Ionis Pharmaceuticals, Inc. (IONS) Earnings Call Transcript & Summary

Great. Good afternoon, everyone. My name is Jess Fye. I'm one of the senior biotech analysts at JPMorgan. And we're continuing the 2021 healthcare conference today with Ionis. I'm joined by the company's CEO, Brett Monia. And I wanted to let you know that instead of going across the hall for a breakout session after the presentation, this year, you can ask a question by clicking the blue Ask a Question button on the webcast. This will send them to me through a portal, and I can ask them to the management after the presentation. So with that out of the way, let me turn it over to Brett.

Thank you, Jess, and good afternoon, everybody. Thanks for joining me today for this presentation. Very pleased to present to you on Ionis Pharmaceuticals, where we are today and what our future looks like from our perspective, a very bright and exciting future. My understanding is that you listeners will be toggling through the slides yourselves. I'll do my very best to remember to identify what slide number I'm on as I go through the slide presentation, so you can follow along. In the next slide, Slide #2, is my forward-looking statements, which I recommend that you review at your convenience. Next slide, #3. I'd like to start by just spending a moment or two on looking to last year, 2020, because it really was a year of strategic importance to Ionis Pharmaceuticals in many important ways. And really, in many ways, it really represented a new beginning for this really exciting company. We had a new leadership team in place, a leadership team that had new vision for Ionis Pharmaceuticals, a vision with a very aggressive agenda, an agenda that we set out to achieve that would bring, if successful, Ionis to even greater successes into the future. And that started with a change to our business model, a business model that traditionally has been focused on partnering for late-stage development and for commercializing products from our pipeline. But that changed last year around this time, in which we revised our business model to [Audio Gap] Ionis building out the Ionis owned pipeline, bringing products towards market -- building out markets and commercializing products ourselves. And that's exactly what we're doing today, making great progress. And that progress has been facilitated, accelerated by the reacquisition of Akcea Therapeutics, which we completed last year and is going exceptionally well. In addition, we sought out to advance our pipeline, our mid-stage pipeline and our late-stage pipeline, to ensure that we are producing medicines or bringing medicines to patients into markets where there's a great unmet need for many years to come, many medicines, many markets, many diseases. And we were very successful in doing that. And in addition, in parallel with all this, we advanced our technology so that we can tackle diseases today and in the future that we were not able to tackle in the past. And that, of course, on the next slide, Slide #4, positions us for a great 2021 and for many years to come. Building on and taking the -- and leveraging what we accomplished from the commercial side last year, this year, we're focused on expanding the Ionis' wholly owned pipeline, building it out, identifying drugs that we're going to bring to the market ourselves. And we're going to prepare those markets for launches. The pipeline is incredibly exciting. We're going to build on the success of 2020 and advance the pipeline, advance our Phase III pipeline in many ways, including a readout of a Phase III trial in ALS this year and adding new Phase III trials as well and completing enrollment into at least 2 ongoing Phase III trials. In addition, we have a long list of very exciting Phase II clinical proof-of-concept readouts coming this year, and leverage the success we had in aerosol delivery, proof-of-concept that we achieved last year. We're going to expand the aerosol-delivered Ionis clinical pipeline as well this year. In addition, the technology advancements are going to start providing dividends in drug development. We're going to take advantage of the progress we've [Audio Gap] LICA delivery so that we're going to advance a new LICA medicine into drug development this year, targeting a new organ system to replicate what we did for liver LICA. And we're going to expand our pipeline by taking advantage of all the investments we've made over the last few years in human genomics to add to the pipeline more novel genetically validated programs for many years. All of this requires a strong financial position to be able to do all the investments we need to do to maximize the value that we can bring to all stakeholders involved with Ionis Pharmaceuticals. In Ionis, we have a very strong bottom line. Our capital position, financial strength that allows us to do all the investments that we need to do to maximize the value of [Audio Gap] and the technology we bring forward. We have a very strong cash position with approximately $2 billion in year-end cash estimated after 2020. And we're on track to meet our 2020 financial guidance. So a very strong balance sheet that allows us to invest in the commercialization products to build that out, our pipeline, the wholly owned pipeline as well as advancing our technology. Ionis Pharmaceuticals has always led in therapeutics. We've never been a follower. We've always sought to pioneer new markets and change the standards of care for patients who are in great need and improve the standards of care for those patients. And we will never stray from that. We'll continue to do this for years to come. In