In an exciting new development NewSouth Innovations Pty Limited (NSi), the commercial arm of the University of New South Wales, has negotiated a collaboration deal with Benitec Limited to support a proof-of-concept study for the development of a Beta III tubulin RNA interference (RNAi) therapeutic for lung cancer. Benitec, an Australian biotechnology company and one of the pioneers of RNAi technology, has rights to commercialise the Michael Graham and Peter Waterhouse patent estates. As part of the collaboration deal Benitec signed a term sheet with NSi securing an option to licence patent applications arising from the Children’s Cancer Institute Australia for Medical Research (CCIA) on Beta III-tubulin as a target for knock down using RNA interference.

A/Professor Maria Kavallaris, Head of Pharmacoproteomics Program at CCIA has long been interested in the role of the tubulin/microtubulin system in mediating tumour resistance to chemotherapy. Two of the most clinically valuable classes of anti-cancer agents target the tubulin system: vinca alkaloids and taxanes. Build-up of resistance to these classes of drugs in cancer patients is associated with aberrant expression of Beta-tubulin isotypes in tumours, lending weight to the thesis that Beta-tubulin isotype expression has prognostic and theranostic value in cancer treatment.

Maria’s team showed that targeting specific Beta-tubulin isotypes using RNAi sensitises cells to the anti-cancer effects of tubulin binding agents and DNA damaging agents, with different isotypes mediating selective responses to a range of clinically relevant drugs.

Since 2006, NSi has been working with the CCIA researchers A/Professor Maria Kavallaris and Drs Pei Pei Gan (PhD Scholar) and Joshua McCarroll (Research Officer) to protect and commercialise the intellectual property arising from this research program. In 2007 NSi partnered with a Californian biotech specialising in clinical isonostic assays based on proprietary technology in capillary electrophoresis to develop the diagnostic application.

In a serendipitous study in 2008, the CCIA team found that targeting Beta-III tubulin alone via vector expressed RNA interference mechanisms inhibited tumourigenesis in mice bearing H460 non-small cell lung cancer (NSCLC) clones, while targeting Beta-II- or Beta-IV-tubulin alone did not affect tumour growth.

“A/Professor Kavallaris showed that not only did turning off Beta III-tubulin enhance the sensitivity to drugs which bind tubulin, but it also enhanced the sensitivity of drugs which bind to DNA. This significantly extends the potential of the RNAi approach to act as an adjuvant therapy for a range of chemotherapeutic drugs. This should be of interest to potential pharmaceutical company collaborators” said Sue MacLeman, Chief Executive Officer, Benitec Limited.

The initial proof of concept work in vitro and in vivo has already been completed. Under the agreement, the CCIA team and Benitec will carry out further studies aimed at optimising the effect in vitro utilising Benitec’s patented technology and targeting the constructs to lung tissue in vivo, with the aim of taking this to a Phase 1 clinical trial as soon as possible.

“We are very pleased to have identified two commercial partners for this patent family, one for the diagnostic application and now one for the therapeutic application. Advancing the two programs in parallel will strengthen the clinical development of the Beta III RNAi therapeutic” said Laura Issa, Commercialisation Manager – Faculty of Medicine, NSi.

Lung cancer is the leading form of cancer worldwide in terms of incidence and mortality. NSCLC accounts for more than 80% of all lung cancers. First line therapy for NSCLC includes a combination of a tubulin-binding agent (TBA) (taxanes, vinca alkaloids) and DNA-damaging agents (platinums - cisplatin, carboplatin; doxorubicin; etoposide). The prognosis for patients with advanced NSCLC however remains dismal as the tumours rapidly become resistant to these drugs. Upregulation of Beta III-tubulin is associated with clinical resistance to these drugs, which is what makes the Benitec-CCIA approach so promising.

“This is a very exciting development and demonstrates how research conducted at the laboratory bench can be translated into better outcomes for patients,” said A/Professor Kavallaris.

NewSouth Innovations is committed to working with the Faculty to identify and develop new opportunities for technology transfer. Researchers are encouraged to contact Laura Issa at NSi at any time to discuss potential IP and commercialisation opportunities at l.issa@nsinnovations.com.au or 9385 5592.