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Medicines Company CC excerpt on PCSK9 Now, let’s move to PCSK9. PCSK9 is a protein that controls the metabolism of the receptor for LDL, the cholesterol component that is most strongly associated with atherosclerosis. Both gain a function and lose a function mutations for PCSK9 that have been described that result in increases or decreases in LDL and atherosclerotic disease respectively. Monoclonal antibodies against PCSK9 are in late development by Amgen, Sanofi, Regeneron and others and recently published Phase 3 studies have demonstrated 40% to 70% reduction in LDL and concomitant reductions in cardiovascular events. We believe PCSK9 inhibition by RNAi has potential advantages over these monoclonal antibodies. Using an IV formulation and delivery our partner Alnylam demonstrated proof-of-concept in a randomized Phase 1, single-blind, placebo-controlled, dose escalation study published in the Lancet. Turning to potential subcutaneous dosing, the GalNAc-siRNA conjugate delivery platform technology of Alnylam is validated for targeted liver-specific proteins. Together, we have been developing a subcutaneous form of PCSK9 RNA interference utilizing Alnylam’s GalNAc-siRNA conjugate delivery platform. Early this year, Alnylam reported non-human primate studies in which ALN-PCS Sub-Q demonstrated robust, durable and clamped knockdown of PCSK9 of up to 96% and reduction of LDL-C of up to 77% with single-dose of this agent in the absence of statins. The data potentially support once monthly and possibly once quarterly subcutaneous dosing regimen. We also anticipate Sub-Q injection volumes of 1 ml or less. Together with Alnylam, we plan to initiate clinical trials with the subcutaneous product candidates shortly. Importantly, ALN-PCS Sub-Q is not an antibody. Amgen recently filed the patent infringement lawsuit against Sanofi, Regeneron related to their PCSK9 antibody. From the Q&A: Umer Raffat - ISI Group Thanks for taking my question. I have three broad questions. I will list them all out together, maybe the first one is on I think the most meaningful disclose, the mostly meaningful thing I learned today was on the possibility of a quarterly PCSK9 regimen. So I want to understand what are the theoretical risks the way you guys think about it sitting here right now, what are the theoretical risks preventing than from happening and what’s the royalty rate down on Alnylam is that around 10% of sales the way we understand it that’s first one. Secondly, on Angiomax litigation, so I am struggling with three tidbits from this call. So on the one hand Clive you mentioned at the Investor Day we will see new information on NDAs and R&D programs so you didn’t mention anything on the Angiomax litigation, but on the foot side you guys did mention you are looking for partnerships in Europe and how legal costs and the litigation are going up by $5 million. So can you help us understand should we expect the hospital resolution or not? Thank you. Clive Meanwell - Chairman and Chief Executive OfficerOkay. Well, first of all I am not going to comment on hospital resolution since it’s an appeal and I think at this stage it will be an appropriate for us to comment on that. Legal costs are legal costs. I mean, there is a four-letter work that’s associated with these kinds of disputes and the $5 million grant unavoidable I guess. Glenn Sblendorio - President and Chief Financial OfficerOver and above and they are costly suits and that’s the additional color I can give you I am sorry. Clive Meanwell - Chairman and Chief Executive OfficerYes. And then in terms of one of the theoretical risks of the three monthly dosing, well, it’s called research. So, there is all kinds of risks. What we can see in the primate models which have generally predicted human responses, Scott is a pretty good sense that monthly is a relatively likely, three months there is a distinct possibility, what do you think? Scott Johnson - Chief Medical Advisor, New Business VenturesYes. I think one thing I would like to point out in terms of the differentiation of this approach versus the antibodies is that we have often times used the analogy of the difference between mopping up the floor versus turning off the closet. PCSK9 inhibition in the liver is achieved by the short interfering RNAs. In contrast to PCSK9, mopping up in the periphery which is achieved by the monoclonal antibodies. The monoclonals are more stoichiometric in other words one for one inhibition of molecule per molecule. So what that allows us we think to achieve here is number one smaller volume dosing from at least what we have seen so far if the non-human primate translates into humans appropriately. And then secondly is the duration of effect. And as Clive just said and our guys said earlier a very robust effect at one month – with the one month dosing regimen and continued influence inhibition up to three months. So that’s what we have seen to-date how that translates into actually the choice I think is remains to be seen with the research we are doing. |
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Msg # | Subject | Author | Recs | Date Posted |
31734 | Re: Medicines Company CC excerpt on PCSK9 | eintracht67 | 0 | 10/23/2014 8:26:26 PM |
31736 | Re: Medicines Company CC excerpt on PCSK9 | sherk | 3 | 10/26/2014 11:23:52 AM |