TEMPE, Ariz., Oct. 13, 2009 (GLOBE NEWSWIRE) -- Capstone Therapeutics (Nasdaq:CAPS) today announced the presentation of pre-clinical data at the American College of Surgeons 95th Annual Clinical Conference in Chicago, IL, demonstrating significant benefit of Chrysalin(R) (rusalatide acetate or TP508) in a model of acute heart disease and elevated cholesterol. The data, as previously announced and as originally published in April 2009, demonstrate that Chrysalin, administered following the onset of ischemia, showed a statistically significant cardioprotective benefit in an elevated-cholesterol porcine model of acute myocardial infarction (AMI or heart attack).
In this pathophysiologically relevant model of AMI with either normal (first cohort, previously published as announced on March 5, 2009) or elevated cholesterol levels (second cohort, previously published and presented today), intravenous administration of Chrysalin produced a significant reduction in infarct size. Importantly, the drug was administered following ischemic insult, which reflects the anticipated clinical scenario of a heart attack.
The study results from the elevated-cholesterol group were published under the title "The Effect of Thrombin Fragment (TP508) on Myocardial Ischemia Reperfusion Injury in Hypercholesterolemic Pigs" in the Journal of Applied Physiology advance online publication with the following citation: J Appl Physiol (April 16, 2009). doi:10.1152/japplphysiol.00071.2009. The abstract and full-text manuscript are available via the following link:
"We are pleased that the American College of Surgeons chose for a formal presentation these landmark pre-clinical study results of Chrysalin in the hypercholesterolemic porcine model of AMI," said Randolph C. Steer, MD, Ph.D., President of Capstone Therapeutics. "These results are the first of their kind in this exceptionally challenging model of AMI. We have previously announced significant progress in understanding the cellular and biologic effects of Chrysalin, and we have demonstrated its effectiveness in a critical care cardiovascular indication of largely unmet medical need. There are an estimated 1.4 million heart attacks per year in the U.S. alone. We believe Chrysalin is a strong development candidate for limiting damage to the human heart in the clinical setting of acute myocardial infarction."
About the Study
The study, performed in the laboratory of Frank W. Sellke, MD, Chief, Cardiothoracic Surgical Research, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center / Harvard Medical School, demonstrated that Chrysalin extensively decreases myocardial injury when administered following a major ischemic insult. Endpoints of the study included infarct size, coronary microvessel function, myocardial function and apoptotic markers.
Methods - Second Group: Elevated Cholesterol
Twenty-one hypercholesterolemic male Yucatan pigs underwent 60 minutes of mid-left anterior descending coronary artery occlusion followed by 120 minutes of reperfusion. Pigs received either saline vehicle (control, n = 7) or one of two doses of Chrysalin as a bolus 50 minutes into the ischemic period followed by continuous intravenous infusion during reperfusion ("1X Dose": 0.5mg/kg followed by 1.25mg/kg/h, n=7; "2X Dose": 1.0 mg/kg followed by 2.50mg/kg/h, n=7).
Parameters measured included global and regional myocardial function, infarct size and coronary microvascular reactivity. Apoptosis/cell survival activity was assessed by Western blotting and TUNEL staining.
Results:
* The size of the area at risk (AAR) was not significantly different among groups, indicating that the initial ischemic injury did not differ. The area of necrosis, however, decreased in a dose-dependent manner in the TP508 groups compared to the control group (p<0.05). The area of necrosis was inversely correlated with serum levels of TP508; the 1X and 2X doses produced a 32% and 54% reduction, respectively, in infarct size. * Global cardiac function [mean arterial blood pressure (MAP), developed left ventricular pressure (DLVP), and positive (+dP/dt) and negative (-dP/dt) first derivatives of left ventricular pressure] was not significantly different among groups. * Regional myocardial function in the AAR (horizontal axis) was improved in the TP508 2X dose group compared to the other groups starting one hour into reperfusion (p<0.05), whereas no difference was observed in the longitudinal axis among groups. * Coronary microvascular responses (endothelium-dependent and -independent relaxation) were improved in the TP508 2X dose group (p<0.05). * The apoptotic (TUNEL-positive) cell count was significantly lower in the AAR of both TP508 groups compared to the control group (p<0.05). The expression of proteins favoring cell survival (HSP90 and phosphor-Bad [Ser112]) was significantly higher (p<0.05) in the TP508 2X dose group, and the expression of cell death signaling proteins (cleaved caspase-3, AIF and PARP) was significantly lower (p<0.05) in the TP508 1X dose group.
Conclusions:
The key finding of this study is that TP508 provides significant, dose-dependent myocardial protection in the setting of hypercholesterolemia during ischemia reperfusion (IR) injury. TP508 administration led to a greater than 50% reduction of infarct size, improved regional left ventricular function, favored expression of cell survival proteins, and attenuated apoptosis. The previously-published portion of the study conducted in pigs with normal cholesterol demonstrated that TP508 decreases myocardial necrosis by 45%. Taken together, these data suggest TP508 may offer a novel approach in protecting the myocardium from IR injury.
About Capstone Therapeutics
Capstone Therapeutics (trade name of OrthoLogic Corp.) is a biotechnology company committed to developing a pipeline of novel therapeutic peptides aimed at helping patients with under-served medical conditions. The Company is focused on development and commercialization of two product platforms: AZX100 and Chrysalin(R) (rusalatide acetate or TP508).
AZX100 is a novel synthetic 24-amino acid peptide, one of a new class of compounds in the field of smooth muscle relaxation and fibrosis. Based on its demonstrated effects in pre-clinical models and safety in clinical trials, AZX100 is currently being evaluated for commercially significant medical applications such as the prevention or reduction of hypertrophic and keloid scarring and treatment of pulmonary disease. Capstone has an exclusive worldwide license to AZX100.
Chrysalin, the Company's novel synthetic 23-amino acid peptide, has been proven in multiple pre-clinical and clinical models to stimulate cellular events leading to angiogenesis, revascularization, and repair of dermal and musculoskeletal tissues. It is currently being evaluated in disorders that involve vascular endothelial dysfunction, such as acute myocardial infarction. The Company owns exclusive worldwide rights to Chrysalin.
Capstone's corporate headquarters are in Tempe, Arizona. For more information, please visit the Company's website: www.capstonethx.com.
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Statements in this press release or otherwise attributable to Capstone Therapeutics regarding our business that are not historical facts are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements, which include the timing and acceptability of FDA filings and the efficacy and marketability of potential products, involve risks and uncertainties that could cause actual results to differ materially from predicted results. These risks include: delays in obtaining or inability to obtain FDA, institutional review board or other regulatory approvals of pre-clinical or clinical testing; unfavorable outcomes in our pre-clinical and clinical testing; the development by others of competing technologies and therapeutics that may have greater efficacy or lower cost; delays in obtaining or inability to obtain FDA or other necessary regulatory approval of our products; our inability to successfully and cost effectively develop or outsource manufacturing and marketing of any products we are able to bring to market; changes in FDA or other regulations that affect our ability to obtain regulatory approval of our products, increase our manufacturing costs or limit our ability to market our product; affects on our stock price and liquidity if we are unable to meet the requirements for continued listing on the NASDAQ Global Market; our need for additional capital in the future to fund the continued development of our product candidates; and other factors discussed in our Form 10-K for the fiscal year ended December 31, 2008, and other documents we file with the Securities and Exchange Commission.
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