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Ionis Pharmaceuticals, Inc. (NASDAQ:IONS)
Q3 2019 Earnings Call
Nov 6, 2019, 11:30 a.m. ET

Contents:

  • Prepared Remarks
  • Questions and Answers
  • Call Participants

Prepared Remarks:

Operator

Good morning and welcome to Ionis Pharmaceuticals Third Quarter 2019 Financial Results Conference Call. [Operator Instructions]. At this time I would like to turn the call over to Wade Walke Vice President Investor Relations to lead off the call. Please begin.

D. Wade Walke -- Vice President of Investor Relations

Thank you Sean. Before we begin I encourage everyone to go to the Investors section of the Ionis website to find the press release and related financial tables including a reconciliation of the GAAP to non-GAAP financial measures that we will discuss today. We believe non-GAAP financial results better represent the economics of our business and how we manage our business. We have also posted slides on our website to accompany our discussion today. With me on today's call are Stan Crooke Chairman of the Board and Chief Executive Officer; Beth Hougen Chief Financial Officer; and Brett Monia Chief Operating Officer. I would like to draw your attention to slide three which contains our forward-looking language statement. We'll be making forward-looking statements which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties so our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional details.

And with that I'll turn the call over to Stan.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Thanks Wade and good morning everyone. Thank you for joining us. Our commitment to innovation has led to the increase in value of our commercial medicines our pipeline and technology which today is reflected in our robust financial performance. Because of our strong performance for the first 9 months of this year we are significantly increasing our 2019 guidance to a significant improvement. We're on track to deliver approximately $1 billion of revenue more than $375 million in operating income and more than $300 million in net income. This means that we expect to deliver our fourth year of operating income and our third year of net income. We're achieving these strong results by continuing to invest as aggressively as justified across every element of our business.

We're achieving successes and making progress broadly throughout the business and we're extremely pleased with SPINRAZA's continued blockbuster performance. SPINRAZA is the worldwide foundation of care for the treatment of all SMA patients of all ages supported by growing body of data Entering Facebook getting stronger the longer they are treated with the product. We're already seeing positive momentum at Akcea since Damien assumed his leadership role. Damien is adding key new members to the Akcea leadership team which we feel is necessary to help the organization reach its commercial and development goal. The first of several addition to the senior management team is Kyle Jenne who was recently promoted to Chief Commercial Officer after leading Akcea's U.S. commercialization of TEGSEDI and WAYLIVRA.

Importantly we're beginning to see momentum build with TEGSEDI and WAYLIVRA. Akcea is expanding the market opportunities of TEGSEDI across the world. With approval in Brazil TEGSEDI is now the first RNA-targeted therapy approved for the treatment of patients with TTR polyneuropathy in Latin America. Given the substantial number of patients with the hereditary form of this disease in Brazil Latin America is a key strategic region for TEGSEDI. PTC Therapeutics has market development and medical support teams in place in Brazil and have plans to start launch activities for TEGSEDI immediately. Akcea is also beginning to make significant progress in the U.K. TEGSEDI is now on the market in the U.K. following acceptance by NICE and the Scottish Medicines Consortium.

Akcea successfully completed pricing negotiations in Germany and successfully completed reimbursement negotiations in Austria and Sweden where TEGSEDI is now on the market. And preparations for additional EU country launches are under way. WAYLIVRA is now on the market in Germany with the FCS patients benefiting from the only medicine approved for the treatment of this devastating disease. Additionally Akcea is preparing for more EU country launches next year. PTC is preparing to expand WAYLIVRA into Latin America. And in the U.S. and Canada we believe new longer-term data and our experience in the EU will support our ongoing efforts with regulators to find a path to the market for WAYLIVRA. Damien and his team have also gained momentum in strengthening and advancing the Akcea pipeline. Most recently we and Akcea entered a collaboration with Pfizer to develop and commercialize AKCEA-ANGPTL3-LRx for the treatment of certain metabolic and cardiovascular diseases. This collaboration with substantial upfront and back-end economics and targeted for diseases that are of very large patient populations is further evidence that our partners have confidence in our technology and it's ability to provide benefit to patients with diseases both rare and much more complex. Additionally Akcea will soon have 2 medicines in Phase III development AKCEA-TTR-LRx and AKCEA-APO(a)-LRx.

And early next year Akcea plans to report data from Phase II studies of AKCEA-APOCIII-LRx and AKCEA-ANGPTL3-LRx. In addition to our recent achievements with medicines in the Akcea pipeline we also achieved multiple value-driving successes across the broader Ionis pipeline this quarter. We're on track to achieve our goal of ending 2019 with 4 Phase III programs under way. Pivotal studies are progressing for patients with Huntington's disease and SOD1-ALS and Phase III programs for TTR amyloidosis and Lp(a)-driven cardiovascular disease are beginning very shortly. We made substantial progress with our medicines other than these to better addressing diseases with large patient populations. In addition to the new collaboration with Pfizer for ANGPTL3-LRx Bayer plans to advance our LICA FACTOR XI medicine for the treatment of patients with thromboembolic disease and GSK licensed our ApoB program for the treatment of chronic hepatitis B virus infection. Our neurological disease pipeline advanced as well. Biogen dosed the first patient in its Phase I/II study for the treatment of patients with Parkinson's disease another large disease.

