Good day everyone and welcome to Ionis Pharmaceuticals third quarter financial results conference call. [Operator Instructions] Leading the call today from Ionis is Dr. Stan Crooke, Ionis’s Chairman and CEO. Dr. Crooke, please go ahead.

Good morning and thanks everyone for joining us on this surprising day for the conference call discussing the third quarter financial results and business highlights. This morning Lynne will provide little more color on our announcement from Monday on phase III clinical trial and [indiscernible] and the advancement of our new program. Following Lynne’s update Richard will provide an update on our pipeline which includes more detail about the positive IONIS-FXIRx we recently announced and then importantly Richard will provide a brief update on what we’ve learned about the pharma events and clinical trials that we’ve discussed before. And Jeff will walk you through the financial results, I’ll wrap up the call and then of course we’ll open it up for questions. Joining me on today’s call are Lynne Parshall, Chief Operating Officer, Liz Hougen, Chief Financial Officer; Richard Geary, Senior Vice President of Development; Sarah Boyce, Chief Business Officer and Paula Soteropoulos, CEO of our wholly owned subsidiary Akcea and Wade Walke, Vice President of Corporate Communications and Investor Relations. And so, will you read our forward-looking language statement for us.

Yes, thanks Stanley. Reminder to everyone this conference call includes forward-looking statements regarding the financial outlook for Ionis business and the therapeutic and commercial potential of Ionis’ technologies and products in development. Any statement describing Ionis’ goals, expectations, financial or other projections, intentions or beliefs including the commercial potential of [indiscernible] is 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 as human therapeutics, and in the endeavor of building a business around such drugs. Ionis’ 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 Ionis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis’ programs are described in additional detail in Ionis’ annual report on Form 10-K for the year ended December 31, 2015, 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. And I’d like to turn the call over to Lynn.

Thank you Wade. Ionis has recently announced the brand name for nusinersen and SPINRAZA. There is one more step for commercialization, I think we all referred to nusinersen and SPINRAZA from now on as well as [indiscernible] we’re tremendously excited about the positive phase III data announced a few days ago from CHERISH evaluating effective SPINRAZA and children with later-onset SMA. In this syndrome analysis patients who receive SPINRAZA had a 4 point improvement [indiscernible] compared to a 9 point decline for their untreated contemporary, a difference from nearly 6 point. The signing was highly significant with the P value of [0.0000002]. What this means is – SMA who are treated with SPINRAZA that stronger over the 15 month of treatment and are able to achieve milestones that could not achieve important study. As you know untreated these problem would have been expected to move motor function because of these positive results in children and study now have the opportunity to be transitioned into the open [indiscernible] and SPINRAZA treatment and the CHERISH study will be set. [Indiscernible] will be presenting detailed data from the CHERISH study in an appropriate medical meeting. These CHERISH data confirm what we’ve already seen across the entire clinical program consistent benefit after treatment with SPINRAZA and patients will all forms with SMA. In the most severe forms of the disease we’re seeing increased survival and achievement of Motor that we’re seeing before in baby food SMA. In all forms of SMA and children are getting stronger after treatment with SPINRAZA. The defects are not factored in our studies with some children being treated with some children being treated with SPINRAZA for nearly five years. We work to observe good safety in over 280 patients treated. We are proud to have designed and conducted a…

Thank you, Lynne. This year we have made substantial progress across our large and diverse pipeline of over three dozen drugs in development. Just last week, we reported positive results from our phase 2 study evaluating IONIS-FXIRx in patients with end-stage renal disease on dialysis. IONIS-FXIRx is a two oral antisense drug targeting Factor XI. Factor XI is a unique target for anti-thrombotic drug because human generic preclinical and clinical studies have shown a decrease Factor XI activity results in decrease clot formation without increasing bleeding risk. Just to remind everyone of our results today we've shown in the study that was published in the New England Journal of Medicine that patients undergoing total knee replacement treated with FXIRx have a seven fold lower incidence of venous thromboembolisms (VTEs) compared to those treated with enoxaparin. The most impressive finding however was that this significantly reduced incidence of VTE was accompanied with no increase in bleeding. This is the first time an anti-thrombotic drug demonstrated an anti-thrombotic effect could be associated from bleeding risk. This means that IONIS-FXIRx has the potential to be useful in many different therapeutic settings especially for patients who are at high risk for blood clots and also at high risk for bleeding. The study we reported on last week was looking at 200 mg and 300 mg weekly doses of IONIS-FXIRx inpatients with severe kidney disease that were receiving dialysis. These patients are very fragile and at a high risk of bleeding. The main goal of this study were first to show that IONIS-FXIRx could be dose safely and patients with severe kidney disease. Second to understand if the drug could effectively reduce Factor XI activity inpatients on dialysis. And third, to identify the best dose to move forward into longer larger studies in this patient…

