Welcome to the Alnylam Pharmaceuticals’ Conference Call to discuss Third Quarter 2014 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 conference over to the Company.

Good afternoon. I am Josh Brodsky, Manager of Investor Relations and Corporate Communications at Alnylam. With me today are John Maraganore, Chief Executive Officer; Barry Greene, President and Chief Operating Officer; Akshay Vaishnaw, Executive Vice President and Chief Medical Officer; and Mike Mason, Vice President of Finance and Treasurer. Laurence Reid, our Chief Business Officer, is also here and available for Q&A. For those of you participating via conference call, the slides we have made available via webcast can also be accessed by going to the Investors page of our website, www.alnylam.com. During today’s call, and as outlined on Slide 2, John will provide some introductory remarks and provide general context for some of our recent progress and activities, Akshay will summarize the clinical and preclinical progress with our pipeline, Mike will review our financials and guidance, and Barry will provide a brief summary of certain business highlights and goals for 2014 and beyond 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 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 recent quarterly report on file with the SEC. In addition, any forward-looking statements represent our views only as of the date of this recording and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligations to update such statements. I will now turn the call over to John.

Thanks, Josh, and it’s great to have you fill in today for Cynthia since she’s not feeling well. And welcome and thanks to everyone for joining us this afternoon. During the third quarter of 2014, in recent period, we continue to execute on our efforts to advance RNAi therapeutics to patients and the market. We reported on several meaningful clinical and preclinical data sets which together continue to reinforce what we believe to be the significant potential of RNAi therapeutics as a whole new class of genetic medicines. Akshay will go through our pipeline progress in more detail momentarily, but I wanted to highlight some key points. First, an important milestone for the period was the six-month clinical data that we reported from our Phase 2 open-label extension or OLE study with Patisiran. With the important caveat that this is an open-label study in a small number of patients, we’re very encouraged by what we believe to be evidence for possible stabilization of neuropathy progression after the first six months of treatment. We believe these new data form the beginnings of an important bridge for RNAi therapeutics from targeted gene knockdown to clinical end points. Indeed, this an important theme for Alnylam going forward as we generate data to establish the key links between targeted gene knockdown and clinical outcomes across a wide range of programs. For example, in our hemophilia program, we’ll look forward to seeing the potential relationship of antithrombin knockdown with increased thrombin generation and reduced annualized bleeding rates in people with hemophilia. In our PCSK9 program, we’ll look forward to seeing the potential relationship of PCSK9 knockdown with decreased LDL cholesterol levels in people with hypercholesterolemia. In our complement program, we'll look forward to seeing the potential relationship with C5 knockdown with hemolysis inhibition and/or lactate…

Thanks, John and hello, everyone. We have indeed continued to make great progress with our pipeline of RNAi therapeutics. Let me begin with our Patisiran program. Patisiran is our lead 5x15 Genetic Medicine Program and is aimed at the treatment of TTR-mediated amyloidosis or ATTR, patients with Familial Amyloidotic Polyneuropathy or FAP. This program is enrolling patients in our Phase 3 of APOLLO trial, our randomized double-blind placebo-controlled study, designed to evaluate the efficacy and safety of patisiran in ATTR patients with FAP. The primary endpoint of the study is a difference in the change in modified Neuropathy Impairment Score or mNIS+7 between patisiran and placebo at 18 months. APOLLO is designed to demonstrate the efficacy and safety of patisiran in support of marketing authorization in countries around the world. We’re pleased with the patient enrollment in APOLLO and we now have over 26 sites in nine countries. In the meantime, at the American Neurological Association meet in October, we presented interim six-month results from our ongoing Phase 2 OLE study of patisiran in patients with FAP. Results showed a mean 0.9 point decrease in mNIS+7 at six months in 19 patients with mNIS+7 data available for the current analysis. This decrease in neuropathy progression compares favorably with the seven to 10 point increase in mNIS+7 at six months that can be estimated from historical data sets in untreated FAP patients with similar baseline characteristics. With the very important caveat that our results stem from an open-label study in a small number of patients, we are encouraged by these data as they suggest evidence for disease stabilization in patisiran treated patients. Of course, we will be very interested to see how these outcomes look at 12 months and 18 months, which is data we should be in a position to…

