Ladies and gentlemen, thank you for standing by. Welcome to the Alnylam Pharmaceuticals Conference Call to Discuss Second Quarter 2016 Financial Results. There will be a question-and-answer session to follow. Please be advised that this call is being taped at the company's request. I would now like to turn the call over to the company. Christine Regan Lindenboom - VP-Investor Relations & Corporate Communications: Good afternoon. I'm Christine Lindenboom, Vice President 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, DA Gros, Senior Vice President and Chief Business Officer, is in the room and available for Q&A. For those of you participating via conference call, the webcast slides can also be accessed by going to the investor page of our website, www.alnylam.com. During today's call, as outlined in slide two, John will provide some introductory remarks and provide some general context; Akshay will then summarize recent clinical progress; Mike will review our financials and Barry will provide a brief summary of our 2016 goals and beyond before opening the call to your question. Before we begin, I would like to remind you that this call contains remarks concerning Alnylam's future expectations, plans and prospects, which constitute forward-looking statements for the purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as well as results of various important factors, including those discussed in our most recently quarterly report on file with the SEC. In addition, any forward-looking statements represent our views only as of the date of…

Thanks, Akshay. I will be referring to slide 21 for a discussion of our second quarter 2016 financial results. We continue to maintain a strong balance sheet ending the second quarter of 2016 with approximately $1.28 billion in cash, including $150 million in restricted investments, from the credit agreements executed in April 2016, as compared coincidentally to the same amount at December 31, 2015. Our financial strength allows us to continue to invest in a broad pipeline of investigational RNAi therapeutics across our three STArs, aligned with achieving our Alnylam 2020 goal. As for financial guidance this year, we remain on track to end 2016 with greater than $1 billion in cash including $150 million in restricted investments. The GAAP net loss for the second quarter of 2016 was $90.1 million or $1.05 per share on both the basic and diluted basis as compared to a net loss of $71.8 million or $0.85 per share on both the basic and diluted basis for the same period in the previous year. Revenues were $8.7 million for the second quarter of 2016 and 2015. Revenues for the second quarter of 2016 included $5.4 million from our alliance with Sanofi Genzyme and $3.3 million from our alliance with The Medicines Company. We expect net revenues from collaborators to increase during the remainder of 2016 due to an expected increase in expense reimbursement for our agreement with Sanofi Genzyme. R&D expenses were $83.2 million in the second quarter of 2016, which included $9.3 million of non-cash stock-based compensation as compared to $67 million in the second quarter of 2015, which included $6.1 million of non-cash stock-based compensation. The increase in R&D expenses as compared to the prior year period was due primarily to higher compensation and related expenses and non-cash stock-based compensation expenses resulting…

Certainly. Our first question comes from Ritu Baral of Cowen. Your line is now open. Ritu Baral - Cowen & Co. LLC: Hi, guys. Thanks for taking the question. My first question is on the ALN-AS1 porphyria program. Can you give us any narrowing of timing on the data that you will be presenting? Could we have it by SSIEM and also what constitutes good data in your eyes, Akshay and John, what's the meaningful reduction in attack rate given the disease burden in acute porphyria? John M. Maraganore - Chief Executive Officer & Director: Thanks, Ritu. It's a great question. So, we are going to be presenting the complete results from Parts A and B, that's the single ascending dose, the multiple ascending dose in the asymptomatic porphyria patients at this meeting in Rome September 7. And we're looking forward to that presentation. I believe it's an oral presentation, yeah, it's a meeting, yeah, it is an oral presentation. And that I think will significantly expand the data that were presented last September which were really the initial data from our porphyria experience. And then, we're planning on presenting the initial recurrent attack patient data, by the end of the year. And as Barry noted in his remarks, we believe that that is hopefully going to be also at ASH, it will be a very busy ASH for Alnylam, but that will be pending abstract acceptance. But we do believe that that's an appropriate venue to present those data. Barry E. Greene - President & Chief Operating Officer: That's going to be the initial experience recurrent-attack patients. I think just in order to calibrate people's expectations, of course, we're still many months away from that. I think it will be encouraging to see as if we can lower levels…

Thank you. Our next question comes from Gena Wang of Jefferies. Your line is now open.

