Stan Crooke - Chairman and CEO Lynne Parshall - Chief Operating Officer Beth Hougen - Chief Financial Officer Wade Walke - Vice President, Corporate Communications and IR

Alethia Young - Deutsche Bank Chad Messer - Needham & Company Whitney Ijem - JPMorgan Andrew Goldsmith - Canaccord Genuity Securities Navdeep Singh - Goldman Sachs Nick Abbott - BMO

Welcome to the Isis Pharmaceuticals’ Year End Financial Results Conference Call. Please note this event is being recorded. Leading the call today from Isis is Dr. Stan Crooke, Isis Chairman and CEO. Dr. Crooke, please begin.

Good morning, everyone. And thanks so much for joining us on our call to discuss our year end financial results. So on the call today, Lynne will review the 2013 accomplishments; Beth will walk you through our financials and our guidance for 2014, and then I’ll focus on our key goals for 2014. We think 2014 is going to be a very exciting year. Joining me on today’s call are Lynne Parshall, Chief Operating Officer; Beth Hougen, Chief Financial Officer; and Wade Walke, Vice President of Corporate Communications and Investor Relations. And so, Wade, will you read our forward-looking language statement please.

Yes. Thanks, Stan. A reminder to everyone this webcast includes forward-looking statements regarding the financial outlook for Isis, Isis’ business and therapeutic and commercial potential of Isis’ technology, and products, and development. Any statement describing Isis’ goals, expectations, financial or other projections, intentions or beliefs, including the commercial potential of KYNAMRO is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and in the endeavor of building a business around such drugs. Isis’ forward-looking statements also involve assumptions that if they never materialize or prove correct, could result its results to differ materially from those expressed or implied by such forward-looking statements. Otherwise these forward-looking statements reflect the good faith judgment of its management; these statements are based only on facts and factors currently known by Isis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Isis’ programs are described in additional detail in Isis’ annual report on Form 10-K for the year-ended December 31, 2012, and its most recent quarterly report on Form 10-Q, which on filed with the SEC. Copies of these and other documents are available from the company. Now, I’ll turn the call over to Lynne.

