have now generated five next-generation drug candidates, which may address significant unmet needs across multiple therapeutic indications."


Background on Skeletal Muscle Activators


Skeletal muscle contractility is driven by the sarcomere, the fundamental unit of skeletal muscle contraction. It is a highly ordered cytoskeletal structure composed of several key proteins. The first, skeletal muscle myosin, is the cytoskeletal motor protein that converts chemical energy into mechanical force through its interaction with a second protein, actin. A set of regulatory proteins, which includes tropomyosin and several types of troponin, make the actin-myosin interaction dependent on changes in intracellular calcium levels. Cytokinetics' skeletal muscle contractility program is focused to the discovery and development of small molecule skeletal sarcomere activators and leverages Cytokinetics' expertise gained from its ongoing discovery and development of cardiac sarcomere activators, including the cardiac myosin activator, CK-1827452, now in Phase II clinical development as a potential treatment for heart failure. In non-clinical models, skeletal sarcomere activators have demonstrated pharmacological activity that may lead to new therapeutic options for diseases associated with aging, muscle wasting, and neuromuscular dysfunction. The clinical effects of muscle wasting, fatigue and loss of mobility can range from decreased quality of life to, in some instances, life-threatening complications. By directly improving skeletal muscle function, a small molecule activator of the skeletal sarcomere may potentially enhance physical performance and quality of life in patients with conditions marked by muscle weakness, including neuromuscular diseases such as amyotrophic lateral sclerosis (ALS), myasthenia gravis, cachexia, sarcopenia and the general frailty associated with aging.















Market Potential for Skeletal Muscle Activators


The conditions that could benefit from a skeletal muscle activator are grievous and severe. ALS, which afflicts between 20,000 and 30,000 people in the United States and is associated with a 3-year mortality rate of 50%. In addition, few options exist for the treatment of other neuromuscular disorders, such as myasthenia gravis, a chronic disease characterized by a defect in the transmission of nerve impulses to skeletal muscles, which afflicts approximately 60,000 patients in the United States. Patients with disorders and conditions with a higher prevalence could also benefit from enhanced skeletal muscle functional performance, including patients with cachexia, intermittent claudication and sarcopenia. Cachexia, a syndrome characterized by a drastic and unintentional loss of body mass, is estimated to be prevalent in 15%-35% of heart failure patients and in approximately 50% of cancer patients. Intermittent claudication, which usually refers to cramping pains in the legs caused by peripheral arterial disease, is a condition that impacts between 1 million and 3 million people in the United States each year. Sarcopenia, which is an age-related loss of muscle mass, strength, and function, is estimated to impact the lives of over 25-30% of the U.S. population over the age of 65 and can result in additional injuries and medical conditions due to limited mobility.


Source

Cytokinetics