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Edited Transcript of IONS earnings conference call or presentation 26-Feb-20 4:30pm GMT

Q4 2019 Ionis Pharmaceuticals Inc Earnings Call

Carlsbad Mar 11, 2020 (Thomson StreetEvents) -- Edited Transcript of Ionis Pharmaceuticals Inc earnings conference call or presentation Wednesday, February 26, 2020 at 4:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Brett P. Monia

Ionis Pharmaceuticals, Inc. - Founder, CEO & Director

* D. Wade Walke

Ionis Pharmaceuticals, Inc. - VP of IR

* Elizabeth L. Hougen

Ionis Pharmaceuticals, Inc. - Senior VP of Finance & CFO

* Eric E. Swayze

Ionis Pharmaceuticals, Inc. - SVP of Research

* Onaiza Cadoret-Manier

Ionis Pharmaceuticals, Inc. - Chief Corporate Development & Commercial Officer

* Richard S. Geary

Ionis Pharmaceuticals, Inc. - SVP of Development

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Conference Call Participants

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* Chad Jason Messer

Needham & Company, LLC, Research Division - Senior Analyst

* Eliana Rachel Merle

Cantor Fitzgerald & Co., Research Division - Research Analyst

* Esther P. Rajavelu

Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst

* Huidong Wang

Barclays Bank PLC, Research Division - Research Analyst

* I-Eh Jen

Laidlaw & Company (UK) Ltd., Research Division - MD of Healthcare Research & Senior Biotechnology Analyst

* James William Birchenough

Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst

* Jason Matthew Gerberry

BofA Merrill Lynch, Research Division - MD in US Equity Research

* Jessica Macomber Fye

JP Morgan Chase & Co, Research Division - Analyst

* Nathaniel Tower

Stifel, Nicolaus & Company, Incorporated, Research Division - Associate

* Rick Stephen Bienkowski

SVB Leerink LLC, Research Division - Associate

* Tyler Martin Van Buren

Piper Sandler & Co., Research Division - Principal & Senior Biotech Analyst

* Vincent Chen

Sanford C. Bernstein & Co., LLC., Research Division - VP

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Presentation

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Operator [1]

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Good day, and welcome to the Ionis Pharmaceuticals Q4 and Full Year 2019 Financial Results Conference Call. (Operator Instructions) Please note, this event is being recorded.

I would now like to turn the conference over to Wade Walke, Vice President, Investor Relations. Please go ahead.

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D. Wade Walke, Ionis Pharmaceuticals, Inc. - VP of IR [2]

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Thank you, Sara. 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 on the call. We believe non-GAAP financial results better represent the economics of our business and how we manage our business. We've also posted slides on our website that accompany our discussion today.

With me on today's call are Brett Monia, Chief Executive Officer; Onaiza Cadoret, Chief Corporate Development and Commercial Officer; Beth Hougen, our Chief Financial Officer; and Richard Geary, Senior Vice President of Development. Additionally, Eric Swayze, Senior Vice President of Research, will join us for Q&A.

I would now like to draw your attention to Slide 3 of the slides that we have for today's call, which contain our forward-looking language statement. We'll be making forward-looking statements, which are based on current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail.

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

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [3]

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Thanks, Wade, and good morning, everybody, and thanks for joining us on today's call. I'm very excited to be speaking to you today in my new role as Ionis' CEO. In 30 years, Ionis has achieved enormous success by delivering on our commitment to help patients with the greatest unmet medical needs. Today, we're building upon that success. In fact, I believe that today, we have the resources and people to make Ionis among the most innovative, productive and highest achieving companies in our industry.

So now to recap last year's achievements. 2019 was an exceptional year. From a financial perspective, as Beth will discuss shortly, 2019 was especially strong. SPINRAZA's blockbuster performance continued and Biogen expects growth again this year. And the commercial launches of TEGSEDI and WAYLIVRA progressed with plans in place to expand to new markets soon.

Together with exceptionally strong R&D revenue, we delivered over $1 billion in revenue, over $400 million in net income and ended the year with $2.5 billion in cash, outperforming even our improved 2019 financial guidance. Importantly, we achieved these exceptional financial results while investing in all areas of the business that we believe have the greatest potential for value creation. And already this year, we're building upon this momentum to achieve even more success.

As Richard will discuss, in 2019, we achieved strategic successes broadly across our pipeline, including in our neurological and cardiometabolic disease franchises. We achieved our primary goal of advancing 4 medicines into Phase III studies. We achieved positive clinical proof-of-concept results for 5 medicines. We advanced 5 new medicines into Phase I, and we advanced 10 new medicines into development, 6 of which are Ionis owned. Also last year, we continued to advance and broaden the scope of our technology.

In addition to moving 2 of our LICA programs into Phase III studies, we demonstrated clinical proof-of-concept for 4 new LICA medicines for indications that represent both broad and rare patient populations, further supporting the potential to expand our technology beyond rare diseases, and we advanced 2 new LICAs into development, growing our LICA pipeline to 16 medicines overall.

Additionally, we initiated clinical proof-of-concept studies to evaluate our progress in optimizing oral and aerosol delivery, with initial results expected later this year. And of course, with positive results from these studies, our technology could benefit greatly by expanding the scope of our drug discovery platform substantially.

Today, Ionis is stronger than ever. Our pipeline of over 40 medicines is broad, deep, mature and growing with multiple programs nearing key value inflection points. And this year, we are prioritizing areas of the business that we believe have the greatest potential to create value, short term and long term, for patients and shareholders. For example, we're advancing our technology by identifying new LICAs, and further optimizing additional routes of drug administration to enhance the overall profile of our antisense platform. And we're identifying novel drug targets to continue replenishing our pipeline with innovative medicines as later-stage programs reach commercialization.

By the end of this year, we also plan to have 6 Phase III studies underway, report clinical proof-of-concept results for 6 or more medicines, with 2 already achieved this year. Initiate 10 or more new Phase II studies and advance at least 5 new medicines into development, including several new and exciting Ionis-owned medicines. Together, these achievements position us well to reach our goal of 10 or more new drug applications through 2025.

