Welcome to the Alnylam Pharmaceuticals Conference Call to Discuss Third 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.

Thank you and 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; Akshay Vaishnaw, Executive Vice President of R&D and Chief Medical Officer; and Michael Mason, Vice President of Finance and Treasurer. In addition, Yvonne Greenstreet, Executive VP, Chief Operating Officer and DA Gros, Senior VP, Chief Business Officer, are 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 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 some general context; Akshay will review recent clinical updates; Michael will review our financials; and Barry will provide a brief summary of upcoming milestones before opening the call for your questions. Before we begin, 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 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 a result of various important factors, including those discussed in our most recent quarter 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 on any subsequent date. We specifically disclaim any obligation to update such statements except as may be required by law. With that, I would like to turn the call over to John.

Thanks, Christine and thank you, everyone, for joining us this afternoon. During the third quarter and recent period, we made important progress in advancing RNAi therapeutics through clinical trials and toward the market while also experiencing an unfortunate setback. Specifically, as you know, we announced in early October that we discontinued development of revusiran, an investigational RNAi therapeutic that was in development for the treatment of hereditary ATTR amyloidosis with cardiomyopathy or hATTR-CM. Akshay will provide more color on this development and we'll also review our recent pipeline progress in more detail. But I would like to provide some introductory context for the call this afternoon. First, following our announcement that we were discontinuing revusiran, we set up an internal team and initiated a comprehensive evaluation of the revusiran data. This type of investigation takes time and there remains uncertainty regarding the cause of the findings that led to the program's discontinuation. As a result, there are many questions that we're simply not able to answer at this point. We will provide a brief update today and then we'll update you on our progress at our upcoming R&D day on December 16. However, to manage expectations, please realize that in the evaluation of this type is not measured in days or weeks, but rather in months and we want to gain as complete a picture as possible before we share any results with you. It is important to emphasize the decision to discontinue development of revusiran does not impact any other Alnylam investigational RNAi therapeutic program in development. As a reminder, revusiran was the only program that used our standard template chemistry, GalNAc delivery technology. Patisiran utilizes a lipid nanoparticle delivery formulation and there are seven other clinical programs in Alnylam's pipeline that use our enhanced stabilization chemistry or ESC…

Thanks, John and good afternoon, everyone. Notwithstanding the revusiran setback, we have otherwise continued to make strong progress with our pipeline of investigational RNAi therapeutics. Let's begin with an update on revusiran. As a reminder, revusiran was being developed for the treatment of hATTR cardiomyopathy. This is an inherited, progressive, life-threatening disease due to a mutation in the transthyretin gene which causes misfolded TTR proteins to accumulate as amyloid fibrils primarily in the heart and nerves. Hereditary ATTR amyloidosis with cardiomyopathy can result in heart failure and death. This disease has very high morbidity and mortality. Median survival is about 2.5 years and there are no approved therapies for treatment of the disease. A double heart and liver transplant is the only current treatment option. Revusiran was being explored in three clinical trials, including the Phase 2 OLE study, the Phase 3 ENDEAVOUR study and the Phase 2 open label study in hATTR amyloidosis patients who have disease progression post [indiscernible] a liver transplant. Following recent reports of new onset or worsening peripheral neuropathy and elevated blood lactate levels in the Phase 2 early study, we asked the ENDEAVOUR DMC to review unblinded safety data. Specifically, the questions we asked were threefold, one, Have you seen any evidence of drug-related peripheral neuropathy in ENDEAVOUR? Two, Does the benefit-risk profile of revusiran justify continued dosing in the trial? And three, If the answer is yes, is there any additional monitoring you would recommend we implement in the trial going forward? The DMC came back to us and informed us that there was no conclusive evidence of drug-related peripheral neuropathy but recommended that we stopped dosing based on a lack of benefit-risk. Upon receiving the DMC's recommendation and reviewing the unblinded data which revealed an imbalance in mortality in the revusiran arm,…

