+ + data and comment + +, page-56

re: + + annual report. drug acv1 to be discussed + From Annual Report:

Pain killer ACV1

"Analysts predict that a safe, well tolerated and
effective therapy for this condition would gain
immediate acceptance by doctors. The potential
market for analgesics to treat neuropathic pain
is estimated at several billion dollars".

"Metabolic’s ACV1
ACV1 is a peptide compound discovered in the venom of the Australian marine cone snail Conus Victoriae which has been found to have profound analgesic properties.

Cone shells have evolved a rich cocktail of peptides in their venom, which together act by a variety of mechanisms in the nervous system to quickly immobilize or kill their prey.

The potential of cone snail venoms as a source of new therapies has been recognised for many years, and the first such compound to be commercialised is the analgesic Ziconotide from Elan Pharmaceuticals.

Ziconotide acts by blocking a component of the central nervous system called the N-type calcium channel, and while it produces substantial relief from pain, also causes substantial side effects at the same dose levels, and must be injected directly into the spine to reduce adverse reductions in blood pressure.

ACV1 acts by an entirely novel mechanism, specifically blocking a subtype of a class of receptors in the peripheral nervous system called, as a group, neuronal nicotinic acetylcholine receptors (nAChR). ACV1 can be administered by convenient routes such as once daily
subcutaneous injections without any apparent
adverse effect at many multiples of the effective
dose, providing substantial relief in animal models
of neuropathic pain".

"Collaboration with a research group in Germany has also confirmed activity of ACV1 on human nerves, increasing the expectation of results in human trials similar to those obtained so far in rats.

This scientific work has recently been submitted for publication in a peer reviewed journal. Other animal efficacy work contracted by Metabolic has also extended our knowledge of the range of activities of the compound, with encouraging results in several nerve
injury models.

Dosing in Phase 1 human safety trials by subcutaneous injection is targeted to begin in Q1 2005.

It is expected that the first indication targeted for ACV1 in Phase 2 clinical trials will be neuropathic pain in diabetics, as this is an easily identified condition suffered by an accessible and numerous patient group.

However, the potential range of indications for ACV1 extends to post-herpetic neuralgia (“shingles”), sciatica
and many other neuropathic pain conditions currently underserved by pharmaceutical treatments".