atl1103 development update

9th February, 2012

ATL1103 Development Update

Antisense Therapeutics Limited (ASX:ANP) is pleased to report significant progress on a number of
fronts relating to the Company’s growth hormone receptor (GHr) targeting drug ATL1103.
Planning for Phase II Study
As announced on 7th December 2011, ATL1103 successfully completed the Phase I clinical stage of
its development demonstrating its safety and tolerability at the doses tested in the study as well as a
preliminary indication of the drug’s relevant pharmacological activity with the reduction of serum
IGF-I and other relevant markers of drug activity in healthy volunteers after only 3 weeks of dosing.
The next study for ATL1103 will be in patients with the growth disorder acromegaly. The Phase II
study’s main objective will be to assess the safety and efficacy of ATL1103 in these patients over a
longer, 3 month, period of dosing. Acromegalics have elevated serum IGF-I levels, therefore the key
efficacy endpoint in this study will be the effect of ATL1103 in reducing the levels of serum IGF-I to
within a normal range in these acromegalic patients.
The Company is well advanced in its planning for the next trial of ATL1103 and expects to be in a
position to commence the trial by or prior to mid 2012 with interim results potentially available in
early to mid 2013. The trial will be run overseas by an experienced clinical research organization.
More details on the trial will be made available in due course when details have been confirmed and
funding arrangements have been finalised.
Scientific Advisory Group
A highly credentialed Scientific Advisory Group of international standing in the field of GH/IGF-I
related diseases such as acromegaly and cancer has also been established to oversee the clinical
development of ATL1103. Members of the advisory group include:
? Dr Pinchas Cohen (MD), Professor and Vice Chair for Research, Mattel Children’s Hospital at
UCLA
? Professor Albert G Frauman (MD, FRACP,FACP, FACCP) , Professor of Clinical Pharmacology &
Therapeutics, The University of Melbourne
? Professor Michael Waters (PhD, DSc), NHMRC Senior Principal Research Fellow, The
University of Queensland
? Professor George Werther (MD, BS, MSc (Oxon) FRACP), Non executive Director of Antisense
Therapeutics, Director of Endocrinology at The Royal Children’s Hospital, Melbourne
? Dr Vivien Bonert (MD), Clinical Coordinator of the Pituitary Centre at Cedars-Sinai Medical
Centre, Los Angeles
Licensing Due Diligence
In further good news, ANP can confirm that after a review of a detailed package of summary
information and data on ATL1103, the Pharmaceutical Company that was referred to in the 7th
December 2011 announcement as expressing interest in ATL1103, is now undertaking more
comprehensive due diligence. ANP is now supplying the pharmaceutical company with an expanded
package of additional data and intellectual property in relation to ATL1103.
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As part of this process, ANP is expecting to receive valuable feedback from this experienced drug
development pharmaceutical company on the clinical development and commercialisation plans for
ATL1103.
This is positive progression towards a potential development partnering and or licensing deal,
however at this stage the outcomes are uncertain and there are no guarantees that the parties will
enter into commercial negotiations and that a partnering deal on suitable terms will be reached
between the parties. With this in mind, ANP will continue planning for a Phase II trial which will add
further significant value to the project whilst it continues to cooperate with this potential licensing
partner and other pharmaceutical companies interested in ATL1103. If a deal is agreed between ANP
and any other party, terms may include payment of development costs, licensing fees, milestone
payments and royalties on drug sales. ANP will keep shareholders informed of any material
developments in relation to partnering and licensing interactions on ATL1103.
Cancer Experimental Program
ANP has previously announced that as part of the ATL1103 Phase I trial, Professor Cohen and his
colleagues in the USA would undertake a cancer experimental program as a preliminary investigation
into the drug’s potential in this field. The cancer marker assays (in-vitro mitogenic and apoptotic
assays) conducted using serum samples taken from subjects from the Phase I trial showed the level
of effect ATL1103 achieved in the Phase I trial to be too subtle for detection in these assays.
Professor Cohen believes, however, that further analysis is warranted as this initial program is just
one of a number of models of surrogate markers of drug activity that can be applied and that the
planned Phase II study should provide greater supporting evidence in relation to the potential of