Thanks, Akshay. I will be referring to slide 16 for a discussion of our third quarter 2016 financial results. We continue to maintain a very strong balance sheet, ending the third quarter of 2016 with approximately $1.2 billion in cash as compared to $1.28 billion at December 31, 2015. Our financial strength allows us to continue to invest in a broad pipeline of investigational RNAi therapeutics 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 third quarter of 2016 was $104.1 million or $1.21 per share on both a basic and diluted basis, including $15.6 million or $0.18 per share of noncash stock-based compensation expense as compared to a net loss of $76.8 million or $0.91 per share on both a basic and diluted basis, including $11.8 million or $0.14 per share of noncash stock-based compensation expense for the same period in the previous year. Revenues were $13.7 million for the third quarter of 2016 compared to $6.3 million for the same period last year. Revenues for the third quarter of 2016 included $7.4 million from our alliance with Sanofi Genzyme, $2.7 million from our alliance with The Medicines Company and $3.6 million from other sources. We expect net revenues from collaborators to increase during the fourth quarter of 2016 due primarily to an expected increase in revenues from Sanofi Genzyme. R&D expenses were $97.9 million in the third quarter of 2016 which included $9.3 million of noncash stock-based compensation as compared to $68.6 million in the third quarter of 2015 which included $6.3 million of noncash stock-based compensation. The increase in R&D expenses as compared to the prior year…

Thanks, Michael. Let's now turn to our 2015 goals and our guidance on upcoming data presentations. With our fitusiran program as reported, we reached full enrollment in our APOLLO Phase 3 study. We look forward to reporting data from APOLLO in mid-2017, less than one year from now. Assuming positive data, we expect APOLLO will enable possible NDA submission by the end of 2017, putting us in a position to potentially launch our first commercial product in 2018. Regarding ALN--PCSsc or as our partners at The Medicines Company call it, PCSK9si, initial data from ORION-1 Phase 2 study will be presented at AHA on November 15. Now with fitusiran for hemophilia, we will have two presentations at the upcoming ASH conference in December -- one covering data in patients without inhibitors and the other covering data in patients with an inhibitor. Each of these presentations will include data from the Phase 1 study as well as from the Phase 1-2 open label extension study. Also at ASH we will have additional data with ALN-AS1. This dataset will provide an initial look at the effect of ALN-AS1 in patients with recurrent porphyria attacks. We plan to present all the data from this study that we have at the time and we will be looking for lowering of ALA and PBG levels in these patients, as well as safety. We expect further data on the effects of ALN-AS1 on recurrent attack to be available in the 2017 time frame. Also at ASH we will present additional follow-up data from our Phase 1-2 trial of ALN-CC5 in patients with PNH, where we have been exploring the potential for ALN-CC5 to treat inadequate eculizumab responders and/or spare the dose frequency of burden of eculizumab infusions. Now, moving to ALN-TTRsc02, a second-generation GalNAc ESC conjugate targeting transthyretin for all forms of ATT amyloidosis, we plan to report initial data from the ongoing Phase 1 study at our R&D day on December 16. We also continue enrolling subjects in our Phase 1-2 trial of ALN-HBV in development for the treatment of chronic HBV infection and we look forward to sharing initial data from that trial in mid-2017. As Michael said, we continue to expect to end 2016 with greater than $1 billion in cash. We look forward to sharing more updates from our pipeline between now and the end of the year. And with that I'll now turn the call back to Christine to coordinate our Q&A. Christine?

Thank you, Barry. Operator, we will now open the call for questions. As a reminder to those dialing in, we would like to ask you to limit your questions to two each.

[Operator Instructions]. And our first question comes from Ritu Baral from Cowen. Your line is open.

The first question is on the DSMB look that you've taken both in ENDEAVOUR and APOLLO. When you ask the ENDEAVOUR DSMB on benefit-risk, were they unblinded to the efficacy data when making that evaluation?

Yes. So, Ritu, they did not have any efficacy data when they made that evaluation. They simply had the safety data unblinded, so they were looking at the overall safety profile and, of course, the benefit side of that, of course, wasn't included in their look, but they were certainly aware of the Phase 2 open label data where admittedly there wasn't a signal like we have with patisiran of any benefit. Anything else to add to that?

I think you covered it, John.

Okay. So, the benefit portion was informed by the Phase 2 open label that we've all seen, but nothing in ENDEAVOUR, okay.

Yes, that's correct.

Okay. And then can you detail -- a second part of that question, can you detail what questions you asked the APOLLO DSMB, the same way that you asked the ENDEAVOUR DSMB?

