Good day, ladies and gentlemen, and welcome to the Alnylam Pharmaceuticals Q2 2018 Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. As a reminder, this conference is being recorded. I would now like to introduce your host for today's conference, Ms. Christine Lindenboom, Vice President of Investor Relations and Corporate Communications. Ms. Lindenboom, you may begin.

Good morning. I'm Christine Lindenboom, Vice President of Investor Relations and Corporate Communications at Alnylam. With me today on the phone are John Maraganore, Chief Executive Officer; Barry Greene, President; Manmeet Soni, Chief Financial Officer; and Yvonne Greenstreet, Executive Vice President and Chief Operating Officer. Akshay Vaishnaw, our President of R&D is unable to join our call this morning. For those of you participating via conference call, the slides we have made available via webcast can also be accessed by going to the Investor page of our website, www.alnylam.com. During today's call, as outlined in slide 2, John will provide some introductory remarks and provide general context; Yvonne will review recent clinical updates; Manmeet will review our financials; and Barry will provide an update on our commercial readiness effort and a brief summary of upcoming milestones before opening the call for your questions. I would like to remind you that this call will contain 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 as a result of various important factors, including those discussed in our most recently quarterly report on file with the SEC. The press release and related financial tables, including a reconciliation of GAAP to non-GAAP measures that we will discuss today can also be found on the Investor page of our website. We believe non-GAAP measures provide useful information to management and investors regarding our financial conditions and results of operation. 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 obligation to update such statements. With that, I will now turn the call over to John.

Thanks, Christine, and thank you, everyone, for joining the call this morning. The second quarter of 2018 and recent period represent a notable and significant milepost in Alnylam's 16-year journey of advancing RNAi therapeutics as a potential new class of medicines. Indeed, we now have our first recommendation for the approval of ONPATTRO, our trade name for patisiran, with the positive CHMP recommendation in the EU. And by the end of next week, we expect to have our first approval here in the U.S. Before I turn it over to Yvonne to address our R&D progress, I'd like to make a few introductory remarks. First, as I just noted, we are now at the cusp of bringing our first RNAi therapeutic medicine to patients in the U.S. and Europe. We are also planning for a regulatory submission in Japan in September and additional regulatory filings in other countries by year's end. At Alnylam, we couldn't be more excited about this very special moment since nothing is more important to us than making a difference in the lives of patients around the world. Secondly, as Barry will highlight shortly, we are building a world-class global team to commercialize ONPATTRO, which we believe has the potential to be a truly meaningful orphan disease medicine. We're launch-ready here in the U.S. and also in Germany, where we expect our first EU launch. In addition, we've been building a highly experienced team in Japan and we plan to follow in other countries as well building a global commercialization effort. Third, we continue to execute on our broader pipeline efforts, especially on our late-stage programs. Notably, we're planning on soon conducting an interim analysis of our ENVISION Phase 3 trial of givosiran in acute hepatic porphyrias. If positive and the safety profile is acceptable, we…

Thanks, John, and good morning, everyone. As John highlighted, it's been a busy quarter and one filled with much excitement and anticipation as we draw closer to our PDUFA date for patisiran. So let's start with patisiran. The CHMP's positive recommendation for marketing authorization of patisiran in Europe is an important step in validating RNAi as a therapeutic strategy and was based on the positive results from our APOLLO Phase 3 study, which with 225 patients is the largest clinical study of patients with hATTR amyloidosis conducted to-date. Barry will discuss the CHMP recommendation from a commercial perspective. But we are very pleased with the Summary of Product Characteristics, or SmPC, that includes our important secondary and exploratory endpoint data, including results reflecting exploratory cardiac parameters. In the meanwhile, we continue to work collaboratively with our colleagues at the FDA towards our goal of achieving regulatory action by our PDUFA date next week. Also, during the quarter and recent period, we published our APOLLO Phase 3 results in The New England Journal of Medicine and also reported on additional data analyses from APOLLO. For example, we recently presented data at the Peripheral Nerve Society Annual Meeting, where new analyses from APOLLO demonstrated that patisiran case of patients showed improvements in overall health status compared to placebo and improvements in neuropathy impairment with patisiran treatment, which were associated with improved ambulatory status. Additionally, an indirect treatment comparison reported at PNS demonstrates the patisiran's impact on measures of neuropathy and quality of life in the APOLLO study relative to those measured in the previously conducted randomized study of tafamidis in hATTR amyloidosis patients with Phase 1 polyneuropathy. While there are limitations of this approach and no head-to-head studies have been conducted, this comparison suggests the benefit for patisiran versus tafamidis in Stage…

