phase 2b clinical trial results

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ASX Announcement ASX code: MBP
Metabolic’s obesity drug -
Phase 2B clinical trial results
• Trial results do not support commercial viability of obesity project: programme is terminated
• Metabolic will focus on development of its high potential pipeline, which includes pain,
osteoporosis and the Oral Peptide Delivery Platform
• Current cash position ~$24 million, sufficient to fund all activities in the medium term
Melbourne, 21 February, 2007. Metabolic Pharmaceuticals Limited (ASX: MBP) announced today that
the Phase 2B trial results for its drug, AOD9604, do not support the commercial viability of the drug as a
treatment for obesity. Development of the drug for this condition is terminated.
Trial results showed that weight loss compared to placebo at the primary and secondary endpoints of 12 or
24 weeks of treatment, was too low to reach statistical significance. The design of the obesity trial included
Phase 3 conditions, such as a broader population of subjects (536 in total) and a formal diet and exercise
programme. Under these additional conditions the AOD9604 treatment did not demonstrate the weight
loss required to support commercial outcomes.
The Company will focus on its other projects, including ACV1 for neuropathic pain (currently in Phase 2
trials) and AOD9604 for osteoporosis, as well as extending the application of its Oral Peptide Delivery
Platform to other high value drugs.
Dr Arthur Emmett, Chairman of Metabolic said “It is the nature of our industry that not all clinical stage
drugs progress from Phase 2 to Phase 3 trials. That is why the Board of Directors has long emphasised
the building of a strong and diverse pipeline. We will progress our programmes for the treatment of
neuropathic pain and osteoporosis, and are continuing with preclinical development of the Oral Peptide
Delivery Platform. These products are aimed at addressing unmet needs in multi-billion dollar markets”.
Metabolic CEO, Dr Roland Scollay, said “We set out to conduct a high quality trial that would be predictive
of a Phase 3 result and provide data to establish the commercial viability, or otherwise of the drug, prior to
committing to the significant expense of a full Phase 3 trial. These objectives were achieved. The
important thing for Metabolic now is that we maintain our focus on advancing the development of our other
programmes, all of which have the potential to generate significant value for shareholders”.
Weight loss at the primary and secondary endpoints of 12 or 24 weeks of treatment, after allowing for the
effects of the diet and exercise programme, was less than 1 kg in all dose groups. There was a subgroup,
predetermined in the trial design, which did show weight loss at the levels seen in the previous trial (see
appendix), but the overall population did not respond consistently. Given the high levels of weight loss seen
in the placebo group (diet and exercise but no drug), it may be that the drug effects were overwhelmed by
the effective weight loss programme, a programme which was consistent with that outlined in the relevant
FDA guidelines. The safety and tolerability of AOD9604 was excellent with no evidence of any difference
from placebo.

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The result of the OPTIONS Study has been announced ahead of schedule due to the clear and definitive
outcomes which required less internal analysis than expected by the Company.
Detailed information regarding the trial design and results can be seen in the Appendix.
Pipeline
ACV1 for Neuropathic Pain currently in Phase 2A clinical trials
The neuropathic pain programme will continue to be a major activity, with the first of two Phase 2A clinical
trials on ACV1 in progress and results due in mid 2007. The second Phase 2A clinical trial is due to
commence in March 2007. ACV1 has shown strong effects in animals and a clean safety and tolerability
profile in a human Phase 1 trial. Neuropathic pain is a large and growing market (US$2.7 billion in 2005).
AOD9604 for Osteoporosis
In animal studies, AOD9604 has shown beneficial effects in the prevention and treatment of osteoporosis.
Ongoing animal studies for the osteoporosis programme are expected to be completed during the second
half of 2007. Further development will be considered in light of the study results and a costing analysis.
Oral Peptide Delivery Platform
Metabolic’s Oral Peptide Delivery Platform achieved proof-of-concept in 2006, following animal studies
testing a newly created oral variant of Metabolic’s pain drug (ACV1) which displayed high levels of oral
availability for the drug which was previously only effective by injection. The Company is currently
designing and testing oral variants of a range of high-value peptide drugs, and will report progress over
2007.
New opportunities
Metabolic will continue its active search for new opportunities to add to the existing pipeline.
Resources
Current cash position of ~$24 million
The Company has sufficient funds to continue all its planned activities in the medium term. Projections
show that as at June 2007, Metabolic will have cash reserves sufficient to progress existing projects to
significant milestones, including ACV1 neuropathic pain trials and the advancement of the Oral Peptide
Delivery Platform.
For further information, contact:
Shareholders
1800 255 018
(free call within Australia)
02 8256 3388
(outside Australia)
Analysts and Institutional Investors
Diana Attana, Assistant Company
Secretary / IRO
[email protected]
T: +61 3 9860 5700
Media
Steve Murphy
Hinton and Associates
T: +61 3 9600 1979
M: 0407 048 275

