Apollo's Oral Insulin - Key Studies Completed For Trial

Main Category: Diabetes
Also Included In: Clinical Trials / Drug Trials
Article Date: 20 Nov 2007 - 3:00 PDT

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Apollo Life Sciences (ASX: AOP) has completed a number of key process optimisation and validation studies as it prepares to move into the Phase I trial of its oral insulin product.

Apollo CEO John Priest said the company's Oradel™ drug delivery technology had passed a series of pre-trial tests showing the technology has the characteristics needed to protect insulin molecules from the harsh conditions of the gastrointestinal tract and deliver a therapeutic dose of insulin across the wall of the intestine into the bloodstream. "This is part of the ongoing building of Apollo's capabilities in the field of oral insulin delivery," said Mr Priest.

The pre-trial studies demonstrated that Apollo's research has unlocked some of the key obstacles to the oral delivery of insulin; notably the (1) efficient incorporation of insulin molecules in protective nanoparticles, and (2) production of nanoparticles of consistent size.

Efficient incorporation of insulin molecules in a protective nanoparticle matrix

A major challenge in developing oral insulin is protecting insulin molecules from being degraded by powerful enzymes and acids in the stomach before they reach the intestine where they are absorbed into the bloodstream.
Apollo has developed an innovative solution to this problem.

The company's Oradel™ drug delivery technology has the features to protect and transport insulin molecules by encapsulating them in a matrix of nanoparticles. Each nanoparticle is made up of a sugar-based (carbohydrate) protective polymer coated with vitamin B12 molecules.

Apollo's Head of Drug Delivery Dr Michael Luke said the nanoparticles containing the insulin molecules were pulled through the wall of the intestine using the body's natural transport system for vitamin B12.

"Once across the wall of the intestine, the bonds holding the nanoparticle together are broken down releasing the insulin payload into the bloodstream," Dr Luke said.

Apollo has developed a unique production method whereby up to 100 per cent of insulin molecules are entrapped in the matrix of the Oradel™ nanoparticles. By maximising insulin entrapment during the production process, Apollo's Oradel™ nanoparticles can deliver up to 160 milligrams of insulin per microgram of attached vitamin B12 (a 36,000:1 payload ratio).

"Apollo's insulin payload ratio of 36,000:1 is an impressive development compared to a recently published study1 that only delivered a 1:1 ratio of insulin to vitamin B12," Dr Luke explained.

Production of insulin nanoparticles of consistent size

Apollo's production method has also overcome a key stumbling block for producing oral insulin through its ability to produce nanoparticles of consistent size.

"This is a critical factor considering that particle size is a key physical attribute that determines the ability of nanoparticles to cross the intestinal wall, said Dr Luke. Dr Luke said recent studies indicate that particles between 100 to 200 nanometres in diameter are the optimal size at which nanoparticles are able to be carried through the wall of the human intestine2.

"Nanoparticles need to be small enough to pass through the intestinal wall but large enough to carry enough insulin to have a therapeutic effect. To satisfy these tight parameters, we believe 100 to 200 nanometres to be the most appropriate diameter range for Apollo's Oradel™ insulin nanoparticles," said Dr Luke.

Apollo has demonstrated, using several validation techniques that it can consistently manufacture insulin-loaded nanoparticles between 100 to 200 nanometres in diameter - an optimal size to carry enough insulin to have a therapeutic effect and still be able to easily pass through the wall of the human intestine.

"Our patented production method consistently delivers 80 per cent of Oradel™ nanoparticles in the optimum 100 to 200 nanometre diameter range without the need for refinement. When we add a refinement step to our production method over 95 per cent of Oradel™ nanoparticles fall within the desired range," explained Dr Luke.

According to Mr Priest, Apollo Life Sciences Oradel™ drug delivery technology has the potential to become a global market leader for the treatment of diabetes.

"The International Diabetes Federation estimates that diabetes currently affects 246 million people worldwide and is expected to affect 380 million by 20253. Apollo's Oradel™ technology is being developed to deliver insulin orally via a tablet - a welcome relief for diabetics that can have up to five painful injections each day," said Mr Priest.

The current global market for diabetes medications is valued at $US18 billion and growing at an annual rate of about 40 per cent. Each year a further 7 million people develop diabetes with two people developing diabetes every 10 seconds1.

Mr Priest added that Apollo can also manufacture nanoparticles of different sizes to transport a range of other drugs.

"For example, Oradel™ technology has shown promise for the oral delivery of anti-inflammatory proteins (TNF blockers) for the treatment of diseases such as rheumatoid arthritis and as an alternative to non-steroidal anti-inflammatory agents like aspirin, which can damage the lining of the stomach and upper digestive tract," said Mr Priest.

The worldwide market for TNF blockers was estimated to be almost US$10 billion in 2006 and growing at over 30 per cent a year.

About Apollo Life Sciences Limited

Apollo Life Sciences (ASX: AOP) is an Australian-based biotechnology company with core expertise in the structure and function of proteins. Apollo's extensive library of over 90 human proteins is a rich source of candidate biopharmaceuticals such as the anti-TNF ALS-00T2 used for psoriasis treatment. Apollo's library of proteins is generating early sales revenues from research and diagnostic testing.

Apollo has leveraged its accumulated knowledge of proteins to improve drug delivery methods of accepted large molecule drugs like insulin that have previously been administered by injection. The Company has developed and patented two major needle-free technologies, the oral Oradel™ platform and the transdermal Intradel™ platform, designed to eliminate patients' discomfort, improve effectiveness and lower the cost of therapeutics in major biopharmaceutical markets. Apollo's lead therapeutic candidates are oral insulin and an oral and topical TNF blocker.

http://www.apollolifesciences.com

1. ChemMedChem (2007). Vitamin B12 as a Carrier for the Oral Delivery of Insulin. ChemMedChem, Communications (advanced online publication). A.K. Petrus, A.R. Vortherms, Prof. T.J. Fairchild and Prof. R.P. Doyle. http://www.chemmedchem.org

2. des Rieuxm, A., Ragnarsson, E.G., Gullberg, E., Préat, V., Schneider, Y.J., and Artursson, P. (2005). Transport of nanoparticles across an in vitro model of the human intestinal follicle associated epithelium. European Journal of Pharmaceutical Science. Volume 25 (4-5). pp. 455-465.

3. International Diabetes Foundation (2007). Diabetes Facts and Figures. http://www.idf.org