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.
SOURCE Mast Therapeutics, Inc.
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