Cytokinetics, Incorporated announced that REDWOOD-HCM (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM) has opened to enrollment. REDWOOD-HCM is a Phase 2 clinical trial of CK-3773274 (CK-274), a next-generation cardiac myosin inhibitor discovered by company scientists, which Cytokinetics is developing for the potential treatment of hypertrophic cardiomyopathy (HCM). REDWOOD-HCM is a multi-center, randomized, placebo-controlled, double-blind, dose-finding clinical trial in patients with symptomatic, obstructive HCM (oHCM). The primary objective of the trial is to determine the safety and tolerability of CK-274. The secondary objectives are to describe the concentration-response and dose-response relationship of CK-274 on the resting and post-Valsalva left ventricular outflow tract gradient as measured by echocardiography during 10 weeks of treatment. Additionally, the trial will evaluate the plasma concentrations of CK-274 in patients with oHCM in relationship to dose. Exploratory objectives include the effect of CK-274 on N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and New York Heart Association (NYHA) Functional Classification. The trial will enroll two sequential cohorts of patients, with an option for a third cohort. Within each cohort, 18 patients will be randomized 2:1 to active or placebo treatment and receive up to three escalating doses of CK-274 or placebo based on echocardiographic guidance. Patients will receive an echocardiogram after two weeks of treatment at each dose to determine whether they will be up-titrated to the next higher dose. Cohort 1 will employ doses of 5, 10 and 15 mg, once daily. The doses in Cohort 2 will be determined following a review of the data from Cohort 1. Overall, the treatment duration will be 10 weeks with an echocardiogram to confirm reversibility of effect two weeks after the last dose. REDWOOD-HCM is expected to enroll patients in approximately 20 investigative sites in North America and Europe. All patients will be eligible to participate in an open label extension study of CK-274. 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 next-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, both in normal models of cardiac function and mouse models of HCM, CK-274 reduced cardiac contractility in a predictable dose and exposure dependent fashion. The preclinical pharmacokinetics of CK-274 were characterized, evaluated and optimized for potential ease-of-use in the clinical setting. A Phase 1 study demonstrated that CK-274 was safe and well tolerated in healthy participants. The pharmacokinetics of CK-274 were generally dose linear, and steady-state appeared evident within 14 days of dosing. Left ventricular ejection fraction decreased in an exposure dependent manner and the PK/PD relationship for CK-274 observed in humans was similar to that observed preclinically when adjusted for differences in protein binding. Specifically, the shallow exposure-response relationship observed preclinically appears to translate to humans and thereby may enable flexible dose optimization in humans. 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. Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disorder 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. In the majority of patients, thickening of the heart muscle in the left ventricular outflow tract obstructs the flow of blood out of the heart. 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 ventricular arrhythmias, atrial fibrillation, stroke, heart failure and sudden cardiac death. There are no current medical treatments that directly address the hypercontractility that underlies HCM.