We also added 3 new medicines to our neurological pipeline 2 partnered with Biogen and 1 that's wholly owned. Importantly we continue to strengthen our position as the leader in RNA-targeted drug discovery and development and our technology continues to advance at an increasing pace. Today we can achieve these substantial financial and businesses successes while continuing to broadly and aggressively invest across our business including investing in growing our commercial medicine and advancing our pipeline and technology. These are of course our highest priorities because we believe these investments have the greatest potential to create patient and shareholder value. And because of the -- our strong balance sheet and cash flow we can achieve all of this and achieve all these goals while also returning value to our shareholders in the near term. So today I am pleased to announce that our Board of Directors has authorized an initial share repurchase program of up to $125 million with the potential for us to consider additional repurchases in the future as part of our overall capital allocation strategy. This action reflects the confidence that we have in our business and our commitment to creating near-term and long-term value. We also believe that at today's stock price buying back our shares is really good investment.

And now I'll turn it over -- turn the call over to Beth to provide a financial update followed by Brett who will update you on our pipeline progress.

Elizabeth L. Hougen -- Senior Vice President, Finance and Chief Financial Officer

Thank you Stan. Our strong financial results continued in the third quarter. In the first 9 months of this year we delivered operating income of $270 million and net income of $189 million both on a non-GAAP basis. We also achieved substantial operating income and net income on a GAAP basis. These strong results were driven by nearly $630 million in revenue a more than 50% increase compared to last year. Growth in both commercial revenues including SPINRAZA's continued blockbuster performance and R&D revenues as our partnered programs advanced contributed to the substantial increase. In the third quarter we maintained our strong balance sheet with $2.2 billion of cash and we expect our cash balance to increase when we receive payments from Pfizer and Bayer this quarter. SPINRAZA generated over $1.5 billion in worldwide net sales through the end of the third quarter an increase of nearly 25% compared to last year. Reflecting SPINRAZA's strong performance our royalty revenue of $212 million increased by more than 25% compared to last year.

The total number of patients on SPINRAZA treatment increased by approximately 11% from last quarter to more than 9300 patients worldwide. New patients starts in both the U.S. and around the world contributed to this growth. In the U.S. adult patients were a significant driver of growth in the third quarter increasing by 8% over last quarter. And as the largest SMA patient segment we and Biogen believe that adult SMA patients represent a continued opportunity for growth. Now approved in over 50 countries and with reimbursement in place in 40 countries the number of patients on SPINRAZA outside the U.S. increased by approximately 18% compared to last quarter. Strong performance in established markets such as the EU and Japan plus rapid uptake in key markets in Latin America and Asia Pacific were primary drivers of this growth. Additionally the first SMA patients in China recently began SPINRAZA treatment. Biogen expects growth to continue in these key markets and believe that the global opportunity for SPINRAZA is much larger than initial estimates with more than 45000 patients in markets where Biogen has a direct presence.

Importantly as the body of evidence supporting the robust profile of SPINRAZA continues to grow we believe SPINRAZA will remain a global foundation of care for the treatment of SMA patients of all ages and type. Turning now to TEGSEDI and WAYLIVRA. We earned $29 million from product sales of TEGSEDI and WAYLIVRA during the first 9 months of this year. The Akcea team continues to make progress with the launch of TEGSEDI. In the U.S. Akcea's focus is on disease education particularly in community centers while maintaining strong relationships with physicians in the academic centers. Additionally use of Akcea's genetic testing program is growing with more than 1000 physicians now using the program. Both of these initiatives are translating into more physicians prescribing TEGSEDI. Outside the U.S. we are extremely pleased that following approval in Brazil TEGSEDI is now the first RNA-targeted therapy approved for the treatment of people with TTR polyneuropathy in Latin America. PTC Therapeutics plans to start their launch activities in Brazil immediately. We also look forward to potentially expanding more broadly in other Latin America countries. Additionally patients are now on treatment in Austria Sweden and in all 4 countries in the U.K. and Akcea's preparations for additional EU country launches are under way. Akcea's patient support program is now up and running across all commercial markets and feedback from physicians has been quite positive.

So we're pleased to see this program expand with the TEGSEDI launch. Patients are now being treated with WAYLIVRA in Germany following approval in the EU. And Akcea is preparing to launch in additional EU countries next year and we look forward to potentially expanding into Latin America also through PTC. Reflecting the substantial and increasing value of our technology R&D revenue increased by more than 65% to $377 million. R&D revenue included $198 million in license fee revenue from Novartis GSK and Alnylam; $100 million from amortization of upfront payment for advancing numerous programs in research and development; and $64 million in milestone payments including nearly $25 million from Biogen which included most recently a milestone payment for initiation of a Phase I/II study targeting LRRK2 for the treatment of people with Parkinson's disease.

We expect to recognize substantially all of the $250 million upfront payment we generated for Pfizer's license of AKCEA-ANGPTL3-LRx in our fourth quarter results. Our recent license of AKCEA-ANGPTL3-LRx demonstrates the increasing economics we can command for our medicines and technology. In addition to the $250 million upfront payment we are eligible to receive up to $1.3 billion in milestone payments and tiered double-digit royalties on net sales. Moreover Pfizer is adding substantial value by conducting future development and regulatory activities and paying for these activities. Additionally we will recognize the $10 million milestone payment from Bayer in full in our fourth quarter results. Bayer will assume the development of IONIS' Factor XI-LRx which represents substantial value to us.

Our non-GAAP operating expenses increased to $412 million in the first 9 months of this year compared to last year. We are investing broadly across our business including investing in commercializing TEGSEDI globally and launching WAYLIVRA in the EU advancing and expanding our pipeline and advancing our technology. Our strong financial performance this year has led us to improve our 2019 guidance. We are now projecting to earn $1 billion in revenue. We are maintaining our original guidance for operating expenses while continuing to aggressively invest across the business. However we do anticipate being at the lower end of the range for both R&D and SG&A expenses. We are increasing our operating income guidance to more than $375 million which represents a more than fivefold increase over last year and importantly represents an operating margin of nearly 40%.

