ANTISENSE THERAPEUTICS LIMITED INVESTOR UPDATE
Dear Investor for Phase I clinical trials oversubscribed shares
I am pleased to report that of ATL1102 and receipt offer.
Antisense Therapeutics of approval on 4
And finally, our strategic
Limited (ATL) has made February 2003 to
substantial progress since conduct this trial;
the June 2002 Investor
• completion of announces important
Update. The highlights
manufacture of advances in the field of
described in this edition of
ATL1102 for use in antisense therapeutics.
Investor Update include:
Phase I and later
• the successful
completion of a package • ATL1101 lead
of pre-clinical animal compound for psoriasis
trials of ATL's drug for selected in Q3 2002, on
the treatment of multiple schedule; and
sclerosis, ATL1102; • successful raising of Mark Diamond, CEO
• confirmation of the site $4.5 million in an
ATL1102 for the treatment Charterhouse Clinical Research Unit at the
Stamford Hospital in London
of Multiple Sclerosis (“Charterhouse”) to conduct the Phase I
clinical trial to assess the safety and
Development Status behaviour (pharmacokinetics) of ATL1102
In October 2002 ATL announced the in human volunteers. On 4 February 2003,
successful completion of a package of pre- approval was received from Charterhouse
clinical (animal) studies, which has enabled to conduct this Phase I study.
ATL to progress arrangements to start
Phase I clinical trials of its product ATL1102 The Phase I trial is expected to commence
for multiple sclerosis (‘MS’). on schedule in March 2003.
The results of the studies on the safety and Manufacturing Status
properties of ATL1102 administered to The production of injectable formulations of
animals have demonstrated the exciting ATL1102 suitable for use in Phase I clinical
prospect of dosing human subjects as trials was contracted out to a US company.
infrequently as once a week or less
frequently, the likelihood of which will be Four formulations are now ready for use in
determined in the Phase I clinical trials. the trial comprising two different
concentrations of the antisense drug
In December 2002, ATL applied to the ATL1102 and two preparations of matching
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placebo, which have the same basic The ATL1101 lead compound was
composition but lack the active selected in the third quarter of 2002 on
compound, ATL1102. schedule and in line with forecasts made
in ATL’s 30 June 2002 annual report. Pre-
The final steps before shipping the clinical efficacy studies are currently
formulations to London for the conduct of underway.
the Phase I study are quality testing and
assessment of the stability of the A topical formulation containing ATL1101
preparations which are currently under has been prepared for this lead
way at a contract organisation in the USA. compound using Isis Pharmaceuticals, Inc
proprietary formulation expertise for use in
Quality testing involves evaluation of the pre-clinical studies.
formulated product to ensure it meets the
product specifications and stability testing Outlook
is important to establish a shelf life of the Upon the successful completion of the
formulated drug. pre-clinical efficacy studies, ALT1101 will
be poised to enter the next stage of pre-
Outlook clinical toxicology studies. These
Upon the successful completion of the toxicology studies are anticipated to
Phase I trial, it is anticipated that an commence during 2004.
application will be made in 2004 for a
Phase IIa trial to assess preliminary About Psoriasis and ATL1101
efficacy in patients with MS. Psoriasis is a chronic, non-contagious
skin disorder, which affects 2% of the
About Multiple Sclerosis and ATL1102 population.
Multiple Sclerosis (MS) is a life-long
chronic, incurable disease, which Although the worldwide market for
progressively destroys the central nervous Psoriasis treatments was more than
system, commonly diagnosed between US$500 million in 2000 and is forecast to
the ages of 20 and 40 years. exceed US$2 billion by 2007 (Frost &
Sullivan), there is an acknowledged need
MS affects about 350,000 people in the for more effective and safer treatments
US where the estimated annual cost of than those currently available.
the disease is more than US$2.5 billion.
Although current treatments are unable to ATL’s candidate for Psoriasis treatment is
slow disease progression, the aims of ATL1101, an antisense compound
therapy are to reduce the duration, designed to block the production of a
frequency and severity of attacks. protein involved in the regulation of cell
growth in Psoriasis.
ATL1102 is a drug under development by
ATL, which aims to prevent the synthesis
of a protein called VLA-4 known to play a Other Projects
part in both the onset and progression of
MS. ATL has several other antisense projects
in its research portfolio including
compounds directed at treating
ATL1101 for the treatment gastrointestinal, cardio-vascular,
of Psoriasis inflammatory, immune and viral diseases
and growth disorders. ATL intends to
announce details of the specific disease
Development Status indications together with the lead
ATL1101 is being developed by ATL in compounds upon successful completion
collaboration with research partner the of pilot animal studies and once the
Murdoch Childrens Research Institute. relevant patent applications have been
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lodged. pre-clinical testing.