Additionally, this year, we're prioritizing the growth and advancement of our Ionis-owned pipeline while further developing our commercial strategies and capabilities to ensure we maximize the value of each of our medicines. As part of this initiative, we recently appointed Onaiza Cadoret to the Ionis leadership team as our Chief Corporate Development and Commercialization Officer. We're thrilled to have Onaiza on the team with extensive experience in building and executing on corporate business and commercial strategy. Her leadership will be invaluable as our pipeline advances forward.

In a moment, Beth will review our 2019 financial results and 2020 guidance, and Richard will recap our latest pipeline achievements and planned 2020 catalysts, and I'll close out the call and moderate some questions.

So now I'll turn the call over to Onaiza, who'll provide some additional insight into her new role at Ionis.

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Onaiza Cadoret-Manier, Ionis Pharmaceuticals, Inc. - Chief Corporate Development & Commercial Officer [4]

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Thank you, Brett, and good morning, everyone. I'm quite excited to join Ionis at this transformative time for the company. As Brett said, we are in a unique position of strength. We have an expansive, deep and advancing pipeline with a growing number of late-stage medicines. Our technology is broadly applicable, enabling us to bring novel medicines to patients. And most importantly, we have a strong experienced team who operate with scientific rigor and innovative mindset and are very committed to delivering transformational medicines to patients with severe unmet needs.

I am excited to assume leadership of the company's corporate development and commercial efforts. Our goal to maximize the value of each medicine in our pipeline remains unchanged. Looking ahead, we plan to pursue this goal by identifying the optimal commercial strategy, pathway and organization for each of our medicines, while preserving our established culture of scientific innovation.

We plan to develop our commercial capabilities, allowing us to bring medicines from our growing Ionis-owned pipeline to patients. In parallel, we will continue to establish strategic partnerships, develop and commercialize those medicines with the potential to address diseases with the largest patient population, such as our most recent collaboration with Pfizer for AKCEA angiopoietin-like 3 LICA.

We also look forward to continuing to support Akcea as they pursue their strategic goals and through the potential addition of a new Ionis medicine to the Akcea pipeline later this year. I look forward to updating you on our commercial strategy as our work evolves throughout the year.

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

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Elizabeth L. Hougen, Ionis Pharmaceuticals, Inc. - Senior VP of Finance & CFO [5]

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Thank you, Onaiza. 2019 was an exceptional year, including financially. We significantly exceeded our 2019 financial guidance, driven by revenue of more than $1.1 billion, nearly double compared to 2018.

We earned over $350 million in commercial revenue and over $770 million in R&D revenue, including nearly $400 million for licensing AKCEA-APO(a)-LRx and AKCEA-ANGPTL3-LRx. Our revenues resulted in substantial non-GAAP operating income and net income of over $510 million and over $400 million, respectively. We also achieved substantial operating income and net income on a GAAP basis.

We achieved these exceptional results while further strengthening our balance sheet. We increased our cash balance to $2.5 billion, and we refinanced a significant portion of our convertible debt, which enabled us to extend the maturity for most of our debt to 2024, achieve a 0.125% interest rate, which reduced our annual cash interest expense by approximately 40% and significantly increase our effective conversion price which may reduce future dilution.

Over the last several months, we also returned value to shareholders by repurchasing 2 million shares of our common stock through a stock repurchase program we implemented late last year. The refinancing of our debt and our share repurchase program underscores the confidence we have in the future of the company and our commitment to creating near and longer-term value for shareholders. And because of our significant financial resources, we were able to execute these transactions while continuing to invest aggressively across our business.

Now turning to our commercial revenue. SPINRAZA generated over $2 billion in worldwide net sales in 2019, resulting in nearly $300 million in royalty revenue to Ionis, an increase of more than 20% compared to 2018. At the end of last year, there were more than 10,000 patients on SPINRAZA treatment worldwide. Biogen achieved this important milestone through growth from adult SMA patients in the U.S. and growth from both existing and newly launched markets outside the U.S. with approximately 45,000 addressable patients in markets where Biogen has a direct presence, we invite and see significant opportunity for growth.

We achieved steady quarter-over-quarter growth throughout 2019, resulting in product sales from TEGSEDI and WAYLIVRA of $42 million for the year. Today, TEGSEDI is commercially available in more than 10 countries.

In the U.S., we achieved growth in new prescribing physicians and patient starts. And of particular note, in the fourth quarter, we saw a 42% increase in new prescribing physicians. We continue to see a mix of cardiologists, neurologists and hematologists in both the academic and community settings.

Additionally, Akcea's market access efforts have continued to translate into broad TEGSEDI coverage for patients in the U.S., for not only today, but also longer term. Outside the U.S., Akcea is focused on reimbursement as they prepare to expand into additional countries this year. In Latin America, PTC Therapeutics is launching TEGSEDI in Brazil, and is working to provide access to TEGSEDI in additional Latin American countries.

WAYLIVRA is now on the market in Germany with FCS patients benefiting from the only medicine approved for the treatment of this devastating disease.

In France, Akcea is enrolling patients in an ATU, a reimbursed early access program. Additionally, Akcea plans to launch in new EU countries this year. And PTC Therapeutics is working to provide access to WAYLIVRA across Latin America, beginning in Brazil this year, assuming approval. In the U.S., we are continuing to work with the FDA with the goal of refiling this year. Through Akcea's efforts, we have a strong foundation for both commercial products that we believe can support expansion into new markets this year.

Our 2019 R&D revenue more than doubled to $770 million, with significant increases in license fees, milestone payments and amortization from upfront payments. This growth demonstrates the substantial value of our pipeline and technology. Our R&D revenue consisted primarily of $490 million in license fee revenue, including nearly $400 million from licensing AKCEA-ANGPTL3-LRx and AKCEA-APO(a)-LRx and $115 million in milestone payments, including nearly $85 million for advancing numerous medicines within our neurological disease franchise, including IONIS-HTTrx, IONIS-MAPTRx and several new programs under our Biogen collaboration.