We're also increasing our net income guidance to more than $300 million and we are increasing our cash guidance to $2.2 billion. Our highest priority investments are our commercial medicines broad pipeline and our technology. Our strong balance sheet and cash flow combined with our commitment to continued profitability means we are also able to begin returning value to shareholders through an initial share repurchase program of up to $125 million. We plan to make stock repurchases under this program over time in open-market transactions and we anticipate that at the conclusion of this initial program we will consider additional share repurchase programs to provide even more value to shareholders. The increasing value of our technology financial strength and ability to return value to our shareholders further distinguishes us from our peers.

And with that I'll turn the call over to Brett to provide an update on our pipeline.

Brett P. Monia -- Chief Operating Officer Senior VP of Translational Medicine & Director

Thanks Beth. Today we have 3 medicines on the market a pipeline of over 40 medicines advancing through development and many more progressing through research toward clinical trials. SPINRAZA is the global foundation of care for the treatment of SMA patients of all ages and all SMA types and Biogen continues to report new even longer-term data demonstrating improved patient performance with prolonged SPINRAZA treatment. In new data from NURTURE study of pre-symptomatic infants now on treatment for approximately 45 months we continue to see kids developing like their normal healthy counterparts. Remember without SPINRAZA these babies would have rapidly succumbed to their disease.

And patients with later onset SMA in the SHINE study some of whom began the study as kids and have now reached adulthood continue to show stabilization or improvement in measures of their disease. Today some patients treated with SPINRAZA in the SHINE study have gained the ability to walk unassisted. Biogen is also preparing to explore the potential of achieving even greater benefit with a higher dose of SPINRAZA. With over 9000 patients on SPINRAZA today including some patients who have been on treatment for nearly six years SPINRAZA's well-established safety profile is supportive of expanded dosing. Biogen's Phase II/III DEVOTE study which we expect to begin soon will evaluate the safety and potential to achieve increased efficacy with a higher dose of SPINRAZA with pure loading doses in SMA patients of all ages including the adults. Additionally we and Biogen are developing a follow-on medicine for the treatment of SMA focused on less frequent dosing which could enter development next year. IONIS-HTTRx also known as RG6042 is progressing in a comprehensive Phase III program in patients with Huntington's disease. Roche recently announced expanded enrollment in the Phase III Generation-HD1 study.

This expansion will enable a more thorough evaluation of each treatment group including the every four month dosing regimen. It also allows Roche to add patients from China to the study. This pivotal study along with the Phase I/II open-label extension and natural history studies are all important elements of Roche's compressive clinical program to thoroughly evaluate the potential of IONIS-HTTRx to be the first disease-modifying medicine for the treatment of Huntington's disease. The Phase III VALOR study of tofersen is also progressing well. Biogen is evaluating this medicine for the treatment of patients with SOD1-ALS in hopes to bring tofersen to patients with this devastating disease rapidly as possible. Biogen also recently initiated a Phase I/II study of our medicine targeting LRRK2 the most common genetic cause of Parkinson's.

This study will enroll patients with LRRK2 mutations as well as patients with sporadic form of Parkinson's disease which together represents over 3 million patients worldwide. Under our collaboration with Biogen we now have 8 medicines in development on top of a substantial research-stage pipeline that together addresses a broad range of neurological diseases including Alzheimer's frontotemporal degeneration and various forms of both ALS and Parkinson's disease and many more. In parallel we've also continued to advance and expand our pipeline of wholly owned medicine. In addition to the advances we're making across our pipeline advances in our technology continued to enhance the performance of our medicines expand their commercial potential and enable a broad and robust pipeline of potentially transformative medicines for many years to come. Today our partners are recognizing substantial commercial potential which is reflected in the increasing value we receive from our collaborations.

This value of course is based on the confidence our partners recognize in our technology to treat a broad range of diseases from rare to the most common diseases affecting millions of patients. For example GSK recently licensed our HBV program and has repeatedly expressed strong enthusiasm about its potential to treat more than 200 million patients around the world with chronic hepatitis B virus infection that are not adequately treated with currently available therapy. Furthermore this year several of our partners have also made substantial investments in medicines developed with our LICA platform technology to address large patient population.

Our partners are attracted to the robust efficacy profile with LICA medicines based on LICA's increased potency enabling low-volume monthly or even less frequent dosing. More importantly our partners are confident in the favorable safety profile of our LICA platform as demonstrated by a total of over 1100 people treated to date with LICA medicine including nearly 300 patients treated for up to one year in the Phase II study of AKCEA-APO(a)-LRx . High partner confidence in our LICA technology is being demonstrated in many ways. For example Pfizer licensed AKCEA-ANGPTL3-LRx to treat millions of patients with certain metabolic and cardiovascular [Technical Issues] Bayer choose to advance IONIS' Factor XI LRx to treat millions of patients with thromboembolic disease and Novartis is advancing AKCEA-APO(a)-LRx in millions of patients with Lp(a)-driven cardiovascular disease. This study together with the outcome study for AKCEA-TTR-LRx for patients with TTR cardiomyopathy will be the first cardiovascular outcomes study for an antisense medicine. Furthermore we continue to innovate and advance our antisense technology.

This investment has paid and continues to pay substantial dividends. Today our antisense drugs incorporate many of these advances to benefit patients across a broad range of uses. Through advancements in medicinal chemistry and optimization and validation of nearly all routes of delivery we can target most organs and cell types with our antisense medicines. For example we have already shown feasibility of aerosol delivery to the lung but with enhanced performance of our antisense medicines along with more potent chemistries we have substantially improved potential for commercial success for a broad range of lung diseases further expanding the reach of our technology. Our first gen 2.5 pulmonary delivered medicine targets the epithelial sodium channel or ENaC in the lung. We are advancing this medicine for the treatment of people with cystic fibrosis and other pulmonary diseases. And we look forward to sharing results from our ENaC Phase I/II study next year along with updates in other pulmonary programs emerging within our pipeline. We have also made substantial progress in advancing oral dosing of our antisense medicine.

