Breakthrough oral delivery for arthritis sufferers

Second major application for the Oradel platform currently in development for oral insulin

SYDNEY, Australia | Feb 21, 2007 | Apollo Life Sciences (ASX:AOP) today announced it has achieved a major breakthrough by successfully reducing inflammation with oral doses of Tumour Necrosis Factor (TNF) blocker. The preclinical studies used OradelTM, Apollo’s technology for oral delivery of large water soluble proteins, including insulin and antibodies.

Like people with diabetes, patients prescribed TNF blockers for inflammation associated with rheumatoid arthritis currently have no alternative to injections. Successful development of Apollo’s tableted TNF blocker would give patients a more convenient way to be treated.

The global market for TNF blockers was estimated to be almost US$10 billion in 2006 (see below) and growing at over 30% a year.

Results from the preclinical studies indicated oral doses of Apollo’s TNF blocker ALS-00T2 using OradelTM significantly reduced inflammation (p≤0.05) to a comparable degree to subcutaneous injection of the molecule. In the studies, inflammation was induced using carrageenan. Solutions were administered daily, either by subcutaneous injection or orally and swelling was measured twice daily. The carrageenan model is classically used in the development of non-steroidal anti-inflammatory drugs.
The studies showed that the OradelTM technology can be used to deliver an antibody-sized drug, such as Apollo’s ALS-00T2, in a more convenient form than is now possible. Large proteins and antibody-based drugs are a growing class of therapeutics that still need to be injected because they are usually destroyed by the stomach’s digestive acids.
“Apollo’s OradelTM protects the protein in the stomach and makes sure the drug travels across the stomach wall to where it can work,” said Apollo’s director of science, Dr Greg Russell-Jones. “This is a breakthrough. We understand no-one else has been able to deliver antibodies and large proteins such as TNF blockers in tablet form.”
“These latest studies show that OradelTM can be used to deliver a wide range of the drugs already in the global protein therapeutics market, which had an estimated value of US$57 billion in 2005. Antibodies are the fastest growing segment of that market and were estimated to represent a quarter of it in 2005. We believe most people will prefer tablets to injections for these drugs, so there is a ready-made market for our OradelTM products,” said Mr Priest.

Revenues for the three leading TNF blocker products have been estimated at almost US$10 billion for 2006. Source: Signals Magazine.

Product name                         Est. 2005 sales (US$)     Est. 2006 sales (US$)
Enbrel - injectable                 $ 3.7 billion                         $ 4.2 billion
Remicade - injectable          $ 3.5 billion                         $ 4.0 billion
Humira - injectable               $ 1.4 billion                         $ 1.6 billion

About Apollo’s OradelTM oral delivery technology
Apollo’s oral delivery technology, OradelTM, is able to entrap large, water soluble proteins up to antibody size within a protective coating, providing protection from degradation in the stomach. The technology also uses targeting agents to promote absorption of the molecule from the intestine.
Oral delivery of proteins is a breakthrough because the stomach’s digestive acids usually destroy proteins before they can be taken up by the body, and the stomach lining typically prevents material from passing into the bloodstream.
Apollo’s OradelTM technology enables controlled release of the active molecule. Preclinical studies indicate it transports large protein molecules, up to 150kDa in weight, within protective structures of around 200nm in size. Each cell in the stomach wall transports the coated material at a different rate, allowing for a controlled release of the drug into the circulation. Once the protective structure is released into circulation, it collapses and the drug is released.
Preclinical studies on the oral delivery technology using large proteins have demonstrated effective delivery of bioactive molecules. Preclinical toxicity studies conducted on OradelTM insulin showed no adverse effects at low or high doses.
About Apollo’s preclinical comparative studies
A series of initial preclinical studies compared the effects of Apollo’s ALS-00T2 delivered by subcutaneous injection or orally using OradelTM over a five day period. ALS-00T2 is a protein, which binds to TNF-alpha in order to reduce inflammation.
Multiple studies were conducted to investigate the efficacy of ALS-00T2 delivered orally compared to subcutaneous injection, using an extended carrageenen-induced paw edema model. Carrageenan has been shown to initiate cellular accumulation of macrophages then polymorphonuclear cells in a mouse footpad. The model provides a test for the ability of treatments to block cellular accumulation. Each experiment consisted of at least three treatment groups: subcutaneous injection of ALS-00T2, subcutaneous injection of ALS-00T2 in Oradel or oral administration of ALS-00T2 in Oradel. Measurements of the affected footpad were taken at regular intervals.
Analysis of the results demonstrated that orally administered ALS-00T2 reduced swelling to a comparable degree to subcutaneously injected ALS-00T2 and that the treatment group results were significantly different from the control (p≤.05).
Further preclinical studies to optimise dosing and formulation are commencing.
About TNF blockers
TNF blockers relieve inflammatory symptoms and slow the speed of joint damage associated with rheumatoid arthritis. They are considered one of the best new arthritis treatments and are increasingly being used for arthritis and other inflammatory conditions such as psoriasis and Crohn’s disease. Protein receptor and antibody-based TNF blockers work by reducing the levels of TNF-a (tumour necrosis factor alpha) protein, which plays a role in causing the inflammation associated with these diseases.
About Apollo Life Sciences Limited
Apollo Life Sciences (ASX:AOP) is a biotechnology company that has made major breakthroughs in the areas of drug delivery and expression of proteins from human cells. Apollo’s combined technologies are expected to lead to more effective and lower cost therapeutics, compared to first generation protein-based drugs.

For more information: For media enquiries: Dr Greg Russell-Jones, Science Director Andrew Huckel Apollo Life Sciences Wilkinson Media 02 9310 1800 02 8001 8888 / 0402 822 622

SOURCE: Apollo Life Sciences

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