Thanks, Yvonne, and good morning, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the second quarter of 2018. I would like to take this opportunity to provide a brief overview of three key areas: our cash position, our second quarter results and our reaffirmed 2018 financial guidance. Moving to slide 15, let me start with our cash balance. We maintained a solid balance sheet, ending the second quarter with approximately $1.48 billion in cash, cash equivalents, marketable debt securities and restricted investments excluding equity securities. Moving to our financial results for the second quarter, we recognized $29.9 million of collaboration revenue during the second quarter of 2018 as compared to $15.9 million during the second quarter of 2017. Revenues for the second quarter of 2018 included $23.1 million from our alliance with Sanofi Genzyme and $6.8 million from other sources. The amount recognized during the second quarter of 2018 relates primarily to the achievement of a $50 million milestone payment due from Sanofi Genzyme upon dosing of the first patient in the ATLAS Phase 3 program for fitusiran during the first quarter of 2018 and recognized using the proportional performance method based on the new revenue recognition standard. As a result of our adoption on January 1 of the new revenue recognition standard, we recognized significantly lower revenues during the quarter and six months ended June 2018 from our alliance with Sanofi Genzyme. To compare under the previously applicable revenue recognition guidance, we would have recognized $16.3 million higher in collaboration revenue during the second quarter of 2018. For the six months ended June 2018, we would have recognized $49.4 million higher in collaboration revenue under the previously applicable revenue guidance. Moving to expenses, our GAAP R&D expenses were $137.6…

Thank you, Manmeet, and good morning, everyone. With CHMP's positive opinion for patisiran in hand and the PDUFA date just over a week away, our commercial capabilities are in place to deliver the first-ever RNAi therapeutic to patients upon approval. As you saw last week, the CHMP recommended that patisiran be indicated for the treatment of hereditary ATTR amyloidosis in adult patients with Stage 1 or Stage 2 polyneuropathy in EU. In its recommendation, CHMP recognized that patisiran treats the disease with positive effects on both the neuropathy manifestations of the disease and on quality of life, as well as affirming the positive impact on cardiac parameters. Importantly, the recommended Summary of Product Characteristics, or SmPC, includes all of the secondary and key exploratory endpoint data from APOLLO, including the exploratory cardiac endpoint results. The SmPC has recommended, include substantial efficacy and safety data from APOLLO that we believe will both provide healthcare providers with robust data upon which they can make prescribing decisions for their patients and will provide payers with substantive data to make reimbursement decisions based on the value patisiran delivers to patients. We continue to engage multiple health technology assessment bodies in countries across Europe, and reimbursement will be negotiated on a country-by-country basis. We expect reimbursement will be granted in accordance with the label. Pending full EC approval of our MAA, our first launch market within the EU is planned to be Germany. Other countries will launch thereafter following negotiations with relevant health authorities. In the U.S., we remain in a launch-ready state, pending FDA approval. Our U.S. field team is on board and we are in a position to get patisiran to patients as soon as possible once the drug is approved. We remain focused on raising awareness and improving patient identification. With three…

Thanks, Barry. And before I open the line for questions, I would like to quickly note that given the timing of this call and pending regulatory actions for patisiran in the U.S. and EU, we will not be able to discuss U.S. regulatory interactions, potential label communications or scenarios or anticipated pricing. We look forward to providing those updates in appropriate time in the near future. Operator, we'll now open the call for questions. For those dialed in, we would like to ask you to limit yourself to one question each and then get back in the queue if you have additional questions.

Thank you. Our first question comes from Gena Wang with Barclays.

Thank you for taking my questions. I will just ask Phase 3 trial design for TTRsc02 and the lumasiran, I just – TTRsc02, just wondering how would you come up with the nine months and also the co-primary endpoint, is there any hierarchy to show meaningful reduction in one versus the other or you have to show both? And then for the lumasiran, the Phase 3 trial design, just wondering if there is any percentage of reduction like the requirement for urinary oxalate reduction?

Those are great questions, Gena. Yvonne, do you want to handle them both?

