Welcome to Ionis Pharmaceuticals Third 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 CEO. Dr. Crooke, please begin.

Good morning, and thanks, everyone, for joining us on today’s call to discuss our third quarter 2017 financial results and recent business highlights. In the past year -- in the past week, we’ve reported substantial progress with inotersen. We’ve provided more detailed data from a Phase 3 study that demonstrated strong evidence of benefit in a well-defined manageable safety profile. Yesterday, we announced we had filed an NDA, an important accomplishment that follows the MAA we filed last week. We believe that meeting the last 2017 filing date for an EU accelerated assessment provides an additional competitive advantage. We’ve announced that we are initiating our expanded access program and that our commercial team has made substantial strides in preparing to launch inotersen. We’ve also had an opportunity to spend a great deal of time with TTR amyloidosis investigators and patients in the last week, and we’re gratified by the uniform enthusiasm displayed for inotersen. We’re optimistic that inotersen will achieve a significant fraction of the market for ATTR after approval and be not only a medical, but also a significant commercial success. What I find particularly exciting is that inotersen is only one part of our story. SPINRAZA sales to date suggests its launch will be one of the most successful rare disease drug launches in history. Inotersen is progressing through registration for STF, a serious disease for which there is no current therapy and no therapy on the horizon. The rest of our pipeline is also progressing nicely. We’re profitable with a pro forma operating income of $90 million, and we project steadily growing revenue in the coming years. We have cash of more than $1 billion and are on track to meet or potential exceed our financial values. In short, we’re in a very strong position. As you…

Thanks, Stan. A reminder to everyone that this conference call includes forward-looking statements regarding the financial outlook for Ionis, Ionis’ business, the business of Akcea Therapeutics 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 SPINRAZA, inotersen and volanesorsen, is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use 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 these 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’re 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, and the most recent quarterly filing which is on file with the SEC. Copies of these and other documents are available from the company. And now I’d like to turn the call over to Lynne.

Thanks, Wade. We remain humbled by the stories of patients being helped by SPINRAZA. I’m excited to see the drug continuing to grow globally. The launch of SPINRAZA continues to go very well. Third quarter SPINRAZA sales of $271 million grew by 33% over the second quarter and again exceeded Wall Street consensus. With year-to-date sales of over $520 million, SPINRAZA is on track to be one of the most successful rare disease drug launches in history. Demand remains strong in the U.S. with Biogen reporting that number of patients on therapy grew by 75% in the third quarter compared to the second quarter. Importantly, Biogen reported that it received hundreds of start forms for patients who are not yet on therapy, further demonstrating the strong demand for SPINRAZA. Another important indication of growing demand is reflected in a number of centers administering SPINRAZA. Biogen reported that in the U.S., at the end of the third quarter, 180 sites had administered SPINRAZA, an increase from 145 sites at the end of the second quarter and that 250 sites have submitted start forms. To make this growing demand and help additional patients gain access to SPINRAZA, Biogen has said that it plans to double the size of its commercial team in the U.S. Outside the U.S., SPINRAZA sales were $73 million in the third quarter. Sales outside of the U.S. had been particularly strong, with first full quarter of the EU sales substantially higher than the first quarter of U.S. sales, in part due to the broad expanded access program Biogen is conducting globally, including in the EU. Biogen is now selling SPINRAZA in 11 countries plus Japan and on a named patient basis in the Middle East and Latin America. SPINRAZA was also recently approved in Brazil and Switzerland, and…

