The potential of these therapeutics to address unmet medical needs in these areas as well as their potential to cure disease, results from the long-term expression of ddRNAi and its demonstrated ability to permanently silence genes which cause these conditions.
Benitec is developing ddRNAi-based therapeutics that target a spinal enzyme that contributes significantly to chronic pain.
Market: Pain is one of the most common symptoms associated with cancer, 65% of all cancer patients experience chronic pain, with 80% of patients being affected in the terminal stage of this disease. This high incidence of cancer pain is set to further increase in the future (Datamonitor). With neuropathic and chronic pain being resistant to conventional opiod therapies, pain continues to be under-treated in cancer patients. Therefore the development of novel treatments for this class of pain which is characterized by central sensitization is a tremendous area of unmet medical need.
Rationale and status: Benitec is devising a novel approach to the amelioration of chronic pain, by designing ddRNAi therapeutics that target a specific spinal enzyme that has been implicated in contributing significantly to the development of central sensitization-mediated pain.
The aim of the chronic pain program is to develop a single intrathecal injection of a ddRNAi construct which results in significant silencing of the spinal enzyme gene to provide pain relief equivalent to that achievable by infusion of opioids. While initially the target clinical group is terminally ill cancer patients, this could be extended to any group of patients suffering chronic or neuropathic pain as a result of a terminal illness, including HIV/AIDS.
After the current proof of concept studies have been completed, the plan is to then conduct preclinical studies, leading to a Phase I clinical trial.
Benitec is developing ddRNAi therapeutics that can be employed in a novel adjunctive therapeutic approach for drug-resistant non-small cell lung cancer.
Market: Lung cancer is the leading form of cancer worldwide in terms of incidence and mortality. Non-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancers. First line chemotherapy for NSCLC includes a combination of tubulin-binding and DNA-damaging agents. However, there is a high mortality associated with the rapid resistance of the tumours to chemotherapy drugs, making the prognosis for patients with advanced NSCLC dismal.
Rationale and status: Benitec is developing a novel approach to overcome the drug resistance of NSCLCs, by designing ddRNAi therapeutics that target and silence the beta III-tubulin gene. The protein for beta III-tubulin is known to be upregulated and is associated with clinical resistance of these drugs (Cancer Research, May 2010.)
The aim of this drug-resistant lung cancer program is aim to increase the sensitivity of the cancer cells to chemotherapeutic drugs.
After the current proof of concept studies have been completed, the plan is to then conduct preclinical toxicology studies, leading to a Phase I clinical trial.
Benitec is developing ddRNAi-based therapeutics that target hepatitis B virus (HBV) key viral genes.
Market: More than 2,000 million people alive today have been infected with HBV at some time in their lives and of these about 350 million remain chronically infected and become carriers of the virus. In the USA alone there are over 1.25 million people living with the consequences of chronic active HBV, and over 60,000 new cases per year.
The application of ddRNAi technology to HBV infection has the potential to revolutionise the treatment of chronic hepatitis B as current therapies have only limited inhibitory effects on viral gene expression and replication in the majority of chronically infected patients.
Rationale and status: In September 2009, Benitec initiated a program for the development of a ddRNAi-based therapeutic for the treatment of chronic HBV infection. The first proof of concept phase is being carried out in collaboration with China-based Biomics Biotechnologies Co. Ltd.
The aim of this HBV program is to directly target the activity of a specific HBV gene with minimum off-target effects on human genes, and thus to provide a unique therapeutic to address the current unmet clinical treatment needs for HBV infection. Several effective RNAi sequences have been identified in the first stage of the collaboration, and in February 2011 Benitec and Biomics agreed to extend the program aimed at designing, manufacturing and testing ddRNAi-based constructs in a preclinical model of HBV infection. Ultimately the therapeutic will be tested in a clinical trial of HBV infected patients.
Until late 2010, Benitec supported the development of an RNA-based HIV/AIDS therapeutic, one component of which was a ddRNAi construct directed at a key HIV replicative gene. This program was undertaken from 2007-2010 in collaboration with the City of Hope research hospital in Duarte, California. The product candidate was taken into a Phase I/II pilot human clinical trial funded by Benitec that produced promising interim results in terms of safety and proof of feasibility. The data was published in Science Translational Medicine in June 2010.
This study is now being progressed by the research and clinical team at the City of Hope Science. Benetic is seeking partners to further develop and advance aspects of their ddRNAi-based cell therapy AIDS/HIV program.
