Deel 5:
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Dr. Geoffrey Cox
The interesting part about ADCC, this has become a subject of great interest, and it really refers to the carbohydrates glycosylation which are associated with many proteins which are produced in mammalian cells, and it varies. In some instances, for instance, some biologicals have no glycosylation associated with them, which is things like human growth hormone and insulin. Other products have glycosylation, but they apparently play a very little part in the activity of the product or the therapeutic benefit of the product. And there are other proteins where this cell cytotoxicity appears to be important and is related to what is considered to be a low fucose level. The transgenic technology which we use, appears to produce proteins with low fucose carbohydrates in a natural fashion. Many companies are trying to do this in other systems by modifying those systems to do that. That could give us some benefit in monoclonal antibodies where additional benefit from ADCC could be important.
The issue with follow-on biologics is my expectation that you will not have a situation where you can define a follow-on biologic purely by analytical purposes. I think my expectations of legislation will allow for and I expect the FDA to also want to see some fairly significant amount of clinical development and also safety criteria, but there is the potential, if you develop a follow-on biologic in that fashion, maybe also to have some characteristics of the glycosylation, which could be beneficial in relation to the originator's product. I think this is something which is still a bit of work in progress at the moment, Roy. It’s something which I thought would be of interest to investors. This technology appears to have some real opportunities in terms of being able to leverage this particular aspect of our glycosylation using this technology.
Allen Seymour - Columbia Management
Yes. I applaud your interest in the follow-on biologics. In particular, I'm interested in -- since most of those things are done, I think in E. coli, maybe you could talk a little bit about besides this ADCC, whether there are any other impediments to your moving ahead in this area, besides financial, I guess, is the real question.
Dr. Geoffrey Cox
Well, I think the impediments to financial… clearly, we link the development of a strategy of follow-on biologics to a partnering strategy and so that's something which we regard as being fairly intimately linked. I think the issue around E. coli is that E. coli doesn't produce proteins with the glycosylation, which I was just describing. So you can use it fairly well for things like human growth hormone or insulin, these types of products. But it's not an appropriate manufacturing system where glycosylation is important. I think people are still considering what types of systems to use going forward.
Obviously, there's a lot of intellectual property around the use of mammalian cell culture, typical CHO-cell type of production systems. We believe that we've got some advantages in that respect in terms of having the freedom to operate using our transgenic technology. We also believe, actually, we have some nice production in terms of being able to produce these proteins under the umbrella of our IP in the United States, which goes through 2021. So I think that this is still an emerging area, and I think it's a little early to say exactly how all of this is going to fall out, but I do believe that we have demonstrated very successfully in the past from a number of collaborations we've had on monoclonal antibody production for big Pharma and big biotech in the late 90s that we can produce these proteins very successfully in large volumes using our production system. I think this is an area which we should pay real attention to and one which we will certainly be updating you with as we move forward in the future.
Cory Kasimov – Oppenheimer
Thanks for taking the questions. I only have two left here. The first one revolves around the DIC Phase II study. If you could provide us with some additional detail on the design and endpoints of that study, and also how many centers LEO is expected to use to enroll the 200 patients?
And secondly, regarding the biosimilars, I too am encouraged to hear of the company's future plans for this space. And realizing that it's very early on here, can you go at all into potential strategy and who'd you be talking to, whether you'd be partnering with existing generic companies, how, where some of these companies may be of your manufacturing technology. Just any way you can expand on any of that.
Dr. Geoffrey Cox
Okay. Let me just deal with the biosimilar piece first. I don't want to be too specific, because this is something that's still kind of a work in progress. I hope that'll be something I can update you with a little bit more detail as we move forward. Clearly, there are a number of fairly significant players that are developing in this particular marketplace, which we would regard as potential targets. Clearly it will be an extremely competitive marketplace, and therefore we would certainly be looking to talk to some of the companies which you can probably identify for yourselves, who would be interested in being able to bring these products through and to commercialize these products for us. So we would really look at ourselves as being the production system for these types of products. That's where our thoughts are at this moment, anyway. We'll obviously see how that develops through the future.
As far as the DIC Phase II study, it's about 200 patients. I don't know the exact number of sites, but it's not a large number of sites, probably on the order of 15, 20 sites, something of that order and limited number of countries in Europe where LEO has a presence, so that they can actually conduct the study principally themselves. The study is based on -- it's a dose ranging study. It is not statistically powered to demonstrate benefit from regards to survival. Certainly, the Phase III study, which follows on with our expectations is that survival will be the primary end point.
This particular study is based on a DIC score and there is an international-accepted DIC score which will be important in terms of bringing the patients into the study and also being able to measure any improvements in those patients who are treated both in the active arm and obviously in the control arm. The control arm is again standard of care. The standard of care is pretty well antibiotics plus fluids. If a physician wants to use heparin in that arm, he or she can do so. Heparin is not allowed in the action arm. You've heard me discuss this before, we believe that heparin is contraindicated with antithrombin in the treatment of this patient population, and therefore it's not allowed in the active arm. We do not allow Xigris in that particular arm. It's against standard of care.
Roy Friedman
Have you budgeted any receipts from Merrimack during 2007?
Dr. Geoffrey Cox
Yes, we have budgeted some receipts from Merrimack, but we don't break those out separately into what would be PharmAthene or Merrimack or whatever. Yes, they are budgeted in our figures for this year.