Thanks, Wade. Good morning, everyone, and thank you for joining us. 2013 was a year of significant achievement in every aspect of our business. Together with Genzyme, we successfully brought KYNAMRO to the market in United States for patient with homozygous familial hypercholesterolemia. KYNAMRO’s approval for chronic use in patient with life long disease highlights the potential of [ISIS] technology and our success in creating drugs that bring benefit to patients with severe disease. We demonstrated in the broad Phase 3 program and KYNAMRO significantly lowered LDL-cholesterol and reduced other atherogenic lipids the independent risk factors for cardiovascular disease. Moreover, KYNAMRO was dozed as a single, weekly, at home injection, that’s easy and convenient to use and using KYNAMRO doesn’t require any restriction on diet or any additional monitoring. Importantly, KYNAMRO can be safely used with the other medications patients with homozygous FH frequently take. These attributes give us confidence in KYNAMRO’s commercial success. While Genzyme does not wanted to give out specific details on sales, what we can say is that while the launch got off to a bit of slow start, sales showed significant quarter-over-quarter growth in 2013 and we believe the sales will continue to increase significantly this year. There are hundreds of physicians who haven’t certified to prescribe KYNAMRO. We believe that the increase number of prescribers will translate into increase prescription of patients on drug. Genzyme tells us that the reimbursement process is working well and they are successfully working with payers to move patient expeditiously from prescription to drug and this is all great news. Genzyme has increased it sales force to support KYNAMRO’s anticipated sales growth. As we enter 2014 we expect to see returns from this increase investment. In addition to marketing KYNAMRO in United States, Genzyme marketing KYNAMRO in Mexico, Argentina and South Korea, and pursuing regulatory approvals in a number of other countries. And of course, Genzyme is continued to supply KYNAMRO on a name patient based outside of the United States including in Europe. Genzyme also working closely with the regulatory authorities in Japan to evaluate the next steps in bringing KYNAMRO to the market in Japan. In addition to Genzyme increasing investment in marketing, we and Genzyme also continue to investment in the clinical development of KYNAMRO to support potential commercial expansion of the drug. The ongoing focus FH study a long-term treatment study in patient with severe heterozygous FH that was design to support filings to expand the indications. This study is on track with data plan in the first half 2015. Assuming its positive Genzyme could use the data from this study from traditional new data to support refilling in Europe for approval. The safety and tolerability we are observing in the study so far are appeared to be consistent with previous studies. We also continue to gain long-term efficacy in safety data through open-label extension study for KYNAMRO in patients who participated in their earlier Phase 3 program. In this study we are seeing with longer term dosing KYNAMRO continues to be safe and well-tolerated. This is consistent with our Phase 3 experience. This data were recently published in the European Heart Journal. In addition, presentations and scientific meetings such as the National Lipid Association Annual Meeting have highlighted data from our Phase 3 study treating children with homozygous FH. We are also encouraged by the strong support for KYNAMRO in the cardiovascular community. This is evidence by positive responses from third-party physician surveys and a large number of published reviews and commentaries. So in short, we believe that the long-term future of KYNAMRO is bright and getting brighter. The approval of KYNAMRO provide significant validation of our technology, our approach to drug discovery and our ability to develop drugs that could have profound impact on patient lives. KYNAMRO, however, is only the beginning. 2013 was the year in which our pipeline matured considerably. We reported clinical data from numerous studies showing that our drug worked in many diseases and many patient populations. This maturation means we now have a pipeline with numerous late-stage clinical programs. We believe that at least five drugs from our pipeline could be in registration for marketing approval by 2018 and that each of these drugs represents a significant commercial opportunity. Three of these five drugs are from our severe and rare disease franchise and represent the success we had in developing drug to treat diseases in the significant area of unmet medical need. We believe that our severe and rare disease for HF is one of the largest in the industry and getting larger as we continue to add new drugs during each year. And while we are on the subject of severe and rare disease, I would like to acknowledge that today is International Rare Disease Day. The theme for this year is Improving Care for People Living with Rare Disease and that is our comment as well. We believe that in such drug offer unique approach to treating severe and rare diseases and we remained focus on advancing our drugs towards the market for these very needy patients. We are also encouraged by the recognition of the various regulatory bodies have given to the need for new treatment for the rare and orphan diseases for which we are developing drug. In particular we are pleased by the EMAs recent positive opinions on ISIS-APOCIIIRx and ISIS-TTRx orphan drug designations. Consist with our commitment to bring much needed treatment for severe and rare diseases to the market. Our drug design to treat spinal muscular atrophy, ISIS-SMNRx rapidly advanced in development during 2013. Earlier this week, we reported initial results from our Phase 2 study of ISIS-SMNRx in infants and children. In our ongoing open-label study treating infants with type 1 SMA, we saw early evidence that infants treated with ISIS-SMNRx might be surviving longer than what would be predicted based on the natural history patient with this disease. It is our first study in infants and we are pleased with how well-tolerated multiple doses of ISIS-SMNRx have been in these babies so far. We also reported interim results from our open-label study in which we are treating patients with type 2 and 3 SMA with multiple doses of ISIS-SMNRx. In this study, we have dose and