We believe we are on the verge of developing a commercially viable oral antisense medicine by combining our gen 2.5 chemistry with our LICA chemistry. The ability to deliver an antisense medicine as a daily tablet would represent yet another significant advance with the potential to provide substantial value to patients enabled once again by our pioneering research. We look forward to sharing results from these early clinical studies next year. The first nine months of this year have been quite exciting highly productive and eventful and we look forward to numerous additional value-driving events through the end of the year and throughout next year. I look forward to providing further pipeline and technology highlights in the months to come.

And now I'll turn the call back over to Stan to close this portion of the call.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Thanks Brett. We built Ionis on a foundation of our efficient technology and today the value of our technology is reflected in our financial strength and it's a product directly of our business model. Our financial strength then gives us the flexibility to maximize the value of each of our medicines and our technology. Our partners are recognizing the value of our technology as demonstrated by the substantial economics of our recent transactions. Our business strategy is succeeding and today we are sustainably profitable. Ionis is delivering more value to patients and shareholders every day.

Importantly we're delivering value while investing in the future potential of our business including advancing our pipeline of over 40 medicines growing our pipeline of wholly owned medicines advancing our technology at an ever faster pace potentially delivering commercially attractive aerosol and oral medicines and enabling new routes of administration while advancing new medicines for broad new therapeutic areas. Our -- on December 13 we plan to host a webcast to discuss many of the recent advances on our technology. This will be a deep dive in the exciting science that we're working on right now that we believe positions the technology to be ever more powerful in the years to come. I look forward to the opportunity to discuss our work with you in this form. And just as an aside this is for real techno geeks.

It's probably not for the faint of heart but we hope you join us anyway. So watch for more information about the webcast which will be announced very shortly. The business successes and financial strength we've built give us confidence that we will continue to deliver value to our patients and shareholders today and in the years to come.

And with that I'll turn the call over for Q&A. Sean if you can set us up for Q&A please.

Questions and Answers:

Operator

[Operator Instructions] Our first question today will come from Chad Messer with Needham & Company. Please go ahead.

Chad Jason Messer -- Needham & Company -- Analyst

Congrats on the very strong financial results. I believe these share buybacks are a really good sort of indicator of how you're feeling about the business.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Thanks Chad. Appreciate it.

Chad Jason Messer -- Needham & Company -- Analyst

Just wondering if you could share your thoughts about some recent comments from Pfizer about -- since the tafamidis launch I believe they said they identified over 4000 patients with TTR cardiomyopathy especially given that you guys are about to start a trial in that indication.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Well I think they know this disease and this space extremely well. And we believe that there is a sizable market opportunity there and we're very confident that the LICA form of TEGSEDI is going to deliver a great performance for us like the other LICA forms of other medicines have done.

Chad Jason Messer -- Needham & Company -- Analyst

All right. Great. And then as you know very excited about the concept of an oral antisense and I'm sure we'll be hearing a lot more about that in the future. But any thoughts on what makes sense to move first either new indications that might not have been as amenable to using a subcu injection or basically newer forms of existing sort of tried-and-true drugs that you have?

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

You will be hearing a lot more about it and you'll first hear it as Brett describes it on December 13 at our upcoming technology webcast. And the answer to your question as I'd say all of the above.

Chad Jason Messer -- Needham & Company -- Analyst

Okay. Thanks so much

Operator

Our next question will come from Jim Birchenough with Wells Fargo. Please go ahead.

James William Birchenough -- Wells Fargo Securities LLC Research Division -- Analyst

Let me add my congratulations and great to see the share buyback and the confidence underlying that. So a couple of questions. I guess number one just thinking about the financial side of things. Could you maybe give us some sense as to how we -- to think about the outlook both in terms of revenues and earnings? Do we expect revenues to be a little lumpy given the contribution of R&D revenues and then to smooth out over time? And just want to make sure we're still guiding or expecting sustainable profitability. And then I've got a follow-up.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Well yes we now are reporting our fourth year of operating income and our third year of net income. And we're very confident and optimistic that next year will be another successful year financially and across the business. We are really excited about the things that are going on in the company and Akcea and look forward to another banner year next year.

James William Birchenough -- Wells Fargo Securities LLC Research Division -- Analyst

And then just in terms of capital allocation I think one of the things you've highlighted historically or maybe even more recently is just investment in technologies that could maintain your leadership in the genetic medicine space. And so could you maybe talk to your efforts to go beyond antisense or extend your dominance in this area of medicine and how you're allocating capital to that?

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Yes. We are excited about that Jim. And it is progressing and it's progressing on 2 or 3 broad fronts. Number one is any access to anything that might enhance the performance of the technology we've invented today. Number two is to expand our use of genomic information to an even greater extent from what we're doing today. And then number three we're looking for the next antisense technology. And if you think about those 3 components of the investment strategy you would expect investments in the first couple of components long before the third because enabling technologies like antisense don't come along every day. So I do expect that you'll begin to see some investments in those areas in the coming months based on the progress that we've made so far.

James William Birchenough -- Wells Fargo Securities LLC Research Division -- Analyst

And then maybe just final question. I know there's not much you can say on partnered programs beyond what partners have said and what you said in your prepared remarks but maybe for your wholly owned pipeline what are the key products that you're most excited about? Maybe a question for Brett. And maybe speak to the visibility we'll get on those wholly owned products over the next year or so.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Brett?