Thank you very much for taking my questions. So the first one for Alnylam, the TTR subcu Phase I trial, based on ClinicalTrials.gov, it seems that enrollment hasn't started and it's not clear by the dosing. Just want to confirm with you that you will start with multiple ascending dose with once-quarterly dosing? And also are you confident that you will be able to present data later this year? John M. Maraganore - Chief Executive Officer & Director: Yeah. I don't – I haven't looked at what our ClinicalTrials.gov entry says there but I can tell you that the study has enrolled volunteers in the study, we have multiple cohorts that have already been enrolled in the study and we're very well positioned to look at data by the end of the year. So, I don't know, Akshay, if you have anything to add to that? Akshay K. Vaishnaw - Chief Medical Officer, EVP-Research & Development: No, I don't. John M. Maraganore - Chief Executive Officer & Director: Yeah. Akshay K. Vaishnaw - Chief Medical Officer, EVP-Research & Development: I think that covers it. John M. Maraganore - Chief Executive Officer & Director: Yeah. I'll certainly take a look and see what ClinicalTrials.gov says, but it's very actively enrolling and we will have data by the end of the year.

And the data will be multiple ascending dose with once-quarterly dosing, is that right? John M. Maraganore - Chief Executive Officer & Director: Well, what we want to test and what you'll see by the end of the year is whether or not we've achieved a quarterly dose profile based on single injection data.

Okay. John M. Maraganore - Chief Executive Officer & Director: Right. So you should be able to see from those data whether or not the durability of TTR knockdown goes out to 90 days or more. And we expect that that dataset will be quite robust by the end of the year.

Okay. Thank you. And then my next question is related to the second-gen GalNAc programs – I mean all the program, if you look at all the programs in clinical development with the second-gen GalNAc just wondering what are the most common drug related adverse events and how many drug related discontinuation? John M. Maraganore - Chief Executive Officer & Director: Yeah. Akshay, you want to handle that? Akshay K. Vaishnaw - Chief Medical Officer, EVP-Research & Development: Yeah. I mean that's quite a few programs to summarize, at the high level Gena, is that the lower doses and infrequent administrations are associated with the second-generation ESC platform and typically as we've guided before once-quarterly or maybe even once every six months dosing has resulted in a very, very good and encouraging safety profile today. I actually, can't – the number is so small of the number of individuals that have dropped out discontinuing, I can't recall off the top of my hand, but it must be very low single-digit. In terms of the adverse event profile, really there is no consistent story to report at this point in time. Obviously, some of these studies are ongoing and placebo-controlled. So we need to look more into those data but at a high level, the safety profile and tolerability profile for the ESC GalNAc looks very different from revusiran.

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

Thank you. Our next question comes from David Lebowitz of Morgan Stanley. Your line is now open. David N. Lebowitz - Morgan Stanley & Co. LLC: Thank you very much for taking my question. There has been some talk recently about taking the cardio data from the polyneuropathy trials and perhaps trying to get that into the labels somehow. What does that mean from the context of potentially some use in the cardiomyopathy? John M. Maraganore - Chief Executive Officer & Director: Yeah. Great question, David, and by the way welcome to our team of covering analysts. Great to have you on board. Akshay, do you want to handle this? Akshay K. Vaishnaw - Chief Medical Officer, EVP-Research & Development: Yeah. I don't want to get into the commercial aspects, but from a clinical regulatory perspective, couple of things to bear in mind. Many of the patients with ATTR amyloidosis of the inherited form have both the polyneuropathy and cardiomyopathy and that's very evident in our APOLLO study where over half of them have some – significant coexisting cardiac disease is also evident in the Phase 2 extension study, the early study for fitusiran. So, the experience one can try and separate the disease into polyneuropathy versus cardiomyopathy. But the vast majority of the patients with detailed mutations have both forms of syndrome. Now the hypothesis that TTR reduction should help both of them is great because our drug will do that and we hope to impact both those aspects of the phenotype. The APOLLO study will give us the first detailed look into that 50%-plus that have cardiac disease, where the TTR reduction cause some significant impact on the cardiac aspect of the phenotype. And if it did so, we would want to bring back to the attention of…