We also recognized nearly $25 million for advancing several programs from our cardiometabolic franchise, including our Factor XI program with Bayer and our medicine for patients with NASH with AstraZeneca.

Our 2019 non-GAAP operating expenses increased to $610 million compared to 2018, driven by investments in our pipeline and technology, consistent with our stated objectives. We also made strategic investments in technologies we believe can expand the reach of our antisense technology and in developing our commercial capabilities.

We continue to be in an enviable position of financial strength. This year, we expect to be meaningfully profitable while continuing to invest aggressively in our strategic priorities. The ability to earn revenue from multiple sources is a key element of our financial strength. We expect growth in commercial revenues, driven by continued strong SPINRAZA performance and growing revenue from TEGSEDI and WAYLIVRA as we expand into new countries. We also expect to achieve important milestones as we advance our medicines in development.

With these multiple sources of revenue, we project earning more than $700 million in revenue this year. We are projecting 2020 non-GAAP operating expenses of $650 million to $690 million. The increase in our projected operating expenses compared to last year is attributable to investments we are making in our Ionis-owned pipeline. These investments include conducting the ongoing Phase III program for AKCEA-TTR-LICA-LRx, and initiating a Phase III study of AKCEA-APOCIII-LRx in FCS patients this year. We also expect to advance our midstage pipeline. Together, these investments support our goal of 10 or more NDAs through 2025.

We built the commercial infrastructure necessary to support TEGSEDI's expansion into new countries ahead of those launches. Because of that, we have the necessary team in place to expand TEGSEDI in the U.S. and outside the U.S. This means we do not need to increase our SG&A expenses to support TEGSEDI's commercial growth. Additionally, we anticipate realizing valuable synergies between TEGSEDI and WAYLIVRA as we launch both medicines in additional countries throughout the year. For these reasons, we are projecting to keep SG&A expenses comparable to our 2019 level, while growing TEGSEDI and WAYLIVRA revenues.

With $2.5 billion in cash at the end of 2019, we have the financial strength to fully execute on our strategic priorities.

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

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Richard S. Geary, Ionis Pharmaceuticals, Inc. - SVP of Development [6]

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Thank you, Beth. As Beth mentioned, 2019 was a year full of important achievements. We made significant progress with our rapidly growing neurological disease franchise. For example IONIS-HTTRx for people with Huntington's disease and tofersen for people with SOD1-ALS entered Phase III studies last year and are progressing on schedule. We recently completed enrollment in our Phase II proof-of-concept study of IONIS-MAPTRx in patients with early Alzheimer's disease several months ahead of schedule.

Biogen has expressed their enthusiasm for this program as an important part of their already robust Alzheimer's disease pipeline. And in fact, late last year, Biogen licensed IONIS-MAPTRx significantly earlier than anticipated, supported by encouraging blinded interim data from the ongoing study.

Additionally, Biogen recently initiated a study of our medicine targeting LRRK2 most common genetic cause of Parkinson's disease. This is an exciting study which includes patients with both familial Parkinson's associated with LRRK2 mutations as well as patients with the sporadic form of the disease. Together, these populations represent over 3 million patients worldwide.

Also, earlier this year, we and Biogen advanced our program for the treatment of Angelman syndrome into development. We are particularly excited with the progress we are making with our pipeline of Ionis-owned medicines addressing neurological diseases. Patient enrollment is now underway in our Phase III NEURO-TTR transform study of AKCEA-TTR-LRx in patients with hereditary TTR amyloid polyneuropathy.

Our Ionis-owned medicine for the treatment of Alexander disease was recently granted orphan drug status by the EMA, recognizing the significant need for therapeutic options for patients with this devastating and fatal genetic disease. We also added several additional Ionis-owned neurological disease medicines into development last year, including treatments for Lafora and prion disease.

Turning to the recent advancements in our cardiometabolic franchise. Enrollment is now underway in the HORIZON Phase III cardiovascular outcome study for AKCEA-APO(a)-LRx in patients with established cardiovascular disease and elevated Lp(a). We're pleased with how rapidly Novartis advanced AKCEA-APO(a)-LRx into Phase III development. And importantly, this medicine is 1 of our 4 medicines to advance into Phase III last year, helping us to achieve one of our key corporate objectives.

At the beginning of this year, we initiated our Phase III CARDIO-T transform outcome study of AKCEA-TTR-LRx in patients with wild-type and hereditary forms of TTR cardiomyopathy. We also reported positive top line results from Phase II proof-of-concept studies for AKCEA-APOCIII-LRx and AKCEA-ANGPTL3-LRx. Both medicines achieved their primary endpoint, demonstrating robust triglyceride lowering and substantial reductions in additional key cardiovascular risk factors with favorable safety and tolerability profiles.

Think it's worth noting that our cardiometabolic pipeline includes 11 LICAs to date, and we now have data from over 1,100 people treated with LICA medicines to date, including a substantial number of patients treated with LICAs for 1 year. With 16 LICAs now in development in multiple therapeutic areas, including 2 in Phase III outcome studies, we have substantial evidence that our LICA technology characterized by greatly increasing potency and improved dosing regimens represents a real-game changer for our technology.

Finally, we advanced several Ionis-owned rare disease medicines into Phase II development last year, including Ionis-GHR-LRx for the treatment of acromegaly, IONIS-PKK-LRx for the treatment of hereditary angioedema and IONIS-ENAC-2.5Rx, our aerosol-delivered medicine for cystic fibrosis and potentially additional pulmonary diseases. All of these programs are on track to report results later this year.

So as you can see, we expect numerous catalysts throughout this year. We expect to have 6 Phase III studies in progress, including a planned Phase III study of AKCEA-APOCIII-LRx in patients with FCS. We expect to report clinical proof-of-concept studies for oral delivery of one of our antisense medicines in cardiovascular disease, and we expect results from multiple Phase II studies.

We also plan to advance numerous new programs into mid- and early-stage clinical development and to add many new Ionis-owned and partner programs into our pipeline. These catalysts, together with our broadening and advancing technology, position us well, [as I have said], to achieve our goal of 10 or more marketing applications through 2025. We will continue to keep you updated on the many pipeline catalysts we expect this year as our medicines continue to advance in development.

