Good afternoon and welcome to the ISIS Pharmaceutical’s First Quarter 2013 Earnings Conference Call. All participants will be in listen-only mode. (Operator Instructions). Please note, this event is being recorded. I would now like to turn the conference over to Dr. Stanly Crooke, Chairman of the Board and CEO. Please go ahead, sir.

Thank you. Good afternoon and thanks everyone for joining us on today’s conference call to discuss our first quarter of financial results. Our agenda for this call is first, Beth will walk you through our financials, Lynne will then review our current partnering accomplishment and then I will close the call by focusing on some of the upcoming data events. We also announced just a few moments ago that we were initiating a public offering of our common stocks, however, we will not be discussing financing on this call today. : Joining me on today’s call are Lynne Parshall, Chief Operating Officer; Beth Hougen: Chief Financial Officer; and Wade Walke, Executive Director of Corporate Communications and Investor Relations. And now Wade, will you read our forward-looking language statement, please?:

A reminder to everyone that this webcast includes forward-looking statements regarding the financial outlook for Isis, business and financial plans and a therapeutic and commercial potential of Isis technology, and product, and development. Any statement describing Isis’ goals, expectations, financial or other projections, intentions or beliefs including the commercial potential 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 of human therapeutics and in the endeavor of building a business around such drugs. Isis’ forward-looking statements also involve assumptions that they can 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, 2012, and its most recent Quarterly Report on Form 10-Q, which are on file with the SEC. Copies of these and other documents are available from the company.:

Good afternoon everyone and thank you for joining us. I am pleased to report that we are profitable in the first quarter with pro forma operating income of $4.5 million and pro forma net income of $1.2 million. In addition to ending the quarter with both operating and main income, we only used about $2 million net during the quarter and ended the quarter with approximately $372 million. We were able to achieve these financial results because of the success of our partnership with Genzyme and GSK from which we earn $32.5 million in milestone payments in the first quarter. We have continued this momentum into the second quarter.: We’ve already received a $30 million upfront fee promotes for our Huntington in this program. And we have additional opportunity in promotes of payment from partners during this quarter and throughout the rest of the year. Our profitability in the first quarter exemplifies the effectiveness and success of our business strategy which provides us with a steady stream of revenue.: One component of our revenue is milestone payments we received from our partners. As our partner drug progressed to later stages of development, the milestone payments we are eligible to receive generally increased. While we have not yet reached the sustainable profitability, other pipeline continues to mature, we have the opportunity to earn milestones payments that can make us profitable. We received a $25 million milestone payment from Genzyme, upon KYNAMRO approval in the United States. With KYNAMRO on the market in the U.S. we are looking forward to earning commercial revenue from our profit sharing arrangement, for KYNAMRO in the future.: We also received a $7.5 million milestone payment from GSK related to the initiation of a Phase 3 study for ISIS-TTRRx has potential to earn more than $230 million…

Thanks Beth. 2013 has gotten off to a great start with the highlight being the approval and commercial launch of KYNAMRO in the United States to treat patients with homozygous FH. Genzyme’s commercial launch is going very well. And many patients call physicians qualified under the REMS program and there is a granting reimbursement for KYNAMRO and there are a number of scripts written. It is to provide a lot of granularity about this progress but we are excited about the commercial potential of the KYNAMRO. KYNAMRO is the first systematically administered antisense drug for chronic disease to be approved and then the combination of many years of hard work perseverance and scientific achievement. The rest of our pipeline beyond KYNAMRO is also progressing very well. Since the beginning of the year, we reported positive Phase 1 clinical data in clinical data in children with spinal muscular atrophy and positive data in endotoxin challenge with ISIS-CRP Rx. We initiated three important clinical studies already this year. A Phase 3 study for our triglycerides patients with Transthyetin Amyloidosis and multiple dose study in infants with spinal muscular atrophy and Phase 2 study micro STAT3 Rx in patients with liver cancer. With the pipeline of 28 drugs, certain drugs that could reach the market by 2017, 9 drugs that will report Phase 2 or Phase 3 data in the next year or so, and a host of promising earlier-stage programs we have numerous opportunities to showcase the advances in the pipeline and the productivity of our NSM drug discovery platform. It’s a testament to the efficiency of our technology, we can generate an advance pipeline with so many drugs and so many different therapeutic areas. Our partnering strategy builds on the efficiency of our technology to maximize the value of our pipeline…

