Cytokinetics Announces Publication of Preclinical Data Demonstrating Fast Skeletal Muscle Troponin Activator Improves Muscl...
24 July 2019 - 9:30PM
Cytokinetics, Incorporated (Nasdaq: CYTK) today announced the
publication of data in The Journal of Physiology demonstrating that
a fast skeletal muscle troponin activator (FSTA) can decrease
skeletal muscle fatigue by increasing the metabolic efficiency of
muscle contraction. The manuscript, titled “Fast Skeletal Muscle
Troponin Activator CK-2066260 Increases Fatigue Resistance by
Reducing the Energetic Cost of Muscle Contraction,” was published
this month. Cytokinetics conducted the research in collaboration
with the laboratory of Professor Håkan Westerblad at the
Department of Physiology and Pharmacology, Karolinska Institutet,
Stockholm, Sweden. CK-2066260 is a preclinical tool compound of the
FSTA class.
“While we have previously generated preclinical
and clinical data demonstrating that FSTAs improve muscle force,
power and the time to muscle fatigue, this is the first time we
have been able to show that the mechanism of action reduces the
metabolic cost of muscle contraction. This class of potential
therapies may offer promise for patients who experience premature
muscle fatigue while performing routine activities,” said Brad
Morgan, Ph.D., Cytokinetics’ Senior Vice President, Research and
Non-Clinical Development.
CK-2066260 is a FSTA from the same chemical
structural series as tirasemtiv, the first-generation FSTA
discovered and developed by Cytokinetics. Similar to tirasemtiv and
reldesemtiv, the next-generation FSTA from a distinct chemical
series, being developed in collaboration with Astellas for the
potential treatment of neuromuscular diseases of impaired muscle
function, CK-2066260 binds directly to fast skeletal muscle
troponin, increases myofibrillar calcium sensitivity and amplifies
the force response to submaximal nerve stimulation. The regulation
of calcium levels associated with muscle excitation and contraction
account for a significant amount of muscle energy utilization.
Because a FSTA lowers the amount of calcium required to produce a
given muscle force, the authors hypothesized that CK-2066260 could
reduce the energetic cost of muscle activation, allowing muscle to
contract for longer.
Key results from a series of in vitro, in situ
and in vivo rodent experiments demonstrated that treatment with
CK-2066260:
- Amplified the muscle force response to subtetanic electrical
stimulation by increasing muscle calcium sensitivity
- Improved the force response under fatiguing conditions
- Produced muscle force at lower cytosolic calcium concentrations
and accompanied by reduced ATP demand and muscle glycogen
usage
- Improved exercise capacity in healthy rats and a rat model of
peripheral artery insufficiency
The authors concluded, “In healthy human
subjects, the FSTAs tirasemtiv and reldesemtiv have been shown to
amplify the skeletal muscle force response to nerve stimulation.
Thus, the performance-enhancing effects of FSTA observed in the
present study may translate to humans and provide a promising
pharmacological treatment to patients suffering from severe muscle
weakness and exercise intolerance.”
About FSTAs
Skeletal muscle contractility is driven by the
sarcomere, the fundamental unit of skeletal muscle contraction and
a highly ordered cytoskeletal structure composed of several key
proteins. Skeletal muscle myosin is the motor protein that converts
chemical energy into mechanical force through its interaction with
actin. A set of regulatory proteins, which includes tropomyosin and
several types of troponin, make the actin-myosin interaction
dependent on changes in intracellular calcium levels. In
collaboration with Astellas, Cytokinetics is developing
reldesemtiv, a fast skeletal muscle troponin activator (FSTA), as a
potential treatment for people with SMA and certain other
debilitating diseases and conditions associated with skeletal
muscle weakness and/or fatigue. Reldesemtiv slows the rate of
calcium release from the regulatory troponin complex of fast
skeletal muscle fibers, which sensitizes the sarcomere to calcium,
leading to an increase in skeletal muscle contractility.
About Cytokinetics
Cytokinetics is a late-stage biopharmaceutical
company focused on discovering, developing and commercializing
first-in-class muscle activators and best-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 and METEORIC-HF. 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 collaborating with
Astellas Pharma Inc. (Astellas) to develop reldesemtiv, a fast
skeletal muscle troponin activator (FSTA). Astellas holds an
exclusive worldwide license to develop and commercialize
reldesemtiv. 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 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 potential benefits of
tirasemtiv, reldesemtiv and CK-2066260, including the potential
ability of CK-2066260 to reduce the metabolic cost of muscle
contraction and benefit patients who experience premature muscle
fatigue while performing routine activities; Cytokinetics’ and its
partners’ research and development activities; 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; Astellas’
decisions with respect to the design, initiation, conduct, timing
and continuation of development activities for reldesemtiv;
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 WeiserVice President, Corporate
Communications, Investor Relations(415) 290-7757
Cytokinetics (NASDAQ:CYTK)
Historical Stock Chart
From Apr 2024 to May 2024
Cytokinetics (NASDAQ:CYTK)
Historical Stock Chart
From May 2023 to May 2024