20 March 2006

Soon it may be possible to treat cancer patients with a new targeted stealth drug – PR-104. The compound is currently undergoing human clinical trials at Waikato Hospital in New Zealand, and the Peter MacCallum Cancer Centre in Melbourne.

The new drug was developed in New Zealand by Proacta Therapeutics, and differs significantly from any other cancer treatments currently on the market. The Chief Executive of Proacta, Dr Paul Cossum, says that PR-104 is designed to be injected intravenously and only activated once inside a tumour, killing only cancer cells and leaving healthy cells unaffected.

“This is in stark contrast to current chemotherapies, which kill any fast-growing cells including gut lining, hair follicles and bone marrow. In addition, preclinical studies suggest that PR-104 could be more efficient, reaching parts of tumours previously inaccessible for other treatments. This could have a significant impact on the percentage of relapses in cancer patients with these types of tumour.”

PR-104 is part of a new generation of cancer drugs known as ‘prodrugs’. Prodrugs are compounds that remain inert in the body until activated within a specific location, giving them the potential to kill cancer cells while leaving normal cells and tissues untouched. The triggers to activate PR-104 should be present in solid tumours because of a unique state called hypoxia or a lack of oxygen. This occurs when the tumour grows so fast or large that it outstrips the development of its own blood supply.

The company is also developing other compounds using the same delivery method as PR-104.

“We estimate that more than 65 percent of the 10 million people who are diagnosed with cancer each year have these types of tumour. Hypoxia is known to increase malignancy, and hypoxic regions of tumours are resistant to current radiation and chemotherapeutic treatments,” says Dr Cossum.

PR-104 is the brainchild of Proacta’s founding scientists, Professors Bill Denny and Bill Wilson at the Auckland Cancer Society Research Centre (ACSRC) at the University of Auckland in New Zealand, and Professors Martin Brown and Amato Giacca at Stanford University in the United States. The four are world-leading authorities in the field of tumour hypoxia. The underlying research for the new drugs by Professors Denny and Wilson spans some 15 years. Today, the PR-104 and related research programmes involve approximately 35 scientists at the University of Auckland.

So far, the ACSRC team has developed two methods of triggering anti-cancer drugs using hypoxic activation. The first and most advanced method is BEP (bioreductive enzyme prodrug) where, for example, PR-104 is activated by enzymes only in the presence of low oxygen concentrations. Where oxygen is more abundant, as in most normal tissue, the drug remains inert and harmless. “The enzymes trigger the PR-104 to become a sort of molecular glue that binds the tumour’s DNA, effectively stopping replication,” says Dr Cossum.

The second method, RAP (radiation activated prodrug), uses targeted radiation to activate the prodrug. Free radicals produced by the radiation react only in hypoxic conditions with the anti-cancer compound to create a reactive cytotoxin.
Proacta now holds exclusive worldwide rights to 25 patent families, across more than nine chemical families. Ongoing development of the portfolio is supported by significant grant funding.

In mid-2004, Proacta raised funding of US$8 million from an international syndicate led by GBS Venture Partners, Australia. Other members of the syndicate are Genentech Inc and Roche, based in the United States and Switzerland respectively, and No 8 Ventures and Endeavour Capital in New Zealand. The company has also received grants from Technology New Zealand and New Zealand Trade and Enterprise.

In December 2005, Alta Partners, a San Francisco-based life science VC firm, invested a further US$4 million in Proacta’s Phase I clinical trials programme. The company plans to seek further funding when it begins wider clinical trials in cancer patients towards the end of 2006.

Proacta Therapeutics is a wholly owned subsidiary of Proacta Inc, a Delaware incorporated company headquartered in California. Dr Cossum says the United States ownership of the company allows it access to significant amounts of venture capital, which will make it more likely that Proacta will succeed.

For further information about Proacta Therapeutics or PR-104, please see the company’s website at www.proactatherapeutics.com.