Welcome to the Isis Pharmaceuticals’ Second 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, sir.

Thanks you and good morning everyone, and thanks for joining us on today’s call to discuss our second quarter financial results. On the call today, Beth will walk you through the financials and then Lynne will highlight recent news and after that I will focus on a few of our upcoming events. Joining me on today’s call are Lynne Parshall, Chief Operating Officer; Beth Hougen, Chief Financial Officer; and Wade Walke, Vice President of Corporate Communications and Investor relations. And now, Wade, will you read our forward-looking language statement please?

Yes, thanks, Stan. A reminder to everyone that, this webcast includes forward-looking statements regarding the financial outlook for Isis’ business 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, including the commercial potential in 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 to 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 if they 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 judgment of its management, these statements are based only on fact 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, and in the most recent quarterly reports on Form 10-Q, which are on file with the SEC. Copies of these and other documents are available from the Company. Now, I’d like to turn the call over to Beth.

Thank you, Wade. Good morning everyone and thanks for joining us. I am pleased to report that we ended the second quarter with pro forma operating profit of $1.1 million. In addition, we maintained our strong cash position with more than $590 million. Our pro forma profitability in the second quarter exemplified the effectiveness and success of our business strategy, which provides us with a steady stream of cash and revenue. Because of the success of our drive in our partnerships, we have generated nearly $75 million in payments from our partners so far this year, including $48 million in the second quarter alone and it continues its momentum into the third quarter. Through the successful execution of our business strategy and as our drugs advance, we generate payments from our partners. These payments come in the form of upfront payments from the initiated collaborations or expanded scope of an existing collaboration, milestone payments as our drugs advance through research and development, payments when our partner’s license our technology to their partners, and payments for the drug we manufacture for our partners. All of these payments result in revenue to us. We recognize some of those payments immediately as revenue and amortize others into revenue overtime as we perform work for our partners. In the first six months of this year we earned $85 million in revenue, which includes revenue from all of these types of payments, as well as amortization from payments we received in prior years. Milestone payments not only bolster our financial results but also signify significant pipeline and partnering successes. For example let me focus on our partner Biogen Idec for a moment. We are at the $14 million milestone payment from Biogen Idec for initiating a Phase I study on ISIS-DMPKRx. This is our second…

Thanks, Beth. Good morning everyone and thank you for joining us. We predicted that 2014 would be an important year with multiple pipeline events that would continue to enhance value. The year is shaping up to be just that. Over the past several years our pipeline of novel drugs has matured from earlier stage drugs into a pipeline of later stage drugs with some significant commercial potential. By the end of this quarter we plan to have five drugs in Phase III development, over a dozen drugs in Phase II development and a number of promising earlier stage drugs designed to treat patients with a broad range of diseases. With this many drugs in development, we have numerous opportunities to report pipeline progress. Just last week we initiated the Phase III program for ISIS-SMNRx, first Phase III study named ENDEAR will evaluate ISIS-SMNRx in infants with Spinal Muscular Atrophy. We remain on-track to initiate a second Phase III study in children with SMA later this year. Both of these studies are registration directive studies designed to provide us with sufficient data on activity and safety to file for marketing approval in the U.S. and abroad for both infants and children with SMA. We and Biogen Idec are also planning to conduct controlled studies in additional patient populations, and we will be providing more detail on these studies in the near future. We are pleased that this program has quickly progressed from preclinical studies into Phase III studies in under three years. Our clinical experience to-date has provided early but encouraging results that support the continued development of this drug for patients with SMA. We and our partner Biogen Idec have a deep commitment to patients with Spinal Muscular Atrophy and their families. We and Biogen Idec have been working extensively…