Thank you. And our next question comes from Alan Carr of Needham. Your line is now open. Alan Carr - Needham & Co. LLC: Hi. Thanks for taking my questions. I mean, when you talk of – actually continue to talk on ALN-TTRsc02, and give us a sense of what Phase 3 trial you might run there, which indication and early or late next year. And then also can you talk about the HBV program, a bit about that trial design, and you said that you'll have some initial data from that next year. What do you expect to have then? Thanks. John M. Maraganore - Chief Executive Officer & Director: Yeah, no, Alan, those are both good questions. The first one is important for us to provide some context on. We probably won't be able to give you a specific answer on it though because it really does depend upon our regulatory discussions with the authorities. But I think as a general rule it's our belief that if we can really establish the relationship of TTR knockdown with clinical endpoints from APOLLO and ENDEAVOUR, that regulators, in discussions we have with them, would be open to considering how TTR knockdown could be used as surrogacy in the disease. Now, that requires discussions, it requires alignment and there will be other, certainly other bells and whistles around that. But once we have those discussions with the regulators, we'll be able to really provide some better clarity on exactly how we go forward there. But in general terms that's how we're thinking about it. Akshay, anything else to add to that? Akshay K. Vaishnaw - Chief Medical Officer, EVP-Research & Development: No, I think you've covered them. John M. Maraganore - Chief Executive Officer & Director: Good. Great. Akshay K. Vaishnaw…

Thank you. Our next question comes from Alethia Young of Credit Suisse. Your line is now open. Eliana Merle - Credit Suisse Securities (USA) LLC (Broker): Hi, this is Eliana for Alethia. Thanks for taking my questions. So with fitusiran, beyond hemophilia, are you planning on starting any studies for other rare bleeding disorders, and if so CAN you update us on your thinking and potential timelines there? Thanks. John M. Maraganore - Chief Executive Officer & Director: Yeah. Ellie, that's a great question. I think it highlights the key point about fitusiran which is that it's really a broad-based agent that can be used across the broad spectrum of bleeding disorders, not just hemophilia A and hemophilia B but also other congenital deficiencies of coagulation factors. And even potentially in some platelet disorders where there is clearly a deficiency of thrombin generation and where our drug may provide some benefit. And we're quite interested in these opportunities. Obviously, these are areas of very high unmet need. There really are no competing drugs in those settings and we're going to begin to explore some of those studies as early as next year. But it's too soon to give you any more specific details on that at this time. Akshay, anything else to add? Akshay K. Vaishnaw - Chief Medical Officer, EVP-Research & Development: No. I think you covered it. John M. Maraganore - Chief Executive Officer & Director: Good. Eliana Merle - Credit Suisse Securities (USA) LLC (Broker): Thanks. Barry E. Greene - President & Chief Operating Officer: Thanks, Ellie.

Thank you. And our next question comes from Anupam Rama of JPMorgan. Your line is now open.

Hey, guys. Thanks so much for taking the question here. Maybe just a quick one on fitusiran and kind of thinking about population subsets here. How are you thinking about the acute trauma surgery setting here for Fitusiran with the dynamics of AT3 lowering with the drug? Thanks. John M. Maraganore - Chief Executive Officer & Director: Yeah, that's a great question, Anupam. Do you want to handle that, Akshay? Akshay K. Vaishnaw - Chief Medical Officer, EVP-Research & Development: Yeah. So we already have very good accumulated data from the ongoing study of how to administer factor replacement if someone does have a bleed whilst they are on fitusiran. And as you know, it's happened on a number of occasions, particularly when the AT3 level hasn't gone down to the steady-state effect. So we know that you can combine the factor with AT3 knockdown in fitusiran-treated patients, you can do that safely and get effective hemostasis. But that's an excellent foundation to build on. As the program goes on, we naturally will want to study the specific question that you're outlining and we will do that and we're going to have conversations obviously with regulators to define the best way to do that. But I think already from the accumulated information, it's clear that one can effectively manage patients in a variety of settings using a combination of AT3 knockdown with fitusiran and factor replacement. John M. Maraganore - Chief Executive Officer & Director: And just as a reminder, Anupam – this is John. I mean, you can immediately reverse the effects of fitusiran with the administration of antithrombin, which is a commercially available product. And so that's always available. Now, obviously, I don't think it makes a lot of sense in the surgical procedure to reverse a pro-hemostatic agent instead of taking advantage of the fact the pro-hemostatic agent is onboard. But clearly, if somebody wanted to reverse the effects, they could do it right away, and that antithrombin can be administered with some frequency, it's got a relatively long half-life, compared to recombinant factor.

