Welcome to Ionis Pharmaceuticals Second Quarter 2017 Financial Results Conference Call. As a reminder, this call is being recorded. Leading the call today from Ionis is Dr. Stan Crooke, Ionis' Chairman and Chief Executive Officer. Dr. Crooke, you may begin please.

Thank you. Good morning, everyone and thank you for joining us on today's conference call to discuss our second quarter 2017 financial results and recent business highlights. We reported pro forma operating income of $54 million for the first half of 2017 and cash with more than $855 million, while our pipeline and technology continue to progress rapidly. Moving as closer to becoming an all-time product sustainably profitable biopharmaceutical company. We are significantly revising upwards, our financial guidance for the year to a pro forma operating income in the mid $50 million range and cash of more than $950 million. Compared to our previous guidance of being breakeven on profitable with the year-end balance of over $825 million. We are obviously being particularly conservative with our guidance this year and Beth will provide more details about all this later in the call. SPINRAZA second quarter sales of over $200 million, once again far exceeded Wall Street expectations and the strong sales thus far obviously contribute to our current and future financial successes. SPINRAZA was approved in the EU, Japan and Canada which provides opportunities for expansion of SPINRAZA sales much earlier in the year and most anticipated. In reticent, that is co-primary endpoints of mNIS+7 and Norfolk Quality of Life in the Phase 3 NEURO-TTR study with a very high degree of statistical significance. This is the fifth positive Phase 3 studies out of the five Phase 3 studies that we've reported in the last 12 months. We in our commercial affiliate, Akcea filed for marketing authorization for volanesorsen in the EU for a familial chylomicronemia numerous syndrome and are on track to file registration dossier in U.S. and Canada in September. Akcea completed its IPO in which they raised over $190 million including strategic investments of $25 million from Ionis and $50 million from Novartis. As a result of the IPO, Akcea is now a majority-owned subsidiary of Ionis will now refer to Akcea as our affiliate. We believe Akcea is now well-positioned to create substantial value for both Ionis and Akcea shareholders. In fact, Akcea's market cap is now nearly $1 billion. While we're still early, we believe that the success of Akcea since the IPO demonstrates how our strategy of committing commercial subsidiaries focused on a specific therapeutic franchise can create value for us our shareholders and the subsidiary shareholders. This really is an opportunity to 1 plus 1 to equals substantially more than two. Joining me in today's call are Lynne Parshall, Chief Operating Officer; Beth Hougen, Chief Financial Officer; Sarah Boyce, Chief Business Officer; and Paula Soteropoulos, CEO of Akcea; Wade Walke, Vice President of Corporate Communications, Investor Relations. And now Wade, will you please read our forward-looking language statement?

Thanks, Dan. A reminder to everyone that this conference call includes forward-looking statements regarding financial outlook for Ionis, Ionis' business, the business of Akcea Therapeutics and the therapeutic and commercial potential of Ionis' technology and products in development. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or belief, including the commercial potential of SPINRAZA, IONIS-TTRRx and volanesorsen is a forward-looking statement and should be considered an at-risk statement. Such statement is subject to certain risks and uncertainties, particularly those inherent in the process of discovery, developing and commercializing drugs that are safe and effective for use as human therapeutics and any 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, 2016 which is on file with the SEC. Copies of this and other documents are available from the company. And now, I'd like to turn the call over to Lynne.