Thank you, Lynne. Because we have spent a great deal of time discussing inotersen, I will be brief. We believe that inotersen has the potential to transform the lives of patients with hereditary ATTR, a devastating progressive and fatal disease. Our goal is to change both how hereditary ATTR is diagnosed and how it is treated with the launch of inotersen, which combines both potential benefit and a convenient once-weekly subcutaneous injection. Simply put, our extensive interaction with patients and physicians confirm that inotersen is likely to be the choice of many because the benefit and the potential freedom from the burden of the disease it provides. Because of the differences in the designs of clinical trials, direct comparisons are challenging between inotersen and patisiran. And we believe both drugs will be used, but we are optimistic that inotersen should command a significant share of the market. Known for quality of life [DN] with a primary endpoint in the NEURO-TTR study. Even though it was a shorter study, 60% of patients improved, which is virtually identical to the patients who improved in the Alnylam study. Looking at mNIS+7, almost 50% of patients in the NEURO-TTR study improved or stabilized in this measure. The combined benefits is not surprising given that the mean reduction in TTR in the NEURO-TTR study was 77% compared to the approximately 80% reported by Alnylam in their study of a longer duration. We don’t measure mean max because our reductions are sustainable and stable over time. Let’s look at the safety profile of inotersen, which now includes the results from the ongoing open-label extension study in addition to the NEURO-TTR study. The safety issues, we identified are straightforward to manage. The every two-week monitoring we are planning should take most patients no more than a few…

Thank you, Sarah. Our successes have resulted in continued strong financial performance in the third quarter, marking the fifth consecutive quarter of pro forma operating and net income. We ended the first nine months of this year with pro forma operating income of $90 million and pro forma net income of $51 million. Importantly, we are on track to meet or potentially exceed our financial guidance of pro forma operating income in the mid-$50 million range and more than $950 million in cash. In the first nine months of 2017, we earned $60 million of commercial revenue from SPINRAZA royalties. We’re pleased with SPINRAZA’s launch results to date and the potential for continued growth in the U.S., EU and in other markets globally. The royalties we have earned so far this year are in addition to the nearly $470 million of SPINRAZA-related revenue we’ve generated to date from Biogen, including the $40 million milestone payment we earned in the third quarter for SPINRAZA pricing approval in Japan. Because we earn tiered royalties on SPINRAZA sales and sales of SPINRAZA grow, so will our portion of those sales. The nominal third-party royalties we pay are fixed, not tiered, and we have no other expenses associated with SPINRAZA. This means that as SPINRAZA sales grow, our profit margin on sales will increase and all that profit drops directly to our bottom line. We also earned R&D revenue of $270 million, a 60% increase over the same period last year. The largest component of our R&D revenue is license fees and milestone payments. Revenue from this component in the first nine months of this year was $176 million. In addition, our R&D revenue in the first nine months of 2017 included $86 million of revenue from the amortization of upfront payments compared to…

Thanks, Beth. We entered the last three months of 2017 in our strongest financial position ever, and we expect to meet or potentially exceed our financial guidance. As demonstrated by the key achievements we have reviewed during our call, we believe this evidence that the Ionis business strategies continue -- continuing to demonstrate its value. The objectives of the Ionis business strategy are to maximize long-term innovation, assure commercial success for our product and unlock shareholder value. We are recognizing significant commercial revenue from SPINRAZA royalty, and we plan to add commercial revenue from inotersen and volanesorsen in 2018. As the company matures, we retain greater control and keep a larger portion of the commercial value of our drugs. In doing so, we’re assuring the highest performance of both late development assets and our commercial activities. Success of Akcea is tangible evidence of the strength of our strategy and the value unlocked when one considers Akcea’s valuation. Let me take a moment to focus on our opportunities in the midterm, that is the next one to three years. We continue to advance our pipeline of nearly 40 drugs, and we anticipate that several drugs currently in mid-stage developmental will enter late-stage development, including Akcea’s three other drugs from our lipid franchise as well as our mid-stage drugs to treat cancer clotting disorders and neurological disorders. Major value of value in the midterm will be the advancement of our LICA drugs, first of which are GalNAc-conjugated drugs targeting liver. We’ve consistently seen ED50 doses of less than 5 milligrams a week with these drugs, which means that to reduce the target by 50%, we would use a dose of less than 5 milligrams a week. And of course, if we want to increase the amount of reduction, we can simply increase…

[Operator Instructions] Our first question comes from Eric Schmidt of Cowen & Company.