Thank you, Richard. We ended the third quarter with operating income and net income, primarily because of the $85 million in licensees we earned. This included the $75 million from Biogen for licensing SPINRAZA, and the $10 million from Janssen for our first development candidate under that collaboration. We maintained our strong financial position by ending the quarter with more than $685 million in cash. In the first nine months of this year, we earned a $186 million in revenue comprised of a $100 million from licensees, $46 million from the amortization of our front payment and $40 million from payments from reflecting the progress of our partner program. And we have the opportunity to earn revenue from additional milestone payments before the end of the year. Our pro forma operating expenses for the first nine months of the year were $217 million and as anticipated in these compared to the same --. The increase in our operating expenses was due in large part to the five Phase 3 studies we are conducting. In addition, Akcea has continued to build the commercial organization and infrastructure needed to launch volanesorsen. As a result of the successes we'd had in our business, we ended the first nine months of the year with the $31 million pro forma net operating loss and $688 million of cash. Our financial results today are in line with our expectations and we remain on track to meet our financial guidance of our pro forma net operating loss in the low $60 million range and the year-end cash balance in excess of $600 million. Looking forward to the potential SPINRAZA approval in launch, we're excited about adding SPINRAZA commercial revenue potentially as early as later this year, our Q1 2017 potentially followed by commercial revenue from volanesorsen and IONIS TTRRx in 2018. And in these commercial revenues to our 15 days of partner revenue position has for continued an increase in financial strength. And now I'd like to turn the call over to Stan for closing remarks.

Thanks, Beth. We in Biogen are profoundly committed to bringing SPINRAZA to patients in the SMA community as rapidly as possible. Now, these new most recent developments that Lynne summarized for you, bring us even closer to having bringing this important new medicine to patients who're just relieving. SPINRAZA is a great example of the power of Ionis's technology to design management's drug with a specific mechanism to treat a severe stable diseases that other platforms can't figure out. In fact, if you think about the remarkable profound effects that we're seeing in both infants and children, it is even more remarkable in real life is actually accomplished by changing the slicing of the single pretty much [indiscernible]. To my mind that is the efficacy of prescription medicine. And rather we have much more to come from our broad pipeline of first-in-class drugs in development. Next step, in Phase 3 data from our Phase 3 drugs volanesorsen for patients with severe triglyceride disorders, FCS and FPL and IONIS TTRRx for patients with TTR amyloidosis. The first study read out from volanesorsen will be our Phase 3 study in patients with really high triglyceride called COMPASS at the end of this year. Followed them by Phase 3 data in the first half of next year from volanesorsen and FCS and from IONIS TTRRx and FAP. We are well along in preparing regulatory filing, so we will be in a position to file for marketing authorization soon after we analyze the Phase 3 data for which program is assuming data [indiscernible]. TSK continues to prepare for the potential launch of IONIS TTRRx and the Akcea is actively preparing for the launch of volanesorsen. We believe these drugs have a potential to live therapeutic benefit to patients who have severe often stated diseases…

Thank you. [Operator Instructions] And our first question today is [Indiscernible] from Needham & Company please go ahead.

Great, thanks, good morning. Very, very exciting this new nusinersen data congratulations. Assuming a broad label, just wondering if you had any thoughts on how to handle dosing that ENDEAR and CHERISH study used slightly different regiment and obviously there is going to be patients on this for extended periods of time, what you guys are going to be recommending in terms of dose frequency?

Lynne why don’t you take that question please.

Sure, we did different dosing in the type 1 infants, so the infant onset patient population both in terms of the induction dose as well as in terms of the frequency of maintenance dosing and both of those dosing regiments we think should be in the label and Biogen is working on detailed instructions to physicians about dosing.

And again I think you should remember that work on this drug is still is six years since we began the resource program, the research program not development. And so work will continue and we know that the doses that we have at least in the entrance we’ve shown we’re giving theoretically maximum conversion in pricing. So we think we got the right dose and as we prolong treatment certainly Biogen will be looking at lengthening dose in the roles and all such things to make it even more convenient for patients.

Okay, great thanks.