Thanks, Lynne. As our pipeline of novel and first or best-in-class drugs continues to advance in clinical development we expect a number of pipeline advanced in the remaining half of the year. Of course we will be dosing our first infant in our Phase 3 SMA study shortly. This will be the first controlled study that we will conduct with ISIS-SMNRx and will allow us to define the benefit that we can bring to these babies. We and Biogen Idec remain very committed to advancing this drug as rapidly as possible and plan to follow the initiation of the infant study with the initiation of the study in children with SMA later this year. And we are also planning additional studies as part of a comprehensive clinical program that will evaluate ISIS-SMNRx. In the fall at a medical conference we plan to provide an update of our open-label Phase II studies on ISIS-SMNRx, we hope to see at that time results that are consistent with our earlier encouraging observations. Next we’ll begin dosing in the first of our Phase III studies on ISIS-APOCIIIRx first study to begin we will evaluate ISIS-APOCIIIRx in patients with FCS and then we plan to conduct Phase III studies in patients with triglycerides greater than 880 milligrams per deciliter. In these studies we will evaluate our drug as a single-agent and in combination with fibrates. We plan to conduct all of these Phase III studies in parallel. Moreover, in support to the two indications we are pursuing will be flashing out a profile by ISIS-APOCIIIRx. For example, we’ll determine if we can replicate the exciting results that we saw in patients with type 2 diabetes. If positive, this would represent a substantial addition to the profile of ISIS-APOCIIIRx. Third, at the end of the year or early next year we plan to report Phase II data from our ISIS-PTP1BRx our novel of insulin sensitizer and ISIS-GCCRx our glucocorticoid receptor drug in patients with type 2 diabetes. These drugs along with our glucagon receptor drug are part of our substantial portfolio of drugs to treat metabolic disorders including type 2 diabetes. We designed each of these drugs to address a significant unmet medical need in specific segments of the diabetes population. We plan to report full data from our novel anti-thrombotic drug, ISIS-FXIRx later this year at a medical meeting, our top-line Phase II results were certainly very encouraging. And finally, we will continue to mature our pipeline advancing drugs into Phase I and II clinical trials and adding new drugs to the pipeline. And with that then I will open up the call for questions. Maureen, if you can set aside please.

and:

Thank you. We will now begin the question-and-answer session. (Operator Instructions) Our first question is Alethia Young, Deutsche Bank. Please go ahead.

Thanks for taking my question and congrats on the clinical and revenue success over the year. Just one, I wanted to get your thoughts on the kind of the natural history study that just came out Dr. Finkel and how it kind of ties to the Phase III study? And I have a follow-up. Deutsche Bank: Thanks for taking my question and congrats on the clinical and revenue success over the year. Just one, I wanted to get your thoughts on the kind of the natural history study that just came out Dr. Finkel and how it kind of ties to the Phase III study? And I have a follow-up.

Well, this is the publication of the study that we have referred to a number of times and we think that this study is the ideal study to use to compare to results that we have in infants with ISIS-SMNRx, because it’s contemporaneous it’s performed by many of the investigators that are in our study and the standard-of-care is similar. We worked with Dr. Finkel and others to assure that our inclusion and exclusion criteria were matched. And as we look at the demographics, we certainly think that the demographics of our patients are similar to the patients that contribute to the 10.5 month survival median endpoint. So it’s the study that we believe is most comfortable, it is a study that we would refer to in the fall when we present the rest of the data. And we’re pleased of course that it is now published and available for full scrutiny.

Great and just as a follow-up, I am just wondering if you could walk us through like the other potential milestone payments over the second half of the year from each of collaborators a little bit? Deutsche Bank: Great and just as a follow-up, I am just wondering if you could walk us through like the other potential milestone payments over the second half of the year from each of collaborators a little bit?

Hi, Alethia, it’s Beth, good morning. So the two most recent ones that you can anticipate are obviously the ones for SMN, the infant study which is $18 million and then the childhood study for SMN that’s $27 million, we mentioned those in the call. We then have other opportunities as we advance TTRRx to earn milestone payments as the drug is under that collaboration in addition to TTRRx advance there are milestone payments associated with those, and there are also milestone payments associated with the advancement of ISIS-STAT3Rx, so those are the ones that I think are probably most to keep your eye on those.

We also have milestones that come from the target validation and drug discovery processes with Biogen Idec and other activities with AstraZeneca and GSK that of course this research so you can’t absolutely predict exactly what, but certainly there will be contributions from those areas as well.

Our next question is Stephen Willey from Stifel. Please go ahead.