Brett P. Monia -- Chief Operating Officer Senior VP of Translational Medicine & Director

Yes. Sure Jim. And thanks for the question. Our wholly owned pipeline is growing rapidly across all therapeutic areas or many therapeutic areas. I suppose the answer depends on how advanced the program is plus -- coupled with how -- what the potential is for that medicine to have a big impact and to be a transformative medicine on the market. I'd have to highlight a couple 3 growth hormone receptor for acromegaly. It's a very exciting program that is in Phase II and is due to read out next year and potentially move on to Phase III. So that could be a wholly owned program that's in patients with acromegaly in Phase III next year. Our TMPRSS6 program is very exciting. It's a program that has the potential to treat multiple disease populations including beta-thalassemia intermedia alpha-thalassemia as well as myelodysplastic syndrome MDS. So lots of opportunity for that drug. It's performed very well in Phase I and it's in Phase II and is moving very rapidly. And then our neuro pipeline is also worth commenting on. Alexander disease prion disease Lafora disease are all moving forward very nicely. And obviously we have validated neurodegenerative diseases with our platform. So that has very high potential upside on that. And then the last thing I would say is watch out for our lung platform our pulmonary disease pipeline. As I mentioned in the webcast our ENaC program is in Phase I is showing great promise. And there's more to come behind that.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

And Jim I would add TTR-LRx is our -- as our #1 asset that's wholly owned. It's going to be commercialized through Akcea. We're really excited about the potential of LICA form of TEGSEDI to deliver incredible value. And if you look at the economics of the large medicines that we have APO(a) APOCIII ANGPTL3 the Parkinson's and Alzheimer's medicines and Factor XI I think people have tend -- have forgotten how extraordinary the data with Factor XI were in that 300-patient knee replacement study. I think it's to some extent a mistake to focus solely on our wholly owned pipeline because the dollars that will come from those large products that are licensed under the economic terms we have are going to matter a great deal. And it's -- and again it's manifestation of the business model we have. So I fully subscribe to what Brett said but I would add the comments that I made obviously since I just did it.

James William Birchenough -- Wells Fargo Securities LLC Research Division -- Analyst

Well, thanks for thanks for taking the questions. Okay, thanks.

Operator

Our next question will come from Tyler Van Buren with Piper Jaffray. Please go ahead.

Tyler Martin Van Buren -- Piper Jaffray -- Analyst

Congrats on the results. I know in the press release under Key Upcoming Events you didn't give a time line of course. But I just want to get your updated thoughts on timing of Huntington's data of course. And then once we get the data with the open label what would you expect these patients to show on the composite endpoint? And what would be a successful outcome with the active therapy?

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

That sounds like a question that Brett should answer and I should avoid.

Brett P. Monia -- Chief Operating Officer Senior VP of Translational Medicine & Director

Thanks Stan and thanks Tyler. Well I mean the data that we're all focused on of course is the randomized Phase III study which is due to as Roche has said file in 2022 range or -- if not sooner. And that's what we're laser-focused on is that randomized pivotal study. Regarding the open-label data Roche has said that they will share the results of that study next year which will include open-label data from both the Phase II study that we conducted as well as the Phase III study -- the initial start of the Phase III study which involved about 100 patients which then the dosing regimen was changed. So there's a lot of data there plus the natural history data. As far as what to look for obviously in a randomized study you're looking for a significant improvement in clinical endpoints compared to the placebo group. That's obvious. And the rating scale for Huntington's is well documented and has been published. As far as the open-label data it's going to be looking for strong trends I would say. It's a small -- relatively small sample size relative to the Phase III randomized study and is going to be compared to natural history data. Both -- they're going to be looking for -- I assume Roche is going to be looking for many of the same benefits in clinical endpoints that are going to be part of the phase -- that are part of the Phase III study maybe just some subcomponents on that such as cognition or motor function or those sorts of things. But they're going to be looking for strong trends in clinical endpoints that differentiate from the ongoing natural history work that they're doing.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Just to add a comment or 2. I -- we remain based on what we're observing encouraged as does Roche about the ongoing open-label study. And I think we were very pleased that Roche made the decision to focus on the every four month dosing. We've always felt that that was the best dose schedule for this medicine. And so all in all we like the decisions that Roche has made and we're encouraged by the performance that we're seeing in the open-label study.

Tyler Martin Van Buren -- Piper Jaffray -- Analyst

Okay. And then on TEGSEDI we're seeing a slower trajectory in the launch relative to Onpattro. So just broadly could you maybe help us understand what's going on other than obviously you guys launched a quarter later? Are you guys maybe in different territories and receiving different uptake in different territories for example in Europe? Should Portugal come online as soon? And then also in the U.S. -- I noticed the slide actually did not list U.S. as a territory. So maybe are you guys seeing slower uptake in the U.S. which is a larger percentage of Onpattro sales?

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Yes. So we certainly are -- we're certainly considering the U.S. a very important market and if it's not on the slide it was an oversight sorry. We -- what we're looking at right now is not so much what happened last quarter but what's happening in the coming quarters. And we are optimistic with the new leadership at Akcea. We're seeing very significant shifts in momentum. I do think that we'll see growth accelerate a bit in the U.S. Obviously Brazil is a really important opportunity for us. We're very pleased with what's happened in Sweden the U.K. and Austria. And so these new markets are important. And of course Portugal is an important opportunity for us too. So TEGSEDI is a little behind of what we hoped. But based on the new team and the progress that we're seeing out of them I think we're optimistic that next year we'll see an even better performance. And hopefully in this next quarter we'll see an improvement.

Tyler Martin Van Buren -- Piper Jaffray -- Analyst

Okay, thanks so much.

