INVESTOR UPDATE - June 2002 by pkj12584


									                      INVESTOR UPDATE – June 2002
Dear Investor

I am pleased to report that Antisense Therapeutics Limited has made substantial progress
since the March 2002 Investor Update. All R & D activities are on track with several
significant advances in our drug development pipeline as detailed below.


   •   Preclinical dosing studies have been completed on ATL1102 for Multiple Sclerosis.
       Detailed toxicology and pharmacokinetic analysis is underway with the results
       expected in 4Q 2002. Identification of the site for conduct of Phase I human clinical
       trials is close to finalisation with the study on track to commence in early 03.

   •   Selection of the ATL1101 Psoriasis lead compound is on track for 3Q 2002 following
       the successful completion of several key experiments using human skin cells at the
       Murdoch Childrens Research Institute (MCRI).

   •   Five new antisense lead compounds have been produced by Isis Pharmaceuticals Inc
       (Isis) designed to treat large disease markets involving viral, skin, growth and
       inflammatory disorders.

   •   The rapid progress in ATL1102 drug development, and in ATL1101 and pipeline
       research since the last update is a clear illustration of the remarkable speed with which
       antisense drugs can be discovered and moved into clinical development compared to
       traditional approaches.

ATL1102 for Multiple Sclerosis

ATL1102 is an antisense inhibitor targeting an immune cell protein called VLA-4. This
protein has been shown to play an important role in the onset and progression of Multiple
Sclerosis in humans.

       Development Status

       Preclinical studies with ATL1102 commenced on schedule in March 2002 and dosing
       was completed in May 2002. Preclinical studies must be completed in animals to
       confirm a drug’s safety before testing in humans can commence. Laboratory
       investigations of blood and tissue samples from this study are currently in progress
       and pathology evaluation to confirm drug safety should be available in the second half
       of 2002.

       All these studies are being conducted in the U.S. at contract laboratories that are in
       compliance with all relevant FDA regulatory requirements.
       The early commencement of preclinical studies with ATL1102 was made possible by
       the rapid development of a suitable injectable formulation, which is a major feature of
       the Isis antisense technology utilised in our drug discovery programs.

       An FDA audited clinical trial centre has been identified, and negotiations to engage
       their services for the running of Phase I human trials are close to finalisation. A
       regulatory approval application to conduct these trials is due to be submitted towards
       the end of 2002, with the study scheduled to commence in early 2003 after approval is

       Manufacturing Status

       Bulk ATL1102 manufactured earlier this year by Isis is now scheduled to be
       formulated into an injectable solution by an FDA compliant U.S. manufacturer. This
       is due for completion by the end of 2002. This drug formulation will be used for
       future human clinical trials including the Phase I safety studies in healthy volunteers
       and the Phase IIa efficacy studies in patients that suffer from multiple sclerosis.

       The Rationale for VLA-4 as a Target Treatment for Multiple Sclerosis

       The monoclonal antibody drug, Antegren TM, which targets the VLA4 protein, is being
       developed by the US based biopharmaceutical company Biogen, which also markets
       the current leading multiple sclerosis treatment interferon beta 1a. In Phase II clinical
       trials, Antegren TM has delivered superior outcomes to those previously reported with
       interferon beta 1a. Results indicate a reduction in the formation of new lesions, a
       marker for multiple sclerosis progress, by 90% or more along with a 45 % reduction
       in the relapse rate.

       On the strength of the Antegren TM Phase II trial results, Biogen has announced the
       commencement of two large Phase III multiple sclerosis clinical trials. This
       enormous financial commitment on the part of Biogen is an indication of their level of
       confidence that a VLA-4 antibody will be effective in modifying the clinical course of
       progression of multiple sclerosis in patients.

       By contrast to acting directly on the VLA-4 protein, ATL’s antisense drug is aimed at
       blocking the production of that disease causing protein before it can inflict further
       damage. With its highly specific mechanism of action and well tolerated drug
       chemistry ATL1102 may potentially have efficacy, safety and dosing route
       advantages over an antibody product. These advantages, together with the knowledge
       gained by the Biogen studies confirming the validity of VLA-4 as a target for multiple
       sclerosis provides the Director’s of ATL with increased confidence in the likelihood
       of success of ATL’s drug development strategy.

ATL1101 for Psoriasis

ATL 1101 blocks the production of the insulin-like growth factor 1 receptor (IGF-1R)
protein. IGF-1R is involved in the regulation of cell growth in Psoriasis. ATL 1101 is being
developed in collaboration with the MCRI as a topical application for use as a first line

       Development Status

       This month, the premier international scientific journal of skin research, the Journal of
       Investigative Dermatology, reported on the MCRI team’s results confirming that their
       antisense drug can enter human psoriasis lesions when applied topically.

