Item 8.01. Other Events.
On May 4, 2021 Cytokinetics, Incorporated (“Cytokinetics”
or the “Registrant”) announced the opening of enrollment in Cohort 3 of REDWOOD-HCM (Randomized Evaluation
of Dosing With CK-274 in Obstructive Outflow Disease in HCM),
an ongoing Phase 2 clinical trial of CK-3773274 (“CK-274”), a next-generation cardiac myosin inhibitor in development
for the potential treatment of hypertrophic cardiomyopathy (“HCM”). Cohort 3 will enroll patients whose background
therapy includes disopyramide.
REDWOOD-HCM: Clinical Trial Design
REDWOOD-HCM is a multi-center, randomized, placebo-controlled, double-blind,
dose finding clinical trial of CK-274 in patients with symptomatic obstructive HCM (“oHCM”). The primary objective
of the trial is to determine the safety and tolerability of CK-274. The secondary objectives are to describe the concentration-response
relationship of CK-274 on the resting and post-Valsalva left ventricular outflow tract gradient as measured by echocardiography during
10 weeks of treatment, to describe the dose response relationship of CK-274, and to evaluate the plasma concentrations of CK-274 in patients
with oHCM.
The trial previously completed enrollment in Cohort 1 and Cohort 2, two
sequential cohorts. Within each cohort, approximately 20 patients were randomized 2:1 to active or placebo treatment and received up to
three escalating doses of CK-274 or placebo based on echocardiographic guidance. Patients received an echocardiogram after two weeks of
treatment at each dose to determine whether they would be up-titrated. Overall, the treatment duration is 10 weeks with an echocardiogram
to confirm reversibility of effect 2 weeks after the last dose. In Cohorts 1 and 2, patients continued taking background medications exclusive
of disopyramide.
Cohort 3 will enroll, in an open label fashion, 8-12 patients whose background
therapy includes disopyramide to assess the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of CK-274 in patients
taking disopyramide. All patients will receive up to three escalating doses of CK-274, titrated based on echocardiographic guidance. Overall
treatment duration will be 10 weeks with a 4-week follow up period after the last dose.
Interim analysis of data from Cohort 1 of REDWOOD-HCM showed patients experienced
substantial reductions in the average resting left ventricular outflow tract gradient (“LVOT-G”) as well as the post-Valsalva
LVOT-G (defined as resting gradient <30 mmHg and post-Valsalva gradient <50 mmHg). These clinically relevant decreases in pressure
gradients were achieved with only modest decreases in average left ventricular ejection fraction (“LVEF”); there were
no dose interruptions due to LVEF falling below 50%, the prespecified safety threshold. Pharmacokinetic data were similar to those observed
in Phase 1 in healthy subjects. In addition, the safety and tolerability data were supportive of continued dose escalation with no serious
adverse events attributed to study treatment reported by the investigators.
Results from REDWOOD-HCM, across both Cohort 1 and Cohort 2, are expected
in mid-2021. Additional information about REDWOOD-HCM can be found on clinicaltrials.gov/.
About CK-274
CK-274 is a novel, oral, small molecule cardiac myosin inhibitor arising
from an extensive chemical optimization program conducted with careful attention to therapeutic index and pharmacokinetic properties that
may translate into next-in-class potential in clinical development. CK-274 was designed to reduce the hypercontractility that is associated
with HCM. In preclinical models, CK-274 reduces myocardial contractility by binding directly to cardiac myosin at a distinct and selective
allosteric binding site, thereby preventing myosin from entering a force producing state. CK-274 reduces the number of active actin-myosin
cross bridges during each cardiac cycle and consequently reduces myocardial contractility. This mechanism of action may be therapeutically
effective in conditions characterized by excessive hypercontractility, such as HCM.
