Second New Zealand anticancer “stealth” drug targeted for clinical development
4 August 2011
A second anticancer “stealth” drug designed by New Zealand scientists has been targeted for clinical development under a collaborative agreement between Proacta Incorporated (San Diego) and Yakult Honsha Co., Ltd. (Tokyo).
For an update on this story in 2012 see also: Local cancer drug approved for first clinical trial in United States and New Zealand
PR610 belongs to an exciting new class of hypoxia-activated pro-drugs for the treatment of cancer, designed by Dr Jeff Smaill and Dr Adam Patterson from the Auckland Cancer Society Research Centre (ACSRC) and Maurice Wilkins Centre for Molecular Biodiscovery.
“The agreement to develop PR610 to clinical trial is another big step for the ACSRC. It is exciting to see it join the series of new drugs that have come out of the Centre. Congratulations to Drs Smaill and Patterson, and all who have worked on this project” says Professor Bill Denny, co-Director of the ACSRC at The University of Auckland and a Maurice Wilkins Centre principal investigator.
“All New Zealanders have an interest in cancer drug discovery and development. We should take pride in seeing such a breakthrough occurring and being led by our local scientific community” says John Loof, CEO of the Cancer Society, Auckland.
PR610 it is part of a pipeline of hypoxia-activated pro-drugs licensed to pharmaceutical company Proacta by The University of Auckland. Proacta entered into the collaboration agreement granting Yakult research, development and commercialisation rights to the first agent in its class, PR509, in Japan in February 2011.
Based on compelling preclinical data for PR610, Proacta and Yakult have announced recently that they will expand their existing agreement to include PR610.
PR509 and PR610 are hypoxia-activated irreversible multi-kinase inhibitors. The pro-drugs selectively target the low-oxygen (hypoxic) conditions found in many solid tumours. Since they are inactive in normal, healthy tissues, they avoid the problem of indiscriminate toxicity associated with standard cancer treatments.
“Our scientists are finding innovative and exciting new ways to target cancer by exploiting the abnormal biological environment created by tumours,” says Professor Rod Dunbar, Director of the Maurice Wilkins Centre. “The agreement to develop PR610 is yet another example of the excellence of drug discovery in New Zealand and its potential to benefit cancer patients worldwide.”
Both PR509 and PR610 have been targeted for development in non-small cell lung cancer that is resistant to established treatments. They are also likely to be evaluated in other cancers such as gastric, breast, and pancreatic cancer.
Auckland Cancer Society Research Centre (ACSRC)
The ACSRC was established in 1956 by the Auckland Cancer Society. Based in the Faculty of Medical and Health Sciences at The University of Auckland, the ACSRC is regarded internationally as one of the world's leading anti-cancer drug development laboratories. The Centre houses over 80 scientists dedicated to discovering new treatments to help improve the lives of patients diagnosed with cancer.
PR509/PR610 research team
A multidisciplinary team of scientists at the ACRSC collaborated to discover and develop PR509 and PR610. Medicinal chemistry was led by Dr Jeff Smaill, with drug design and synthesis performed by Drs Guo-Liang Lu, Ho Lee and Amir Ashoorzadeh. Cancer biology was led by Dr Adam Patterson with Drs Maria Abbattista, Steve Jamieson and Jagdish Jaiswal supporting the biological evaluation of drug analogues. Radiation chemistry was performed by Associate Professor Robert Anderson and Dr Andrej Maroz. Technical support was provided by a large team including Kendall Carlin, Annie Hsu, Sisira Kumara, Sunali Mehta, Alexandra Mowday, Michelle Puryer, Denis Simonov, Sophie Syddall, Aaron Thompson and Wouter Van Leeuwen. Drs Jeff Smaill and Adam Patterson and Professor Bill Denny are all Maurice Wilkins Centre investigators.
Proacta is a San Diego based biotechnology company dedicated to the development and commercialization of hypoxia-activated oncology drugs. Proacta is currently conducting a phase II study of PR104, a hypoxia activated alkylator, in patients with relapsed or refractory leukaemia. In addition, Proacta has a pipeline of hypoxia-activated prodrugs for the treatment of cancer that are licensed from the University of Auckland in New Zealand.
Yakult is a leading Japanese company focused on the development and marketing of pharmaceuticals, foods, beverages, and cosmetics. With respect to its pharmaceutical business, Yakult has an emerging presence in oncology.