Great. Thanks so much for taking our question, guys. John M. Maraganore - Chief Executive Officer & Director: Thanks, Anupam.

Thank you. And our next question comes from Mike King of JMP Securities. Your line is now open.

(46:28), you covered everything pretty comprehensively. I also have a fitusiran question which was a certain similar thing to what you guys have done or are planning to do with the ALN-CC5. Would you contemplate maybe combination therapy with fitusiran and there's a long [Technical Difficulty] (46:48) clotting factors or things like [indiscernible] (46:53) those novel agents are approved? John M. Maraganore - Chief Executive Officer & Director: Yeah, Mike, thanks for the question. I think in the case of fitusiran, we're very confident that fitusiran as monotherapy would provide effective hemostasis in patients that have hemophilia A or hemophilia B with or without inhibitors. Obviously, if a patient has a bleed, and just to put this in context, Mike, even patients that are on routine prophylaxis will have bleeds. And when they have a bleed, they treat themselves with more factor. So, if and when a patient on fitusiran has a bleed, they will treat themselves with recombinant factor or with bypass agents if they have inhibitors, but of course the frequency of that is expected to be significantly reduced compared to normal. So, it's not really – I don't think you could really make a comparison to ALN-CC5, that's a very different type of circumstance, because here with fitusiran in hemophilia we are clearly encouraged by the data we have so far showing that we can achieve ABRs – a mediated ABR of 0 in patients with hemophilia without any need for replacement factor altogether. But of course in the larger real world there will occasionally be bleeds that occur just like it does with routine prophy, and those patients will treat themselves with their recombinant factor or their bypass agent.

Have you had a discussion with the regulators about what kind of data you might need in a NDA package (48:29-48:36) number of patients or... John M. Maraganore - Chief Executive Officer & Director: Yeah, Mike, we've had extensive and very constructive and encouraging discussions with both EMA and FDA on the program, as it relates to the Phase 3 studies and the data that would be required for an approval, if those studies turn out to be positive. And we'll obviously provide those details when we initiate the Phase 3 studies in early 2017. Akshay, anything else to add to that? Akshay K. Vaishnaw - Chief Medical Officer, EVP-Research & Development: No, nothing. John M. Maraganore - Chief Executive Officer & Director: Yep. Yeah. But Mike, I don't think there is anything that's particularly different than past guidance on this as it relates to the endpoint being the annualized bleeding rate, the fact that we would look to both patients with heme A and heme B that we would likely to do two separate studies, one in inhibitors, one in non-inhibitor patients, et cetera. Those are generally consistent and will be preserved.

Yeah, no, I understood. I'm just trying to get a sense of sort of what kind of data the FDA and the EMA may need for sort of practice of medicine or management of the disease as opposed to (49:48) here is an ABR rate that we can generate. They often ask questions of that nature, that's why I ask. John M. Maraganore - Chief Executive Officer & Director: Yeah. No, understood. Now, we have good clarity on that, and obviously when we start the studies, we'll provide the details of the study design as we always do at that time.

Great. Thanks so much. John M. Maraganore - Chief Executive Officer & Director: Thanks, Mike.

Thank you. Our next question comes from Madhu Kumar of Chardan Capital. Your line is now open.