Thank you, Wade. I have to say that working as part of the SPINRAZA team continues to be one of the most gratifying things I ever had the opportunity to do. Every day, I am touched by stories of patients and families who are benefiting from SPINRAZA treatment. It's also gratifying to see the launch of SPINRAZA is going extremely well with SPINRAZA sales far exceeding Wall Street expectations for the second quarter in a row. Biogen reported second quarter sales as SPINRAZA of $200 million, which were principally in the U.S. SPINRAZA was also recently approved in EU, Canada and Japan. In their earnings call, Biogen said various sales metrics are not improving as expected, the number of slide now administer in SPINRAZA has grown and the number of sides submitting start forms and coverages SPINRAZA expanded with many more patients being covered and more policies covering all types of SMA. SPINRAZA is transforming the treatment paradigm for patients with SMA and where these patients are cared for. One example of this is seamless Type 2 patients who often requires spinal fusion to correct spinal deformities that arise from the muscular weakness inherent with SMA. Although the surgery complicates the intrathecal administration of SPINRAZA, there is strong demand for the treatment and physicians are already finding successful ways to administer SPINRAZA to these patients. SPINRAZA is also changing the practice of spinal surgeries in SMA patients, guidelines for these surgeries have recently changed so that these patients will more easily maintained access to intrathecal therapy post-surgery. Of course, their early treatment allowing patients to maintain muscle function, spinal deformities and the result and need for spinal surgeries should be reduced. In June SPINRAZA was approved in Europe with a broad label and Biogen began selling in Germany in the…

Thank you, Lynne. Our successes have resulted in another quarter of strong financial performance. Importantly, Q2 was our fourth consecutive quarter of pro forma operating income and pro forma net income. We ended the first half of this year with pro forma operating income of $54 million and pro forma net income of $34 million. Based on our strong financial performance in the first half of the year and our projections for the rest of the year, we are revising upwards our original financial guidance to breakeven or profitable at the operating line on a pro forma basis. To know we are projecting pro forma operating income in the mid $50 million range. We are also revising upwards our originally year end cash guidance of over $825 million to new year end cash guidance of more than $950 million. Because we have several large potential payments in the second half of 2017, we are being particularly conservative of our guidance this year. In the first half of the year we earned $28 million of commercial revenue from SPINRAZA royalties. The royalties we have earned today are in addition to the nearly $400 million in total SPINRAZA related revenue we have already generated for Biogen, including the $50 million EU approval milestone payment. And now that SPINRAZA is approved in Japan, we anticipate earning a $40 million milestone payment once pricing is determined. We are pleased with SPINRAZA's launch results in the U.S. and the potential for continued growth in the U.S., EU and in other markets globally. SPINRAZA's strong sales to-date are an important driver of our improved guidance. Importantly, we are in tiered royalties as SPINRAZA sales. This means that sales of SPINRAZA grow, so will our portion of those sales. In contrast, the nominal third party royalties we…

Thanks, Beth. We are pleased with all of our accomplishments thus far in 2017, particularly the impressive SPINRAZA sales which led in part to our improved guidance. The SPINRAZA launch momentum has been highly encouraging, suggesting that SPINRAZA has blockbuster potential. More importantly, SPINRAZA giving patients and families suffered from [indiscernible] a life-changing therapy. We're also encouraged by the potential to significantly expand the number of patients who have access to SPINRAZA now as approved in the EU, Japan and Canada. We look forward to watching SPINRAZA sales in the U.S. continue to grow and adding revenue from around the growth. We're pleased to have completed the IPO for our commercial affiliate Akcea. Transforming Akcea into a public company fulfilled our goal of creating our first independent commercial affiliate with the single clear focus, which is to successfully commercialize an important segment of our pipeline. Akcea is well-funded and the team is properly incentivized to achieve successes both in the near and long-term. Clearly, this should create value for both Ionis and Akcea shareholders. In the first part of the year, we made substantial progress in moving our late-stage assets towards commercialization as well as continuing to advance our pipeline of first-in-class drugs. We and Akcea filed for marketing authorization for volanesorsen in EU. We reported positive Phase 3 data for inotersen putting us on track to file for marketing authorization in the U.S. and EU by year-end. We advanced our large and growing neuro-degenerative disease franchise, Ionis VIIB-7-Rx marks the seventh neurology drug under our Biogen collaboration to inter-development. The Phase 1/2 study of Ionis HTTRx, which is partnered with Roche completed enrollment and we planned to initiate an open label extension study in the second half of 2017 and the reported data late this year early next year.…

I would be happy to, Dr. Crooke. We will now begin the Question-and-Answer Session. [Operator Instructions]. And your first question will come from Jim Birchenough of Wells Fargo. Please go ahead.

