Ladies and gentlemen, thank you for standing by. Welcome to the Alnylam Pharmaceuticals Conference Call to discuss the Second Quarter 2015 Financial Results. There will be a question-and-answer session to follow. Please be advised this call is being taped at the company's request. I would like to turn the call over to the company.

Good afternoon, everyone. I'm Josh Brodsky, Senior Manager of Investor Relations and Corporate Communications at Alnylam. With me today are John Maraganore, Chief Executive Officer; Barry Greene, President and Chief Operating Officer; Akshay Vaishnaw, Executive Vice President of R&D and Chief Medical Officer; and Mike Mason, Vice President of Finance and Treasurer. In addition, D.A. Gros, our new Senior VP and Chief Business Officer, is in the room and available for Q&A. For those of you participating via conference call, the slides we have made available via webcast can also be accessed by going to the Investors page of our website, www.alnylam.com. During today's call, as outlined on slide two, John will provide some introductory remarks and provide general context for some of our recent progress and achievements. Akshay will summarize recent clinical progress. Mike will review our financials and guidance, and then Barry will provide a brief summary of recent business highlights and goals for 2015 and beyond, before we open the call for your questions. I would like to remind you that this call will contain certain remarks concerning Alnylam's future expectations, plans and prospects, which constitute forward-looking statements for the purposes of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements and as a result of various important factors, including those discussed in our most recent released quarterly report on file with the SEC. In addition, any forward-looking statements represent our views only as of the date of this recording and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligations to update such statements. With that, I will now turn the call over to John. John M. Maraganore - Chief Executive…

Thanks a lot, Barry. Operator, we will now open the call up for questions. And as a reminder to those dialed in, we would like to ask you to limit your questions to two each.

. Our first question comes from Anupam Rama with JPMorgan.

Hey, guys. Thanks so much for taking the question. I know you announced a development candidate today for targeting TTR that could support once monthly or even quarterly dosing. I'm wondering if you could help put into context the improvement in potential dosing frequency into the context of the medical unmet need in FAP and FAC that you see. Thanks. John M. Maraganore - Chief Executive Officer & Director: Yeah. It's a – Anupam, it's a great question and before I turn it over to Akshay to answer the question fully, I'll just say that we're very excited about this development candidate. It's been in the works for quite some time, and we're going to share a lot of specific data on this at the OTS Meeting in October, which is being held in – where is it being held – in Europe someplace. Sure. Netherlands. So, let me now turn it over to Akshay to address the second part of your question. Akshay K. Vaishnaw - Chief Medical Officer & Executive Vice President: Yeah. Hi, Anupam. I mean, we are very committed, and have been for some time, to the TTR space and the range of diseases, FAP, FAC, SSA, and we're developing a range of options. We have intravenous patisiran. Of course, we also have subcutaneous approaches. And TTRsc02, our announcement today looks to us, based on everything we understand about these (ESC)-siRNA conjugates that we are building now, to be by far and away the most potent and best conjugate we've built in association with the program. And it looks, at least based on animal work, like it could readily be a once-monthly to once-quarterly injection at low doses. And I think ultimately, a product like that is going to be very important in the management of these patients, as we look across the spectrum of TTR diseases. And we will feather that in, and create that as an option for patients, as the entire sort of programs develop. But we are pretty excited and confident, based on understanding of the ESC platform, that this is going to be a very important low dose, infrequent option for patients.

Awesome. Thanks for taking our question. John M. Maraganore - Chief Executive Officer & Director: Thanks, Anupam.

