University of Westminster develops groundbreaking method to test hepatitis C cure

BIOMEDICAL SCIENCES 17 FEBRUARY 2014

Researchers at the University of Westminster have developed a groundbreaking method which can be used to test a new innovative cure for hepatitis C, a liver disease caused by the hepatitis C virus (HCV).

The cure is the first of its kind ever to be tested in humans and comes in the form of a drug based on gene therapy which is under development by the Australian company Benitec Biopharma.

Around 150 million people worldwide are infected with hepatitis C, and more than 350,000 people die every year from hepatitis C related liver diseases. Hepatitis C is one of the leading causes of liver cirrhosis and cancer, and one of the most common and seriously infectious conditions in the world (according to the World Health Organisation (WHO)).

Although treatments are already available for hepatitis C, these are lengthy, have low chances of success, cause significant side-effects, or the virus is already becoming resistant. The new drug, TT-034, developed by Benitec Biopharma, is based on the biological mechanism for which the Nobel Prize in Physiology or Medicine was awarded in 2006. Unlike anything else currently available to patients, this treatment works with a single injection to directly destroy the hepatitis C virus and remove the infection. The drug is currently undergoing clinical trials in the US with results expected in the coming months.

Dr Sterghios A. Moschos, MSB, Director of Westminster Genomic Services at the University of Westminster, developed the comprehensive and innovative method by adapting state-of-the-art genome sequencing technologies to show exactly how the new drug works. The research was conducted in collaboration with the European Bioinformatics Institute and Benitec Biopharma.

Dr Moschos said: “Our entirely new method to test the new drug has had a major impact on building robust confidence in this innovative therapy. For the first time ever we have shown that there are more ways to hit the hepatitis C infection than previously thought possible, and that this treatment works like a combination of multiple drugs. Our approach has helped Benitec Biopharma, to obtain permission to start clinical trials much earlier than we expected. This is unprecedented for gene therapy, particularly for a disease for which treatments already exist.”

For further information you can read the research paper published on Molecular Therapy Nucleic Acids at nature.com.

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About the University of Westminster:

The University of Westminster boasts a vibrant learning environment attracting more than 20,000 students from over 150 nations and we continue to invest in our future with new developments, research projects and new ideas.

We offer highly attractive practice-based courses which are independently rated as excellent, many with international recognition. Our distinguished 175-year history has meant we lead the way in many areas of research, particularly politics, media, art and design, architecture and biomedical sciences, and our position in the city of London allows us to continue to build on our close connections with leading figures and organisations in these areas as well as in the worlds of business, information technology, politics and law.

Our commitment to educating graduates for the needs of professional life attracts high quality students from within the UK and around the globe.

Internationalism, employability and sustainability are key elements in the University of Westminster’s vision for the future and we strive to ensure the very highest standards are met and maintained.

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Benitec cleared for first-in-man hep C trial

By Dylan Bushell-Embling   |   Posted in Autoimmune on 15 January, 2014

Benitec Biopharma (ASX:BLT) has been granted approval to proceed with a first-in-man trial of its single-injection hepatitis C treatment candidate TT-034.

The US FDA has advised Benitec that it can conduct the trial, after reviewing the Investigational New Drug (IND) application the company filed in early December.

“We are very pleased with this outcome, which establishes Benitec as a clinical-stage company,” Benitec Biopharma CEO Peter French said.

TT-034 is a therapeutic designed to treat hepatitis C with a single injection. It is based on gene-silencing technology known as DNA-directed RNA interference (ddRNAi), originally developed at the CSIRO and then exclusively licensed to Benitec.

The treatment itself was developed by US-based Tacere Therapeutics, which took out a licence to the ddRNAi technology from Benitec in 2006.

Benitec acquired Tacere and TT-034 in 2012 through an all-stock deal worth around $1.5 million before licensing fees

The global market for hepatitis-based treatments is estimated at $6.5 billion, and is expected to more than double in value by 2015.

