At a time that Big Pharma continues to slash internal research and early-stage development, it is not surprising to witness GSK buy access to such capabilities from ISIS which has proven quite effective therein. In fact, efficient drug discovery and early-stage development is one of the major benefits of developing therapeutics based on RNA gene silencing, whether antisense or RNAi. Moreover, the deal in which GSK provides ISIS with 5-6 targets that apparently cannot be addressed by conventional means (small molecules, recombinant proteins and monoclonal antibodies), highlights the attraction of using RNA Therapeutics to address hitherto undruggable targets. Some of these targets are in the rare disease field which is rich with molecularly well defined targets (e.g. single-point mutations, gain-of-function mutations, repeat expansions etc) that are particularly well suited for RNA Therapeutics and that has developed into a high-value area for the pharmaceutical industry.
By paying ISIS $35M in upfront now and another potential $20M in milestones for each candidate up to phase II, GSK gives more or less free rein to ISIS to create drug candidates against these targets and gets the option to fully license them without having to enter into a competitive bidding contest. While this may preclude in many cases the types of financials that ISIS achieved in their Genzyme deal for mipomersen, ISIS benefits that somebody already has a vested interest in licensing the targets it is working on. Selecting the right targets is often a challenge for smaller biotech companies that aim to eventually license drugs to Big Pharma. In fact, ISIS, which has declared that it wants to remain a small-sized biotech company that will not develop drugs on their own past phase II, had a few drug candidates handed back to them recently and it remains to be seen what kind of interest some of their drug candidates they came up with on their own for metabolic disease and CRP will garner.
The deal naturally triggered discussions what it might reveal about the dynamics within the RNA Therapeutics industry. Clearly, GSK has a significant interest in RNA Therapeutics as also evidenced by their relationship with microRNA Therapeutics company Regulus in which ISIS holds a ~50% interest and which is physically located at ISIS. In their conference call, ISIS’ management hinted that this prior exposure to ISIS antisense technology is what made GSK choose ISIS (and not Alnylam) as their hub for RNA Therapeutics development.
I agree that this deal, unless it is largely for mechanisms of action that are not aimed at gene silencing or for therapeutic areas for which RNAi Therapeutics have not fully caught up yet, makes a deal between GSK and Alnylam, as a follow-up to their Sirna/Merck relationship that expired about 1 1/2 ago, a little bit less likely. It also puts GSK, maybe feeling a bit burned after their increasingly controversial acquisition of the early-stage platform, anti-ageing company Sirtris Pharmaceuticals, into the category of Big Pharma that wishes not to be left behind in potentially revolutionary drug development technologies, but not make an immediate large financial commitment through in-house research. It is unlikely, however, that an Alnylam would have an interest in accommodating such plans as, like all successful stand-alone biotech companies today, it aims to eventually become an integrated pharmaceutical company, and for it to get there, Roche-like large non-exclusive platform licenses are the preferred way of funding this ambition for now.