Profile: Proacta Inc
Proacta Inc. is a spin-out, clinical-stage pharmaceutical company founded in New Zealand by Maurice Wilkins Centre principal investigator Professor Bill Denny and associate investigator Professor Bill Wilson, both of the Auckland Cancer Society Research Centre (ACSRC), and Professors Martin Brown and Amato Giaccia from Stanford University. The company raised $US8 million in Series A Financing at its formation in 2004.
An entirely new way of treating cancer
The founding scientists are world authorities in the field of tumour hypoxia (abnormally low oxygen). Proacta, which was created based on their intellectual property, aims to find new ways to treat cancer using hypoxia-activated “prodrugs” that target cancer cells.
The prodrugs are administered in inactive form, and transform into powerful anticancer drugs only in the hypoxic conditions found in most solid tumours as a consequence of their disordered blood supply. High concentrations of the active drug can therefore be reached within tumours, while the prodrug remains dormant in healthy tissues, avoiding the collateral damage associated with standard chemotherapies.
This is an entirely new treatment approach for cancer.
Clinical trials in New Zealand and the United States
The first of Proacta’s prodrugs, PR-104, delivers a DNA crosslinking agent to tumours and was taken to clinical trials in New Zealand and the United States in 2006.
Subsequent Phase II trials, principally in the United States, in non-small-cell lung cancer, hepatoma and leukemia, did provide some responses, but these were not deemed sufficient to continue the drug’s development. Ongoing research by Maurice Wilkins Centre investigators at the ACSRC is focused on identifying biomarkers that can predict sensitivity to PR-104, which will be needed for resumption of clinical trials.
The first clinical trial of the second of Proacta’s prodrugs, called PR610, began in New Zealand and the United States in 2012. PR610 generates an inhibitor of the ErbB family of receptor tyrosine kinases in tumours and has remarkable tumour retention properties. PR610 represents the first of a new generation of “stealth” prodrugs able to target dynamic (or shifting) hypoxia, releasing its deadly payload over many days.
The current Phase I/II study is investigating suitable doses in patients with a range of solid tumours, while monitoring side-effects, blood levels and anti-tumour activity in patients with non-small cell lung cancer that has become resistant to standard treatment. Subsequent trials will evaluate the drug in other cancers.
Pipeline of anti-cancer drugs
PR610 is one of a series of hypoxia-activated prodrugs, invented by Associate Professor Adam Patterson and Dr Jeff Smaill from the ACSRC and Maurice Wilkins Centre, which has been licensed to Proacta. The company, which is now based in San Diego, has an agreement with Yakult Honsha Co Ltd (Tokyo) for research, development and commercialisation of PR610 in Japan.
The Maurice Wilkins Centre is proud that the founders of the company, and the scientists developing subsequent prodrugs in Proacta’s pipeline, are members of its network. The Centre has provided partial salary support for the research, which has also been supported by grants from the Foundation for Research, Science and Technology, Health Research Council of New Zealand, and Proacta.