Yeah, hi guys, Stan congrats on a great quarter and all the progress. Two questions, I guess just one looking at your guidance for the second half of the year. I just would hope you could dig a bit deeper on what looks like at least from the guidance down from first half on net income, but really an increase I what we should expect increase in SPINRAZA sales and funded R&D. So, I just wondering if this is really just conservatism around the off from GSK. And then the second part of it is how should we think about the GSK's often in the context of their comments around divesting their orphan disease business. Thanks.

Thank you. And thanks for the kind words. I think we're as excited as you about the performance in the first half of the year. In the first half of the year, we achieved a number of significant licenses and milestones that generated a good bid of revenue as that said. In the second half of the year, we also have a quite a number of large milestones that we make we see. And certainly not just the GSK milestone. So, the numbers we've given you do reflect a high level of conservatism because we probabalize all of those and particularly things late in the year get probabalized significantly lower. So, we're optimistic that the second half of the year we'll see performance that's very attractive. With regard to GSK, they have contractually defined date by which they must make a decision about inotersen. And in the meantime, we and they are working together very well, in preparing the regulatory dossier and they are making good progress on getting ready to launch. Obviously, GSK is going through quite meaningful transition, so we are prepared for whichever decision GSK makes and in fact we deep delighted, absolutely delighted do have Inotersen back if that were their decision.

And Stan just following up on that, if you did have that event where they decided to divest everything in return inotersen to you, would you avoid any disruption to the filing time wise and do you think you can launch it yourself on the same time schedule?

We - as I said, we are working GSK very carefully and closely to get the dossiers ready, they're moving along right on schedule and it's a part of our preparation for whichever decision GSK makes, we've prepared for the possibility they would return into us, and we think we can need to schedule that we've laid out. And we are preparing right now to manage the drug commercially and when I think the best thing that I can say about that is simply I think it's probably much more sensible just to wait for the GSK decision and let me assure you that we're prepared to do what this drug deserves because we think it's a great drug.

And thanks for taking the question Stan.

Thank you.

The next question will be from Do Kim of BMO Capital Markets. Please go ahead.

Hi, thanks for taking my question. Just a couple of on SPINRAZA, you mentioned that the prevalence of SMA might be higher than they had originally anticipated, could you probably ask your perception of the SMA population and whether that's changed since the launch or when you started investigating SPINRAZA?

Well, the demand is really impressive and so, I would refer to Biogen, but everything we see is consistent with what they said.

Okay. Thank you. And looking at the market outside of U.S. and Europe, perhaps you could talk about the sides of the SMA population in Japan and any other countries that you think could provide a meaningful contribution to sales growth?

Lynne, perhaps you can take that question, please.

Yes. Biogen and their earnings call [indiscernible] through a general distribution [indiscernible] size of the population in Europe is, you would expect is somewhat larger than in the U.S. and in Japan and somewhat smaller but there, unfortunately there is significant population of this disease distributed globally, it's not a disease where you tend to see Familial pockets as with some other rare genetic diseases and so it is a widely and relatively evenly with population distributed disease.

Okay. Thank you for taking my questions.

Thank you.

The next question will come from Stephen Willey of Stifel. Please go ahead.

Yeah. Thanks for taking the question and congratulations on all the progress. I guess may be just in the Inotersen question, I guess to following the success of the neuro study can you maybe just characterize the internal urgency around developing a lighter conjugated version of Inotersen and maybe if you can just talk a little bit about how the development of such a follow-on product that might be impacted by the Glaxo decision if at all?

We feel a great deal of agency internally to develop LICA, because we are confident that it's easy for us to do and given the consistency of the performance of the LICA's would substantially enhanced the profile of their drug. And with regard to development of the LICA, I really can't comment on what GSK might do, but obviously this is going to be a very successful drug commercially I think far more than we thought. And so, it would be clearly enhanced risk of any company GSK or us to extend that franchises lifeline, a life span. So, we would expect to feel the same urgency that we do. We are certainly compared to develop ourselves and we also feel that with the encouraging data from the cardiac subpopulation that we have, that we are in a much better position to design studies that would provide definitive proof of benefit in patients with cardiac form of the disease as well. So, there is a very substantial opportunity to increase the number of patients for whom inotersen could be - it could benefit.

