Four legs good

It doesn't attract the limelight, but Australia's vet biotech sector is making strides, reports Melissa Trudinger

Biotechnology is often seen as the saviour of the global pharmaceutical industry, or as the future of agriculture. But there is another side of biotechnology just as important, that focuses on using the technology to improve animal health.

"There is a lot of research going into animal health applications, but it tends to be overshadowed by human health applications," says Dr Chris Prideaux, program leader for vaccines and therapeutics at CSIRO's Australian Animal Health Laboratory (AAHL), a strong player in Australia's animal biotechnology sector.

For decades, production animals have been routinely fed antibiotics to promote growth, largely as a result of preventing the diseases that regularly infect them. But faced with a growing army of antibiotic resistant pathogens that readily infect humans as well as animals, governments around the world are contemplating bans on the use of human antibiotics on production animals.

The possibility has created a flurry of research into alternative ways of controlling infectious diseases in animals, via vaccines or specific therapeutic products to control specific pathogens. And the newer biotechnologies are assisting the process.

In addition, the new technologies of genomics, proteomics and cloning are opening up new possibilities of production animals that have been selectively bred for improved quality characteristics, disease resistance and even functional foods.

A handful of Australian biotechnology companies are focusing their efforts on animal biotechnology, seeing a niche market where the skills of Australian researchers can be commercialised. At the top end is Australia's big biotech company, CSL, whose animal health division provides most of the animal vaccines on the Australian market.

According to Gordon Hands, the divisional manager for CSL Animal Health, the company has focused primarily on vaccines and diagnostics, with products spanning the majority of production animals excluding poultry, as well as horses, cats and dogs. CSL scientists are also using their immunological expertise to develop new therapeutics based on immune responses, such as an oestrus control vaccine used to control ovulation and related behaviour in horses, and a porcine vaccine that reduces boar taint -- a quality issue caused by high levels of male hormones -- without castration.

The division is responsible for around eight to nine per cent of CSL's total revenues, and according to Hands, a significant proportion of it is reinvested into the R&D programs. "The key to our success in the marketplace is having such a strong focus on vaccines -- it allows us to compete with larger companies," Hands says. CSL has the lion's share of the vaccine market in Australia and is also a significant player in the US market, where most of their competitors are multinationals.

Hands says most of CSL's animal health products are developed internally, although the company has a US subsidiary in the animal health sector as well, which focuses on the development of products for the US market. And the company frequently works with researchers in the public sector, at the vet schools and agricultural research institutions around the country, both in sourcing new vaccines and technology, and in development and field testing of new products.

Prima BioMed, best known for its immunological approaches to human disease, is also eyeing the vaccine market, through its subsidiary PanVax. The company's DCTag adjuvant technology, which enhances the T cell immune response, has shown promise in animal models in improving the efficacy of viral vaccines.

"We saw it as an immediate opportunity for the technology," says Prima CEO Marcus Clark. "We expect animal products to be the first on the market for DCTag. The veterinary industry has its own rigid regulatory requirements, but they are still less onerous than human trials."

Clark says the company is hoping to complete a deal later this year for use of the DCTag technology in animal vaccines. He sees the companion animal market as the initial opportunity, with production animals requiring more rigorous toxicology studies.

A new company looking at novel approaches to vaccines is Imugene, which is commercialising innovative technologies coming from CSIRO's AAHL and Murdoch University through its subsidiaries VectoGen and Paragen. Managing director Dr Warwick Lamb says that the quality of research coming out of the public sector is extremely good, but the veterinary and animal health market is an under-serviced area of biotechnology, an attractive opportunity to Lamb and co-founder Graham Dowland.

As with many of the other animal health biotech companies, Imugene's products are vaccine-related. VectoGen is developing a series of vaccines and immunotherapeutics for production animals, specifically pigs and poultry, based on an adenovirus delivery system invented by AAHL researchers. The technology can be used to deliver proteins including antigens from pathogens as well as cytokines, immunological proteins that VectoGen is developing as growth promoters. While the products are still 3-4 years from the market, Lamb says that the company has several evaluation and sublicense agreements with multinational animal health companies Merial and Intervet.

"In the early stages of Imugene, we think this is the fastest way to market," he says. "As cash flow from those products comes on line, we'll be looking to produce our own."

Imugene's other company, Paragen, is targeting the companion animal market with a flea vaccine developed by Murdoch University scientists. "Flea products worldwide are the largest animal health sector," says Lamb. "We're fortunate to have a very promising and novel way to move into that market. It's actually ground-breaking research."