time dependent increases in Hammersmith scores. These results are consistent with our observations from our previously reported single dose study, which provides us even more confidence in this drug. And finally, for the first time, we reported data from a new assay we developed to demonstrate dose and time dependent increases in SMA protein level in the cerebral spinal fluid of children retreated with ISIS-SMNRx, confirming that ISIS-SMNRx is acting to the mechanism from which it was designed. This data consistent with the results we saw in animals and all of these results continued to support our enthusiasm for this drug and our plan expeditiously proceed to the Phase 3 program. We plan to begin the Phase 3 study in infant shortly and then initiate a Phase 3 study in children with type 2 and type 3 spinal muscular atrophy later this year. We will earn an $18 million milestone payment from our partner Biogen Idec when we initiate the infant Phase 3 study and various additional milestone payments as the study progresses. We also earn a significant milestone payment from Biogen Idec when we begin the Phase 3 study in children. We are also very pleased with the progress we are making the novel triglyceride-lowering drug ISIS-APOCIIIRx. Last year we reported five sets of Phase 2 data on ISIS-APOCIIIRx. In these studies, ISIS-APOCIIIRx significantly reduce triglyceride in all patient group study, regardless of the patient incoming triglyceride level and was effective both as the single agent and were combined with other triglyceride-lowering drug. In addition, ISIS-APOCIIIRx improved measures of glucose control and demonstrated consistent trends in enhancing influence sensitivity in patient with type 2 diabetes. This is important because as many as 30% of severely triglyceride patients are diabetic or pre-diabetic. All of these data support our plan to begin a Phase 3 program this year into different patient populations. First Phase 3 study will be in patients with FCS and second will be in patients with severely high triglyceride. In addition to advancing our ISIS-SMNRx and ISIS-APOCIIIRx towards Phase 3 development, ISIS-TTRRx is a year into its Phase 3 program in patients with amyloid polyneuropathy. When you have several patients in the study have been treated for almost a year and we are on track to complete enrollment in 2015 and complete the study in 2016. As a result, we believe that ISIS-TTRRx could be a very important commercial asset for ISIS in the near-term. The profile of ISIS-TTRRx as a convenient once weekly low volume injection is being very well attracted by patients in this ongoing study and we believe will be convenient and attractive commercial presentation for the drug. Because we are developing ISIS-TTRRx with our partner GSK, we earn milestone payments in licensing fees if this drug advances. In fact, we’ve already earned $24 million in payments from GSK associated with the advancement of ISIS-TTRRx including $14 million related to the ongoing Phase 3 study. As the study progresses, we are eligible to earn an additional $46 million in milestone payments from GSK prior to GSK licensing the drug. So I just spent a lot of time talking about our late-stage drugs. In addition to these drugs, the rest of our pipeline is also advancing rapidly. In 2013, we initiated five Phase 2 programs, including advancing three drugs to treat Type 2 diabetes under Phase 2 clinical studies. We also reported clinical data on ISIS-APOCIIIRx, an important addition to our cardiovascular franchise. In addition, we and AstraZeneca continue to advance our cancer programs. We previously reported early promising data on ISIS-STAT3Rx and hope to be able to report more data from current Phase II lymphoma study later this year. AstraZeneca is also conducting a Phase II study of ISIS-STAT3Rx on patients with liver cancer. All these advancements and the positive data we’ve recorded had translated into real value for ISIS and our shareholders. And this is just the tip of the iceberg. Because of the efficiency of our technology, we are able to continue to add drugs to our pipeline. These are drugs that could significantly impact the management of diseases in many different therapeutic areas. For example, last year, w added to our pipeline, ISIS-DMPKRx, a drug we’re developing with Biogen Idec to treat myotonic dystrophy Type 1. These are terrible progressive disease and one for which they have limited therapeutic options. We added ISIS-ANGPTL3Rx, a drug that has the potential to lower multiple lipid parameters in patients with severe disease. We plan to initiate clinical studies on both of these drugs this year. If were to go on all of the other exciting activities in our earlier stage programs that take all of our time and that wouldn’t get talk to you about our excellent financial results. So I move on to discuss our partnership successes from last year. Last year, we successfully executed our business strategy by adding new partnerships and expanding our existing partnerships to advance on severe and rare diseases and cancer programs. In September, we significantly expanded our alliance with Biogen Idec completing our fourth collaboration with them in less than two years. Fourth collaboration represent a very significant investment by Biogen Idec in antisense technology from which we have the potential to earn milestone payments and licensing fees in excess of $4 billion plus double-digit royalties. Coupling our antisense technology to Biogen Idec’s expertise, we believe that we can build a large and valuable neurological disease franchise well beyond what we could do on our own. Our collaboration with AstraZeneca is also up to a great start. As I mentioned earlier, we’ve a broad Phase II program underway for ISIS-STAT3 and we will be reporting date from that program later this year. Together with AstraZeneca, we added ISIS-ARRx, a drug to cure prostrate cancer to the pipeline. And AstraZeneca plans to initiate a Phase I, II study on ISIS-ARRx this year. Our GSK collaboration also made important progress last year as we advanced three drugs from this partnership into development. Most recently we advanced ISIS-GSK3Rx into Phase I study and healthy volunteers and we hope to be able share more about the target of this drug with you this year and when study advances. So 2013 was a very successful year and we believe it sets a stage for an equally successful year in 2014. And with that, I’ll turn the call over to Beth.