Operator

Our next question will come from David Lebowitz with Morgan Stanley. Please go ahead.

David Neil Lebowitz -- Morgan Stanley -- Analyst

Would you be able to give us a run-through of the recent HBV data? And I guess talk about the reason that the non-LICA form of the drug is being pushed forward as opposed to the LICA form.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Yes. It's -- we don't have a full answer to that question. What we do believe is that HBV infection has an effect on the asialoglycoprotein receptors. So we didn't see the level of increased potency that we expected but we saw also great performance out of the parent. And so we agreed with the decision that GSK has made. And we're excited about what we're seeing with that drug. It's also a little farther along. So overall I think the performance of the parent was very exciting. I haven't seen those kinds of viral reductions in quite a while and it looks like a good drug. Brett do you want to add anything to that?

Brett P. Monia -- Chief Operating Officer Senior VP of Translational Medicine & Director

No I don't Stan. I think you got it. You covered it nicely.

David Neil Lebowitz -- Morgan Stanley -- Analyst

You covered it nicely.

Operator

Our next question will come from Vincent Chen with Bernstein. Please go ahead.

Vincent Chen -- Bernstein -- Analyst

Congratulations on the progress. I'm intrigued about the less frequently dosed SMA drug that you alluded to and how that might work. I have a bit of a geeky question about this one. Broadly what's the approach to this? I realize you probably won't say what the technology is but is it more a matter of increasing the half-life of the active fraction of drug? Is it increasing the dose? Is it increasing the amount of drug that enters the cell or that escapes the endosome? Is that increasing potency or something else to the extent you could provide some color? And could you readily apply this to other programs in the portfolio such as the Huntington's program? And what implications might this have for the therapeutic windows of this drug?

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

These are really solid questions. And we'll get into more detail on December 13 and I think you'll enjoy what we can tell you then much more than what I'm going to tell you now. We continue to invest obviously in all of those areas of medicinal chemistry. And remember that the neurological program is relatively newer compared to other programs and so we're still exploring novel additional chemistry approaches that we think can add some value there. We know that these drugs distribute very broadly in the central nervous system and we understand the factors that define how long they last. So it's just taking all of the knowledge that we have plus all that we've learned over 30 years and applying it. We will be talking about endosomal release. That gets very technical and complex and I don't think I want to get into it or try to explain it on this call. But that's another area of very very active progress for us. And improving delivery within the cell as well as improving delivery to the cell are all focal points for the -- of what we're doing in core antisense reserve. Did that help you? I hope.

Vincent Chen -- Bernstein -- Analyst

Yes. I look forward to the 13th.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Yes. We'll be talking at some length about all that.

Operator

Our next question will come from Ritu Baral with Cowen. Please go ahead.

Ritu Subhalaksmi Baral -- Cowen -- Analyst

I did want to follow up Stan on the new CNS programs that you mentioned. I believe you mentioned that there were 2 new programs with Biogen and then 1 wholly owned. Can you elaborate a little more? Were they some of the ones that Brett mentioned the prion disease etc? Would love to know what's in the pipeline and what sort of time lines we could be seeing for clinical data from the additional programs CNS programs.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Yes. So Brett will take that. But before we get into that I want to remind people of how exciting tofersen is. And we are -- based on all of the observations with that medicine we and Biogen are really excited about that drug and that is an important relatively near-term opportunity. And so with that addition I'll turn the question over to Brett.

Brett P. Monia -- Chief Operating Officer Senior VP of Translational Medicine & Director

Sure thing. Thanks Ritu. So we're continuing and we'll continue to add new exciting programs to the neuro pipeline with Biogen. The 2 recent programs that were entered into our development pipeline are targets that are undisclosed at this point Ritu. But the wholly owned program is our Lafora drug and we've talked about Lafora disease before which is a glycogen storage disease of the CNS. So we're very excited about that program. The prion drug you mentioned before is not a Biogen drug. It's a wholly owned program by -- from Ionis and we're expecting that to reach development shortly. And that really has a rather -- that's not an ultrarare disease. That's a disease with very significant populations to be treated. So yes more and more drugs are coming. We don't disclose them with Biogen right up front but our wholly owned pipeline for neuro continues to expand as well.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

And it's a little early Ritu to just give you even a general sense of when there's going to be clinical data. I think we'll hold off on that until next year when it would become much clearer.

Ritu Subhalaksmi Baral -- Cowen -- Analyst

Got it. And then the pulmonary programs that you're going talk a little bit more about on December 13 are those programs based on I guess new formulations like encapsulation or something involving enhancement agents like your oral program? Or are these sort of pure -- is it a pure potency play for delivery?

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

It's a pure potency play. You'll recall that we showed quite a many years ago that these agents are really very nice to deliver by aerosol. We took the IL-4 drug into clinical trials and and we demonstrated a broad distribution a meaningful pharmacology. We didn't feel it was in the end quite good enough to continue developing for asthma and that -- given all the other medicines are available but that blazed the trail. And so these are formulated very simply just in saline and they could be administered then by any of the devices that you know about. And so the key change is the increase in potency and we are seeing really remarkably exciting performance now in the lung. And like every organ that we work on before we really move drugs forward we invest in understanding the organ and how these drugs distribute not just into the organ but in the various cells in the organ. And so we know all that. And Brett will share some of that with you at the December 13 call.

Ritu Subhalaksmi Baral -- Cowen -- Analyst

Great. Congratulations on that oral poster at DIA. Everybody was at that poster to the exclusion of the open bar.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

We're excited. If you remember -- we'll remind you on the 13th that we already showed it was feasible with KYNAMRO. What we needed was just a big step up in potency and we think we got it. And you'll be hearing a lot more about that in the coming months not just from us.

