Antisense Therapeutics Projects Update

• ATL/TV1102 for Multiple Sclerosis
• ATL1101 for Prostate Cancer
• ATL1103 for Growth & Sight Disorders

Visctoria, Australia | February 12, 2009 | Antisense Therapeutics Limited (ASX:ANP) is pleased to provide the following update on its current projects including the development progress being made on lead drug ATL/TV1102 .

1. ATL/TV1102 for MS 

As previously advised, ANP’s licence partner   Teva Pharmaceutical Industries (Teva) is responsible for performing and funding the ongoing research and development of ATL/TV1102.

In June 2008 the Company reported that ATL/TV1102 had demonstrated significant reduction in disease activity in relapsing remitting multiple sclerosis patients in a Phase IIa clinical trial. The Principal Investigator for the trial, Volker Limmroth MD PhD, Chairman of the Department of Neurology, Cologne City Hospitals, Germany, was quoted as saying the results of this international multi-center clinical study were very encouraging and demonstrated a highly significant effect for ATL/TV1102 on disease activity in MS patients. The trial results were presented at the World Congress on Treatment and Research in Multiple Sclerosis in September 2008.

Based on the positive results from the Phase IIa trial, Teva advised that it intended to conduct additional pre-clinical and clinical research before continuing to a Phase III study with this unique and promising antisense drug.

As part of the program to support the longer term clinical trials of ATL/TV1102 in MS patients, Teva are currently conducting chronic (extended duration) toxicology studies which were initiated late Q3’08. These studies are now well advanced and ANP expect Teva to have completed them by the end of this calendar year.

ANP will receive a further milestone payment from Teva upon completion of these toxicology studies and Teva’s confirmation to commence the next clinical trial of ATL/TV1102. The toxicology program being conducted and funded by Teva is a major cost component of the late stage development program for ATL/TV1102. ANP is very pleased to have an experienced drug developer and top 20 global pharmaceutical company undertaking this key activity. In accordance with the license agreement between Teva and ANP, Teva are to pay ANP future milestone payments up to US$100Mill on the successful development and commercialization of ATL/TV1102 in the MS application plus low double digit royalties on drug sales. To date Teva have paid US$6Mill in milestone payments. One third of all milestone payments received by ANP are passed on to  ANP’s technology collaboration partner, ISIS Pharmaceuticals Inc. .

ATL1101 for Prostate Cancer

In October 2008, ANP announced positive results from a preclinical research study into the effects of ATL1101 on human prostate tumour growth. The study, which was conducted in collaboration with Professor Martin Gleave, Department of Urological Sciences, University of British Columbia and Director of The Prostate Centre at Vancouver General Hospital - a leader in prostate cancer treatment and drug development, showed that ATL1101 significantly suppressed human prostate tumour growth in a mouse model of prostate cancer.

Details of the study were presented at the New York Academy of Sciences Annual Meeting of the Oligonucleotide Therapeutics Society, Harvard Conference Centre, Boston in October 2008. There is much interest in ATL1101’s disease target. ATL1101 has a novel mechanism of action being an RNA silencing second generation antisense drug that targets the insulin-like growth factor -1 receptor (IGF-IR). IGF-IR is an important target for cancer treatment.

ATL1101 and its uses are protected by an extensive intellectual property portfolio position that was recently strengthened with the allowance of a US patent until 2024. ANP have also completed certain pre-clinical development activities including some toxicology studies on ATL1101 which would reduce the time and cost of entering human clinical trials. Having already created significant value in ATL1101 and consistent with ANP’s business approach of partnering the development and commercialization of its product pipeline, ANP is currently in discussions with various parties regarding the ongoing development of this project.

3. ATL1103 for Growth and Sight Disorders

ATL1103, ANP’s novel second generation antisense drug for growth and sight disorders, is currently well advanced in pre-clinical toxicology studies. These mouse and primate toxicology studies are a major part of the pre-clinical program necessary for planned human clinical trials. ATL1103 is designed to block the growth hormone (GH) receptor and thereby reduce levels of the hormone insulin-like growth factor-1 (IGF-I) in the blood. It is a potential treatment for  diseases associated with excessive GH action such as the human growth disorder, acromegaly and the sight disorder, diabetic retinopathy.

In animal study results previously reported by the Company, ATL1103 demonstrated its intended therapeutic action by significantly reducing IGF-I levels in the blood. ATL1103 has also demonstrated its intended therapeutic action in an animal model of retinopathy by significantly reducing retinal neovascularisation - the growth of abnormal new blood vessels in the retina of the eye. The toxicology studies which commenced in May 2008 are nearing conclusion with dosing now complete. The study report is on track for completion in the second half of 2009. ANP is very pleased with the progress being made on all its projects and looks forward to providing further updates as they occur.

Background Information

Antisense Therapeutics Limited (ASX: ANP) is an Australian publicly listed biopharmaceutical drug discovery and development company. Its mission is to create, develop and commercialise antisense pharmaceuticals for large unmet markets. ANP has two drugs in development and two drugs in pre-clinical research. ATL1102 (injection) is in the advanced stages of a Phase IIa trial as a potential treatment of multiple sclerosis. ATL1103 is a second-generation antisense drug designed to lower blood IGF-I levels and is entering preclinical development as a potential treatment for acromegaly and vision disorders. ATL1102 (inhaled) is at the pre-clinical research stage as a potential treatment for asthma. ATL1101 is a second-generation antisense drug at the pre-clinical research stage being investigated as a potential treatment for prostate cancer. ATL1102 has been licensed to Teva Pharmaceutical Industries Ltd.

