Stan Crooke – Chairman and CEO Wade Walke – VP, Corporate Communications and IR Lynne Parshall – COO Beth Hougen – CFO

Alethia Young – Deutsche Bank Jim Birchenough – BMO Capital Markets Nicholas Abbott – BMO Capital Markets Nicholas Bishop – Cowen and Company Chad Messer – Needham & Company Prakhar Verma – Stifel, Nicolaus Whitney Ijem – JPMorgan Navdeep Singh – Goldman Sachs Josh Schimmer – Piper Jaffray

Welcome to the Isis Pharmaceuticals’ First Quarter 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 for joining us on today’s call to discuss our first quarter financial results. So this morning, Lynne will highlight some of the recent business successes and Beth will walk you through the financial results and I'll close by focusing on a few of the upcoming events. Before we get into the call proper, I want to spend a minute discussing Isis SMNRx. The first thing I want to do is reiterate that we, Biogen Idec and the investigators are all tremendously encouraged by the data that we presented and as we have always planned, we're getting the Phase III studies underway. We began those Phase III studies with a very high level of optimism. We've had some questions about the data and I just want to see if I can answer some of those questions. First, there was some confusion on the median age of the 12 milligram cohort. Just to remind you the study was staggered. To ensure safety, we dosed the 6 milligram infants first, then we started the 12 milligram cohort which was almost six months later. Thus for the median age of the 12 milligram cohort was on April 7, by definition significantly less than the 6 milligram cohort. One other important point to make is that the 12 milligram cohort was enrolled in the middle of cold and flu season which is a time of the year that's very problematic for these great fragile infants. We believe that the continuing evidence that our muscle performance in these infants is encouraging and supports our continued enthusiasm and so does everyone else. Obviously, as the study matures we'll have the opportunity to talk in more detail about the survival and other characteristics of the infants in this study. Next, let's talk about the number of SMN 2 genes in these infants. Only one infant in the study from the protocol efficacy population had three copies of the SMN II gene. Rest of the infants had only two copies. For the infants who have just recently enrolled, we've not received the results from the SMN copy number test, but we fully expect that they will have two SMN gene copies given the rarity of type one infants with three SMN II gene copies and the clinical presentation of these statements. A certain factor that was confusing was the accidental death. We obviously can't discuss the specifics of the death, but what we can say is that it was in a baby that was 13.5 months old and that baby was doing very well. And, as the baby was continuing to do well an unfortunate very tragic accident took this baby's life. Before the accident, everyone involved was encouraged by the observations that were being made about this baby in the study. Now finally, the exclusion criteria for infant study confused. I think the most important point is that we selected these criteria along with Dr. Finkel to match the characteristics of the type I B infants in Dr. Finkel’s natural history study with which we are comparing our results. We think the infants in our study are quite similar to the type I B infants that were in Dr. Finkel's study. The exclusion criteria basically meant that the type I A patients were excluded from our study and of course they are not included in the curve that we are comparing our study to as that curve is the type I B infants. Also it’s important to remember that Dr. Finkel’s results are quite contemporary, and the infants in our study are being studied at basically the same centers that were contributors to Dr. Finkel’s natural history study. So we do think that as we compare our type I B infants, to Dr. Finkel’s type I B infants, the natural history study that Dr. Finkel has represents a very contemporary and reasonably well matched comparator for the infants in our study. Obviously as we proceed with our Phase III trial, we'll be doing the control comparison that we've always planned to do. So I hope that helps clarify some of those questions that have been raised and to reiterate, we remain very optimistic to ISIS-SMNRx is likely to bring value to both children and infants within SMA. So now let's move into the thrust of the call, the financials. Joining me on today’s call are Lynne Parshall, COO; Beth Hougen, CFO; and Wade Walke, Vice President of Corporate Communications and Investor Relations. And now, Wade, will you read our forward-looking language statement please?

Certainly, thanks, Stan. A reminder to everyone that this webcast includes forward-looking statements regarding the financial outlook for Isis, Isis’ business and the therapeutic and commercial potential of Isis’s 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 you 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 cause 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, 2013, which is on file with the SEC. Copies of this and other documents are available from the company. Now, I’ll turn the call over to Lynne.