fact, we're going to accelerate it. And the way that we're going to accelerate this in the near term and in the mid-term, and of course, the longer term really is to focus on and see how -- and to take advantage of 2 leading therapeutic franchises today at Ionis. The first is our leading neurology franchise. We have shown with our platform that we can address all major [Audio Gap] of the brain with our antisense medicines and target all CNS cell types. This allows us to target virtually all forms -- all neurodegenerative diseases where there is a large unmet medical need, whether they're rare diseases like ALS and Huntington's disease and Prion disease or [Audio Gap] and Parkinson's disease. And in fact, we have drugs for all these indications in development today. The second leading franchise we're going to continue to deliver pioneering new medicines for patients is in cardiometabolics. We have a leading metabolic franchise today, which is addressing essentially all of the major cardiovascular risk factors that are known, that are relevant today to treat cardiovascular diseases, whether it's cardiovascular diseases that require better antithrombotic drugs or better lipid lowering or antihypertension drugs or other risk factors that cause cardiovascular disease. We're there. We're all over in our pipeline. We know -- everybody knows that the #1 cause of death globally today is -- remains cardiovascular diseases. And we believe this franchise has the ability to have a major impact on reducing cardiovascular-related deaths around the globe with this pipeline with this leading franchise. So let's take a slightly deeper dive -- I'm sorry; that was Slide 8, now moving into Slide 9, I forgot already -- a deeper dive into these 2 leading franchises, where they are today on Slide 9 again. In neurology, we have 3 ongoing Phase III trials in progress, 8 medicines in clinical development, more than half of which are wholly owned Ackea/Ionis. The cardiometabolic franchise, also 3 ongoing Phase III studies with 12 medicines in clinical development today. More than half, again, are wholly-owned by Ionis. So now on Slide 10, I'd like to take you through our late-stage pipeline, our [Audio Gap] pipeline, a late-stage pipeline that I believe is one of the most exciting late-stage pipelines in the biotech industry bar none. 5 medicines across 6 Phase III trials in progress, all where there's a large unmet medical need, addressing large unmet medical needs. Tofersen, our first of several drugs for the treatment of ALS, this particular drug is addressing ALS due to mutations in a gene called SOD1. Tominersen, our leading medicine for the treatment of Huntington's disease. And then 3 cardiometabolic Phase III drugs, IONIS-TTR-LRx for the treatment of all forms of TTR amyloidosis. IONIS-APOCIII-LRx is in Phase III development for a rare disease called familial chylomicronemia syndrome, FCS. And then pelacarsen, another program from our -- another Phase III program in our cardio franchise, targeting a very large indication cardiovascular disease due to high levels of a risk factor called lipoprotein(a). And I want to delve now a little deeper into all these programs, starting on Slide 11 with our neuro Phase III programs. On Slide 12, I want to introduce to you -- I'm sure most of you are aware what amyotrophic lateral sclerosis, ALS or Lou Gehrig's disease. It's a fatal disease with an enormous unmet medical need. This disease is characterized by motor neuron loss in the cortex, in the brain stem, in the spinal cord, which is a very rapidly progressing disease that ultimately leads to death after just a few years after symptom onset. Death is typically by respiratory failure. There are multiple causes of ALS known today. There are genetic causes, in which there are several genes when mutated, their gain of toxic function mutation such as SOD1, C9 and FUS, which represent about 50% of the prevalence of symptomatic ALS today. And then there's the forms of ALS in which there are no known genetic cause, which represents the majority of ALS, the prevalence of ALS patients today. Slide 13. We are committed at Ionis to treat all forms, all causes of ALS today. Not only are we committed, we have the drugs in the pipeline that we think can do exactly [Audio Gap] drugs in development targeting all causes of ALS today, led by tofersen in the Phase III VALOR study targeting SOD1-ALS, fully enrolled and rolling forward. IONIS-C9Rx targeting another genetic form of ALS due to mutations in the gene C9ORF. And then a third genetic form of ALS due to mutations in the gene called FUS. We're about to start a clinical study with our FUS -- with our medicine -- antisense medicine targeting FUS in a pivotal Phase III study to start later this year. In addition, we have 541, which is targeting the forms of ALS in which there's no known genetic cause of ALS -- broad ALS. And then we have more drugs coming forward to treat broad ALS as well that will be moving into the pipeline in the future. So Slide 14. First, the 4 medicines targeting ALS. The Phase III VALOR study is now fully enrolled, with data due out -- Phase III data due out in -- this year -- later this year in the second half of the year. It's potentially -- and we expect it to be our next commercial medicine. In addition, a Phase III study is to be started this year called ATLAS in patients with SOD1 mutations that are presymptomatic. They haven't developed ALS yet. So presymptomatic SOD1-ALS Phase III is projected to begin this year. And as a reminder, we demonstrated robust reductions in SOD1 in a Phase II study in patients with SOD1-ALS and strong trends