And with that, I'll turn the call back over to Brett to close this portion of the call.

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [7]

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Thanks, Richard. Before we end today, I'd like to remind everyone that this Saturday, February 29, is Rare Disease Day. And in recognition of this important day, please join me in thanking the patients, families and advocates who have been our partners in developing medicines to transform the lives of patients in need. I'd like to invite everyone to follow Ionis on Twitter and LinkedIn to learn more about how Ionis is raising awareness for the millions of people worldwide living with a broad range of diseases, including thousands of identified rare diseases, most without adequate treatment options.

Today, we're at a unique place in the history of Ionis. Our pipeline is broader and more mature than ever before with numerous programs nearing key value inflection points. This year, we plan to use our financial strength to invest aggressively in all areas that have the greatest potential to create value for patients and shareholders, including growing and advancing our Ionis-owned pipeline, further developing our commercial strategies and capabilities to ensure we maximize the value of each of our medicines, expanding the reach of our technology by, for example, optimizing different routes of drug administration and discovering new LICA strategies, and identifying and increasing investments in complementary technologies that will also expand the reach of our antisense platform.

And with that, I'd like to now open the call for Q&A.

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question comes from Jason Gerberry with Bank of America.

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Jason Matthew Gerberry, BofA Merrill Lynch, Research Division - MD in US Equity Research [2]

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So I guess just on ANGPTL3, I was hoping, have you guys had a chance to discuss the recent data with Pfizer? Any commentary that you can provide on that program and how you're thinking about the profile, relative to some recent interim data from Arrowhead?

Second question is just on Huntington's ahead of tomorrow, some extension data from the earlier study. If you can set the table for what we could expect and the importance of those updates just in terms of understanding the broader safety profile of HTT ASO.

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [3]

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Sure. Jason, thanks for the question. So starting with angiopoietin-like 3, as you know, we've partnered that program prior to the unblinding of the Phase II data last year, and we and Pfizer were thrilled with the outcome, the Phase II results in that study. We achieved our primary endpoints with very high statistical significance, a number of secondary endpoints positioning this drug very well for later-stage development.

And certainly, Ionis and Akcea and Pfizer have gone through the data or continuing to go through the data in quite extensive detail and forging the path forward -- next steps for this medicine to later-stage development. And we plan on sharing this data in detail in the second half of this year at a medical meeting to be determined. But short to say, we're very excited as is Pfizer and Akcea about Phase II results. We view them as being quite -- very, very positive.

I don't really like to comment on other people's programs. I'm not very close to those programs. I focus more on -- exclusively really on Ionis programs. But we like our medicine, and we believe we have the first and best-in-class medicine for targeting angiopoietin-like 3.

As far as Huntington's, the Huntington's program remains on track. It is, of course, targeting the root cause of Huntington's disease. The Phase III program is on track to deliver results in 2022 on schedule. And that's the basic message from the CHDI presentation that you'll hear about tomorrow. There's a lot of other presentations at the meeting, too. But quite simply, the message is that we have the premier program for targeting -- potentially targeting Huntington -- for targeting Huntington's disease that will potentially bring this medicine to patients in the near future. Roche is very excited about the program, and the message is that the Phase III study remains on track.

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Operator [4]

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Our next question comes from Jim Birchenough with Wells Fargo.

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James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [5]

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Congrats on all the progress and the broadening pipeline. Couple of questions. I guess, just on capital allocation, with $2.5 billion in cash, could you talk about your priorities for capital allocation and whether we should expect additional share repurchases?

Also wanted to just touch on, if you could, the revenue guidance for greater than $700 million, which is below the $1.1 billion from last year. But I guess, if we back out the $4 million onetime payments, it's suggesting growth beyond that. So if you can comment on that.

And I guess, the final bit is with the coronavirus, just wondering if you could comment on your exposure for your supply chain to Asia? What kind of cushion you have, if there is any exposure?

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Elizabeth L. Hougen, Ionis Pharmaceuticals, Inc. - Senior VP of Finance & CFO [6]

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Jim, it's Beth. Thank you for your questions. I'll start off with capital allocation. And as Brett has laid out, our priorities are to continue to invest aggressively across the business to focus on our Ionis-owned pipeline, to advance our technology, to invest in complementary technologies, to broaden the reach of our technology. And with the addition of Onaiza on our leadership team, we are now defining further our commercialization strategy and building capabilities. And so that will also be an area of investment for the company. So I see, first and foremost, our investments and our capital being allocated to those areas of significant value creation for the company.

In terms of share repurchase, certainly, with our stock where it is today, we believe it's a very attractive investment opportunity. And so that's something we'll be considering into the future. And we have a portion of our 1% notes that are coming due in about 1.5 years or so. And then we'll be looking at what the appropriate actions are for addressing those notes as we go forward.

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [7]

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Thanks, Beth. And with respect to coronavirus, Jim, at Ionis, we take great pride in preparing for a potential crisis before they ever happen, and we've been focused on this potential pan epidemic and talking about how we're going to protect our employees, our clinical trials, as well as our supply chain, and we don't see any hiccups along the way. I'll ask Richard to comment on how we manage our supply chain with respect to the question.

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Richard S. Geary, Ionis Pharmaceuticals, Inc. - SVP of Development [8]

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Yes. Specifically on supply chain, of course, all of our API, we're not dependent on China for supply, which may be one of the questions. Certainly, all of our clinical supplies are manufactured right here. And then the drug supply chains that supply our drugs are also not only multiple pack-up opportunities, but also not dependent on China.

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [9]

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So we're in good shape.

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Operator [10]

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Our next question comes from Esther Rajavelu with Oppenheimer.

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Esther P. Rajavelu, Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst [11]

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Just a couple quick ones for me. How much of your 2020 guidance is driven by SPINRAZA versus other sources? And then I have a quick follow-up.