Thanks, Wade. And I want to apologize in advance I’m fighting a little bit of a head cold. So if I sound a little croaky as we go through this, please bear with me. But 2014 is off to a great start. We reported positive Phase II clinical data on both ISIS-SMNRx and ISIS-APOCIIIRx. We started new clinical studies. We added new drugs to the pipeline, and our partnerships continue to vibrant and successful. These accomplishments abate for a busy first quarter, and they set the stage for another year of growth. In addition to Stan’s comments on ISIS-SMNRx, let me make a few other important points. We entered Phase III with much optimism for a number of reasons. First, ISIS-SMNRx has been well tolerated in both infants and children to-date. The increases in muscle function scores we've observed in both the children and infants are encouraging both when you look at average and when you look at individual patients. As Dr. De Vivo pointed out, even small changes in muscle function scores could provide significant benefits for these patients. We began developing ISIS-SMNRx our hope was to delay progression. The results we've observed to-date have been consistent from mouse to human, infant to children and study-to-study. The effects we've observed were dose and time-dependent. The increases in SMN protein we’ve observed to-date suggest that ISIS-SMNRx is acting through the mechanism for which it was designed. All of these reports support our optimism as we advance ISIS-SMNRx into planned Phase III studies in both infants and children with SMN later this year. We plan to initiate the Phase III study in infants in the middle of the year and the study in children later in the year. We reported the final data sets from our Phase II study and our novel triglyceride-lowering drug ISIS-APOCIIIRx at three different medical meetings. In our Phase II studies we consistently observed significant reductions of triglycerides, apoC-III and non-HDL as well as significant increases in HDL. Even more important than any individual result is the totality of the data. We observed improvements in the lipid profile of patients irrespective of their incoming triglyceride levels, improvements in triglycerides were similar whether ISIS-APOCIIIRx was administered as a single agent or in combination with fibrates. Also we reported last week, we saw a statistically significant reduction of hemoglobin A1-C and other measures of glucose control, plus trends towards enhanced insulin sensitivity in patients with type to diabetes a condition that affects nearly a third of very high triglyceride patients. These observations are both remarkable and important. We've shown for the first time that after only 13 weeks of treatment ISIS-APOCIIIRx lowered apoC-III and after glucose control in these patients. These results confirm that by lowering triglycerides glucose control improves and diabetes could be better managed. Adding these potential benefits in glucose control to the significant triglyceride lowering we've observed could provide benefit to patients with severely high triglycerides. We are also pleased with the safety and tolerability profile we’ve observed so far. ISIS-APOCIIIRx is a newer second generation drug, not only our newer second generation drug is more potent but these drugs are also showing in the clinics that they have fewer and milder injection site reactions in flu like symptom. We are on track to initiate the first Phase III study of ISIS-APOCIIIRx in patients with FCS in the middle of this year and the second Phase III study in patients with triglycerides greater than 880 milligrams per deciliter later in the year. Our Phase III study of ISIS-TTRRx in patients with familial polyneuropathy is also going well on track to complete enrollment as scheduled. We began dosing more than a year and we've already opened the open-label extension study so the patients can rollover into this study to continue to receive drugs after they complete their 15 months of dosing in the pivotal study. In addition to these drugs in late-stage development we have a pipeline of maturing products. This year have numerous opportunities to showcase the advances in our pipeline and the productivity of our Antisense drug discovery platform with 32 drugs in our pipeline and the ability to add three to five new drugs each year. I could spend the entire call discussing our pipeline. Instead I hope you will be able to join us in New York on May 22 for our R&D Day. During this presentation, we plan to provide more detail on development programs as well as highlight the advances we continue to make in Antisense technology. It's a testament to the efficiency of our technology that we can generate in advance the pipeline with so many drugs in so many different therapeutic areas. Our partnering strategy is designed to take advantage of this efficiency to create and develop an exciting pipeline of first-in-class drugs. Our partnerships provide us with significant value, not only when we initiate the alliance and receive upfront payments, but also as our partnered drugs progress. For example, we see if more $40 million at upfront payment through license, since we began the collaboration, we advanced four drugs into development and that the opportunity is to do more. This remarkable productivity which can only be achieved through the power of Antisense technology resulted in approximately $43 million in milestone payments with the opportunity to receive up to additional $1.2 billion in license fees and milestone payments as well as tier double-digit royalties. Our alliance with GSK also highlights the broad utility of Antisense technology to create drugs for patients with many different diseases. Together with GSK we are developing ISIS-HBVRx to treat hepatitis B virus ISIS-GSKIVRx to treat the undisclosed ocular disease and our Phase III drug ISIS-TTRx to treat TTR amyloidosis, a severe and rare disease. Other targets we are advancing within our GSK collaboration represent additional therapeutic opportunities. We had a number of successes in our other partnerships as well. This year we selected a development candidate to treat patients with Huntington's disease. In less than a year from beginning our collaboration, we and Roche have advanced ISIS-HTTRx into development. We will begin evaluating this drug in patients early next year once we’ve completed the necessary studies to support clinical development. And as I said it’s earlier Biogen Idec we will continue to report results on ISIS-SMNRx to support our enthusiasm for this drug and for advancing ISIS-SMNRx in to Phase III development. We are also preparing to start the first clinical study on ISIS- DMPKRx, a Generation 2.5 drug to treat patients with myotonic dystrophy Type 1 and we are making progress in our broad neurological disease collaboration and hope to move at least one additional drug into development this year. We’ve also made exciting progress on the cancer front. Together with AstraZeneca we’ve planned to begin developments shortly on ISIS-ARRx, the second anti-cancer drug from our alliance and the third generation 2.5 drug in our pipeline. We are continuing to evaluate ISIS-STAT3Rx in patients with advanced metastatic liver cancer and in patients with advanced lymphomas. In fact, we and AstraZeneca are each conducting Phase II studies in this program as a reflection of the strong collaborative nature of this relationship. So as you can see, we have multiple opportunities to create and maintain value with our partners and also on our own. So with that, I’ll turn the call over to Beth.