in slowing progression of the SOD1-ALS disease in that Phase II study, which bodes very, very well for the outcome of the Phase III VALOR study, but more than that, really lends confidence to us and really provides hope for patients with all forms of ALS that for the first time, we could pioneer this new market, we can pioneer a new medicine for the treatment of all forms of ALS, something that's never ever been done before. Moving on to Slide 15. Our second Phase III program, Huntington's disease, another severe, rare genetic fatal disease in which the unmet medical need is enormous. This is a disease that, again, is passed down from generation-to-generation. It's a monogenic disease. It's mutation in a single gene, the Huntington gene, CAG expansions. It's more slowly progressing than ALS, in that following symptom onset, the disease usually progresses over a period of a couple of decades before death, which inevitably happens -- ensues and happens. It's a more prevalent patient than ALS with approximately 80,000 patients in major markets today with symptoms of Huntington's disease, and far more than that, harbor the Huntington gene mutation who are yet -- who haven't developed it yet, they're presymptomatic. Very large unmet need. And of course, a drug that penetrates this market will be another pioneering medicine, pioneering a new market, providing hope for patients. Tominersen is potentially the first ever disease-modifying medicine for the treatment of Huntington's disease. The GENERATION HD1 Phase III study is fully enrolled also with projected Phase III data expected on track next year in 2022, targets the root cause of Huntington's disease, the Huntington mutant protein, received PRIME designation in Europe. And as a reminder, we've demonstrated durable, robust reductions of mutant Huntington protein in patients suffering with this disease in Phase II development. All right. Slide 17. Moving on to the Phase III programs from our cardiometabolic franchise, IONIS-TTR-LRx, IONIS-APOCIII-LRx and pelacarsen. I want to first say, all 3 of these drugs benefit greatly from the very attractive profile of our LICA chemical platform, LICA chemistry. LICA chemistry is a breakthrough for antisense medicines. It greatly enhances the profile of our medicines in many, many different [Audio Gap], greatly and reproducibly enhances potency thirtyfold or so over non-LICA medicines, enabling us to dose very conveniently for patients once a month, once a quarter, based on our choice. We prefer once a month. And of course, thousands of patients gene clinical trials to date so far, we've seen an outstanding tolerability and safety profile that's been 100% reproducible across all programs, giving us tremendous confidence in the drugs that are in our pipeline using this LICA chemistry. Okay. Slide 19, TTR amyloidosis. I think most of us are familiar. This is a disease area that has received a great deal of attention recently, a devastating and fatal disease. Patients suffering from this disease is the consequence of the production of TTR protein wild type or mutant from the liver, which forms amyloid deposits in various organ systems, causing multi-organ failure, whether it's peripheral nerves or the heart or the kidney or other organ systems, resulting in a progressive disease that progresses at a rate that is complex [Audio Gap], whether it's hereditary or nonhereditary. It depends on the types of mutations. It's -- there are different causes for the rate of progression. Nevertheless, the end result is -- almost always leads to death. It's not a small population. It's around a large population, especially when you consider the TTR cardiomyopathy patient population, which is estimated to exceed 200,000 patients suffering from TTR cardiomyopathy around the globe now that many people believe that -- that's kind of their estimation. Moving on to Slide 20. IONIS-TTR-LRx has the potential to be a foundational therapy for all forms of TTR amyloidosis. The hereditary form, including the hereditary polyneuropathy form as well as the broad cardiomyopathy patient population [Audio Gap] TTR amyloidosis. We have 2 ongoing Phase III studies, the NEURO-TTRansform in patients with hereditary polyneuropathy and the Phase III CARDIO-TTRansform study, a cardiovascular outcome trial in patients suffering from TTR cardiomyopathy. The polyneuropathy Phase III study is due to read out next year and cardiomyopathy in 2024, uses our LICA chemistry. And as a reminder, we've shown in our Phase I study with like -- with TTR LICA very robust reductions in TTR levels, exceeding 90% or so reductions in that clinical trial, boding very well for this medicine in this patient population. The next medicine in our Phase III pipeline from our cardiometabolic franchise addresses diseases related to severe triglycerides. This is Slide 21. High triglyceride levels is known -- are known to of cause all kinds of different types of diseases, including cardiovascular diseases as well as very serious metabolic diseases, including fatal pancreatitis. apoC-III apolipoprotein C-III is the master regulator, the most important mechanism for the regulation of triglycerides in the body. We have the potential best-in-class mechanism for triglyceride-related cardiometabolic disease management by targeting apoC-III with our APOCIII-LICA medicine, and that includes the rare population in which patients have [ triglycerides 1,000 ] familial chylomicronemia patients, FCS, as well as the broad patient population suffering from high triglycerides, whether it's the severe HTG population or the cardiovascular patients who suffer from high triglycerides