SAN DIEGO, Feb. 18, 2014 /PRNewswire/ -- Mast Therapeutics,
Inc. (NYSE MKT: MSTX) today announced new data from its randomized,
placebo-controlled, nonclinical study of MST-188 (low dose and high
dose) in a model of chronic heart failure.
The Company previously announced that a single, two-hour
infusion of MST-188 improved left ventricular systolic function
that was significant immediately (at the end of MST-188
administration) and remained significant at one week (and, in some
cases, at two weeks) after MST-188 administration. In
particular, MST-188 demonstrated a statistically significant
improvement in left ventricular ejection fraction, end-systolic
volume, stroke volume and cardiac output.
The Company today announced that:
- MST-188 resulted in statistically significant and progressive
reductions in troponin-I, at both 1 week and 2 weeks after MST-188
administration. Specifically, at 2 weeks post-administration,
compared to baseline values, mean reduction (improvement) in
troponin was 46.7% for low-dose MST-188 and 48.8% for high-dose
MST-188. In contrast, troponin increased 7.7% in the control
group.
Troponin is an intracellular protein that is released from
cardiomyocytes (heart muscle cells) following injury and/or
death. In patients with heart failure, multiple studies have
demonstrated a strong association between elevated troponin levels
and poor clinical outcomes. Recent data, published in the
Journal of the American College of Cardiology, confirmed that
increasing troponin during hospital stay was associated with
increased 180-day all-cause mortality. It is hypothesized
that preventing myocardial damage, as evidenced by reduced levels
of troponin, might favorably influence survival.
- MST-188 resulted in statistically significant and progressive
reductions in plasma N-terminal pro-brain natriuretic peptide
(NT-proBNP), at both 1 week and 2 weeks after MST-188
administration. Specifically, at 2 weeks post-administration,
compared to baseline values, mean reduction (improvement) in
NT-proBNP was 54.5% for low-dose MST-188 and 61.4% for high-dose
MST-188. In contrast, NT-proBNP increased 3.5% in the control
group.
NT-proBNP is released from the heart following increased cardiac
wall stress, typically as a result of the increased fluid volumes
that are common in heart failure. Studies have associated
persistently elevated natriuretic peptide concentrations during
hospital stay with poor prognosis. Recent data, published in
the Journal of the American College of Cardiology, found that
persistently high NT-proBNP levels during hospital stay (as well as
worsening heart failure) were associated with increased 180-day
all-cause mortality.
- Improvements in left ventricular function were achieved with
minimal effect on left ventricular end-diastolic pressure,
end-diastolic volume, systemic vascular resistance or heart rate,
suggesting that mechanisms other than vasodilation (i.e.,
alteration in cardiac loading conditions) may be
involved.
John R. Teerlink, M.D., Professor
of Medicine at the University of California,
San Francisco and Director of the Heart Failure Program and
of the Clinical Echocardiography Laboratory at the San Francisco
Veterans Affairs Medical Center, said: "The observation that a
single, short infusion of MST-188 positively affected troponin and
NT-proBNP levels at 2 weeks is intriguing. In patients with
heart failure, acute decompensation is a time of increased
vulnerability, where disease progression accelerates and the risk
of organ damage increases. An acute intervention that alters
the trajectory of decompensation, whether by decreasing cardiac
workload or preserving heart tissue, has the potential to minimize
organ damage and improve long-term outcomes. I look forward
to studies of the safety and efficacy of this promising new
agent."
Martin Emanuele, Ph.D., Senior
Vice President, Development of Mast Therapeutics, said: "The
reduction in troponin suggests MST-188 is limiting ongoing
cardiomyocyte loss, possibly through its membrane-sealing activity
and limiting unregulated calcium entry into the cell and calcium
overload. This would represent a novel mechanistic approach
to heart failure. Most existing treatments target indirect
methods that reduce workload on the heart and provide short-term
symptomatic relief, but may not directly improve heart function.
In contrast, MST-188 may preserve heart tissue and directly
improve heart function. If MST-188 limits the accelerated
cardiac damage that occurs during acute decompensation, it could
translate into better longer-term outcomes, such as reduced
re-hospitalization and increased survival. Notably, the data
we announce today are consistent with prior studies showing MST-188
improved cardiac function without increasing cardiac energy
requirements, a critical advantage for any new therapeutic in heart
failure."
