Cytokinetics Announces Topline Data from Phase 1 Clinical Study of CK-4021586

Cytokinetics, incorporatedCytokinetics, incorporated

Cytokinetics, incorporated

Data supports advancement toward phase 2 clinical trial in heart failure patients with preserved ejection fraction expected to begin in the fourth quarter of 2024

Complete data from the phase 1 study will be presented at a medical conference in the second half of 2024

SOUTH SAN FRANCISCO, Calif., May 8, 2024 (GLOBE NEWSWIRE) — Cytokinetics, Incorporated (Nasdaq: CYTK) today announced topline data from the Phase 1 study of CK-4021586 (CK-586). The study met its primary and secondary objectives of evaluating the safety, tolerability, and pharmacokinetics (PK) of single and multiple oral doses of CK-586. The data supports the advancement of CK-586 to a Phase 2 clinical trial in patients with heart failure with preserved ejection fraction (HFpEF), which is expected to begin in the fourth quarter of 2024. CK-586 is an inhibitor of Cardiac myosin in development for potential treatment. of a subgroup of patients with HFpEF.

“These data reinforce the potential of CK-586 as a drug candidate designed to directly impact underlying hypercontractility in a subset of patients with HFpEF,” said Fady I. Malik, MD, Ph.D., Executive Vice President of Cytokinetics, Research. and Development. “Based on previously reported positive phase 2 results aficamten in patients with non-obstructive HCM, we are confident in this approach in HFpEF as the conditions have a similar profile. We look forward to initiating the Phase 2 clinical trial of CK-586 in the fourth quarter, expanding the potential of our cardiac myosin-led development platform focused on specialized cardiology indications.

Phase 1 design and key findings

The primary objective of this Phase 1, randomized, double-blind, placebo-controlled, multi-part single and multiple escalating dose clinical study was to evaluate the safety, tolerability, and pharmacokinetics of CK-586 when it is administered orally in single or multiple doses to healthy participants. . The study design included seven single-ascending dose cohorts (10 mg to 600 mg) consisting of 10 participants each, and two ascending multiple-dose cohorts (100 and 200 mg once daily) consisting of 10 participants each. The study met the primary objective, demonstrating that CK-586 was safe and well-tolerated in healthy participants with linear pharmacokinetics. Pharmacodynamics were assessed by echocardiography and as expected. No serious adverse events were observed and the discontinuation criteria were not met in the study.

About CK-4021586 (CK-586)

CK-4021586 (CK-586) is a novel, selective, oral, small molecule cardiac myosin inhibitor designed to reduce hypercontractility associated with heart failure with preserved ejection fraction (HFpEF). In preclinical models, CK-586 reduced cardiac hypercontractility by decreasing the number of active myosin cross-bridges during cardiac contraction, thereby reducing contractile force, with no effect on calcium transients. In some patients, HFpEF is a condition that resembles nonobstructive hypertrophic cardiomyopathy (HCM) in that patients have higher ejection fractions, thickened heart walls, elevated biomarkers, and symptoms of failure. cardiac. In a phase 2 clinical trial in patients with non-obstructive HCM, aficamtena cardiac myosin inhibitor also developed by the Company, was well tolerated, improved patient-reported outcomes (Kansas City Cardiomyopathy Questionnaire (KCCQ) and New York Heart Association (NYHA) Functional Class) and biomarkers, measures which are also relevant to HFpEF, lending support to this mechanism of action in HFpEF.

About heart failure

Heart failure is a serious illness that affects more than 64 million people worldwide.1 About 6.7 million Americans have heart failure, and that number is expected to rise to more than 8.5 million by 2030.2 About half of heart failure patients have heart failure with preserved ejection fraction (HFpEF)3and the prevalence of HFpEF is increasing.2,4 Approximately 75% of patients with HFpEF will die within five years of their first hospitalization and 84% will be rehospitalized.2 Despite widespread use of standard treatments and advances in care, the prognosis for patients with heart failure is poor.5