Yes, I can't quote verbatim, but essentially they were informed of the findings from the ENDEAVOUR study and they were asked to review the data from the APOLLO study for mortality imbalance and whether any modifications were required and they came back with the notification that the study could continue unmodified.

Did you ask them very specifically about the blood lactate elevations or peripheral neuropathy?

The questions we posed to them were in connection with mortality imbalance, as I outlined. I mean, Ritu, for what it's worth, of course the Phase 3 database is blinded and so forth and we can't read that out, but you'll note that we've had the Phase 2 early study running for several years now and we've never reported any serum lactate elevations there with respect to those 25-odd patients.

Right. So, moving to what you're going to have at ASH specifically with fitusiran, can you give us any more detail about the patient counts, the duration of treatment and the doses that you might be presenting in the inhibitor and noninhibitor patients?

Let me give you some color. So, the two studies, the two different reports, without inhibitors and with inhibitors, right? So, in the group without inhibitors, that is going to be the first time you see results from our Phase 2 open label study. So, those are the patients that have rolled over, patients without inhibitors that have rolled over from Part C and have gone into the new protocol. And so these patients, of course, have been receiving two different dose levels -- 50 milligrams monthly, 80 milligrams monthly is the other dose and these patients have been treated now out to, up to 16 months of treatment. So, we'll have all those data looking at bleeding, looking at antithrombin knockdown, safety, of course, very important. And then the other study in the inhibitor population is actually a cohort of approximately 15 patients now that are in that study and it includes patients with, obviously patients with inhibitors in all cases and there we will report on knockdown, safety, thrombin generation increases and bleed rate data.

And that's from the 50 and the 80 monthly dose?

That's correct. That will include both 50 and 80 milligram data.

How long of treatment duration we have from the 80 dose?

Well in the open label study it goes on for, you know, many, many months. In the inhibitor study it's a little bit more limited because the 80 milligram cohort was only initiated back in July.

Thank you. Our next question comes from Geoff Meacham from Barclays. Your line is open.

I also wanted to follow up on fitusiran. If you guys look at the competition here, I'm just trying to think what could be even more differentiated commercially? Is it possible to get to quarterly dosing? I'm not sure what you have to show PK-wise or safety-wise to get there?

Yes, great question, Geoff. Look, we're currently focused on the monthly dose regimen, but we do acknowledge that the durability of our platform allows us to envisage less frequent dosing. And we'll generate data in due course over time to support that potentially as part of lifecycle management for the program. But right now the focus really is on monthly dosing with the product.

And, Geoff, let me just jump in. The most important thing, as you are aware, for people with hemophilia to not bleed and they're challenged with factor, even longer-acting factor on peak-and-trough levels. We'll share data at ASH, but as you've seen, we've got fairly clamped pharmacology and if that confers lack of bleed, that is probably the best thing for these patients. The fact that it's a low volume monthly dosing, assuming safety, it's hugely a benefit as well. But it's very important that they don't bleed.

And just to follow up on the APOLLO study, maybe just walk us through kind of what the gaiting factors are provided the trial is successful. What needs to be done to get the NDA and EMA done pretty rapid turnaround?

Yes. Well, the most important thing is that we do a formal database log once the last patient has completed the last visit and we have rigorous NTCB compliant database and we will conduct the necessary regulatory meetings in parallel with that and share data with regulators. And that will then lead to -- a lot of this will, of course, is not sequential, it is going on in parallel in various workstreams and that will lead to right up with the NDA both -- across all elements from the manufacturing, the preclinical, the clinical research, etc. And that's essentially the key body of work that would lead to the NDA and EMA submission here and in Europe.

I wasn't as clear given the patisiran development, has the safety or sort of tolerability or toxicity kind of request do you think changed when you think about the filing for patisiran?

No, we don't believe so, because as we've shared on publications in the past, with progressive data that is coming from the patisiran phase early, that patisiran tolerability has looked encouraging to date. On the efficacy side, from the single arm open label study, we've had a lot of interesting and encouraging news with respect to stabilization and regression of neuropathy. And I think that all bodes well for the APOLLO Phase 3 data that we talk about the DMC, encouragement that we received recently as well. And so I think that drug is unto itself is not the hypothesis that patisiran [indiscernible] TTR knockdown and confirmed benefit in neuropathy is still very much alive and we feel very encouraged. So, that all we brought together and submit as part of the NDA.

