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• Hepatitis B – ‘Hepbarna ™ ’  Hepatitis B virus (HBV) infection is currently incurable and represents a significantly larger public health problem than HCV. Hepbarna™ is similar in design to TT- 034, utilizing the same delivery vector, enabling it to leverage much of the toxicity and biodistribution data obtained in the Company’s HCV clinical development program. In conjunction with the Company’s collaborator, Biomics Biotechnologies, Benitec is optimising the design of DNA constructs, and the Company’s US laboratory is preparing to undertake a range of in vitro validation experiments. 

• Neuropathic pain.  The research collaboration with Professor David Yeomans at Stanford University will focus in the first instance on re-validating the previously developed constructs in vivo. ™ 

• Genetic disease – ‘Pabparna ’ . Benitec’s treatment for oculopharyngeal muscular dystrophy (OPMD) – which is being developed in collaboration with the Royal Holloway, University of London – continues to progress. 

## Licensed Programs 

In addition to the Company’s in-house development programs, Benitec has licensed its ddRNAi technology to four biotech companies. As each of these companies advances their clinical development their success further validates ddRNAi. Each program is outlined below: 

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• HIV/AIDS – Benitec’s US-based licensee Calimmune Inc. has recently received approval to commence dosing patients in the second cohort of their Phase I/II stem cell-based clinical trial in people living with HIV/AIDS. Approval to move into the second group of patients confirms that there were no safety issues or treatment-related adverse events observed during the dosing of the first cohort. The Cal-1 therapy utilises ddRNAi-based gene silencing technology along with additional proprietary technology to reduce the ability of HIV to enter immune cells. The trial is entitled “Safety Study of a Dual Anti-HIV Gene Transfer Construct to Treat HIV-1 Infection” . 

• Huntington’s disease – Benitec’s non-exclusive license allows uniQure to develop a treatment for Huntington’s disease using the company’s ddRNAi gene silencing technology. uniQure listed on the NASDAQ in early 2014, raising around $90M so is wel resourced to be able to advance this program towards the clinic. 

• Retinitis pigmentosa  – Benitec’s licensee Genable Technologies Ltd is developing GT308 for retinitis pigmentosa using ddRNAi to silence the disease-causing mutant gene. Genable was been granted orphan drug designation from the FDA; this status means Genable will gain seven years of market exclusivity in the US once the product is approved. 

• Breast cancer – Benitec has granted a license to Regen Biopharma for the development of a ddRNAi-based therapy called dCellVax. Regen recently announced the successful silencing of the IDO gene in dendritic cells, an approach that in animal models has demonstrated the ability to induce regression of breast cancer. 

## Intellectual Property 

Benitec’s patent estate includes a combination of technology patents and program-specific patents. Technology patents are based on research in the 1990’s conducted by Dr Michael Graham (now Chief Scientist at Benitec) and colleagues at CSIRO. These patents form the basis for a dominant position in DNA-directed gene silencing for therapeutic use in humans. The program patents are aimed at establishing strategic patent protection for Benitec’s programs in development in key jurisdictions including the US, Europe, Australia, China, Japan and Canada 

## Key developments: 

• International patent application filed for the AMD program. This patent filing is aimed at the use of ddRNAi in the treatment of wet age-related macular degeneration including identifying target sequences for RNAi activity. 

• European opposition hearing was conducted for the Graham European patent EP1555317 in the presence of patent opponents, BASF SE and Galapagos NV. Despite a favourable preliminary ruling, the formal hearing reversed its initial findings and upheld the opposition, revoking this Graham patent. Benitec, along with CSIRO, has the opportunity to appeal this decision. The Graham patent family also includes two pending applications in Europe, EP070008204 and EP10183258. 

• Benitec has licensed third party IP to strengthen its position in Europe. The company has executed a license agreement with Galapagos NV in Europe, which grants Benitec the rights to use RNAi in human therapeutics and diagnostics under the Galapagos patent EP1444346. The rights include the right to sub-license. 

• The European Waterhouse patent EP1068311 has been scheduled for an opposition hearing at The Hague in January 2015. The opponents to this patent are BASF SE, Strawman Limited, Carnegie Institution of Washington/University of Washington and Syngenta International AG. The preliminary review from the EPO is favourable. 

