Cytokinetics Announces Preclinical Data for CK-2127107 Presented at MDA Scientific Conference
March 22 2017 - 7:30AM
Cytokinetics, Inc. (Nasdaq:CYTK) today announced that preclinical
data for CK-2127107 were presented at the MDA Scientific Conference
in Arlington, VA, showing that this next-generation fast skeletal
troponin activator (FSTA) improves muscle function in mouse models
of spinal muscular atrophy (SMA). In collaboration with Astellas
Pharma Inc. (TSE:4503) ("Astellas"), Cytokinetics is developing
CK-2127107 as a potential treatment for people living with SMA and
certain other debilitating diseases and conditions associated with
skeletal muscle weakness and/or fatigue.
“These data support our ongoing Phase 2 clinical
trial of CK-2127107 in adolescent and adult patients with SMA,”
said Fady I. Malik, MD, PhD, Cytokinetics' Executive Vice
President, Research and Development. “The increased muscle force at
sub-maximal nerve stimulation frequencies in mice inform the
potential for CK-2127107 to increase muscle function in patients
living with motor neuron dysfunction.”
Preclinical Study Design and
ResultsThe objective of this study was to investigate the
effect of CK-2127107 on skeletal muscle function in two mouse
models of SMA with varying levels of disease severity. The study
evaluated CK-2127107 in 2B/2B-Neo Intermediate SMA mice (similar to
Type II SMA), in collaboration with Lurie Children’s Hospital and
Hung Li SMA mice (similar to Types III and IV SMA). These
mouse models exhibit significant nerve dysfunction and/or muscle
atrophy and a decrease in maximum muscle force production. Muscle
force production was assessed by electrical stimulation of the
sciatic nerve and plantar flexor force was measured in response to
a range of stimulation frequencies (10-200Hz).
Single doses of CK-2127107 increased isometric
force in situ in response to sub-tetanic nerve stimulation in both
mouse models. In the 2B/2B-Neo SMA mice, force output at a
physiologically relevant sub-tetanic stimulation frequency (30Hz)
was significantly increased following dosing of CK-2127107 at 10
mg/kg (p<0.01) and 30 mg/kg (p<0.001). In the Hung Li
SMA mice, force output at sub-tetanic (30Hz) nerve stimulation
increased with 30 mg/kg of CK-2127107 to levels higher than
wild-type control mice (p<0.001). In both the 2B/2B Neo
and Hung Li SMA mouse models there was a leftward shift of the
force-frequency response curve indicating a calcium sensitizing
effect of CK-2127107 in the skeletal muscle of these mouse models
of SMA with nerve dysfunction and muscle atrophy. These results
suggest that CK-2127107 and other FSTAs may be viable therapeutics
for improving muscle function in SMA.
About SMASMA is a severe
neuromuscular disease that occurs in 1 in every 6,000 to 10,000
live births each year and is one of the most common fatal genetic
disorders. Spinal muscular atrophy manifests in various
degrees of severity as progressive muscle weakness resulting in
respiratory and mobility impairment. There are four types of SMA,
named for age of initial onset of muscle weakness and related
symptoms: Type I (Infantile), Type II (Intermediate), Type III
(Juvenile) and Type IV (Adult onset). Life expectancy and
disease severity vary by type of SMA. Type I patients have the
worst prognosis, with a life expectancy of no more than 2 years;
Type IV patients have a normal life span but eventually suffer
gradual weakness in the proximal muscles of the extremities
resulting in mobility issues. Few treatment options exist for
these patients, resulting in a high unmet need for new therapeutic
options to address symptoms and modify disease progression.