Operator

Our next question will come from Jessica Fye with JPMorgan. Please go ahead.

David Neil Lebowitz -- Morgan Stanley -- Analyst

This is Daniel for Jessica Fye. In light of the platelet decline observed with the HBV LICA product can you make the case for why this is a product-specific issue versus a reason to worry about the other LICA products as well?

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

No I won't do that. I'll tell you it's not an issue at all. There's a lot of confusion about that. What actually happened was very minor declines in platelets that are not even -- not remotely clinically significant and it was just the way the data were presented. There really is no significant platelet issue even at doses of 480 milligrams a month with the LICA drugs. That's what those data actually show. Brett do you want to add anything to that?

Brett P. Monia -- Chief Operating Officer Senior VP of Translational Medicine & Director

Just to add to that those were -- as you said Stan those were very high doses and the drops in platelets were not clinically meaningful in any way. So really it has no bearing at all on our LICA platform. And again the confidence that has been demonstrated by the licensing of drugs like Factor XI-LRx and ANGPTL3-LRx and Lp(a)-LRx (sic) [APO(a)-LRx] by Novartis and Bayer and Pfizer just illustrates the confidence in our LICA platform from not just an efficacy but also safety and tolerability.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Even at 480 milligrams a month we did not have a single patient who got below normal level if I recall correctly in that study.

Brett P. Monia -- Chief Operating Officer Senior VP of Translational Medicine & Director

That's correct. That's correct Stan.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

So it was simply the way that it was presented that caused the confusion. We regret that but that's -- those are the facts.

David Neil Lebowitz -- Morgan Stanley -- Analyst

Great, thanks. Taking my question, guys.

Operator

Our next question will come from Mani Foroohar with SVB Leerink. Please go ahead.

Mani Foroohar -- SVB Leerink LLC Research Division -- Analyst

Congratulations on the results. First of all on behalf of your investors thank you for returning capital to shareholders rather than the reverse which seems to be the norm in my coverage.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

By the way we're not normal.

Mani Foroohar -- SVP Leerink -- Analyst

I have a couple of quick questions. First regarding the ENaC opportunity how do you guys think about the role of that in cystic fibrosis patients? Given there's a number of fairly effective oral therapies would that be developed as an add-on? Would it be developed in failures? And then I have one more question after.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Yes. One of the most interesting things about that is that it's directed -- directly at the cause of the disease. It's not a modulator. It's not a modifier. It improves the performance of that sodium channel and in fact reduces it. And so at least in -- based on animal data and early returns from the clinic we think we have a significant winner there not just for cystic fibrosis but other lung disorders. And what I like about it is it's a primary mechanistic approach to managing the disease that's accessible to antisense and really very fairly difficult to do with other technologies because of their lack of specificity. Brett do you want to add anything?

Brett P. Monia -- Chief Operating Officer Senior VP of Translational Medicine & Director

Yes. Just -- maybe I'll just add this. Mani the ENaC mechanism should do all of what you said. It should be useful for patients that progress on small-molecule CFTR inhibitors or activators. It should be effective for -- as add-on therapy and as well as those that have mutations that are not treatable. So the 10% 15% of patients that are not treatable with the combo small molecules for CFTR are going to be treatable with ENaC because of its mechanism of action. And as Stan mentioned cystic fibrosis is -- we think is just one indication. We think that this drug has the potential to treat a much broader population as well or patients with different types of pulmonary diseases.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Yes. I would add one more comment. We as a general rule want to lead as we had with SPINRAZA APO(a) APOCIII all of -- Factor XI and so on. So for us to pursue an opportunity in cystic fibrosis we really had to be very convinced that we had something that could do something very substantial these patients could use and we believe that. And we believe that the mechanism can provide benefit in a number of other important pulmonary diseases. And so this is for us a much more important investment than simply cystic fibrosis which is important but it's a broader investment.

Mani Foroohar -- SVB Leerink LLC Research Division -- Analyst

Okay. And for my follow-up when I look at the TTR-LRX study correct me if I'm wrong but it sounds like you guys are allowing essentially unlimited tafamidis use in both arms? Tafamidis obviously is an active drug in cardiomyopathy with an overall survival benefit. How do you think about maintaining balanced drop-ins since presumably you'll have efficacy and the placebo patients will do worse so you may have more tafamidis drop-in in the placebo arm? Like how do you expect to maintain balance? And how do you think about the impact on powering assumptions for the scale of the study as a whole?

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Brett?

Brett P. Monia -- Chief Operating Officer Senior VP of Translational Medicine & Director

Yes. Sure Mani. So as -- you're referring to the cardiomyopathy study obviously and we're allowing patients to have standard of care in the control group or -- on top of TTR LICA. And we'll -- and we will stratify appropriately so that we're not imbalanced for patients on tafamidis patients on any other forms of standard of care that they wish to take. So we can control for that. And our powering assumptions are based on the wealth of data that's out there from the Pfizer tafamidis Phase III study as well as our own study with TEGSEDI in same -- in similar patient populations. The other thing I wanted to -- maybe I can just add to that Mani is just to draw your attention and remind you that we have an investigator study Phase II study in progress in which we're looking at TEGSEDI in patients with cardiomyopathy both wild type and hereditary. That's with Dr. Merrill Benson in Indiana University and we just -- he just presented an update on patients that have been treated for three years or longer with TEGSEDI in which he has shown strong evidence for patient benefit on all kinds of clinical end points compared to natural history. So we also have that data to fall back on the natural history and the performance of TEGSEDI in patients with cardiomyopathy. So we feel very confident in the powering assumptions of our Phase III cardiomyopathy study and we -- we are confident that will be well balanced in our treatment arm versus our control group.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

And things are getting ready to get under way in a big way here. So yes we will -- you should be hearing from us about all that in the very near future.

