Good day ladies and gentlemen and welcome to the Isis Pharmaceuticals Year-End Financial Results Conference Call. Leading the call today from Isis is Dr. Stan Crooke, Isis Chairman and CEO. Dr. Crooke, please begin.

Good afternoon and thank you for joining us on today's conference call to discuss our year-end financial results. Lynne will discuss the financials and some of the key highlights that contributed to our success in the last year. After that, I will focus on the year ahead and focus in particular on the key goals for 2011. Joining on us on the call today are Lynne Parshall, COO and CFO; Richard Geary, Senior Vice President, Head of Development, Beth Hougen, Vice President of Finance; and Kristina Lemonidis, Director of Corporate Communication. Kris, will you read our forward-looking language statements please.

I sure will. Good afternoon everyone. A reminder to everyone, this webcast includes forward-looking statements regarding Isis's business, the financial outlook for Isis as well as Regulus, its jointly-owned subsidiary and the therapeutic and commercial potential of Isis technologies and products and development. Any statement describing Isis' goals, expectations, financial or other projections, intentions or beliefs 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 building a business around such drugs. Isis' forward-looking statements also involve assumptions that if never materialized or proved correct could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Isis's 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, 2009 and its most recent quarterly report on Form 10-Q, which are all on file with SEC. Copies of these and other documents are available from the company. And with that, I'll turn the call over to Lynne.

Thanks, Kris. The purpose of my porion of the call today is to report our financial performance for 2010 and to describe our guidance for 2011. 2010 was another successful year with Mipomersen once again the focal point. Mipomersen will continue to be a key area of focus as we prepared the initial regulatory filings for marketing approval this year. We remained financially strong, exceeding our financial guidance for 2010. We ended the year with a pro-forma net operating loss of $36.2 million, which was significantly better than the mid-to-high $40 million range we projected and we ended 2010 with almost $475 million in cash, exceeding our cash guidance by nearly $25 million. Our continued financial strength is a result of our successful business model. As I’ve explained before our revenue consists to several different components including amortization of up front fees we received from our partners, R&D revenue we earn from our collaborative relationships, milestone payments and sublicensing fees. In 2010, we had new revenue from all of these sources. We initiated new collaborative relationship with GSK, the [proprieties] with our first partner in our severe and rare diseases franchise. We began recognizing revenue from amortization of the $35 million upfront payment we received from GSK in 2010. We also earned more than $15 million in milestone payments in sublicensing fees as our partners advance drugs in our pipeline. The cash we raised from partnership supports investment in our pipeline and technology. Our operating expenses for 2010 were higher than 2009, principally due to increases in costs relating to completing the initial Mipomersen Phase 3 program and advancing Mipomersen towards its first regulatory filings for marketing approval. Our costs also increased due to maturation and expansion of our pipeline and the completion of our research to optimize our Generation…

Thanks Lynne, 2011 will be a transitional year for Isis, a year in which Mipomersen will move from the clinic through the regulatory process and continue on its path for commercialization. A year in which we are looking forward to multiple opportunities to present data from clinical trials on many of the drugs in our pipeline while expanding the pipeline by adding several new development candidates and as always we’ll continue to advance Antisense technology. Of course the most exciting and the most significant events this year should be the Mipomersen filings for marketing approval in Europe and the United States. Genzyme and we are on track for the EU filing in the first half of the year. Because the U.S. filing will now be slightly different from the EU filing, it may shift into the second half of 2011. Both filings are proceeding well. The Genzyme-Isis team is focused and fully engaged in both the U.S. and Europe. We continue to be pleased with the regulatory progress in Europe and we’ve also made significant progress with the FDA. In our recent discussions, they indicated both that our filing plan was adequate for homozygous FH and thus a path to our filing for severe heterozygous FH does not in require an outcome study. Let me just take a minute to talk about the fatal conditions that we’re planning to treat with Mipomersen. In recent years, the understanding as the genetic of homozygous FH has evolved. We now know that there are many different mutations in a variety of genes that lead to the clinical presentation of homozygous FH. So we know that the genetic diagnosis of homozygous FH goes way beyond just LDL receptor mutations. This is of course why homozygous FH patients continue to be defined and diagnosed and…

