As a small country, New Zealand has always needed to punch above its weight to be noticed, whether in sports, entertainment or science. With its rugby team the All Blacks recent winners of the Rugby World Cup, and the global success of the "Lord of the Rings" and "The Hobbit" film trilogies, there's another area where New Zealand is overachieving considering its population of just 4 million: cancer immunotherapy.

The country produces more than its fair share of specialists in this field. "In New Zealand, look under every rock and you'll find an immunologist," explained Richard Furneaux, director of Wellington's Ferrier Research Institute, a carbohydrate chemistry-based drug and materials development facility, also with a strong focus on immunology.

New Zealand's first and most prominent biotechnology company, Genesis Research and Development Corp. Ltd., had its roots in immunology. A pioneering venture in its heyday in the late 1990s, the company attracted top international immunology talent to New Zealand, until several high-profile failures at phase II led to funds drying up and the company suspending operations in 2010. Many of the firm's scientists remained in New Zealand going on to form companies of their own that today make up the backbone of the industry, including Innate Immunotherapeutics Ltd., developing a drug for multiple sclerosis, among others, and Living Cell Technologies Ltd., a cell implant company focused on treatments for Parkinson's disease and diabetes. Both companies are based in Auckland.

Another key resource is Wellington's Malaghan Institute of Medical Research, where 80 researchers and support staff are singularly focused on immunology. With the Malaghan Institute and the Ferrier Institute, and strong cancer immunotherapy proficiency in the local universities of Otago, Wellington and Auckland, New Zealand has been quietly amassing resources in this area over a number of years. And in the last six months in particular two new entities have stood up aiming to take this expertise to the next level: commercialization.

The first is Wellington-based Avalia Immunotherapies, formed earlier this year on the back of a long-term government-funded research program led by Gavin Painter from Ferrier along with Ian Hermans from the Malaghan Institute. With a immunotherapeutic cancer vaccine platform technology, the company aims to focus initially on solid tumor cancers, such as melanoma or prostate cancer.

Avalia's technology incorporates an activation mechanism different to almost every other immunotherapy approach currently available or under development. The key point of difference is the specially designed molecules that simultaneously deliver components into patient's dendritic cells, part of which can then activate natural killer (NK) T-cells. The activation of the NK T-cell then feeds back and activates the dendritic cell. In most other vaccines the adjuvant component activates antigen-presenting cells triggering pattern recognition receptor molecules that exist on the cell surface.

"There are some great vaccines that use this approach. Our approach is different however and uses another immune cell to do that same process," said Painter, chief technology officer at Avalia, adding that an Avalia immunotherapy product would be complimentary to other companies' products.

"In the immunotherapy space, it's starting to become clear that every therapy is a component of an immunotherapy toolbox," said Painter.

Fifty percent of the company is currently jointly held by Viclink, the commercialization arm of Wellington's Victoria University, and Malaghan. Additional investment comes from VC Powerhouse Ventures, the New Zealand Venture Investment Fund, and Malcorp Biodiscoveries Ltd. "We have enough money in place to complete a reasonable portion of our preclinical plans. Our aim is to have the preclinical candidate in an indication defined by February or March [of 2016]," Painter said. And once defined, remaining data would be completed over the next six months. With an investment roadshow set for February, March is the goal for receiving follow-on funding. "We'll do a small phase I after that," added Painter.

Avalia has on board one of the world's leading experts in the field of NK T-cells, Ian Hermans as chief scientific officer; he's also an associate professor at the Malaghan Institute. While working at the UK's Oxford University in 2004, Hermans made the seminal discovery that NK T-cells could be used as a dendritic cell trigger for immunotherapeutic applications.

"There were three or four papers that came out around the world at the same time on this discovery, and Hermans was named on two of them. Some of this research is what we are keying into at Avalia," explained Painter.

The other project recently emerging from New Zealand's immuno-oncology strengths is SAPVax (standing for Self-Adjuvanting Peptide Vaccines), an as-yet unincorporated entity coming out of Auckland University led by researchers Rod Dunbar and Margaret Brimble. Dunbar is also the director of the Maurice Wilkins Center, a nationwide Auckland-headquartered drug discovery research network. Currently still at the investor-seeking stage, university tech transfer unit Auckland Uniservices owns the entity pending a modest NZ$8 million (US$5.5 million) initial outside investment.

"We've already identified our first clinical candidate, and we've shown we can manufacture it under GMP. Progression to clinical trial is likely to be very rapid after that initial investment. Our strategy has been to select and prioritize a first product with a second close behind, while remaining open to use of our technology platform to target a wide range of indications." As its first indication, SAPVax will concentrate on nasopharyngeal cancer, according to Dunbar.

Similar to Avalia, SAPVax has developed a technology platform to produce its immunotherapy product, in SAPVax's case one that includes both the peptide and the adjuvant.

"Our adjuvant technology is a clip-on technology that enables very simple synthesis of the final molecule in a standard peptide synthesis facility. In fact the chemistry is designed specifically to work with standard solid phase peptide synthesis (SPPS) in order to enable rapid, flexible manufacturing of many different adjuvanted peptides. And our unique chemistry was published shortly after we patented it," said Dunbar.

International recognition of Auckland University's immuno-oncology expertise is growing. On Dec. 9 a research collaboration was signed between the university and the Guangzhou Institutes of Biomedicine and Health, of Guangzhou, China, with the scope of the agreement covering immunotherapy, but also stem cell therapy, regenerative medicine and metabolic diseases. The agreement is the first of its type for a New Zealand university in China.

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