Development Status & Outlook As previously announced, ATL is on track
Six lead antisense compounds have been and on budget to meet these milestones.
produced for ATL since its listing in
December 2001, for disease targets In December 2002, ATL successfully
relevant to the treatment of viral, skin, raised additional capital of $4.5 million
growth and inflammatory disorders. Pilot (with the issue of 60,275,268 shares), in
efficacy studies in animals are underway an oversubscribed offer, for the purpose
for two of these compounds. of funding the next stage in the
development of these key lead
Additional pilot efficacy studies are compounds and to progress the pipeline.
expected to be completed by the end of This share issue was approved by
the 2003 financial year. A select number shareholders of the company at a general
of successful candidates may then be meeting.
progressed into formal pre-clinical
development including animal toxicology Queensland Investment Corporation, an
studies. active institutional investor in the
biotechnology sector, became a
substantial shareholder of the company
Recent Shares Offer with the acquisition of 14 million shares in
At the time ATL listed on the ASX the share placement for $1.05 million
(December 2001), the prospectus giving it a 5.1% interest in the company.
indicated that total proceeds raised of
$13.6 million would be sufficient to fund Other major participants in the issue were
the Company’s activities until early 2003, existing shareholders Circadian
at which point ATL’s candidate drug for Technologies Limited and Isis
the treatment of Multiple Sclerosis, Pharmaceuticals Inc who were issued
ATL1102, would reach the stage of 10,333,333 shares for $775,000 each.
Phase I clinical trials and ATL1101 for the Circadian’s and Isis’s interests in the
treatment of Psoriasis would enter company are now 23.5% and 14.6%
Phase I – a relatively small number of
What are the Steps healthy volunteers are treated to test the
in drug testing? safety of a new drug.
Phase II – selected patients showing a
1. Pre-clinical trials number of common features, such as
These are performed in animal models age, sex and severity of the disease
to test toxicity and efficacy of the drug participate in trials to establish the
and properties related to its uptake, effectiveness of the drug.
distribution and metabolism. The
outcomes of pre-clinical testing Phase III – large numbers of patients
determine whether clinical trials will from the ‘clinical setting’ who are widely
proceed and also influence the representative of the patient population
conditions selected for clinical trials. are enrolled in the trial. Patients come
from all walks of life, often from a
2. Clinical trials number of participating centres.
All clinical trials involve testing on The aim of Phase III trials is to
humans whose participation is voluntary. determine whether a new treatment is
any better than the standard treatment in
There are three levels: a direct comparison of the two.
ANNOUNCEMENTS FROM ISIS SPELL GOOD About Antisense
NEWS FOR ANTISENSE-BASED DRUGS Therapeutics
Antisense Therapeutics Ltd
is an Australian publicly
Successful tests on a new oral formulation listed (ASX: ANP)
of Isis anti-inflammatory drug biopharmaceutical drug
Until recently, antisense inhibitors, similar to most discovery and development
biologically derived medicines, could not be company.
delivered orally in the form of a tablet, capsule or ATL’s mission is to create,
powder. develop and commercialise
Recognising the benefits of delivering drugs in this novel antisense
convenient form, Isis has committed considerable pharmaceuticals for large
resources to producing a new, second generation of unmet markets. Its two most
antisense formulations that can be administered advanced projects target
orally, making them more acceptable to patients Multiple Sclerosis
than an injectable treatment. (ATL1102), and Psoriasis
In November 2002, Isis announced the successful
completion of a Phase I study of its capsule form of The Company’s access to
an anti-inflammatory antisense drug. The plasma these projects is derived
concentrations reached by the drug were indicative from its technology and
of tissue concentrations being high enough to research collaborations with
produce a therapeutic benefit. Isis Pharmaceuticals Inc.
and the Murdoch Childrens
This study is a watershed not only for being the first Research Institute.
antisense research program to overcome what was California-based Isis is a
thought to be a significant technical hurdle, but also world leader in the field of
for dramatically broadening the therapeutic and antisense drug technology
commercial potential for antisense compounds. and has a market
The data indicates that other second generation capitalisation of
compounds have the potential for oral approximately US$276
administration, which obviously would provide a million.
significant advantage over other types of The collaboration agreement
administration. We will pursue an oral dosage form with Isis provides ATL with
as development of ATL1102 progresses. extensive access to Isis’s
Treatment Groups from a Phase III trial of an antisense drug discovery
anti-cancer drug about to be revealed technology of relevance to
the treatment of viral, skin,
The Isis investigational anti-cancer drug Affinitac growth and inflammatory
(a trademark of Eli Lilly) is the subject of two disorders. ATL plans to
Phase III trials for the treatment of non-small lung commercialise its pipeline via
cancer. One of these involves a comparison of licensing/collaboration
Affinitac with two treatments currently in use, agreements with major
carboplatin and paclitaxel. biotechnology and
Isis has announced that the findings from this trial pharmaceutical companies.
will be analysed in March. ATL’s major shareholders
Positive results will provide the basis for a new drug include Circadian
application (NDA) to the US Regulatory Agency: Technologies Limited (ASX:
Food and Drug Administration. An announcement of CIR), Isis Pharmaceuticals
the successful completion of this pivotal study Inc. (NASDAQ: ISIS),
should have a significant positive impact across the Queensland Investment
whole antisense sector. Corporation and the Murdoch
Childrens Research Institute.
Contact Information: Website: www.antisense.com.au
Managing Director - Mark Diamond +61 3 9827 8999
Investor Relations - Natalie Korchev +61 3 9827 8999