US-based biopharmaceutical company Cytokinetics has dosed the first subjects in a Phase I clinical trial of CK-4021586 (CK-586), a cardiac myosin inhibitor intended to treat heart failure with preserved ejection fraction (HFpEF).

The trial’s primary objective is to evaluate the safety, tolerability and pharmacokinetics of CK-586 when it is administered orally in single or multiple doses to healthy subjects.

The randomised, double-blind, placebo-controlled study and will be conducted in several parts.

It includes eight single-dose cohorts and four multiple ascending-dose cohorts, each of which has enrolled ten patients.

A final optional cohort will involve 12 subjects and investigate the effect of food on CK-586 in an open-label, two-period crossover arm.

Cytokinetics Research and Development executive vice-president Fady Malik said: “We are pleased to announce the initiation of the Phase I clinical study of CK-586, a cardiac myosin inhibitor with a mechanism of action distinct from aficamten.

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“As a pioneer in the mechanics of cardiac myosin inhibition, we believe this mechanism may impact the underlying hypercontractility found in certain patients who have heart failure with preserved ejection fraction and look forward to pursuing this clinical hypothesis with CK-586.”

CK-586 is a novel, selective, oral small molecule that has been found to decrease the number of active myosin cross-bridges during cardiac contraction, thus reducing cardiac hypercontractility, in preclinical models.

Cytokinetics is also developing a cardiac troponin activator, CK-136, to treat right ventricular heart failure.

Based in San Francisco, California, the company works to discover, develop and commercialise muscle activators and inhibitors for treating diseases that compromise cardiac muscle performance.

Last month, it announced that it would cancel its Phase III COURAGE-ALS trial in amyotrophic lateral sclerosis (ALS) following a failed interim analysis.

A Data Monitoring Committee recommended terminating the trial after it was determined that reldesemtiv did not affect the primary endpoint of ALS Functional Rating Scale-Revised (ALSFRS-R) after 24 weeks.