Benitec Biopharma (ASX:BLT) shares were trading 8.7% higher at $0.75 as of around 12.30 pm on Wednesday

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Benitec's hepatitis C therapeutic selected for oral presentation at AASLD conference and TT 034 program

Sydney Australia, 5 August 2013: Benitec Biopharma Limited (ASX Code: BLT), today announced that its ddRNAi-based gene silencing program for hepatitis C (HCV) has been selected for an oral presentation at the November 2013 meeting of the American Association for the Study of Liver Disorders (AASLD) being held in Washington DC. This meeting, The Liver Meeting®, is a pre-eminent worldwide conference for researchers working in the area of liver diseases.

In the session featuring "New Agents for HCV Therapeutics", Benitec has been selected to provide an oral presentation on TT-034, its novel gene silencing therapeutic. TT-034, which is expected to enter a first-in-man Phase I/II clinical trial later this year, has the potential to be a one-shot cure for chronic HCV.

The company's Senior Vice President R&D, Dr. David Suhy, who will deliver the presentation, commented: "We are excited to be selected for an oral presentation at this prestigious meeting. This is a strong indication that our program is of significant interest to the liver disease community."

Benitec also announces that the US Food and Drug Administration (FDA) has advised the company that it does not see the need for a final pre-investigational new drug (IND) meeting for the TT-034 program, allowing the Company to finalise its IND. Clinical trials are able to commence 30 days after the application is filed with, and subsequently accepted, by the FDA.

For more information please contact: Dr Peter French | Chief Executive Officer Phone: +61 (02) 9555 6986
pfrench@benitec.com | www.benitec.com

About TT-034: TT-034 is a potentially transformative therapeutic that is intended to provide a "one-shot-cure" for hepatitis C with a single injection. Preclinical studies have shown that the vector used to deliver TT-034 specifically targets liver cells where it transfects almost every cell without causing toxic effects. TT-034 is designed to prevent development of viral resistance (a major problem for most hepatitis C drugs) by simultaneously silencing three separate highly conserved regions on the virus genome. Studies have demonstrated that a single treatment of TT-034 is active out to 180 days (the duration of the studies).

About Benitec Biopharma Limited: Benitec Biopharma Limited is an ASX-listed biotechnology company (ASX Code: BLT) based in Sydney, Australia. The company has a pipeline of in-house and partnered therapeutic programs based on its patented gene-silencing technology, ddRNAi. Benitec is developing treatments for chronic and life- threatening human conditions such as hepatitis C, hepatitis B, wet age-related macular degeneration, cancer- associated pain, drug resistant lung cancer and oculopharyngeal muscular dystrophy based on this technology. In addition, Benitec has licensed ddRNAi technology to other biopharmaceutical companies who are progressing their programs towards the clinic for applications including HIV/AIDS, retinitis pigmentosa and Huntington's disease. For more information on Benitec refer to the Company's website at www.benitec.com.

Source: Benitec Biopharma Limited

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HCV clinical trial application submitted to Recombinant DNA Advisory Committee (RAC)

-- Benitec progresses hepatitis C therapeutic towards the clinic

-- Application for RAC review of hepatitis C clinical trial protocol received by NIH

-- Application expected to be considered at the June RAC meeting

SYDNEY, April 16, 2013 /PRNewswire/ -- RNAi-based therapeutics company Benitec Biopharma Limited (ASX Code: BLT) today announced that the company's wholly owned US subsidiary, Tacere Therapeutics Inc., has submitted an application to the US National Institutes of Health's Recombinant DNA Advisory Committee (RAC) .

The RAC submission document comprises the full clinical trial protocol for its first-in-man ddRNAi-based therapeutic (TT-034) for hepatitis C virus (HCV) infection, as well as the safety and toxicology data and responses to questions concerning the objective and rationale for the proposed trial. Most of this material will be utilised in the subsequent US Food and Drug Administration (FDA) Investigational New Drug (IND) application for TT-034.

The RAC review is a required step for a product that involves gene therapy vectors before a clinical trial can be initiated. The RAC process results in recommendations that are disseminated to various bodies, including the Company and the FDA. The review can be administrative or include a public hearing. If the application is subject to a hearing, this is expected to be part of the next RAC meeting in June 2013.

