ropren is a pharmaceutical, page-27

Solagran Limited
Solagran Limited
ACN 002 592 396
Level 11
492 St Kilda Road
Melbourne 3004
Victoria
Australia
Tel 61 3 9820 2699
Fax 61 3 9820 3155
21 February, 2007
Company Announcement
Excellent Results from Australian Ropren Trials
The Directors of Solagran Limited are pleased to provide a summary of the key findings and
implications of the Ropren Neurocognitive Effects Trial conducted by the Brain Research
Institute (BSI) at Swinburne University in Melbourne. This trial, which was conducted
throughout 2006, produced findings consistent with previous research in Russia and provides
excellent baseline data in relation to the impact of Ropren treatment on healthy elderly
volunteers.
Context and Purpose
The Swinburne Neurocognitive Effects Trial was initiated for two reasons:
1. To understand and calibrate the impact of Ropren treatment on the cognitive
functioning of healthy elderly volunteers. Trials conducted in Russia had already
established that Ropren had a multi-faceted impact on clinical populations – including
patients suffering from Alzheimer’s Dementia;
2. To begin to engage with the Australian research community. Over the past few years,
commentators in Australia have questioned the veracity of the results of trials
undertaken with Ropren at prestigious Russian research institutions. These doubts
appeared to stem from the extent of the biological activity noted in the findings from
the Russian trials, as well as a general scepticism directed towards Russian scientific
research.
Prior to the commencement of the Swinburne trials, a number of trials had been completed in
Russia to assess the impact of treatment with Ropren on the brain. The most significant
were:
�� A comprehensive three stage research program undertaken at the I.M. Sechenov
Institute of Evolutionary Physiology and Biochemistry in St Petersburg during the period
from late 2003 to mid 2005. One of the aims of this research was to understand the
effects of Ropren on three key enzymes in the liver and brain, namely
Acetylchoninesterase (AChE), Butyrylcholinesterase (BuChE) and Monoamine Oxidase
(MAO). All three enzymes are involved in neurotransmission. The principal findings from
this research were communicated to the market on 4 October, 2005. The results of the
first stage of this research have already been published in the prestigious Annals of the
Russian Academy of Sciences. The results of the remaining two stages will be published
in due course;
�� A pilot trial conducted with Alzheimer’s Dementia patients in early 2005 at the
Skvortsova-Stepanova Psychiatric Hospital in St Petersburg. A summary of the results of
this trial were contained in an announcement to the ASX on 20 September, 2005.
The Institute of Evolutionary Physiology’s Neurotransmission Studies demonstrated that
Ropren quickly restored damaged enzymatic systems in both the liver and the brain of
laboratory animals, and also helped to restore damaged neurotransmission. Significantly,
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Ropren was able to restore the rate of catalytic serotonin deamination reactions in the brain
to normal levels, pointing to the recovery of damaged neurohumoral regulation throughout
the entire body. The lead researcher, Professor Khovanskikh, suggested that this may have
been due to Ropren’s direct participation in the process of repairing damaged cellular
membranes. He also considered that the speed with which Ropren acted was extremely
significant – potentially fast enough to prevent the onset of delayed neuronal cell death in
instances of brain trauma, hypoxia following a stroke or heart attack, and ischemia where a
blockage or constriction of a blood vessel leads to brain damage. This research program also
provided solid evidence in support of the contention of Solagran’s Executive Chairman in
relation to the existence of a causal link between liver function and the incidence of
neurodegenerative disorders, emphasising the importance of maintaining balance in the
enzymatic systems of both the liver and the brain.
The Skvortsova-Stepanova Alzheimer’s Trial involved 40 patients who had been suffering
from Alzheimer’s Dementia for between six months and four years. 25 were given Ropren
and 15 were given Gliatilin (Choline Alphoscerate). Four months treatment with Ropren led to
an average 38 percent improvement in cognitive function based on the Mini Mental State
Examination (MMSE), together with the elimination of most of the other symptoms
associated with Alzheimer’s disease, including depression. The trial also demonstrated that
treatment with Ropren led to a normalisation of the activity of key enzymes in blood plasma –
again pointing to a link between liver degeneration and the incidence of neurodegenerative
disorders like Alzheimers’s Dementia. The research team was surprised to find that eleven
patients experienced an improvement of 50 percent or more in their MMSE score. Six
experienced an improvement of 100 percent or more.
Understanding the impact of Ropren treatment on healthy volunteers was therefore of great
interest.
Principal Findings of the Swinburne Trials
100 healthy volunteers aged 60-85 were recruited for the double blind, placebo controlled
Neurocognitive Effects Trials conducted by Swinburne’s Brain Sciences Institute (BSI). The
trial involved oral administration of Ropren delivered in VegeCaps manufactured by Cardinal
Health in Melbourne for a period of 12 weeks. The effect of Ropren was measured using
blood biochemical analysis, batteries of cognitive and other psychological tests,
computerised brain analyses and EEGs. Blood tests and EEGs were taken at the beginning
and at the end of the 12 week period. Cognitive and psychological testing occurred every
four weeks. 80 participants completed the full trials program.
The results of the trials are entirely consistent with the findings from previous Russian
research – even though the VegeCaps used for this trial only had the Bioeffective R dose
concentration developed for the treatment of chronic liver disease, not the higher
concentration used in the Russian Alzheimer’s trials.
In his confidential report to Solagran, the BSI team leader Professor Con Stough noted that
the Australian trials results provide “substantial evidence that Ropren is an interesting and
exciting compound that improves a range of cognitive, brain and biochemical variables in
healthy elderly adults.”
