The Kill Bills

By Vincent Heeringa, May 31, 2007 @ 11 pm

Idealog May/June 2007, page 50. Photographs by Godfrey Boehnke

Two New Zealand scientists—both called Bill—are pioneering a radical cancer treatment. In the process they’re rewriting the way New Zealand science does business. Idealog reports on the multimillion-dollar progress of Proacta 

The day I meet Bill Wilson, he’s got a gash on his head. “A tussle with a recalcitrant pine tree,” he says flatly. “Don’t ask.”

But I do ask. He’s much too laconic to be taken at face value. The tree, it turns out, is worse off, thanks to Wilson and his chainsaw.

Wilson’s garden is one thing. Wait till you see what he can do to a cancerous tumour.

Together with another softly-spoken scientist, Bill Denny, Wilson is becoming the scientific equivalent of a smart bomber. Leading a team at the Auckland Cancer Society Research Centre (ACSRC), the two Bills are pioneering a novel cancer treatment based on a simple idea. Solid tumours typically have few blood vessels, which means they are hypoxic (oxygen-deprived). Imagine, asked one Bill of the other in the early 1980s, if a cancer drug could be activated only under hypoxic conditions.

Twenty-odd years later, the Bills have their invention, the imaginatively-named PR-104. Unlike conventional chemotherapies that blast everything in their path, PR-104 is activated only when it comes into contact with the hypoxic tumour. Think of it like a smart bomb, wiping out an Al-Qaeda hideout and yet leaving the rest of Kabul intact.

At least, that’s the theory.

In the war on cancer, what happens in the lab is not necessarily what happens in the field.

But that’s where the Kill Bills’ story gets interesting. The science behind PR-104 is not new, but it is problematic. Few researchers have managed to make hypoxia-activated drugs work because parts of the body are moderately hypoxic, such as the retina, bone marrow and testes. Other scientists who tried the approach have left lab subjects blind, impotent or dead.

The work at the ACSRC is different. The science is very thorough and, so far, trials suggest the technology has overcome these awful side effects. The results are so compelling they have caught the attention of some of the world’s leading pharmaceutical investors. In 2004, Proacta, the company formed by the University of Auckland to commercialise the research, successfully raised US$12 million to take the drug into phase one clinical trials. This was an unusually large amount for a Kiwi biotech company to attract. It gets better. The success of the trials and other milestones met by the company, such as hiring top-notch biotech executive Paul Cossum as chief executive, led to a second investment round in March this year. It raised a pleasing US$35 million which will be used to run phase two clinical trials on PR-104 and identify new candidates for the company’s drug ‘pipeline’.

“This time, however, the Bills’ steely resolve concerns not just the science but the business model as well.”

The investment in Proacta is by far the largest made to date in any one Kiwi biotech firm. And while the investors probably mean little to you and me, they are a who’s—who of San Francisco biotech—Clarus Ventures, Delphi Ventures, Alta Partners and Genentech—and Melbourne’s GBS Ventures.

Chief executive Cossum says the success of the last funding round and his own decision to join the company came down to one thing. “It’s the cleverness of the idea, followed by thoroughness of the science,” he says. “I’ve been in biotech for over 20 years and I’d say that I’ve never come across science that is so well done.”

Bill Denny’s pokey office in the Auckland Medical School is just the sort of inauspicious place to start a revolution. Old veneer furniture sits on standard-issue Ministry of Education carpet and dusty textbooks line the shelves.

Someone’s read them at some stage. Between them, Denny the chemist, biologist Wilson and their Stanford-based colleagues Amato Giaccia and Martin Brown can claim more than 1,000 academic papers and 85 patents.

Over the years, no fewer than seven cancer drugs have originated from the ACSRC, four directly from Denny. In each case they have been sold or produced under contract for other labs or pharmaceutical companies to develop into commercial drugs. This time, however, the Bills’ steely resolve concerns not just the science but the business model as well. Along with the other New Zealand shareholders in Proacta, they’re determined to retain New Zealand part-ownership and involvement as far down the commercialisation track as possible. Three Kiwi companies have invested, including the government, through the New Zealand Venture Invesment Fund. Wellington-based venture capital firm No 8 Ventures has invested US$3 million.

Jenny Morel, No 8’s managing director, says it was an easy decision to support the second round of funding because the company has fulfilled all its promises. “It was a much harder decision to invest the first time around. But once you decide that hypoxia matters in solid tumours then it’s an easy decision to back the Bills. They’ve got a huge patent portfolio in this area and their science is very, very good.”

The Trial

Commercialising a therapeutic drug is expensive. Here’s the path Proacta must follow to reach the end of clinical trials

Milestone	Millions
Identify drug candidate and submit for phase one FDA trials	US$12 million private investment money; about NZ$15 million public research
Build company capability; identify next set of drug candidates; run phase two trials	US$35 million
Enter next candidate for phase one trial; run phase three trial involving several hundred cancer patients	US$100 million

Proacta’s success so far is exciting. Even more gratifying is what it means for those labouring to create an international class biotech sector. Denny and Wilson say they don’t think of themselves as pioneers. “But I suppose if you put it like that, 20 years ago there was nothing like what we have now in terms of knowledge and investment.”

Morel goes further, claiming that Proacta is at the forefront of an emerging industry. “There’s so much that’s happening alongside Proacta,” she says. “We’re now running numerous clinical trials in New Zealand which in itself creates capability and infrastructure. There are new scientists being brought in—it’s not just the Bills. They now have a whole team of post-grads and a really top-class scientist called Adam Patterson. Then there’s the fact that the scientists are being deeply involved in the business and that we now have a small cluster of companies like Proacta, such as Antipodean and Protemix. It’s all building capability and links that we didn’t have even five years ago.”

This is welcome news for an industry that is struggling to live up to its own hype. Biotech has long been a favourite of the government’s economic development programme, but spectacular successes are hard to find.

That could be why the announcement of the US$35 million in March was greeted by the government with such enthusiasm. Economic Development Minister Trevor Mallard says the fact that New Zealand science has attracted significant funding from such high-level US investors is an enormous endorsement. “It shows that New Zealand can take our biotechnology and medical science ideas and convert them into global success … It is also very satisfying to see that the public investment in Proacta, via the New Zealand Venture Investment Fund, is also paying off, with this strong endorsement by the international commercial community.”

From here it gets harder. Cossum says phase three clinical trials will require a US$100 million investment. It’s unlikely much of that sum, if any, will be found in New Zealand. Already the head office has shifted to San Diego to front the investment rounds. Just how long New Zealand can maintain active links to Proacta will be interesting to watch.

A lot is riding on its success. Not least, the tumour victims awaiting the arrival of a Denny-Wilson smart bomb. Here’s hoping.