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Elizabeth L. Hougen, Ionis Pharmaceuticals, Inc. - Senior VP of Finance & CFO [12]

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Esther, it's Beth. So as you can imagine, SPINRAZA was a significant portion of our commercial revenues in 2019, and we [invite] and continue to see growth for SPINRAZA, frankly, in the U.S. and outside the United States. So I would expect to continue to see SPINRAZA being a significant portion of our commercial revenues as the year unfolds.

And then adding to that, of course, we have TEGSEDI and WAYLIVRA as they expand into new countries in Europe, in particular. And then we have a very substantial base of R&D revenues anchored by significant amortization of upfront and milestone payments and then built on by -- with licensing fees and milestone payments as our partnered programs in development continued to advance.

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Esther P. Rajavelu, Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst [13]

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Got you. And for WAYLIVRA, the resubmission of the marketing authorization in the U.S., what are -- what do you have -- what do you need to complete to be able to refile this year?

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Richard S. Geary, Ionis Pharmaceuticals, Inc. - SVP of Development [14]

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Yes. Great question. This is Richard. Nothing to complete except writing up the results. So all of the expanded studies in open label as well as expanded access are being added to the filing, and bring us to about a threefold increase in exposure in patients and as well as additional safety data, which is very supportive.

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Esther P. Rajavelu, Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst [15]

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So that's -- we should expect that to happen sooner than later in the year then, based on what you're saying?

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Richard S. Geary, Ionis Pharmaceuticals, Inc. - SVP of Development [16]

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I think we're guiding to a timing, but certainly, we are expecting to file this year.

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Operator [17]

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Our next question comes from Paul Matteis with Stifel.

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Nathaniel Tower, Stifel, Nicolaus & Company, Incorporated, Research Division - Associate [18]

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This is Nate on for Paul. Firstly, for the LRRK2 Phase I/II, can you review the study structure? And specifically, beyond safety and PK/PD, are you -- or what exploratory markers of efficacy are you collecting? And then I have a follow-up.

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [19]

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Eric, we haven't disclosed much on the details of the LRRK2...

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Richard S. Geary, Ionis Pharmaceuticals, Inc. - SVP of Development [20]

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I don't believe we've disclosed things beyond that we're treating both genetic patients with LRRK2 mutations as well as the general population.

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [21]

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It's correct.

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Richard S. Geary, Ionis Pharmaceuticals, Inc. - SVP of Development [22]

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And of course, it's a first in-human study. So the primary endpoint is safety, but you can imagine there's lots of secondary biomarkers and exploratory end points that we'll look at. Yes.

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [23]

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More will come out on that study as the program matures.

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Nathaniel Tower, Stifel, Nicolaus & Company, Incorporated, Research Division - Associate [24]

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All right. Got you. Well, maybe a second pipeline question. On the C9ORF program, are we thinking about this in the right way that's primarily going to be addressing the gain of function aspects? And if that's correct, are you worried at all about the loss of function aspects of C9ORF?

And secondly, would you consider moving from ALS into C9ORF FTD as well?

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Richard S. Geary, Ionis Pharmaceuticals, Inc. - SVP of Development [25]

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So yes, good questions, both. Yes, you are thinking about it correctly that we are addressing predominantly the gain of function aspects of the C9ORF72 gene, which is causal for C9ORF72-ALS and FTD. An important thing about our drug is it is targeted such that it only decreases the mutant form of C9ORF72 by the location in which we target the gene. So we don't expect to decrease all C9ORF72 function, if, in fact, there was an important component of that to safety or disease.

However, I would emphasize that much of the preclinical data really suggests that it is a gain of function disease pathogenesis process. So I think that medicine is another one that's like many of ours that's directly on target and on mechanism. And as you point out, C9ORF72 is also implicated in FTD. And with Biogen, we're actively considering how to move that drug forward in both ALS and FTD.

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [26]

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Yes, and I'll just expand on that a little bit, Nate, by reminding you and others how we're attacking ALS with Biogen. Our SOD1 program, of course, is in Phase III for another genetic form of ALS -- SOD1-related ALS in addition to C9ORF as a second one. And recently, we added a third medicine into the Ionis Biogen pipeline for sporadic forms of ALS, and much broader nongenetic forms of ALS. So we're doing a full-court press on all forms of ALS, and I think there will even be more coming.

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Operator [27]

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Our next question comes from Chad Messer with Needham & Company.

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Chad Jason Messer, Needham & Company, LLC, Research Division - Senior Analyst [28]

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Great. Maybe if you can just start with the TTR Phase III program now that you've got those 2 studies up and running. Can you maybe set some expectations for enrollment timing? You guys have some experience enrolling -- rolling trials in the space? And is it your sense that it's easier or harder to enroll now that there are commercially available options for these patients?

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [29]

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Appreciate the question, Chad. Thank you. Yes, we're very excited, Ionis with Akcea, we're now underway in 2 Phase III studies for both the cardiomyopathy, the larger population, which includes of course, hereditary and wild-type and the polyneuropathy patient population, separate Phase III, where we're targeting essentially the same label as TEGSEDI.

As far as expectations go, we're looking for these studies to complete in the 2022, 2023 time frame and enrollment is actively underway for both studies and is going well. As for challenges related to enrollment and how competition, particularly stabilizers, may impact that, we actually believe that our trial design for cardiomyopathy offers many advantages for patient enrollment. The fact that we allow patients to take standard of care, which of course, depending on the geography you happen to be in, stabilizers could be the standard of care, and therefore, that's no hindrance to enrolling our study.

So the work that folks like Pfizer are doing to identify patients and get them on to tafamidis, I believe, will help our enrollment -- in the speed of our enrollment as well as just the disease awareness, the great work that they're doing to make people aware of this disease.

Hereditary polyneuropathy is certainly going to be a challenge to enroll. There's no question about that. There are multiple drugs approved for this rare-type patient population with TTR amyloidosis and there are other clinical trials in progress as well. However, with the great work that Akcea is doing to identify patients and investigators and the work they're doing with Akcea Connect as well as our strong relationships with investigators from our NEURO-TTR Phase III study, we're confident we'll be able to enroll this study on track, and we're feeling good about it.