Hi, this is Prakhar Verma for Steve. Thanks for taking my question. So just two questions, one on regarding the Phase III program, have you completed your discussions with FDA regarding the Phase III design and where are you in that process? And second question on the STAT3 program, do have any update on the Phase II expansion study and FCS patients? Thank you. Stifel Nicolaus: Hi, this is Prakhar Verma for Steve. Thanks for taking my question. So just two questions, one on regarding the Phase III program, have you completed your discussions with FDA regarding the Phase III design and where are you in that process? And second question on the STAT3 program, do have any update on the Phase II expansion study and FCS patients? Thank you.

Answer to the first question is, yes, we have completed our discussions with the FDA and the European regulatory authorities. Those discussions contributed to the design of the Phase III program. And based on those discussions, we are moving forward aggressively and optimistically that the package we have put together will be approval. So, all is going very well with that drug. And then the next question is on STAT3, we think there will be an opportunity to update the Phase III program later in the year. And our hope is that we’ll be able to update both, the lymphoma and general and extension cohort as well as the liver cancer results that -- from the study that AstraZeneca is conducting.

Our next question is Nicholas Abbott, BMO Capital Markets. Please go ahead.

I just want to step back a little bit and ask as you consider which areas to invest in terms of research, given your ability to acquisitively interrogate these pathways, are you swayed by for example the macro amount of interest all of a sudden in NASH and in immune-oncology over the last 12-18 months in terms of directing efforts to research that you perhaps can come up with a set of programs that’s going to be more comprehensive and pretty much anybody else out there? Thanks. BMO Capital Markets: I just want to step back a little bit and ask as you consider which areas to invest in terms of research, given your ability to acquisitively interrogate these pathways, are you swayed by for example the macro amount of interest all of a sudden in NASH and in immune-oncology over the last 12-18 months in terms of directing efforts to research that you perhaps can come up with a set of programs that’s going to be more comprehensive and pretty much anybody else out there? Thanks.

Well, we look at all kinds of factors as we decide where to focus our research, unmet need, feasibility of antisense, organ in which the target is expressed. And places where we think antisense can uniquely bring value. We have been interested in NASH for quite some time and we’re much more encouraged about the opportunity at NASH today. More from our own experience that have been from the enthusiasm around the rest of the world although that’s nice too and the experience that was most informative to us was the MRI study that we did on KYNAMRO which proved to our satisfaction that it is possible in a cost effective way to evaluate changes in liver fat, and define a positive effect. So, we are keenly interested in NASH, and we have a number of targets that we’ve demonstrated that appear to reduce liver fat and so this is an exciting area for us and we now think the Phase II study is really quite feasible that would be proof of concept. With regard to cancer, of course cancer is an interesting spot and an interesting space and a complicated space. The things that we have learned over the recent past that are most exciting to us is how much activity we have in the stromal cell the cell that feed cancer cells and as we’ve learned more about that we’ve increased our interest in targeting that space as well as the cancer cells themselves and you will of course know that the stromal cells include parenchymal cells in the organs where the cancer is found as well as cells that appear to be inflammatory cells that have migrated to the site. So, we have a very keen interest there and the final point on that is that, if you look at what’s going on in both the tumor and the stromal cell that is responding to the cancer, a lot of those changes are driven by changes in non-coating RNA and of course the ability to target non-coating RNA is very much in our sweet spot. So, the answer to both your questions Nick is a resounding yes.

BMO Capital Markets: Okay, thank you.

Our next question is from Chad Messer, Needham & Company. Please go ahead.

Great, thanks for taking my questions. I have just a couple, if I may start out with a clarifying question on milestone payments in the release it says that you ended the quarter with around 591 million in cash not including 41 million received after the quarter ended, was that all or partially recognized during the quarter or is that 41 million milestones earned in the third quarter? Needham & Company: Great, thanks for taking my questions. I have just a couple, if I may start out with a clarifying question on milestone payments in the release it says that you ended the quarter with around 591 million in cash not including 41 million received after the quarter ended, was that all or partially recognized during the quarter or is that 41 million milestones earned in the third quarter?