You know, I'm very happy to. So, we were pleased to get alignment with the FDA around the study design for TTRsc02, particularly the agreements around essentially a single arm open label study being able to read across to the placebo arm APOLLO. We have two primary endpoints ahead, mNIS+7 and the Norfolk-QOL and nine months, we see it as a reasonable timeframe which to assess the impact of TTRsc02 on these endpoints.

And then the question on lumasiran?

Could you remind me the question on lumasiran?

Yes. Question is what the level of – do we have an absolute requirement for urinary oxalate drop?

So, essentially, what we need to do, so significant lowering of ALA with givosiran compared to placebo is something that we feel is well within our reach given the impressive data that we generated so far in the Phase 1/2 study.

Right. But the question was on lumasiran with so – just – we did have to show, Gena, the reduction in urinary oxalate.

Oxalate, yeah. We have done a terrific job kind of aligning around biomarkers for helping our program. So, sorry, I heard givosiran, but John has corrected me and it's lumasiran on the question around urinary oxalate level.

Good. Does that answer your question, Gena?

Yes, thank you.

Thank you.

Thank you. Our next question comes from Terence Flynn with Goldman Sachs. Terence Flynn - Goldman Sachs & Co. LLC: Hi, thanks for taking the question. Maybe just ahead of the tafamidis data that we're all focused on later this month, maybe just remind us what you guys will be looking for with respect to the data and then in terms of next steps for TTRsc02 on the wild-type side, when might you be in a position to share your thoughts there? And is there an effect size where you might not elect to conduct a superiority trial there just as we think about framing the data? Thank you.

Yeah. Thanks, Terence. Let me take it and then maybe Barry and Yvonne can chime in as well. These are the things that's on my mind. One is, is the effect seen in wild-type only or is there also an effect in hereditary ATTR? I mean, biochemically, there is a reason to believe that a stabilizer can shift the equilibrium for wild-type protein to be non-amyloidogenic better than it can shift the equilibrium for a mutant protein. And so that's going to be very interesting to look at how strong of an effect is there in the hereditary setting versus the wild-type. So, that's sort of first and foremost on my mind because if tafamidis doesn't show a strong effect in hereditary, then I think obviously that enhances our competitive position in that setting. The second thing I'm going to look for personally is whether the 20 milligram dose is the same as the 80 milligram dose or is 80 milligrams different and the reason that's of interest, Terence, is if 20 milligram and 80 milligram are the same, then tafamidis really is no different than what we saw before, at least in the neuropathy studies. And so, therefore, organic corroborates its potential that maybe the effects are being driven in the wild-type setting by a more favorable role of the stabilizer in that context. And then, finally, obviously whatever the treatment effect is, is it the 50% level that I think people are expecting or is it a more modest level in the 25% type of range but those are the three things that are on my mind. I don't know Barry and Yvonne, if you guys have different views of things that you're looking for?

Yeah. Those are all the right views of the data. I guess in addition and it's not clear how much of this we even are going to learn when the detailed data are presented is, if you think about this from a patient perspective and I reflect on APOLLO, again, in a hereditary setting, patients are progressing and their disease is debilitating. What they want is for the disease progression to stop or for many of the manifestations of these to reverse, which is what we saw on APOLLO. The majority of patients had stable or reversal of many disease manifestations that's what the patients want. Will we see that in the overall tafamidis dataset or do patients just continue to progress but at a slower rate? And Terence, you also asked about effect size in terms of showing superiority. I think we will have to see the data, analyze when they launch and to understand whether kind of a standalone wild-type trial or head-to-head makes more sense at that time. It's too early right now to predict. Yvonne?

No, good. I think clearly we have some thoughts about how to progress but I think we need to wait to see the full dataset from the trial, before we can finalize the final study.

Yeah. I mean, I think the only other thing I would just add is the sort of timing for separation of a fact between drug and placebo will be of interest as well in the study. Terence Flynn - Goldman Sachs & Co. LLC: Thanks a lot.

Thank you. Our next question comes from Ritu Baral with Cowen. Ritu Baral - Cowen & Co. LLC: Hey, guys. Thanks for taking the question. I guess, my first question is a follow-up to Terence's and how you're thinking about the competitive landscape, assuming that tafamidis will come into the market in 2019, not to mention (35:53), I mean, are you hearing anything about doctors potentially warehousing milder patients, mutant patients for an oral compound or what is your messaging around that and I got a follow-up?