Thanks, Lynne. Good morning everyone and thank you for joining us. I am pleased to report that we maintained our strong financial position by ending the first quarter with more than $630 million in cash. We received more than $20 million through our partners including approximately $12 million from Biogen Idec to support continued development of ISIS-SMNRx. These payments illustrate that our business model is consistently generating cash and revenue as the drugs in our pipeline advance. We also ended the first quarter with a pro forma net operating loss of $23 million. We are on track to meet our guidance of a pro forma net operating loss in the low $50 million range even though our first net operating loss was higher than our guidance may suggest. This was in large part because of the variation in the timing revenue from milestone payments from our partners as their drugs progress in development. You may recall that in our year end call in February, we projected 2014 revenue of more than $160 million including more than $45 million in amortization of upfront fees and more than $110million in milestone payments, because we are generating such a significant amount of our revenue from the milestone payments, our revenue and our pro forma net operating loss look fluctuate on a quarterly basis. This can also result in year-over-year fluctuations such as we experienced this quarter to Q1 last year in which we earned more than $30 million in milestone payments. These variations and the timing of revenue are consistent with our projection and are the natural results of our large mature pipeline and our partnering successes. As Lynne mentioned, our partnerships provide us with significant value from upfront payments when we initiate the collaboration but also from milestone payments as our drugs advance toward the market. As our pipeline of partnered drugs expand and matures, the milestone payments we are eligible to receive generally increase in value. And with numerous partnerships encompassing multiple drugs, we have many opportunities throughout this year to earn milestone payments as our drugs continue to progress. We will earn an $18 million milestone payment from Biogen Idec when we begin the Phase III study which is planned for the middle of this year and a $27 million milestone payment when we begin the planned Phase III study until – later this year. We are also about to begin the first human study of ISIS-DMPKRx for patients with myotonic dystrophy Type 1 for which we will earn a $14 million milestone payment from Biogen Idec and when ISIS-ARRx advances into the clinic, shortly we will earn a $15 million milestone payment from AstraZeneca. And of course, we have numerous opportunities to earn milestone payments from GSK as we advance the Phase III study of ISIS-TTRRx, advanced ISIS-HBVRx and ISIS-GSK IVRx as well as add other drugs into development. I’ve listed some of the near term milestones we planned to earn. If there are many more milestones spread out over the year, that we believe that we can earn as our drugs progress. For this reason we are confident we can meet our guidance of more than $110 million in milestone payments. In addition, in the first quarter we earned revenue of $17 million from the amortization of upfront payments which puts us on track to meet this component of our projection. Our partnering strategy also takes advantage of our dominant intellectual property estate through the success of our satellite company. In these partnerships, we earned revenue from our partners when they license our technology to their partners. For example, we earned $7.7 million earlier this year from Alnylam for their transaction with Genzyme. The increase in our pro forma operating expenses in the first quarter was in line with our projections and as you’d expect, the primary driver of the year-over-year increase was and will continue to be our recurring pipeline. In addition got our Phase III study of ISIS-TTRRx we are preparing to begin a total of four Phase III studies between ISIS-SMNRx and ISIS-APOCIIIRx. We are also conducting Phase II studies on eight drugs, and we've advanced our earlier stage drugs as added new drugs to our pipeline. We’ve planned to end 2014 with three drugs into Phase III development and nine drugs into Phase II development plus numerous earlier stage drugs. This represents a significant expansion and maturation of our pipeline. Nevertheless, we continue to keep our spending increases consistent with our projection. Our achievements to-date positioned us for continued financial strength. As such we remain on track to meet our financial guidance for the year of a pro forma NOL in the low $50 million range and year-end cash of more than $575 million. And now I'll turn the call over to Stan.