Our next question today is Stephen Willey from Stifel, please go ahead.

Yes, good morning thanks for taking the questions. Could you just provide a little bit color around the period of time by which buyer had to exercise [indiscernible]?

They have – I don’t want to be too specific. They’re in that evaluation period now and when they complete that we will of course let you know of what the next steps are.

Okay. And then, I guess maybe for Richard I know that minor bleeding [indiscernible] meaningful, but you maybe just put out a little bit of characterization around those events/

Yes, those minor bleeding events are common in this patient population in fact it was the minor bleeding events we’re seeing in all of doses including the placebo but the count was bit higher on the 300 mg, in all cases these were of course considered not clinically significant.

Remember Steve, we still have indwelling of catheters in – and so there are giving apron there is a lot going on with them and they have constant – what we saw mostly with that [indiscernible].

Maybe just lastly, there has been a lot of discussion around I guess some of the regulatory feedback by the competitor of yours as received in the SLA space, I guess just wondering if you could make any comment as to other – this now I guess changes the strategy with which Biogen goes to market in terms of urgency, in terms of – try to accelerate rate of patient rehabilitation on boarding? Thanks.

I think Biogen and we’re in urgent and have been in urgency since the first day we were introduced to SMA. We don’t need commercial reasons to feel the sense of urgency – since children gain benefit from Biogen. And we think we got by far the best drug that works in all forms of the disease with solid randomized sham controlled data to say that the drug is unequivocally safe and efficacious. And so, we like our physicians and we’re looking forward to the drug bringing benefit and bring it – Lynne do you want to anything to that.

Yes, I would like to add one thing because obviously we’re happy that any alternatives might exist for patients with SMA and we conducted a very robust clinical program looking at forms of the disease and shown very consistent and positive data in all of these settings. So when you think about this from a commercial perspective I think it’s important put in perspective that the patient who could initially be available to a competitor should they get their drug approved eventually is very small portion of the commercial opportunity for this drug. If Biogen suggest a successful – across label for [indiscernible] based on the strong data package that we have. All of the patients who exist today who have SMA are potential patients for the drug commercially whereas if a drug were to be approved for just type 1 patients in their first three to six months of age that’s 400 patients for year, 400 to 500 patients for year.

We think we’ve got a great drug. And we hope that the other drug will come that we think our drug is going to fundamentally change this disease, that’s what I think is important takeaway.

Okay, I appreciate the commentary and congrats on the progress.

The next question today is Eric Schmidt from Cowen & Company, please go ahead.

Good morning, and congrats on a progress with SPINRAZA, maybe for Lynne, can you able to quantify how many centers the drug is currently available or how many centers you might be ready to launch with this, if the launch did come to an year end and then when you look toward the launch, what do you think will be rate limiting, would it be reimbursement or the logistics of actually getting centers to dose the drug or patient education? Thanks.

So, I can tell you, this isn’t – that the number of centers in the United States, we’ve 20 centers in the United States involved in our trial, there are about 40 to 50 SMA centers totally and about 150 neuromuscular centers in the United States. And all of those are potential sites to have capacity at launch. Biogen is very actively working with these sites to make sure that the ones which didn’t have experience with the drug in the clinical trials already and I think getting these up and ready is rapidly impossible as a top priority for them and that will obviously mean that the backlog of patient to our [indiscernible] to get assets so that the drug can be processed as rapidly as possible.

And in terms, what could be rate limiting?

Well, I think initially capacity is rate limiting and that is price focus right now. Again there are many, many patients out there especially for getting – who want to access to the drugs and being able to bring those patients in and get them started on the drug as rapidly as possible to facilitate it. The more centers you have that tend or board those patients so that is one of Biogen’s highest priorities.

And the data of course put from them is emphasis on identifying the instance pre-symptomatically generically and so I think that’s another important bit of work that’s going is to get the community educated and making sure that these babies are diagnosed much more rapidly then they’re today.

And SPINRAZA royalty is concurrently in the same quarter there, they’re realized by Biogen?

That will our expectation Eric, there will be slight delay initially because we will have to obviously get their reports but we would expect to be booking them at the same time that they’re booking now to product sales.

Thank you.

Our next question today is [Indiscernible] please go ahead.

Good morning, this is Olivia Ryan covering for El and I just have one question. With this recently reported child onset CHERISH data in your opinion still be a part of the approval consideration given it was reported a month after both the U.S. and E.U. filings?

Lynne do you want to answer that.