Okay. Barry, do you want to handle it?

Yeah. So, if we're talking about the hereditary setting, given the disease awareness that's been going on, you have that setting in both neurologist and cardiologist. It's not practiced for either of those to try to warehouse patients for future and obviously, people are trying to get their patients, if applicable, into the Expanded Access Programs and we're seeing, as I mentioned, that uptake. On the wild-type setting, other than the generic NSAID diflunisal, there is nothing available for these patients. So, I wouldn't say they're warehousing but they certainly are waiting for drugs to be available that are potentially more effective to treat their patients.

I mean, clearly for a disease like hATTR amyloidosis, I think physicians will be keen to treat their patients as soon as they possibly as soon as drugs become available rather than keep patients waiting for a medicine that may or may not come to market downstream.

Does that answer to your question, Ritu? Ritu Baral - Cowen & Co. LLC: Yeah. And just a follow-up there actually, you mentioned the whole neurologist, cardiologist thing. We've done a series of calls with doctors recently and one interesting thing we noticed was cardiologists, FAC specialists were complaining about the level of awareness of TTR amongst the community neurologists whereas they say that the awareness in the community cardiologists is quite good. And we didn't know if that was just specialty competitiveness or is that something that you're seeing and how might the Alnylam attract results that you said the 6,700 tests and 460 diagnosis, how does that feed into the specialist split and awareness?

Yeah. Barry?

Yeah. So what your KOL observed is also what we're observing. And if you think about cardiology community, they've been dealing with amyloidosis for some amount of time starting with AL amyloidosis driven by something like multiple myeloma where they treat with chemotherapy and see positive results. So, they've been aware of amyloidosis for some amount of time. TTR is a newer phenomenon in the cardiology community, but the receptors were on for amyloidosis in general and at least the large practices, they understand how to look for amyloidosis, some of them may not be able to differentiate the cause of amyloidosis but they knew to look. The neurology setting was not necessarily looking for this disease. So, things like Alnylam Act and disease awareness and these congresses are really important tools to raise awareness in both communities as we go forward and clearly once we have a label and can promote, then awareness, particularly in the neurology community will go up exponentially. Ritu Baral - Cowen & Co. LLC: So, can we assume that, that is a particular focus post launch, neurologist awareness versus cardiologist awareness?

I wouldn't say versus, I'd say awareness across the whole medical community is a big focus of ours. These patients are also at gastroenterology offices. So, wherever the patient hits in their journey, our goal is to not have seven or eight specialists be seen before a patient get diagnosed over four years, but have a patient be diagnosed much earlier.

Yeah, this is one of the reasons why we've been very interested in the growth of specialized amyloidosis centers of excellence where you have the full range of clinicians available with those diagnosed patients and also to treat them. Ritu Baral - Cowen & Co. LLC: Very helpful. I'll get back in the queue. Thanks, everyone.

Thanks, Ritu.

Thank you. Our next question comes from Vincent Chen with Bernstein. Vincent Chen - Sanford C. Bernstein & Co. LLC: Good morning, and congrats on the progress.

Thank you. Vincent Chen - Sanford C. Bernstein & Co. LLC: Another question on TTRsc02 study that you are announcing today, what dose you are moving forward in that study? Is this a 25 milligram Q3 month dose that was previously highlighted in your poster ISA, or are higher doses being tested?

Yeah. 25 milligrams Q3 monthly is the planned dose going forward, Vincent. Vincent Chen - Sanford C. Bernstein & Co. LLC: And what was the rationale for the selection of that dose? How do you think about the trade-off between greater knockdown and potentially some increase in efficacy from there versus the risk of side effects as you push TTR down to lower and lower level?

Well, Vincent, based on modeling, we feel that – well, not feel, but we have data that shows convincingly that 25 milligrams achieves a patisiran-like TTR knockdown effect. So we should be saying 80% to 90% type of TTR knockdown. And we now know, from a safety perspective, that up to over four years at this point knockdown of TTR at that type of level is well tolerated in patients. So we think that's the right level of TTR knockdown to achieve, and we can replicate that faithfully with the 25 milligram Q3 monthly dose regimen. Vincent Chen - Sanford C. Bernstein & Co. LLC: I guess, well, is there any point where the data you've shown so far shows good safety and efficacy. I guess, the question I wonder about is if you – I guess, there are a few doses that you've sort of previously shown in the Phase 1 that get to even deeper and deeper level. Was there any consideration to sort of exploring further levels of knockdown just to see if you could sort of eke out even greater efficacy than what you've seen so far?