Brett P. Monia -- Chief Operating Officer Senior VP of Translational Medicine & Director

Great, thanks.

Operator

Our next question will come from Paul Matteis was Stifel. Please go ahead.

Nathaniel Tower -- Stifel Nicolaus & Company -- Analyst

This is Nate on for Paul. Maybe just to put a finer point on the prior question about ENaC. On the clinical studies would you think of enrolling all CF patients? Or would you narrow it down to patients who aren't currently eligible for CFTR modulator?

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

I don't think we want to get into details of the clinical development program beyond what Brett said. We think it's an agent that can be used as a single agent and we think it can be used in combination. And we believe it can be used in patients who have mutations that are unresponsive to current therapy. I'll leave it there.

Nathaniel Tower -- Stifel Nicolaus & Company -- Analyst

Got you. That makes sense. Then could you just discuss the inhaled dosing route given the pulmonary mucus burden? I mean I know it translates on it but is that a crazy concern? Or is that something you guys have looked at so far?

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

No it's not a crazy concern at all. It's something we looked at very carefully. We had the benefit of having clinical experience with IL-4 in meaningful asthmatic patients. And then we looked very very carefully in animals and asked "Does a significant mucus barrier affect distribution to the bronchioles and to the layer -- the smaller airways?" And the answer was no. And based on the early returns in the clinic we believe the humans are telling us no as well. So absolutely something that we were concerned about but we think we've resolved it. And I think that Brett will be sharing some of that with you on December 13. Is that right Brett?

Brett P. Monia -- Chief Operating Officer Senior VP of Translational Medicine & Director

Yes. There's correct Stan.

Nathaniel Tower -- Stifel Nicolaus & Company -- Analyst

Got you. And then maybe one more on HBV. Message understood loud and clear on the platelet declines but can you help us understand why GSK was dosing at 120 mg per week in the first place?

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Yes. Because we didn't see the sort of -- that is the only time -- we've got now 13 14 LICA -- liver LICA drugs in development. That is the only example where we didn't see the expected level of increase in potency and we know it's tied in some fashion to the HBV infection. But beyond that it's still very much a research project throughout what happened. But that's the reason. We just didn't get the level of potency that we have seen with the other 12 or 13 liver LICAs.

Nathaniel Tower -- Stifel Nicolaus & Company -- Analyst

Gotcha. Interesting. Thanks for the call.

Operator

Our next question will come from Ellie Merle with Cantor Fitzgerald. Please go ahead.

Eliana Rachel Merle -- Cantor Fitzgerald -- Analyst

Just in terms of the Factor B program could you explain a little bit more of your scientific rationale or I guess your decision to target Factor B versus D and I guess your perspective on the clinical advantage or key differences between the targets? And I guess given that your partner Roche has already studied programs looking at Factor D and geographic atrophy with somewhat sort of mixed results maybe you can comment on your thoughts on Factor B versus D specifically in geographic atrophy.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Well I will comment that we typically -- when we're in one of these pathways like clotting factors and complement and so on look at everything. It's easy for us to do. And so we look at all of the various factors. And based on all the data we had we believe that Factor B offers a significant advantage potentially in benefit and safety compared to some of the other complement factors. So it's based on data. Brett do you want to add anything to that?

Brett P. Monia -- Chief Operating Officer Senior VP of Translational Medicine & Director

Yes just a little bit. It's just -- it's certainly based on the data we've generated directly looking at different complement factors in our animal models but also where Factor B lies in the alternative complement pathway. It's -- I don't want to get into the fine details but it's a more relevant target to that pathway than Factor D. And of course what's really really interesting and important to remember is that Roche developed the Factor D antibody and they came to the conclusion that Factor B was a better target which is why they've partnered with us on this program for age-related macular degeneration. So it's based on our data as Stan said. It's based on what we would expect in the pathway the complement pathway. And we're not the only ones that believe in Factor B Roche does too.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

And the study is progressing well. So we're going to have some answers and it's going to be a while. But the study certainly is progressing. Wade how many more questions? I think we should probably bring this to a close.

D. Wade Walke -- Vice President of Investor Relations

That is the last one Stan.

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Okay. Well that's great. Well thanks everyone. We appreciate your attention on this busy day. And we look forward to continuing to deliver great results this year -- the rest of this year and next year and look forward to sharing some of the nuts and bolts the pixels behind the big picture with you on December 13 as we focus on the technology and the advances that we're making.

Operator

[Operator Closing Remarks].

Duration: 66 minutes

Call participants:

D. Wade Walke -- Vice President of Investor Relations

Stanley T. Crooke -- Founder, Chairman, Chief Executive Officer and President

Elizabeth L. Hougen -- Senior Vice President, Finance and Chief Financial Officer

Brett P. Monia -- Chief Operating Officer Senior VP of Translational Medicine & Director

Chad Jason Messer -- Needham & Company -- Analyst

James William Birchenough -- Wells Fargo Securities LLC Research Division -- Analyst

Tyler Martin Van Buren -- Piper Jaffray -- Analyst

David Neil Lebowitz -- Morgan Stanley -- Analyst

Vincent Chen -- Bernstein -- Analyst

Ritu Subhalaksmi Baral -- Cowen -- Analyst

Mani Foroohar -- SVB Leerink LLC Research Division -- Analyst

Mani Foroohar -- SVP Leerink -- Analyst

Nathaniel Tower -- Stifel Nicolaus & Company -- Analyst

Eliana Rachel Merle -- Cantor Fitzgerald -- Analyst

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