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Profile: Pathway Therapeutics Inc

Pathway Therapeutics is a spin-out pharmaceutical company established in New Zealand by Maurice Wilkins Centre principal investigators Professor Bill Denny and Professor Peter Shepherd.

Establishing the company

In 2008 Professors Bill Denny and Peter Shepherd and their co-invesitgators had made exciting discoveries of new inhibitors of phosphatidylinositol-3-kinase (PI3K) and mTOR that had the potential to treat cancer and inflammatory disease.

However significant extra funding, not available from research granting agencies, was required to develop these drugs through to the stage where they could be trialled in humans. So the pair worked with the University of Auckland’s commercialisation arm, Auckland Uniservices Ltd, to establish a vehicle to do this, and the spin-out biotech company Pathway Therapeutics was established in 2008.

The formation of the company attracted more than $12 million in venture capital into New Zealand from overseas and several million of this was spent in Maurice Wilkins Centre laboratories in the further development of these drugs. Progress was rapid and just three years later the United States Food and Drug Administration accepted an Investigational New Drug application for its drug candidate PWT33597, a dual PI3K/mTOR inhibitor, allowing the company to commence early phase clinical testing.

The company subsequently moved to San Francisco to be closer to sources of United States investment, at which stage most development work moved to the United States. This is an example of how the Maurice Wilkins Centre looks to develop its science towards better clinical and economic outcomes.

Complementary expertise

The company sprang directly from a project initiated in the Maurice Wilkins Centre in 2006, which brought Professors Denny and Shepherd together. Bill is a medicinal chemist who co-directs the Auckland Cancer Society Research Centre while Peter is an expert in cell signalling in the Department of Molecular Medicine & Pathology. The project saw them working with medicinal chemist and fellow Maurice Wilkins Centre investigator Associate Professor Gordon Rewcastle. Later, structure based design expertise from Dr Jack Flanagan and pharmacology and biology expertise from Drs Stephen Jamieson and Christina Buchanan was utilised, demonstrating how the Centre’s breadth of expertise allows multidisciplinary teams to be built very rapidly.

Through working together on an initial Health Research Council of New Zealand* project grant, the researchers created new classes of drugs to inhibit PI3K, a family of four signalling proteins (alpha, beta, gamma and delta) that controls critical cell processes, from growth and proliferation to metabolism and survival; one of these classes was taken up by Pathway.

Abnormal PI3K activity is implicated in several diseases, including cancer, and PI3K inhibition is a “hot topic” in international cancer research. Mutations in PI3K alpha are some of the most common genetic abnormalities in cancer, with errors or multiple copies of the gene found in a wide range of tumour types such as breast, colon, and lung cancers.

(*HRC, the agency responsible for managing the New Zealand Government’s investment in health research)

Academic-commercial synergy

The work, which sprang from a Maurice Wilkins Centre-initiated collaboration, has grown into a multi-disciplinary programme of commercially-funded drug research and development, which has received subsequent funding from both the HRC and the Cancer Society, culminating in a 5-year HRC programme grant awarded in 2013

“Our work demonstrates how commercially-focused research can synergise with traditional scientific outcomes,” says Peter. “The work began with an HRC grant, moved into commercially-supported drug development, and has now moved back to grant-supported research, enabled substantially by the commercial experience. Drug development is an inherently high-risk enterprise, but we learn more from each endeavour. This work has to date generated 18 scientific papers and 4 patent applications, with many more to come.”

The Maurice Wilkins Centre has continued to support this area of research by providing long-term salary assistance for two key scientists in the PI3K inhibitor programme, by support for structure based drug design capability and by purchasing a computer-controlled robot critical for screening drug candidates. The Centre is now supporting international linkages that will seek other leads to drugs that will target these enzymes by building a collaboration with the Chinese National Centre for Drug Screening in Shanghai.