Hi Chad, it’s Beth. Those were all revenues that we earned in the second quarter but because of the payment terms the cash just didn’t come in until the third quarter. So, we have received all that cash at this point and then it will be in our balance in the third quarter.

Great, thank you, that’s very helpful. And then I had a question on KYNAMRO revenues I think we haven’t seen any reported and I know that it’s a profit share and that won’t happen until the franchise is profitable, but is there anything you could share with us qualitatively how things are going now that we are several quarters into the launch here? Needham & Company: Great, thank you, that’s very helpful. And then I had a question on KYNAMRO revenues I think we haven’t seen any reported and I know that it’s a profit share and that won’t happen until the franchise is profitable, but is there anything you could share with us qualitatively how things are going now that we are several quarters into the launch here?

I will answer that briefly and then Lynne can amplify. We continue to see encouraging signs sales are continuing to grow, Genzyme continues to invest significantly in KYNAMRO and so we remain optimistic that KYNAMRO will be a meaningful contributor to our revenues in the coming years. We also continue to see just good data coming and focus FH will be a title to look at and then there are other data events that we think are important that could be exciting as well. So, we are encouraged, we wish we could share more information with you but that’s what we can share today. Lynne, do you want to add anything to that?

No, you said everything.

Great, thanks. And then one more if I may, so TTR you are enrolling your Phase III study in the polyneuropathy patients. If I’m remembering correctly that’s actually a smaller cut than the cardiomyopathy patients, what are the plans to potentially expand in and I can’t remember if we ever discussed this before, what was the rationale for starting with polyneuropathy? Needham & Company: Great, thanks. And then one more if I may, so TTR you are enrolling your Phase III study in the polyneuropathy patients. If I’m remembering correctly that’s actually a smaller cut than the cardiomyopathy patients, what are the plans to potentially expand in and I can’t remember if we ever discussed this before, what was the rationale for starting with polyneuropathy?

Let me answer the second question first. The rationale was that the polyneuropathy patients have fewer cardiovascular, they do have some cardiovascular risk but they have fewer cardiovascular risk and we felt that those cardiovascular risks were something that we wanted to get a really meaningful experience and we also thought that the endpoints for evaluating the polyneuropathy has been well worked out and so we just felt that polyneuropathy was the best first spend or the better first spend I guess. And as I may have mentioned, the decision to begin a study in cardiomyopathy patients is the decision that GSK will make. And we’re in the process of developing our plans for that now and when we can discuss those we certainly will.

Our next is from Cory Kasimov, JPMorgan. Please go ahead.

Good morning, this is Whitney on for Cory. First question is, I realize you probably won't say, what conference you're expecting to provide an SMN update, but can you outline maybe some of the potential conferences or highlight some of the major neurology conferences in the second half? JPMorgan: Good morning, this is Whitney on for Cory. First question is, I realize you probably won't say, what conference you're expecting to provide an SMN update, but can you outline maybe some of the potential conferences or highlight some of the major neurology conferences in the second half?

I don’t think I should do that. There are a couple of conferences in the fall that we’re paying attention to. They are large conferences and we’ll present at one of them. You’ll get a thorough update of the Phase II program, both in infants and in children, and we’re very excited about what we’ll be able to tell there.

And Whitney, we have an accepted abstract, we won’t keep you in the dark. We’ll let you know where the data will be presented.

Got it and then next question is just on ISIS-PKK, I am not seeing it on clin trials, so I guess can you maybe tell us what dose are you evaluating or how frequently you are dosing that product? JPMorgan: Got it and then next question is just on ISIS-PKK, I am not seeing it on clin trials, so I guess can you maybe tell us what dose are you evaluating or how frequently you are dosing that product?

It’s weekly dosing and it’s our standard dose -- initial patient dose regimens, 100 and 200 and 300 milligram dose escalation kind of thing. This drug works just like the other generation to antisense drugs and the doses will be very similar.

Our next question is Eric Schmidt of Cowen and Company. Please go ahead.