About cytokinetics

Cytokinetics is a late-stage specialty cardiovascular biopharmaceutical company focused on the discovery, development and commercialization of first-in-class muscle activators and next-generation muscle inhibitors as potential treatments for debilitating diseases in which performance of the heart muscle is compromised. As a leader in muscle biology and the mechanics of muscle performance, the company develops small molecule drug candidates specifically designed to impact myocardial muscle function and contractility. Cytokinetics prepares for regulatory submissions for aficamtenits new cardiac myosin inhibitor, following positive results from SEQUOIA-HCM, the pivotal phase 3 clinical trial in obstructive hypertrophic cardiomyopathy. Aficamten is also currently being evaluated in MAPLE-HCM, a phase 3 clinical trial of aficamten monotherapy versus metoprolol monotherapy in patients with obstructive HCM, ACACIA-HCM, a phase 3 clinical trial of aficamten in Patients With Non-obstructive HCM, CEDAR-HCM, a clinical trial of aficamten in a pediatric population with obstructive HCM, and FOREST-HCM, an open-label extension clinical study of aficamten in patients with HCM. Cytokinetics also develops omecamtiv mecarbil, a heart muscle activator, in patients with heart failure. Additionally, Cytokinetics is developing CK-586, a cardiac myosin inhibitor with a mechanism of action distinct from that aficamten for the potential treatment of HFpEF, and CK-136, a cardiac troponin activator for the potential treatment of HFrEF and other types of heart failure, such as right ventricular failure resulting from cardiac contractility altered.

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Forward-looking statements

This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Cytokinetics disclaims any intention or obligation to update these forward-looking statements and claims the safe harbor of the law for forward-looking statements. Examples of such statements include, but are not limited to, statements, expressed or implied, regarding the potential benefits of CK-586 for patients with heart failure with preserved ejection fraction (HFpEF) and our ability to start a phase 2 clinical trial of CK-586 in the fourth quarter of 2024, if ever. These statements are based on management’s current expectations, but actual results may differ materially due to various risks and uncertainties, including, without limitation, potential difficulties or delays in the development, testing, regulatory approvals for the initiation of testing, advancement or sale of the product or the manufacturing or production of Cytokinetics drug candidates that could slow or prevent clinical development or approval of the product; Cytokinetic drug candidates may have undesirable side effects or inadequate therapeutic efficacy; the FDA or foreign regulatory agencies may delay or limit Cytokinetics’ ability to conduct clinical trials; Cytokinetics may not be able to obtain or maintain patent or trade secret protection for its intellectual property; standards of care could change, rendering Cytokinetic drug candidates obsolete; and competing products or alternative therapies may be developed by others for the treatment of indications that Cytokinetics’ drug candidates and potential drug candidates may target. For more information about these and other risks relating to Cytokinetics’ business, investors should review Cytokinetics’ filings with the Securities and Exchange Commission.

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Diane Weiser
Senior Vice President, Corporate Affairs
(415) 290-7757

The references:

  1. James et al. GBD 2017 Disease and Injury Incidence and Prevalence Contributors. Lancet 2018; 392: 1789-858.

  2. Bozkurt B, Ahmad T, Alexander KM, Baker WL, Bosak K, Breathett K, Fonarow GC, Heidenreich P, Ho JE, Hsich E, Ibrahim NE, Jones LM, Khan SS, Khazanie P, Koelling T, Krumholz HM, Khush KK , Lee C, Morris AA, Page RL 2nd, Pandey A, Piano MR, Stehlik J, Stevenson LW, Teerlink JR, Vaduganathan M, Ziaeian B; Members of the editorial board. Epidemiology and outcome statistics of heart failure: a report from the Heart Failure Society of America. J Card Failure. 2023 Oct;29(10):1412-1451. doi: 10.1016/j.cardfail.2023.07.006. Published online September 26, 2023. PMID: 37797885; PMCID: PMC10864030.

  3. Dunlay SM, Roger VL, Weston SA, Jiang R, Redfield MM. Longitudinal changes in ejection fraction in heart failure patients with preserved and reduced ejection fraction. Circular cardiac failure. 2012 Nov;5(6):720-6. doi: 10.1161/CIRCHEARTFAILURE.111.966366. Published online August 30, 2012. PMID: 22936826; PMCID: PMC3661289.

  4. Yancy CW, Jessup M, Bozkurt B et al. 2013 ACCF/AHA Guidelines for the Management of Heart Failure: Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Traffic. 2013;128:e240-e327.

  5. Jhund PS, MacIntyre K, Simpson CR et al. Long-term trends in first hospitalization for heart failure and subsequent survival between 1986 and 2003. Circulation. 2009;119:515-523.