The other advantage to the neuropathy study, of course, is the fact that it's an open-label study. So patients will not be on placebo. We're going to be comparing the results of that study to a historical control, which of course, will help enrollment as well as the fact that the sample size is significantly smaller than our Phase III NEURO-TTR study. So there will be challenges for polyneuropathy, but I think we can manage them.

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Chad Jason Messer, Needham & Company, LLC, Research Division - Senior Analyst [30]

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Yes. And then just on the polyneuropathy study that has an interim. Is that meant to be something you can file on? Or are you just trying to get an earlier sense for efficacy?

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [31]

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We will look at the interim analysis data at 8 months and make decisions based on data, and those would be data-driven decisions. I want to remind you that at 8 months in our NEURO-TTR TEGSEDI Phase III trial, we saw a high statistical significance with TEGSEDI as well as at -- of course, at the end of the study at 15 months. So we have a very nice comparison at our interim analysis at 8 months in the TTR LICA study that we'll be able to compare to historical controls. And we want to get this medicine to patients, as does Akcea, as rapidly as possible, and if the data supports it, off we go.

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Operator [32]

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Our next question comes from Vincent Chen with Bernstein.

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Vincent Chen, Sanford C. Bernstein & Co., LLC., Research Division - VP [33]

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A couple for me. So the first one on Huntington's, just sort of following up on the earlier. What should we be looking for in the updated data tomorrow? I guess in your view, we'll get some data -- updated data on the safety, the biomarkers, including neurofilament light chain, what does a good outcome look like in terms of the updated safety and biomarker data, including neurofilament?

And then a second question on somewhat of a different topic. I was just wondering if you could provide any color on the relative mix of product sales in terms of, I guess, WAYLIVRA versus TEGSEDI and then for TEGSEDI U.S. versus OUS?

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [34]

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Eric, would you like to touch on the biomarker data at the...

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Eric E. Swayze, Ionis Pharmaceuticals, Inc. - SVP of Research [35]

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Yes. I mean I don't really want to get ahead of our partners, Roche, who is presenting the data tomorrow. But really what's being presented should be thought of as an extension of the data that they've already presented. And I'd also note that the safety profile that has been presented of the drug is outstanding. The Phase III trials, as Brett mentioned, is on track and is scheduled to read out in 2022, and we're very pleased with the progress of the drug and pleased with the way Roche is advancing it.

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [36]

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Yes. The way I see it, Vincent, is the key message is the fact that the Phase III trial is on track, as Eric said, and as I said earlier. And Roche is very excited about the program. The bimonthly dosing is looking excellent and it's moving forward on pace. We will be issuing on Friday, a sort of a round up, a short summary, of all the presentations on our Huntington drug, so we can capture it. We'll post that to our website. And we'll also distribute it to our analysts. Beth, would you take the division of TEGSEDI...

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Elizabeth L. Hougen, Ionis Pharmaceuticals, Inc. - Senior VP of Finance & CFO [37]

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Sure. So the -- as you can imagine, since WAYLIVRA was just launched late in 2019 and in Germany really only, the vast majority of the revenue in 2019 was TEGSEDI. And we were pleased to see steady progress quarter-over-quarter with quarter-over-quarter growth in 2019. We think that sets an important and strong foundation for continued growth this year. And we look forward to moving WAYLIVRA and TEGSEDI into new countries this year. In terms of the mix between U.S. and ex U.S., that's -- that's information that we and Akcea are not sharing at this point.

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Operator [38]

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Our next question comes from Ellie Merle with Cantor Fitzgerald.

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Eliana Rachel Merle, Cantor Fitzgerald & Co., Research Division - Research Analyst [39]

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Just on the oral program now that you're committing to 2024 proof-of-concept data, can you walk us through what exactly we'll get in this readout? And I guess, what specifically would constitute, from your perspective, proof-of-concept for oral delivery? Are there specific levels of protein knockdown relative to this that you -- that you're running in parallel that you'd be looking for? Or just can you sort of walk through what in your perspective would constitute proof-of-concept for oral?

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [40]

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Sure. Thanks for the question, Ellie. So yes, we're very excited about the clinical trial in progress, evaluating the potential for commercially viable oral delivery with our partner, AstraZeneca. And as you mentioned, the plan is to have data readout from that study second half of this year.

What does proof-of-concept mean aside from -- for safety and tolerability is the bioavailability pharmacokinetics support that we expect to achieve that will -- that was predicted based on our extensive preclinical data that would support commercially viable oral dosing. More than that, we have the ability to assess the effects on target reduction, biomarker reduction in the clinical trial, is designed with that in mind, with that intent. And we'll have crisp data readouts on all that -- in that -- once that data reads out.

The other aspect of this topic that I'd like to expand on, if you will, is that we're not sitting still on the development of formulations to further increase and enhance oral bioavailability. We actually have active work research ongoing at Ionis, where we are already making substantial, significant improvements in the potential for oral delivery, even beyond that with the formulation we have in our clinical study right now. So we're continuing to make advancements in oral delivery, and we're hoping to even bring those on in the future.

Further, we're -- we've identified a number of Ionis-owned products that we're planning to bring into development as an oral pill soon after -- right behind the Ionis AZ collaboration. So this isn't -- there is many oars in the water, if you will, in the oral front, and we're feeling pretty good that we're going to have success in making oral commercially viable for our platform.

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Eliana Rachel Merle, Cantor Fitzgerald & Co., Research Division - Research Analyst [41]

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Got it. And just one quick follow-up, if I may. Just for Brett, I mean, it seems like you have a lot of programs in development. You have many readouts this year. I think in your slides, you called out that you have 4 proof-of-concept readouts this year. I guess which program or which data sets are you most excited about?

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [42]

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Well, it's hard to pick one. I mean with a pipeline of more than 40 drugs, all which have the potential to be transformative in nature, it really is and if we went around the table here, we'd probably get 6 different choices. But in the shorter term, well, we have the rare disease buckets, and we have the broad disease populations, right? And it's hard to not include Lp(a) in a choice and a selection for drugs. I mean, this is such a large patient population, we're so far ahead of any form of competition. The Phase III study with Novartis is progressing extremely well. And the commercial opportunity for -- and the opportunity for patients is so enormous. So you got to include that one.