Thanks, Akshay. I will be referring to Slide 21 for a discussion of third quarter 2014 financial results. This quarter we maintained a strong balance sheet with 915 million in cash, cash equivalents and marketable securities. Our GAAP revenues for the third quarter of 2014 were 11 million as compared to 9 million in the third quarter of 2013. GAAP revenues this quarter included 5.5 million related to our collaboration with Takeda, 3.4 million related to our collaboration with Monsanto and 2.1 million related to our collaboration with The Medicines Company, research related licenses and other sources. This includes a $1 million payment from Arrowhead for the advancement of their AAT program to the start of GLP tox studies. Arrowhead is licensed for their AAT program with Alnylam intellectual property under the Roche agreement that they acquired in 2011. Moving to expenses, R&D expenses were 46.3 million this quarter as compared to 34.5 million in the prior year period. This increase was due to additional expenses related to the significant advancement of our clinical and preclinical programs. We expect that research and development expenses will increase slightly for the fourth quarter of 2014 as we advance certain programs into later stages of clinical development. G&A expenses were 9.9 million in the third quarter of 2014 as compared to 6.8 million in the third quarter of 2013. The increase in G&A expenses in the third quarter of 2014 as compared to the third quarter of the prior year was due primarily to an increase in general business activities and certain professional services during the third quarter of 2014 as compared to the same period last year. For the fourth quarter of 2014 we expect that the G&A expenses will remain consistent with the third quarter of 2013. GAAP net loss for the third quarter of 2014 was 44 million as compared to a GAAP net loss of 29.7 million for the same period in the previous year. Regarding our equity investment in Regulus Therapeutics, the fair market value of our investment in Regulus as of September 30, 2014 was 41.3 million as compared to 45.5 million at the end of 2013. As of October 31, 2014 the value of this investment has increased to 117.7 million. With respect to guidance for 2014, we are now increasing our year-end cash guidance and expect we will finish the year with greater than 860 million in cash, which provides us with a strong balance sheet to invest in a broad pipeline of genetic medicines and to maintain financial independence through multiple product launches. Of course, starting in 2015, we expect a significant share of the expenses on our patisiran and revusiran programs to be shared with Genzyme pursuant to the terms of our alliance agreement. Accordingly, we see our non-GAAP net loss to be beneficially impacted by this alliance starting in Q1 2015. I will now turn the call over to Barry.

Thanks, Mike. As you’ve heard from John and Akshay, we’ve had a tremendously productive third quarter in recent period as we continued to lead the translation of the science of RNAi into the industry’s leading pipeline of RNAi therapeutics. In addition to the steady presentation of clinical and preclinical data, we had a very productive quarter with regard to our intellectual properties estate. Specifically, we receive the Notice of Allowance from the U.S. Patent Office for a new patent broadly covering conjugate-based delivery of RNAi therapeutics known as the Manoharan ’478 patent which has now issued. As we believed before this patent issuance further strengthens our view that anyone developing GalNAc-Conjugates for RNAi therapeutics will require a license from Alnylam's IP portfolio. We certainly open to providing such licenses on a target-by-target basis for disease areas outside our core strategic interest. We also received two Notice of Allowances from the U.S. Patent Office for patent applications from the Tuschl II family, the '262 patent and now issued '829 patent. These new patents have very wide claims. They exemplify Alnylam's leading IP position in the entire field of RNAi therapeutics. Now I'll turn to our 2014 goals and guidance. As we’ve announced at the start of the year, we now expect to significantly exceed our original 5x15 guidance. When we launched or Alnylam 5x15 strategy in January of 2011, we stated that we expected to have five programs in clinical development by the end of 2015. We now expect to exceed that guidance with six to seven programs in clinical development by the end of 2015, including at least two programs in Phase 3 and five to six programs that will have achieved human proof-of-concept results. We’re on track to achieve this expanded guidance. With regards to our patisiran program, we…

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

Thank you. (Operator Instructions) Our first question comes from the line of Alethia Young from Deutsche Bank. Your line is open, please go ahead. Alethia Young – Deutsche Bank: Hey guys, congrats on the progress this quarter. And I'm glad that name changed. That’s pretty cool.

Well, it's an non-proprietary name for ALN-TTRsc and we want to introduce you today. Alicia Young – Deutsche Bank: I guess two questions I get commonly and one of them is around the strategy forward in hemophilia. Are you thinking about maybe going more after the inhibitors in rare bleeds and how do you think about maybe eyeing for that potential study? And then the second question is just when you look at the data coming at AHA, I know we’re only looking at five weeks, but at least all kind of some biomarkers for just the six weeks at [indiscernible] but I guess I am just wondering how you think about contextualizing these two data sets based on difference in time durations or if there is anything to read at all?

