Cytokinetics Announces Initiation of Phase 1 Clinical Trial of CK-3773274, a Cardiac Myosin Inhibitor
“The start of clinical trials for CK-274 marks an important milestone in our continuing innovation of potential sarcomere-directed medicines,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development. “Our scientists pioneered this emerging area of muscle pharmacology and have now advanced a next-generation drug candidate that was optimized for pharmacokinetic properties and therapeutic index. This first trial will elaborate on CK-274 and its potential to be best-in-class and we look forward to reporting data in 2019.”
Phase 1 Clinical Trial Design
The primary objective of this Phase 1 double-blind, randomized, placebo-controlled, multi-part, single and multiple ascending dose trial is to assess the safety and tolerability of single and multiple oral doses of CK-274. The study design includes eight single ascending dose cohorts and three multiple ascending dose cohorts, with eight healthy subjects per cohort. Additional objectives include describing the pharmacokinetics (PK) of CK-274 and its pharmacodynamic effects (PD) as measured by echocardiography, as well as characterizing the relationship between the two with regards to cardiac function. Additional information can be found on www.clinicaltrials.gov.
CK-274 is a novel, oral, small molecule cardiac myosin inhibitor that company scientists discovered independent of its collaborations. CK-274 arose from an extensive chemical optimization program conducted with careful attention to therapeutic index and pharmacokinetic properties that may translate into best-in-class potential in clinical development. CK-274 was designed to reduce the hypercontractility that is associated with hypertrophic cardiomyopathy (HCM). In preclinical models, CK-274 reduces myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state. CK-274 reduces the number of active actin-myosin cross bridges during each cardiac cycle and consequently reduces myocardial contractility. This mechanism of action may be therapeutically effective in conditions characterized by excessive hypercontractility, such as HCM.
In preclinical models of cardiac function, CK-274 reduced cardiac contractility in a predictable dose and exposure dependent fashion. In preclinical models of disease, CK-274 reduced compensatory cardiac hypertrophy and cardiac fibrosis. The preclinical pharmacokinetics of CK-274 were characterized evaluated and optimized for potential ease-of-use in the clinical setting. The initial focus of the development program for CK-274 will include an extensive characterization of its PK/PD relationship as has been a hallmark of Cytokinetics’ industry-leading development programs in muscle pharmacology. The overall development program will assess the potential of CK‑274 to improve exercise capacity and relieve symptoms in patients with hyperdynamic ventricular contraction due to HCM.
About Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, affecting approximately 1 in 500 individuals worldwide. HCM is a disease in which the heart muscle (myocardium) becomes abnormally thick (hypertrophied). The thickening of cardiac muscle leads to the inside of the left ventricle becoming smaller and stiffer, and thus the ventricle becomes less able to relax and fill with blood. This ultimately limits the heart’s pumping function, resulting in symptoms including chest pain, dizziness, shortness of breath, or fainting during physical activity. A subset of patients with HCM are at high risk of progressive disease which can lead to atrial fibrillation, stroke and death due to arrhythmias. There are no current medical treatments that directly address the hypercontractility that underlies HCM.
Cytokinetics is a late-stage biopharmaceutical company focused on discovering, developing and commercializing first-in-class muscle activators and best-in-class muscle inhibitors as potential treatments for debilitating diseases in which muscle performance is compromised and/or declining. As a leader in muscle biology and the mechanics of muscle performance, the company is developing small molecule drug candidates specifically engineered to impact muscle function and contractility. Cytokinetics is collaborating with Amgen Inc. (“Amgen”) to develop omecamtiv mecarbil, a novel cardiac muscle activator. Omecamtiv mecarbil is the subject of GALACTIC-HF, an international Phase 3 clinical trial in patients with heart failure. Amgen holds an exclusive worldwide license to develop and commercialize omecamtiv mecarbil with a sublicense held by Servier for commercialization in Europe and certain other countries.
This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”).
Vice President, Corporate Communications, Investor Relations
Source: Cytokinetics, Incorporated