The trials report also states that:
�� Several cognitive variables were improved due to Ropren. These were all complex rather
than simple cognitive processes. Nearly all involved some form of memory rather than
just executive functioning or decision making. For example, Ropren treatment led to:
�� Consistently improved spatial working memory over the three month treatment period
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�� Significant improvement in the speed of retrieval of information from long term
memory
�� Improved verbal learning and consolidation of verbal material into long term memory
�� An important finding was the speeding up of brain Event Related Potential (ERP)
responses during working memory tasks. ERP is an electrical brain response to a
cognitive task. The components of ERP portray how the brain processes information. For
example, one component is associated with attention – another with decision-making.
Ropren caused a consistent improvement in both latency and amplitude measures of
ERP components. Latency means the speed with which the brain processes information.
Amplitude means the strength of the response, with higher amplitude suggesting more
efficient and stronger processing of the signal by the brain. This finding, which is
underpinned by EEG data, indicates improved neural efficiency and better cortical
information processing.
�� EEG measures strongly support the changes in cognitive function observed.
�� Several blood biochemical markers were improved – perhaps the most significant
findings being an improvement in liver function and a normalisation of cholesterol levels,
as evidenced by a reduction in Low Density Lipoproteins (LDL) and an improvement in
the LDL/HDL ratio.
�� Further analysis can be done with the existing data to try to determine whether the
changes observed in blood biochemical markers correlate with the observed
improvements in cognitive functioning.
�� There were no differences in the reported side-effects between the placebo group and
the Ropren experimental group.
�� Ropren treatment was well tolerated by trial participants.
Potential Implications
There are four potential implications from this work that the Solagran Board considers
important:
1. Research conducted in Australia has now added to the already strong body of
evidence suggesting that Ropren has the potential to be used as a safe and effective
means with which to both prevent and treat brain and neurodegenerative disorders,
as well as chronic liver disease. A good deal more evidence will be revealed when
Solagran is able to release the results of the chronic alcoholics trial completed in St
Petersburg late last year. Leading Russian psychiatrists and neurologists privy to
these results have already advised Solagran that they are planning to use Ropren to
treat drug induced psychoses and other psychiatric and neurological conditions
arising from drug and alcohol abuse, once Ropren is entered into the Russian
Pharmacopoeia.
2. Solagran now has further evidence suggesting that cholesterol levels could be able to
be normalised by balancing the enzymatic function of the liver with Ropren, rather
than by blocking the liver’s synthesis of an enzyme required to produce cholesterol,
as is the case with existing cholesterol lowering drugs like Lipitor. Solagran’s
research makes this doubly important now. Not only is there the risk of liver side
effects arising from long term Lipitor use. There is now the emerging possibility of a
link between the incidence of these side effects and the onset of neurodegenerative
disorders.
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3. The improvement in cognitive function achieved during the trial is significant, since all
trial participants were healthy volunteers – having what was considered to be sound
cognitive functioning at the commencement of the trial. The normalisation of
cholesterol levels which occurred in parallel with an improvement in liver function is
equally significant. Further testing of these effects in clinical populations (i.e. patient
groups with impaired cognitive function or abnormal cholesterol levels) will provide
additional important information about the activity of Ropren.
4. The fact that Ropren appears to enhance cognitive function in healthy volunteers,
while at the same time normalising enzymatic activity known to be associated with
neurotransmission, raises the possibility of it being used as a prophylactic to help
prevent neurodegenerative disorders, as well as a potential treatment with which to
overcome them.
Next Steps
Over the next few weeks, Solagran, its patent attorneys, and its research partners in St
Petersburg, will review the Swinburne trials report and underlying data – particularly the
blood biochemistry and EEG results. They will then discuss the path forward with the
Swinburne BSI team. This process will enable data related to Ropren’s effect on healthy
volunteers to be compared to that relating to Alzheimer’s patients. This will lead to both a
deeper understanding of the activity of Ropren and a joint publication in a peer reviewed
journal.
The BSI has recommended a number of further research projects to learn more about
Ropren’s potential. It has also recommended that Solagran conduct a similar study with a
much larger population using brain imaging technology to more clearly demonstrate the
nature and the speed of Ropren’s impact on the brain.
These recommendations will be considered in the context of Solagran’s overall clinical trials
program – and particularly in the light of the results of the yet-to-be-released chronic
alcoholics trial. The results of that trial are far more significant than those being revealed
today in this announcement. A summary of the key findings of the alcoholics trial will be
released as soon as all relevant intellectual property protection work is complete.
Once Ropren has entered the Russian pharmacopoeia as a new pharmaceutical substance
to treat chronic liver disease – as is expected to occur soon – the opportunity to complete
Phase IV trials to address other indications will open up.
Commercial Consequences
The Directors believe that the apparent ability of Ropren to normalise cholesterol levels and
balance enzymatic activity in both the liver and the brain is significant – particularly once the
link between liver function and neurodegenerative disorders has been established
unequivocally. This would mean that Ropren could be used as a prophylactic against such
disorders – as well to help prevent cardiovascular disease. It could also enable patients with
abnormal cholesterol levels to treat their condition, without the risk of long term liver side
effects potentially leading to a neurodegenerative condition later in their life. Russian trials
have already demonstrated that it should be possible for those who already have liver
problems arising from the side effects of cholesterol lowering drugs, to use Ropren to quickly
restore a healthy liver function.
The Directors consider that there is now substantial evidence supporting Solagran’s
contention that Ropren can potentially be used as a safe and effective treatment for
neurodegenerative disorders, as well as for chronic liver disease. This evidence is already
sufficient to satisfy a number of opinion-leading Russian psychiatrists and neurologists who
have been privy to the results of recent Ropren trials in Russia. These clinicians plan to use