       This indication of topical availability is a major advance over the MCRI’s work
       previously reported in the 2000 article in Nature Biotechnology, a leading
       biotechnology journal. In the earlier paper the MCRI team had reported the same
       antisense inhibitor returned psoriatic lesions to a normal appearance in animal models,
       when injected into lesions.

       ATL eagerly anticipates the next phase of this work, in which ATL1101, a second-
       generation antisense drug based on Isis technology targeting the IGF-1R (known to
       play a central role in psoriasis), will be tested in topical formulations. Three second
       generation antisense inhibitors have been tested in experimental models at the MCRI,
       with preliminary results on efficacy indicating that the selection of the ATL 1101 lead
       compound is on track for 3Q’02 after which pre-clinical efficacy studies will
       commence as soon as we have confirmed the optimal topical formulation.

Other Projects

As indicated in our March Investor Update, Antisense Therapeutics is seeking to expand its
product pipeline by identifying disease targets that might be suitable for intervention with
antisense based drugs.

I am pleased to be able to report that Antisense Therapeutics now has an additional five lead
antisense compounds for disease targets relevant to the treatment of viral, skin, growth and
inflammatory disorders.

       Development Status

       Several of these compounds will be tested in pilot animal efficacy studies, which are
       expected to be completed by the end of this year. A select number of successful
       candidates will then be progressed into formal preclinical development. ATL intends
       to announce details of the specific disease indications together with the lead
       compounds once relevant patent applications have been lodged.

       Rationale for these Projects

       ATL will critically assess the results of these studies and determine on a case by case
       basis whether further development work will be undertaken by Antisense
       Therapeutics or alternatively out-licensed to other pharmaceutical companies in return
       for substantial licensing income. As an illustration of the latter alternative, Isis
       recently completed an early stage licensing deal whereby Isis licensed their PT1B
       inhibitor for diabetes in a deal worth US$50 million on the strength of successful
       animal efficacy studies.

Developments in the Pharmaceutical Industry Involving Antisense Based Drugs

Recently there have been important business and scientific developments in the field of
antisense. Eli Lilly & Co. reported positive results from Phase II clinical trials of
AffinitacTM, Lilly’s antisense lung cancer treatment licensed from Isis Pharmaceuticals Inc.
This drug has now entered Phase III human trials and according to releases issued by Isis and
Lilly, a new drug application (NDA) may be filed as early as next year. As reported in our
Prospectus, Isis announced in September 2001 that Isis and Lilly formed a strategic
partnership in a deal which provided US$200 million in committed funding to Isis.

Genta Inc., an American biopharmaceutical company specialising in cancer products,
recently entered into an agreement with Aventis, a major European owned international
pharmaceutical company, to jointly develop and commercialise its new antisense drug
“GenasenseTM”. This drug is currently in human Phase III trials for blood cancer indications.
As indicated in Genta’s public announcement “collectively, this agreement will provide up to
US$480 million in cash, equity, and convertible debt to Genta”. As reported in the press, it is
believed that this is the 2nd biggest collaboration ever transacted in Biotech history.

The Genta/Aventis and the Lilly/Isis collaborations described above, confirm the acceptance
of antisense technology and its commercial potential by major pharmaceutical companies.

We enclose for your information copies of our last two press releases for ATL1102 and
ATL1101. As you may be aware, ATL1101 received broad media coverage recently
(television and press). Accordingly, we have also enclosed an article that appeared on page 3
of The Age on Wednesday, 5 June 2002 relating to this media coverage.

As ATL is committed to providing timely and detailed updates for investors, we will be
releasing data on our development activities as and when appropriate along with shareholder
updates each calendar quarter.

Thank you for your continued support.

Yours sincerely

Mark Diamond

   CEO – Mark Diamond 61 3 9827 8999
   Investor Relations - Natalie Korchev 61 3 9827 8999

Other information:

                                                                          ANTISENSE THERAPEUTICS
        Australian team tests new multiple sclerosis treatment
        Using antisense drug technology