: So, we’re very excited about it. We’ll have initial clinical data at ASH, which I think will be of interest to people, but then obviously the more complete data set from the Phase 1 will likely be at the ISEH meeting in June of next year. And then regarding the TTRsc or revusiran Phase 2 data, I really encourage people to really focus on tolerability data. This is a population that elderly frail that have con meds, including diuretics that have renal impairment, and I encourage people to focus on the TTR knockdown that we see and to confirm that in fact we're seeing translation of that knockdown between volunteers and patients. With five weeks of treatment, I think people should not expect to see much of anything on the clinical endpoint data, because frankly it's too short of a treatment. I think where that gets more interesting with revusiran is now with the start of our open-label study where we're going to be treating patients for two years and of course we'll be reading out data at least once a year and updating people on that as we continue or as at that time we'll be accruing patients into our Phase 3 study with revusiran in TTR cardiac amyloidosis. So that's my perspective. I mean, Akshay, I don't know if there is anything to add to that, but please chime in. : So, we’re very excited about it. We’ll have initial clinical data at ASH, which I think will be of interest to people, but then obviously the more complete data set from the Phase 1 will likely be at the ISEH meeting in June of next year. And then regarding the TTRsc or revusiran Phase 2 data, I really encourage people to really focus on tolerability data. This is a population that elderly frail that have con meds, including diuretics that have renal impairment, and I encourage people to focus on the TTR knockdown that we see and to confirm that in fact we're seeing translation of that knockdown between volunteers and patients. With five weeks of treatment, I think people should not expect to see much of anything on the clinical endpoint data, because frankly it's too short of a treatment. I think where that gets more interesting with revusiran is now with the start of our open-label study where we're going to be treating patients for two years and of course we'll be reading out data at least once a year and updating people on that as we continue or as at that time we'll be accruing patients into our Phase 3 study with revusiran in TTR cardiac amyloidosis. So that's my perspective. I mean, Akshay, I don't know if there is anything to add to that, but please chime in.

No, I think you covered all the main points, John.

Thank you. And our next question comes from the line of Ted Tenthoff with Piper Jaffray. Your line is open, please go ahead.

Hi, Ted. Ted? Maybe he can call back.

All right. We will go to our next question which is from Alan Carr with Needham & Company. Sir, your line is open. Please go ahead. Alan Carr - Needham & Company: A couple of questions. One of them, you mentioned there were some enrollment challenges earlier with AT3. I wonder if you could comment briefly on that. And then you mentioned in a previous question that you'd be expanding that program aggressively. I'm wondering if that's something that maybe you plan on learning a lot of [indiscernible] in 2015 assuming the data here? And then also can you comment a couple of your neuro programs here, GO1 and AGT, and how many of these do you think will be running in parallel in 2016?

Do you want to handle the first one on AT3 and then I'll handle the preclinical?

I think overall the AT3 program obviously is terribly exciting. It's going well. The preliminary data in May I think has set the scene for part B of the study in hemophilia subjects with the knockdown that we showed there in healthy volunteers. Alan, when you have a new indication, you sometimes learn factors that influence your study design and we've learned things as we've gone on and we've made some sensible changes to protocol. The enrollment is going really well now and I think we're back on track. And as we guided, we'll be presenting data both at ASH for the early cohorts in the hemophilia portion of the study as well as the complete study first half of next year. So I don't think there is any really big meaningful delay here and I think still feeling great about this program and the quality of the data you're seeing.

And Alan, you had a second question on AT3 and I want to make sure we captured related to just what we… Alan Carr - Needham & Company: Do you think you'll be able to expand aggressively with these other Phase 2 trials in hemophilia next year?

Akshay, you can answer too. I mean, absolutely. We're not giving guidance yet for 2013, but it's going to be a big year for that program in terms of what types of trials we expect to run. And we're going to be very aggressive on it because we think it's an important opportunity and there is just enormous amounts of disease burden in people inflicted with hemophilia that we want to solve with this approach. Anything to add to that, Akshay?

No.

And then on your question on the preclinical programs, we're very excited about both of the ones you mentioned. I mean, GO1 in primary hyperoxaluria, ultra-rare orphan disease, very high unmet need, animal data with our GalNAc-conjugate siRNA shows very impressive efficacy in these preclinical models. The genetic data supports the target very nicely. It's really just in our sweet spot of where we can have a high impact drug. And obviously with our GalNAc technology there's just not a single liver target in the world that we can't go after with this approach and we're going to do this one and it's going to be a great program for us. And the goal is to have that in the clinic in 2016. And then in the angiotensinogen program which is I think really an amazingly exciting program in the setting of hypertensive disorders of pregnancy, including preeclampsia, I mean this is a very innovative program. We haven't given guidance on this one yet in terms of when we'll be in the clinic. As you can appreciate, Alan, it's got a much more complex development plan that one has to think through. We're talking about potential use in pregnant mothers. So we're not going to give guidance on that yet until we have our arms around the development path going forward. But it's a program that we're very committed to. The unmet need in preeclampsia is unbelievably high and the morbidity associated with that disorder for mothers and her infants is just something which this approach has the potential to be meaningful for and therefore we're just not going to let it go unanswered. And so we'll advance it, but we need to get our arms around the development path further for reasons that I think you can appreciate.