Thanks, Beth. Well, we are off to a good start in 2014 and we’ve had – I think important clinical successes already. We think the value of technology and the pipeline continue to increase and there is still a great deal of opportunity to have investors better understand the value that our pipeline and technology represents. We have the resources we need to continue to advance the drugs in our pipeline, add new drugs to our pipeline and to continue to advance Antisense technology. So let me just focus first on Phase III events that we have coming up. As we discussed, we continue to be encouraged with the results from our Phase II studies evaluating SMNRx and infants, children with SMA and a Phase III study in infants with SMA is planned to begin at the middle of the year and the other Phase III study in children just a bit later. Of course, both the outcomes of those Phase II in infants and children are continuing so later this year we’ll have an opportunity to update you on both of those studies. Second, ISIS-APOCIIIRx continues to perform remarkably well. We’ve observed statistically significant decreases in the hemoglobin A1-C and positive effects on lipid parameters such as triglycerides, apoC-III and HDL. These data confirm and support our optimism for ISIS-APOCIIIRx and as you know, we are getting ready to begin the Phase III program with the first study to begin in patients with FCS. Next the Phase III study of ISIS-TTRRx is enrolling well with patients with familial polyneuropathy. We are on track to complete this enrollment in this study in 2015. And if positive, we believe this study should support registration of ISIS-TTRRx. We also continue to work with GSK to finalize development plans for patients with cardiac form of the disease. Now let's shift focus to the numerous Phase II events we have coming up. We plan to report Phase II data in the first half of this year from our novel drug targeting factor 11 which is designed to more effectively reduce thromboembolic events. Next, this will be a very important year for our type II Diabetic franchise. We have three drugs designed to treat type II diabetes in Phase II trials. Most advanced drug in this franchise is ISIS-CGRx or the gluco receptor Antisense drug. We’ve completed enrollment for this drug and the Phase II study in patients with type II diabetes and plan to report the results of that study shortly. The next drug in our metabolic program is likely to have important Phase II data. Here is our ISIS-GCCRRx our glucagon receptor drug. This is a drug that we hope to develop for patients with Cushing's disease and patients who have type II diabetes driven largely by glucocorticoid stimulus. Finally we plan to report Phase II data from our novel and we believe safer insulin sensitizer ISIS PTP-1B RX later this year or very early next year. We plan to initiate a Phase II study in fact on GCCRRx in Cushing syndrome. Cushing syndrome is an orphan disease caused by prolonged exposure to high levels of glucocorticoids and as such we believe ISIS-GCCRRx could provide benefit to these patients and we look forward to getting that study underway. We are planning to start the Phase II program in ISIS-APOCIIIRx. We believe there are substantial achievable commercial opportunities for this drug that do not require outcome studies. We also plan to start a Phase II program in ISIS-HBVRx which is partnered with GSK. From our earlier stage pipeline, we have a number of drug accomplishment plan to initiate clinical trials this year including ISIS-DMPKRx, ISIS-PKKRRx and ISIS-ARRx. DMPK is for the treatment of myotonic dystrophy, PKK is targeting to severe rare disease and antigen receptor is targeted to the treatment of androgen dependant or androgen responsive prostate cancer. Some of these drugs are partnered and will provide us with significant milestone revenue this year and of course, we continue to grow the pipeline. Now before, I turn the call over for questions I wanted to remind everyone that later this month we are hosting an R&D Day in New York City. During this event, we’ve planned to provide an update on later stage drugs and highlight some of our earlier stage drugs as well which often gets very little time and get lost in such a large diverse pipeline. We also plan to discuss the important advances that we've made in our technology, using our Antisense drug discovery and development technology, we can develop drugs to multiple targets within the body including liver, bone route, bad cells, tumors, kidney and muscle. We could administer Antisense drugs through a variety of routes including systemically intrathecally and locally. And, of course, we've shown in multiple therapeutic areas that Antisense drugs can provide a positive effect on disease. We continue to develop the next generation technology that enhances the therapeutic profile of our drugs as well. Our generation 2V technology is now incorporated in three drugs in our pipeline. All of these drugs will be in clinical development this year and we would expect them to be significantly more potent even our very potent generation 2 drugs. It is the broader applicability of our technology and the large safety base of well over 9,000 subjects treated with Antisense drugs and the clinical demonstration of activity that have allowed us to maximize the value of our drugs and our technology. And we intend to continue to pursue this course. Let me hope that you will be able to join us for this event and with that, then Emily, if you can set us up for questions.

(Operator Instructions) And our first question is from Alethia Young of Deutsche Bank. Please go ahead. Alethia Young – Deutsche Bank: Great, thanks for taking my question and congrats on the forward movement with SMA. I have one question and a follow-up. So on the SMA just I wanted to talk a little bit more about in the Phase III design, like how you are incorporating the kind of the learnings that you've got – received from other studies? For example, I think you mentioned about the cold and stuff and then also at the closing period it looks a little faster. So just give me some color on that that would be great. Thanks.