David Suhy, Ph.D., Tacere's US-based, Senior Vice President of Research and Development commented, "Completing this submission is an important step in moving TT-034 into the clinic. We look forward to receiving the Committee's recommendations and then moving ahead with an IND and initiating the clinical trial for TT-034 this year. It has been very gratifying to oversee the development of a first-in-class therapeutic from concept to the clinic."

About TT-034

TT-034 is a potentially transformative therapeutic that is intended to provide a "one-shot-cure" for hepatitis C with a single injection. Preclinical studies have shown that the vector used to deliver TT-034 specifically targets liver cells where it transfects almost every cell without causing toxic effects. TT-034 is designed to prevent development of viral resistance (a major problem for most hepatitis C drugs) by simultaneously silencing three separate highly conserved regions on the virus genome. Studies have demonstrated that a single treatment of TT-034 is active out to 180 days (the duration of the studies).

About Benitec Biopharma Limited:

Benitec Biopharma Limited (ASX Code: BLT), based in Sydney, Australia, has a pipeline of in-house and partnered therapeutic programs based on its patented gene-silencing technology, ddRNAi. Benitec is developing treatments for a range of chronic and life-threatening human conditions. Benitec has licensed its ddRNAi technology to other biopharmaceutical companies who are advancing their programs toward the clinic for applications including HIV/AIDS, retinitis pigmentosa and Huntington's disease. For more information on Benitec refer to the Company's website at www.benitec.com.

For more information please contact:

Dr Peter French|Chief Executive Officer
Phone: +61 (02) 9555 6986 | pfrench@benitec.com | www.benitec.com

SOURCE Benitec Biopharma Limited

RELATED LINKS

http://www.benitec.com

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Also See:

• Benitec Selects University of California, San Diego as a Site for Phase I/II Clinical Trial of TT-034 in Patients with Hepatitis C Infections
• HCV "One-Shot-Cure" ddRNAi Therapy Study Starting

Benitec Selects University of California, San Diego as a Site for Phase I/II Clinical Trial of TT-034 in Patients with Hepatitis C Infections

SYDNEY, April 15, 2013 /PRNewswire/ -- RNAi-based therapeutics company Benitec Biopharma Limited (ASX Code: BLT) today announced the selection of the University of California, San Diego (UCSD), Health Sciences as the second site for its upcoming phase I/II first-in-man trial for TT-034 in Hepatitis C infections (HCV). Benitec previously announced the selection of Duke Clinical Research Unit as the other site. TT-034 is being developed as a potential "one-shot-cure" for HCV.

A consultant and sub-principal investigator for the study from UCSD Health Sciences will be Robert Gish, M.D., clinical professor of Medicine and medical director of Hepatology. Dr. Gish is a renowned hepatitis researcher with previous experience using RNAi based therapeutics for HCV. He has over 500 publications in the field and is a fellow of the American College of Physicians and the American Association for the Study of Liver Disease.

"I look forward to working with Benitec and Duke University on this important program," Dr. Gish commented. "This is the first time that this therapeutic modality is being tested in humans, and if it is successful I believe it can be a significant step forward, not only for HCV treatment but potentially also as a treatment modality for Hepatitis B."

The principal investigator for the study at UC San Diego is David Wyles, M.D., associate professor of Medicine at the UC San Diego AntiViral Research Center, the clinical research site that will be conducting the trial. His research interests include the laboratory evaluation of new antiviral therapies for HCV, drug resistance to HCV antivirals, and HCV viral fitness.

Peter French, Ph.D., chief executive officer of Benitec said, "We are elated that UC San Diego and Dr. Gish will participate in this study. We now have two top clinical research teams working with Benitec on this trial. This constellation of expertise will greatly benefit our HCV program and can help demonstrate the power of our ddRNAi technology in the clinic. Having our two clinical centers in place moves us a step closer to initiating the Phase I/II clinical trial, which we expect to occur during the second half of 2013."

The phase I/II clinical trial is an open-label dose escalation study to evaluate the safety and activity of single doses of TT-034 in patients with chronic HCV genotype 1 infection who have failed previous treatments. The trial is expected to involve 14 patients in 5 sequential dose cohorts. Additional consolidation cohorts may be added during the study to confirm the results of the trial. The primary safety endpoints are dose limiting adverse events. The primary end points are serum viral load reduction and degree of hepatocyte transduction (measured through liver biopsies). There is a pre-specified interim read on safety and activity within months of trial commencement.

