2014

Phosphagenics Reports Superior Pre-clinical Cholesterol Results from APA-01 and Atorvastatin Combination

    MELBOURNE, Australia, Jan. 30 /PRNewswire-FirstCall/ -- Phosphagenics
 Limited ("Phosphagenics") (ASX: POH, AIM: PSG, OTCQX: PPGNY) today
 announced results of a pre-clinical study demonstrating that the
 combination of its APA- 01 product candidate and the statin atorvastatin
 (Lipitor(TM)) significantly reduced serum lipids and inflammatory proteins
 involved in the development of atherosclerosis.
 
     Study Design
 
     The purpose of the study was to determine whether a combination of the
 statin drug atorvastatin and APA-01 could reduce serum lipids, inhibit
 atherosclerotic lesion progression and reduce proinflammatory cytokines and
 other biomarkers of inflammatory disease more effectively than the statin
 alone.
 
     Studies were performed in ApoE mice, animals that spontaneously form
 atherosclerotic plaques and represent a well-established model of human
 atherogenic hyperchosterolemia.
 
     During the first 16-weeks of this 24-week study, all animals in the
 experimental group were maintained on a standard diet, followed by an eight
 week treatment period in which this diet was supplemented with 21% fat and
 0.15% cholesterol, an atherogenic diet expected to accelerate
 atherosclerotic progression. All animals in the experimental groups
 received drug treatment in both their normal and high-fat diets at various
 dosing regiments throughout the 24-week study. Control group animals
 received no drug treatment and were maintained on either the same diet as
 the treatment groups or on a standard diet.
 
     Study Results
 
     Effects on Serum Lipids
 
     The study results indicated that among the animals treated with the
 APA-01 and atorvastatin combination, total cholesterol levels fell by up to
 an additional 12% compared to those animals treated with atorvastatin
 alone. Total HDL-C (good cholesterol) levels increased by up to 37% in
 combination drug-treated animals, while LDL-C (bad cholesterol) levels were
 further reduced by up to 24% with the combination, as opposed to
 atorvastatin alone. The combination also caused a decrease of 92% in
 triglycerides levels compared to 72% with atorvastatin alone.
 
     Effects on Biomarkers of Inflammation
 
     APA-01, combined with atorvastatin, enhanced the statin's effects on
 lowering inflammation that contributes to the development of
 atherosclerotic plaques. Reductions occurred in final plasma levels of 23
 cytokines that were measured. Following 24 weeks of treatment with various
 doses of APA-01 and atorvastatin, a statistically significant reduction
 occurred in a number of cytokines including IL-1B, IL-10, G-CSF, GM-CSF,
 IFN-y, MCP-1, and RANTES compared to control and these decreases were
 greater than with either compound alone and appeared to be somewhat
 dose-dependent.
 
     Effects on Atherosclerotic Plaque Progression
 
     Atherosclerotic lesions were significantly elevated following
 incorporation of the high-fat high-cholesterol diet in all animals compared
 to animals maintained on the regular, rodent diet for the 24-week study
 period. The effect of the combination treatment of APA-01 combined with
 atorvastatin appeared to cause a trend toward decreased aortic lesions, but
 these were not statistically significant.
 
     Commenting on the study results, Dr. Esra Ogru, Executive Vice
 President of Research and Development at Phosphagenics, said, "Current
 therapies for atherosclerosis focus on drugs that lower serum cholesterol
 levels. Experimental and clinical evidence suggests that the efficacy of
 these drugs may also be related to their ability to reduce oxidative stress
 and inflammation in the endothelium, or blood vessel lining, where
 atherosclerotic plaques develop. We believe that APA-01's apparent
 enhancement of a statin's anti-inflammatory functions could potentially
 provide a novel therapeutic approach to treating atherosclerosis."
 
     Atorvastatin is the world's largest selling drug with sales of US$13.6
 billion annually and is the primary contributor to the US$35.2 billion
 market for statin drugs globally.
 
     "In particular there is an unmet need for a more effective treatment
 for elevated triglycerides and APA-01 has demonstrated efficacy in this
 area in this preclinical study. We are now assessing the impact of these
 results before determining our future strategy. However, the insulin,
 oxycodone and Phospha E(R) clinical programs will remain our priority for
 this year," Dr. Ogru said.
 
     About Atherosclerosis
 
     Atherosclerosis, or the build-up of fatty deposits (plaques) on
 interior blood vessel walls, is a progressive process initially involving
 endothelial dysfunction and accumulation of lipids on the linings of blood
 vessel. Atherosclerotic lesions develop as a result of inflammatory
 stimuli, subsequent release of various cytokines, proliferation of smooth
 muscle cells, synthesis of connective tissue matrix, and accumulation of
 macrophages and lipids. Atherosclerosis is involved in the development of
 coronary heart disease, myocardial infarction, and stroke, among other
 diseases.
 
     About Phosphagenics Limited
 
     Phosphagenics is a Melbourne-based, globally driven biotechnology
 company focused on the discovery of new and cost effective ways to enhance
 the bioavailability, activity, safety and delivery of proven pharmaceutical
 and nutraceutical products.
 
     Phosphagenics' core technology is built around the science and
 application of phosphorylation, a process where the addition of a phosphate
 group has been found to enhance the bioavailability, activity and safety of
 existing pharmaceuticals and nutraceuticals, as well as to assist in the
 production of drug delivery platforms.
 
     Phosphagenics' shares are listed on the Australian Stock Exchange (POH)
 and the London Stock Exchange's Alternative Investment Market (PSG). An ADR
 -- Level 1 program was established in the U.S. with The Bank of New York
 Mellon (PPGNY) for U.S. investors to trade in Phosphagenics' stock on the
 'over-the- counter' market. In July 2007, this was upgraded to the
 International OTCQX, a new premium market tier in the U.S. for
 international exchange-listed companies, operated by Pink Sheets, LLC.
 
     For more information, please visit Phosphagenics' web site at
 www.phosphagenics.com.
 
     Safe Harbor Statement
 
     This press release contains forward-looking statements based on current
 expectations of future events. If underlying assumptions prove inaccurate
 or unknown risks or uncertainties materialise, actual results could vary
 materially from the Phosphagenics' expectations and projections. Risks and
 uncertainties include general industry conditions and competition; economic
 conditions, such as interest rate and currency exchange rate fluctuations;
 technological advances and patents attained by competitors; challenges
 inherent in new product development, including obtaining regulatory
 approvals; domestic and foreign health care reforms and governmental laws
 and regulations.
 
 
 

SOURCE Phosphagenics Limited

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