Welcome to the ISIS Pharmaceutical's First Quarter Financial Results Conference Call. Leading the call today from ISIS is Dr. Stanley Crooke, Isis' Chairman and CEO. Dr. Crooke, please proceed. Dr. Stanley Crooke – Chairman and Chief Executive Officer: Thank you. Good afternoon and thanks everyone for joining us on today’s call to discuss our first quarter financial results. Lynne will walk you through our financials for the first quarter of this year and then spend some time highlighting KYNAMRO's growth opportunities and the potential value drivers for Isis beyond KYNAMRO. After that, I’ll give you a brief update on what we have already accomplished this year. Joining me on today’s call are Lynne Parshall, COO and CFO; and Beth Hougen, Vice President of Finance; and Richard Geary, Senior Vice President of Development; and Kristina Lemonidis, Director of Corporate Communications. Kris, will you read our forward-looking language statement, please? Kristina Lemonidis – Director of Corporate Communications: Sure. Well, thanks Stan. Good afternoon everyone. I remind you to everyone this webcast includes forward-looking statements regarding Isis' business, the financial outlook for Isis, and therapeutic and commercial potential of Isis technology and products in development. Any statement describing Isis' goals, expectations, financial or other projections, intentions or beliefs including the planned commercialization 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 of human therapeutics, and in the endeavor of building a business around such drugs. Isis' forward-looking statements also involve assumptions that it never materialize or prove correct could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Isis' forward-looking statements reflect the good…

(Operator Instructions) The first question comes from the line of Ted Tenthoff, Piper Jaffray. Ted Tenthoff – Piper Jaffray: Excellent. Thank you so much for the updates on the recent communication around the pipeline. One quick question around the KYNAMRO filings in Europe and U.S, I appreciate your update on the manufacturing side what else has to be done in (indiscernible) and kind of where are we in that European review process?

Ted, our European process, they are proceeding up to date their variety of questions and answers more questions and more answers you go through in Europe and that process is going just the way you would expect just in the timeframe that you would expect. Ted Tenthoff – Piper Jaffray: Okay. Should we be expecting approval on the backup this year?

Genzyme has not given approval days. What they had said is they are planning on launching in Europe this year. Ted Tenthoff – Piper Jaffray: Okay, perfect. Excellent, that’s very helpful.

Your next question comes from the line of Salveen Richter, Canaccord. Salveen Richter – Canaccord: Thanks for taking my questions. Just in terms of KYNAMRO, I know your CHMP recommendation could come shortly. Is there any way to get a sense as you go through your discussions with this regulatory division in EU whether they are looking at homozygous FH differently from how they are looking at severe homozygous FH.

(indiscernible) all we can do is just reiterate what we've been saying for some time. The guidance that we received indicated that they would consider KYNAMRO in this filing for homozygous FH and severe and nothing is happened would causes to questions what they hope what they told news those guidance meetings. Salveen Richter – Canaccord: Great. And then just given that you guys got standard review, did you get any clarification from the FDA is to why it's a standard review and not priority review?

We- the FDA didn't tell us. We didn't ask, but we are actually really looking forward at this point to approval and launch and we are really drilled with all of the activities going on in Genzyme and Sanofi to put this drug on the market promptly following approval. Salveen Richter – Canaccord: Great. and then just one last question, Lynne if I can, I think in the beginning of the year you guided to perform a net loss in the low $40 million range or is that still on track given the delay in U.S. revenue.

So given that delay, Salveen what, I said little bit earlier and I said it's little too early in the year to say. We based our guidance we did include both milestones in this year's guidance. But we also give very conservative guidance and we also don't put any new transactions into our guidance calculation. So, I think it's a little too early in the year for us to comment on that. Salveen Richter – Canaccord: Okay, thank you.

The next question comes from the line of Chad Messer, Needham & Company. Chad Messer – Needham & Company: Yes, thanks for taking my question, it's actually on the spinal muscular atrophy program, I know you said you got a ongoing Phase I trial it's like a dose-escalation trial I believe in children and that data would becoming next year, but I was wondering if you can give us a little bit more information on what that dose-escalation trial looks like and whether or not there will be any chance to – given that it's a Phase 1 updates particularly on safety ahead of when final data just gives I do believe you are using a direct injection into the cerebrospinal fluid to that one.

Yeah, that's right and just to give you a little more color. This is I almost identical to the interest, the interest – the intrathecal injections that were given for SOD-1, which we just reported out our dose-escalation study there. The study itself is a single dose. Single dose administration in children between the ages of 2 and 14 and these are children who have SMA and it's a type 2 disease so they have lack of function due to the SMA. They received one dose, there – then followed for a period of time. A dose escalation occurs on schedule with the over site of a Data Safety Management Board. Then dose-escalation has gone just as we have scheduled it and we are well into – well into that study.

There have been no safety issues today and in fact as the study progresses, patients will be allowed to redose, and the lower dose will be allowed to a more into our Phase 2 program. That is our plan, because these are very sick children and remember that the clearance of the drug from the central nervous system is very slow. So, we don't yet know how frequently one would have to dose with these things, one of the things it will be trying to learn over the next couple of years, are we going to doze every six months, or three months, or nine months or every year. We just don't know, but so far things are going really, really well. Chad Messer – Needham & Company: Okay, thanks for the update.

(Operator Instructions) The next question comes from the Nicholas Bishop, Cowen and Company. Nicholas Bishop – Cowen and Company: Good evening. I have a question – couple of questions on a few different things. The first one is just on the current filings are just the status with the FDA. So, clearly I hear you are not getting priority review, but it wasn't clear to me yeah the FDA is officially accepted the application yet just want to clear up.