Okay. And when you just mentioned the cardiac mitosis population and I know you said in your opening comments that there is some intention to post the inotersen result from the coming month but should we expect to see some formal presentation of the data within the cardiac subgroup prior to that publication.

Our focus right now is pretty consumed with by getting the registration dossiers done, that's our number one job. As soon as that's behind this then we will look at presentation and publication of the data, but we have that job in front of us and that takes for us and everything else.

Okay. And may be this one last question on SPINRAZA, I know there has been a lot of discussion around the spinal surgeries and mostly I guess type 2 and type 3 patients. I guess some of our doctor conversations would suggest that this is something that can be circumvent and it's certainly circumvent in other disease settings, but I guess can you may be just talk a little bit about the approach between yourself and Biogen, is there going to have to be some kind of formal feasibility study done in order to kind of apply some of the other procedures that are used to circumvent the spinal fusion and other disease settings into SMA, Thanks.

No, we don't believe so. We believe that those procedures are standard for doing LP's and they are actually being employed now in some centers as I understand and from Biogen. I think the most important way to think about this is that in the second quarter, Biogen reported more than $200 million in revenue, in sales up substantially from the first quarter and exceeding all expectations. We look forward to SPINRAZA continuing to grow in the U.S. and of course add revenue from around the world. There is a need to address spinal fusion surgery so that patients can get SPINRAZA, it's actually great news. It says that the written value even in patient's firm limitations include substantial scalable deformities is recognized by the practitioners, so when we heard - what we had, caused us to feel great about where this drug is heading. And the final thing I would say, the thing we hope for long-term is that as we treat patients with SMA and we keep them from deteriorating in terms of muscle performance and muscle strength. We won't encounter sclerosis in the way we do today and the patients with SMA. After all the sclerosis is secondary to the generalized muscle weakness. So, we think that's one of the long-term benefits to SPINRAZA then we are really looking forward to seeing if it emerges because certainly to-date all that we see says it should.

All right, thanks guys. Thank you for taking my questions.

Okay. Thanks, Steve.

The next question will come from Vincent Chen of Bernstein. Please go ahead.

Congratulation on the progress, and thank you for taking my questions. I have a question first about the upcoming Huntington's readout. What do you looking for there in terms of assessing whether you have adequate target engagement? How much of those Huntington approach need decline for you to believe that you are likely to achieve a clinical enrollment effect and how do you expect to CSF Huntington approaching levels are correlate to Huntington approaching levels and clinically relevant regions of the brain such as the [indiscernible] in the cortex?

We believe it will correlate well and there is a quite a bit of information that is behind that that comment. And we have a specified percent reduction that we have, I don't want to get into that. But it will be - we would expect it to be does dependent and statistically significant. And of course, with Huntington's, we have a quite a bit, quite a number of other measures of disease progression or benefit and we'll be using all of those and we are using them all in initial study and as we contemplate additional development of course those will be incorporated as well. So, we're feeling quite good about our ability to detect target engagement and about our ability to quantitate benefit.

So, thinking about some of these other endpoints at the data release how far out from the start of dosing where most patient to be and how much shareholder reorganization data in particular be while I recognize the trial small and reorganization endpoints to be messy, target event that was certainly seem very early in the preclinical studies of approximately eight weeks after dosing if I recall correctly. Would you expect to see at least a directional benefit on the cognitive battery and how would any sign of improvement on the targeted assessment battery composite score and inform your view on whether you have indeed established proof of concepts and which dose take forward?

Well, for us proof of concept is target reduction, because Huntington's cause the disease. And I think since there has been no therapy that was mechanism directed, it's difficult to know the patent which different components of the Huntington disease and infestations will benefit at what pace. But they are measurable and of course by the time, this have study is moved along with the ultimately, we'll extension. We will have a quite a number of lots of observations of being patients. And so, we'll certainly be looking at all those parameters and we hope that we see positive trends. But if we see meaningful HTT reduction in CSF, that will be sufficient.