Thank you, Lynne. We substantially exceeded our cash guidance and significantly improved upon our pro forma NOL guidance. We also ended the year in the strongest financial division in the company’s history with more than $650 million in cash and a pro forma NOL of $40 million. We achieved these financial results by effectively executing our business strategy and successfully advancing the drugs in our pipeline. These results illustrate that our business model is working by consistently generating cash and revenue as our drugs progressed and allowing us to maintain a modest and predictable expense level. Today in our pipeline, we have one drug for every 12 ISIS employees. A comparable number and pharmaceutical company would be in the thousands of employees and if you subtract marketing and sales, it would be many hundreds. This limited infrastructure is only possible because of the efficiency of the antisense technology platform we’ve built. Our 2013 year end cash balance of more than $650 million with an increase of approximately $300 million over the prior year. The substantial improvement in our cash position was driven in large part by more than $220 million we received partners of which $130 million came from upfront payments from Biogen Idec and Roche. And over $90 million came from a variety of payments associated with our advancing pipeline. We ended 2013 with a pro forma NOL of $40 million which was added above our initial guidance from last February as well as our revise guidance from later in the year. Revenue was $147 million, a 44% increase over 2012 and reflects the maturation of our pipeline and the partnering successes we had in the year. We recognized revenue from these sources of $42 million, primarily from the amortization of upfront fees we received from Biogen Idec, AstraZeneca and Roche. We also achieved the significant number of milestone payments when we advanced our partner drugs. We earned more than $80 million in milestone and licensing payments from six of our partners associated with partners on nine different drugs. So we can consistently generate revenue in cash from multiple partners and numerous drugs. It’s also a reflection of the success of our partnering strategy. This strategy supports our ability to remain financially strong while expanding and advancing our pipeline and continuing to improve our technology. As Lynne discussed, we made significant pipeline progress in every therapeutic area including moving ISIS-TTRRx into Phase III development and advancing ISIS-APOCIIIRx and ISIS-SMNRx to the point where each is poised to begin Phase III study. We also initiated numerous clinical studies and added new drug to our pipeline. We accomplished all of this with only a modest increase in our expenses over 2012. 2014 has the potential to be another great year for the company. We’re continuing to make investments in the pipeline in technology while projecting a pro forma NOL in the low $50 million range and in ending cash balance of more than $575 million. Already this year, we generated more than $16 million from Biogen Idec and Alnylam which has gotten the year off to a very strong start. One of the advantages of our partnering strategy is with a significant portion of our revenue comes from the amortization of upfront fee and as such is predictable. We expect revenue from the source in 2014 to be in access of $45 million. Our business strategy and partnership ensure that we have a steady stream of milestone opportunities each year although each year they may come from different sources. Because of the significant growth at our pipeline, we are projecting to earn milestone payments in access of $110 million. That’s a $30 million increase compared to 2013. As in 2013, these milestone payments come from multiple partners and multiple drugs because we have so many opportunities, we’re confident that we can achieve this guidance. Our partnering strategy also takes advantage of our dominant intellectual property estate through the success of our satellite company. In these partnerships, we run revenue from our partners when they licensed our technology to their partners. For example, we are $7.5 million earlier in this year for Alnylam for their transaction with Genzyme. As you know Genzyme began marketing KYNAMRO in 2013. As we noticed before we have a profit-sharing arrangement with Genzyme for KYNAMRO, not a royalty. This means that we will earn a portion of KYNAMRO’s profit rather than portion of KYNAMRO sales. With this type of arrangement, we will record revenue from KYNAMRO on our P&L when KYNAMRO was profitable. In 2013, the initial launch year, Genzyme made significant investments to support launch and future revenue growth. Genzyme continues to invest in KYNAMRO through market expansion, increasing sales support in the United States and as Lynne mentioned, working closely with the regulatory authorities to evaluate the next steps to bring KYNAMRO to the market in Japan. In addition, the FOCUS FH study continues to progress and we are looking forward to data early next year. We anticipate that these continued investments in KYNAMRO will translate into significant revenue growth this year and in the coming years. We are already seeing the benefit of these investments as sales of KYNAMRO continue to increase on share. We believe that this trajectory will continue in 2014. However, to be conservative given the increasing level of sales support and the ongoing development efforts, we’ve now concluded any KYNAMRO profit share revenue in our 2014 guidance. Of course, if KYNAMRO outperforms the plan, this could represent upside practice here. We now have a matured pipeline that will mature further as we start four plans Phase 3 studies this year. As such, we expect our expenses to increase. The increase in 2014 reflects expenses to support the Phase 3 studies we plant to conduct, including our ongoing Phase 3 study for ISIS-TTRRx and two Phase 3 studies each for ISIS-SMNRx and ISIS-STAT3Rx. In addition, this year, we plan to have numerous drugs in later stage clinical studies and we plan to advance our earlier stage drugs as well as add new drugs to our pipeline. So, all this rolls up into our projected financial guidance of the pro forma NOL in above $50 million range. And the year end cash balance in excess of $575 million. In short, we are projecting another year of significant financial strength. And with that, I will turn the call over to Stain.