Thanks Lynne. We are continuing to deliver all the promise of antisense. We believe that the value of antisense technology in our pipeline is just beginning to be realized. Our retaining select drugs in our general pipeline longer, we believe that we’ll be able to participate more in the commercial success of these drugs. As Lynne mentioned, we have a number of successes already this year, KYNAMRO approval has gotten a year off to a great start, gaining approvals for a drug by the FDA for chronic use is the most challenging and rewarding task in drug development. It’s a goal that we’ve worked toward for many years and it’s the beginning of what we hope will be many, many more Isis drugs to reach the market. In addition to our successes in partnering our pipeline continues to advance as exemplified by very recent clinical activities. We report the positive data in children with spinal muscular atrophy demonstrating that ISIS-SMNRx was well tolerated at all those levels. In addition, concentration drug in the cerebral final fluid were consistent with levels predicated by our pre-clinical work suggesting that dosing could be (inaudible) as every six to nine months. Although this study was not designed to provide evidence of activity and it was just a single dose we absorbed improvements in the Howard Smith a functional motor score which is a scale that’s used to evaluate motor performance or muscular performance in these children. We currently evaluating this drug in (inaudible) clinical studies one in infants and one in children with SMA we find the report these data from these studies made in 2013, 2014. AstraZeneca broaden the evaluation of ISIS-STAT3Rx in the patients who have lever cancer, the study is getting underway, we’re also evaluating ISIS-STAT3Rx in ongoing Phase 2 study…

Thank you, sir. We will now begin the question and answer session. (Operator Instructions) The first question will come from Nicholas Bishop of Cowen and Company. Please go ahead.

Hi, good evening and thanks for taking my questions. The first one is on the SMA trials, the one that you are about to initiate in infant patients, when you get the point of transitioning between Phase 2 and the Phase 3, do you expect to disclose data from that first Phase 2 portion, and I guess the same question for the (inaudible) patients or we want the data closure plans B from the Phase 2 be (inaudible)?

We do plan to disclose the data and we expect to be able to discuss later from those two trials, late this year and early next year.

Okay, great. Next we are then on the CRP program, I understand you could explain a little bit about the outcomes you are looking at with that you believe would, which poof of concept in an indication like RA by assuming don’t expect a significant ACR20 responses. So, just what the outcomes you are looking out there?

The primary endpoint in all the Phase 2 trials is CRP reduction of course. But rheumatoid arthritis study we are looking at slightest symptoms of rheumatoid arthritis including all components that make up ACR20 to ACR50s joint count of physician assessment, patient assessment. And what we hope to see is at least trend in a favor of the drug with a correlation between the reduction in CRP and suggestions of improvement and disease. Obviously, as their study progresses and complete we will be able to analyze data and present it. We are looking at several doses with top dose 300 to 400 milligrams a week. So another thing that we will be looking at is tolerability. Remember that this CRP drug is exemplary of this new crop of generation 2 drugs. Same chemistry as KYNAMRO and earlier generation 2 drugs for the better screening, advances and screening have allowed us to generate drugs that appear to be at least twice as potent as KYNAMRO and significantly better tolerating. So another thing that (I’m crazy) to pay attention to is, how we feel about the side effect profile of the drug? Now, the atrial fibrillation study which is in progress and will be reported this year, but sometime next year, is similar and they will be looking at the ability to reduce CRP in patients who have elevated CRP and we will be monitoring these patients with – (inaudible) patients who have such severe recurrent atrail fibrillation that they have pacemakers. And so we are monitoring the incidence of requirements for pacing prior to drug during drug treatment and then after drug is discontinued in that study. And again, we hope for, as these are notably small Phase 2 trial, at least trends that support the drug maybe active in the treatment of that problem.

Okay. That’s great.

Did it answer the question?

Yeah, that’s very helpful, thanks a lot. Just one last one, I think I will get back in the queue and STAT3 program. Just wondering, if you will see any data updates and how is going that program and then a second question is, if you can talk about why (inaudible) was selected as sort of the first indication and what the other high promise indications in the STAT3 (inaudible).

I don’t think we are presenting anything at ASCO this year, you will recall that we did present top-line data from the earlier experience that we had in lymphoma. But that studies are going well and we too expect to be able to report to results of that study in the not too distant future. The choice of liver cancer was a choice made jointly by ISIS and AstraZeneca and it’s based on the biology, STAT3 is thought to be activated in many of these patients and to be a real driver in the disease and need, there is still a great need for improved therapy in ACC. And of course, what you want to expect is that we and AZ will select additional vacations where the similar situation obtains. That is clear evidence, biological evidence that STAT3 is a major player in the cancer and clear on that medical need that we think STAT3Rx can meet.

Okay, great.

Stan may I answer just one little thing. I actually do think we will have data on ISIS STAT3Rx at ASCO but it will be data from the Phase 1 study not from the either of the ongoing Phase 2 study.

Oh, I’m sorry, I was wrong. Yeah, that is going to increase, but we have already seen those data that won’t much new there.

Okay, thanks.