ATL/TV1102 is a second generation antisense inhibitor of CD49d, a subunit of VLA-4 (Very Late Antigen-4). In inflammation, white blood cells (leukocytes) move out of the bloodstream into the inflamed tissue, for example, the CNS in Multiple Sclerosis (MS), and the lung airways in asthma. The inhibition of VLA-4 prevents white blood cells from entering sites of inflammation, thereby halting progression of the disease. VLA-4 is a clinically validated target in MS. Antisense inhibition of VLA-4 has demonstrated positive effects in a number of animal models of inflammatory disease including MS, the MS animal data having been published in a peer reviewed scientific journal.
Multiple sclerosis is a lifelong chronic disease of the central nervous system which is believed to affect as many as 2.5 million people worldwide. Global drug sales for MS are in excess of $US 6 billion and are expected to grow with the introduction of novel treatment options. There remains a high demand for  more effective and better tolerated treatments.

ATL1101 is an antisense inhibitor of IGF-IR, which has shown potent activity in laboratory studies, including in human cancer cells. IGFIR is one of the best known of a family of cell signaling molecules that are referred to as “anti-apoptotic”. These molecules prolong cell survival by inhibiting programmed cell death (apoptosis). The connection between IGF-IR activity and prostate cell tumorigenicity has been studied for many years. Drugs targeting IGF-IR are designed to slow down tumour growth and make tumour cells more susceptible to cell death. Inhibition of IGF-IR is also designed to make tumour cells more susceptible to killing by cytotoxic treatments like radiation therapy and chemotherapy. Such therapeutic approaches are under investigation in several large pharmaceutical companies, lending support to our own antisense-based strategy against the same target.

Prostate cancer is the second most frequently diagnosed cancer in men after skin cancer. It is estimated there will be 218,890 new cases diagnosed in the U.S. this year. Around 1 in 6 men will develop prostate cancer, a third to a half of whom will recur after local treatment and risk progression to metastatic prostate cancer. Metastatic disease invariably progresses to hormone refractory or castrateresistant prostate cancer  (CRPC) if given enough time. Prostate tumours are initially androgen (male sex hormone) dependent, and can be  treated with androgen ablation therapy (the term “castration” can be used to describe removal of the source of androgen), however once the disease progresses to its most dangerous and aggressive form, CRPC, treatment options are limited and prognosis is poor. Treatment options depend on disease severity and include radiation and chemotherapy, which are designed to induce programmed cell death (apoptosis) of tumour cells. There is a pressing need for the development of new treatment options.

ATL1103 is a second generation antisense drug designed to block growth hormone receptor (GHr) expression thereby reducing levels of the hormone insulin-like growth factor-I (IGF-I) in the blood and is a potential treatment for diseases associated with excessive growth hormone action. These diseases include acromegaly, an abnormal growth disorder of organs, face, hands and feet, and diabetic retinopathy, a common disease of the eye and a major cause of blindness. Acromegalic patients are known to have significantly higher blood IGF-I levels than healthy individuals. Reduction of these levels to normal is accepted by clinical authorities as the primary marker of an effective drug treatment for the disease. GHr is a clinically validated target in the treatment of acromegaly. In the case of diabetic retinopathy, published clinical studies have  shown that treatments producing a reduction in IGF-I levels retarded the progression of the disease in patients. ANP have published scientific papers demonstrating suppression of blood IGF-I levels in the mouse and inhibition of retinopathy in a mouse retinopathy model using an antisense drug to the GHr (Wilkinson-Berka et al., 2007, Molecular Vision 13, 1529- 38;Tachas et al., 2006, J Endocrinol 189, 147-54) and ANP have previously reported that ATL1103 injection suppressed circulating levels of IGF-I in primates. ATL1103 commercialisation is covered by  atent applications to at least 2023, and the potential for extensions to 2029 in some countries.

Acromegaly is a serious chronic life shortening disease triggered by excess secretion of growth hormone (GH) by benign pituitary tumours. Oversupply of GH over stimulates liver, fat and kidney cells, through their GH receptors, to produce excess levels of Insulin-Like Growth Factor-I (IGF-I) in the blood manifesting in abnormal growth of the face, hands and feet, and enlargement of body organs including liver, kidney and heart. The primary treatments for acromegaly are to surgically remove the pituitary gland and/or drug therapy to normalize GH and serum IGF-I levels. In North America, Europe and Japan there are approximately 40,000 diagnosed acromegaly patients with about half requiring drug therapy. In 2004, the total acromegaly market was valued at US$780M and forecast to grow with the introduction of newer and more effective medications.

Diabetic retinopathy is one of the leading causes of vision loss. Over 5 million Americans aged 18 and older are affected by diabetic retinopathy. Around 12,000-24,000 patients with diabetic retinopathy lose their eyesight each year in the US alone. This condition is caused by new blood vessel formation in the retina or macula (the central part of the retina). In diabetes, high blood glucose can cause oxygen deprivation in certain tissues, which can stimulate factors that induce additional blood vessels in the retina. These new blood vessels may break and bleed into the eye leading to scarring within the eye. Surgical ablative treatments such as photocoagulation (laser therapy) are available but are not completely effective, may cause partial vision loss, and can only be used a limited number of times. There is presently no pharmaceutical therapeutic approved for the treatment of diabetic retinopathy.

SOURCE: Antisense Therapeutics Limited

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