Document date: Tue 27 Aug 2002 Published: Tue 27 Aug 2002...

Document date: Tue 27 Aug 2002 Published: Tue 27 Aug 2002 10:16:43
Document No: 193843 Document part: A
Market Flag: Y
Classification: Progress Report
METABOLIC PHARMACEUTICALS LIMITED 2002-08-27 ASX-SIGNAL-G

HOMEX - Melbourne

+++++++++++++++++++++++++
POSITIVE RESULTS FROM AOD9604 OBESITY DRUG ORAL PHASE 2A HUMAN
CLINICAL TRIAL

* RESULTS INDICATE AOD9604 IS ACTIVE AFTER ORAL DOSING
* MAXIMUM MARKET POTENTIAL
* DAILY DOSE SAFETY TRIALS SCHEDULED FOR Q4 2002
* DAILY DOSE EFFICACY TRIALS PLANNED FOR 2003


Metabolic is very pleased to announce the successful completion of
its Phase 2A human clinical trial of obesity drug AOD9604 by
single-dose oral administration, showing positive results.

"This landmark result is the company's most important milestone
achieved to date. Oral administration, the preferred mode of drug
delivery, will maximize the commercial potential of AOD9604," said
Chris Belyea, Managing Director.

"In all the trials performed so far, AOD9604 has consistently shown
that humans respond to AOD9604 with increased fat metabolism, without
side effects having been seen. This latest result provides key
evidence that the oral activity shown in animals also applies to
humans. We look forward with anticipation to forthcoming trials and
our expectation is that AOD9604 will safely produce a meaningful
weight reduction after daily oral dosing."

Increased average fat breakdown compared to placebo was observed at
all dose levels of AOD9604 (9, 27 and 54 mg) lasting several hours
after administration, reaching statistical significance at 27 mg. Fat
breakdown, a signal of drug activity, is followed in the blood by
measuring levels of non-esterified fatty acids (NEFA). NEFA is a
marker, evident after a single dose, of fat metabolic changes that
are expected to result in weight loss after extended daily dosing.

Preparations are now under way for a safety study dosing once-daily
for one week to be conducted before year end in preparation for an
extensive weight reduction study for 2003.


TRIAL DESIGN AND RESULTS

The double-blind trial was conducted in 16 clinically obese but
otherwise healthy male volunteers aged 35 to 60. Each received the
following single oral doses of AOD9604 in random order: placebo (0),
9, 27 or 54 mg. Each dose was separated by an interval of 2 weeks.

The aim of the trial was to assess oral activity, safety and
tolerability of the drug in clinically obese volunteers after single
oral doses. The decision end-point to assess oral activity was
observation of an increase in fat breakdown that was expected to
occur over several hours after each dose.

As with the previous two clinical trials there were no safety or
tolerability concerns associated with the drug at any dose.

In the previous Phase 2A study by intravenous AOD9604 administration,
fat breakdown was measured before dose and at several times in the
hours after dose while fasting. The volunteers broke their fast after
the two-hour measurement. Fat breakdown naturally increases during
fasting and drops substantially after a meal. The enhancing effect of
the AOD9604 action was observed in these studies during the two hours
after dose, where fat breakdown increased more on average in treated
volunteers compared to placebo volunteers.

In this oral study, the design was similar except we extended the
fast to 4 hours after the dose to gather more data during fasting. We
saw the same effect of a similar magnitude, continuing for the
duration of the fast. For all times later than 30 minutes after the
dose and at all oral dose levels of AOD9604, the rise in fat
breakdown during the fast was greater than placebo.

The 27 mg dose showed the greatest response, reaching 38% more than
placebo at 4 hours, after which the fast was broken. The effect at
the 27 mg dose was statistically significant compared with placebo.
See graph below of the placebo-subtracted response. The plotted
values indicate how much greater the increase in NEFA from pre-dose
was after AOD9604 treatment than after placebo treatment. The "error
bars" are plotted for the 27 mg dose.

The lower response observed at the highest (54 mg) AOD9604 oral dose,
if it is confirmed in later studies, would be consistent with
observations at high doses in the Phase 1 trial by intravenous
administration (conducted in lean patients). It would also be
consistent with results from in vitro tests on isolated fat tissue
from humans and animals, and with whole animal studies.

This single dose oral study, like the previous intravenous study, was
not designed to measure weight reduction, which would be expected to
be observed only after extended daily dosing. However, in this trial
the most active fat breakdown dose (27 mg) resulted in the greatest
average weight change one week after dose, a reduction of 0.2 kg
relative to placebo. Although this change is in the right direction,
it is not statistically significant, and therefore is not conclusive
evidence that the drug will cause weight loss in humans. The study
projected to take place next year will be designed to provide this
evidence, in which 40 or more patients will be treated at several
doses once daily for 1 or more months.


NEXT STEPS

A manuscript of these trial results combined with the results from
the intravenous trial will be submitted to a peer-reviewed journal.

The protocol for a safety trial involving one week of once-daily
dosing has been submitted for ethics approval. In this trial safety
and tolerability are the only end-points. Young and old obese male
adults (nine only in each dose group) will be given oral AOD9604
daily for one week to check for any adverse effects. This is a
regulatory requirement before conducting longer term daily dosing
studies.

Assuming successful completion of the one week safety trial, expected
by year end, an extensive Phase 2B weight reduction trial in at least
150 patients will commence in 2003. The timing of the commencement
will depend on the design, to be determined with input from the US
Food and Drug Administration. The main aim will be to establish
weight loss after extended dosing and to determine the best dose
range.

With $11.5 million currently on hand and $12 million expected to be
received on the exercise of the MBPO options by July 31 2003, the
company has sufficient funds for its activities until at least the
end of 2003.


9TH INTERNATIONAL CONGRESS ON OBESITY

Assoc. Prof Gary Wittert MD at the Royal Adelaide Hospital, principal
investigator of the trial, will be presenting these clinical results
at the 9 th International Congress on Obesity, in Sao Paulo Brazil,
later today.


NEXT ANNOUNCEMENT

We will provide our regular quarterly shareholder update in relation
to the Company's other projects and activities shortly.


AOD9604 OBESITY DRUG - BACKGROUND

Metabolic's candidate obesity drug, AOD9604, invented at Monash
University, acts specifically on the body's fat cells to enhance the
breakdown of stored fats and inhibit the synthesis of new fat. This
result is biochemically similar to the slimming effects of physical
exercise. AOD9604 has proven to be effective in reducing obesity in
laboratory animals through once daily oral administration, with no
effect on food intake.

The drug is modelled on the active fat reducing portion of the human
Growth Hormone (hGH) molecule. hGH occurs naturally in the body and
is involved in promoting growth. In addition it has pronounced
effects on body fat. Scientists at Monash University have shown that,
when dosed to animals, AOD9604 has the fat-reducing effects of the
intact growth hormone without its other unwanted effects having been
observed.

Obesity is the Western world's most pressing health problem, suffered
by over 20% of the population. The obese as a group spend 77% more on
health care, compared with 28% more by smokers. AOD9604 may provide a
safer and more effective obesity treatment than currently available
drugs. The anticipated absence of adverse side effects on mood or
digestion may lead to a high level of doctor and patient acceptance.


CONTACT DETAILS

website www.metabolic.com.au
CEO Chris Belyea +61 3 9826 0949
CFO David Kenley +61 3 9826 0949