The next question will come from Chad Messer of Needham & Company. Please go ahead. Chad Messer – Needham & Company: Great, thanks for taking my question. I know one thing, I am very much looking forward to is the upcoming APOCIII data and obviously it will be important to see if you can get the decreases in patients that you saw in healthy (inaudible) but I am equally interested in seeing the safety profile of CIII and how that plays out in patents that are, you probably at more risk for problems particularly those patients on fibrates, so what safety data are we going to get in the Phase 2?

Well, we will have 13 weeks of treatment with APOCIIIRx in patients with severely elevated triglyceride and a subset of those patients who are taking fibrates. We will of course be evaluating liver safety and all the other components of safety that you would expect. The thing that I am watching because I am very confident that we will have a very well tolerated drug. Yes, these are a little harder things to (inaudible). But what I want to do is, I want to feel good about the news in side effects and just inside reactions flu like syndromes and those kinds of things. And I am not mistake that I will. In addition, somewhat later this year, we will have data from the more routinely elevated triglycerides in-patients with Type 2 diabetes. There again what I want to see is triglyceride lowering in that study we are only looking at 300 mg. And in that study we will have the opportunity to ask if the tolerability profile, looks the same in patients who are diabetic. And I think that will be of use to know. And we will have the opportunity to evaluate whether lowering triglyceride and APOCIII might have potential benefit in increasing insulin sensitivity. We won’t have sufficient numbers to draw from conclusion about them, all we hope to do is to see some trends that suggest that they maybe another opportunity for the drug. Chad Messer – Needham & Company: Great, thanks, looking forward to getting the data.

Okay. I am sorry we were very (inaudible) about this drug, (inaudible) about this drug. Thanks Chad.

(Operator Instructions). The next question will come from Salveen Richter of Canaccord. Please go ahead.

Hi there, this is Andrew Goldsmith on the line for Salveen. I really don’t want to talk about the race, but maybe more generally kind of looking at your very health cash balance on the lower burn rate, you may be talking generally about, if you are also looking for assets or what you might look further?

I am not, Lynne I will let you answer that, within the limits that we have.

So Andrew if as, you know, by the facts as I am talking really now it’s the right time take the next step in the evolution of our business strategy. When we look at the wealth of assets that we in our pipeline and the fact we are adding 3 to 5 new drugs every year, we really look at those drugs is fitting into as I described from 3 separate bottoms. One is drugs like I say like CRPRx, which we believe that we can take to an important phase to value, prove per value point and license them so that large pharmaceutical companies can do the long broad profiling of phase 3 and putting the drugs on the market. : But we now believe that there are assets with the different set of criteria that we have the knowledge experience, confidence of the platform, confidence of the target up to take even further along through clinical development ourselves. And those are the things like it was ISIS-STAT3Rx (inaudible) drug or PKK drug where we can’t believe that we can do relatively straight forward Phase 2 studies that will be extremely predictive of Phase 3 results where we can identify certain set populations that are small enough that the Phase 3 program should be rapid and manageable, both in terms of resources and in terms of dollars and where we believe that we’ve developed the expertise and the networks and the knowledge and the relationships with KOL to move those drugs forward extremely successfully much further along and develop it, meant allowing us to retain an even larger share of the commercial outside of the drugs. So, it, one of the nice thing is because our platform is so efficient and fills the pipeline so well. We can look…

That’s about as much as we can answer at the moment of course we will happy to chat with you as we progress in the offering.

Okay, wonderful. And then maybe I could just ask, do you have any kind of updates on how KYNAMRO uptake is going today?

Lynne why don’t you take that too.

Yeah, the launch is going well. We have a quite number of physicians who are qualified reimbursement from payers, a number of scripts written and so we think it’s going very well. As we said at the end of the year, we think this quarter is too early to start giving handicapping and giving granularity but we are working with Genzyme on being able to do as we go through the year.

I can add that focus on age continues to go extremely well as well we’re confident, we’re going to complete that on schedule and the blinded performance of the drug continues to be very impressive to me. So, we’re looking forward to that getting done and being able to broaden the indications and get approval in Europe.

Great. And then maybe I can just create a quick modeling question, and how you recognizing the $30 million Roche upfront, is that amortized?

Yes, any license fee is amortized over the duration of the collaboration. Andrew Goldsmith – Canaccord: Yeah. Great. Thank you very much.

Thank you.

And ladies and gentlemen that would conclude our question-and-answer session. I would like to turn the call back over to Dr. Crooke for his closing remarks.

Thank you very much. We appreciate your continued interest. We think 2013 is off to a great start and we think the rest of the year, looks to us like it should be very much the same kind of story. Look forward to talking with you more about the progress that we’re making as the year unfolds. Thanks a lot.