Thanks, Beth. So, now, I’ll shift focus on 2014. We expect 2014 to be another important year for Isis with multiple pipeline events that we hope will continue to enhance our value. Of course, the first quarter has been dominated by news of ISIS-SMNRx. Although we are still early in the development of ISIS-SMNRx, what we’ve observed so far is very encouraging to us, to Biogen Idec, to the investigators, to the patients and to the parents. We look forward to providing a more detailed update on the progress of this drug in April at the American Academy of Neurology meeting in Philadelphia. Even more importantly, we entered partnership with Biogen Idec to finalizing our Phase 3 plans. As we get those studies underway, we look forward to sharing our plans with you. 2014 is another important year for our other Phase 3 assets. Our partners at OncoGenex and Teva plan to report the results of the Phase 3 trial in human prosate cancer on Custirsen. Isis bears no expense for the development Custirsen, but does receive a share of payments, OncoGenex receives from Teva plus royalties. So all this is upside for us. ISIS-TTRRx is already well along in the Phase 3 study and patients with TTR amyloidosis. We have patients in this study who have been treated for almost a year. We plan to complete the enrollment in this study in 2015 and if positive, we believe the study will support registration of ISIS-TTRRx in patients with the familial polyneuropathy. We are also working with GlaxoSmithKline to finalize development plans for patients with cardiac 1 of this disease. In the lipid franchise, the most important event this year will be the start of the two Phase 3 studies in patients with FCS and the second inpatients with severally high triglycerides. We are looking forward to our End-of-Phase 2 meetings and once those are completed, we will share our plans with you. Expanding and advancing the rest of the lipid franchise is also important. We plan to start the Phase 2 program in ISIS-SMNRx shortly. We believe this is substantial, achievable, commercial, opportunities for this drug. Additionally, we plan to begin development of ISIS-ANGPTL3Rx, a drug design to lower all atherogenic lipids. Later this year, we plan to share data from that study with you and discuss how all the drugs from our lipid franchise fit together strategically. And this will also be quite an important year for our type 2 diabetes effort. Today, we have three drugs designed to treat type 2 diabetes in Phase 2 studies. Each drugs works through a unique mechanism and could be use at different points in the treatment of patients with type 2 diabetes. The most advanced drug in these franchisees are drugs designed to reduce the production of glucagon receptor, ISIS-GCGRRx. This drug could be a very potent effective agents for those patients who already have advanced type 2 diabetes. In animals, we show that this drug is dual mechanism of action that reduces glucagon signalling and increases GLP-1 and may protect the pancreas. We are evaluating this drug in a Phase 2 study and patients with type 2 diabetes, and plan to report the results of that study in the middle of the year. Next drug in our metabolic pipeline that is likely to have an important Phase 2 clinical data is ISIS-GCCRRx. This is our drug designed to reduce the glucocorticoid causing diabetes. This drug is quite interesting because of its potential value in the treatment of type 2 diabetes and its potential to treat a number of rare diseases and syndromes for example, Cushing's syndromes is a rare disease caused by excess secretion of cortical hormones. We plan to initially develop ISIS-GCCRRx to treat patients with Cushing’s disease. Here, again we plan to report data from the Phase 2 study of ISIS-GCCRRx in patients with type 2 diabetes later this year or early next year. The third drug, we have in Phase 2 development for type 2 diabetes is a novel insulin sensitizer ISIS PTP-1B RX. This study is enrolling well. We hope to be able to share the results of that study later this year or early next year as well. Finally, I want to go ahead and highlight is our novel drug targeting Factor XI, ISIS-FXIRx that is designed to reduce thromboembolic events. We are now completing a 300 plus patient Phase 2 study, which were comparing the efficacy in safety of ISIS-FXIRx to enoxaparin. In this study, we are pre-treating patients who are undergoing total knee replacement and evaluating the affects of 200 or 300 milligrams of ISIS-FXIRx weekly compared to 40 milligrams of enoxaparin daily. We hope, just that at least equal antithrombotic activity and less bleeding. ISIS-FXIRx like other antisense drugs should not have any drug interactions. This drug should not require a special monitoring and could be an ideal agent to use in patients who were taking many other medications. We plan to report the results of this study in the middle of this year 2014. As we have a large meteor pipeline of first in class drugs, we have a very full agenda and an exciting line up of news flowing this year. In the first half of this year, we will report the results on ISIS-SMNRx, ISIS-GCCRRx and ISIS-FXIRx. We also look forward to OncoGenex and Teva reporting results on Custirsen. Additionally, we are initiating two more Phase 3 programs for quite a number of other clinical trials. In short, it’s going to continue to be an exciting time at Isis. As we look towards the second half of the year, we see an equally full agenda. So, 2014 is off to an excellent start and we are optimistic that it will continue. So now before I open the call up for questions, just let me summarize our major goals for the year. Together with Genzyme, we will continue to support KYNAMRO development, marketing and commercialization activities. These include advancing the FOCUS FH study with the goal to report the data from this study in 2015. Genzyme is marketing and selling KYNAMRO in the United States, supporting commercial launches in Mexico, Argentina, South Korea, and pursuing approval in a number of other countries. We will continue to mature a pipeline of novel, first-in-class drugs. In the near term, we plan to report clinical results from the Phase 2 studies on ISIS-SMNRx at the upcoming AAN meeting. We and our partners plan to report data on from up to seven drugs in late-stage development, including Phase 2 data on ISIS-FXIRx and ISIS-GCGRRx. We and our partners will advance a pipeline and plan to initiate up to five Phase 3 studies, including Phase 3 studies on ISIS-APOCIIIRx and ISIS-SMNRx and initiate Phase 2 studies on up to three drugs. We plan to broaden our pipeline by adding up to five new drugs in both partnered and unpartnered programs. We plan to continue to make substantial advances in antisense technology, and of course we will continue to successfully execute our business strategy to generate revenue and cash, an exciting year. And so with that, we’ll open the call up for questions. Emily, if you can set us up for questions please.