About Mast Therapeutics
Mast Therapeutics, Inc. is a
publicly traded biopharmaceutical company headquartered in
San Diego, California. The
Company is leveraging the MAST (Molecular Adhesion and Sealant
Technology) platform, derived from over two decades of clinical,
nonclinical and manufacturing experience with purified and
non-purified poloxamers, to develop MST-188, its lead product
candidate, for serious or life-threatening diseases with
significant unmet needs. MST-188 is a cytoprotective,
hemorheologic, anti-inflammatory and anti-thrombotic agent that has
potential utility in a wide range of diseases and
conditions.
The Company is enrolling subjects in EPIC, a pivotal phase 3
study of MST-188 in sickle cell disease. In the first quarter
of 2014, the Company plans to initiate a phase 2, clinical proof of
concept study in acute limb ischemia that will evaluate whether
MST-188 improves the effectiveness of existing thrombolytic
agents. The Company also is evaluating development options in
heart failure. More information can be found on the Company's
web site at www.masttherapeutics.com. (Twitter: @MastThera)
Mast Therapeutics™ and the corporate logo are trademarks of Mast
Therapeutics, Inc.
Forward Looking Statements
Mast Therapeutics cautions
you that statements included in this press release that are not a
description of historical facts are forward-looking statements that
are based on the Company's current expectations and assumptions.
Such forward-looking statements include, but are not limited to,
statements regarding MST-188's prospects in heart failure,
including related to its potential to demonstrate ability preserve
heart tissue and directly improve heart function in humans and
increase survival, and the Company's development plans for MST-188
in heart failure and in acute limb ischemia, including the timing
of initiation of any clinical studies. Among the factors that
could cause or contribute to material differences between the
Company's actual results and the expectations indicated by the
forward-looking statements are risks and uncertainties that
include, but are not limited to: the risk that investigational
drugs that demonstrate efficacy in nonclinical studies may fail to
demonstrate safety and/or efficacy in clinical studies; delays in
the commencement and/or completion of clinical studies, including
as a result of difficulties in obtaining regulatory agency
agreement on clinical development plans or clinical study design,
opening trial sites, enrolling study subjects, manufacturing
sufficient quantities of clinical trial material, being subject to
a "clinical hold," and/or suspension or termination of a clinical
study, including due to patient safety concerns or lack of funding;
the potential for institutional review boards or the FDA or other
regulatory agencies to require additional nonclinical or clinical
studies prior to initiation of any planned phase 2 clinical study
of MST-188; the uncertainty of outcomes in ongoing and future
studies of MST-188 and the risk that MST-188 may not demonstrate
adequate safety, efficacy or tolerability in one or more such
studies; the potential that, even if clinical studies of MST-188 in
one indication are successful, clinical studies in another
indication may not be successful; the risk that, even if clinical
studies are successful, the FDA or other regulatory agencies may
determine they are not sufficient to support a new drug
application; the Company's reliance on contract research
organizations (CROs), contract manufacturing organizations (CMOs),
and other third parties to assist in the conduct of important
aspects of development of MST-188, including clinical studies, and
regulatory activities for MST-188, and that such third parties may
fail to perform as expected; the Company's ability to obtain
additional funding on a timely basis or on acceptable terms, or at
all; the potential for the Company to delay, reduce or discontinue
current and/or planned development activities, including clinical
studies, partner MST-188 at inopportune times or pursue less
expensive but higher-risk and/or lower return development paths if
it is unable to raise sufficient additional capital as needed; the
risk that, even if the Company successfully develops MST-188 in one
or more indications, it may not realize commercial success with its
products and may never generate revenue sufficient to achieve
profitability; the risk that the Company is not able to adequately
protect its intellectual property rights relating to the MAST
platform and MST-188 and prevent competitors from duplicating or
developing equivalent versions of its product candidates, including
MST-188; and other risks and uncertainties more fully described in
the Company's press releases and periodic filings with the
Securities and Exchange Commission. The Company's public filings
with the Securities and Exchange Commission are available at
www.sec.gov.
You are cautioned not to place undue reliance on forward-looking
statements, which speak only as of the date when made. Mast
Therapeutics does not intend to revise or update any
forward-looking statement set forth in this press release to
reflect events or circumstances arising after the date hereof,
except as may be required by law.
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SOURCE Mast Therapeutics, Inc.