Well, I mean, we certainly explore that internally. We think that the best approach from a regulatory science perspective is, however, to have a comparable level of TTR knockdown. In the future, we can always explore going up in dose. But having from a regulatory framework perspective, the 25 milligram dose is the right approach and the FDA has agreed with that. Vincent Chen - Sanford C. Bernstein & Co. LLC: Great. Thank you very much. I'll hop back in the queue.

Yeah. Thanks, Vincent.

Thank you. Our next question comes from Madhu Kumar with B. Riley.

Hi, guys. Thanks for taking my question. So the first one is kind of, how do you think about the relative product lifecycles for ONPATTRO versus TTRsc02 and hATTR?

Yeah. I mean, let me start and then maybe Barry and Yvonne can chime in as well. I mean, we obviously – with ONPATTRO, we have a terrific medicine that is going to make a big difference in the lives of patients with hereditary ATTR amyloidosis. We believe that all patients within that disease setting can benefit from ONPATTRO, and that's what we've demonstrated with the APOLLO Phase 3 study. With TTRsc02, the initial Phase 3 study that we just outlined today is going to make TTRsc02 available for the same patient population that currently ONPATTRO is going to serve. And that will provide patients with a choice between using patisiran or ONPATTRO or having a subcu option. And we suspect that many patients will continue taking ONPATTRO because it's worked well for them, they are not bothered by infusions, and they continue to take ONPATTRO. But other patients, particularly new patients that get diagnosed, will likely go on to the subcutaneous option given once a quarter, a very favorable type of convenience profile for them. And then, of course, when we think about other settings in ATTR amyloidosis like the wild-type setting and even the pre-symptomatic genetic carrier setting, which is of great interest to us, we believe that TTRsc02 is going to be the go-forward molecule and we'll be making our Phase 3 and late-stage investments behind that molecule. So Barry or Yvonne, anything to add, did I cover it?

You covered it.

No, I think you covered it very nicely.

And, Madhu, does that answer your question?

Yes, great. And then kind of a more factual question. What fraction of patients in the APOLLO open label extension trial had come off the study in terms of like finished the trial?

They finish the trial when they hit five years of treatment. And we don't have anybody at five years yet, but we will start – I think this year, we'll have our first five-year veteran coming off the study and going onto, obviously, commercial drug.

And for the sc02 Phase 3, is there any sense of how much of a headwind that could create for the ONPATTRO launch? Particularly, do any patients have to be treated in U.S., Europe or Japan to support approval in those geographies?

Yeah. Maybe Yvonne could comment as well, but let me just say the following, which is we were very mindful of that dynamic. There are going to be many countries around the world where even with an approval we won't have reimbursement in place. And, of course, we will be enrolling some U.S. patients as well. We do need to do that. But we don't believe it will meaningfully impact patisiran or ONPATTRO's launch at this point. Yvonne, anything else to add?

No, that's correct. We will be very thoughtful about site selection here to make sure we minimize the issue that you've highlighted, Madhu. And we feel very confident that we'll be able to both enroll patients into TTRsc02 study, as well as deliver on the opportunity for ONPATTRO.

Okay, great. Thanks for taking my questions.

All right. Thanks, Madhu.

Thank you. Our next question comes from Anupam Rama with JPMorgan.

Hey, guys. Thanks for taking the question, and congrats on all the progress. Maybe I could ask a question on givosiran with a potential launch here in maybe 2019 timeframe, one of the questions we get is, how large of an opportunity could this be, and I think there is a range of estimates out there. Maybe you could help us understand some of your prelaunch activities, what we should be thinking about, is there a patient queue that's building and factors that might impact the long-term sort of launch curve? Thanks so much.