Thanks, yes, I think, as we said it at our SMNRx conference, we've learned a lot and these are pioneering studies and from them – in the infant I think the things that are most important – the most important lessons are one, we need to be as aggressive as possible in getting these infants into the study as quickly as possible. These are really very fragile babies and they are deteriorating steadily. So the sooner we can enroll these infants and the sooner we can treat, the better opportunity we have to bring benefit. The second thing that we know is that, we have a really well-tolerated drug today. And this allows us then to be even more aggressive in introducing the drug into these infants and we think that's going to have an important benefit, because again, these infants are very fragile and deteriorating and unfortunately at rapid rate. If we look at the benefits that we are seeing with the dose schedule that we have, we're certainly optimistic that with the new schedule it looks even better. And then third, these infants typically die because they can't breathe. They have a very weak respiratory muscles and as a consequence as they deteriorate, they get colds and flus and other sort of mucus problems that normal babies have and they recover from them. With these babies all of those things are potentially lethal events. And so being as assertive as possible in getting these patients into good care in the hands of good physicians aggressively treating their lung health, making sure that their lungs are as clean as possible and then managing whatever effects that they have I think is another important thing that has been brought home to us as an important step that we will be taking in the Phase III program. There are other lessons that we've learned from the children and other important lessons about the infants. But I think those three lessons about infants are probably the most important at least to summarize in my view. Alethia Young – Deutsche Bank: Great, thanks. And one follow-up on hepatitis B. I am just wondering the data that you presented at even with the Scripps Institute, is that the same molecule that you'll be using in Phase I?

I am not sure, I think it is, I am almost certain it is what we see but I’ll have to check on that. Alethia Young – Deutsche Bank: All right. Thanks.

And the reason I think so is that I think that it’s the same virus and I believe it’s the same molecule. Often we will make a species to specific, I want to take that back. I think that may have been an earlier molecule, now that I think about it and I think a molecule we have in the clinic is a similar but a slightly different sequence, slightly different position and so slightly different chemical. Sorry, I now remember. Thanks. Alethia Young – Deutsche Bank: No problem, great. Thanks for the color.

Our next question is from Jim Birchenough from BMO. Please go ahead. Nicholas Abbott – BMO Capital Markets: Hi, it’s Nick in for Jim this morning. Just carrying on the theme of SMA, at the meeting I had a chance to speak to (Inaudible) how you pronounce her name and her poster and she described to me this little two-year-old had lost the ability to crawl and then began to creep and then crawl and stand and he is now taking a few steps. I am wondering if current tools such as the Hammersmith tool, you think fully capture the potential for SMN to transform functionality beyond probably anything that people could have imagined. And then just on type I, how feasible is it that you can do a trial with newborns screening to get these babies basically diagnosed in utero? Thanks.

Let me answer the first question and Lynne, maybe you can talk – you can deal with the second. First of all, when we talk about the magnitude of the fact that we’ve observed with ISIS-SMNRx, I don’t think we do just as too the observations. It’s not simply as some means shifted positively which they have. But it’s some of the remarkable observations and for example, the child you just described that are very encouraging. And I thought that Dr. De Vivo did a wonderful job of helping put real faces and bodies and aspirations associating all those with these numbers and as he said, a small change in Hammersmith two points or three points can have a profound consequence on children. And, what we are – so the Hammersmith is an effective and valid tool, but you are right, Nick, it’s a rather blunt instrument and it doesn’t begin to describe the value that some of these patients are experiencing. And we are working to create finer instruments and some of those will be the six minute walk test, not create, but use some of these like the six minute walk test, and the upper arm strength measures to further validate and then of course I think the individual patient descriptions will be a great value in understanding what the drug is doing. And I think there will be value in dealing with the regulatory process as well. So, and I look at that as a very high quality problem. We started with the hope that we would delay progression. It is remarkable what we are observing to-date and as I have said multiple times, these studies are on control. You have to weigh that carefully. But it’s very hard not to be encouraged that the Phase III studies – as we begin to control Phase III studies. Did I answer that first question okay? Nicholas Abbott – BMO Capital Markets: Yes, you did. Thank you.

And, Lynne?

Yes, just one more (Inaudible) we have said a lot of times looking at the Hammersmith and other measures and we think the Hammersmith is actually a very robust tool to look at all but, the very healthiest of these patients and the very sickest of these patients. When you get to one end or the other of the Hammersmith score, you find that they are just not very many things that the child is capable of doing or improving on, but the good news is, most of the SMA patients are in fact type 2 and that is – for the more severe type III, Hammersmith is also great and even for the less severe type III. It is a useful instrument augmented as Stan said, by some other instruments that we are looking at. And we’ve been pleased in the early days that all of these instruments are pointing the same direction and so the consistency of what we’ve seen. With regard to newborn screening, great idea, and we are looking at implementing a study exactly like that. It’s on the drawing board. So we are working with our partnership to consider that.