About CK-2127107Skeletal muscle
contractility is driven by the sarcomere, the fundamental unit of
skeletal muscle contraction. It is a highly ordered cytoskeletal
structure composed of several key proteins. Skeletal muscle myosin
is the cytoskeletal 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. CK-2127107, a novel skeletal
muscle activator arising from Cytokinetics' skeletal muscle
contractility program, 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. CK-2127107 has demonstrated
pharmacological activity that may lead to new therapeutic options
for diseases associated with muscle weakness and fatigue. In
non-clinical models of SMA, a skeletal muscle activator has
demonstrated increases in submaximal skeletal muscle force in
response to neuronal input and delays in the onset and reductions
in the degree of muscle fatigue. CK-2127107 has been the
subject of five completed Phase 1 clinical trials in healthy
volunteers, which evaluated safety, tolerability, bioavailability,
pharmacokinetics and pharmacodynamics. In addition to the Phase 2
clinical trial in patients with SMA, Cytokinetics is collaborating
with Astellas on the conduct of a Phase 2 clinical trial in
patients with chronic obstructive pulmonary disease. Two additional
clinical trials of CK-2127107 are planned to begin in 2017, one in
patients with ALS and one in elderly subjects with limited
mobility.
About Cytokinetics and Astellas
Collaboration In 2013, Astellas and Cytokinetics formed a
partnership focused on the research, development, and
commercialization of skeletal muscle activators. The primary
objective of the collaboration is to advance novel therapies for
diseases and medical conditions associated with muscle impairment
and weakness. Under the collaboration, Cytokinetics exclusively
licensed to Astellas rights to co-develop and potentially
co-commercialize CK-2127107, a FSTA, in non-neuromuscular
indications. In 2014, Astellas and Cytokinetics agreed to expand
the collaboration to include certain neuromuscular indications,
including spinal muscular atrophy (SMA), and to advance CK-2127107
into Phase 2 clinical development, initially in SMA. The
agreement was further amended in 2016 to provide Astellas exclusive
rights to co-develop and commercialize CK-2127107 and other FSTAs
in non-neuromuscular indications and certain neuromuscular
indications (including SMA and ALS) and other novel mechanism
skeletal muscle activators in all indications, subject to certain
Cytokinetics’ development and commercialization rights;
Cytokinetics may co-promote and conduct certain commercial
activities in North America and Europe under agreed scenarios.
About Cytokinetics
Cytokinetics is a late-stage biopharmaceutical
company focused on discovering, developing and commercializing
first-in-class muscle activators 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 increase muscle function
and contractility. Cytokinetics’ lead drug candidate is tirasemtiv,
a fast skeletal troponin activator (FSTA). Tirasemtiv is the
subject of VITALITY-ALS, an international Phase 3 clinical trial in
patients with ALS. Tirasemtiv has been granted orphan drug
designation and fast track status by the U.S. Food and Drug
Administration and orphan medicinal product designation by the
European Medicines Agency. Cytokinetics is preparing for the
potential commercialization of tirasemtiv in North America and
Europe and has granted an option to Astellas Pharma Inc. for
development and commercialization in other countries. Cytokinetics
is collaborating with Astellas to develop CK-2127107, a
next-generation fast skeletal muscle activator. CK-2127107 is
the subject of two ongoing Phase 2 clinical trials enrolling
patients with spinal muscular atrophy and chronic obstructive
pulmonary disease. Cytokinetics is collaborating with Amgen
Inc. to develop omecamtiv mecarbil, a novel cardiac muscle
activator. Omecamtiv mecarbil is the subject of GALACTIC-HF, an
international Phase 3 clinical trial in patients with heart
failure. 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.
Astellas holds an exclusive worldwide license to develop and
commercialize CK-2127107. Licenses held by Amgen and Astellas are
subject to Cytokinetics' specified co-development and
co-commercialization rights. For additional information about
Cytokinetics, visit http://www.cytokinetics.com/.
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
Cytokinetics’ and its partners’ research and development
activities; the design, results, significance and utility of
preclinical study 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, including risks
that current and past results of clinical trials or preclinical
studies may not be indicative of future clinical trial results,
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, and 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 CK-2127107; Cytokinetics may incur
unanticipated research and development and other costs or be unable
to obtain additional financing necessary to conduct development of
its products; 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:
Cytokinetics
Diane Weiser
Vice President, Corporate Communications, Investor Relations
(415) 290-7757
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