Yes, I do. We of course, have been seeking the regulator to appraise of the fact of these CHERISH data are coming as we’ve gone through the review process since the regulators didn’t have – do have these data.

As we said in the press release we don’t expect the new data to alter the timeline for approval.

We definitely don’t think it will flow anything down.

Okay, alright, great, thank you very much and congrats.

And that’s based on lots of interactions with regulatory services.

Our next question today is Do Kim from BMO Capital Markets, please go ahead.

Good morning, thanks for taking my question. I just wanted to confirm if you could confirm for us which phase II drugs you think will be going into phase III next year and including any of those you haven’t mentioned today. And if you have to pick one which one would you say you’re most enthusiastic about?

Do you mind if we delay that till January when we do pipeline update, I want to do it justice I mean that’s obviously where the need it and I want to make sure that we cover it properly for you. So I’m sorry to delay, but I think it’s just going to be a lot better when you see the whole pipeline put together with all the data that are coming and then we can walk you through what we think is the next exciting round of drugs, certainly FXIRx is one and [indiscernible] is another on our mind but there are many others.

Maybe there I could ask you about an earlier pipeline to work for your DMPK phase I, phase II trial, you’re currently looking at the plastic form of the disease, do you think that is the population you will be going after in later stage development or would it make sense to move in to an earlier form the chart out of it?

We’re just finishing the molecular analysis now looking at the level of activity and all the other things show, we’ll be telling all about that in our pipeline update and you’re certainly right, I think with every reason we think about the early reforms of the disease as well as the type of disease that we’re selling today. But, we will talk about that in January as well.

Okay, great, hopefully looking forward to your update.

Okay, thanks.

Our next question today is Paul Matteis from Leerink please go ahead.

Great, thank you very much and congrats on all the progress in the recent data I had a couple, one general question and then one specific commercial question. I was wondering if you could expand a little bit on how you define clinically meaningful platelet declines, is there, when you talk about – across different diseases is there a quantitative thresholds and does that vary based on the indication of the drug?

No it doesn’t it pretty standardized of course, the normal levels depending on the lab either 150, 140,000 and a meaningful change as it change, and the count is variable so you want to confirm them. Clinically a meaningful changes, a confirmed change that takes that result in a great one thrombocytopenia it’s very rigid. So and obviously that’s a long way from being at weighting risk. Richard you may want to amplify on that.

No that was perfect.

It’s a very rigid requirement.

Okay, sounds good. And then, on the source, I was just wondering if you could give an update on your patient identification efforts ahead of a launch and where you’re hoping to be at regarding that up on March? Thanks a lot.

Sure, I’m happy to answer that. So we’re actively doing a lot of work to help identify patients pre-launch and that’s through various mechanism starting first and foremost with education about the disease, peer-to-peer education and actually also having field people on ground both in U.S. and Europe meeting with these physicians and identifying patients and nearly simplifying the diagnosis because the diagnosis of these patients is quite simple. History of pancreatitis with no other causes, so we’re working and building a database towards that tracking the patients that we are identifying and that’s something the detail of which we won’t give numbers or anything but obviously we’re building momentum there and will be in place to have those patients identified prior to launch.

It helps us a lot in the issue that we build a true intellectual leadership franchise in this space with all of the – we’ve the largest group of lipid lowering drugs of any company of any size in the world. And so, we’ve now has 7, 8 years of working with essentially all the KOL in the lipid space and as we expand drugs we move into new KOLs like FBL, KOLs and so on, but I think that helps us a lot in both recruitment of patients and understanding the patients and would also I think is going to be very helpful with the launch of the long source and hopefully additional member of our lipid franchise.

Great, thank you.

Our next question today is Roy Buchanan from Janney Montgomery Scott, please go ahead.

Actually my question has been answered it was about the MPK so we should look for that phase II in January?

Yes.

Okay, thank you.

Our next question will be Jessica Fye from J.P. Morgan, please go ahead.

Hi guys this is Ryan on for Jeff I appreciate you taking our questions. For DMPK I think you said you’re using the stat look for end points to study further so could you elaborate on what those end points could be? And also can you please remind us what the highest dose you’re looking at and help us understand why you’re ultimately deciding not to pursue the cohort with 12 weeks for the dosing, I think that suggested some excitement, just curious what changed?