I was just going to add, Geoff, that we -- Akshay's earlier comments on what we're doing, many parts of the NDA or many of the datasets needed for the NDA are already complete. And so we're very much focused on that submission in a very timely manner.

Thank you. Our next question comes from Alethia Young from Credit Suisse. Your line is open.

I just wanted to go back to revusiran since people didn't ask in the beginning. Are you now thinking that probably the drug didn't have enough efficacy and these people are really in a bad condition? And can you just comment if there is any kind of commonality or anything you saw in concomitant medications that were used in that study so far?

Yes. I mean, Alethia, certainly the Phase 2 of the open label extension study for revusiran hadn't given any clear efficacy signal, as we all know and contrast rather significantly to the patisiran [indiscernible] study with the neuropathy data being quite encouraging. And so at the time that the revusiran studies were terminated, there was no clear efficacy signal. I think it's fair to say that and moreover we have the imbalance and mortality and the causes for that, of course, could be lesion. And I think as you and others have discussed with us in the past, one of them could just be a simple baseline imbalance due to what is a severe cardiac disease with a mortality of median of two and a half years. And so that baseline imbalance could result in this kind of an outcome, but that could interplay with many other factors including other comorbidities of concomitant drugs or drug-drug interactions. Remember, these patients are elderly, many of them on 5 to 10 drugs and so it's a complicated picture we're going to have to work through. And as far as the concomitant medications are concerned, it will be the usual litany of diuretics, inotropes and anti-arrhythmics that unfortunately these patients need to take. And some of the complicated drugs like amiodarone are protein bound and their PK changes rapidly if the degree of protein binding is altered. And so all of this needs to be gone through carefully for us to evaluate what happened here to lead to this drug's striking imbalance in mortality.

And then just on hemophilia, have you guys had the end of Phase 2 meeting to make sure that you're on track for the early 2017 start?

Yes, Alethia, we've had a range of interactions with FDA and EMA during the course of this year. We have one more round with each, but we very much are feeling on track with our early 2017 start. Just as a reminder, early in our guidance is Q1 and Q2, so we're going to hit that start date, but we're very much focused on it and we're excited about the program and moving along with our discussions to get it started.

And just a follow-up. Like did they -- are they like discussing in context of your other, so like the revusiran study or patisiran or do they kind of look at it in a vacuum?

No. They have not. They obviously understand this package. Patisiran is a stand-alone program and that's how they look at it.

Thank you. Our next question is from Anupam Rama from JPMorgan. Your line is now open.

This is Hugo [ph] on the call for Anupam. Thank you for taking our questions. Is the natural history of FAP with cardiac disease different in patients who have FAP?

You know, essentially, it's hard to look at the cardiac mortality and morbidity in isolation like that in FAP versus non-FAP. Really, one needs to look at the spectrum of mutation and each has a different propensity to cause cardiomyopathy and each has a different sort of severity or outcome in cardiomyopathy range. So, you have mutations like V30M that can be associated with cardiomyopathy but tend to have run a slightly milder course and not lead to the rapid progression that some other mutations are associated with. For example, V122 ILE leads to a cardiomyopathy without much neuropathy and a fairly aggressive course of that cardiomyopathy. And then you have a mutation like T6DA which causes both severe cardiomyopathy and neuropathy. So, when we talk about a median survival of two and a half years in patients with cardiomyopathy, we're looking at a totality of all those data plus all those mutations. But within there, the mutations will have more aggressive cardiomyopathy and may or may not have neuropathy. So, it's a little bit complicated about trying to go through a spectrum of findings. Finally, I would add that the picture essentially is of a spectrum of neuropathy and cardiomyopathy in TTR-associated mutations and so in the APOLLO Phase 3 study for patisiran, 53% of the patients had both neuropathy and cardiomyopathy as part of their syndrome.

Thank you. Our next question comes from Ted Tenthoff from Piper Jaffray. Your line is open.

Appreciate the update on revusiran earlier and also the pipeline. Trying to get a sense of how you will be reporting the TTR subcu 02 or TTRsc02 data and sort of what the gaiting factors are for potentially advancing whether the just FAT or whether you would consider exploring that drug in cardiomyopathy patients as well?

