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

Hello, everyone. Thanks for attending today's session. My name is Kostas Biliouris, and I am one of the biotech analysts here at BMO Capital Markets. It's a pleasure to have here with me the CEO of Ionis Pharmaceuticals, Brett Monia. And thank you, Brett. Thanks for joining us today. It's a great pleasure to have you here. And maybe we can start with a high-level overview of the company, and then -- for those who are not familiar with Ionis, and then we can take it from there with more specific questions. Thank you.

Sounds great, Kostas. Thank you for the invitation to be here today. It's a pleasure to provide an update on the great progress we're making at Ionis. So Ionis, for those that aren't that familiar with the company, we are a well-established biotech company, now nearly 34 years old. We were created to really pioneer a new way of discovering and delivering treatments for patients suffering with serious diseases, both chronic diseases as well as subchronic diseases. That new sector, the new field that we essentially helped create is focused on RNA, RNA as a drug target. The original platform that we spend most of the vast majority of our existence focusing on and validating is called antisense, which binds to RNA targets RNA and manipulates the RNA function to benefit certain diseases. Since that time, the field has expanded to include siRNA too, it's very similar to antisense oligonucleotides. They work slightly differently, but most of it is the same. And most of the learnings that we have developed over the decades we've been at this at Ionis are applicable -- directly applicable to siRNA, and we're using both platforms today for drug discovery and delivering our treatments to patients. Most people are probably familiar with traditional platforms like small molecule pills or maybe even monoclonal antibodies. Our platform is very differentiated from those platforms and offers several advantages, one of which is that almost all targets are druggable. So we can go after a target that is known to cause a disease, like for example, a mutation in a gene called SOD1 that causes ALS. And we can target it with our platform, but that target is not amenable to small molecules or monoclonal antibodies. And there are many, many drug targets like that, that we can develop. The other advantage versus monoclonal antibodies is they can only work on the outside of the cell, the extracellular space, but not intracellularly. And intracellular targeting is actually very -- within the cell is very important for drug discovery for many targets. And then thirdly, the efficiency. Because it's a platform technology, our drugs are very similar from one drug to another, whether we're treating neurodegenerative disease or a cardiovascular disease. They're very similar. So we can discover and develop these drugs very efficiently that quickly because the similarities -- there are so many similarities from one drug to another. We don't have to reinvent the wheel for every drug that we develop. Based on that, we've developed one of the richest pipelines in the industry today with five -- soon to be five products on the market, and a Phase III pipeline, which is the latest stage of the pipeline, the final stage before potential approval of nine drugs in Phase III development for a range of diseases for 11 different disease indications. So that's where Ionis is today. We're a well-capitalized company. We have more than $2 billion in cash in the bank and a steady revenue stream from both commercial products, partnerships, and through other means as well. So we're doing quite well. And maybe I'll just pause there, Kostas, and see what other questions you may have.

Thank you, Brett, for the great introduction of the company. Maybe we can touch on the ESG priorities of the company. I know you have published a couple of reports showing the great progress you have done on this front. Maybe if you can talk about the priorities on the ESG with regards to patients, with regards to employees, diversity, [ who is in ] your environment. If you can touch on these factors around ESG would be great. Thank you.

Sure, Kostas, happy to. So corporate responsibility is always central to everything we do at Ionis. And honestly, it's been a key priority for the company since its inception, even before ESG became so popularized in the industry and prioritized the way it is. At Ionis, we're committed to discovering, developing and delivering treatments for patients suffering from serious diseases, which, of course, is -- provides a great benefit to those individuals, to society, we're committed to making to the future -- a better future for everybody. We've recently taken several additional steps forward to further strengthen and fine-tune our commitment to corporate responsibility. And in fact, we're going to be publishing an updated detailed report on the areas of focus for the company in April of this year, reflecting on everything that we're doing, all the newest initiatives and so on. So stay tuned for that, and I really invite everybody to take a look at that report. Briefly, one of the top priorities is to continue to be innovative, research and development, innovation, commitment to innovation. In fact, innovation across all aspects of our business with patients at the center, patient advocacy as a central focus for the company. That has been strengthened significantly over the last little bit, and we will continue to drive value for -- with patients always in mind, in our minds to deliver innovation and value for them. The second is to support our employees and our communities. We are very committed to diversity. And in inclusion, we have quite a number of diversity and inclusion groups. Here at Ionis today, you'll see that in our -- when we publish our report and it's growing, and it's expanding. And in fact, we have culture statements in all of the rooms at our company. And one of the culture statements in our culture -- sets of culture statements is that prejudicial barriers are foreign to our values, and that's how we operate, and we'll continue to operate in that manner. And we've also done a lot in the community over the years, including teaching programs, reaching-out programs, patient meetings, investments into organizations that are benefiting patients even beyond pharmaceuticals to help them be able to work through their -- any of the challenges that their disease faces or causes them to face. And we're highly responsible from an environmental and mental aspect to minimize the environmental footprint that we work against. We actually have one of the largest solar farms at Ionis, our headquarters in the San Diego, Southern California area. And we are highly committed, always have been and continue to be highly committed to integrity and in proper ethics. And the way we conduct our clinical trials, the diversity that we try to include in our clinical trials, so we have a good diversity set of patients in our trials and more on that. So again, what I would recommend to everybody is that you really look at the details when we published our latest report in April of this year, which will also include a dashboard on how we're doing metrics wise compared to various measures and what we seek to improve upon as we go forward.

