Iliad hits homer with first drug

Unlisted Melbourne drug-development company Iliad Chemicals has reported promising results from a pre-clinical trial of its first anti-cancer drug, developed with its proprietary Multicore drug-synthesis technology.

And George Jessup, MD of Start-up Australia Ventures, which invested AUD$1 million in Iliad's start-up in May, 2003, says his company will invest another AUD$1 million to fund further development of the new cancer drug.

Iliad's 'designer' molecule inhibits the growth of blood vessels that nourish and oxygenate tumours. CEO Dr Bernard Flynn describes it as a 'vascular targeting' drug, rather than an angiogenesis inhibit, because it is also active in established tumour blood vessels, as well as inhibiting new blood-vessel growth.

Flynn said researchers at the Peter MacCallum Cancer Centre in Melbourne had tested the drug in mice that accept xenografted human cancer cells, and found it was 50 times more potent than Iliad's initial experimental compound, a mimic of combretastatin.

Combretastatin is a plant compound, found in the bark of the west African bush willow - not a true willow, but a African species in the plant family Combretaceae.

Combretastatin's promise as an angiogenesis inhibitor powers came to light in 1997; four years later, the international journal Nature reported it was highly effective in destroying tumours by depriving them of a blood supply.

But like the now widely used breast- and ovarian-cancer drug taxol, from the bark of the Pacific yew tree, combretastatin is a large and complex moelcule, and difficult to synthesise on an industrial scale.

Flynn said Iliad's Multicore technology, developed by chemists at the Australian National University in Canberra, enables synthetic chemists to explore a diverse range of core structures for promising drug molecules, and then to 'tweak' side-chain structures around the core to enhance the molecule's affinity for target receptors, or to modify its pharmacokinetics.

Iliad researchers synthesized a range of combretastatin mimics and selected several that showed 30 to 50 times the activity of combretastatin as previously tested by researchers at the Peter MacCallum Cancer Centre.

Flynn said the development puts Iliad in the enviable position of having a range o drug leads which it could test for efficacy, toxicology and drug-like characteristics. These tests would allow an optimal choice of the company's drug candidate for pre-clinical studies, scheduled to begin in early 2005.

Start-up Australia's Jessup described the power of Multicore technology as "impressive' and said he was impressed that Iliad had been able to demonstrate efficacy with its first candidate molecule.

"The MultiCore technology is applicable to a wide range of drug development programs and I expect Iliad will have a significant impact in a number of therapeutic areas.

"We are now investing another $1 million to fund the further development of its cancer drug. This follows on from a previous investment of $1 million in 2003."

Flynn said his company is keen to extend Multicore technology, which was applicable to a wide range other molecules, including biological compounds found in plants, and terrestrial and marine organisms, as well as to 'legacy' compounds that could be exhumed from the research literature and reanalysed.

"The initial lead compound doesn't have to be a naturally occurring compound," he said. "We begin with an initial lead compound, and we 'rediscover' its original activity by creating a number of with different cores, that feature some of the pharmacophoric units from the original.

"Some structures fit our Multicore capability better than others, but in principle, it's applicable even to quite unusual molecules, as long as we can identify their structure. Combretastatin is quite unusual."

Flynn said Iliad planned to begin Phase 1 human clinical trials in 2006, and said an ASX listing was "one of the most likely paths for the future".