Yeah. That's great question. Just like hATTR amyloidosis, it is an underdiagnosed disease. And so, a lot of our efforts are around improving medical education and patient diagnosis. One of the things that we've done is extended our Alnylam Act program to the porphyria setting. And I think it was last week or the week before we presented at our RNAi Roundtable that out of about 100 or so samples that we've tested, somewhere in the range of 15 or so have come back positive for the mutation. So that's a pretty encouraging hit rate, better than we frankly expected from that program so far, and we'll see how that continues going forward. So, we do believe it is under-diagnosed. We obviously will be spending a lot of time. We're currently doing it to improve medical education. Of course, we do believe that in the system, right now, there are a few thousand patients in the U.S. and Europe. We do believe that the uptake for givosiran in those diagnosed patients will be quite rapid given the extreme burden of that disease and if everything plays out in ENVISION, like we've seen in the earlier studies, the very high degree of therapeutic impact that givosiran shows. But there will be growth thereafter based on improved medical education. Barry, anything to add to that?

Yeah. So those are all very important points. And let me emphasize that porphyria will remain an ultra-rare disease, we believe, and our key is, within an ultra-rare, frankly, to find everybody. In addition to what John mentioned, we've been working with the porphyria network to strengthen the next set of physicians that are coming up and looking for the disease, younger, kind of, more aggressive types that are going out to the community to educate and we've seen good uptake with that. Alnylam Act is a good proof point and ENVISION quicker than we thought, is another proof point that being out there raising disease awareness is helping. And just to give you the background fact, we presented these already, so the average patient journey here is over 13 years with the average patient seeing over three, for example, gastroenterologists. So, we can shorten that journey to months, not years, and get the first physician they interface with do an appropriate diagnosis, which is not that difficult. We see great uptake, whether it's double, triple or quadruple, the numbers, it's too early to say right now. But as John mentioned, we know about a few thousand patients already.

Thanks for taking the question.

Yeah. Thanks.

Thank you. Our next question comes from Alan Carr with Needham & Company. Alan Carr - Needham & Co. LLC: Hi. Thanks for taking my questions. One around the TTR program with sc02, I assume the EMA is on board too. Yvonne mentioned the FDA and what are your latest thoughts on design for some of the other registration trials for sc02? I suppose it's all dependent on the tafamidis data, but wonder if you can give us a sense of that. And then the follow-up is, tell us a little bit more about your plans with CNS effort. Thanks.

Yeah. Those are great questions, Alan. Let me start with sc02, the regulatory interactions in Europe are ongoing. So there's nothing to report there at this point in time. But we do expect that we'll have similar success in Europe. I mean, we've had past dialogues with the European authorities on this whole field. So, we feel that we'll reach alignment there as well. Regarding future trials on TTRsc02, we do need to see the TAF (50:26) data that's coming up on the 27th of this month and we really look forward to it. And for all the reasons I commented before, is it wild-type only, hereditary versus hereditary, is that – is 20 milligrams the same as 80 milligrams, all of these different factors I brought up before, that will influence our thinking on a wild-type study for TTRsc02. Right now, as I sit here today, I think we have to assume that will be a randomized study comparing both drugs to each other, because that is the right thing to do and that's the relevant study that physicians will want to see. And that's certainly how sitting here today, we're thinking about it. Other studies will also begin in 2019 for TTRsc02. We haven't finalized our 2019 plan yet. But we do believe that the other studies such as the pre-symptomatic carrier study can also start at that point in time. Regarding CNS, really excited about those data. We'll have more data at OTS in October from that effort. It is really a game changer from a scientific perspective. And just like we opened up delivery to liver many years ago – not many years ago but some years ago, opening up delivery now to the CNS is going to really only expand the number of opportunities we have with RNAi therapeutics. And our goal is to have our first development candidate by the end of the year and then to have our first CTA filing in late 2019 or early 2020 with that program. And what you're going to see thereafter, Alan, is a steady flow, I mean, a continued flow of programs targeting liver-expressed disease targets because they are many, many more things to do there, but a continued flow thereafter of balanced programs in the CNS and also in liver targeted opportunities. So I think I've answered your question. Alan Carr - Needham & Co. LLC: Anything beyond, I mean, so it's primarily liver, you'll be putting some effort in CNS but any other target organs in mind or is that just those two?

We've got a few more things. We've got a few more things cooking.

And I think it is important to understand (52:42) to do in the liver.

Yeah, exactly. Alan Carr - Needham & Co. LLC: All right. Thanks for taking my question.

Yeah. We don't find ourselves at a loss for things to investment. Alan Carr - Needham & Co. LLC: Okay. Thanks for taking my question.

Thanks, Alan.

Thank you. Our next question comes from Maury Raycroft with Jefferies.