(Operator Instructions) And our first question is from Alethia Young, Deutsche Bank. Please go ahead. Alethia Young - Deutsche Bank: Thanks for taking my question and congrats on the progress around SMA and I’m really wishing that’s for the patients here, but why don’t focus on something else today. You know I know kind of we might have some proof-of-concepts around myotonic dystrophy maybe next year, but just can you give us a little bit more detail about disease and how it compares versus SAM, and then also how the market compares as far as the initial prevalence? And then just confirm or reconfirm around the timelines and your expectations there but getting a little bit of proof-of-concept interesting program? Thanks.

Well, the most important difference is that myotonic dystrophy is a disease that will be treated peripherally with systemic antisense drugs and the treatment needs to take place in muscle. And we’re just in the process of getting the studies underway. And so I would rather -- we think the market opportunity is substantial as does Biogen and we’d rather get into more of those details a little later as we really begin to know more about what the profile of our drug looks like.

Our next question is from Jim Birchenough of BMO. Please go ahead. Nick Abbott - BMO: Hi. Good morning. It’s Nick Abbott for Jim this morning, who is home with the flu unfortunately. In terms of SNA program, what data have you shared with FDA and what feedback have you got from them in terms of their level of excitement or their desire to get this drug to the market in an expeditious fashion?

Well, we’ve had of course a productive relationship with the FDA and the European authorities since we began this project, and they have been very supportive and facilitating our activities. We’ve already had our end of Phase 2 meetings, and so they’ve had the opportunity to see quite a bit of data that were presented at that time. They continue to be supportive and very enthusiastic about the drug so far as we can tell. Obviously, I can’t speak for the FDA other than to say that they’re very responsive and we have a clear path to move our drug forward. Lynne, do you want to add anything?

I would just echo what Stan said. The FDA has been very -- their interactions have been positive and supportive and they have not -- they don’t have in front of them the current, recent set of data and we would after AAN plan on sharing that with them. Nick Abbott - BMO: I guess that was really my point is, if you know from the natural history of type 1 that whatever the data show and you’re clearly showing 20 patients that you’ve changed the natural history as far as we know it. Would FDA really want you to do a place-controlled trial? I mean, obviously, you don’t know, but that when you present the data to them after AAN, is that one of the things that you want to test the waters for?

My preference is not to speculate about that. I think why don’t we just let these babies mature, let the data mature. And as we began to understand the real impact that we have that we seen to be having on these babies, we will confront those opportunities and decisions and when we do, we will discuss them of course. Nick Abbott - BMO: Okay, thank you.

Our next question is from Chad Messer of Needham & Company. Please go ahead. Chad Messer - Needham & Company: Thanks for taking my question. It’s always impressive to get overview of all the activities going on over there. My question is actually on KYNAMRO and I know you can’t share any sort of quantitative metrics or Genzyme won’t let you share them which is unfortunate. But is there anything qualitative you can tell us about the launch and the patients that you’re having success with? So like specifically here we learnt recently from Aegerion that an unexpectedly large number of patients are getting scripts written but not filling them and that’s mostly likely due to the tolerability issues and the diet. Is this something you have any anecdotal information that you can share with us, or are you getting patients on your drug that specifically are intimated by the dietary restrictions of lomitapide, is that a big selling factor?

Chad, I have to say first that of course we don’t have direct access to that information. Everything that we know, it comes from Genzyme. And the things I am comfortable saying is we remain very impressed with the commitment, the energy and support that Genzyme, Sanofi is focusing on our drugs. We’re very pleased with the expansion of their sales force and the quality of effort there. As we look at our drug, we think there are many attributes that KYNAMRO has that should make it highly successful in the marketplace and compete very well against lomitapide, including the fact that there is no diet requirement, there are no drug interactions. And we low our all iatrogenic lipids. And we’re seeing the responses to the profiles as we hear about it from Genzyme that one would predict. Lynne, do you want to -- is there some more color you can provide.

Yeah. I think the only thing that I would say, Chad, just to put that in perspective is Genzymes marketing and sales technique as you would want and expect are focused on positive attributes of our drug, not counter selling what might be potentially negative attribute to the different drug. And so we do think patients are taking KYNAMRO because of the whole breadth of this positive set of attributes and one that I would add to the list. Stan gave you is because of our pregnancy category B, it’s a more interactive alternative for women of child bearing than pregnancy category acts potentially. But we’re hearing back from the field is that the overall profile of KYNAMRO is driving patients to physicians to prescribe it and driving patients to want to take it.