(Operator Instructions) And our first question comes from the line of Eun Yang from Jefferies. You may proceed. Eun Yang – Jefferies & Company: Thanks very much. Question to you Lynne, I heard you in your prepared remark that the 25 million milestone that you guys are expecting from Genzyme, is upon the NDA acceptance by the FDA. But my understanding was that the first 25 million milestone is upon regulatory filing, whichever come to first between U.S. and Europe can you clarify that?

So the first milestone is a U.S. milestone and it’s for the acceptance of the filing, which typically happens 30 to 60 days after the NDA is filed. Eun Yang – Jefferies & Company: And then is there…

It’s not approval. Eun Yang – Jefferies & Company: I know, but is there a milestone for EU filing?

No, it’s for the U.S. filings. Eun Yang – Jefferies & Company: Okay. And then the second additional 25 million, is that the approval upon U.S. approval or Europe approval?

It’s for U.S. approval. Eun Yang – Jefferies & Company: I see, okay. And the second question is any update on the study that required for severe heterozygous FH patient in the U.S. (inaudible) design?

We’re still working at the details of that with the FDA and so until we’ve finished working on the details we’re not going to provide a lot of detail about that. Eun Yang – Jefferies & Company: Okay. Thank you.

Your next question comes from the line of Mark Monane from Needham & Company. Please proceed. Mark Monane – Needham & Company: Thank you very much for the comprehensive review, I have a couple of questions. First for Lynne, does your figure at the end of the year for the cash position of Isis, does that count any collaborations that you make for them or does it count the milestone payment that went over, how did you get to that?

So Mark, as I have said our projections as we pay always are conservative and don’t assume any new transactions. But our projections do include the milestones from Genzyme for the first milestone, the $25 million milestone that I mentioned. Mark Monane – Needham & Company: Great. And then I heard Stan say, tell me if I’m right Stan that Mipomersen commercial success is a priority for 2011, did you talk about any more trials that are being done by Isis or Genzyme on the either different doses or perhaps the trial that, I think that you were talking about in January potentially to get a broader label?

We didn’t discuss it although, we didn’t answer the question for Yang. As you know, we are pursuing alternative dose schedules, daily dose, three times a week and weekly dosing and we will continue to work on that. The goal there for long term is to provide patients the choice of how they want to give themselves the drug. And as we mentioned in our answer earlier, we are in well long in the process of designing the additional trial for severe and we won’t be discussing the details of that until we are confident that we have solid agreement with the FDA. Mark Monane – Needham & Company: Got it. And then just a final question, Stan I thought I heard you say that one of the advantages of the antisense technology was to target on drugable targets and that it was a plan to go forward targeting different targets that weren't available or working or tempted by other people. I guess the question for me is, does it matter in your opinion and what you know and for my guess what Richard knows how the CRP level is reduced may be as reduced by Lipitor or maybe it's reduced by the antisense compounds. Does it is matter how the PCSK9 target is reduced by an anti-body or antisense, do you have a point of view there?

Well with CRP I think what matters with CRP as I understand it's sort of the maximum reduction in CRP that a statin will generate is, anywhere from 15 to 30%. We would like to think we have to wait until we generate all the data in Phase 2, but we would accept to be able to provide doses that we do CRP by virtually in the level we want. I think most people who think about CRP would like to see their patients below one and it's a very rare patient who has really elevated in CRP that achieves their target with statin. So I look at CRP and I say our strategy there is really quite the same as with most of our drugs, if our drug would be used in combination with other drugs to achieve targets that are unachievable with existing agents. With regard to PCSK9 there are lots of theoretical reasons why reduction on PCSK9 to an antisense mechanism might be more attractive than to molecule antibody, but I think it just remains to be determined which method appears to be the most attractive as you generate clinical data that, that define the profile. Mark Monane – Needham & Company: Thanks very much for the added information.