While the companion animal market has some excellent opportunities, it's also the hardest to get funding for, especially in Australia. According to Dr Steven Holloway, a veterinarian surgeon and lecturer at the University of Melbourne's School of Veterinary Science, it's almost impossible for researchers interested in these areas to come by funding. "There isn't much biotechnology research being done unless it is a good model for human disease," he says. "In terms of biotechnology there is a lot of things that could be done, but none of them in Australia."

At best, it puts Australia into a consumer role, and at worst it is contributing to the brain drain, says Holloway, who notes that the lack of a commercialisation culture and in small animal science in Australia is in part to blame. Ironically, many companion animals suffer from similar 'lifestyle' diseases to their human owners, including obesity, diabetes and high blood pressure. And a number of human drugs, including chemotherapeutics, are regularly used to treat pets, Holloway says. But the small market size, especially in Australia, restricts the development of companion animal therapeutics and products.

Holloway is worried that the proposed bans on the use of human antibiotics in animals will extend to the use of other human drugs in animals. "A blanket ban on all human drugs in dogs and cats would severely restrict veterinary practice -- I hope it doesn't come to that," he says.

A unique product for the companion animal market being developed by Peptech Animal Health (PAH), a subsidiary of Peptech, is a contraceptive vaccine. Currently awaiting NRA registration for use in Australia, the product provides at least six months of contraceptive activity via a unique product that controls the reproductive hormones, and a 12-month version is in development.

According to Dr Tim Trigg, the managing director of PAH, the product has tremendous potential as a contraceptive product in a variety of animals, and also as a treatment for hormonal conditions like benign prostatic hyperplasia which commonly afflicts older male dogs, and as an alternative to castration to control behaviour. And the product is not just suitable for male animals; versions for female animals are also a possibility. Uses in wildlife management, zoos and game parks are also envisaged.

While PAH's first animal product, a peptide used to induce ovulation in mares, is being marketed by the company, with the help of animal health company Fort Dodge for US distribution, Trigg says PAH is actively seeking partnerships to help with the development and marketing of the contraceptive, recognising that the market is too big for them to handle on their own. In Australia alone, he says, 64 per cent of households have pets, and in the US there are 56 million dogs. "The potential markets are very large. The driver will be people seeing that it is doing its job." But the biggest challenge in developing these products, says Trigg, is keeping the cost down, an issue echoed by CSL's Gordon Hands.

"One of the key issues that we're facing is the increase in the cost and time to develop new products," says Hands. Part of that, he says, is that more complex vaccines are being developed, but it is also due to increasingly tight regulatory standards. "They are becoming much more closely aligned to human standards."

At the heart of the issue is the fact that the majority of animal health products are used for intensive production, and the producer has to make an economic decision about using the vaccine or growth promoter. The trend toward antibiotic-free production is working in favour of vaccine development though, and Hands says it is becoming a major driver for biological animal health research.

And in Australia, market size is a significant issue. Along with New Zealand, we have a large part of the global sheep market, and our cattle market is pretty large as well, but compared to the US and Europe, our pig and poultry numbers are small. While companies like CSL can justify developing vaccines for the Australian market, smaller companies need to access the global markets, and often the only way to do that is to license products at an early stage.

"We have to look for synergies with the international market," says Chris Prideaux, from the AAHL. "We have alliances with some of the major veterinary pharmaceutical companies around the world to develop vaccines."

Adding to the mix is the fact that Australia is free of many pathogens that cause problems around the world, particularly viruses like foot-and-mouth disease. "To be honest, the areas we choose are looking at world markets with applications to be taken up in the US, Japan and Europe," says Prof Ivan Caple, dean of the School of Veterinary Science at the University of Melbourne. "A lot of health products are not necessary in Australia as we have healthy animals. All we can develop is the idea, and then sell it into overseas countries."

One unique niche that Prideaux sees as an opportunity for animal health biotechnology is the development of quantitative tests of animal welfare. "A lot of biotechnology is driven by consumers and animal welfare is very important to them," he says. The tests would measure parameters like cytokine profiles and other physiological indicators. "We know that the immune system suffers when animals are suffering from poor welfare or stress." Prideaux says such a test would provide a much-needed scientific measure of welfare rather than just taking an emotive view.

"I'd like to think there was a role for Australian companies to make an impact on Australia and world markets," he says.