And then a question switching interacting just a moment back to TTR launch preparations, We've heard from some of the physicians we've spoken to that your competitors have been doing a lot more in field air for launch and drive excitement among both the patient and physician community sort of the typical rare diseases pre-launch market development activities whether its educational programs, diagnostic efforts, GSK and Ionis together are much more well-resourced and just a matter of these specific, we've spoken to [indiscernible] gating factor and determining the level of investment. How should we think about your go to market strategy here, GSK's level of investment and commercialization and how you are driving familiarity with disease and with your drug?

I'll make one comment and then Lynne will hand the question if that's okay. In the end, there is certainly room for more than one drug in the treatment of TTR amyloidosis and we're confident that the profile of Inotersen is significantly more attractive than our competitor. We think that the ease of use and the easy monitoring for the well identified potential address events and the extraordinary efficacy we saw and the fact that we achieved both improvement in the NIS+7 and mode of components and substantial improvement in quality of life and local components. We'll make this drug extremely attractive drug two practitioners and in our conversations with the physicians who use those drugs were extremely encouraged by what they tend to say. So, we think this is going to major commercial success. Lynne, do want to address the question about market preparation and GSK?

Yeah. The thing that I would say is having multiple companies conducting clinical trials working with patients, working with healthcare providers, working with the advocacy community has in fact substantially increased awareness of the disease across the board. And so, all of activities that go to creating those relationships from a successful my dynamics, don't start when you're in Phase 3 data, they started well before with the obviously our IONIS' efforts, GSK's efforts since well with the efforts of Alnylam and Pfizer another sure, working in the TTR amyloidosis area. GSK is obviously as you said has substantial resources like we have been involve with a market preparation they're doing good job, but we're also confident given the level of preparation that's been done already including as I said preparations in the community that where GSK to return direct to us, we'll be able to step into their shoes very rapidly.

Want to just to add, from our perspective the conversations we've had with physicians, the conversations we've had with the patient efficacy groups and regulatory conversations have shown very clearly to us after that there is really substantial enthusiasm for Inotersen. So, we'd like to profile, we like the enthusiasm that we're hearing and we're looking forward to saying this drug via a tremendous commercial success bring real value to these patients.

And the next question will be from Eric Schmidt of Cowen and Company. Please go ahead.

Thanks for the question and my congrats on all the progress as well. Stan, I hate to just sort of beat the dead horse but rather than sort of parse out your words, is it fair to say on the Inotersen often decision that you just don't know what GSK is going to do and they really haven't communicated anything to you since their change in strategy announced a couple of weeks ago?

That would be fair to say.

Okay, and then maybe for best on the SG&A you talked continued growth of Q2 level, so just was put on clear what the event continues to on your growth or whether Q2 sets a new range for future growth in both the third and fourth quarter is obviously paid royalties increase and maybe even Akcea's cost, precaution cost accelerates?

Right. It will be both actually, it will be year-over-year growth but Q2 need to reflect not only Akcea continuing growth in preparation for commercialization [indiscernible] but also, it's a very significant increase quarter-over-quarter in the SPINRAZA Q1 over Q2 and SPINRAZA fails and so with some license fees portion of that SG&A increase in Q2. So, you could see that continue as line of sales continue to grow which is what we expect.

That's it from me. Thanks very much.

One added comment with regard to financials. It is me it's just remarkable statement about the efficiency of Inotersen's technology that we can be finishing up this phase 3 work all the Phase 2 and Phase 1 studies adding five more drugs to the pipeline and R&D costs are not rising. And that's the part of the financial management that I look to most closely. Clearly as you get ready to launch a drug like volanesorsen there going to be precommercialization expenses that we think are well justified and are being well managed by Paula and team.

The next question will be from Jessica Fye of JPMorgan. Please go ahead.

Hey guys. This is Ryan [ph] on for Jess. Thanks for taking our question. Stan, I guess given the number of agents in your growing pipeline, is there any update to your thinking about partnerships versus, I think in your prepared remarks you've talked about perhaps additional sort of spin-offs later in the future. So just would like to get your thoughts on that?

