Peplin spruiks promising new compound

Brisbane's Peplin Biotech Ltd (ASX:PEP) has had a good week, reporting a promising new indication for its lead anti-cancer compound PEP005, and promising activity from a new compound of undisclosed provenance.

Peplin's UK collaborators have reported that PEP005, which the company has been developing as a treatment for non-melanoma skin cancers, is showing extremely potent activity against a number of leukaemic cell lines, and against cells from patients with one of the deadliest blood cancers, relapsed acute myelogenous leukaemia (AML).

And Peplin has also announced that researchers at the Cooperative Research Centre for BioProducts have demonstrated anti-cancer activity in a compound produced by tissue-cultured cells from a plant that has not previously been grown in tissue-culture.

Peplin MD and CEO Garry Redlich would not reveal whether the plant was petty spurge (Euphorbia peplis), source of Peplin's lead compound, PEPOO5, but said the new compound was chemically related to PEP005.

Redlich said the company had a satisfactory system for growing petty spurge in the field as a source of PEP005, which did not involve tissue culture.

The company is not disclosing the identity of the plant, to ensure that "we remain in the lead in what we believe is a an important interesting area of chemistry. We want to pursue every possible route to biosynthesis," Redlich said.

He said Peplin wanted to explore the full range of synthetic possibilities for compounds related to PEP005, to reduce the risk that fossickers will find a rival compound it may have overlooked.

Citing the example of the breast-cancer drug Taxol, isolated from the bark of the Pacific yew, Redlich said, "Everybody has been crawling over Taxol for a decade looking for new analogues, and a few have fallen into the hands of Bristol-Myers Squibb."

Good news for PEP005

Although Peplin is currently focusing on skin-cancer applications for PEP005, the molecule has shown activity at very low concentrations against a very broad range of cancer cell types. It is a novel protein-kinase inhibitor, a member of a class of novel drugs that inhibit enzymes crucial to cell replication.

Prof Janet Lord's research group, at the Medical Research Council Centre for Immune Regulation at Birmingham University, has now reported that PEP005 was highly effective against a number of established leukaemic cell lines at very low (nanogram per millilitre) concentrations of drug.

Lord's group said PEP005 arrested the growth of leukaemic cells, caused them to differentiate -- revert to normal shape and behaviour -- and induced programmed cell death, or apoptosis.

Primary blast cells from two patients with one of the most intractable forms of leukaemia, acute myelogenous leukaemia (AML), showed significant responses to PEP005 within 24 hours at similarly low drug concentrations.

The American Cancer Society estimates the number of Americans presently suffering from some form of leukaemia at more than 670,000. The World Health Organisation says there are around 380,000 new cases of AML each year. Older people are at highest risk, but AML can strike as early as age 25.

"The outlook for the majority of AML patients is very bleak and new drugs are urgently required," Dr Lord said.

Dr Peter Welburn, Peplin's Director of Clinical and Regulatory Affairs, who is currently in the UK coordinating development of PEP005, said the compound could be in a leukaemia clinical trial in the first half of next year.

"We are making great progress in finalising pre-clinical studies in toxicology in preparation for our first Investigational New Drug filing with the FDA for skin cancer," he said.

"Much of that work will be directly relevant in supporting an early evaluation of a systemic formulation of PEP005 in patients with refractory leukaemia."