MyoKardia has commenced dosing of patients in a Phase I trial of small molecule MYK-224 for the treatment of hypertrophic cardiomyopathy (HCM).
HCM is characterised by excessive heart muscle contraction and decreased filling ability of the left ventricle. It results in debilitating symptoms and cardiac dysfunction.
MYK-224 is developed to specifically target the heart’s cardiac myosin motor protein to normalise contractility and filling. It is expected to offer some dosing advantages to select HCM patients.
In preclinical studies, MYK-224 was found to mitigate hyperactive myosin proteins with known pathogenic HCM mutations.
MyoKardia added that the compound modulates cardiac myosin without any impact on myosin-actin cross-bridge kinetics or calcium homeostasis.
The randomised, placebo-controlled Phase I study is designed to compare the safety, tolerability, and pharmacokinetics of MYK-224 to placebo in healthy participants.
Subjects in the single and multiple-ascending dose trial will be randomised into cohorts of eight. Echocardiography will be used to evaluate the pharmacodynamic effects of the drug candidate on heart function and dimensions.
Top-line data from the Phase I trial is expected to be reported next year.
MyoKardia chief development officer June Lee said: “The initiation of our Phase I clinical study of MYK-224 in healthy volunteers allows us to further expand our disease-area leadership in hypertrophic cardiomyopathy.
“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.”
MYK-224 expands the company’s pipeline targeting the heart muscle’s sarcomeric proteins to treat disorders associated with excessive or inadequate contraction or abnormal relaxation.