MyoKardia, Inc. announced that the first patient has been dosed in the company’s Phase 2 clinical trial of danicamtiv in people with primary dilated cardiomyopathy thought to be caused by genetic mutations of the sarcomere. Danicamtiv is MyoKardia’s most advanced clinical candidate being developed for the treatment of genetic dilated cardiomyopathy and other targeted populations with conditions of reduced systolic function. DCM is a disease of the myocardium characterized by left ventricular enlargement. The weakened and distended left ventricle lacks sufficient contractile force to adequately pump oxygenated blood out to meet the body’s needs. Danicamtiv binds directly to and activates myosin, the heart’s motor protein, to boost the power of each contraction without impacting the ability of the heart to relax and fill with oxygenated blood. In clinical studies, danicamtiv has been well tolerated and has been shown to activate myosin, resulting in enhanced left ventricular contractility, including meaningful improvements in stroke volume, and improved left atrial volume and function. MyoKardia’s Phase 2 study of danicamtiv will enroll patients with DCM with documented genetic variants of MYH7 or titin. Pathogenic variants in single genes encoding proteins of the sarcomere have been associated with the contractile dysfunction underlying approximately 20-30% of dilated cardiomyopathies. Patients with these genetic mutations may be particularly suited to treatment with danicamtiv since danicamtiv’s mechanism may correct the very defect that results in cardiac dysfunction. The MYH7 gene mutations are known to reduce the force-generating capacity of the heart by impairing the formation of myosin-actin cross-bridges responsible for cardiac muscle contraction. Biochemical assays using cardiac fibers with variants in MYH7 indicate danicamtiv can rescue the impaired force production that the mutation causes. Titin, an essential component of the sarcomere, provides structure, flexibility and stability as the muscle proteins contract and relax. In MyoKardia’s in vitro studies of engineered tissues with titin variant, contractility was augmented by 31% using a danicamtiv-like myosin activator.