Perfect. Thank you so much, Brett. Maybe we can talk a little bit about the drugs that have already been approved and are commercial in your pipeline. You have drugs approved that are being commercialized with partners. Maybe you can talk about what is approved so far, and then we can move to the products that potentially can be approved pretty soon.

Sure. So today, we have, at Ionis, have conceived, discovered and developed five treatments that are on the market today, all of which are being commercialized by a partner with the exception of one, which we will be co-commercializing with a partner ourselves. And the first to highlight is SPINRAZA. SPINRAZA was a breakthrough treatment for neurodegenerative, neurodevelopmental disease called spinal muscular atrophy. This is a genetic disease, in which data flicks about 50,000, 60,000 patients, individuals around the world, estimated to be with this disease. And there's different forms of SPINRAZA -- of SMA. The most fatal form or the most aggressive form is a form that afflicts babies, in which volume diagnosis soon after birth, when babies are born essentially normal-looking, they succumb to the disease and perish within a year or two. It was the #1 genetic cause of infant death in the world prior to the discovery and development of SPINRAZA. We're very proud of that. And then today, SPINRAZA is the foundation of treatment for all forms of spinal muscular atrophy, including the milder patient populations, the adult population. We licensed that drug to Biogen and they're commercializing it, and it's a very successful drug. And this year, we had another neuro drug from our neurology portfolio approved, QALSODY, which again, we discovered and you can see it developed for a form of ALS, amyotrophic lateral sclerosis, a genetic form in which we -- that drug was approved based on really truly remarkable efficacy. We were the first to show that ALS is actually a treatable disease. And we have other ALS programs in process. So Biogen is commercializing that drug with us as well. WAYLIVRA is an approved product for a genetic cause of severely elevated triglycerides called FCS. That drug is being commercialized by PTC, a partner of ours in Latin America and by Sobi in Europe. That drug will be taken over by our wholly owned drug, olezarsen, which we can talk about, which is Phase III development right now and approaching the market. And then there's TEGSEDI for TTR polyneuropathy -- TTR amyloidosis with polyneuropathy, a genetic severe fatal polyneuropathy that is on the market globally and is being commercialized by our partner, Sobi in the United States and Europe and by PTC in Latin America. That drug TEGSEDI will be overtaken by a better form of that drug called eplontersen, which we expect will be approved in a few weeks by the FDA here in the United States. And in that drug, we actually are commercializing that drug with AstraZeneca in the United States, a co-commercialization partnership. So those are the five drugs that are on the market today and we expect a whole lot more coming in the near future as well.

Great. And since you already touched on that, maybe you can talk a little bit about your drug in ATTR, first polyneuropathy and then cardiomyopathy, which is called eplontersen. And the FDA will -- should decide whether approve this drug in polyneuropathy. Can you talk a little bit about the upcoming decision and then the market in polyneuropathy, what other companies are having drugs which are similar to your drugs? And then the market in cardiomyopathy, who are the key players there?

Yes. Eplontersen is one of our most exciting -- one of the most exciting drugs in our pipeline. We have a lot of them, very exciting drugs. Eplontersen is targeting the cause of a disease called TTR amyloidosis, which is -- primarily manifests as a severe polyneuropathy, which is fatal, ultimately fatal, causes wasting and eventually death. That's a genetic cause -- there's a mutation in the TTR gene that causes this type of disease. And then there's the cardiomyopathy indication, heart failure, which both can be genetic, the same mutations as in the polyneuropathy or nongenetic, It's just that protein is a bad actor and causes accumulation and buildup of plaque, if you will, in the heart causing heart failure, right? And people die due to heart failure, their hearts just can no longer pump. We're developing eplontersen for both disease indications. The first is the polyneuropathy, which is a rare disease, but it's on the higher end of prevalence in rare diseases. About at least 50,000 individuals suffer from TTR polyneuropathy globally. We reported Phase III data, interim data last year, which Phase III is the final step in drug development. Interim data last year, and then the full data set this year, and the data was remarkably strong. We showed highly, highly statistically significant reversion in the disease in several endpoints. And based on that data, we filed for approval for the polyneuropathy indication first in the U.S., and now we're in -- which is -- which we have a decision date in three weeks, called a PDUFA date, December 22. And we're feeling very good about eplontersen in the U.S. And then it's also under review in Europe and in Canada for potential approval and in other geographies as well. The eplontersen profile, the efficacy profile looks very strong, as I said. And we think that eplontersen has the potential to be the treatment of choice for TTR polyneuropathy, not only based on its efficacy and tolerability and safety profile, which is very strong, but also because of the convenience that patients can take this drug at home. Once per month with a simple injection in their thigh or using a simple auto injector or painless injection, low volume, that we think will be a real advantage for our drug from a convenience standpoint as well as efficacy. And then we turn our attention to the heart failure indication, cardiomyopathy. This is a big population. This is hundreds of thousands of individuals. I think it's estimated to be 500,000 plus of individuals suffer from heart failure due to TTR buildup in their hearts. We have another Phase III study that's in process with that patient population targeted specifically. That study is the largest ever conducted in this patient population. It is fully enrolled with more than 1,400 patients and is due to read out as early as first half of 2025 in a cardiovascular outcome trial. So what we're measuring is the ability of eplontersen to save lives, mortality endpoints as well as to prevent events from occurring that will put them in a hospital, so hospitalizations as well. We're very excited about the prospects of the heart failure trial and the polyneuropathy strong data even gives us even greater confidence in the outcome of the heart failure trial. So there are treatments out there today. There's competition within our class as well as there's a small molecule called tafamidis that's on the market today for TTR cardiomyopathy. But patients are still -- their disease is still progressing on tafamidis. So there's some big need for more effective treatments, either in combination or alone to treat this disease. And we think eplontersen is well positioned to meet the need -- to meet the needs of patients around the globe. Again, eplontersen is a partnership with AstraZeneca in which we're co-commercializing in the United States. And then AstraZeneca is responsible for commercializing outside of the United States.