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Appendix 1: The OPTIONS Study trial design
Number of subjects: 536 subjects enrolled, approximately equal numbers of men and women
Key subject selection criteria: �� BMI (Body Mass Index) 30-45 kg/m2;
�� Age 18-65 years; and
�� A waist circumference of more than 102 cm for males and 95 cm for females,
in otherwise healthy subjects.
Rationale: A previous Phase 2B trial involved no formal diet and exercise programme. In
that trial all five dose groups of AOD9604 produced average weight loss greater
than placebo after 12 weeks of treatment. The response was bimodal for both
genders with the best dose group at 1mg, which fell short of significance (p=0.1,
p=0.05 required) on the primary analysis but reached significance in the female
subgroup.
This OPTIONS Study was designed to explore doses at and below 1mg and to
seek to confirm the prior observations with a formal diet and exercise
programme more similar to Phase 3 conditions in line with relevant FDA
guidelines.
Blinding status: Double-blind
Placebo controlled: Yes
Treatment route: Oral (tablets)
Study design: A four-week run-in period commencing at enrolment (week -4) involved the start
of a dietician-supervised diet and exercise programme, with all subjects
receiving placebo in a single-blinded manner. At week 0 the subjects entered
the double-blind period and were randomised to one of the once daily dose
levels of AOD9604 or placebo. At week 24 the treatment and the diet and
exercise programme ended. At week 28 the subjects were given final
assessments and exited the study.
Dose groups: 0, 0.25, 0.5 and 1 mg
(the 0 group was the placebo group)
Primary endpoints: �� Statistically significant weight loss after 12 weeks of treatment for any one of
three daily AOD9604 oral doses of 0.25 mg, 0.5 mg and 1 mg compared to
placebo; and
�� Safety and tolerability.
The trial was powered for an 80% chance of achieving significance on the
primary endpoint if the weight loss compared to placebo was 1.8 kg.
Secondary endpoints: �� Weight loss over 24 weeks of treatment;
�� Comparison of the effects of the three different dose levels;
�� Waistline reduction over 24 weeks of treatment;
�� Body fat reduction assessed by whole body DEXA scans; and
�� Improvement in risk factors such as glucose control and lipid profiles over
24 weeks of treatment.
Trial sites: 16 clinical trial sites throughout Australia
Contract Research Organisation: Kendle Pty Limited

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Appendix 2: Results of the OPTIONS Study
Subject demographics: 56% female (one-third post-menopausal), 44% male
Average height 170 cm
Average weight 106 kg
All dose groups similar
Subjects attending each visit: Dose Group 0mg 0.25mg 0.50mg 1.0mg
Week 0 125 127 125 125
(randomisation)
Week 12 106 103 101 98
(primary endpoint)
Week 24 92 90 90 85
(end of treatment)
No significant difference between groups.
Primary endpoint –
weight loss outcome and
comment:
Not met.
A plot of weight change over the course of the study for the full analysis set is
provided on the following page.
Pre-defined subgroups for secondary analysis were stratified into gender, initial
BMI (<35 or >=35 kg/m2), and weight loss response to the 4 weeks of diet and
exercise before randomization (<2 kg or >=2 kg).
Examination of the subgroups shows that females with low response to the diet
and exercise before randomisation show similar effect sizes to those reported in
the previous trial.
Our conclusion is that AOD9604 does not combine or synergise with successful
use of an ongoing diet and exercise programme, but may show some effect with
moderate weight loss effort in females.
Primary endpoint – safety: Preliminary analysis shows no evidence of any difference between placebo and
any of the AOD9604 treatment groups on safety or tolerability.
Secondary endpoints: No relevant findings.

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All data (N=503)
-5
-4
-3
-2
-1
0
1
2
3
-8 -4 0 4 8 12 16 20 24 28
Week (0 to 24 treated)
Average Weight change from
randomization (kg)
Placebo
AOD 0.25mg
AOD 0.50 mg
AOD 1.0 mg
Females with low ( < 2kg ) weight loss before treatment
(N=149)
-5
-4
-3
-2
-1
0
1
2
3
-8 -4 0 4 8 12 16 20 24 28
Week (0 to 24 treated)
Average Weight change from
randomization (kg)
Placebo
AOD 0.25mg
AOD 0.50 mg
AOD 1.0 mg