Our next question comes from Ritu Baral with Cowen. Ritu Baral - Cowen & Co. LLC: Hi, guys. Thanks for taking the question. Could we - John M. Maraganore - Chief Executive Officer & Director: Thanks, Ritu. Ritu Baral - Cowen & Co. LLC: Could we get a little more detail on the FAC injection site reactions that you mentioned? Could you characterize the diffuse rash a little better, and where along the treatment duration did the really problematic reactions emerge, since it was in the open-label? John M. Maraganore - Chief Executive Officer & Director: Sure. Akshay, you want to speak to that? Akshay K. Vaishnaw - Chief Medical Officer & Executive Vice President: Sure. Yes, I mean, Ritu, we described three patients today that had discontinuations, and of the three, two had diffuse rash. And by diffuse rash, what I mean is a rash extending somewhere beyond the injection site. And with respect to where they were in terms of the duration of the exposure, you know, I think all the patients are out into many months of exposure. They are all at slightly varying stages, and these patients weren't necessarily the most advanced in terms of the extent of exposure. In fact, there are other patients who have been dosed longer and are doing just fine. So I don't think there is any evidence that this is some exposure-based event. Ritu Baral - Cowen & Co. LLC: So, there was no associated anaphylactoid reactions, or was there – did they have reactions that got worse and worse, or was it sort of...? Akshay K. Vaishnaw - Chief Medical Officer & Executive Vice President: No, none that were reported. And in fact, there were no sort of anaphylactoid reactions or reactions that got worse and worse. Ritu Baral - Cowen & Co. LLC: Got it. And then, my second question is on the porphyria data. Given it's so early, was that just a function of enrollment, or were you seeing a biological effect essentially – or biochemical effect, earlier than you had expected? John M. Maraganore - Chief Executive Officer & Director: Well, Ritu, let me answer that. I mean obviously, we'll have to wait just a few weeks here before we talk about the specific effects and any data regarding that. You know, we, of course, are able to look at these patients. We've had good enrollment in this study. The study is being performed in Sweden. The site there is extremely poised. They've done studies in these ASH patients before, and so we've been very pleased with the enrollment. So that's helped considerably. But let's wait till this mid-September meeting, you know, in Germany, and we'll have an opportunity of sharing those specific data with you. Ritu Baral - Cowen & Co. LLC: Got it. Fair enough. I had to try. Thanks, guys. Barry E. Greene - President & Chief Operating Officer: Of course. John M. Maraganore - Chief Executive Officer & Director: Thanks, Ritu.

Our next question comes from Robyn Karnauskas with Deutsche Bank.

Hey, guys. This is Ale on for Robyn. Thanks for taking the questions. John M. Maraganore - Chief Executive Officer & Director: How are you?

Good, how are you? John M. Maraganore - Chief Executive Officer & Director: Great.

So my first question is on PCSK9. At this upcoming readout, will we get a good feel if quarterly dosing is possible? And secondly, how do you think the recent approvals and labels affect your market opportunity? John M. Maraganore - Chief Executive Officer & Director: Yes. So I will answer the first part, and then maybe Barry can answer the second part. You know, obviously, in the study, we're going to report all the data we've got. It's about 70 subjects worth of data. These are subjects that had elevated LDL cholesterol at baseline. In the multi-dose phase of the study, we also explored on statins and off statins. And we've been able to follow subjects beyond 90 days from the single dose phase of the study so to the extent that the pharmacology supports quarterly dosing, we'll be able to infer that very clearly from the quarterly dose – from the subjects that get single doses that are followed for considerable long periods of time. So I think we'll certainly be able to address the profile of the drug at this upcoming presentation. And let's just wait for the presentation before we get into any further detail. But Barry, you want to talk with about the recent approval and label - Barry E. Greene - President & Chief Operating Officer: Yes. Absolutely. John M. Maraganore - Chief Executive Officer & Director: And our thoughts on that? Barry E. Greene - President & Chief Operating Officer: Absolutely. And just to emphasize the point we made earlier, first in class synthesis inhibitor with the once monthly or less frequent subcutaneous opportunity, we think is incredibly competitive. So from the regulatory path perspective setting up the commercial opportunity, we find a tremendous synergy between our belief set and what's now been proved out in Europe and the U.S. which is that, on LDL lowering, as long as the cardiovascular outcome study is up and running, a drug with can be approved. So we find that rewarding as well as the label that was granted so far. And then the pricing is consistent with our belief set, on that $10,000 to $15,000 per patient per year price set. So they are defying the market that a first in class RNAi synthesis inhibitor can come behind and I think have a big impact on the market that's being defined by the PCSK9 antibodies.

Great. Thanks. And then just a quick follow up on hemophilia, can you characterize the PK or give context as to what doses we might start to move into the threshold of over or greater than 66% knockdown? John M. Maraganore - Chief Executive Officer & Director: Yes. I think what you're asking is, what doses do you think will get us to the consistent over 66% knockdown?

Yeah, yeah. John M. Maraganore - Chief Executive Officer & Director: The first dose cohort monthly is using the equivalent of 75 micrograms per kilogram times three monthly; in other words, 225 micrograms per kilogram monthly. And we are going to be very likely exploring dose escalation as well beyond that dose. And again, we'll have a considerable number of additional subjects, 9 to potentially 12 additional subjects worth of data at ASH, again, pending abstract acceptance. So there will be a lot of information there, and we're very encouraged by the program. We thought the data at ISCH were very exciting, and we believe that we'll continue to show the important approach that this can present for hemophilia patients.

Great. Thanks, guys. John M. Maraganore - Chief Executive Officer & Director: Great. Thank you.

Our next question comes from Geoff Meacham with Barclays.

