Our portfolio of precision cardiovascular therapeutics includes multiple cardiac muscle activator programs aimed at increasing contraction of the heart muscle to improve blood flow. We are initially targeting precision indications in systolic heart failure and specifically, dilated cardiomyopathies (DCM).
MYK-491 is an orally-administered small molecule designed to increase the number of myosin-actin cross-bridges formed during cardiac muscle contraction while having minimal impact on diastolic function. The goal is to increase the ensemble force of contraction and improve cardiac output during systole without detracting from the ability of the heart to relax and fill with blood during diastole. MYK-491 is currently in a Phase 1/b2a multiple-ascending dose clinical trial. Up to 40 DCM patients with stable heart failure will be randomized to receive either MYK-491 or placebo for one week, during which time patients will be monitored to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of MYK-491. We anticipate reporting data from the Phase 2a study in the fourth quarter of 2019.
Our Phase 1 clinical development program for MYK-491 principally evaluated the safety and tolerability of MYK-491 in healthy human subjects and dilated cardiomyopathy patients. In DCM patients with stable heart failure, administration of MYK-491 resulted in approximately 10 percent relative increases from baseline in cardiac contractility across multiple echocardiographic measures, including stroke volume, left ventricular ejection fraction and fractional shortening. In increasing the heart’s contractility, MYK-491 did not appear to meaningfully change duration of the contraction or the heart’s ability to relax and fill with oxygenated blood. Overall, these data were consistent with results previously reported from the single-ascending dose trial of MYK-491 in healthy volunteers.
MYK-491 was generally well tolerated across the range of oral doses tested in our first-in-human, Phase 1 clinical trial in healthy volunteers. Adverse events observed were benign and transient. Results from our Phase 1a and Phase 1b studies served to inform the starting dose for the Phase 2a study.