Congrats to Lynne on starting a new chapter and best of luck to Brett on the new role. I guess my question’s around the inotersen partnership discussions. Sounds like the talks are well along there. Maybe Stan or Sarah can just kind of address Ionis’ conviction that a partner is the right strategy for maximizing shareholder value given how late you are here in the development and regulatory process. And maybe specifically focus on how a partner could expand the pie? Like, what does partner bring in that you guys can’t really do yourselves?

Thanks, Eric. We are well along. And one of the things that we’ve done over the last few months is knowing that we have competition with patisiran. We’ve tried to take a very sober look at what we expect out of inotersen in the marketplace. And to do that, we’ve invested many hours of conversations with patients, investigators and probably as importantly, physicians who are not investigators but take care of these patients. We walk away from those conversations very confident that inotersen is going to take a quite significant portion of the market. We also believe that the market is a significant market. So armed with that, we have not significantly changed our expectation for -- from partnering and we are pleased with the level of interest we have. We have made great deal of progress in getting ready to commercialize. And so the opportunity then to optimize our partnership to take the most advantage of inotersen’s potential, I think, is very real. And so I think you can -- you could imagine any number of outcomes. One, we choose to market it entirely ourselves. We’re ready to do that and getting stronger every day; or two, we find a partnership in some part of the world that adds value and provides the added marketing strength that we think will help in identifying patients in the number of diverse physician communities and take care of them; or three, an even different kind of partnerships. We’re looking at all of those forms. We are measuring our progress in getting ready to launch, and we think we’re in possession of the information we need to make the best decision to assure success.

Our next question comes from Jim Birchenough of Wells Fargo Securities. Please go ahead.

Let me add my congratulations to Lynne and Brad on your new roles. I’ve got three, really, and that would be on inotersen for Sarah perhaps. Maybe describe how you go about identifying target physicians given the broad categories of cardiology, neurology and hematology. Is there some way to kind of narrow the commercial focus? And then for Stan and Lynne, just on the collaboration with Biogen. Could you remind us where you’re at with that collaboration? What timelines might exist on the collaboration? And whether there’s an opportunity to expand it? And then maybe finally for Brett. Just on the LICA TTR. Is there an opportunity to develop that more rapidly? Given the validation of TTR reduction, do you think you’re going to need to do the full NEURO-TTR types of study? Or could that get approved on a surrogate like TTR reduction?

Maybe I’d start with the first part of your question about identifying physicians. And as you say, like the three core fall into cardiology, hematology and neurology. From cardiology, we’re actually doing a process of both national advisory boards as well as regional within the U.S. There’s also certain claims database clues that we can do. Specifically looking at some diagnostic tests that gives us indications as to cardiologists who maybe seeing these patients. With regards to neurology, it’s more sort of the peripheral neuropathy specialists at the starting point. And with hematology, one of the logical places to look is the multiple myeloma experts who are often, by default, also the people treating AR amyloidosis and quite often, patients with ATTR are also referred to the hematologists. So it’s kind of three separate mechanisms to identify the level of each of these specialties. And we’re pretty far along with regards to building those customer lists and what that target audience looks like.

With regard to Biogen, I think the partners, both Biogen and we, are thrilled with the performance of the collaboration today. SPINRAZA, of course, is a wonderful success and it’s great privilege to be associated with that. The number of drugs in development that Biogen has from the collaboration makes the Ionis participation in their pipeline perhaps as important as any other component that they could have, and that continues to expand. And the range of diseases gets larger. Something that we haven’t really spent much time discussing is that we also have quite a number of neurological disease drugs for our own account, and that will continue to expand as well. We are highly positive about our relationship with Biogen and they are equally positive. So clearly, we want to continue to advance our SMA franchise with new and improved versions of SPINRAZA. And certainly, our expectation is this collaboration will continue and be successful and potentially expand.

