Item 8.01. Other Events.
On January 11, 2021 Cytokinetics, Incorporated ("Cytokinetics" or the
"Registrant") announced that the U.S. Food and Drug Administration ("FDA") has
granted orphan drug designation to CK-3773274 ("CK-274") for the treatment of
symptomatic hypertrophic cardiomyopathy ("HCM"). CK-274 is a next-generation
cardiac myosin inhibitor in development for the potential treatment of HCM.
The FDA, through its Office of Orphan Products Development (OOPD), grants orphan
status to drugs and biologic products that are intended for the safe and
effective treatment, diagnosis, or prevention of rare diseases or conditions
that affect fewer than 200,000 people in the United States. Orphan drug
designation provides a drug developer with certain benefits and incentives,
including a seven-year period of U.S. marketing exclusivity from the date of
marketing authorization, waiver of FDA user fees, and tax credits for clinical
research.
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 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 will enroll two sequential cohorts, with an option for a third cohort.
Within each cohort, approximately 18 patients will be randomized 2:1 to active
or placebo treatment and receive up to three escalating doses of CK-274 or
placebo based on echocardiographic guidance. Patients receive an echocardiogram
after two weeks of treatment at each dose to determine whether they will be
up-titrated. Overall, the treatment duration will be 10 weeks with an
echocardiogram to confirm reversibility of effect 2-weeks after the last dose.
REDWOOD-HCM is expected to enroll patients in approximately 20 investigative
sites in North America and Europe.
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.
The second cohort of REDWOOD-HCM is open for enrollment in centers in North
America and Europe. Enrollment in Cohort 2 of REDWOOD-HCM is expected to
complete in Q1 2021 and full 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 www.clinicaltrials.gov.
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.
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 and
follow us on Twitter, LinkedIn, Facebook and YouTube.
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; the ability to
complete enrollment of Cohort 2 of REDWOOD-HCM in Q1 2021 and the impact of the
COVID-19 pandemic on such enrollment (for further information regarding the
historical and potential prospective impact of the COVID-19 pandemic on our
business operations and clinical trials, please refer to Cytokinetics' Form 10-Q
for the quarterly period ended September 30, 2020); Cytokinetics' and its
partners' research and development activities; the timing of enrollment of
patients in Cytokinetics' and its partners' 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' or its
partners' ability to conduct clinical trials; Cytokinetics may be unable to
obtain or maintain patent or trade secret protection for its intellectual
property; Cytokinetics' partners decisions with respect to research and
development activities; standards of care may change, rendering Cytokinetics'
drug candidates obsolete; competitive products or alternative therapies may be
developed by others for the treatment of indications Cytokinetics' drug
candidates and potential drug candidates may target; and risks and uncertainties
relating to the timing and receipt of payments from its partners, including
milestones and royalties on future potential product sales under Cytokinetics'
collaboration agreements with such partners. For further information regarding
these and other risks related to Cytokinetics' business, investors should
consult Cytokinetics' filings with the Securities and Exchange Commission.
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