Silence Therapeutics in RNAi Therapeutics Deal with AstraZeneca

Silence Therapeutics, formerly known as SR Pharma/Atugen, disclosed today the signing of a significant collaboration agreement with AstraZeneca. In addition to initial upfront investments of £7.5M (~$15M), Silence stands to receive up to £200M in future developmental milestone payments plus royalties on any resulting drug sales. For this, AstraZeneca may target up to 5 genes for therapeutic purposes using Silence Therapeutics’ AtuRNAi platform with a focus on respiratory diseases.

The AtuRNAi platform is at the heart of Silence Therapeutics. AtusiRNAs are blunt-ended, double-strand oligos with a particular 2’O-methylation pattern that induce post-transcriptional gene silencing. Silence believes that its AtuRNAi platform sufficiently differentiates it from competing RNAi platforms, most notably Tuschl siRNAs, to be considered proprietary. Indeed, the European Patent Office has been a good ally of the company by granting them a core patent relating to this technology earlier this year and restricting the scope of the competing Kreutzer-Limmer patents before that. This has allowed Silence to attract a number of reputable collaborators even before today’s deal with AstraZeneca.

It will be interesting, however, to see whether the value of the AtuRNAi patents are as significant as is claimed, since the seminal Tuschl II patent series demonstrates the use not only of 3’ overhang siRNAs, but also those without such overhangs. It should be noted that while retaining RNAi activity, blunt-ended siRNAs have been shown to be less potent than 3’ overhang siRNAs. Moreover, Tuschl II, to which Alnylam Pharmaceuticals holds exclusive rights, covers siRNA modifications in general and 2’O-methylations in particular. Only last week, Alnylam has strengthened this position by securing exclusive rights to ISIS’ fundamental nucleic acid modification patents for the use in RNAi Therapeutics.

Indeed, at least one licensee appears to have started to doubt the strength of the AtuRNAi IP position. After it had licensed two AtuRNAi agents from Silence that have entered phase I clinical studies this year, Quark subsequently decided to be covered through Alnylam’s InterfeRx siRNA licensing program as well.

However, unless Alnylam feels threatened in its ability to negotiate high-value collaborations due to secondary RNAi IPs such as the AtuRNAi platform, I do not expect them to resort to legal measures at this point. Today’s deal should be seen as yet another validation for the RNAi Therapeutics platform and the considerable funding stream flowing in should strengthen the whole field. Silence has certainly proven its business savvy, now is the time for them to show that they can also execute on their own cancer focussed clinical programs.