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DdRNAi Is In The Eye Of The Beholder

|Includes:Benitec Biopharma Ltd (BNIKF)


Benitec's DNA Directed RNA Interference (ddRNAi) literally is or has been in the eyes of many beholders; albeit that these beholders are limited to mice and large animals at this point in time. This research, where ddRNAi constructs have been injected into the eyes of lab animals, has been conducted in order to advance treatments for a range of eye disease. The application of ddRNAi to human beholders will come when Genable Technologies (a ddRNAi licensee) applies this technology to the treatment of Retinitis Pigmentosa (NASDAQ:RP). The company was forecasting the start of human trials by the end of 2013 but this date has slipped. The application of ddRNAi to Age-Related Macular Degeneration (NYSE:AMD) will be fast-tracked by Benitec itself once a second tranche of capital raising has been approved (subject to shareholder acceptance) in April of this year.


When RNA Interference (RNAi) was considered as a viable means of treating human diseases, many in the field thought that its application to ocular diseases would be the first to show success. This was in part due to the conserved nature of the eyes and ocular diseases. Trials using synthetic siRNA (a competitive technology to ddRNAi) were commenced in humans but ultimately proved to be unsuccessful. To some extent these trials exposed some of the then limitations of siRNA technology. One of these limitations was the that the treatments only had a short-term effect and this is a limitation that can be removed with the use of ddRNAi as ddRNAi can produce a continual supply of therapeutic short hairpin RNA (shRNA) molecules.

For this reason, the application of shRNA to treat ocular diseases has been advanced by a number of research teams for a range of afflictions such as RP, AMD, and Retinal Neovascularisation.


Genable Technologies is using gene therapy to treat RP. RP is a group of inherited eye disease for which there is no cure. It is estimated to affect 1 in every 3,500 to 4,000 people in the US and Europe.

Genable's first drug candidate, GT038, is targeting rhodopsin (RHO)-linked autosomal dominant retinitis pigmentosa (adRP). GT038 has been designed to use a suppression and replacement technique where the faulty gene is silenced using ddRNAi and a normal copy of the gene is supplied via an Adeno-Associated Virus (NYSE:AAV). It has been engineered so that the normal gene avoids the suppression provided be the ddRNAi construct.

This form of the disease affects approximately 30,000 patients in the US and Europe. The company has received Orphan Disease status from both the European and US regulatory authorities. It estimates the market to be worth about $500M pa.

The company is yet to publish a new date for the start of its clinical trial but I would speculate that it will be later this year.


AMD is the leading cause of blindness and sight loss in Americans over the age of 65. With an aging population this affliction is set to increase. About 1.75 million US residents have the disease and this is forecast to grow to 3 million by 2020.

The disease has two forms, Wet and Dry, depending on whether the degeneration is caused by invasive blood vessels or not. Dry is the more common form and wet the more serious.

There is no cure but monthly injections can delay its progress.

When Benitec acquired Tacere it not only acquired a treatment for Hepatitis C but also the design for a treatment for Wet AMD. While this program is only at the start of its pre-clinical development, it is set to build on the previous work done with the siRNA trials as the first version of the treatment, TT-211, targets the expression of vascular endothelial growth factor A (VEGF-A ) which is the same target as those previous studies.

TT-211 is being designed as a single injection that will provide years of protection against the disease and this approach is supported by independent research.

The company estimates this market to be worth $2B in the US alone.

TT-211 also represents the next generation of ddRNAi technology. The shRNA is modelled into a microRNA (miRNA) backbone (ShMir) and ShMir will be the next development in ddRNAi. TT-211 will have cell specific promoters and its design is being optimised to deliver ShMir to all the layers of the retina from one intravitreal injection.

The follow on drug, TT-231, is already being designed to treat both Dry and Wet AMD. This ShMir will incorporate three shRNA's targeting as yet unnamed proteins.

Approval of the company's second tranche of capital raising is essential if this next generation of technology is to advance.


Benitec's ddRNAi technology is being used by many research teams around the world to find cures for ocular diseases including RP and AMD. The first in human trial is likely to be when Genable treats its first patient, probably later this year. Benitec's own program is at an early stage but it has the promise of a treatment for the yet incurable AMD.

The estimated market for RP and AMD combined is about $2.5B in the US alone.

Disclosure: I am long BNIKF.

Additional disclosure: The views expressed here do not represent investment advice.

Stocks: BNIKF