ATL1103 in cancer with an anticipated more substantial reduction in serum IGF-I based on the longer
and potentially higher doses to be used in the Phase II trial. Furthermore, the expected synergistic
effect of reducing serum IGF-I and inhibiting GHr has shown promise in preclinical models and could
prove valuable in human patients.
Professor Cohen commented “The Phase I study outcomes are very encouraging for our ongoing
cancer experimental program. In the planned Phase II study where acromegalic patients with
elevated IGF-I and GH will be dosed for a longer duration at potentially higher doses, we anticipate
greater effects of ATL1103 with a larger reduction of the relevant pharmacological endpoints, which
would in turn give important validation to the drug’s potential in cancer prevention and therapy.“
ANP and Professor Cohen remain committed to exploring ATL1103’s potential in cancer prevention
and therapy and so will continue to work together with the assistance of the newly formed Scientific
Advisory Group (of which Prof. Cohen is a member) to investigate ways to appropriately assess
ATL1103’s potential in this field including as part of the next acromegaly clinical trial.
ATL1103 and Somavert® Combination Opportunity
In another development, ANP has identified a further potential application of ATL1103 for use in
combination with an existing marketed drug for acromegaly – Somavert® with this combination
opportunity potentially adding to ATL1103’s already significant commercial prospects as a
monotherapy (for use on its own).
Data from the Phase I trial of ATL1103 including its specific effect in reducing Growth Hormone
Binding Protein (GHBP) levels supports the potential for synergistic clinical benefits to be derived
from the use of ATL1103 in combination with Somavert. Somavert is reported to bind to GHBP in
preference to cell surface GHr in patients; therefore the combination with ATL1103 would potentially
allow for Somavert to be freed up to bind to more cell surface GHr which could increase drug
activity.
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The combination could allow Somavert to be used at lower/less frequent doses in acromegaly
treatment (currently Somavert requires daily injection), thereby reducing treatment costs and
improving patient compliance. The combination of the two drugs could also potentially open up other
disease applications such as some cancers where a more significant reduction in IGF-I may be
required. ANP’s Scientific Advisory Group is supportive of the concept of this combination therapy
approach and its potentially clinical benefits.
A provisional US patent application 61/594,532 entitled “Combination therapy” has recently been
lodged which seeks to provide protection for the use of ATL1103 and Somavert in combination until
2033.
In concluding, Antisense Therapeutics CEO and Managing Director, Mark Diamond commented
“Antisense Therapeutics has worked very hard to position ATL1103 for commercial success and
increase its value on a number of fronts. We are pleased with the drug’s successful development so
far, as well as the interest it has generated within the pharmaceutical industry. We are excited with
the development and commercialization progress made on ATL1103 and we look forward to
reporting on these activities as they continue to advance.”
Somavert® is a registered trademark of Pfizer Inc.
Background Information
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 and IGF-I action. These diseases include acromegaly, an abnormal growth
disorder of organs, face, hands and feet, diabetic retinopathy, a common disease of the eye and a major cause of
blindness, diabetic nephropathy and some forms of cancer. 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 and improve vision in patients. Scientific papers have been
published on the suppression of blood IGF-I levels in mice (Tachas et al., 2006, J Endocrinol 189, 147-54) and inhibition of
retinopathy in a mouse retinopathy model (Wilkinson-Berka et al., 2007, Molecular Vision 13, 1529- 38;) using an antisense
drug to the GHr. ANP have also previously reported that ATL1103 suppressed circulating levels of IGF-I in primates and
that 3 month toxicology studies had been completed. ATL1103 commercialisation is covered by patents to at least 2024,
with the potential for extensions up to 2029 in some countries and 2030 in the US.
Antisense Therapeutics Limited (ASX: ANP) is an Australian publicly listed biopharmaceutical drug discovery and
development company. Its mission is to create, develop and commercialise second generation antisense pharmaceuticals
for large unmet markets. ANP has 4 products in its development pipeline. ATL1102 (injection) has successfully completed a
Phase II efficacy and safety trial, significantly reducing the number of brain lesions in patients with multiple sclerosis.