Benitec Licenses “Hot Mouse”

MOUNTAIN VIEW, Calif.—To push the frontiers of diabetes and obesity treatments, the US-based headquarters of Australian RNAi specialist Benitec recently signed an exclusive licensing agreement with the Garvan Institute of Medical Research, based in Sydney, Australia. Under the terms of the license, Benitec has exclusive rights to any RNAi drugs resulting from the validation of Garvan's "hot mouse" technology as a model of human diabetes and obesity.

Benitec also entered into discussions to establish a collaboration with Garvan to develop the RNAi therapies. As Benitec CEO Sara Cunningham explains, the company pursued both the research collaboration and licensing agreement because the work is still in the discovery phase, and it will take additional collaborative effort to get from the identification of the hot mouse gene, c-Cbl, as a potential target for Type 2 diabetes and obesity to its validation.

"We will work closely with the Garvan over the coming year to assess if c-Cbl is truly a druggable target—can we actually suppress it in a mouse model in a clinically relevant manner," she says. "And does the suppression using RNAi result in a desirable phenotype? Meaning, is this a valid target for diabetes and obesity?

"The reason we've taken a license now is that we feel strongly that this has enormous potential and wanted to solidify our IP position, and thus our rights to commercialization, prior to the extensive target validation work ahead of us."

The hot mouse technology was developed by Dr. David James, professor at the Garvan Institute. According to Dr. James, the c-Cbl knockout mice have lived normally for 2 years (old age by human standards) but continue to display the glucose tolerance of young mice. Diminished glucose tolerance is one manifestation of Type 2 diabetes.

As he explains in a press release: "The unique aspect of this project is that we will focus on developing therapies that turn food into heat (energy) instead of storing it as fat."

Working with not-for-profit groups like the Garvan is becoming second nature to Benitec, following as it does on their HIV clinical trials collaborations with Los Angeles' City of Hope. Says Cunningham, this has been less of a strategic decision on their part and more a desire to capture opportunities as they present themselves. "City of Hope is unique by having the Center for Biomedicine and Genetics (CBG) on campus," she says. "The CBG is in essence a non-profit biotech—with business development, GMP manufacturing, QA/QC, and regulatory personnel. And by being located next to the General Clinical Research Center and the Bone Marrow Transplant unit, we will be able to do all of the manufacturing and clinical trials on their campus. We have been extremely fortunate in this partnership in that we can access their infrastructure, rather than having to duplicate it."

She adds that the Garvan deal had a similar element of serendipity, but in this case, Benitec will supply the infrastructure to close the translational research loop. "As we have grown in the past couple of years to being a full-fledged biotech in our own right, we can bring the commercialization instinct to a pre-eminent Australian institution," she explains. "Everyone in our US headquarters has extensive experience in developing and commercializing technologies in a start-up setting. The marriage of California biotech and Australian research is a powerful one and one we hope to extend to other institutions and biotechs in Australia."

The work will be distributed based on expertise. The Garvan has the hot mouse, so much of the animal modeling work will take place there. Benitec has expertise specifically in RNAi drug development, so it will do the sequence selection, validation in tissue culture, and mouse models, and transfer the ddRNAi vectors to the Garvan.

More generally, she is very excited about the prospects for RNAi-based therapeutics, a market that Frost & Sullivan last year proposed would surpass $55 million by 2010. According to the same survey, in the same timeframe, the market for RNAi-based targeting and research would reach almost $150 and $100 million, respectively.