(Operator Instructions) Our next question comes from the line of Mike King with JMP Securities. Your line is open. Please go ahead.

If I could maybe follow up, it sounds like Alethia and I are talking to the same investors or probably talking to the same KOLs, both on AT3. And I am still going to call it TTRsc for now. Just on AT3, I am just curious about -- one question that came up to me was I guess some investors have talked to KOLs that feel that a development path in inhibitor patients would have to go on top of NovoSeven. Can you comment about that?

NovoSeven is used to treat bleeding, not to prevent bleeding. And so any development path of the drug in inhibitor patients would of course require or have to include the need to use Factor VII or for that matter FEIBA if there is a bleed. And so that’s certainly part of the process of understanding our development plan for the product in that setting. But it’s not that NovoSeven is used for prevention. These are patients that don’t have anything for prevention and go throughout the course of their year bleeding 20 plus times a year and then of course treat themselves with drugs like NovoSeven or FEIBA. Of course, our goal here would be to reduce that instance of bleeding from 20 plus times a year to a much smaller number and that’s where the real value proposition would exist for patients with inhibitors.

But you did say that -- so you do want to develop AT3 as well for on demand use as well? Correct or not?

Absolutely. No, we don’t think this is just for inhibitors. We think it has a broader potential, because we’re talking about a drug that’s a once monthly subcutaneous injection. It’s a transformative therapy for people with hemophilia.

And just to be clear, Mike, when we mentioned on-demand patients, it would be prophylaxis in that patient group 2 rather than treatment when [Multiple Speakers] preventing bleed there too. The key here is resetting the coagulation cascade that dramatically brings down annual bleeding rates across all these patients.

And then just to turn up again to the TTRsc patient population. John, you pointed out the elderly and frail. But in more of a real world, I mean this is a FAP population with FAP involvement. Is it fair to say that this is not a representative population of sort of what you would conceive as the average FAP patient that’s out there in the United States at this time?

Maybe Akshay, you can answer that.

Mike, I think what we’re trying to emphasize is that the Phase 2 study is very importantly trying to establish the safety of revusiran in TTR cardiac amyloidosis. There is a spectrum of patients in there. But the most important underlying feature in common with Phase 2 and Phase 3 will be these patients have [indiscernible] is a significant medical disorder with a significant five-year mortality in general. Forget in this very nasty amyloidotic disorder and then renal impairment associated with that. And so we’re just emphasizing that those facts have been important to the study and we've established safety in that context. And I am sure in Phase 3 patients will have heart failure and renal impairment and we’ll be glad that we’ve studied them in Phase 2 to establish the baseline profile.

Mike, keep in mind that the FAC patient group, many of these patients have a two year to four year life expectancy. So as John and Akshay mentioned, they are frail. Now certainly with a potential treatment in revusiran and our DISCOVERY effort where our aim is to start identifying these patients earlier and earlier. But in today’s world, they have heart failure.

I was going to ask you about DISCOVERY. I didn’t want to run afoul of your two question rule. But, I am just curious with regard to that and maybe just count as a follow up. Do we know what sort of average age of diagnosis is for a FAC patient without any FAP involvement versus someone who is sort of purely a FAC patient? Are they that much different?

I mean the typical FAP patient with the polyneuropathy will be in their 40s, early 50s. They can be older but they’re definitely going to be younger than a typical TTR cardiac amyloidosis patient. They’ll be in their 50s onwards. And I think the mean FAC age will probably end being somewhere around 65 or so.

And the mean age in the Phase 2 study will probably be in the 70s.

Yeah, it will be higher.

But they won’t have the [indiscernible] and the other aspects of FAP that will impact, will they?

In and out with wasting disorder the body does not [indiscernible] they may well have lost some weight due to that issue. But it’s a different disease. I think we have to establish the safety profile. I think we’re feeling confident that the Phase 2 data set is a significant step forward for us in terms of understanding the safety and knockdown and setting us up for Phase 3 in a corresponding population.

Thank you. And our next question comes from the line of Ted Tenthoff with Piper Jaffray. Your line is open. Please go ahead.