On the other hand, in our rare disease bucket, I have to -- I gravitate towards ALS. I mean there's no -- there are no treatments for this terrible neurodegenerative disease. And Ionis with Biogen is, as I said earlier, is the analogy of a full-court press on all forms of ALS, which we are doing now. Our SOD1 program is due to read out for the first of multiple ALS drugs. As a reminder, that drug showed a really remarkable -- provided really remarkable evidence of efficacy in [that short] 3-month study in patients with SOD1-ALS, and now the Phase III is going to read out next year.

As Eric referred earlier, we have a C9 program, that's also a Phase II program that's going to read out next year, and now we have a drug for sporadic ALS. So I would lean towards those 2 programs, but I can take all day talking about our pipeline. There's lots and lots of drugs there to be very excited about.

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Operator [43]

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Our next question comes from Tyler Van Buren with Piper Sandler.

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Tyler Martin Van Buren, Piper Sandler & Co., Research Division - Principal & Senior Biotech Analyst [44]

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Just had a brief follow-up on your comments on capital allocation earlier. You mentioned potential complementary technologies that you're looking at. So just wanted to get your updated thoughts or interest in tissues, specific technologies, there's some emerging out there tissue-specific RNA technologies, and one example is antibody conjugates. So I just wanted to get your thoughts there.

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [45]

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So thanks, Tyler. We're very thrilled to be in a position of such a strong financial position that allows us to invest in technologies that complement our antisense platform and expand the reach of our antisense platform and do even more than that. We're investing in genomics to identify novel targets for -- to continue to replenish the pipeline as new drugs reach commercialization, novel targets that are genetically linked. We're working with the companies and academic collaborators to work on pathways that lead to the selection of novel targets as well. And we're working internally and with -- externally with Cloud2 collaborations with new LICA technologies.

Just late last year, we completed a partnership with a genomics company to identify novel targets and with another company to identify novel strategies -- LICA strategies, to expand the reach of antisense to newer organ systems, new cell types. We're making great progress. Antibody conjugates and their derivatives are just one aspect of the types of strategies we're taking. I view that as one tool in a toolbox of approaches with LICAs that we have and we're developing and we're working on ourselves. So they have the potential to work, but I believe that we have many different strategies that are showing promise to getting into the cell types that are less sensitive to antisense today.

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Operator [46]

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Our next question comes from Jessica Fye with JPMorgan.

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Jessica Macomber Fye, JP Morgan Chase & Co, Research Division - Analyst [47]

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Just following up on one of the earlier questions about angiopoietin-like 3. Can you just talk a little bit about how you see that product positioned, relative to APOCIII-LICA. Is APOCIII-LICA really going to focus on the indications that you've previously discussed for WAYLIVRA?

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [48]

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Thanks, Jess, and I appreciate the question. So angiopoietin, first of all, of course, we're thrilled with the results from the Phase III studies that Ionis Akcea unblinded and presented top line data on our -- announced top line data for both programs, APOCIII-LICA and angiopoietin-like 3 LICA. Both hit the primary endpoints, both are positioned very well for Phase III trials down the road.

There is overlap in both of these medicines in the atherogenic lipids that they manage, that they control, triglycerides, remnant cholesterol, LDL cholesterol, effects on -- positive effects on HDL. But there's also a significant enough difference between these 2 drugs that we believe, as does our partner Pfizer, for angiopoietin-like 3, and of course, Akcea too, that they differentiate significantly sufficiently well that they will have a different profile in patients with cardiovascular disease.

I think that APOCIII-LICA is the most potent triglyceride lowering target drug out there today and angiopoietin-like 3 brings a number of other advantages, such as the effects on cholesterol in addition to the significant triglyceride lowering and positive effects on HDL. So I think they differentiate enough to be very important and meaningful additions to the cardiovascular -- to the treatment of cardiovascular disease in the future, as is our partner Pfizer and Akcea.

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Operator [49]

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Our next question comes from Mani Foroohar with SVB Leerink.

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Rick Stephen Bienkowski, SVB Leerink LLC, Research Division - Associate [50]

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This is Rick on the line for Mani. I have 2 questions for you. First, just broadly speaking, about the opportunity set for the oral delivery of ASOs. Do you think oral delivery could potentially be a good fit for any liver-directed therapy? Or do you think the technology is best utilized in specific areas like cardiometabolic indication?

And second, just given the increasing focus on your wholly owned pipeline, could you give us a sense of how you're currently viewing the relationship with Akcea? Do you think it would make sense at any point to think about bringing the remainder of Akcea back into the company? I'm really just looking for any commentary on how you view the relationship with Akcea evolving as more focus is based on your internal pipeline?

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [51]

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Sure thing. Thanks, Rick. So the oral, the -- the progress we're making on oral delivery is successful, has the potential to reach all of our liver programs. That's what's really so exciting about it. It's not just this one particular clinical trial, but it's also the potential impact it will have on any of our LICA liver-like programs, including drugs that target APOCIII or angiopoietin-like 3 or Factor XI, TTR and so forth. And we're focused on that.

And as I said in one of the questions earlier, we've already identified additional liver targets that we're moving forward to oral studies in the clinic. So it does have a very broad reach if successful. And as I also mentioned, we're continuing to even improve on the current formations, which are showing a lot of potential.

We're changing gears. We're very excited about Akcea, and we're committed to Akcea's success and are confident we're going to be very successful. Our fully owned -- our wholly owned rare disease pipeline is growing and expanding. And there's lots of opportunities to bring these drugs to maximize commercial value of each of these medicines in different ways. And Akcea is certainly one of those options that are available. And as we mentioned earlier, we're already in negotiations, discussions with Akcea about the potential addition of a new medicine -- a rare disease medicine in the pipeline later this year.