And Jim, regarding the TTR LICA. First off, we have great-looking drug that we’ve identified based on preclinical data. And as was mentioned, we’re moving this drug forward rapidly with high priority and expect to be in clinical testing next year. With respect to the speed at which we can develop it, absolutely, we do not expect to have to do this, a replication of what we do for NEURO-TTR. We’ve learned so much from that study that we believe that there are many opportunities to advance this drug forward to the finish line much more rapidly for treating all forms of TTR amyloidosis. And that includes the wild-type patient population, too. Regarding biomarkers, those are obviously on our radar. What we might be able to do, those will involve regulatory discussions, of course, when we need that type of feedback. But certainly, everything is on the table, and we’ve considered that type of strategy.

And just to add to what Brett said. Something that I think is very important is the performance of our GalNAc drugs has been highly consistent. We haven’t seen meaningful variations in potency from drug to drug, and all of them are giving us potencies in the 4 to 5 milligram per week range ID50. And we’ve had absolutely no adverse events of consequence in any of these trials. And so as we progress, and we now have 11 GalNAc drugs in development and most of them now are in clinical trials, and we have an ever greater number of patients being treated longer and longer with these drugs. We really have an extremely high level of confidence that these drugs are going to perform extremely well and give us all the profile enhancements that we hoped when we began the effort.

Our next question comes from Stephen Wiley of Stifel. Please go ahead.

My congrats as well to both Lynne and Brett on their new roles. Just a couple of questions on Huntington’s actually. So just wanted to confirm that this is going to be, the top line data announcement will be an Ionis-led communication, and then also kind of we’ve talked about the quantification of huntingtin protein reduction, the CSF, I’m also wondering if there’ll be an opportunity to also communicate and quantify reduction of wild-type huntingtin protein in the CSF? And just a point of clarification around the measurement of clinical outcomes, specifically TFC, is this something that will be measured at the end of dosing? Or will this be measured at the end of the follow-up period?

So first, we will be communicating about the Huntington’s program in the near future. And both Roche and Ionis are enthusiastic about the observations that we’ve made to date. Our primary focus is safety. Our secondary focus is HTT reduction, and we will probably provide a summary of all that and then much more detailed data at an upcoming scientific meeting. Huntington’s, of course, is quite different from SMA in that the symptoms are much more longer-lasting and the challenge of measuring them in short term is significantly higher, of course. So I would focus everyone on are we reducing Huntington’s and do we have safety and do we have any even soft preliminary indications of potential benefit? If we get any of that, that would be a bit of a surprise to me because of the nature of the disease. But certainly, we think we have an agent that is going -- has the potential to be an important advance in the treatment of Huntington’s. Lynne, do you want to add anything to that?

I understand. So you will be able to differentiate between reductions in both wild-type and mutant huntingtin protein?

Yes. Sure, although I don’t think it’s a terribly important question.

Okay. And maybe just one quick follow-up for Brett regarding the preclinical LICA TTR candidate. Is that the same ASO payload as inotersen? And if not, maybe just -- is it different on nucleotide length? Is it different on Gen 2.5 versus Gen 2.0? Just curious if there’s any differentiating features there beyond LICA?

Gen 2.0 molecule, and it’s not the exact chemistry, inotersen but it’s very similar.

Well, the sequence is the same. And you may be asking questions that relate to chemistries and siRNAs versus ASOs. The chemistries that we report -- of course, we define the chemicals very clearly and the basic chemistry is not significantly different in any way. With siRNAs, there’s a great deal of variation in what various companies are putting into those molecules, whether there -- how many 2-prime methoxys, how many 2-prime 4-Os, what other sorts of modifications are in there. They seem to vary a lot from drug to drug, depending on a lot of factors, but it seems to us at least most importantly, the sort of side effects that are seen in short-term clinical trials.

Our next question comes from David Lebowitz of Morgan Stanley.

I’m curious what are the -- what’s the status of the launch preparations for volanesorsen? And how are the efforts going in identifying patients for that?

