solbec to commence pre-clinical mesothelioma immun

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SOLBEC TO COMMENCE PRE-CLINICAL STUDY TO CONFIRM
PRELIMINARY FINDING OF IMMUNITY TO MESOTHELIOMA
Summary:
• Solbec to commence further pre-clinical studies of Coramsine™ in combination with
CpG as a treatment for malignant mesothelioma and melanoma in a mouse model.
• The study aims to confirm and extend preliminary findings, announced in November
2004, that combination therapy in mice may induce lasting immunity to malignant
mesothelioma which may then result in a cure.
• The study aims to determine appropriate preliminary measures of immune response in
humans.
Perth, Australia. 3rd February 2005. Solbec Pharmaceuticals Ltd (ASX:SBP) has announced
the commencement of a pre-clinical study to confirm and extend the findings of an earlier
investigation into the effect of Coramsine™ combined with CpG in the treatment of murine
mesothelioma.
The study will be carried out by the Tumour Immunology Group at the University of Western
Australia.
The study is comprised of four key experiments, The outcomes of the four (4) groups of
experiments within the study will be used to inform decisions regarding any future clinical trials
of Coramsine™/CpG in patients with cancer.
One of the four experiments has been designed to determine if the results are affected by
background genetic factors. Combined treatment will be tested and compared to two strains of
mice with different genetic backgrounds.
The study will also determine whether the immunological characteristics of the cancer will affect
the ability of the therapy to induce remission or immunity. To do this, the combined treatment
regime will be applied to mesothelioma in two different mouse strains and to malignant
melanoma in one mouse strain. Melanoma is typically regarded as an immunogenic cancer that is
able to provoke an immune response without additional immunotherapy, whilst mesothelioma is
not.
An additional element of the present study, will involve preliminary quantification of appropriate
measures of immune stimulation such as the T cell response to tumour antigens in patients treated
with Coramsine™. This aspect of the study is to provide the researchers with the appropriate
measures for monitoring immune activity during a subsequent clinical trial.
The CpG to be used in the study has been supplied by Hybridon Inc., pursuant to a material
transfer agreement announced in December 2004.
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It is anticipated that all experiments will be completed by June 2005.
For further information, please contact
Stephen Carter Rebecca Christie
Managing Director Director
Solbec Pharmaceuticals Ltd Buchan
Phone +61 (08) 944 67555 +61(02)92932836
[email protected] [email protected]
FURTHER INFORMATION
APPENDIX
In accordance with ASX and AusBiotech Draft Code of Best Practice on Reporting for Biotechnology, Medical Device
and other Life Sciences Companies, Solbec provides the following information.
Background
Coramsine™ is Solbec’s lead compound. It is a fixed combination of solamargine and solasonine, two glycoalkaloids
extracted from Solanum linnaeanum. Coramsine™ is subject to the usual pharmaceutical regulatory requirements
before it may be marketed and is under development for the treatment of cancers and in a topical formulation for the
treatment of psoriasis.
Solbec owns the rights necessary to commercialise Coramsine™ and other intellectual property rights associated with
the product.
Pre-clinical Studies and Clinical Use
Patients with various cancers were treated in Australia under the Special Access Scheme (Compassionate Use).
Anecdotal reports following this use were sufficient to prompt additional research to complement the formal clinical
development process of Coramsine™ that began at the end of 2003.
Investigation of the mode of action of Coramsine™ found that the compound selectively kills cancer cells through the
process of necrosis, rather than apoptosis and further indicated that treatment would not compromise immune response,
unlike most cytotoxic compounds. The decision was consequently taken to test Coramsine™ in combination with
immunotherapy.
A series of experiments was undertaken in which established tumours in a mouse model of mesothelioma were treated
with Coramsine™ and a number of immune system stimulators. It was found that treatment with CpG-oligonucleotides
had a synergistic effect with Coramsine™. CpG-oligonucleotides trigger a response in the immune system by binding
to Toll-like receptors.
The experimental evidence of synergy was developed by an experiment in which BALB/C mice were inoculated with
AB1-HA mouse mesothelioma tumour cells. Mice were treated with Coramsine™ (14mg/kg, i.p.) and CpG (10ug/dose,
i.t.). Tumour size and survival time of the mice were monitored against controls. All control groups experienced shorter
survival and more rapid tumour growth than mice treated with the experimental combination. In the experimental
group, two mice experienced complete remission of their disease. An attempt to re-induce AB1-HA mesothelioma in
the one surviving mouse from this group failed, providing preliminary evidence that this mouse had developed
immunity to the cancer.
Results from PhaseI/IIA clinical studies of Coramsine™, have enabled Solbec to determine a safe dose for use in
future trials. A phase I trial of CpG in the US has shown it to be safe for administration to patients.
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The preliminary finding of immunity in a mouse model for mesothelioma requires validation before consideration of a
clinical trial programme to determine the clinical safety and efficacy of the combinational therapy can be contemplated.
In the new study, Coramsine™ will be used in conjunction with IMOxine™, a synthetic CpG-oligonucleotide from
Hybridon Inc, which is believed to be a more potent stimulator of the immune system than the conventional CpG used
in the earlier study.
Four key experiments are planned.
1. Attempt to reproduce the findings of the earlier study in BALB/C mice with AB1-HA mesothelioma: Tumour
growth and median survival time will be monitored. Anti-tumour immunity and protection against rechallenge
will also be assessed .
2. Investigation of the efficacy of combined therapy against a similar tumour in mice of a different genetic
background the study will look at C57/BL6 mice inoculated with AE17-OVA mesothelioma cells. The
outcomes will be measured as in Experiment 1.
3. Examination of the efficacy of combined therapy in a different tumour. C57/BL6 mice will be inoculated
with B16-OVA melanoma cells. The outcomes will be measured as in Experiments 1 and 2.This tumour line
has been chosen to determine if there is any difference in efficacy of the combined therapies depending upon
the immunological status of the tumour.
4. Preliminary quantification of ex-vivo T cell responses to tumour antigens in patients treated with
Coramsine™. this study will review interferon gamma levels and CMV/EBV responses to assess both anti
tumour responses and response of the existing immune memory cells. these results will assist in the
assessment of response to combination therapy in a proposed clinical trial and will provide additional
information on the interaction between Coramsine™ and the immune system.
About Solbec
Solbec Pharmaceuticals Ltd identifies naturally-occurring compounds with potential in the development of better
therapies for debilitating conditions and life-threatening diseases. The company is currently progressing its key project,
Coramsine™, through Phase I/IIA clinical trials for the treatment of mesothelioma and malignant melanoma, and as a
topical treatment for psoriasis. Solbec's two proprietary ingredients in Coramsine™ were isolated from the fruit of a
weed known as the Devil’s Apple (Solanum linnaeanum). They show activity against some cancers and cause
potentially therapeutic changes to the immune system. In addition to human health, Coramsine™ has potential
application in the areas of animal health and diagnostics. Solbec’s business strategy is to partner or out-license
Coramsine™ for the final stages of pre-commercial development and marketing.
See www.solbec.com.au