Hi, good morning, and thanks for taking my question. John, you provided some perspective on expectations for tafamidis and what you'll be looking for there. Can you comment on the inotersen CHMP letter and also the EU label and any thoughts on how those position that program?

Yeah. I mean, obviously, those are probably questions that are best asked to our friends over at Akcea and Ionis. From our perspective, just focusing on the facts, our indication statements are different in our SmPCs. We have, as you know, an indication for the treatment of hereditary ATTR amyloidosis in patients with Stage 1 or Stage 2 polyneuropathy. Their indication statement is for the treatment of polyneuropathy in Stage 1 or Stage 2 hATTR patients. So, what is the treatment of the disease, mainly hATTR amyloidosis, which is what our indication statement is, the other is a treatment of neuropathy which is what their statement says. Of course, our SmPC includes cardiac data. They don't have any cardiac data that hit statistical significance as we know from The New England Journal paper. So, there are important differences between the labels that we think are meaningful and we'll just leave it at that, at this point in time. We'll see how that plays out in the U.S. in the coming week or so from our side and then a few weeks later for them and we'll just go from there.

Great. And maybe if I can ask a quick one on lumasiran, so I think there's some data we are expecting in second half from Dicerna. It's a different enzyme oxalate pathway they are targeting but will their data have any read through to your program?

I don't think so. I mean, obviously, they are targeting LDHA. We've done preclinical work looking at LDHA. It's obviously a target that we think can be operative to lower oxalate level. So, I will expect that they should see that. We believe that GO is a better enzyme to target, mostly from concerns which you've seen pre-clinically around elevating liver pyruvate levels which may not be the right thing to do. So we'll start to see how the data come up from a safety and efficacy perspective for them versus what we've shown already, which is very encouraging efficacy and essentially normalization of urinary oxalate with a very acceptable and favorable safety profile.

Got it. Okay. Thank you very much.

Thank you.

Thank you. Our next question comes from Konstantinos Aprilakis with JMP Securities.

Thanks very much for taking my question. And let me add my congrats on all your progress. So just a quick one on sc02, you discussed long-term preventive study in patients that carry TTR mutations were asymptomatic, can you give us an idea of the potential cost of such a trial and your efforts to gauge how interested patients might be in being treated before they manifest symptoms?

Yeah. Konstantinos, we're still vetting the design. We think it's a really important setting. We do know that there is quite a bit of interest from the KOL community and while we haven't really gone to the patient community yet with the program, I'm sure the basic concept of preventing even a smidgen of disease before – by treating beforehand I think just makes complete sense medically. Yvonne, anything else to add to that?

No, I think it's really sort of too early to be detailed around cost and size.

Yeah, I mean, maybe it could be a long study, Konstantinos. It may require a period of time but there are enrichment strategies that we are actively exploring that might shorten that time. But it is clearly the right way to think about treating these patients longer term.

Okay, great. Thanks, guys. Congrats again.

Thank you.

Thank you. And we do have time for one final question from Chris Marai with Nomura/Instinet. Christopher N. Marai - Nomura/Instinet: Hey, good morning. Thanks for taking the question. Appreciate the update on sc02 and the Phase 3 study design. I know that looks like it's going to focus mostly on the mNIS+7, looks like that sort of patients there. And so wondering if you could comment on the potential for data in patients with cardiac disease, it's a nine-month study it looks like and are you adequately powered to show some of the potential benefits in cardiac the way that you observed them in APOLLO? Thank you.

Yeah. Thanks, Chris. We are including cardiac endpoints in the study. And in APOLLO, at nine months, we were able to show statistically significant differences between drug and placebo on cardiac parameters. So, we do expect to be able to show those differences in the TTRsc02 Phase 3 absolutely. Christopher N. Marai - Nomura/Instinet: Okay. Thank you.

Good. Thank you. Okay.

Ladies and gentlemen, thank you for participating in today's question-and-answer session. I would now like to turn the call back over to management for any closing remarks.

Right. Well, thanks to everyone for joining us today. We look forward to updating you on our continued progress in the coming week. We might have another call relatively soon as you guys can imagine. And we are very excited and albeit at the cusp of bringing RNAi therapeutics to patients around the world. So, thanks, everybody, and have a great day. Bye-bye.

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program. You may all disconnect. And have a wonderful day.