who need that therapy to control their triglycerides. Slide 22. IONIS-APOCIII-LRx is one product that has the opportunity to treat all indications related to elevated triglycerides. The FCS BALANCE study is actively recruiting and underway, the Phase III study with data readout in 2023. We're planning and putting our final touches on the initiation of a second Phase III study in a broader triglyceride indication to start later this year. And as a reminder, we have used -- we have tested this mechanism in many ways, demonstrating robust triglyceride reductions across many patient populations, including IONIS-APOCIII-LRx, giving us, again, confidence in the outcome of these late-stage clinical studies. And then finally, the third Phase III study -- Phase III medicine, 5 overall. The third from our cardiometabolic pipeline targets another cardiovascular risk factor called lipoprotein(a), a major untreated cardiovascular disease risk factor that's genetically determined at birth, that is the levels of Lp(a) genetically determined at birth. If you have high Lp(a) levels above a certain threshold, you're at high risk for cardiovascular disease, heart attacks and strokes. And the higher it is, the greater the risk. In addition, there are no treatment options today. There's no way to manage Lp(a). No statin can control it; PCSK9s do not control it. Diet, exercise does not control it. And yet, this is a very large patient population, exceeding 8 million people around the globe suffering from cardiovascular disease through high Lp(a) levels. Moving on to Slide 24. Pelacarsen is a potential solution for these millions of patients in great need for a therapy to control their Lp(a). Obviously, pioneering new markets here. This is expected to be the first disease-modifying treatment for the control of Lp(a)-driven cardiovascular disease ever. The Phase IIIa HORIZON study is -- it's a cardiovascular outcome trial, actively recruiting with the projected Phase III data in 2024. And recruitment is going very well. It's granted -- it's been granted Fast Track Designation by the FDA. And as a reminder, in our Phase II study of nearly 300 with the high Lp(a) levels in cardiovascular disease, we were able to drive Lp(a) levels down into the normal range, and nearly 98% -- or actually 98% of the patients in that Phase II trial to normal, getting them, if you will, out of harm's way, giving us, again, confidence in this critical large Phase III outcome trial. So I think you'll agree with me that Ionis has one of the most exciting late-stage pipelines in the industry. Of course, these 5 medicines, 6 Phase III clinical trials with data coming out every year, as you can see from programs through 2024, '21, this year with SOD1-ALS and then '22, '23 and '24. So really sets us up for great things in the future, including setting us up for tremendous growth for the organization going forward. We are on the brink of waves of medicines coming from our pipeline to patients to the market over the next several years. We project 12 or more, 12 is a conservative estimate in my view, marketed products by the end of 2026, the first new product potentially next year entering into our commercial pipeline. Medicines coming from our leading neurology franchise, wholly owned and partnered; our leading cardiometabolic franchise, wholly-owned and partnered; as well as other programs outside of these 2 franchises that we expect to reach to market in the future. And all of this, of course, drives the growth of the company, positions us, Ionis, to deliver double-digit revenue growth over the next few years, very exciting. And not surprisingly with a pipeline like ours and all the progress we're making and the success we're having in the pipeline, 2021 is being teed up for a really exciting year from a catalyst standpoint. We have a lot of data readouts coming this year. I already touched on tofersen for the Phase III readout in the second half of this year. From our neuro franchise, we also have C9Rx drug in Phase II now. And then our tau program in mild Alzheimer's disease in the second half of the year. And then non -- very -- several Phase II programs that are completed or completing now that are outside of these 2 franchises, acromegaly, cystic fibrosis, hereditary angioedema will also read out in the first half of this year. And then we have many key study initiations coming -- being -- coming forward this year, pivotal Phase III trials, including the SOD1-ALS study I referred to earlier, the presymptomatic SOD1-ALS study there as well as the pivotal study for our FUS, our antisense medicine targeting FUS-ALS; and then third -- a second indication for APOCIII-LRx; and then other key Phase II study starts as well. Now on Slide 27, I forgot to say that. So then to wrap it up on Slide 28. Really, these are really exciting time at Ionis Pharmaceuticals. We are well positioned to achieve tremendous growth in the near term as well as, of course, in the long term. We're positioned to transform the lives of patients and drive substantial growth for all stakeholders involved. We are advancing the pipeline. We're advancing the technology on all fronts. We are pioneering new markets and changing and improving the standard of care for patients. And very importantly, of course, we have the financial might to be able to invest in all aspects of the business, the commercialization, the pipeline, the technology to allow us to achieve all of our strategic priorities and maximize the value of Ionis for all stakeholders involved. Thank you very much. And with that, we'll turn it over to questions and -- the question-and-answer session.

