Some time ago, I referred to the excellent work being carried out by the team at Gradalis. Well, this private company has just announced that is about to commence a Plll clinical trial for its treatment (Vigil) of Ewings Sarcoma. This will be the first Plll clinical trial to employ shrna technology.
There are a number of points that should be made with regard to this achievement. The first is that Vigil is an adjuvant therapy. It is not a standalone treatment. It works in concert with the existing drugs Irinotecan and Temozolomide.
This may be a lesson for Benitec (BNTC) to learn. Instead of developing standalone treatments (such as BB-401/501), it may be better, in the first instance, to aim at developing adjuvant treatments – as was the case with their BB-103 treatment for HBV. I say this because, at present, there has been no research team that has managed to manufacture a drug that produces the right amount of shrna’s in the right human cells, so that the drug qualifies as a standalone treatment. Getting the shrna balance right has proven to be a difficult task. If the shrna levels are too high, toxicity and cell death occurs. If the shrna production is too low, it is non-therapeutic. This was the case with Benitec’s TT-034 treatment for HCV. Future cancer research (as directed by Benitec’s largest shareholder, Nant) may well benefit from aiming at producing combination treatments.
The second point is that Vigil employs a bi-functional shrna. This is a variation to the canonical shrna process. As the Graham patents have now expired, even the half of the bi-functional shrna that may have been covered by Benitec’s IP is now unencumbered by such patents. So Gradalis’s success may highlight the potential that shrna technology has, but Benitec won’t receive any financial benefit if Vigil is commercialised.
Another point that is worth considering is that Gradalis has had a major focus on oncology treatments since its inception. This is in contrast to Benitec, which has chased targets in viral diseases, oncology, nervous system and ophthalmic diseases. This diversity may not be the best way forward for pipeline development that is not covered by the agreement with Axovant (AXON).
At present, it is unclear as to what future R&D will look like. We do know that Axovant will fund the development of the treatment for OPMD as well as five additional indications. What we do not know is where the new revenue from the Axovant deal will be spent. Benitec’s new management has been tight-lipped about this. In fact, there has been no news coming out of the company in recent times; a stark contrast to previous regimes.
The Chairman did say, “Our management team is focused exclusively on expanding the research, development, and commercial opportunities for the core ‘silence-and-replace’ platform with the dual goals of enhancing patient benefit and generating shareholder value.” But where does this leave BB-401/501 and Nant’s oncology focus?
It is time for management to break the silence and articulate to shareholders the direction that the company will take. Perhaps the best course of action is to have just two paths, autosomal “silence and replace” targets and oncology, with viral and ophthalmic disease being shed in the process?
Disclosure: I am/we are long BNTC.
Additional disclosure: This article is my opinion and is not intended to be investment advice. Readers should do their own research.