The other thing that I think it’s important to remember is that we and Genzyme are investing in expanding the opportunity with KYNMBRO with focus of age which is going well. And we’re optimistic that that study will be very positive. And so I think if you think about the longer term future, while -- while Genzyme and we are investing in creating that longer term future. I think that longer term future is very bright. Chad Messer - Needham & Company: Great. Thanks for the added information.

Our next question is from Cory Kasimov with JPMorgan. Please go ahead. Whitney Ijem - JPMorgan: Hi, this actually Whitney on for Cory this morning. Thanks for taking the question.. I guess, first on SMA in sort of the emerging competitive landscape. I think we’ve seen trials from PTC and Novartis initiated this year. Just wondering, do you have any information on those candidates?

PTC is Roche drug. And we don’t have any new information on that drug other than that it’s -- how it works and why it works is still not understood. The other thing I would say is that enrollment in our studies with SMNRx is really impressive in the support of the families of SMA, the SMA foundation and the parents. Patient is as positive as I’ve seen for any drug that I’ve been associated with. Whitney Ijem - JPMorgan: Got it. And then can you just quickly remind us the design of the GCGR trial, I mean what data we should expect to see when that reads out?

This is a study in patients who have Type II diabetes, uncontrolled on metformin. It's a randomized double-blind placebo control trial 13 weeks. And we’re looking at 100 and 200 milligrams a week of GCGR. But we hope to see a significant reductions in fasting blood glucose. And of course with 13 weeks, you don't have nearly enough time to get to equilibrium line on hemoglobin A1c but we're hopeful that we’ll see some improvement in hemoglobin A1c. And of course, we’ll be watching also for tolerability issues, because this target is associated with small molecule that -- small molecules that have been looked at is associated with what appears to be manageable target related ALT elevation, so all of those things we’ll be looking at.

In addition to fasting glucose, we also have a number of shorter-term measures like glucose control that are built into the study, again because it’s a three-month study.

We also will be looking at GLP-1. Remember that in animals, we see a significant increase in GLP-1, and we think that could be a very important feature of the drug, as that added mechanism should make it. This drug, we expect based on animal data to be extremely effective and to be able to work and to be used in people who have advanced diabetes as well as earlier. We will also look at hypoglycemia. We think in animals and in our Phase 1 trial, we did see hypoglycemia. And we think there are mechanisms that explain that. So we want to look careful that as well. And we’re very excited about this drug. Whitney Ijem - JPMorgan: Got it. Thanks for taking the questions.

Our next question is from Salveen Richter of Canaccord. Please go ahead. Andrew Goldsmith - Canaccord Genuity Securities: Hi, good morning. This is Andrew on the line for Salveen. Could you just remind us about the economics, particularly the royalties for SMN, I believe it’s a 10% royalty? Can you give us any color if it’s high, low, or if it’s tiered, and if that differs between the type 1 and the 2, 3?

Yes, it’s not a 10% royalty, it’s an ascending double-digit royalty. We haven’t given out what the tiers are, but it is a tiered royalty. And it does not differ. It will be same drug in infants and children. It doesn’t differ between the two indications.

And as Lynne mentioned earlier, there are quite substantial milestones (inaudible) and regulatory milestones that matter a great deal to us. Andrew Goldsmith - Canaccord Genuity Securities: Okay, great. And then just a follow-up on KYNAMRO and the FOCUS FH read data, just hoping if you could give any kind of clarity on how you see the competitive landscape, particularly against the PCSK9s and I guess population?

Well, I thing the PCSK9s are working well but in folks who have LDL-receptors. And our focus with KYNAMRO is homozygous and severe where we think KYNAMRO have a very good profile that would be competitive with what the PCSK9 inhibitors do. Remember also that our strategy for the lipid franchise was to create in KYNAMRO a drug that could be used in combination with PCSK9 inhibitors. And so for the really severe patients, I can easily see combinations between our drug and PCSK9 inhibitors that I don’t think would be nearly subtractive with an MTP inhibitor. Andrew Goldsmith - Canaccord Genuity Securities: Okay. Thank you very much.

(Operator Instructions) And our next question is from Navdeep Singh of Goldman Sachs. Please go ahead. Navdeep Singh - Goldman Sachs: Hey, good morning, guys. And thanks for taking my questions. May be a quick one on SMN. Just wondering if you could give us some color on the amount of data, how many patients and what kind of follow-up time from the 12 milligram cohorts you will have ready by AAN? And then I have a follow-up. Thanks.

Yeah. I would prefer not. I mean, we’re -- it is the 12 mg doses are just really going on now and it’s enrolling a lot. So whatever number I gave you would be wrong today. It's only a couple of months and we’ll -- we'll be all that at the end. Navdeep Singh - Goldman Sachs: Okay. And then I understand you're not providing KYNAMRO sales, but any sense on how many patients are on KYNAMRO?