Hey, guys. It's actually Mike (41:05) in for Geoff. Thanks for taking the question. John M. Maraganore - Chief Executive Officer & Director: Hey, Mike (41:08). How are you?

Good. Thanks. Just with respect to the ALN-CC5 program, you mentioned beginning dosing in PNH by year-end 2015. Could you maybe just remind us what endpoints you'd be looking at there, and then sort of how you're thinking about the bar to sort of moving that program forward? Thanks. John M. Maraganore - Chief Executive Officer & Director: Yeah. Absolutely. Let me have Akshay answer that. Akshay K. Vaishnaw - Chief Medical Officer & Executive Vice President: Yeah. Sure. Of course, first and foremost, we'll want to understand safety in that population. Beyond that, PNH patients with the validation of C5 as a target offer a range of other very important biochemical and other endpoints. So LDH, lactate dehydrogenase, is a very important marker for clinical efficacy. And just as eculizumab has shown, we hope to show reductions in LDH. And underlying that, the basis for that reduction in LDH would be reductions in hemolysis, which would be associated with reductions in C5. So we'll also aim to show substantial reductions in C5 levels, just as we've begun to show in the Phase 1 study in healthy volunteers associated with significant suppression of serum hemolysis. So, those are some of the key datasets and I think that they set us up hopefully to show clear validation of ALN-CC5 for PNH, accelerating us into Phase 3. John M. Maraganore - Chief Executive Officer & Director: Yeah. And I'll just add to Akshay's comments, Mike, that at ASH – at the upcoming ASH Meeting, we would expect to have results of our single dose – complete single dose results combined with a multi-dose result and our expectation is very much that we will see a very complete inhibition of serum hemolytic activity, just as we've seen in non-human primates. So, that is something that we'll present in December. And then by starting our first PNH patients by the end of the year, we'd expect to see these type of LDH data that are very de-risking and important, probably sometime in 2016, right. So – but that's how the news flow – you can expect the news flow to go on that program at this point.

Okay, great. Thanks, guys. John M. Maraganore - Chief Executive Officer & Director: Thank you.

Our next question comes from Terence Flynn with Goldman Sachs. Cameron A. Bradshaw - Goldman Sachs & Co.: This is Cameron filling in for Terence. Thanks for taking our question. John M. Maraganore - Chief Executive Officer & Director: Hi, how are you? Cameron A. Bradshaw - Goldman Sachs & Co.: Doing great. Thanks. So, just a follow-up on the rash in press release, can you give us any more details on the severity of the rash? And how these patients were treated? Were they biopsied? And if so, can you tell us what the findings were? And then finally, were these the three patients that were part of the initial cohort of six patients that had a rash or are they different patients? Thanks. John M. Maraganore - Chief Executive Officer & Director: Yeah, Akshay, do you want to handle that? Akshay K. Vaishnaw - Chief Medical Officer & Executive Vice President: Yeah, so in terms of severity, the patient – the two patients with the diffuse rash. One was a mild rash and one was deemed to be severe. Neither were serious adverse events, so not of the magnitude requiring hospitalization or anything. They – it all resolved spontaneously and so really required no specific treatment that I need to describe. And in terms of the investigation of biopsy or such, of course, we're bringing you all of the clinical data as we have it today. We're doing everything to understand these events and at the later disclosure in the year when we'll announce the six months data on this study, we'll have many more details and we'll share at that time. John M. Maraganore - Chief Executive Officer & Director: Yes, go ahead.

Our next question comes from Alan Carr with Needham & Company. Alan Carr - Needham & Co. LLC: Thanks for taking my questions. John M. Maraganore - Chief Executive Officer & Director: Hi, Alan. Alan Carr - Needham & Co. LLC: Hi. Coming back to the rash, anything – you're running a Phase 3 also. Can you comment on what you're seeing from the safety perspective there around the rash and discontinuation rate? And then also with the AS1 program moving along here, do you have any estimates of when that might move into registration trials? Would that be a little sooner than you expected? Thanks. John M. Maraganore - Chief Executive Officer & Director: Yes. Sure, Alan. Well, Akshay, do you want to handle both those questions? Akshay K. Vaishnaw - Chief Medical Officer & Executive Vice President: Sure, yeah. So with respect to the revusiran and rashes in the Phase 3 ENDEAVOUR study, of course we started the study towards the end of last year. It's proceeding nicely. More details to follow. But with respect to the safety itself, it is a randomized double-blind, placebo-controlled study so I'm sure, Alan, you are not supposed to hear me say that I can't really speak to the safety. But suffice it to say that the overall conduct of the study is fine and it's ongoing and we're excited to continue with it. So with respect to the AS1, as we announced today, we're excited to present the initial data from the study and we will be looking at very important biochemical markers, such as ALA and PBG, which is the mediator that's believed to off acute intermittent porphyria. And as that dataset develops through this year and the early part of next year, I think we'll want to give guidance…

Our next question comes from Mike King with JMP Securities.

