Phosphagenics reports pre-clinical progress

Melbourne drug developer Phosphagenics (ASX:POH) has pulled a dozen-odd plump but otherwise healthy rabbits out of the hat after completing the first arm of a three-armed preclinical study of its anti-atherosclerosis drug candidate APA-01.

The company reported today that the rabbit trial's results have reinforced evidence from in vitro trials for the efficacy of its lead compound in reducing atherosclerotic plaques -- fatty deposits in the arteries, a leading cause of heart attack, angina, dementia and stroke.

The rabbit strain used in the trial is genetically predisposed to develop atherosclerosis. Three test groups of six rabbits, and one control group were fed for four weeks on a very high cholesterol diet. The test groups were treated daily with low, medium and high doses of APA-01 throughout the trial.

The first arm of the multinational trial, which is being run in Switzerland, the US and Australia, was designed to assess APA-01's ability to prevent the development of atherosclerosis. The study showed that the drug greatly slowed or prevented the deposition of atherosclerotic plaque in the rabbits.

The company said the rabbits in the test groups had about 60 per cent fewer plaque lesions in their arteries, relative to the control animals, and also had a 30 per cent reduction in expression of the CD 36 receptors, which mediate the uptake of cholesterol by macrophages.

The CD 36 receptor binds the low-density lipoprotein ApoE, which transports cholesterol -- macrophages scavenge surplus cholesterol in this way, but then penetrate artery walls where they are transformed into cholesterol-rich foam cells, the primary components of atherosclerotic plaques.

Phosphagenics' VP of research and development, Dr Esra Ogru, said the reduction of expression of the CD36 receptor was an important finding, because it indicated the drug find applications in many diseases caused by inflammation.

Ogru said the result was very positive for the company, because promising in vitro results did not always translate to animal models. He said the fact that the results, obtained in a well-established animal model commonly used in atherosclerosis studies, were so impressive they boded well for human studies that are aimed to commence later this year.

The second arm of the preclinical trial program, already under way, is testing whether Phosphagenics' drug can reduce existing atherosclerotic plaques.

Targeting statins

The third, which began recently, will test whether APA-01 can enhance the activity of today's market-leading anti-cholesterol drugs collectively known as statins.

Ogru said this arm was potentially of greatest commercial significance to her company, since several of the statins -- the world's most profitable drugs -- are due to come off patent in the next few years.

Drug companies are seeking to 'evergreen' their drugs -- find new formulations that will earn them lucrative patent extensions. They have been unable to find formulations that enhance the drugs' notoriously poor absorption.

Ogru said in vitro trials of APA-01, in combination with a market-leading statin, had shown the Phosphagenics compound substantially enhanced the statin's activity. It was not yet clear whether the enhanced activity results from an additive or synergistic effect.

She said APA-01 is a semi-synthetic molecule, with phospholipids-like properties. Its ability to reduce atherosclerotic plaque was discovered several years ago when a company chemist decided to develop a highly phosphorylated form of a natural compound common to most plants.