For Peter Gluckman, science has always been about making a difference. Back in the 1980s, Gluckman — a University of Auckland endocrinologist and one of New Zealand’s most distinguished scientists — was exploring brain damage in newborn babies. He was among the first researchers to unlock a curious puzzle of the human brain: after a devastating event like a stroke or head injury, brain cells take hours, sometimes even days to die.

Gluckman became interested in developing a treatment that would act during this ‘therapeutic window’ to halt the slow march of dying cells. In this case, making a difference meant making enough money to shepherd a drug all the way through development and trials to an international market. Gluckman knew he needed to find a place for his science in the commercial world.

His pioneering research laid the intellectual foundation for one of New Zealand’s most promising biotechnology companies, Neuren Pharmaceuticals. Neuren sports a portfolio of drugs aimed at exploiting the therapeutic window for acute events like stroke and head injury, but also chronic conditions like Alzheimers and Parkinson’s disease.

But neuroprotection is one of the riskier games in biotech, analysts say, especially for applications like stroke or traumatic brain injury. The last 20 years have seen numerous drugs that work in lab rats but not people, drugs that might work provided you had the foresight to take them before an unpredictable event, and promising compounds squandered on flawed trials. What was once touted as the next lucrative pharmaceutical frontier is now strewn with expensive failures.

Neuren has responded to these financial and scientific challenges by transforming itself into an increasingly global entity. Its strategy has been to find partners in its target market who provide expertise, exposure, and shoulder costly parts of the development process. In fact, labelling Neuren as a ‘New Zealand company’ is almost missing the point. Neuren is Auckland-based, listed on the Australian stock exchange, with a big pharma shareholder, has offices in Sydney and Maryland, and consultants and research partners across the UK, Australia and the US. CEO David Clarke likes to call Neuren a “virtual company”, because you’ll rarely find his core team in the same country at the same time.

Neuren is still years from putting a product on shelves, but its strategy is yielding encouraging results. In April, Neuren sought approval to launch phase II clinical trials for its lead product, Glypromate. Instead, the US Food and Drug Administration announced that if Neuren successfully completed a small phase IIa trial, it could proceed straight to phase III, the final round of human trials. Neuren estimates the decision will save it two years and A$6 million (NZ$6,395,650). One month later, the US Army expanded a contract to undertake pre-clinical testing on Neuren’s second compound, NNZ–2566. Not bad for a company with 18 employees. The trick, Clarke believes, is not to think narrowly as a ‘New Zealand company’, but to build the necessary bridges to take homegrown science to the world marketplace.

GPE becomes Glypromate
Neuren’s scientific journey began with GPE, a small mole-cule derived from Insulin-like Growth Factor 1 (IGF-1), a naturally occurring protein that encourages cell growth. Gluckman became intrigued by GPE in the 1980s after Swedish researchers noticed that it seemed to exert positive influences on brain cells. Over the next decade, Gluckman set out to find just what GPE could do.

At the same time, Gluckman was searching for an entrepreneurial platform for his work. In 1995, he became the founding scientist of NeuronZ, a subsidiary of Uni-Services, the University of Auckland’s commercial arm. (Later, in 2001, Gluckman’s work on growth hormones launched EndocrinZ, another UniServices spin-off backed by Pharmacia and Upjohn, now Pfizer.) Over the next five years, NeuronZ became increasingly excited by GPE’s ability to prevent cognitive decline in rats and sheep.

Coincidentally, Pharmacia owned the rights to GPE, but was not investigating its neuroprotective qualities. NeuronZ acquired the patent for GPE as a neuroprotective agent, and gave it the catchier name of Glypromate.

Gluckman and his team believed they were onto something good. For starters, Glypromate seemed to benefit more than one cell type: neurons and glial cells. Because IGF-1 exists naturally in the brain, Glypromate could be safely given in strong doses. But perhaps most importantly, Glypromate appeared to work for up to 11 hours after a brain injury occurs.

In 2004, NeuronZ and EndocrinZ merged to form Neuren. Clarke had a clear vision from the start: “start getting partnerships in the US as early as possible”.

Neuren followed the expert prescription for small biotech companies isolated from major markets: exploit your science without shelling out on infrastructure. Neuren holds first rights to intellectual property from the University of Auckland’s Liggins Institute, eliminating the need to build expensive labs or hire dozens of scientists. It already had one international stakeholder in Pfizer, for which it also performs contract research. Building on its researchers’ academic networks, Neuren entered collaborations with the University of Texas Medical School in Houston, North Carolina’s Duke University, and also with Metabolic Pharmaceuticals in Melbourne.

But perhaps one of Neuren’s most crucial early steps was to open a US office headed by Larry Glass, an American scientist and former CEO of a company with research links to the US Army. Neuren set up shop in Bethesda, Maryland, near the FDA, the National Institutes of Health, and its most high-profile research partner, the Walter Reed Army Institute of Research (WRAIR).

The value of Neuren’s partnership strategy can be glimpsed in a trip to WRAIR, an imposing brick complex nestled in a leafy Maryland neighbourhood near Washington, DC. Its prestige is almost palpable. Black-and-white photographs of quaintly moustachioed scientists who developed its famous malaria vaccine line the lobby walls; Eisenhower died in the stately main hospital several miles away.
WRAIR runs a programme on neuroprotective treatments for traumatic brain injury, an increasingly urgent concern for the army. The weapon of choice for America’s adversaries in Iraq is explosives, explains Dr Frank Tortella, the head of WRAIR’s applied neurobiology department. In previous conflicts, soldiers rarely survived close-range explosions. Now, sophisticated body armour protects them from dying, but not from the shock waves triggered by a blast. An army study found that two-thirds of soldiers returning from Iraq display the insidious symptoms of brain injury: abrupt mood swings, an inability to form coherent sentences, or debilitating depression.

Because WRAIR doesn’t develop its own drugs, Tortella’s mission is to ‘cherry-pick’ from the private sector. The arrangement gives WRAIR access to promising products, while its private partners benefit from sophisticated brain models developed by Tortella’s team.

Tortella hadn’t heard of Neuren until Glass approached him. He was impressed with Neuren’s second compound, NNZ–2566, a more potent analogue of Glypromate. Under an agreement formed in May 2004 and expanded this July, Walter Reed will support half the pre-clinical trials for NNZ–2566, while Neuren retains commercial rights to its non-military uses (the US Army estimates that 1.5 million Americans suffer traumatic brain injuries each year). “It’s a two-way street,” says Tortella. “We need them and they need us.”