Good afternoon, guys. Thanks for taking my questions. I just wanted to – I don't want to harp on this incidence of rash, but I did want to come back to Akshay, because I'm not sure he answered the previous question regarding the denominator of patients, so this was three out of how many at the time that were in the revusiran OLE? John M. Maraganore - Chief Executive Officer & Director: Yeah. I mean, Akshay can comment as well. But the answer there is of the patients that went into OLE, 25 patients went into the OLE. Akshay K. Vaishnaw - Chief Medical Officer & Executive Vice President: Sorry. Yes, I think the question asked about six patients. John M. Maraganore - Chief Executive Officer & Director: Yeah. That's right. There's not six patients. Akshay K. Vaishnaw - Chief Medical Officer & Executive Vice President: Yeah. John M. Maraganore - Chief Executive Officer & Director: 25 patients went into the OLE. Akshay K. Vaishnaw - Chief Medical Officer & Executive Vice President: Right.

Okay. So it's not three out of six. It's three out of 25. Akshay K. Vaishnaw - Chief Medical Officer & Executive Vice President: Oh, yeah. John M. Maraganore - Chief Executive Officer & Director: Yes.

Okay, great. That's a lot different. And then I'm just curious, remind us again about, you characterized the new TTR inhibitor as second gen chemistry, but I thought technically revusiran was second gen chemistry. So, perhaps you can just illuminate for us, what the difference between revusiran would be relative to the new TTR inhibitor. John M. Maraganore - Chief Executive Officer & Director: Akshay, you want to handle that? Akshay K. Vaishnaw - Chief Medical Officer & Executive Vice President: Sure. Revusiran is the first conjugate we built, Mike, and that was the first in the clinic, it was the first to show that GalNAc conjugated sRNAs could be very effectively delivered to (49:20). It being the first generation, naturally the potency and dose that's required is higher than what we've seen with subsequent use of chemistries with the second generation that we call ESC GalNAcs. And in fact, the entire pipeline beyond patisiran and revusiran, all these other amazing programs that we're now exploring, hemophilia, C5, porphyria, et cetera, these are all based on the second generation chemistry, PCS et cetera, and one of the learnings from that. And I think we've reported data both for AT3 and C5 is the substantially greater potency associated with the second generation and durability, which leads us to make these statements. So Q monthly Q quarterly dosing at lower doses, with all those programs and the second generation ESC GalNAc and of course, with that, as you reduce exposure, all exposure-related adverse events would also go down. So overall, it's a very exciting package, I think, with the ESC folks. (50:23)

Right. So if I can sort of paraphrase from your comments, Akshay, the revusiran is different than everything, every construct that comes from – comes behind it, correct? Akshay K. Vaishnaw - Chief Medical Officer & Executive Vice President: Correct. John M. Maraganore - Chief Executive Officer & Director: That's exactly right. That's correct, Mike.

Great. Okay, super. Now I just want to shift quickly to patisiran to ask you – I know, John, we had spoken recently a couple weeks ago about your taking a look after 100 patients had been on patisiran for 18 months. But I'm also – I'm asking, is there a possibility of a either shorter interval or lesser number of patients, now that you would be comfortable talking about, as far as when the next analysis occurs, or is that number still fixed? John M. Maraganore - Chief Executive Officer & Director: Yeah, no, Mike, I think what we discussed was what the potential is for an interim analysis for efficacy with the APOLLO study. And where we are on that is, we are going to have discussions with FDA and EMA to explore that. What I think I commented to you is that it would be reasonable to consider something like half the study population at the 18-month endpoint as a type of way of doing that type of analysis, which would take you into sometime next year, for when that would take place. But if and when we reach agreement with the regulatory authorities on this, we'll come back and provide guidance. There are other reasons to not do it, right. There are other reasons to say, let's not take a hit on our power and just complete up the study. So, we'll have to – we'll get back to you on that when we have clarity with regulators on the path forward. But what I was referring to is really a logical way to think about doing an IA, would be at sort of the mid-mark from an accrual standpoint, at the 18-month endpoint.

Great. Thanks for the clarification. John M. Maraganore - Chief Executive Officer & Director: Great. Thanks, Mike.