The strategy really hasn't changed and that strategy has always been as we mature and become more financially secure, we focused on deals that were strategically the right fit. There is no longer simply about getting a partner and some money. And so, our approach is to look at each drug at each stations and pipeline. To look at each drug at stages of pipeline. And optimize the partnering for or commercialization choice if we might make for that drug. So, what you'll see is a continuation of that strategy with us retaining drugs longer and retaining more and more drugs for own account to commercialize through a commercial subsidiary. Having such a large pipeline that for larger indications that require outcome studies or indications that might be higher risk will partner them and of course continue to generate to partner revenues that to larger extent cover our R&D expenses today. So, I can't it's difficult to be more specific on that, but that's basically the strategy. Lynne do you want to add anything to that?

No, I don't have anything to add Stan.

Great. Thanks for taking the question.

You bet.

The next question will come from Yale I-Eh Jen of Laidlaw & Company. Please go ahead.

Good morning. And I also add my congrats for the performance. Just a quick one, the first one is given you guys started having continued quarter with the pro forma operating income and the net incomes. Do you anticipate maybe starting next year 2018 you could start have more sustained about maybe profitability or you don't want to make that particularly yet?

So, we're certainly working towards and optimistic that we will be a multi-product sustainably profitable company with the variation in partner revenue and in terms of milestones and so on quarter-by-quarter things vary. But we think we're well on our road to being sustainably profitable.

Okay. Great, that's helpful. And just again get back to the SPINRAZA in terms of the spinal - execution for surgery. You mentioned in the prepared statements that there is industry find some solutions on that. In the bigger scale, do you anticipate this ultimately will be a resolvable issue that for patient who currently already in Type 2 or Type 3 that can be treated even they have been in surgery before and have issues associated with that.

I think the short answer these patients to be treatable and these procedures are available and they tie of course historically not to SPINRAZA but they need to do our punctures and patients with final reform of they under need to do other source of interventions. And so, from our mind, it's a problem that has to be solved. There is tremendous energy behind solving the problem and the solutions already exists and in the long-run, the best answer for these patients would be SPINRAZA prevents the need for spinal surgery because they don't have sclerosis, so that's what we're looking for due long-term. We understand and it's an over adjusting issue that physicians were dealing well by just being very helpful support with that procedures exist and we're confident that the patient who need SPINRAZA will be able to get SPINRAZA.

Okay, great. Thanks, Bob, for taking the question and congrats

Thanks so much.

Your next question will come from Paul Matteis of Leerink Partners. Please go ahead.

Hi, this is Rene [ph] for Paul Matteis. Thanks very much. I want to ask you if maybe provide a little more color on the Neurological collaboration that you guys have with Biogen. Is there anything that you can disclose about the bit 7-Rx do you guys talked about in terms of target or timeline development and there is a potential for more assets to merge under this collaboration?

The answer to the second is, I would say there is a guarantee that additional drugs well I mean science I shouldn't guarantee. But there is a very high probability that there will be more drugs added as a result of the collaboration. Remember the collaboration is very broad and had been really remarkably successful with seven drugs that currently in development and substantial advances in understanding where these drugs built and how they work in the brain which is broadly opportunity consistently do more and more targets and more and more diseases and more and more regions of the brain as we've learned that they're all - all these things are achievable for us. So, it's a very broad pipeline already, we'll give broader and it doesn't simply focus now on rare deceases it focuses on - and so there are large deceases that were approaching with Biogen collaboration like Alzheimer's, Parkinson's disease and then a wide range of best common diseases that are like spinal [indiscernible] and Richard do you want to comment on the development paths for 7-Rx

Well, we're rapidly moving these compounds into preclinical, it generate moves at the same rate for all these compounds and they're into the clinic fairly quickly. So, while we don't yet have a disclosure on this, is specific target. I can assure you that we move these forward quickly and Biogen of courses involved in most of these compounds even in the development, even in the early development stages other than that I don't have any more.