Your next question comes from the line Eric Schmidt from Cowen And Company, you may proceed. Eric Schmidt – Cowen and Company, LCC: Good afternoon and thanks for taking my questions. Lynne, I just wanted to make sure I heard the final points of your 2011 guidance correctly. Did you say that total revenues would increase by more than $10 million year-on-year and OpEx by 10 to 15?

What I said was revenues by 10 and expenses by approximately 15. Eric Schmidt – Cowen and Company, LCC: Thank you. When is it appropriate for you to have direct conversations with Sanofi? I assume that you couldn’t have had any yet?

As you know we have ongoing interactions with Sanofi through our partnership through Regulus. If you are referring to specific interactions around Mipomersen I would rather just not answer that question to say that we are working with our colleagues at Genzyme and eventually with Sanofi to be sure that Mipomersen get everything that’s viewed. Eric Schmidt – Cowen and Company, LCC: Let me ask it a different way Stanley, you got any sense either from Genzyme or other avenues that Sanofi is not committed to Mipomersen.

No, quite the contrary. Eric Schmidt – Cowen and Company, LCC: Thanks and last question is about Regulus and the ownership structure, I’m just kind of wondering whether their counts of point in time when you or they kind of outgrow the current ownership and it makes sense to look at different structures.

We set Regulus to be successful and what that would mean eventually is that it would become a public company. Eric Schmidt – Cowen and Company, LCC: And you would maintain your ownership and your share and your losses at that point in time? Obviously there would be some dilution that you have now addressed and otherwise monetizing that?

I think we’re committed to Regulus being successful and advancing the use of antisense drugs to reduce micro RNA’s and what we’re,, I think we’re very pleased with the start that Regulus has. We’re no longer putting money in, we’re taking money out, which is well ahead of where we thought we might be. And obviously as it matures we’ll continue to look at the progress it makes and opportunities to monetize in a variety of ways make decisions that we think are appropriate for sure. Eric Schmidt – Cowen and Company, LCC: Last question about the EME, about the EMA and when will you with it finally approaching now in the first half of this year, when will you know whether you’ll be able to file for this with your heterozygous FH population?

Lynne, hope you will answer that.

Well, based on the interactions that we’ve had so far, we have a very high level of confidence that we will be able to file for that in Europe. Eric Schmidt – Cowen and Company, LCC: Okay, so Lynne has the next update for us. Just you filed for heFH and if we don’t hear anything we’re assuming you’re on track.

Yep. Eric Schmidt – Cowen and Company, LCC: Thanks.

Well, not HE.

Sorry, thanks for correcting that, Stan.

It’s important because we do plan a heFH filing in Europe at some point. Eric Schmidt – Cowen and Company, LCC: Yeah, absolutely. My fault.

All right then.

So, Eric I think we’re feeling very optimistic. Eric Schmidt – Cowen and Company, LCC: Okay. Thank you.

Shiv Kapoor – Morgan Joseph & Co. Inc.: Thanks for taking my questions and congratulations on the recently reported data on the CRP drug. My question is, what kind of Phase 2 are you planning on running, will you running two studies to start with, one in multiple myeloma and the other in RA and what are you looking for in your Phase 2 studies, what will be the endpoints?

Richard Geary, would you like to deal with that?

Sure, I’d be happy to. So initially, and for this year, we are planning to move into two Phase 2 programs, one in rheumatoid arthritis in which the endpoints will be of course CRP but also symptomology in the disease and the second is in multiple myeloma for which we will be looking at not only the reduction of CRP but also symptomology and chemosensitization. So those are the endpoints and the studies that we have planned for this year and I think and did I answer all your questions. Shiv Kapoor – Morgan Joseph & Co. Inc.: What kind of endpoints will you be looking at, what kind of results would you expect?

In the rheumatoid arthritis, it will be the typical scoring. Shiv Kapoor – Morgan Joseph & Co. Inc.: ECR.

