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Antisense Therapeutics Limited (ASX:ANP) ATL1103 Background and Development Update

ATL1103 Summary Background and Development Update
 
Following Antisense Therapeutics Limited’s (ASX:ANP) recently concluded Rights Issue, the Company is now in a position to proceed with the further development of its exciting growth hormone receptor antisense drug - ATL1103 and provides the following background and update in relation to this key development project for the Company.
 
1. The drug – ATL1103
2. The disease applications
3. Development of ATL1103 so far
4. Development path and strategy going forward
 
1. The drug – ATL1103:
 
ATL1103 is an antisense compound derived from Antisense Therapeutics’ technology collaboration with Isis Pharmaceuticals Inc. (ISIS) in the US. ISIS is a world leader in antisense drug discovery, development and commercialization. ATL1103 is a second generation antisense compound where modifications to drug chemistry increase potency, tolerability and allow for more convenient dosing regimens.
 
ATL1103 is rationally designed to block the production of its target, the human growth hormone receptor (GHr). By inhibiting GHr production predominantly in the liver, ATL1103 in turn reduces levels of the hormone insulin like growth factor (IGF-I) in the blood (serum). There are a number of diseases that are associated with excess GH and IGF-I including certain growth and sight disorders as well as some forms of cancer.
 
2. The disease applications:
 
Growth disorder – Acromegaly
 
Acromegaly is an abnormal growth disorder caused by a benign tumor of the pituitary gland that produces excess growth hormone and associated increases in serum IGF-I in adults. It is known to affect over 85 thousand adults in the US and Europe. The current first line pharmaceutical treatment for acromegaly has sales of US$1Billion per annum, however is only effective in approximately 60% of patients so there is still the need for better new treatments.
 
Antisense Therapeutics is developing ATL1103 as an alternative treatment option which it expects to be lower in cost, easier for patients to administer and potentially more effective and safer to use than current therapies.
 
Acromegaly is an “Orphan drug” indication as defined by the Regulatory Authorities (e.g. FDA) who approve drugs for marketing. The Regulatory Authorities provide companies with incentives to develop orphan drugs which means that ATL1103 would receive certain regulatory advantages that would significantly lower its development costs.
 
Sight disorders – Diabetic retinopathy
 
Diabetic retinopathy is a disease of the eye where new blood vessels form in the retina at the back of the eye which can lead to blindness. It is a leading cause of blindness affecting more than 5 million people in the US alone.
 
There is no approved drug treatment for the advanced form of diabetic retinopathy known as proliferative diabetic retinopathy.
 
ATL1103 is designed to block the production of proteins associated with the cause of diabetic retinopathy by targeting GHr and thereby reducing IGF-1 in the blood. This is an approach validated by proven clinical benefit seen in studies of other treatment modalities where the activity of GH and serum IGF-I in the eye is reduced.
 
Diabetic nephropathy
 
Diabetic nephropathy (DN) is a progressive disease of the kidney glomerulus caused by high blood sugar (diabetes). About 40% of type II diabetics have DN and 6 million patients in the US, Europe and Japan have clinically significant forms of the disease.
 
Serum IGF-I and local kidney GH-IGF-I have roles in the pathogenesis of diabetic nephropathy. Reducing serum IGF-I in the blood and GH activity in the kidney is a validated therapeutic approach in the treatment of diabetic nephropathy patients.
 
Cancer (Breast)
 
Breast cancer is the third most prevalent cancer in the world and it has been reported that rates of the disease increased two fold in premenopausal women with higher levels of serum IGF-I. In addition, elevated GHr expression is observed in breast cancer tissues.
 
Clinically significant disease remission was achieved in breast cancer patients who had part of their pituitary gland surgically removed, which in turn reduced their GH and associated serum IGF-I levels, thereby supporting the potential of ATL1103 as a treatment for breast cancer.
 
3. Development of ATL1103 so far:
 
ATL1103 is an exciting clinical development opportunity that has successfully passed through the research and pre-clinical stages of development.
 
The therapeutic activity of ATL1103 has been confirmed in animal pharmacology studies, where ATL1103 has shown the successful suppression of serum IGF-I levels in both normal mice and primates. Normalizing serum IGF-I levels is the therapeutic goal in the treatment of the growth disorder acromegaly. In a previously conducted mouse animal study, antisense to the GHr significantly inhibited retinal neovascularisation in the eye, supporting the potential of ATL1103 as a future treatment for the sight disorder diabetic retinopathy.
 
ATL1103’s demonstrated therapeutic activity in mouse and primate studies in inhibiting GHr and reducing serum IGF-I is also an indicator of the potential of the drug as a future treatment for diabetic nephropathy and cancer.
 
ATL1103 has also successfully completed toxicology (safety) studies in mice and primates. Supporting the ATL1103 development program, Antisense Therapeutics has assembled an extensive and comprehensive patent portfolio which protects the drug and its applications until 2025 in the United States, with related patents in Australia and New Zealand and applications under examination in Europe, Japan, and Canada.
 
4. Development path and strategy going forward:
 
The next steps in the development of ATL1103 involve preparations for human clinical trials which are planned for 2011.
 
In collaboration with Isis Pharmaceuticals, sufficient raw material supplies for the trial have been manufactured. Antisense will now formulate these material supplies into injectible product for the clinical trial. An appropriate clinical trial application will be completed and submitted by the Company. The clinical trial application will be for a single and multiple dose study of ATL1103 designed to confirm the safety and tolerability of the drug in healthy volunteers as well as to demonstrate the level of effect of ATL1103 on growth hormone activity and IGF-I levels in the blood. Reducing elevated levels of serum IGF-I to normal is the therapeutic endpoint in the treatment of acromegaly, and is an important therapeutic marker for the treatment of diabetic retinopathy, nephropathy and some forms of cancer.
 
Post this trial and with successful outcomes, Antisense Therapeutics would then look to partner ATL1103 for the sight disorders/cancers indications with drug development and commercialisation companies in those specialized fields. Antisense would look to continue its own development of ATL1103 for growth disorders (acromegaly) to further enhance the value of the drug for this indication by conducting additional clinical trials (Phase II initially). As the disease acromegaly is designated orphan drug status, development of ATL1103 is more affordable and the registration process more stream-lined, making acromegaly an ideal lead indication for Antisense to further develop.
 
Following Antisense Therapeutics’ recent Rights Issue and combined with existing cash reserves, the Company has funding to proceed with the development of ATL1103 with the next step to manufacture injectible product for use in the planned clinical trial.
 
The development of ATL1103 is consistent with the Company’s strategy to develop antisense compounds for unmet medical needs and where the antisense technology provides clear advantages over the competition resulting in significant market opportunities.
 
Antisense Therapeutics is pleased to report on its exciting growth hormone receptor antisense drug ATL1103 and now looks forward to providing shareholders with further updates in relation to the drug’s progress and further development.
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