So Akcea is well along in building both our U.S. and their European commercial structures, and they have teams in all of the key markets in Europe already. They have been, actually, for quite some long time, doing work in a variety of ways to identify patients and they have a substantial database of patients already identified. They’ve been using a number of strategies, obviously being very involved in the medical community as the physicians were treating these patients as well as a number of database searches that made major medical facilities. And what they’re finding, which isn’t very surprising with a disease like this, is that if you go and ask a physician, do you of these patients? They may say, I have one. I might have two. And then they go work with a direct the database search with a physician using the diagnostic criteria and find that, of course, there are quite a substantial number more. So they have, as I said, a variety of different initiatives underway, which are all being very productive and are right on track with their database in terms of patient identification in the U.S. as well as ex-U. S.

To my mind, some key steps that they’ve taken that are -- I think are tremendously important that we haven’t probably emphasized quite enough is, first, I think they’ve done a great deal to galvanize the FCS community. And today, we have a much more active FCS community that’s engaged in much more aggressive self identification of signs and symptoms. Second, we’ve engaged in a very active educational program from regulators. And I think what we know today and what we see out of the regulators is a much better sense of how severe this disease is and how desperately it needs treatment. And third, the patient survey that was done was really instructive to all of us. It demonstrated that the symptoms associated with the disease are much more day-to-day and much more telling and far more aggressive than what’s really understood by us or the community. And then fourth, the natural history study of Dr. Gaudet, which is an important benchmark, should be published here before very long. Now all of those things, I think, contribute to a very substantial increase in disease awareness. And as with any rare disease, particularly when there is only 1 drug and only 1 choice, and that’s called volanesorsen, I think we recognize, and Paul and team are doing a good job of it, that one of the key elements is to actually build the market, to build the awareness, to get those patients identified. I think they’ve done, just as Sarah has, identify the key physicians who are sort of the catchment physicians for these patients or as with neurologists or surgeons and a variety of other people. So my sense is that in addition to all the progress they made in building the organization, there’s been really tangible progress in defining the disease, the patients, the physicians and educating about it that I think is going to tell in the commercial success of volanesorsen. We’re extremely pleased with the work that Akcea has done and also very pleased with the growth in recognition of the severity of the disease. It was rather remarkable to us when we began that even physicians who took care of these patients extensively did not understand how bad the circumstance for these patients was. So we think we’re far along compared to where we were a few months ago.

Our next question comes from Jessica Fye of JP Morgan.

I’m curious how you think about the potential to get the cardiac data from NEURO-TTR on the inotersen label? And also how you’re thinking about potential reimbursements for cardiomyopathy patients? And then I just want to make sure I understood one of the comments you made earlier referencing, I think, potentially faster path forward for wild-type cardiomyopathy patients. How should we think about future clinical studies to extend the label into cardiomyopathy?

In terms of your -- the first two questions, Jess, we obviously are pleased with the cardiac data that we have. And our goal was to get all of that data into the label. And in terms of reimbursements, really interesting because we think about this disease as being polyneuropathy and cardiomyopathy but in fact, it’s a continuum. And when you talk to physicians who have cardiomyopathy, patients who they call cardiomyopathy patients, they will say many of them have polyneuropathy symptoms. And as we saw in our study, of course with the polyneuropathy patients, over half of them had cardiac involvement with their disease. And so I think that reimbursement is not going to be difficult because these patients will have -- of course, it’s going to be dependent on the label, but even if the label were to be limited to polyneuropathy, as I said, most of the cardiomyopathy patients have some polyneuropathy involvement. And I’ll let Brett talk about the development path forward to the LICA.

Just to clarify, the biomarker work that I referred to earlier, I believe, would be limited to the civilian disaster patient population we studied. I think it would be less likely we’ll be able to use a biomarker for the wild placements we have not studied in that patient population in a randomized controlled study to date. Of course, we’ll look in several options in that patient population. What I was really referring to was this patient population we studied, which was a hereditary form.