About TT-034

TT-034 is a potentially transformative therapeutic that is intended to provide a "one-shot-cure" for Hepatitis C with a single injection. TT-034 works through RNA interference (RNAi), which is a naturally occurring regulatory process in cells that acts to "silence" genes after they have been transcribed from DNA into messenger RNA. Benitec's proprietary ddRNAi approach involves the introduction of a DNA vector that produces short hairpin RNAs (shRNAs) that are processed by the cell into siRNAs. This approach emulates the cell's own gene silencing mechanism and provides long term activity (months). Moreover, the virus vector used to deliver the TT-034 construct, an engineered non-replicating adeno-associated virus (AAV8), targets almost exclusively liver cells (where HCV replicates). TT-034 is further designed to prevent viral escape through mutations (a major problem for most HCV drugs) by using three different shRNAs to simultaneously target three separate highly conserved regions in the HCV genome. In mice and monkeys, TT0-034 has been shown to transduce 100% of hepatocytes in the liver and provide high shRNA activity for 180 days (the duration of the studies), without adverse effects.

About UC San Diego Health Sciences

University of California, San Diego Health Sciences comprises clinical and academic entities -- UC San Diego Health System, the region's only academic health system; UC San Diego School of Medicine, one of the top US research-intensive schools of medicine; and Skaggs School of Pharmacy and Pharmaceutical Sciences. The US National Institutes of Health (NIH) ranks UC San Diego Health Sciences as one of the top institutions in research funding per faculty member, and the School of Medicine is in the top 10 in total NIH research funding. Part of the University of California system, UC San Diego -- founded in 1960 -- is renowned for collaborative and cross-disciplinary research that transcends traditional boundaries in science, engineering and the humanities.

About Benitec Biopharma Limited:

Benitec Biopharma Limited (ASX Code: BLT), based in Sydney, Australia, has a pipeline of in-house and partnered therapeutic programs based on its patented gene-silencing technology, ddRNAi. Benitec is developing treatments for chronic and life-threatening human conditions. Its most advanced program is TT-034 for the treatment of chronic HCV infection. Benitec has licensed ddRNAi technology to other biopharmaceutical companies who are advancing their programs toward the clinic for applications including HIV/AIDS, retinitis pigmentosa and Huntington's disease. For more information on Benitec refer to the Company's website at www.benitec.com.

For more information please contact:

For UCSD:

Ms. Jackie Carr, Communications Director, UCSD Health System

Phone: +1-619-543-6163. jcarr@ucsd.edu. http://som.ucsd.edu

For Benitec:

Dr. Peter French, Chief Executive Officer

Phone: +61 (02) 9555 6986. pfrench@benitec.com. www.benitec.com

SOURCE Benitec Biopharma Limited

Web site: http://www.benitec.com

Source

Also See: HCV "One-Shot-Cure" ddRNAi Therapy Study Starting

HCV "One-Shot-Cure" ddRNAi Therapy Study Starting

RNAi-based therapeutics company Benitec Biopharma Limited announced Duke Clinical Research Unit, the early phase unit of the Duke Clinical Research Institute (DCRI), in Durham, North Carolina, as a site for its upcoming phase I/II first-in-man trial for TT-034 in Hepatitis C. TT-034 is being developed as a potential "one-shot-cure" for Hepatitis C (HCV).

ddRNAi: expressed RNA interference technology

ddRNAi (DNA-directed RNAi) is a unique platform technology for silencing unwanted or disease-causing genes. In the context of therapy, ddRNAi avoids many of the drawbacks of other gene silencing technologies and produces much longer-lasting effects.
Benitec Biopharma pioneered ddRNAi and was the first company to demonstrate expressed RNAi in human cells. We hold a dominant intellectual property position in RNAi, with over 40 issued global patents for the human use of ddRNAi.

Learn how ddRNAi could target countless human and viral genes. Track our pipeline programs using this exciting technology. View the scope of our patents in ddRNAi. Join us in developing transformational solutions for human health.