Great. Brett, we'll just give it a second for your colleagues to pop up here. And while that's happening, I'd remind folks that you can send a question by hitting that Ask a Question button online. That will populate a portal, and then I can ask those questions to management. But I wanted to start with one that has been coming up a lot recently, which is, in your presentation at the Investor Day in December, you highlighted your expectation of having 12 or more medicines on the market in 2026. Which of those programs are you most excited about? And can you talk to us about the market opportunities?

Sure, Jess. Thanks for the question. We're excited about all of the programs in the pipeline, of course. That's probably not a surprise to you that I said that. But for the purposes of focus and organizing what we're most excited about in the -- let's focus on the near term, let's focus on the Phase III pipeline. Tofersen, which I highlighted in my presentation, has the potential to be the first ever disease-modifying drug for ALS. And it has -- Biogen, our partner for tofersen, has said that they see that market at around the $0.5 billion to $1 billion or so range in combination with a drug like C9ORF, which is in Phase II development. So 2 rare indications for ALS. But more than that, we're very excited about the larger rare disease indications, which are much larger than ALS. Our TTR LICA program for cardiomyopathy, and of course, the hereditary forms is an enormous opportunity -- market opportunity as is the Huntington program, which is -- has a very large unmet need, again, a larger patient population than SOD1-ALS. And then you get into the programs that are in Phase III that are for patients in the millions. Millions of patients suffering from high triglycerides, the severe high triglyceride patient population, for example, where we're targeting APOCIII-LICA as well as pelacarsen for Lp(a) in the 8 million to 10 million patient range. So those are huge market opportunities. And I have to highlight those as well. And then, of course, we're also excited about many of the rare disease programs that are wholly owned by Ionis today as well the acromegaly, hereditary angioedema. And very important is our drug that is now in patients with cystic fibrosis, which represents a very exciting opportunity for a drug [Audio Gap]. We're agnostic to the CFTR mutation, our ENaC program. So I guess, I would stop there and say that those are the ones in near term that I would focus on and we're most excited about.