And I guess, the final comment is, while I think there’s plenty -- I think we’ll be fairly straightforward to access patients with cardiomyopathy, I do think, long term, this great value in outcome work that demonstrates, really demonstrates, advantages. So we continue to be interested in long-term pursuit of outcome studies with the LICA in particular.

And just follow up on that comment about the FAC patients having polyneuropathy as well. Does that apply to the wild-type cardiomyopathy patients? Do they also have polyneuropathy?

Not nearly so much, no. They typically are, as you know, older and they typically have primarily cardiac involvement. It’s a somewhat different circumstance.

Our next question comes from Paul Matteis of Leerink Partners. Please go ahead.

I just have a couple on Huntington’s. My first question is can you just kind of -- be curious to your opinion on what magnitude of HTT knockdown in the CSF would be -- would represent, say, a great outcome, just a good or okay outcome and a not so great outcome? And then secondarily, I’m wondering when you look at HTT changes in the CSF, how important is it to you to understand where actual knockdown is occurring in the brain, be it either the back of the brain or the cortex or the frontal lobe?

Well, what we hope to see is just dose-dependent reduction. I think if we get dose-dependent reduction, we have everything we need because we know we have great safety and so we can always just dose and get the level of reduction that we hope for. I guess, the better answer to the question is that heterozygotes are normal. And so at least in animal studies, anywhere from 30% to 50% of reduction, if I remember correctly, and I have to double check with Frank on that, but if I remember correctly, were beneficial. We certainly hope to get greater than that. And I think quite important to know that you’re getting reductions in the areas of the motor cortex and other areas where the disease manifests itself. And so, we’ve invested a great deal of effort, both with Biogen and with our colleagues at Roche to really understand after an intrathecal injection where our drugs are accumulating. And we’re quite encouraged by all the data we’ve seen because we see substantial drug activity, not just drug concentration but activity across the board in the neurological pipeline in almost all regions of the brain and the spinal column. And of course, it’s those data that supported that moving into much broader range of diseases than something like SMA that’s led us into Parkinson’s and Huntington’s and Alzheimer’s and a wide range of other diseases. We think that we have access to almost all the areas of the brain and spinal cord that we need to treat most of the significant central nervous system diseases. We’re very excited about it as is Biogen and as is Roche.

Okay. And then what, if you were to rank clinical endpoints in terms of importance, what’s most interesting to you either in this study or for a future pivotal trial?

David, I would like to defer that because I don’t feel I know enough about Huntington’s disease -- or Paul, sorry, forgive me. You can call me George if you like. I’m just learning more about the clinical signs and symptoms of Huntington’s, and I’d rather wait until we have some real experts on the call to deal with that, and that’s going to happen pretty soon.

Our next question comes from Gena Wang of Barclays. Please go ahead.

So I have two on inotersen and then a one quick one on Huntington program. So regarding pricing, so I’m pretty sure you’re already talking to a lot of peers on reimbursement. So given the data, we all saw like a very impressive data and also on the medical need, like what would be a good benchmark that you can guided us to think about the inotersen pricing?

Well, my preference is not to answer that question today. We are in the process of doing all that work and we have a competitor. I have noticed and noted with interest that Alnylam has sort of signaled Soliris-type prices, if I understood it correctly, but we’re not prepared to do that today.

Okay. And then another question is about the patient identification. So can you just remind us what would be the number of patient you think it will be, addressable patient population for inotersen? And then how many patients have you already identified?

Yes. So if you look at the epidemiology that’s available today, so the consensus, about 10,000 patients with the polyneuropathy form of the disease and about 40,000 with the cardiomyopathy form. In both cases, I’m talking about hereditary. Now one of the keys to this is that I think when that data was put together and when we started the data, we thought this event was two different diseases when in fact, it’s not. And there’s a very high level of overlap that Lynne alluded to so the patient population available, we believe, to be much larger than just the polyneuropathy form of the disease from a traditional perspective because the cardiomyopathy patients, guess what, it’s the same disease and they have polyneuropathy. In terms of patient numbers and patient numbers that we have identified, obviously, this is a competitive program, so we’re not going to give details around that. But suffice to say, we are very far along in our KOL and physician mapping as well as our patient journey mapping. So we have, we believe, a pretty good idea as to how people move through the system, the pains along the diagnostic journey and where those intervention points are as well as building on CRM system. And we’re also in the process of deploying our MSL team as well, which will really accelerate that program.