In preclinical models of cardiac function, CK-274 reduced cardiac contractility
in a predictable dose and exposure dependent fashion. In preclinical models of disease, CK-274 reduced compensatory cardiac hypertrophy
and cardiac fibrosis. The preclinical pharmacokinetics of CK-274 were characterized, evaluated and optimized for potential ease of titration
in the clinical setting.
About Hypertrophic Cardiomyopathy
HCM is a disease in which the heart muscle (myocardium) becomes abnormally
thick (hypertrophied). The thickening of cardiac muscle leads to the inside of the left ventricle becoming smaller and stiffer, and thus
the ventricle becomes less able to relax and fill with blood. This ultimately limits the heart’s pumping function, resulting in
symptoms including chest pain, dizziness, shortness of breath, or fainting during physical activity. A subset of patients with HCM are
at high risk of progressive disease which can lead to atrial fibrillation, stroke and death due to arrhythmias. There are no FDA approved
medical treatments that directly address the hypercontractility that underlies HCM.
About Cytokinetics
Cytokinetics is a late-stage biopharmaceutical company focused on discovering,
developing and commercializing first-in-class muscle activators and next-in-class muscle inhibitors as potential treatments for debilitating
diseases in which muscle performance is compromised and/or declining. As a leader in muscle biology and the mechanics of muscle performance,
the company is developing small molecule drug candidates specifically engineered to impact muscle function and contractility. Cytokinetics
is preparing for regulatory interactions for omecamtiv mecarbil, its novel cardiac muscle activator, following positive results
from GALACTIC-HF, a large, international Phase 3 clinical trial in patients with heart failure. Cytokinetics is conducting METEORIC-HF,
a second Phase 3 clinical trial of omecamtiv mecarbil. Cytokinetics is also developing CK-274, a next-generation cardiac myosin
inhibitor, for the potential treatment of HCM. Cytokinetics is conducting REDWOOD-HCM, a Phase 2 clinical trial of CK-274 in patients
with obstructive HCM. Cytokinetics is also developing reldesemtiv, a fast skeletal muscle troponin activator for the potential
treatment of ALS and other neuromuscular indications following conduct of FORTITUDE-ALS and other Phase 2 clinical trials. The company
is preparing for the potential advancement of reldesemtiv to a Phase 3 clinical trial in ALS. Cytokinetics continues its over 20-year
history of pioneering innovation in muscle biology and related pharmacology focused to diseases of muscle dysfunction and conditions of
muscle weakness.
For additional information about Cytokinetics, visit www.cytokinetics.com
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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 intent or obligation to
update these forward-looking statements and claims the protection of the Act's Safe Harbor for forward-looking statements. Examples of
such statements include, but are not limited to, statements relating to the timing, design and results of Cytokinetics’ Phase 2
clinical trial of CK-274; the potential benefits of CK-274; Cytokinetics’ research and development activities; the timing of enrollment
of patients in Cytokinetics’ clinical trials; the design, timing, results, significance and utility of preclinical and clinical
results; and the properties and potential benefits of Cytokinetics’ drug candidates. Such statements are based on management's current
expectations, but actual results may differ materially due to various risks and uncertainties, including, but not limited to, potential
difficulties or delays in the development, testing, regulatory approvals for trial commencement, progression or product sale or manufacturing,
or production of Cytokinetics’ drug candidates that could slow or prevent clinical development or product approval; patient enrollment
for or conduct of clinical trials may be difficult or delayed; Cytokinetics’ drug candidates may have adverse side effects or inadequate
therapeutic efficacy; the FDA or foreign regulatory agencies may delay or limit Cytokinetics’ ability to conduct clinical trials;
Cytokinetics may be unable to obtain or maintain patent or trade secret protection for its intellectual property; standards of care may
change, rendering Cytokinetics’ drug candidates obsolete; and competitive products or alternative therapies may be developed by
others for the treatment of indications Cytokinetics’ drug candidates and potential drug candidates may target. For further information
regarding these and other risks related to Cytokinetics’ business, investors should consult Cytokinetics’ filings with the
Securities and Exchange Commission.