We haven't gotten the 60-day point yet, Nick, so, we haven't done gotten that letter yet. Nicholas Bishop – Cowen and Company: Okay. Then I wondered about the SOD-1 program in ALS. Actually, I haven't seen the data from ANN, but were there any efficacy measures that were attempting together in that Phase I trial and is there plan to continue developing this particular candidate for that small fraction of the ALS market, and I wondered if you can elaborate all on your strategy for addressing the broader ALS market.

A short answer to the first question is we know efficacy measures in that trial. We did try to measure SOD-1 levels and CSF, but they are very low. The strategy that to just put a little more flush to it was that for our first drug that we took intrathecally we wanted to be sure that we had a drug that was focused on patients who had really severe illness because we wanted to be sure that we build the strong relationship with the neural division of the FDA and also the similar people in Europe. So, we deliberately selected as you know (indiscernible) drug targeted to a very rare mutation that's associated with very severe even more severe with normal ALS in a very few patients. And the main purpose for that was to build our relationships with the regulatory agency and develop a safety experience with intrathecal administration, so, that worked wonderfully. And I think the evidence that it worked well is the response that we are getting from regulatory agencies in the U.S. and Europe with regard to our SMA drug. Having shown that we can do this safely now, we are now working – we will now develop a different SOD drug when the targets normal as well as mutant SOD-1 and that of course gives us a much more of the patient population to work with and so that's been our strategy and I think that's and I think it's worked really well. Nicholas Bishop – Cowen and Company: Okay, that's great. And then just last one if I could on the CRP program. I remember you previously talking about addressing multiple myeloma, I'm wondering if you could elaborate on what happen to that plan and just more generally what kind of profile would you like to be able to present potential licensers next year for CRP.

Yes, we still plan to look at, but what has happened is that we've been able to get the atrial fibrillation study move forward. And in our original planning we were confident that we can get on atrial fibrillation study done and as we got more experience and talked to more investigators, we realized that we can get atrial fibrillation study underway now and so, we push that forward because that's a much more important opportunity and a much more logical opportunity than was multiple myeloma and much easier for us to evaluate and so we've been balancing, which opportunities to push and which opportunities to wait until we had the additional data. We did begin looking at multiple myeloma and we will probably go back and look at multiple myeloma, but when we have more data and when we can look at the multi-sites rather than a single site. It's exciting to us about CRP right now is that the product study is going well? We are rolling patients with very high CRP level and so, we will data from that. The endotoxin study is underway and we will have data from that and the atrial fibrillation study is about to get underway and so we will have data from all of those studies. What we believe – what we are very confident is we will show that we can reduce high levels of CRP effectively. This drug is already demonstrated that mainly and we expect to reduce that. And the profile that we think will get people excited is if we show a reduction in signs and symptoms of rheumatoid arthritis and/or we show a reduction in the incidents and severity of atrial fibrillation. We think we have a very solid opportunity on both of those trials exactly that. I don’t think anyone doubts that CRP has a potential to be an enormous product opportunity. The question is, are you going to be able to provide encouraging data that suggest the lowering CRP can improve disease behavior. And do you have a development path that can get to the drug to the market in a reasonable timeframe with both rheumatoid arthritis and atrial fibrillation will have both those things we hope. Certainly the development path for both is notably straight forward and not nearly is challenging as something like acute coronary syndrome or post myocardial infarction or those sorts of things. Nicholas Bishop – Cowen and Company: Okay, great. Thanks very much.

Next question comes from the line of Stephen Willey from Stifel Nicolaus. Stephen Willey – Stifel Nicolaus: Yeah, thanks for taking my question. Just a quick question I guess on the TTR program with GSK with respect to, I guess maybe some of the secondary efficacy end points you may or may not be looking at with respect to trying to see I guess there is any kind of disease modifying effect and I guess kind of secondarily to that if you believe kind of not down of TTR expression will indeed have some kind of disease modifying effect at a plaque level?

Hope so, we think there is good reason to believe that it should because we will be reducing both the normal and mutant TTR and we've shown already that we can reduce TTR to undetectable levels. So, our hope and data that we have supported is that by reducing both mutant and normal, we will reduce the potential for additional plaque formation and maybe will cost some practice solution. And so we will certainly be looking for that, I don’t think we have to see that to get the drug approved, but we are hopeful. Richard, do you want to add or subtract anything to that?

No, just to say that a lot of the secondary measures are under discussion and we are in development of the protocol. So, I think we will be premature that to be very specific on that, but certainly looking at measures that there are consistent with the progression of this disease, this peripheral neuropathy that is developed by this disease. Stephen Willey – Stifel Nicolaus: Can you just remind us what schedule dosing duration or treatment period is going be the Phase II?

So, it's a once a week dosing similar to KYNAMRO and the duration of dosing is up to 18 months. But one year…

But I should hedge all in that what we will do, once we have finalized the protocol because we’re talking about Phase II and III program is that we will give you a more detail about the protocol once it's finalized. I just – we are in the midst of all of that now we've had very positive interactions with regulators with a strong support from drug just give us a little bit more time and we'll be able to share all of that with you. Stephen Willey – Stifel Nicolaus: I understood, thanks for the call.

You bet. If there are no more questions, then were there more questions in.

There are no more questions. I would like to turn the call back to Dr. Stanley Crooke, Chairman and CEO for closing remarks. Dr. Stanley Crooke – Chairman and Chief Executive Officer: Well again thank you very much. I think in summary, KYNAMRO continues to progress. We are looking forward to the approval of KYNAMRO this year and Europe. And we have a pipeline that we think it's very exciting with five drugs that could reach the market while KYNAMRO is still growing and lots of opportunities in our cardiovascular metabolic cancer and other pipelines for very significant licensing transactions over the timeframe as well. Thank you very much.