October 1, 2005 (Vol. 25, No. 17)

Nations Collaborate to Avoid Redundancy and Create Synergy

Longtime archrivals on the cricket and rugby fields, New Zealand and Australia have begun to look beyond competition toward collaborating for the sake of biotechnology. In June 2005, AgResearch (Auckland), New Zealand’s chief livestock research agency and part of the government-sponsored Crown Research Institutes, signed a joint venture partnership agreement for sheep genomics with Meat and Livestock Australia (MLA, Victoria).

The goal of the collaboration, which also includes Utah State University (Logan, UT), is to identify functional sheep genes to improve animal health, welfare, and productivity, says Andy West, Ph.D., CEO of AgResearch.

“In many respects, Australia and New Zealand lead the world in livestock genetics research. By working together on sheep genomics, the competitive advantages we already have will only be strengthened,” says West.

“This collaboration will also benefit the global sheep industry, which is important to ensure a long-term future,” he adds. The work will complement a collaboration between Australia’s Institute for Molecular Bioscience at the University of Queensland (IMB, Brisbane) and New Zealand’s Ovita (Dunedin) in sheep epigenetics and the development of a new generation of antiparasitic drugs for sheep.

“Given each country’s strong biotech sector, geographic and economic similarities, and physical proximity, it just makes sense to work together,” West observes. Australia and New Zealand possess strong natural resources and agricultural, animal, and human health technologies; the expectation is that by joining forces, the two can form a critical mass in biotech that neither might attain separately.

Indeed, together New Zealand and Australia constitute a rapidly growing biotech hubthe world’s fifth largest biotech center, worth a combined NZ$14 billion, employing over 10,000 (with over 40% of the region’s biotech employees residing in New Zealand).

Australia has about 400 core biotechs, with about 43% focusing on human therapeutics, 17% in agbiotech, and 15% in diagnostics. It has also made significant investments in aquaculture and marine biotechnology, environmental sciences, stem cell research, and nanotechnology.

In June, a new $104.5 million biotech research center opened in Melbourne, Bio21 Institute, part of a $400 million Bio21 cluster in Victoria.

New Zealand has 53 biotechs and 28 research institutesalso heavily weighted in human therapeuticsand as an agriculture-based society, it is putting substantial efforts in plant and animal sciences.

In addition, New Zealand has a long history of developing large animal-based technologies, excels in genomics, reproduction, and cloning, and also boasts the world’s best animal health. It is developing its unique genetic and geological diversity and bioprocessing ability, and is committed to research in bioremediation and biocontrol.

Biotech Taskforce

A 2003 biotechnology taskforce, convened by the NZ government’s Growth and Innovation Framework, which identified biotechnology as one of three sectors for potential future development, recommended that the two countries work more closely to capture synergies and avoid redundancies.

“Since then, the federal and state governments of each country have encouraged collaborations by establishing dedicated funding for that purpose,” West explains.

There are over 60 Australian-New Zealand trans-Tasman commercial biotech collaborations in place spanning human therapeutics and agricultural biotech. The region’s two largest forestry R&D powers, Australia’s CSIRO (forestry and forestry products) and New Zealand’s Scion (a Crown Research Institute), have formed a joint venture, Ensis, to improve forestry industry profitability.

The two nations’ plant scientists are collaborating in a number of ventures to improve cancer-fighting nutrients in vegetables. “Partnering with Australian biotech companies enables Kiwi firms to accelerate their development not only in the trans-Tasman market, but globally,” according to Pete Hodgson, New Zealand’s associate minister of industry and regional development.

Biotech Partnership

In June 2004, the Australia-New Zealand Biotech Alliance formed, and shortly after the Australia New Zealand Biotechnology Partnership Fund (ANZBPF) was founded with $12 million to be distributed until 2007, says Stephanie Tulloch, ANZBPF program manager. New Zealand Trade & Enterprise is the NZ government agency that administers the ANZBP fund.

Venture capital activity is accelerating in the region: three new funds with over $430 million in capital have been established in the past half-year alone. Of the three, the $150 million BioPacific Ventures (Auckland) is focusing on the region’s agriculture and plant-based biotech, with an emphasis on Trans-Tasman, Australia-New Zealand cooperation.

In March 2005, the ANZBPF announced the first grants for four trans-Tasman biotech projects. The ANZBPF provides 2550% of eligible project costs, with the condition that recipients match funding from private sector sources.

Proacta Therapeutics (Auckland), a wholly owned subsidiary of Proacta (San Diego), was awarded $2.19 million over three years, which is helping support 35 scientists’ work on hypoxia at the University of Auckland Cancer Society Research Centre.

“Hypoxic regions of tumors are notoriously hard to treat; chemotherapy and radiation usually do not penetrate to the core of tumors, which means they cannot be totally eradicated,” says CEO Paul Cossum, Ph.D.

It is estimated that at least 65% of cancer patients have tumors with hypoxic regions that have been untouchable by any therapy, notes Dr. Cossum.

Proacta’s lead drug, PR-104 (tirapazamine), is activated by low levels of oxygen and appears to produce a bystander effect, killing cancer cells in nonhypoxic areas as well.

Although the company assumed that the drug would be used in combination with traditional chemotherapy and/or radiation, the bystander effect may render the drug effective alone, explains Dr. Cossum. The company plans to file an IND shortly for its lead compound and commence dosing its first patients by the end 2005.

The technology came from the University of Auckland’s Cancer Society Research Centre, and is being developed in collaboration with hypoxia experts at Stanford University (Stanford, CA).