Okay. Great. There's a number of questions coming in about ATTR in particular. So I'm just going to pick the one that sort of seems to sum them up the most which is, how does the Ionis approach compare to the Alnylam approach? And what is the potential advantage? Is it dosing, depth of response, breadth of response? How do they compete coming later to market? Presumably that's referring to the LICA program?

Yes. I'll touch a little bit on the development program. And then maybe Onaiza could talk a little bit about how we see the market shaping out, which is really what this comes down to. So as I said in my presentation, we're planning the -- for the polyneuropathy study to read out next year. Our LICA medicine, I don't believe there's anything out there that will show a greater efficacy than our LICA medicine with greater than 90% reductions in TTR that we're expecting to see with our dosing regimen. On the other hand, the cardiomyopathy patient population is really the biggest opportunity, right, TTR cardiomyopathy, where as far as I can tell and we are moving very quickly in this Phase III study were due to read out around the same time as our competitors in the TTR cardiomyopathy space. So there, the question is, is there a room for 2 silencers in that vast market space? And then, Onaiza, maybe you could talk a little bit about that, if you're on.

Yes. Sure. Happy to. Yes, as Brett said, we're very excited about TTR LICA. It's an exciting product for us. As he said, the market is large, epidemiology suggesting 250,000 patients. 90% of that is cardiomyopathy. We believe strongly biologically and mechanistically that we see silencers as the first choice before stabilizers, such as tafamidis and AG10. And I think the good news is that tafamidis is available now, is doing quite well, right? Bodes well for market extension, and they're doing a good job with patient diagnosis and awareness. I think they'll probably hit about $1 billion this year. So yes, certainly a very dynamic and evolving treatment paradigm for us. We do believe we are in a very strong position to become foundational therapy. First of all, we have the largest trial in cardiomyopathy. This gives us the opportunity to get subgroup data on patients with and without tafamidis. We also expect to get data in both cardiovascular outcomes and meaningful morbidity measures such as hospitalization, other functional measures that really set us up well for uptake with payers and providers and patients. So we are very well-positioned competitively in the evolving treatment paradigm. We have a very easy, self-administered monthly injection via subcu that we plan to launch as well an auto-injector that will really help penetrate the full market. But the data -- the efficacy data is what we're most excited about.

Thanks, Onaiza.

Got it. With the update from the Huntington's natural history study as well as the open-label data for tominersen coming in the first half of this year, how do you expect that to inform expectations around the pivotal study in Huntington's?

So we are -- and our partner, Roche, are 100% focused on the outcome of the Phase III GENERATION HD study. This is the study that is powered appropriately with respect to duration of treatment side, number of patients and properly controlled. And it's going to read out in next year. And Roche has also said that, if positive, they intend to file next year as well. So we're not that far away in the Phase III readout. As for the open-label extension data that Roche will present, they actually haven't put down out the timing yet for when they're going to talk about that. They have presented [Audio Ga] meetings every spring. So it's a good possibility that it will be in the first half of this year as well as the natural history data. It's hard to say how that's going to read into anything to set expectations of the Phase III study. I really don't think outside of demonstrating continued durable reductions in Huntington protein with acceptable safety and tolerability. I think that, that is going to be the key factor that's going to really read into the study, because the Phase III study is the one that's really kind of be needed to really test the hypothesis of whether or not lowering mutant Huntington protein will impact the disease progression. The endpoints that will be shared from the open-label extension still have not been nailed down, and they've not been communicated by Roche. And they are not necessarily the same endpoints that are going to be used in the Phase III trial. So it will be very interesting, more information, more data that we'll speak to the Phase III Huntington trial -- tominersen trial. But really, it's the Phase III trial that we really need to get to and really see the results.