Long-term, the goal has got to be in all of these patients to institute treatment as early as possible and certainly, we, the investigators and our friends at Biogen Idec are aligned in that effort. Nicholas Abbott – BMO Capital Markets: Great, thank you very much.

You bet.

Our next question is from Nicholas Bishop of Cowen and Company. Please go ahead. Nicholas Bishop – Cowen and Company: Hi, thanks. Good afternoon and thanks for taking the question. I have a question on the apoC-III program. Just curious as to whether you have already completed the requisite meetings for the FDA to vet the Phase III program and just in general, what remains between now and starting up those Phase III trials? And then I have a follow-up.

We don't like to comment in detail about our regulatory interactions. But what I can tell you is that we are in the process of dotting eyes and crossing teeth and finalizing the protocols for both of the Phase III studies at this point.

And we're encouraged by the supportive attitude of the regulatory agencies that we've experienced so far. Nicholas Bishop – Cowen and Company: Okay.

That is – we should not answer to your question. Nicholas Bishop – Cowen and Company: Thanks for that. So the follow-up is just a little bit on some of the pipeline programs you didn't mentioned too much today. Just curious when we might see an update on four programs specifically and those are the STAT3 program, EIF4e, the CRPRx and FGFR4?

The EIF-4 we'll update at our R&D date. Stat3, we think later this year, of course, we have to work in concert with AstraZeneca. But we are certainly – we certainly continue to be encouraged by what we are seeing. FGFR4 is in a holding pattern right now because we're waiting to get a particular study that looks at metabolic consequences and so it will be – that study will get started a little later this year we hope. It's a very specialized study that has to be done in basically one center and as soon as we get everything organized and can manage that we'll do it. And CRP, we're finishing analysis of a study in atrial fibrillation and it would be a while because of the analysis is very complex and then once we have all that done, we will decide where we want to take CRP next. Nicholas Bishop – Cowen and Company: Okay. So just on the EIF4e answer, we'll see some data at the R&D Day? Is that what you meant?

Yes, you will. Nicholas Bishop – Cowen and Company: Okay. Thank you

You bet.

Our next question is from Chad Messer of Needham & Company. Please go ahead. Chad Messer – Needham & Company: Thanks for taking my question. I was wondering if you could discuss a little further your kind of strategy for moving forward and potentially partnering the diabetes programs, you have several of them. I assume that insofar as large Phase III trials would be needed as next steps for some of these programs, they are probably more amenable to partnering rather than keeping yourself as you have with apoC-III. Is the preferred strategy one-off at a time after proof-of-concept to look for partners? Or might you consider some kind of global diabetes kind of partnership, particularly given that we have several data readouts that are proof-of-concept stage near-term?

So you are correct, these three drugs all fall in the bucket of drugs that we would prefer to partner after a step-up in value that would come from a well-done Phase II study. And you are also right that we are going to have data on all three within a few months of one another, within six months of one another anyway. The only slight difference to that would be glucocorticoid where we can see at least one and perhaps several indications that might not require large Phase III and large outcome studies, one being cushionoid then there some other glucocorticoid-driven lipid dystrophies. So – and we have quite a bit of interest in those – in that group of drugs and so we are certainly considering opportunities that would include putting all three of those and others into a partnership. There are some benefits to that, but in the end, what we are going to do is look at the numbers and make the best financial decision that we can make. Chad Messer – Needham & Company: Okay. Thank you.

You bet.

Our next question is from Prakhar Verma of Stifel. Please go ahead. Prakhar Verma – Stifel, Nicolaus: :

We have not disclosed the timing for that. So all that I am able to say today is that there should be additional updates this year. Prakhar Verma – Stifel, Nicolaus: Thank you.

Our next question is from Cory Kasimov of JPMorgan. Please go ahead. Whitney Ijem – JPMorgan: Hi, this is Whitney on for Cory this morning or it’s afternoon, I guess. Just wanted to follow-up on the last question, have you guys said whether you'll present the SMN update at a conference or will it be a press release or how will we get the next update?

We haven't said and of course we are not in absolute control of that, because it depends on whether conferences are available and so on. So, what I'd ask is that just everybody hang on. We understand there's meaningful interest and we have the keen interest in providing additional information as it's developed. And so we will do our best to find a good forum in sometime a little later this year. Whitney Ijem – JPMorgan: Got it and then on TTR and cardiac disease, you mentioned sort of discussion is still ongoing with that trial. What are the rate limiting steps or points of discussion before getting a trial there up and running?

