Merck’s Alan Sachs, on RNAi’s Big Challenge: Delivery, Delivery, Delivery
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of the things we are told are true are things we can confirm to be true enough to have value.
X: So I guess that means there’s a lot of hype here, right?
AS: There’s a lot of hype, and there’s a lot of ideas. But it’s not a straightforward problem. Injecting something in the bloodstream, leading to something appearing in the cytoplasm in the RNA-silencing complex, there are a lot of black boxes between those two steps. People who are entering the field start with a white paper. It’s much like people who started on targeted therapeutics years ago started with a white paper. If it were so easy, one would have to describe why so few examples exist. The same is true in the RNAi delivery process. You can write down the steps. You can write down what you think will happen. But then you have to put it in a 50-nanometer particle that’s safe and potent to deliver.
X: OK, so you have a graph that shows the 250 or so opportunities that you’ve evaluated. You’ve actually consummated a handful of collaborations? Have they been announced?
AS: No. But we’ve done a lot of evaluations in anticipation of collaborations. A few have proceeded to collaborations, and we don’t disclose those. We generally don’t unless it’s something unusual. There’s a lot of activity we’ve done that we can’t or choose not to disclose.
X: Why? Because of the competition?
AS: It’s a combination of the competition, and from our seat, a misunderstanding of the intent of the collaboration. That is, the field is so ready to put money in, we don’t want a Merck collaboration to be read as a sign of approval. The goals of our collaboration, after an initial period, are to develop something that is usable in the non-human primate.
Ian McConnell: It’s fundamentally about managing expectations.
X: On a different train of thought, what kind of delivery technologies do you like or think have promise at the moment?
AS: There are three main areas of delivery. First are lipid-based delivery systems. At the time of our acquisition of Sirna, they had successfully shown lipid-based delivery to the liver. Initially, it was through a collaboration with what is now called [Vancouver, BC-based] Tekmira. That was really the leading standard for the area. Several [applications to begin clinical trials] have been filed with the FDA. We spent a lot of internal research money and time on novel lipids. The liability of that platform is absolutely its safety. As you know from writing about the area, the biodistribution of lipid is focused toward the liver. Which has some indications that are useful for IV therapy, but it’s restrictive with respect to cancers and diseases of other organs.
We’ve also moved into two other delivery areas. One is polymer-based delivery. It’s exemplified by the Mirus delivery system that Roche fully acquired in 2008 for $125 million. That’s a really nice delivery system because it’s a targeted delivery system. But, it too, has liabilities as does every delivery system.
The last one is a conjugation to RNA system. You directly attach to the RNA molecule a targeting agent. It’s a defined complex, which for local delivery, works well. It can work well for systemic delivery as well. By local I mean something like injection into the joint.
X: What kind of data do you have in hand at this point to support your programs? What’s the best thing that happened in this department in 2009?
AS: There have been a lot of breakthroughs in the department. I think one thing I emphasize, and is good to capture, is that the value for this space is in the commercial product. That’s the long-term goal. The short to mid-term goal may be somewhat opaque to a biotech company, because they don’t have the same pipeline needs as someone like Merck or another large company. It’s about increasing … Next Page »