I think there’s a lot of benefit to be had because there’s Pfizer and there will be Alnylam and Ionis. And I think that will substantially enhance the identification of patients for all of the participants in that market, which will be a great thing for patients.

Great. And then just one very quick question on huntingtin. Could you just remind us the mechanisms in terms of targets? Do you target specifically mutant Leus in a huntingtin protein? Or target also wild type as well?

No, we target both. We have the ability to target the mutant. But as we look at the entire disease and characteristics of the disease, we concluded it’s a little bit like amyloidosis in that the mutant, of course, produces inclusions and cell and so on and then that accumulates all kinds of huntingtin and other stuff. So we had -- it was one of the interesting choices. Do we focus on simply the mutant or the total? We looked. We believe there’s no reason to be meaningfully concerned about the safety of reducing all of Huntington’s. And so our choice was to reduce all the potential causes of continuing the disease process. We have time for one more question and then we’ll have to go.

Our next question is from Yale Jen of Laidlaw & Company.

First of all, my congrats to Lynne and Brett. And just two questions here. The first one, again, for inotersen that I know you guys are active in preparing the market. At the same time, you, I think, also in partners -- partnering. And given the timeline probably by mid-next year, the drug can get approved. So how’s the mentality or thoughts you guys have right now as how you hand it out to a partner, is that the case? And before that, are you just guys just full force to prepare it for -- there’s only -- you’re going to market it by yourself?

I think the most important thing we’re looking at, I-Eh, is what is the company that we might choose ready to contribute immediately to launch? Do they have the infrastructure, the field force, the experience to aid us in one of the markets in terms of launching the drug? And so our calculus here is what should we do to maximize our penetration in this market and maximize our competitive edge? And our focus is principally on what resources can they bring immediately to bear to make that launch successful. We have a number of choices. Obviously, we also look at the dollars that they’re prepared to invest in us in getting the drug in, but more importantly, what is going to be their investment going forward in the marketplace? And in the meantime, we’re well along the way to being ready to launch ourselves. And as that progresses obviously, our threshold for taking a partner on becomes higher.

That’s very helpful. And my last question here is that, allowing that there’s -- recognize that the LICA will be probably a very important element for you guys going forward, could you just highlight maybe by -- let’s say, by end of 2018, how many sort of more clinical advanced LICA drugs maybe on your pipeline so people have a better sense on that?

Thank you. I don’t have the specific numbers in my head but just offhand, we will have completed Phase 2 studies on substantially more than 6 or -- I would guess 5 to 8 GalNAc LICAs by the end of 2018 and maybe more. We should have, I think, 10 or 11 in clinical development by then and maybe more. I think that’s about right. Would you say, Brett?

Yes, I’d say so.

And then two very important and large studies are the APO-A and APOCIII-LRx Phase 2b dose ranging studies and I’m sure that will be multiple hundreds of patients.

And both the APO-A and C is actually well along, and we already have a substantial longer term data in that study and if, like, every other GalNAc like in our pipeline is performing impeccably. And we’ll be trying to share our experience there as it progresses and then we’ll try to summarize our overall experience for you at some point next year. With that, we’ll bring the Q&A to an end. I’d like to thank everyone for their interest. We’re tremendously excited about the position we have and look forward to next year being a year in which we have commercial revenue from SPINRAZA, which will be increasing commercial revenue from volanesorsen, commercial revenue from inotersen. Our partnering strategy delivering -- continue to delivering great value, Akcea being successful and progress in Inotersen, helping people to understand it’s going to be a very successful competitor in the marketplace.

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