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TARGETING THE SARCOMERE TO IMPACTHEART FUNCTION

Omecamtiv Mecarbil

Cytokinetics is developing omecamtiv mecarbil, a novel, selective cardiac myosin activator for the potential treatment for heart failure with reduced ejection fraction (HFrEF).

Omecamtiv mecarbil stimulates cardiac myosin, a protein responsible for converting chemical energy into the mechanical force that results in contraction of the heart. It is designed to improve cardiac muscle performance, potentially helping patients preserve cardiac function and quality of life, avoid hospitalizations, and decrease the risk of death due to heart failure. Preclinical research has shown that cardiac myosin activators increase cardiac contractility without affecting intracellular myocyte calcium concentrations or myocardial oxygen consumption.

Omecamtiv mecarbil was the subject of seven Phase 2 clinical trials, including COSMIC-HF, which evaluated omecamtiv mecarbil in patients with chronic heart failure and left ventricular systolic dysfunction.

Omecamtiv mecarbil is the subject of a comprehensive Phase 3 clinical trials program comprised of GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure), a large, Phase 3 global cardiovascular outcomes study, and METEORIC-HF, (Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure), a Phase 3 clinical trial designed to evaluate the effect of treatment with omecamtiv mecarbil compared to placebo on exercise capacity.

After a median duration of follow-up of 21.8 months, GALACTIC-HF demonstrated a statistically significant effect of treatment with omecamtiv mecarbil to reduce risk of the primary composite endpoint of cardiovascular (CV) death or heart failure events (heart failure hospitalization and other urgent treatment for heart failure) compared to placebo in patients treated with standard of care. The effect of omecamtiv mecarbil was consistent across most prespecified subgroups and with a potentially greater treatment effect suggested in patients with a lower left ventricular ejection fraction (LVEF ≤28%, n=>4,000, hazard ratio, 0.84; 95% CI 0.77, 0.92; interaction p=0.003). Omecamtiv mecarbil also significantly decreased NT-proBNP concentrations by 10% (95% CI 6-14%) at Week 24 compared to placebo. No reduction in the secondary endpoint of time to CV death was observed. Adverse events, including major ischemic cardiac events, were balanced between the treatment arms.