As far as the future of Akcea in relation with Ionis, that's the topic for discussion down the road. Right now, Akcea is doing well, and they have a very full and exciting agenda or pipeline -- agenda, which is really an agenda that's comprised of both pipeline and getting WAYLIVRA approved in the U.S. and continuing progress with TEGSEDI and getting WAYLIVRA launched. But with APOCIII-LICA, now in their pipeline and planning to start Phase III in FCS later this year, with TTR-LICA having undergone 2 Phase III studies already in progress, it's quite a lot on their plate. And we believe that they're on track to deliver on their strategic goal. So that's what I'd say about that right now. I hope that -- Rick, that addresses your question.

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Operator [52]

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The next question comes from Salveen Richter with Goldman Sachs.

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Unidentified Analyst, [53]

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This is [Ross] on. Can you help us understand the breakdown of product sales to TEGSEDI and WAYLIVRA and some of the gating factors for both of these launches here? Specifically, I'm looking for some additional color on your comments that the prescribing base for TEGSEDI grew about like 4% Q-over-Q. I'm just trying to think about what factors drove this significant uptick, and where these physicians are coming back? And then I have a follow-up.

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Elizabeth L. Hougen, Ionis Pharmaceuticals, Inc. - Senior VP of Finance & CFO [54]

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It's Beth. So the breakdown of TEGSEDI and WAYLIVRA, as I said, is primarily TEGSEDI because WAYLIVRA was launched in Germany late in 2019. And they're -- right now Akcea is expanding WAYLIVRA out across additional countries in Europe, but they started with Germany, and that's a relatively small patient population in Germany with FCS, and so a small -- very small portion of the product revenues in 2019 were WAYLIVRA. So the vast majority were TEGSEDI.

In terms of the growth in prescribing physicians, a lot of that is a function of the work that the Akcea team is doing with their genetic testing program, getting out not only into academic centers, but also into the community settings, expanding the number of physicians that are utilizing the Akcea genetic testing program to identify patients who could be potential patients for TEGSEDI and then getting those physicians onboard and getting those identified patients onboard with TEGSEDI.

So I think that's where a lot of the growth is coming from, and we're looking forward to the continued success of that program and other programs that Akcea is engaged in right now to grow TEGSEDI revenues this year. And also, frankly, to grow WAYLIVRA revenues working with similar programs.

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [55]

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Thanks, Beth.

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Unidentified Analyst, [56]

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Got it. That's really helpful there. And then just finally, how should we be thinking about, with the plan, likely market entry this -- later this year and the impact to SPINRAZA use?

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [57]

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I'll start. Sure. SPINRAZA continues to be global foundation of care for all forms of SMA, Ross, and as Beth mentioned earlier, Biogen is expecting continued growth of SPINRAZA despite the potential for additional competition down the road. And it's setting a very -- SPINRAZA has set a very high bar on efficacy and safety that competitors are going to have to meet to be significant competitors for the SMA population.

It's hard to comment on competition when so little data has actually been presented. And so I really don't want to comment on the potential for other drugs in this space like risdiplam. Suffice to say that we're very confident that SPINRAZA will continue to perform very well for all forms of SMA this year and for years to come.

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Operator [58]

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Our next question comes from I-Eh Jen with Laidlaw & Company.

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I-Eh Jen, Laidlaw & Company (UK) Ltd., Research Division - MD of Healthcare Research & Senior Biotechnology Analyst [59]

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Just one that's a bit of a link on the previous one, which is that you guys going to file -- refile WAYLIVRA later this year as well as you're going to start a pivotal study for APOCIII-LICA in FCS. So is there any connection with the relationship or expectation of those 2 events?

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [60]

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I-Eh, thanks for the question. Those 2 events are not linked in any way. We're having very productive Ionis-Akcea discussions with the FDA on WAYLIVRA. And as Richard indicated, we now are in an envious -- a fortunate position of having a lot more data to make the case that this important medicine should be approved in U.S. and planning to refile later this year. In no way is this linked to APOCIII-LICA.

We obviously have a lot of patients. Obviously, it's the same patient population, which is the point to your question. But in no way are these filings, the one for potential approval in the U.S. with the start of the Phase III trial, in any way linked together. These are moving forward independently, and we don't see any impact that WAYLIVRA could have on the urgency that we have to get the Phase III study with APOCIII-LICA moving.

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I-Eh Jen, Laidlaw & Company (UK) Ltd., Research Division - MD of Healthcare Research & Senior Biotechnology Analyst [61]

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Okay. Great. And maybe just a quick follow-up, which is that how much stock repurchasing at this point is still left?

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Elizabeth L. Hougen, Ionis Pharmaceuticals, Inc. - Senior VP of Finance & CFO [62]

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We have fully executed on the stock repurchase program, the initial program that our Board approved. So that is wrapped up right now. And as I said earlier, with where our stock is trading right now, we think it's a great investment. So we may be looking to expand that into the future.

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Operator [63]

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Our next question comes from Gena Wang with Barclays.

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Huidong Wang, Barclays Bank PLC, Research Division - Research Analyst [64]

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Sorry. I got my line muted. So I just ask one question regarding the SOD1 data expectation. Brett, do you have any thought what you would consider as a very impressive data or meaningful data?

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Brett P. Monia, Ionis Pharmaceuticals, Inc. - Founder, CEO & Director [65]

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Thanks, Gena. And, Sara, this will be the last question. We're running long on time. So as I mentioned earlier, we're very excited about the SOD1-ALS program. If you recall, the Phase II study was 3 months in which the clinical endpoints that were -- some of the clinical endpoints that were looked at in the study that really made everyone so excited about it were the ALS functional rating scale and respiration -- improvements in respiratory function in that trial. And as I mentioned earlier, the results were remarkable, really stunningly positive and that was only 3 months.

Biogen executed a very efficient Phase III program, which they basically added a new cohort to the ongoing Phase II study, so that they can start that study very quickly. And the way to simply think about it is that the endpoints are essentially the same as they were in the Phase II study. We're just looking for even greater efficacy than we saw at 3 months.

Thank you. So thank you again, everybody, for joining us today. We're obviously very excited for this year, and we look forward to updating you on our progress as the year unfolds in. Wish everybody a great day. Thank you very much.

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Operator [66]

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