Thursday 30 May 2002, Multiple sclerosis (MS) affects thousands of Australians. There are few
treatments and most have side effects or other disadvantages.
“We aim to use a fundamentally different kind of drug chemistry (“antisense”) to create a new way to treat
MS, and reduce its impact on the lives of millions of people across the world,” says Mark Diamond, CEO
of Antisense Therapeutics”.
“Following the convincing demonstration of activity in an animal model of MS, we have started pre-clinical
toxicology trials in conjunction with Isis Pharmaceuticals and hope to start clinical trials in Australia early
in 2003.
Multiple sclerosis affects 12,000 to 15,000 Australians, and about two and a half million people around
the world. MS is a chronic disease that usually first appears between the ages of 20 and 40.
MS appears to be an autoimmune disease in which the body damages its own nerve cells. The cause is
unknown and there is no cure. Improved drugs have become available in recent years that reduce the MS
attacks. However there are significant issues with the use of these drugs.
“We need better ways to treat MS. We believe antisense drugs offer a new way forward,” says Mark
“Our target is a protein called VLA-4 which helps white blood cells enter tissues to fight disease.
Individuals with MS have excessive amounts of this protein which causes white blood cells to migrate to
the central nervous system and attack healthy nerve cells”.
 “Most conventional drugs modify the activity of disease causing proteins in the body. Our antisense drug
would go to work earlier, stopping the body from making the VLA-4 protein that is responsible for MS
progression. We hope our antisense drug will provide efficacy, safety, and dosing advantages over other
agents being developed for MS”.
“We are using drug chemistry technology developed by Isis Pharmaceuticals, the global leader in
antisense technology. Isis Pharmaceuticals have been developing and refining their antisense technology
over the past 13 years. They have the only approved antisense compound on the market in the world.”
Mark Diamond says, “Most people with MS can manage their condition with current drugs.”
“What we are aiming to achieve with our VLA-4 antisense, is to demonstrate a significant slowing down in
the progression of the disease, so as to offer patients relapse free, longer periods of remission. That
would substantially improve the quality of life for people with MS.
 Antisense is a Melbourne-based company specialising in antisense technology.

For further information:

What is MS:
Antisense and MS:
What is antisense:
Contact:        Mark Diamond, Antisense Therapeutics Ph (03) 9826 0949
                Barbara Pesel, Pesel & Carr           Ph (03) 9663 0886

                                                                  ANTISENSE THERAPEUTICS

Antisense psoriasis cream - a step closer

Melbourne researchers are developing an antisense treatment for psoriasis skin lesions.

Today the international Journal of Investigative Dermatology reports that an antisense drug,
when applied topically, can enter human psoriasis lesions and be delivered to the right place to
treat psoriasis.

Dr Christopher Wraight, leader of the research team at the Murdoch Childrens Research Institute
says: “These results give us, and our partner, the Melbourne biotech company Antisense
Therapeutics, the confidence to move to pre-clinical studies”.

“Psoriasis affects 200,000 to 300,000 Australians,” he says. It is a chronic and poorly
understood skin condition. The main feature of psoriasis is red scaly patches of skin that come
and go throughout life. It is an uncomfortable and distressing condition.

The causes of psoriasis are unclear. We do know that it involves an abnormal immune response
in the skin in which the affected cells grow more rapidly. We expect our cream to slow the
growth of these cells.

Our research shows that the affected cells grow faster in response to a growth factor (IGF-I). Our
antisense drug stops each cell from responding to this growth factor, by blocking the cell s
production of its receptor protein.

Making sense of antisense

Antisense drugs offer a new way forward for many hard-to-treat conditions, says co-inventor
Professor George Werther, Director of the Centre for Hormone Research at the Murdoch
Childrens Research Institute, and a director of Antisense Therapeutics.

Most conventional drugs modify the activity of disease causing proteins within the body once
they are produced. Antisense drugs will go to work earlier, stopping the body from making these

Antisense drugs contain a synthetic genetic sequence which binds to messenger RNA, the
working copy of our genetic code that guides the manufacture of proteins. The research team has
created a unique sequence that will only bind to the messenger RNA that is making the target
protein, in this case the IGF-1 receptor protein, to stop its production.


The research team has already shown that the drug can help psoriatic skin cells heal if it is
injected in to the skin. This was reported in Nature Biotechnology in 2000.

Dr Paul White, lead author on the new paper and based at the Victorian College of Pharmacy
says: “Our results show that psoriasis lesions are easier to penetrate than we had previously

“We will be taking the next generation of the drug to pre-clinical studies and then it will undergo
several years of clinical testing”, says Christopher Wraight. “Our next step will be to invite
volunteers to help us in the next stage of testing”.


Background information on psoriasis is available at:
On antisense technology at:
Further information:
   ƒ   Mark Diamond at Antisense on (03) 9826 0949
   ƒ    Narelle Curtis at Murdoch on (03) 8341 6249 and/or
   ƒ   Barbara Pesel at Pesel & Carr on (03) 9663 0886


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