Well, those are discussions between us and GSK and I just leave at that for the moment. Lynne, do you want to add?

Yes, I was just saying, we and GSK are finalizing a plan for what we think the study should be, it also – I think it’s important that we do have cardiac measurements in our ongoing FAP trial. Whitney Ijem – JPMorgan: Got it. Thanks for taking the questions.

For us, I think the most important thing is to move very aggressively on the first indication. And we are pleased that the Phase III study is enrolling as well as it is and we are certainly pleased with the tolerability that we are seeing and so on in that study. And you will be hearing a bit more about that.

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. Just a quick follow-up on SMNRx. So, you’ve accrued a good amount of data in terms of the Phase II trials for SMNRx, do you believe that you can potentially obtain breakthrough designation for that compound from FDA? And then I have a quick follow-up.

We think we probably could. We got such a great working relationship with the FDA right now on its program. I am not sure what extra it would get us – might get us some benefits with Wall Street, but we think, we are working closely with the agency on this program and so, I don’t know that it would really help with anything. Navdeep Singh – Goldman Sachs: Okay thanks, Lynne and a quick question on the pipeline. So you are planning to release Phase II data for the FactorXI in patients undergoing total knee replacement and Phase II data for GCGR in patients with type II diabetes. What kind of data are you going to be providing for Wall Street and what would you consider a successful outcome for both Phase II assets? Thanks.

So, the first answer, the answer to the first question is, in this quarter we will provide top-line data for both those drugs both those studies. We are very hopeful that we will then call that up with a much more detailed presentation of the data at the American Diabetes Association Meeting in June and probably ASH in November. And we want to preserve the opportunity for those presentations and so we will limit our comments to top-line data. With regard to the – glucagon receptor drug, remember that in animals, it was perhaps the most receptive agent for Type II diabetes that we’ve seen and it was an agent that could work at very late-stage diabetes and appear to work both by reducing glucagons drive and increasing GLP-1and then seem to preserve the pancreas. So this is a 13-week study. And obviously our drugs at 13-weeks had not reached their maximum. They don’t really reach their maximum effect throughout that 26 weeks. So, in 13-weeks, we would be very happy with half-a-milligram percent hemoglobin A1-C improvement at 100 milligram and maybe it’s greater at 200 milligrams. With regard to factor 11, this is a study that compares Fact II doses of factor l1, 200 milligrams and 300 milligrams of factor 11 a week , two 40 milligrams in patients who have a very prone thrombotic event that is total knee replacement and what we hope to demonstrate with Factor 11 is, at least equal to an Oxiparan efficacy and deep pain thrombosis and less bleeding. And, obviously, if we got performance that was at in some way better than an – that would be a great thing. But the study is designed to show equivalence. Navdeep Singh – Goldman Sachs: Okay thanks a lot, Stan.

You bet.

Our next question is from Yaron Werber of Citigroup. Please go ahead.

Hi, this is actually (Inaudible) in for Yaron. First of all congratulations on moving SMNRx forward. And just had a quick question about the entry criteria again for the infant study. So I was wondering if you could just one more time go over the pulmonary entry criteria. Certain infants between your study and Dr. Finkel's study and perhaps give us a little clarity as to what percent of infants is excluded? And then I had a quick follow-up question about, perhaps end-points.

I will try, and then Lynne, you step in and fill in the blanks. The whole purpose of the exclusive entry criteria that were developed by our team with Dr. Finkel was to match as closely as possible the 1b patients there were inherent and that is a current natural history start and I think the most important thing for people to hear is that we think that the babies who are in our study as closely as possible, match those studies that have that 1b curve with a median of time to either permanent ventilation or death of about 2.5 months. The exclusion criteria then were designed to exclude 1As and basically these are infant steps are in very desperate condition and typically will come before they could even get through the process of getting enrolled in the clinical trial. And beyond that, just as the exclusion criteria meant that all the other babies qualified. I think, Dr. Finkel said that in the conference. So, I don’t have the exact number but I think it’s very, very few if any babies were excluded. So, again, so far as we know today, both in terms of the babies that were enrolled and the centers that enroll them, we were as close to Dr. Finkel’s only group of babies as we can make it.

I just want to reiterate what Stan said, we work closely with Dr. Finkel to design the criteria for entry into the study to make sure that we were as close as you could be creating an apples-to-apples comparison.