Maybe you can tell us – I'm thinking a shot in the dark -- obviously we'll be up in Boston next week, maybe you can tell us a little bit about the hepatitis B program and sort of the competitive environment around that exciting marketplace and sort of what you plan to show us and kind of what the plans are for 2015 there?

Thanks, Ted. And hopefully we’ll see you at the [liver] meeting next week as well. The HBV program, obviously very excited about, it came out of our acquisition of Sirna, the deal that we did earlier this year. And of course Merck -- Sirna has generated some very compelling data in chimps and chronically infected chimps showing an over two log reduction of surface antigen levels in chronically infected animals. And of course they developed this initially with a lipid nanoparticle approach that we don’t think is the right approach in hep B because lipid nanoparticles really need premedication from a tolerability standpoint and that just wouldn't work in hep B. In fact, that’s one of the reasons that Merck didn’t pursue that approach because of the premed challenges with the LNPs. But of course we’ve got this beautiful GalNAc technology that allows us to overcome that. And so over the course of the year, we’ve been working to convert the siRNA that was previously in encapsulated in the LNP into a GalNAc-conjugate and we’re making tremendously great progress, you’ll see some updates on that next week. We expect to have our development candidate by the end of the year in that program. And then we’re going to turn the Alnylam crank on that program and do what we’ve now done and shown everybody that we can do reproducibly time and time again by filing our CTA in that program and we expect that to happen around year's end of next year and then advancing to Phase 1. Now I think what you can expect from our program is that we’re going to have a robust siRNA, very potent, one that has to be very wide therapeutic index and one that allows us to move very quickly into clinical development to demonstrate the ability of this drug to knock down surface antigen levels and then ultimately in larger studies to show improved zero conversion rate. So, we’re excited about the program. I think there's quite a bit of interest in what we’re doing for good reasons. I think the clinical validation of our GalNAc platform is incontrovertible. Look at all the data you see today, look at even the Regulus data in some regard and you can quickly I think extend the beliefs that says our program will probably be the best-in-class approach, it's certainly going to be the only one that will be subcu in the RNAi fields in HBV and we think it's going to be the winning strategy. It's a big, big market, huge unmet need, lots of opportunity and again, lots of interest in the program.

(Operator Instructions) Our next question comes from the line of Stephen Willey with Stifel. Your line is open. Please go ahead.

Just to follow up on Mike’s question regarding I guess the FAC versus FAP. So I guess is it safe to assume that you would expect the FAC patients entering the open-label extension study to have meaningfully different baseline cardiac biomarker data relative to the subset of FAP patients with cardiac involvement that we saw at ANA?

That is indeed true. The patients in the Phase 2 study with revusiran have established TTR cardiac amyloidosis and so there's various cardiac biomarkers BNP, troponins, et cetera. So this radiologic data it's based on will be different and show, will establish marked disease.

And then just a follow-up to I think a comment that you made, John, regarding, or Barry, the additional IP that’s been solidified around the GalNAc conjugate and I think you had made a comment around being willing to ascribe licenses on a target-by-target basis that are outside of the core therapeutic focus. Is it safe to say or safe to assume that essentially every program within your pipeline right now is kind of considered to be within the core therapeutic focus?

I would that’s a good assumption, Steve. I mean, obviously we’re not going to be that interested in -- we’re interested in advancing our medicines to patients and obviously in a fiduciary manner maximizing the value of that effort to our shareholders. And that means that when you've got a program that you're investing in and making it a proprietary program, you don’t typically want to invite competitors in it even if they are not necessarily a strong of a competitor based on the technical data. That's just the nature of pharmaceutical R&D and it's been that way in the industry for ever. And so, anything that we're working on, we’re not interested in licensing because we have a competitive program that we are maximizing the value of that for Alnylam shareholders. But a good example is in the case of our Regulus relationship, we licensed some of our GalNAc technology and we don’t have a competing program in HCV and they have access to our technology to our miR-122 and we’re delighted with the opportunity to build value for our shareholders based on that license that we’ve given them and I think that’s a good example of it. And we'll do that for other companies and we've got targets of interest to them that aren't of interest to us and that's part of the way that we think about building value. Akshay, do you have anything to add to that?

No.

Thank you. And I'm showing no further questions at this time. And I would like to turn the call back to management for any closing remarks.

Great. Well, thanks everyone for joining us this afternoon. I mean obviously the year has been transformational for the company and there's still lot more to come. So we look forward to sharing with you further updates and we'll be obviously in touch in the weeks and months to come. Thank you very much.