Yes, that's a great question, Ted. So, for starters, we plan on presenting the data at our R&D day. So, if you come to that event which I'm sure you will, we'll be presenting the Phase 1 data at that exact event. And then in terms the regulatory strategy there, clearly with FAP, with the polyneuropathy indication, we believe we can leverage the experience that we have with patisiran in APOLLO as the way that we would consider developing that drug. Cardiomyopathy now, of course, will require a completely different study and I think that we would want to understand what would happen with revusiran in the cardiomyopathy setting before we would boldly embark in a new cardiomyopathy study. So, that requires, in my opinion, better clarity around that path. Akshay, do you agree with that?

Yes. I think you covered it, John.

I think that makes a lot of sense. So, looking forward to the data updates.

Thank you. Our next question comes from Alan Carr from Needham Company. Your line is open.

Can you clarify the number of deaths? Was it 16 and 2 or 17 and 2? It sounded like you found another one later.

Yes, following the sweep of all the sites, it turned out to be 17 to 2.

All right. And I'm wondering, given these two setbacks in the last few months, does that affect your all's strategy here in terms of adding more programs and that sort of thing? And I believe in the past you've talked about adding at least once a year a new program, bringing into clinical development. Is that impacted by what's happening in the last few months? And, also, can we have an update on the HBV program? Thanks.

Well, look, we're going to be at our R&D on December 16 and obviously we'll provide guidance for the coming year as part of that. But I think that what we have in front of us right now is an amazingly compelling pipeline by our glances and with eight active clinical programs. And our nearest term focus right now is really on getting ready for NDA submissions and launch of patisiran, Phase 3 starts with fitusiran and Phase 3 starts with porphyria. And that's sort of our primary focus and so we'll go through that in great detail on December 16 at our R&D day. Regarding HBV, that Phase 1 study started during the quarter. We started dosing single ascending dose with volunteers and we'll be transitioning to patients in the coming period. So, that program is moving along. Now, obviously in volunteers we're only looking at safety, we're not looking at any element of effect because volunteers don't have HBV infection. But when we move to patients, we expect to see effects on surface antigen levels in patients infected with HBV and that will be a 2017 readout for that program.

You might move into patients in the first half of 2017; is that the plan?

In the coming period, Alan, is the answer right now. We should be within the next months or so.

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

So, maybe just a quick follow-up on fitusiran in hemophilia. Wondering what range of ABR do you think would be competitive for patients with inhibitors?

Look, it's a great question, Gena. If you look at the literature out there, prophylaxis that isn't commonly done in these patients with either FEIBA or [indiscernible], but the greater amount of data is with FEIBA achieves in ABR, a median ABR of 7 in patients with inhibitors. And patients that are on demand typically have ABRs that are in the 20s, if you look across the literature. So, we would be very satisfied to see ABR values that are in the low single digits, because that would be highly competitive and a profile that would be obviously, frankly, pretty transformational for patients with inhibitors. And I think for the most part that's a very competitive range. The lower the better, of course and we'll forward to updating you on that at ASH.

Okay. So, when you say low single digit, are you we talking about 3 to 5?

Well, low single digits to me is between 1 and 5, but, again, lower the better and we'll forward to presenting those data at ASH for you.

And I have a quick question regarding the srr-9 sequence. So, for antitrypsin program, previously you mentioned that it is [indiscernible] sequence specific leading to the liver tox. For the TTR program, so the TTRsc02, they share the same sequence as revusiran, so the question here is how much do we know about the excessive tox and also is there a concern on TTRsc02 sequence?

Yes. So, we have a lot of data, Gena, from our preclinical studies that is very, very clear that when you do observe a tox to FAP it tends to be, it's almost always sequence driven. And so we have that understanding from our preclinical studies and we believe that that's what is operative here in the case of the AAT program. The difference between revusiran and TTRsc02, of course, is, I think, a completely different topic, completely different matter. We don't really understand the revusiran story. The revusiran story was not about a liver toxicity. It was some other event that led to an imbalance in mortality. It had nothing to do with liver signal, per se. So, it's very different. And, of course, the big issue or the big -- not issue, but the big opportunity with TTRsc02 is that if we're able to achieve much lower dosing with less frequency, we should have an exposure difference that is huge compared to revusiran. So, that exposure difference, of course, is what gives us confidence in that program as being one that will advance forward and provide important benefit for patients.