Fine. There are whole set of various molecular end points that are looking at the target that’s being reduced and the projected changes in pricing advance that you would expect based on reduction of target that involve muscle biopsies, and de-sequencing and PCR and these are just studies that haven’t been done before. So it’s taking some time to perfect all those techniques, make sure we’ve got them validated and all that. And I think that the highest dose we use Richard was 600 mg per week. Remember that this is – even with the generation to far I wish this is scaling muscles of tissue that doesn’t accumulate a lot of these drugs, so with those we expect it to be relatively high compared to say liver or kidney target which is what we got.

And for SMA I’m not sure if you can comment, but just curious if there are – which items of the Hammersmith functional scale you saw improvements in CHERISH and did any patients came with ability to walk?

Yes. I should qualify that comment as we’ve had type 2 walks for the first time and we’ve type 3 walk in the initial trial. And what we’re seeing in the radar onset study is that, we will ask this sorts of things that we saw in the infant trial which is that every sensitivity analysis and every significant end point is all in the same direction all looking really very positive.

Great, thank you.

Biogen will be presenting a detailed data from CHERISH after the study concludes which means after we get all the patients rolled over in the shines and can have the final database of walk.

And you probably remember that we’ve both the Hammersmith, we also have what’s called upper limb module for patients who nearly are severely affected to look at the limb strength and there is electrophysiology and lot of other things that are in these studies.

Great, thank you.

[Operator Instructions] And our next questioner is Salveen Richter from Goldman Sachs, please go ahead.

Hi thanks for taking my questions this is actually Carey on for the line of Salveen, congrats on the CHERISH data and the progress. I have a couple of questions, first for SPINRAZA can you elaborate on Biogen’s regulatory strategy and time line outside the EU and U.S. what other countries are you prioritizing and are Japan and Latin America important markets you’re looking at? I do have a follow up question.

No we submitted in Europe and we’re submitting and Biogen is submitting in all the major countries around the world and Japan is, all the areas of the world are important certainly Japan is on track. Lynne do you want to add or subtract anything from that.

No, I just wanted to confirm that Latin America and Japan are both very important and Biogen is so concerned of both.

And we continue to be pleased with the regulatory response to the drug and the data we have not just in the U.S. but around the world.

Thank you and just one follow up question on DMPK 2.5 so will you be presenting protein knockdown data and is this a predictive of efficacy and then just kind of more general question about your platform, in terms of –

We are lowering in RNA and so the key things that we want to look at both total reduction of target RNA and the changes in slicing it’s essentially useless if we don’t see the predictive changes in slicing as a result of reducing the target. Usually biopsies so you are working with very small amount of tissue.

Remember this is a disease of toxic RNA and it’s not a protein disease, it’s the RNA itself is causing the dysfunction in the muscle, so very much the focus is on the RNA in the downstream effects.

Okay. Thank you. This usually translate into efficacy?

Yes, at least in, we have never done study like this before, but we have a fairly broad program and looking at toxic RNAs Huntington’s for example the disease is probably related both to the toxic RNA and to the protein it’s made and everywhere we go, we see a great correlation between a validated target reductions that is validated toxic RNA and therapeutic benefit. Each clinical trial on this disease of course is unique and we have to ask it in the species of interest ultimately in men, look at the answer in the right trial in men.

Okay. Thank you.

And next question today is from Charles Polsky from William Harris Investors, please go ahead.

Hi Stan, congratulations on all the great progress, Stan you just mentioned Huntington’s and my question related to asking for a quick update on the status of the program and when we might expect to hear some data in actual patients with Huntington’s disease?

Well, as progressing where we’re and I will let Richard just give you a little more detail.

So, the Huntington study is progressing well, enrolling well and the expectation is that we will have data to share in the second half of 2017.

And these of course are Huntington’s patients, although folks being treated in Huntington disease.

Is that delivered equally?

Yes, it is.

Thank you, Stan.

Good to hear from you Charlie, it’s been a while.

[Operator Instructions] This will conclude our question-and-answer session I would now like to turn the conference back over to Dr. Crooke for any closing remarks.

First of all, I want to thank everyone for joining us on the call today and for paying attention to us and other things that are going on. And I think this is a pivotal moment for the company we think is going to be – is going to make profound difference in patients with [indiscernible] and their families, I think it’s going to be substantial commercial success and we are really focused now on the other Phase 3 programs and bringing along the really exciting Phase 2 pipeline that we have with the best of the lot moving forward and we look forward to talking to you as we said in January. We will be good between then and as well. Well, thank you very much.

The conference is now concluded, thank you all for attending today’s presentation you may now disconnect your lines.