Stan, may I add just two things that there might make this useful bit VII is in our quite pipeline. We don't put anything in our pipeline until we have a drug that's moving forward to the clinical. So that's the time at which we initiate all the IND supporting PAPs and PK works. So, these are all one's something that in the pipeline is typically within 12 to 18 months spread to 18 months actually initiating first in human clinical trials. So, these are not research programs. One way you think get an idea of the breath of the research and the progress that the research that were doing which is what then lead can drug discovery and leads to the pipeline is the very large number of target sanction milestones that we announced. And again, often we don't say what the target is because that's important competitive information at an early stage, but if you follow the releases that we've put out in the frame for consequences that we put out When we hit target sanction mile stone, that's what triggers drug discovery program and so again those target sanction programs will typically be 18 months or so from going into the pipeline. So that all will give you an idea of the flow when you really seen many of those target sanction announcements to give you an idea of really that strong amount of activity that's going on in these Biogen programs.

Okay. Helpful. Thank you very much.

We are running a bit long so I'm going to take two more questions and then we'll wrap up.

Thank you, sir. Your next question James Birchenough of Wells Fargo Securities, LLC

Hey, guys. Thanks for taking the follow-up. Just on SPINRAZA and the royalty rate seems like this quarter was at the lower end not unexpectedly 11% to 15% range. We're expecting - maybe comments on how quickly that could ramp up to the higher end of the range and when you hit a certain sale threshold that the reset here or that's going to be the going forward royalty?

Lynne do you want to answer that.

No, the royalties are tiered on an annual basis and the ramps are pretty quickly.

Got it. And then just one other follow-up. We noticed a new program listing for PKK in chronic mind [ph] range seems like that an investigator sponsor trial. But is that area that IONS is going to be developing in and how do we think about PKK as a target relative towards lot of site around thins like CGRP? Thanks.

Yeah. We are interested in PKK as a target and there are number of indications and with the current [ph] job that we have what we decided to do is whatever look at migraine syndrome because there is substantial evidence that the target as you [ph] laugh and obviously as we move forward it will be developing a traditional indication as you would expect. So, we are interested and we're interested both in the target and in the issue of migraines as a disease very poorly treated in these days and that'll need a better and better treatment.

Thanks for the second follow-up.

And the next question will come from Chad Messer of Needham & Company, LLC.

Great guys. Thanks for - thanks for fitting in my question. At one point in time, Glaxo was on the words of starting a cardiomyopathy study in TTR amyloidosis, just wondering I know things are kind of [indiscernible] waiting for their decision for but if you're making that decisions and you very well maybe is that still necessary or is like a kind of take precedence there?

Well, I think the most important point to make is that based on the experience that we have in the current phase III trial that just finished, I think we've a very nice, a very good sense of the design of the trail that would be - would measure outcome in that cardiac population. And we do think that having that as a formal education, would add tremendous value. And so, we would certainly engage in Phase 3 evaluation for that indication we think improving value is always directly to go and the best way to generate value.

Okay. And just to add, would it make sense to go straight to LICA or is that too far behind?

What I'd like to do on that is - first of all I would say that - that inotersen itself is an attractive drug that we would develop for the cardiac indications independent of LICA. And we would be loving the LICA through development as rapidly and there are many ways we can be more efficient generally in developing a follow on. So, we would move that - that forward just rapidly as possible. And then we will make a final decision about what we do depending on timing and performance as the months move out.

Thanks. Congratulations on the quarter and looking forward to an exciting rest of the year.

Thank you. With that, I want to bring the call to the close. Thanks so much for your attention and many good questions. All of us of course remain proud and to feel privilege to be a part of this SPINRAZA story and SPINRAZA is continuing to change the lives of more and more SMA patients and families every day. So just as an exciting and gratifying moment in our history. I think more broadly with inotersen, with volanesorsen and the entire pipeline that we have, if the value that we have created is beginning to be much more tangible and much more visible to many, many more people. When you add to that the fact that the technology continues to advance at a rapid rate, so that every step forward will make even better growth, I think it puts us in a great place to build an exciting future for ourselves, our shareholders and the patients that we want to serve. So, thanks everyone for the opportunity to talk and we look forward to keeping you updated of our progress.

Thank you, sir. Ladies and gentlemen, the conference has now concluded. Thank you for attending today's presentation. At this time, you may disconnect your lines.