Imugene unveils details of piglet product

North Ryde animal-health biopharma Imugene Limited (ASX:IMU) is fast-tracking the commercialisation of its recently acquired receptor mimic technology (RMT).

Imugene announced this week that its first commercial product will be an oral preventative for E. coli-caused post weaning diarrhoea, or colibacillosis, a major killer in the pig industry.

Imugene’s MD Dr Warwick Lamb said the project will put Imugene in competition with the polymer antimicrobial developed by WA biotech company Chemeq.

Lamb said the new RMT platform technology was a valuable complement to Imugene’s existing portfolio, particularly its adenoviral delivery vector system, to increase the range of diseases the company can prevent.

Imugene has already developed the processes necessary to scale up production to 10,000-litre fermentation tanks. It will contract out manufacture of new RMT therapeutics, to avoid the delays and capital expenditure involved in building its own production facilities.

Large-scale production will allow it to proceed directly to evaluation trials for commercial registration. Imugene expects it will take only eight to 12 months for the Australian Pesticides and Veterinary Medicines Authority to approve the product – the approval process for oral therapeutics is shorter.

RMT came out of South Australia’s infamous Garibaldi salami food-poisoning episode, in which a child had died and several others suffered irreparable kidney damage from a toxin secreted by a pathogenic strain of E. coli that survived the company’s production processes.

Adelaide University researcher Dr Adrienne Paton identified the deadly toxin as shigatoxin, and with her husband Professor James Paton, and Dr Renato Morana, had developed a soluble mimic of native receptors on gut wall.

The piglet colibacilosis product mimics a shigatoxin receptor called GP3. Given orally, it decoys free toxin molecules in the lumen away from the gut wall, and immobilises them. The capture process is about 99.99 per cent efficient, effectively rendering the microbe non-pathogenic.

Early on in the research phase, Paton and her colleagues became aware that literature descriptions of the shigatoxin receptor in the gut were inaccurate.

They experimentally “tweaked” sever of toxin receptors described in the research literature by adding sugar residues, then exploited their enhanced avidity for the target toxins to select the most promising variants.

Lamb said SMT technology s potentially applicable to all heat-labile toxins produced by pathogenic E. coli, the major cause of kidney failure in children. The toxins also cause bran damage.

Pathogenic E. coli infections in children cannot be treated with antibiotics, which induce dying bacteria to secrete even more of the lethal toxins.

“Because soluble mimic receptors don’t kill the bacteria, there is no chance for resistance to emerge,” Lamb said.

SMT is applicable to a range of other gut pathogens, including rotavirus and some protozoan parasites, and because most of the target receptors are fully conserved between species, the preventative therapeutics could be used in other livestock species – and potentially, in humans.

For the present, Imugene will concentrate on the porcine colibacillosis market, the largest veterinary market internationally.

The main independent external trial of the E. coli receptor mimic has been planned for the third quarter of 2004. The trial will be undertaken by Primary Industries Research Victoria, one of Australia’s leading independent research facilities in the field of E. coli disease in pigs and will commence in the next few weeks.

The product has performed extremely well in the laboratory and we expect this efficacy to be reproduced in the first external trail,” said Lamb.

“Our adenoviral vectors are entering the commercial phase after 18 months of work, and now that it’s humming along, we have the capacity to bring something else along.

“It’s a very elegant technology, and we can produce SMT products cheaply and in bulk and market them ourselves, rather than license them to distributors.”