We were also aware of differences in management of pulmonary function in infants. And so we tried to be sure that we were in centers that handle pulmonary lung care. In roughly the – as close to the same way as Dr. Finkel. What’s difficult to match is parents. And, you have to put yourself in this horrible situation these parents were in and you want to make sure that parents who enroll in the study as much as possible are committed to being aggressive in managing the babies’ health, but there are parents who quite appropriately make the decisions that the interventions are – that the baby is suffering. And so, those are things that you can’t match and try if you will in a study you’ll have some parents that aren’t, that are not quite ready for a clinical trial and in the Phase III study we hope that that will be reasonably balanced.

And, again the overlap of the sites between Dr. Finkel’s natural history study and our Phase II study was intentional, because the range of standard – obviously the range of canceling is the same and the range of standard of care should be similar because they are in the same centers with the same physicians.

Again to emphasize it’s not controlled, this is, we are comparing this to a contemporaneous natural history study and we’ve done everything we know how to do to make sure that the centers and the babies are as matched to the one week curve to Dr, Finkel reported as possible and we think they are.

Terrific. Thank you. I think that will help alleviate some of the concerns here. And then just a quick follow-up, I was wondering if you could comment on perhaps the amount of ventilation assistance that's given the infants and perhaps the number of hospital visits that these infants required, because I think that somewhere that you could really show benefit.

Yes. There is a lot that we could discuss that we – that gives us a great deal of encouragement and we try to be very careful about how much we share because its approach. What we can – we had a 13.5 months old baby who had an accident and died. That we haven’t discussed, but that baby was 13.5 months old and doing really well. We’ve had many experiences of babies who became – who got a lung infection and got better. And all kinds of other anecdotes that we could share. We don’t – I am not going to do anymore of that than what I just did because, I think it encourages more speculation and what I think we’ve tried to do is present all the caveats and the issues that we’ve faced. And all the data so that any rational person can look at the information and draw the conclusions and see if they agree with the conclusions that we have. We think the infant study is highly encouraging and we are confident that the infants in our study are closely matched to the type I b babies and Dr. Finkel’s study and certainly the muscle performance data the developmental milestones and other things that we are observing gives us substantial encouragement. Lynne, do you want to add? I just don’t feel that it’s appropriate to go into any more detail of that.

No, thank you so much. I really appreciate that and congratulations again on the advance there.

Thank you.

Our next question is a follow-up from Jim Birchenough of BMO. Please go ahead. Birchenough – BMO Capital Markets: Great, thanks for taking my follow-up question. Just in relation to attendance at the AACR, I understand that in the Hodgkin's disease cohort of the STAT3 trial that there may have been evidence of pseudo-progression, which obviously is a phenomenon that occurs at the immune checkpoint inhibitor. So I'm wondering if there is ongoing work either at Isis or at AstraZeneca on combining STAT3 inhibition with immune checkpoint inhibitors. Thanks.

There is quite a bit of interesting information both from animals and the humans studies that have to do with Stat3’s role both at the tumor and in stormal cells and stormal tumor interactions and then the immune system interaction and so there is a great deal of conversation about all that and a lot of thinking going on about what ought to be the development focus as we go forward with Stat3. And I can’t predict exactly how that’s going to turn out, obviously, AstraZeneca will make the final decisions. But my suspicion is that a development plan will represent trying to take advantage of both the direct tumor-cidal effect and the stormal effects and there will be a variety of combinations that look at questions like the one you just raised. Birchenough – BMO Capital Markets: Great, thank you very much.

You bet.

Our next question is from Josh Schimmer – Piper Jaffray. Please go ahead. Josh Schimmer – Piper Jaffray: Okay, thanks for taking the questions. Apologies if you've addressed this, but for the apoC-III Phase III trials on hyper-triglyceridemia, can you us a sense of what those trials might look like the duration of follow-ups, the number of patients enrolled and entry criteria?

We plan to do that after we get the studies started. But in brief, the FCS study will be a randomized comparative trial that looks at patients who are clearly FCS. The – and it will be randomized, I think, one-to-one and I expect it will treat six months to a year and with the primary endpoint being triglyceridemia reduction and of course there will be a number of stochastic analyses, what fraction get to 500 or what fraction get to a 1000 and so on. And the other trial for 880s will be very similarly designed. In addition, we will be doing quite a number of other studies in other patient populations to flush out the profile of the drug to take advantage of its potential benefit in diabetes and alike. But we will share the design of the study with great detail once we get it underway, we don’t want to do that until we finalize the study and we know that the study is agreed by the regulatory agencies somewhat. Josh Schimmer – Piper Jaffray: Great, thank you.

If there are no more questions, I think we will bring the call to an end. Again, thanks everyone for participating and also thanks for the questions. I think the questions on SMN were particularly noteworthy because they focus on some of the confusions that I think have led to some misunderstandings and hopefully we've helped clarify those. Thanks.

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