Cytokinetics Announces Preclinical Data for CK-3773274 and CK-3772271 Presented at the AHA Scientific Sessions 2020
November 16 2020 - 7:30AM
Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that
preclinical data for CK-3773274 (CK-274) and CK-3772271 (CK-271)
were shared in poster presentations at the American Heart
Association (AHA) Scientific Sessions 2020. CK-274 reduced
contractility and left ventricular outflow tract (LVOT) peak
pressure gradient in cats with naturally occurring hypertrophic
cardiomyopathy (HCM) and left ventricular outflow tract obstruction
(LVOTO). In the Dahl/Salt sensitive rat model of heart failure with
preserved ejection fraction (HFpEF), CK-271 attenuated the
development of fibrosis and diastolic dysfunction.
“We’re pleased to share preclinical data that
builds on the growing body of evidence for our pipeline of cardiac
myosin inhibitors,” said Brad Morgan, Ph.D., Cytokinetics’ Senior
Vice President, Research and Non-Clinical Development.
“Collectively, these data demonstrate the potential of this
mechanism of action to reduce or arrest the development of cardiac
hypercontractility in animal models which may support application
in patients with diseases of hypercontractility including HCM and
HFpEF.”
Previous preclinical data has shown that CK-274
produces exposure related effects on cardiac contractility in
healthy animals and mouse models of HCM. New preclinical data
demonstrated dose-related changes in left ventricular (LV) systolic
function and reductions in LVOT peak pressure gradient in cats with
naturally occurring HCM and LVOTO due to the A31P mutation in
cardiac myosin binding protein C (cMyBP-C). Treatment with CK-274
(1 mg/kg) reduced mean left ventricular (LV) fractional shortening
at 6, 24, and 48 hours post-treatment (mean reduction 13.6%, p =
0.03; 15.4%, p = 0.01; 11.6%, p = 0.02, respectively). In addition
to lowering the hypercontractility in cats with naturally occurring
HCM and LVOTO, CK-274 reduced the left ventricular outflow tract
peak pressure gradient in concentration related manner (median
pressure gradient at baseline 27.1 mmHg [interquartile range {IQR}
18.3–33.3] vs 24 hours post-drug, 7.3 mmHg [IQR 14.2–19.7], p=
0.01). CK-274 was well tolerated and no changes in heart rate were
observed for any treatment group over time.
A preclinical study of CK-271 demonstrated that
treatment with this novel small molecule cardiac myosin inhibitor
attenuated the development of fibrosis and diastolic dysfunction in
an animal model of HFpEF. Previous studies have shown that CK-271
reduces cardiac myosin ATPase activity in vitro and cardiac
contractility in vivo in healthy rats and dogs. In this study of
the Dahl/Salt Sensitive rat hypertension model of HFpEF, six weeks
of treatment with CK-271 reduced fractional shortening (HS: 53.8
±1.4 vs HS + CK-271: 42.7 ±1.0%, p< 0.0001) and reduced high
salt diet-induced diastolic dysfunction, including reductions in
isovolumic relaxation time (IVRT) (HS: 22.8 ±0.6 vs HS + CK-271:
19.5 ±0.5 ms, p< 0.0001) and left atrial area (HS: 42.5 ±2.2 vs
HS + CK-271: 35.4 ±0.8 mm2, p< 0.0001). CK-271 also reduced the
development of cardiac fibrosis induced by a high salt diet (HS:
5.0 ±0.6 vs HS + CK-271: 3.5 ±0.3%, p< 0.05). These results
suggest that cardiac myosin inhibition may be a novel approach to
mitigate the development of HFpEF.
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 collaborating with Amgen Inc.
(Amgen) to develop omecamtiv mecarbil, a novel cardiac muscle
activator. Omecamtiv mecarbil is the subject of an international
clinical trials program in patients with heart failure including
GALACTIC-HF, of which topline results were recently reported, and
METEORIC-HF, which is ongoing. Amgen holds an exclusive worldwide
license to develop and commercialize omecamtiv mecarbil with a
sublicense held by Servier for commercialization in Europe and
certain other countries. Cytokinetics is developing reldesemtiv, a
fast skeletal muscle troponin activator (FSTA) for the potential
treatment of ALS and other neuromuscular indications following
conduct of FORTITUDE-ALS and other Phase 2 clinical trials. The
company is considering potential advancement of reldesemtiv to
Phase 3 pending ongoing regulatory interactions. Cytokinetics is
collaborating with Astellas Pharma Inc. (Astellas) to research,
develop and commercialize other novel mechanism skeletal sarcomere
activators (not including FSTAs). Licenses held by Amgen and
Astellas are subject to specified co-development and
co-commercialization rights of Cytokinetics. Cytokinetics is also
developing CK-274, a novel cardiac myosin inhibitor that company
scientists discovered independent of its collaborations, for the
potential treatment of hypertrophic cardiomyopathies. Cytokinetics
has granted Ji Xing Pharmaceuticals Limited an exclusive license to
develop and commercialize CK-274 in China and Taiwan, in accordance
with Cytokinetics’ planned global registration programs.
Cytokinetics is conducting REDWOOD-HCM, a Phase 2 clinical trial of
CK-274 in patients with obstructive HCM. 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’ preclinical trials of CK-274 or CK-271; the
potential benefits of CK-274 or CK-271; 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.
Contact:CytokineticsDiane WeiserSenior Vice
President, Corporate Communications, Investor Relations(415)
290-7757
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