MyoKardia Begins Dosing in Phase 1 Clinical Study

MyoKardia, Inc. recently announced it has dosed the first subjects in a Phase 1 clinical study of MYK-224, a small molecule candidate being developed for the treatment of hypertrophic cardiomyopathy (HCM). HCM is a progressive disease in which the excessive contraction of the heart muscle and reduced ability of the left ventricle to fill can lead to the development of debilitating symptoms and cardiac dysfunction, ranging from shortness of breath and reduced exercise capacity to heart failure and sudden cardiac arrest. MYK-224 selectively targets cardiac myosin, the heart’s motor protein, with the aim of normalizing contractility and filling.

“The initiation of our Phase 1 clinical study of MYK-224 in healthy volunteers allows us to further expand our disease-area leadership in hypertrophic cardiomyopathy,” said June Lee, MD, MyoKardia’s Chief Development Officer. “Patients experiencing symptoms of HCM currently lack adequate pharmacologic treatment options. Advancing a second HCM candidate in our portfolio is consistent with our focus on, and commitment to, providing HCM patients with new therapies that target the underlying cause of their disease.”

The Phase 1 clinical trial is intended to evaluate the safety, tolerability and pharmacokinetics of MYK-224. The trial is a randomized, placebo-controlled, single and multiple-ascending dose study that will enroll adult healthy volunteers into cohorts of eight, randomized 3:1 to MYK-224 or placebo. Pharmacodynamic effects on cardiac function and dimensions will also be assessed using echocardiography. MyoKardia anticipates providing topline results from the Phase 1 study in mid-2020.

MYK-224 is designed with distinct physicochemical properties that may enable certain dosing advantages for some HCM patients. In preclinical studies, MYK-224 was shown to attenuate hyperactive myosin proteins containing known pathogenic HCM mutations. Additionally, MYK-224 modulates cardiac myosin without affecting myosin-actin cross-bridge kinetics or altering calcium homeostasis.

MYK-224 joins MyoKardia’s growing portfolio of therapeutic candidates targeting sarcomeric proteins of the heart muscle to address cardiovascular diseases of excessive or insufficient contraction or impaired relaxation. MyoKardia’s lead clinical-stage therapeutic candidate for HCM, mavacamten, is currently being studied in the Phase 3 EXPLORER-HCM clinical trial for the treatment of obstructive HCM, where topline data are expected in Q2 2020, and in the Phase 2 MAVERICK-HCM clinical trial in non-obstructive HCM, where topline data are expected in Q4 of this year.

Hypertrophic cardiomyopathy (HCM) is a disease of excessive contraction of the heart muscle in which the walls of the heart thicken and prevent the left ventricle from expanding, resulting in a reduced pumping capacity. HCM is the most common form of heritable cardiomyopathies and is estimated to affect one in every 500 people. In approximately two-thirds of HCM patients, the path followed by blood exiting the heart, known as the left ventricular outflow tract (LVOT), becomes obstructed by the enlarged and diseased muscle, restricting the flow of blood from the heart to the rest of the body. HCM is a chronic disease and can be progressive and disabling. For some patients, exertion can result in fatigue or shortness of breath, and a patient’s ability to participate in normal work, family or recreational activities. HCM has also been associated with increased risk of related co-morbidities including atrial fibrillation, heart failure, or rarely sudden cardiac death.

MyoKardia is a clinical-stage biopharmaceutical company pioneering a precision medicine approach to discover, develop and commercialize targeted therapies for the treatment of serious cardiovascular diseases. MyoKardia’s initial focus is on the development of small molecule therapeutics aimed at the muscle proteins of the heart that modulate cardiac muscle contraction and underlying diseases of systolic and diastolic dysfunction. MyoKardia applies a precision medicine approach to develop its therapeutic candidates for patient populations with shared characteristics, such as causal genetic mutations or disease subtypes. MyoKardia has discovered a pipeline of product candidates directed at diseases driven by excessive contraction, impaired relaxation, or insufficient contraction. Among its discoveries are three clinical-stage therapeutics: mavacamten (formerly MYK-461) in Phase 3 and Phase 2 clinical trials for hypertrophic cardiomyopathies (HCM); MYK-491 in Phase 2 for patients with stable heart failure; and MYK-224, in Phase 1 development for HCM. MyoKardia’s mission is to change the world for people with serious cardiovascular disease through bold and innovative science.