The current delay may indicate a company-changing development....

The current delay may indicate a company-changing development. Benitec is not presenting at the liver meeting this year (hep b 2019) but Merck is slated to present on hep b for the first time. Benitec presented last nov. Check it out yourselves.

https://www.aasld.org/events-professional-development/liver-meeting

Below is more evidence that our hep b program was sold or partnered last November -

The Benitec hep b lead scientist now works with David Suhy here -

https://www.earli.com/about#advisor

He left Benitec sept last year.

Senior Scientist

Benitec Biopharma Ltd

August 2015 – September 2018 3 years 2 months

San Francisco Bay Area

Pipeline program development:
I am the scientific lead on preclinical research and development of Benitec’s gene therapy programs in Oncology (Head and Neck Squamous Cell Carcinoma, HNSCC) and Hepatitis B Virus infection
• Key member of team responsible for strategy, timeline, and execution of development plan
• Primary scientific liaison for clinical assay development, validation, and data reporting for the BB-401 program evaluating plasmid-directed antisense RNA against EGFR in HNSCC lesions – currently in Phase II clinical trials

Gene delivery technologies:
I lead the development of novel delivery technologies for Benitec’s gene therapies. I design non-viral (nanoparticle) formulations and have guided development of a non-viral HBV candidate through early in vivo proof-of-concept (AASLD 2018). I also contribute to the evaluation of novel engineered AAV mutants for enhanced transduction and tissue tropism
• Develop and optimize a novel non-viral ‘CELiD’ DNA vector for increased transgene expression and long-term persistence compared to plasmid DNA
• Conceptualize, design, and execute pre-clinical proof-of-concept studies using in vitro cell-based models and in vivo small animal models. Conduct screening experiments using reporter genes, followed by efficacy studies in the relevant mouse models of HBV infection and HNSCC tumor xenografts
• Contribute to the development of a scalable process for non-viral as well as viral vector (AAV) manufacturing using the baculovirus/insect cell system
• Manage collaborations and contracts with CROs

New technologies/Business Development:
• Key member of BD/partnering team at BIO 2018 and 2017. Identified potential partners, organized meetings, and led discussions of Benitec’s scientific platform and programs with pharma/biotech teams.
• Evaluate external technologies from academic and industry partners for collaboration and licensing

From the Liver Meeting last Nov -

https://plan.core-apps.com/tristar_aasld18/abstract/73323aac9567c427110c68c5f8bed7d3

Dr. Badriprasad Ananthanarayanan, Dr. Michael Graham, Dr. Tin Mao, Dr. Vanessa Strings-Ufombah, Dr. Shih-Chu Kao, Mr. Kermit Zhang, Dr. Peter Roelvink and Dr. David Suhy, Benitec Biopharma Ltd

Body

Background:

We have previously demonstrated that a single dose of BB-103, a gene therapy vector using an AAV capsid to deliver a cassette expressing three anti-HBV short hairpin RNA (shRNA), can result in the durable and potent suppression of HBV viral load and HBsAg in a chimeric mouse model of HBV infection. However, systemic delivery using viral capsids can be challenging due to manufacturing complexity, pre-existing neutralizing antibodies, and the inability to repeat dosing due to induced immunity. Recently, Closed-Ended Linear Duplex (CELiD) DNA vectors that have the ability to produce persistent gene expression have been described. Here, we examined if non-viral CELiD vectors expressing anti-HBV shRNAs could cause meaningful suppression of HBV infection in a mouse model.

Methods:

CELiD DNA was produced using an optimized baculovirus/insect cell expression system and downstream purification. In initial experiments, durability of expression from CELiD DNA versus plasmid DNA was assessed by luciferase expression over 6 months. For anti-viral studies, a mouse model of long-term HBV infection was established in NOD/SCID mice by Hydrodynamic Injection (HDI) of plasmid DNA encoding the HBV genome. CELiD DNA expressing the same three anti-HBV shRNAs as in BB-103 were co-administered with HBV DNA by HDI. Suppression of HBV infection was assessed over the course of 10 weeks by weekly monitoring of serum HBV DNA, HBsAg, and HBeAg.

Results:

HDI administration of CELiD DNA encoding a luciferase reporter in a naïve mouse model produced robust levels of luciferase expression which persisted for the duration of the 6 month experiment, while expression from plasmid DNA rapidly declined after administration. In the HBV model, administration of CELiD DNA resulted in a 1.75 log decrease (below LLOQ) in serum HBV DNA compared to control DNA expressing non-targeted shRNA at day 70. Furthermore, CELiD DNA reduced serum HBsAg by 1.89 log and HBeAg by 0.89 log (both below LLOQ) as compared to the control. HBV viral load continued to drop through the entirety of the 70 day experiment with no rebounds in serum HBV parameters.

Conclusion:

Non-viral CELiD DNA vectors expressing anti-HBV shRNAs produced strong and persistent knockdown of HBV parameters following a single administration in the HDI mouse model. This suggests that CELiD DNA expressing anti-HBV shRNAs, when delivered by an appropriate liver-directed reagent, may be a promising therapeutic for chronic HBV infection.