Well just a quick one on the various Phase I studies you have started up the PKK, the AR, and the DMPK, are those being studied in patients or volunteers? Cowen and Company: Well just a quick one on the various Phase I studies you have started up the PKK, the AR, and the DMPK, are those being studied in patients or volunteers?

Let’s see, let’s start with angiopoietin-like 3.

Androgen receptor…

I know but let’s start with angiopoietin-like 3, he didn’t ask you but angiopoietin-like 3 is being studied in normal volunteers and that study is fairly advanced now. Then PKK, I can’t remember is it normal volunteers, I think first normal volunteers and then quickly into patients. SMN is…

DMPK.

DMPK.

It is let’s say it is a short study in normal volunteers and then quickly into the patients.

And what was the other one you got?

Androgen receptor.

Androgen receptor is in patients, in patients with prostate cancer.

And then on the new candidate, the Roche Huntington’s program, when might be a reasonable timeframe for an IND? Cowen and Company: And then on the new candidate, the Roche Huntington’s program, when might be a reasonable timeframe for an IND?

Sometime in the next 06 to 12 months. I would say.

Push out to next year.

So, next year? Cowen and Company: So, next year?

Yes, I think early next year, now again, that will be another interest equally delivered antisense drug.

So that would go into patients? Cowen and Company: So that would go into patients?

It will.

(Operator Instructions) Our next question is Navdeep Singh of Goldman Sachs. Please go ahead

Hi, this is Lisa in for Navdeep. Thanks for taking my questions. Just on SMNRx would be possible to specify how long the follow-up will be and then how many patients when you prevent the updated data at a medical meeting? Goldman Sachs: Hi, this is Lisa in for Navdeep. Thanks for taking my questions. Just on SMNRx would be possible to specify how long the follow-up will be and then how many patients when you prevent the updated data at a medical meeting?

We’ll say all about it when we present the data.

Okay and then a follow-up on TTRRx, can you just provide us some color around the safety profile because I understand TTRRx is derived from the same version and platform technology of KYNAMRO, so do you anticipate similar safety issues that you saw with KYNAMRO to also rise with TTRRx? And think in healthy volunteers you saw some injection site reactions although they were mild? Goldman Sachs: Okay and then a follow-up on TTRRx, can you just provide us some color around the safety profile because I understand TTRRx is derived from the same version and platform technology of KYNAMRO, so do you anticipate similar safety issues that you saw with KYNAMRO to also rise with TTRRx? And think in healthy volunteers you saw some injection site reactions although they were mild?

No, we don’t expect the same profile as KYNAMRO. Remember KYNAMRO had a number of liver effects that were tied to reduction of ApoB100. So in addition to its platform effects, the efforts on the liver were tied to the target. Second, as we’ve said quite a number of times, advances in screening methodology have supported quite significant improvements in tolerability and potency generation to ASOs that are sort of later vintage than KYNAMRO. We are seeing the double the potency we’re seeing fewer and ease, very minimal injection site reactions of all these agents. And we’re not seeing flu-like syndromes, we’re rarely have ever seen a flu-like syndrome these days. With regard to that trial, the safety and tolerability of the drug has continued to be I think very attractive. We of course are blinded with the data at the drug safety monitoring board watches the information and we are quite encouraged by the performance of the drug so far.

Okay, great. And then lastly as you are going into patients into your lab trials what stage of patients that you think that you think can come on the trial? Thank you. Goldman Sachs: Okay, great. And then lastly as you are going into patients into your lab trials what stage of patients that you think that you think can come on the trial? Thank you.

Are you asking about TTRRx?

Yes, exactly. Goldman Sachs: Yes, exactly.

Well, these are patients who have high significant disease and so they are relatively advanced patients I don’t know if there is a specific item that you are asking maybe and then...

The patients are late stage one patients and stage two patients.

Thanks so much. Goldman Sachs: Thanks so much.

Having no further questions, this concludes our question-and-answer session. I would like to turn the conference back to Dr. Crooke, for any closing remarks.

Thanks everyone for joining us. I think we’ve had an important and successful first half of the year and I think the second half of the year is going to be pretty full of important pipeline events of various sorts and we look forward to sharing that information with you as we progress.

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