Thank you. Our next question comes from Terence Flynn from Goldman Sachs. Your line is open.

This is Cameron filling in for Terence. I was just wondering for ALN-CC5, can you maybe remind us what's gaiting to starting the Phase 2 combo trial with Soliris by this year-end? Thanks.

Yes. So, Cameron, thanks for that. Obviously, again, per Alan's question earlier, we will be updating everybody on our December 16 R&D day. We're going to be presenting new data at ASH from ALN-CC5 in patients that we're getting continue dosing with ecluzimab on top of ongoing ALN-CC5 pharmacology. I think those data will be of interest to people and we'll certainly look forward to presenting them. But I think in terms of guidance, our guidance has been to start that Phase 2 study by the end of the year and, of course, we'll also update people on our plans at our December 16 R&D day.

Thank you. Our next question comes from Michael King from JMP Securities. Your line is open.

Real quick, just wanted to ask you regarding the EAP for patisiran. John, you used the term those patients who qualify. Can you talk about that and are those going to be patients that mimic the patients in the APOLLO study or do you think you might broaden it or modify it in any particular way?

Yes. I mean, essentially, Michael, these are patients that are similar in phenotype to what has been occurred in the APOLLO study, broad spectrum mutation, stage 1, stage 2 diseases that will range from single digits up to a significant double-digit number and they didn't get a chance to participate in APOLLO. Because for one or other reason they screen failed or they weren't diagnosed at that time or they didn't have access to a site. And, of course, as we know, this disease is certainly more prevalent than we previously thought. And so we think there will be a good number of eligible patients who unfortunately are progressing despite current available treatments for them and so may take part in this study.

Will you take anybody that may have been on TTRRx?

You know, I outlined the inclusion/exclusion criteria, Michael, so let me leave it at that.

Okay. And then just, Akshay, if I could just come back. I hate to keep coming back to revusiran, but I just had one question. You had mentioned, you used the term metabolically labile. I don't know if you can talk about that in the context of revusiran and particularly related to TTR02sc and what modifications or differences there might be that could reduce or eliminate any untoward [indiscernible]?

Yes. I would point to the fact that essentially between the standard template chemistry and the enhanced stabilization chemistry approaches, we use the same sort of menu of options in terms of the chemical modifications. And they comprise diet modifications, [indiscernible] modifications on the sugar or [indiscernible] changes. The big difference is that we learned from going from SEC to ESC, to use the modifications more strategically they would harm stabilization of the siRNA. Consequently the ESC is just a lot more stable in biological matrices and protected from these phases longer. As a consequence they are more potent and durable and we've shared many of those datasets resulting in our Phase 1 studies. Now, the issue of metabolic lability is that a drug like revusiran which was more susceptible to dose degradation and therefore needed to be dosed a lot higher, 500 milligrams weekly as opposed to 100, 200, 300 milligrams every three months or six months as we're noting with some of our other programs. Revusiran will generate a range of metabolite rapidly once it enters the system and so you won't find much [indiscernible] revusiran onboard. So, that's a different picture from the result with ESCs which are much more stable and will tend not to yield those metabolites and most of the drug or much of the drug will be excreted ultimately intact.

Michael, we can estimate in broad terms that the overall exposure, then, is amplified -- overall exposure differences amplified significantly greater as it relates to metabolites. So, that, of course, is very encouraging for us if that were a reason for the revusiran safety findings, then of course their ESC platform we have much, much lower overall exposure which is very reassuring.

Thank you. Ladies and gentlemen, that does conclude our question-and-answer session for today's call. I would now like to turn the conference over to John Maraganore for any closing remarks.

All right. Well, thanks, everyone, for joining us this afternoon. We expect the rest of 2016 to be very data-rich with important clinical results and we look forward to sharing them with you. Obviously, five separate programs will be discussed and I think this will highlight the opportunities in front of us. And, of course, finally as a person born in Chicago, I have to conclude by saying go Cubs! So, thank you. Bye.

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