Proacta is also developing a second class of hypoxia-targeted drugs, dinitrobenzamide mustards, in tandem to the lead compound. The company is in the process of selecting its second lead from one of the two classes, and aims to file an IND for a second compound in mid-2006.

Proacta Therapeutics is one of a growing number of New Zealand and Australian biotech companies opening operations in the U.S., an indication of the increasing globalization of biotech, says Bert Aldridge, North American marketing and communications manager, New Zealand Trade & Enterprise.

Sexually Transmitted Diseases

New Zealand’s Industrial Research (IRL, Auckland) and Melbourne-based Starpharma received NZ$945,000 (about US$652,000 currently) in ANZBPF funding to develop carbohydrate (glyco-) dendrimer drugs for sexually transmitted diseases (STDs).

IRL is one of nine stand-alone companies under the aegis of the NZ government’s Crown Research Institute. Like the other eight, IRL is government-owned but competes with other companies for research funds, notes Richard Furneaux, Ph.D., carbohydrate chemistry technology platform manager at IRL.

IRL’s manufacturing unit, GlycoSyn, is providing expertise in drug design, synthesis, and manufacturing for Starpharma’s topical antiviral compound SPL-7013, VivaGel, which is active against multiple STDs, including HIV, chlamydia, herpes simplex virus, hepatitis B, and human papilloma virus, according to the company.

VivaGel is a a water-based dendrimer microbicide. Dendrimers are large, complex biocompatible molecules built piece by piece, tiny balls with a dense network of branches that present a polyvalent array to receptors, explains Dr. Furneaux.

“VivaGel’s dendrimers are like microscopic soccer balls with many hooks’ that work like Velcro,” he says.

The challenge in developing dendrimers as drugs is producing a single chemical entity, which is what IRL’s expertise can accomplish, adds Dr. Furneaux.

Starpharma has completed a Phase I trial with VivaGel and is in the process of planning for expanded safety trials to begin next year. As the owner of only two cGMP facilities in New Zealand for small molecule drug production, IRL is looking to partner with other Australian and New Zealand companies to produce some of the other 80 small molecule drugs in development in both countries, Dr. Furneaux says.

IRL is also collaborating with the Albert Einstein School of Medicine (New York City) and BioCryst Pharmaceuticals (Birmingham, AL) for carbohydrate drug development.

Melbourne’s Metabolic Pharmaceuticals and Auckland’s Neuren Pharmaceuticals are using their NZ$635,000 (US$585,000) ANZBPF award to develop a drug for spinal cord injury or stroke, and multiple sclerosis.

Separately, Metabolic is developing drugs, neuroactive peptides, for obesity and pain, and Neuren is working on therapeutics for neuroprotection and metabolic disorders. Their collaboration focuses on developing a class of Neuren’s neuroregenerative peptides (NRPs), to treat peripheral neuropathy, motor neuron disease, and brain and nerve repair following spinal cord injury.

“There are substantial synergies between our two companies,” says Neuren CEO David Clarke. “We have complementary experience in protein chemistry and neural peptides, and overlapping interest and experience in growth hormone biology.”

The NRPs are geared to markets other than those targeted by Neuren’s Glypromate, which is in Phase II development for cardioprotection during coronary artery bypass graft surgery, and NNZ-566, a Glypromate analog in development for traumatic brain injury, and Metabolics’ ACV-1 for neuropathic pain.

In August, Neuren announced positive results with NNZ-2566, in testing by the U.S. Department of Defense at the Walter Reed Army Institute of Research (Bethesda, MD). “Concerning collaborations, everyone thinks it’s about science and business development,” says Clarke. “But it’s just as much about people.” The collaboration with Metabolic works well because of a similarity in cultures and an ability to compromise, he notes.

Crops and Pastures

NZ’s Wrightson (Wellington), the country’s oldest and largest agricultural firm and private agricultural research group, and Australia’s Molecular Plant Breeding Cooperative Research Centre (MPB, Melbourne) received NZ$3 million funding from the ANZBPF to develop and commercialize improved varieties of ryegrass and tall fescue for agriculture in temperate regions.

MPB’s mandate is to ensure the competitiveness of the Australian crop and pasture industries, worth about $18 billion per year.

“The project has the potential to create a significant increase in feed quality and animal production from pasture, reaping substantial economic benefits for pastoral farmers,” Wrightson CEO Barry Brook says.

“Our collaboration allows us to tap into MPB’s expertise to enable us to produce a plant that is more nutritious and more easily digestiblehigher levels of fructose and lower levels of lignan using genes from these plants, not foreign genes,” says general manager, research and business development, Warwick Green.

In addition, less methane (greenhouse gas), an environmental concern for New Zealand, should be produced with more efficient digestion, according to Wrightson.

“We hope there will be more opportunities going forward for other areas of collaboration with Australia,” Green notes.

The deal is also significant for Wrightson because it will enable the company to further expand its large seed business into South America, Green says.

“Different countries have different climates and agricultural practices, and therefore there are different needs for grass species. In temperate pastoral regions in North and South America, tall fescue is widely used, while ryegrass is more important in New Zealand and Europe.”

At the start of his career, in the early 1980s, the idea that New Zealand could become a player in pharmaceutical drug development was considered laughable, confesses Dr. Furneaux. “But now we’re standing where the spotlight is shining,” he asserts.

“Often the closest neighbors become the fiercest competitors, like on the ballfield, but in biotech, there’s no reason we can’t collaborate,” Dr. Furneaux adds.

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