SYDNEY and DURHAM, NC - "We are very excited to be working with Duke, a world renowned research institution with significant experience in this area," said Peter French, Ph.D., Chief Executive Officer of Benitec. "The TT-034 trial marks the transition of Benitec to a clinical stage company. We expect that positive results from the trial will provide a value inflection point for the company, and also be a validation for our ddRNAi technology as an effective platform for therapeutics."

The phase I/II clinical trial is an open-label dose escalation study to evaluate the safety and activity of single doses of TT-034 in patients with chronic HCV genotype 1 infection who have failed previous treatments. The trial is expected to involve 14 patients in 5 sequential dose cohorts. Additional consolidation cohorts may be added during the study to confirm the results of the trial. The primary safety endpoints are dose limiting adverse events. The primary activity end points are serum viral load reduction and degree of hepatocyte transduction (measured through liver biopsies). There is a pre-specified interim read on safety and activity within months of trial commencement. The clinical trial is expected to begin enrolling patients during the second half of 2013.

Duke's principal investigator for the study will be Keyur Patel, M.D. Dr Patel has previous experience with oligonucleotide therapeutics in HCV, is a recipient of the prestigious American Association for the Study of Liver Diseases (AASLD) Shelia Sherlock Clinical and Translational Research award and has over 100 citations in peer-reviewed publications.
"TT-034 is a potentially transformative new treatment," Dr. Patel commented. "A therapeutic that could cure an HCV patient with a single injection would obviously be a big step forward compared to even the best treatments that are currently on the horizon, as they all involve comparatively lengthy regimens with a combination of several drugs."

About TT-034: TT-034 is a potentially transformative therapeutic that is intended to provide a "one-shot-cure" for Hepatitis C with a single injection. TT-034 works through RNA interference (RNAi), which is a naturally occurring regulatory process in cells that acts to "silence" genes after they have been transcribed from DNA into messenger RNA. Benitec's proprietary ddRNAi approach involves the introduction of a DNA vector that produces short hairpin RNAs (shRNAs) that are processed by the cell into siRNAs. This approach emulates the cell's own gene silencing mechanism and provides long term activity (months). Moreover, the virus vector used to deliver the TT-034 construct, an engineered non-replicating adeno-associated virus (AAV8), targets almost exclusively liver cells (where HCV replicates). TT-034 is further designed to prevent viral escape through mutations (a major problem for most HCV drugs) by using three different shRNAs to simultaneously target three separate highly conserved regions in the HCV genome. In mice and monkeys, TT0-034 has been shown to transduce 100% of hepatocytes in the liver and provide high shRNA activity for 180 days (the duration of the studies), without adverse effects.

About the Duke Clinical Research Unit: The Duke Clinical Research Unit (DCRU) is a state-of-the-art research facility located within the Duke Medicine campus that provides infrastructure support to sponsors and investigators who are testing new drug candidates and other cutting-edge therapies, or seeking to identify and validate novel biomarkers. The DCRU has more than 20 years of early-phase clinical trial experience and has successfully conducted more than 150 early-phase studies, including 80 phase 1 studies. The experience, support systems and infrastructure of the DCRU enable provision of the highest level of program management and services for early-phase clinical trials, including quality processes, accurate reporting, and regulatory expertise. The DCRU combines the clinical expertise and scientific leadership of one of the most prestigious academic medical centres in the world with the operational capabilities of a full-service contract research organization. The DCRU is part of the Duke Clinical Research Institute. The DCRI is a comprehensive academic research organization and the only one of its kind that can offer all the services of a commercial contract research organization with the academic credibility and expertise of an academic medical center.

About Benitec Biopharma Limited: Benitec Biopharma Limited (ASX Code: BLT), based in Sydney, Australia, has a pipeline of in-house and partnered therapeutic programs based on its patented gene-silencing technology, ddRNAi. Benitec is developing treatments for chronic and life-threatening human conditions. Its most advanced program is TT-034 for the treatment of chronic HCV infection. Benitec has licensed ddRNAi technology to other biopharmaceutical companies who are advancing their programs toward the clinic for applications including HIV/AIDS, retinitis pigmentosa and Huntington's disease. For more information on Benitec refer to the Company's website at www.benitec.com.

Source: PR Newswire

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