Yeah, and in the multiple myeloma I think we are doing two things, we are going to be pre-treating people who have Rhesus because of high levels of Vince John's proteins and so on. And there are those people who undergo em freezes and that with pretty heavy cytokine storms and lots of symptoms and we’ll see if that are trying that better and then we will be looking at response rates and the usual things in the trial that looks at just ongoing treatment of multiple myeloma. I think I tried isn’t it Richard.

That’s correct. Shiv Kapoor – Morgan Joseph & Co. Inc.: Okay, thanks a lot.

You bet.

Your next question comes from the line of Carol Werther from Summer Street. You may proceed. Carol Werther – Summer Street Research: Thanks for taking my question. At the time of the filing in the U.S., can you just give us an idea of how large the package is and how many patients you have out on the premier since they have one year?

Sure. Richard can probably give a little more accurate numbers than I.

Okay. So for one year, the number is 107 and that is for the twelve month greater than or equal to one year.

And the total number of patients subjected to we treat is about 700, Richard?

Yeah, it’s over 700, it’s about 733, something like that.

And that includes, every trial we get is placebo controlled. So all four Phase 3 trials of course is placebo controlled and meet the well controlled definition and our Phase 2 trials were as well Carol, as you remember. Carol Werther – Summer Street Research: Right, okay. And then what kind of monitoring do you anticipate to be on the label for liver safety?

Lynne, do you want to deal with that?

Of course, we’re not going to know Carol until we get to that point with the agency and so anything that we would say is conjuncture, but we do expect as with all lipid lowering drugs that there would be monitoring of ALP elevations, probably more frequently in the beginning and less frequently over time. That’s exactly what we’ve done with the statins and we would expect something similar. Carol Werther – Summer Street Research: Okay, thank you.

(Operator Instructions) Your next question comes from the line of Charles Polsky with William Harris Investors. Please proceed. Charles Polsky – William Harris Investors: Hi, guys. When I think if CRP roughly I think as a marker of information and given the study reduced CLP levels I'm just curious if in other drugs particularly in Mipomersen there were patients who saw injection side reactions. Was there any reduction in the injection side reactions in a CRP lowering drug versus Mipomersen with the less of an issue?

No, the first point is that Mipomersen it self causes no long-term increase in CRP and secondly, we have evaluated Mipomersen extensively in terms of just it's proinflammatory potential and be reporting those data we are very encouraged by what we have seen. Charles Polsky – William Harris Investors: Okay, my question was so is the CLP lowering drug…

I'm getting to that, so in the study we had only in the highest dose had elevated CRP and so I think we really can’t comment on whether it's ISRs injections have reactions or less or more. We certainly didn't see much in the way of injection side reactions. But we don't believe injections side reactions are associated with our secondary two CRP releases. Richard you may, so it's a question that’s awful and one that we asked from time to go when we no longer think of injection side reactions having much to do with CRP. Richard you want to amplify on that?

That's exactly right and we actually will be reporting data both at the ACC and then additionally the Phase 1 study why we looked that multiple markers and there is no between ISRs and CRP. Charles Polsky – William Harris Investors: Its okay.

It was exactly the question we have been asking for the last few years and it turns out there are – there seemed to entirely on the latest phenomena. Charles Polsky – William Harris Investors: Okay, thank you.

You bet.

At this time, I am showing no further questions in queue. I would like to turn the call back over to Dr. Crooke for any closing remarks.

If there are no further questions, I want to thank you again for your attention and just to recapitulate, we look 2011 and our primary focus in 2011 is to assure that Mipomersen is, the files are appropriate and we move to our commercial success with Mipomersen. We are encouraged by what we are, by the progress being made both from the U.S. and Europe and we are very encouraged by the progress that Genzyme is making in getting ready to commercialize the commercial. We also look forward to significant news events from our pipeline that will sort of dot the landscape throughout the year. Thanks very much.

Ladies and gentlemen that concludes today’s conference, we thank you for your participation, you may now disconnect. Have a great day.