So -- yes we know how many patients are on KYNAMRO but again that's information on Genzyme considers at this point to be competitive, intelligence and so I apologize, we're not free to give you that. Navdeep Singh - Goldman Sachs: Okay. Then maybe on TTR, maybe you could discuss the overall profile of TTR versus the Alnylam product and when we should expect Isis to initiate the Phase III studies in FAC patients. And just wondering on -- is there a rate lending stuff there, do you still have to talk to FDA on the trial design and what not?

So the profile for our TTR drug, it is very attractive. It's a once a week drug, that’s being very well tolerated, easy to use. Patient can administer the drug themselves. The current drug that Alnylam is developing requires IV Infusions and coming into an infusion center. And so we believe not only are we substantially ahead, we think that our drug has a profile as much more attractive. And the potencies are roughly equal. The level of activity is more than sufficient. It's in the plus 80% level depending on the maximum level, the activity is roughly the same. So we're very optimistic about TTR both against the disease and against the competition and the FAC decision is principally a business decision by GSK. Navdeep Singh - Goldman Sachs: Okay, thanks a lot and congrats on the progress.

Thanks very much.

And our next question is a follow-up from Nick Abbott of BMO. Please go ahead. Nick Abbott - BMO: Hi, just two quick follow-up. I was interested by your comment about the GCGRRx as there maybe some protection of pancreas. Wondering if you could just elaborate on that and then more broadly, what are your goals for the antisense technology, what are the top three on your wish list of things you would like to be able to deal with this technology? Thanks.

Well what we have observed in animals is that we preserve the pancreas. And the mechanism is thought to be both effective. We reduce along the glucose drive and we increased GLP-1. And of course demonstrating that in human beings is, it will require some time. But I think the level of activity that we expect is based on animal data that it should be substantial and the GLP-1 increases we hope will be meaningful. And those will be signpost to tell us that we're seeing in men what we're seeing in animals. And just because no ones asked about Factor XI, I can't in this call without encouraging you to think about Factor XI. There are still plenty of opportunity for improved treatment of thromboembolic disease. And we think Factor XI is FXIRx is very exciting opportunity and encourage you to spend some time thinking about it and we would be glad to talk about it. With regard to technology, we already know that it works, we know that it works broadly in multiple organs, we're not limited to a single organ, and we demonstrated that we can give antisense drug by every route of administration, including oral, although certainly not ready for primetime. So our main goals are to continue to expand the pipeline and expand the uses and routes of administration of antisense to make oral administration available and move forward to next level -- the set of drugs that we have, that we think are going to be somewhere in the 5 to 10 times more [potent] range than the drugs that we have in the clinic right now. We want to continue to explore our Generation 2.5 drugs for difficult to reach tissues like cancer and muscle. And so those are our main goals. And we're sort of in a period of just exponential growth and our understanding of how antisense drug were and using that information to create progressively better performing drugs over the next two decades is sort of our long-term goal. Does that answer your question? Nick Abbott - BMO: Yes. So it’s just -- sorry on the GCGRRx. So is that -- do you think there is something difference between exogenous gluten administration, which is associated with pancreatitis versus this endogenous gluten production?

We think the amounts and the types and all sorts of things, whether it's pulsatile or not pulsatilel. So there are variety of things that maybe different, but I think the key thing as we need to look at the data that we have from this Phase 2 study and see what kind of profile we have at this drug and then we'll go from there. Nick Abbott - BMO: Okay. Great. Thanks very much.

And our next question is a follow-up from Alethia Young of Deutsche Bank. Please go ahead. Alethia Young - Deutsche Bank: Great, thanks. So on Factor XI, I'm just curious about like your -- will you press release and then have data at the medical meeting and then what medical meeting might be a potential opportunity for that data?

We will press release it, we will almost certainly have a webcast and then the data will get presented in a verity of meetings and the meetings that make most sense for it are things like ASH and so on. But again, we will, as the data emerge, obviously if the data aren’t as positive as we hoped, then it’ll get into the meetings in one way. And if they are as positive as we hoped, then it will get into meetings with a very different feeling. Alethia Young - Deutsche Bank: Great. Thanks for the follow-up.

You bet. With that, I think the hour is dragging on. I think we probably out to bring it to close. And in closing, I would say that we've spent a good time talking about the pipeline and we're very excited about number of drugs in the pipeline with glucagon receptor in Factor XI being central in the first half of the year as well as getting the Phase 3 programs underway. And we continue to experience extraordinarily high levels of interest in our technology, the drugs that we have in development and in partnering, and so we're very optimistic that we will certainly achieve our business goals as well. Thank you very much.

The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.