Oculopharyngeal Muscular Dystrophy (OPMD)
- OPMD is a rare progressive muscle-wasting disease caused by a mutation in the poly(A)-binding protein nuclear 1 (PABPN1) gene with an estimated prevalence of 15,000 patients in Western countries.
- The disease is characterized by eyelid drooping, swallowing difficulties (dysphagia), proximal limb weakness, and death due to aspiration pneumonia and malnutrition.
- Typical age of onset for OPMD patients is in their 40’s-to-60’s.
- Dysphagia is a severe, life-threatening complication of OPMD and can lead to chronic choking, regurgitation, aspiration pneumonia, and in severe cases, death.
- There is currently no effective drug therapy for OPMD. Available interventions are limited to temporary palliative care and do not address underlying progressive muscle weakness.
The Benitec Approach
- We believe our ddRNAi approach to ‘silence and replace’ the mutant PABPN1 protein will result in the correction of the muscular dystrophy and of key clinical features of OPMD including progressive atrophy and muscle weakness associated with nuclear aggregates of insoluble PABPN1. Our proprietary approach combines the essential elements of the initial two-vector system into a single recombinant AAV vector.
Hepatitis B (HBV)
- Worldwide, 2 billion people have been infected with the hepatitis B virus (HBV), with chronic infection having a global prevalence estimated at 257 million people.
- According to the World Health Organization, in 2015, hepatitis B resulted in an estimated 887 000 deaths, mostly from cirrhosis and hepatocellular carcinoma (i.e. primary liver cancer).
- Chronic infection with hepatitis causes 80% of all hepatocellular carcinoma and more than 500,000 people die each year from this lethal cancer.
- There is a need for safe and effective therapeutics that can promote the restoration of a host immune response through targeted hepatitis B surface antigen (HBsAg) knockdown offering HBV patients the potential for ‘functional cures’ by eliminating virus producing cells.
The Benitec Approach
- We believe that a combination of BB-103 and a nucleoside inhibitor (NUC), a type of drug currently used to treat the HBV in infected individuals, may suppress a number of HBV parameters in humans including HBsAg. The HBsAg is a known contributor to immunosuppression and HBV chronicity. The ability to suppress HBsAg may thus help spur the patient’s own immune system to produce anti-s-antigen antibodies which is expected to eliminate their need for their daily anti-viral treatments to control the disease.
- Our pre-clinical results demonstrate that a one-time treatment of BB-103 added on top of a daily dosing regimen of a NUC, results in a far superior suppression of HBV parameters, including a greater than 4 log drop in HBV DNA and greater than 2 log drop in HBsAg in human chimeric liver mouse model.
- BB-103 is the only gene silencing agent that guarantees perfect compliance, providing the opportunity to reduce the development of drug resistance.