Hey, guys. I only have two questions. First one is for the ALN-AAT program. Besides suppression of antitrypsin, what do you think would be like the most measurable read-out for the liver disease? Akshay K. Vaishnaw - Chief Medical Officer, EVP-Research & Development: Yeah. It's a great question, Madhu. Do you want to ask your second one, and then we can go through them? Go ahead.

Oh sure. So the other one with ALN-PCSsc, so obviously the main issue with the PCSK9 family is the cardiovascular outcome trials (50:45). So what would be like a hazard ratio that would make you feel really confident for ALN-PCSsc moving forward? John M. Maraganore - Chief Executive Officer & Director: Okay. Those are two great questions. Akshay, do you want to handle both of them? Akshay K. Vaishnaw - Chief Medical Officer, EVP-Research & Development: I can handle the first one. The lip read out with respect to AAT, so beyond the AAT knockdown, what ultimately matters of course to patients is does that result in clinical benefit with improvement in liver outcomes. And there are a number of ways to look at that. There is liver elastography, which is increasingly validated as the measure of the degree of fibrosis in the liver. Secondly, there are panels of markers that reflect the extent of ongoing fibrosis in the liver, and a test for that is validated and used in Europe, and we can think about incorporating that. And then finally, as being used very productively in trials, particularly in biologic liver disease, you can do pre- and post-biopsies and score the biopsies for degree of fibrosis. And so we're looking at the full range of possibilities there, and based on dialogue with regulators though, obviously we'll come back to you and let you know more. One of the particularly interesting things about the biopsy approach in AAT liver disease is that there are these characteristic lesions seen on the biopsy, PAS positive lesions on AAT livers. And it will be very interesting to see how AAT knockdown result is going to change in the number and size of those PAS-positive granules, and that can be a very important histologic…

All right, thanks, guys. John M. Maraganore - Chief Executive Officer & Director: Sure. Thanks, Madhu.

Thank you. Our next question comes for Ted Tenthoff of Piper Jaffray. Your line is open. Ted A. Tenthoff - Piper Jaffray & Co. (Broker): Great. Thank you. Actually a lot of the questions have been answered here. I wanted to get a sense maybe for the longer term with respect to the (53:52) manufacturing at your facility that you're building out. What scale do you think that facility is going to be able achieve for the $150 million investment? I mean clearly patisiran will be the first test. But sort of high level, how much drug do you think you can push out of that, and maybe thinking it just in terms of a sequential list – patisiran, revusiran, and fitusiran, how many of these do you think you might be able to get out of that facility before having to expand? John M. Maraganore - Chief Executive Officer & Director: That's a great question, Ted. You want to take it, Barry? Barry E. Greene - President & Chief Operating Officer: Yeah. So we designed the Norton facility to be a multi-train facility, so that we can run multiple products simultaneously if we are as successful as we hope to be in our pipeline. And Ted, how much drug would be produced by the plant is highly dependent on dose and frequency of that drug. And we're gratifyingly seeing in particular GalNAc-ESC's highly potent, infrequent medicines. And if that continues play out we pretty much can support the entire Genetic Medicines pipeline from that manufacturing facility. Now, as the Cardio-Metabolic and Hepatic Infectious Disease programs come online, given the end there of millions and millions of patients, that prompt up would probably require another investment in yet another facility, which if those programs hit, we're very prepared to do.…

Thank you. And at this time, I'm showing there are no further participants in the queue. I would like to turn the call back to management for any closing remarks. John M. Maraganore - Chief Executive Officer & Director: Well, thanks to everyone for joining us this afternoon. We certainly expect the rest of 2016 to be an exciting period for Alnylam, with lots of clinical data that we'll be sharing. And then finally, I just want to end by saying how we grateful we are to the patients and investigators participating in our studies, and how we remain deeply committed in developing these medicines for all of you to make a difference in your lives. So with that, I will now close the call. And have a great day, everybody.

Ladies and gentlemen, thank you for your participation on today's call. This concludes your conference. You may now disconnect. Everyone, have a great day.