Our next question comes from Ted Tenthoff with Piper Jaffray. Ted A. Tenthoff - Piper Jaffray & Co (Broker): Great. Thanks. Can you hear me okay? John M. Maraganore - Chief Executive Officer & Director: Yeah. Hi, Ted. Ted A. Tenthoff - Piper Jaffray & Co (Broker): Hey. How are you guys? John M. Maraganore - Chief Executive Officer & Director: Good. Ted A. Tenthoff - Piper Jaffray & Co (Broker): Thanks so much for a thorough update. A lot of questions answered. I guess a quick one, if I may, on hepatitis B. Obviously, a very dynamic market. So really, where do you sort of see the role of RNAis fitting into hepatitis B therapy? And remind me, if you would, sort of what the construct, or what the – what ALN-HBV actually is. John M. Maraganore - Chief Executive Officer & Director: Yeah. Ted A. Tenthoff - Piper Jaffray & Co (Broker): Are there multiple sequences within that? John M. Maraganore - Chief Executive Officer & Director: Yeah. So, let's go – let's address the first question and then the second question. So, in terms of where this fits in, we believe, and the community believes and agrees with us, that an agent that can substantially knock down surface antigen has the potential of changing the dynamic of... Ted A. Tenthoff - Piper Jaffray & Co (Broker): Yeah. John M. Maraganore - Chief Executive Officer & Director: ...how HBV is managed. Surface antigen is known to be tolerogenic. It's one of the mechanisms whereby HBV can elude immune detection. And so, clearly, having an agent like an RNAi therapeutic that can substantially knock down and significantly multi-log knockdown of surface antigen, is something that we think we can achieve with ALN-HBV. And I often refer to the Regulus…

Our next question comes from Michael Schmidt with Leerink.

Hey. Good afternoon, and thanks for taking my questions. John M. Maraganore - Chief Executive Officer & Director: Hi, Michael.

Hey. I'm sorry to harp on this, but one more on the rash. My question there is – were these one-off events, or did they occur repeatedly in the same patients, and what might a biologic explanation be? And then the other question was on PCSK9. I know The Medicines Company is taking over Phase 2 development. But I was wondering what Phase 2 plans might look like in terms of magnitude, extent and timing? John M. Maraganore - Chief Executive Officer & Director: Great. Well, I think, on the second one, first, if I may – and then I'll hand it over to Akshay – we'll give more guidance on that in the coming weeks. Right. So, as we present data, there will be additional guidance in terms of plans going forward. So please stay tuned on that one, Michael. But then Akshay, do you want to handle the first question? Akshay K. Vaishnaw - Chief Medical Officer & Executive Vice President: Yes, sorry. Just to recap the question, Michael, were they recurrent was the question?

Yes, recurrent or one-off events and what might the sort of mechanistic explanation be? Akshay K. Vaishnaw - Chief Medical Officer & Executive Vice President: Yes. In terms of mechanism, I think we will accept that subcutaneous therapeutics, regardless of class, are associated at some discrete level with injection site reactions. And even with revusiran in the Phase 2 study, we reported some injection site reactions, which in some subjects were recurrent. So you know, no surprise there for us. And, indeed, in these three individuals, some of them were recurrent. The diffuse rash that I described wasn't a recurrent diffuse rash as such. And that's how we've got the clinical understanding at the moment. You know, with respect to the pathophysiology, I think someone else asked about if we got biopsies. You know, we're trying to understand all of this right now and later in the year when we present the 6-month data, we'll present all the laboratory analyses that we are doing to try and characterize this further. But, the clinical understanding is as I described it today and in the press release. John M. Maraganore - Chief Executive Officer & Director: And I'd just add, Michael, that, you know, this is related to other oligonucleotide therapies as well. Drisapersen has an over 70% incidence of injection site reactions. Mipomersen has equally great level of injection site reactions. You know, we're not seeing that high of incidence in our study. And so this is really oligonucleotide type things. But it also happens with other classes of drugs. It happens with protein therapeutics, Embrell, others. So it is part of drug development and obviously it's something which we want to be transparent about and that's why we're reporting it. But the full data will come out when we present our data it in November with the 6-month update from revusiran. The good news is that patients – the vast majority of the patients are tolerating the drug well and continue on study.

Yeah, understood. Great. Thank you. (59:49) John M. Maraganore - Chief Executive Officer & Director: Yeah, good. All right. Thank you.

And I'm not showing any further questions at this time. I'd like to turn the conference back over to our host. John M. Maraganore - Chief Executive Officer & Director: Okay. Well, thank you, everybody. Appreciate the time today. As I said earlier, this is going to be a very data-rich period in the back half of the year and we can't wait to share all the data with you, all right. Thank you. Bye, bye.

Ladies and gentlemen, this does conclude today's presentation. You may now disconnect and have a wonderful day.