Okay. Got it. Maybe switching to cardiology. Have you had any feedback from the FDA on your plans to move IONIS-AGT-LRx into the Phase IIb study in uncontrolled hypertension and Phase II in heart failure with reduced ejection fraction? And when could you initiate those trials?

Yes, Jess, we're not -- we don't typically talk about our conversations or negotiations with FDA on clinical trials. But suffice it to say, these are all systems go -- green light go forward on the start of the Phase IIb studies for refractory hypertension this year and also the heart failure study this year. We're planning to start both studies this year. We haven't, like, nailed down the timing in more detail than that. The hypertension study, we're building off of the really exciting results we presented at a high level last year in patients refractory -- having refractory hypertension, that is around 2 or 3 medicines to control their blood pressure, and we will improve that and normalize many of the patients, their blood pressure. We're going after a slightly sicker patient population in a bigger study to help us set dose for a Phase III trial. And then the heart failure study is -- will be starting also this year. And there, we really want to demonstrate, again, safety in this patient population to demonstrate that by inhibiting AGT from the liver, by inhibiting the RAS angiotensinogen pathway by targeting the liver AGT that it will be safe for patients. And we'll also look for biomarkers [indiscernible] that are related to improving heart function, ejection fraction, heart performance.

Okay. And for the next oral formulation of ION449, what's the latest time line there?

So we're making -- we continue to make great progress on the preclinical side in oral formulations and strategy. It's not just formulations. It's also how we present the molecule, capsules, tablets, microparticles, all these other things. And we're making really good progress. And we'll see. Our objective is to move a new oral program into development by the end of the year. It'll more than likely come from an Ionis wholly owned program, but that's the plan right now.

Okay. Got it. You started out the presentation talking about the strategy to keep more of your products wholly owned and commercialize them independently. And related to that, you've also talked about kind of within that approaching indications that have a rapid path to market and then expanding out from there once you kind of establish a commercial foothold in different disease areas. So just thinking about that a little more specifically, what are the factors that you're hoping to characterize in these markets as you enter them before launching commercial efforts in larger indications?

Yes. That's a great question and a perfect question for Onaiza Cadoret. I'd like maybe you take a crack at that, Onaiza?

Sure. Yes. I think, as we said, we're clearly looking to pioneering markets, change standards of care. At the Investor Day, I highlighted that we will put our stake in the ground in durable franchises in neurology and cardiometabolic. And the reason is because we have really a large set of late-stage products there, but we also see a really strong future pipeline coming in, right? So that gives us kind of that foothold. We leverage the expertise we currently have and then continue to have a momentum, and hopefully, a virtuous cycle of very strong launches to create those durable franchises in both neurology and cardiometabolic. Now as we see other products with larger indications coming in those areas, I couldn't see why we couldn't expand into broader diseases over there, right? Because you've already developed some great relationships with the specialists in the area. You have strong regulatory relationships, and you've got your patient assistance programs, and you're kind of humming, as I call it. So that becomes a really good way for us to think about. We've got some expertise. We -- again, we can figure out ways to kind of get to the large GP populations through some co-commercialization if we need to at that point in time, and yes, if we need to kind of help ourselves with some of the field efforts that would be needed. So that's really kind of a key area for us to think about. And we'll evolve from there. We're going to be opportunistic by other disease areas as they come along. It will be based on commercial data and clinical proof of data. And we've kind of decided to make those decisions on really key decision gates that you get all the way from early pipeline development to commercialization. So -- but really putting some strong foothold into neurology and cardiometabolic.

Okay. Great. We're just about out of time here. So I think we'll leave it there. But thanks, everyone, for tuning in, and thanks so much to the Ionis team as well.

Thanks very much, Jess. Thanks, everybody, for listening. Have a great day.

Thanks, everyone.

Thank you.