Great. Thanks. And maybe on the polyneuropathy side, let's start there. There is another drug with similar mechanisms by -- approved by a couple of drugs actually that are approved in polyneuropathy by Alnylam. Can you remind us what the differentiating characteristics are for your drug which can help with getting market share there in this space in polyneuropathy?

Yes. It's unfortunate and sad, but surprising also that the vast majority of patients with TTR polyneuropathy are not on any treatment today. Around the world, including the United States, less than 20% of patients are on treatment today. And that's mostly driven because these patients undergo a long sort of journey of misdiagnosis after misdiagnosis. And then finally, if they're lucky, they will get a genetic confirmatory diagnosis of the disease. This disease gets confused with other forms of polyneuropathy sometimes such as Charcot-Marie-Tooth disease or diabetic polyneuropathy. And that's one of the reasons why. The other reason why is that just go find -- you have to go find the patients because it is a rare disease. Our drug is -- the efficacy and tolerability profile looks great and it's highly competitive with the competitor that you just referred to, Kostas. I think the key differentiating factor for our drug, which based on all the research we've done is the preference for the flexibility, the freedom, the independence of patients to be able to self-administer using a simple auto injector, low volume that patients can do, treat themselves when -- at their convenience, wherever they are once per month, whereas our competitor requires the drug to be inserted by a health care provider, which means that you have to schedule appointments, right? You have to commute to go to where you need to go to. Physicians have to schedule their staff to see patients, that kind of thing. It's not preferred based on the research that we and AstraZeneca have done. So we think that, that's a significant advantage. And the other advantage and one of the reasons why I highlighted patient finding -- patient diagnosis, I should say, is a challenge, is to take advantage of the global presence, the global strength of AstraZeneca, our partner, which is in all corners of the world with a very sizable commercial organization, not just in the United States and Western Europe, but also in China and in other countries in Asia and in Latin America. All of this, we think, will allow us to find patients more effectively than we would have been able to do alone as well as coupled with the convenience of a self-administration profile.

Great. Very helpful. And can you remind us when should we expect approvals in other places outside of the U.S. Potentially, you may get an approval this year in the U.S. When should we look for approvals ex U.S. in the locations you just mentioned?

Yes. In Europe and Canada, we would expect approval next year. And then following that, we're probably -- there may be other geographies late next year that we would get an approval in. But certainly, the filings for approval are going to be rolled one over after -- one after another. So there will be a continuous approval process that we expect for eplontersen for polyneuropathy. And we are filing globally. And so it will be a continuous process.

Perfect. And maybe on the cardiomyopathy side, can you touch on this space, which is very different. We have a drug which is approved already in cardiomyopathies -- from tafamidis. Potentially, we may have a second stabilizer from BridgeBio sometime next year. And then we have Alnylam which also is developing an RNAi therapy. And then we have eplontersen and then gene editing therapies that are being developed by Intellia. So can you maybe give us a view around how you expect each space to go in terms of who gets what and maybe with that sequence potentially?

So I think it's -- the United States is a great benchmark for what will happen as drugs roll out across the world around the globe. So in the United States, using that as an example, today, tafamidis is a standard of care for patients with TTR cardiomyopathy. The majority of patients with -- that are diagnosed are on treatment today with tafamidis, and tafamidis provides benefit to patients. But there's still a lot of room for improvements. Patients are still progressing in their disease and dying of heart failure. There's a lot of room for improvement, and the need has grown substantially. There are -- tafamidis works through a mechanism in which a dysfunctional protein, the drug binds to a protein that's misfolded, dysfunctional, and it tries to refold it or prevent it from unfolding and being dysfunctional. And that's how the BridgeBio drug works as well. So the protein, which is produced from the liver gets into the circulation where it then tries to get cleaned up by the small molecule drug tafamidis or acoramidis, which is the BridgeBio drug. Our mechanism is a silencing mechanism. We blocked the production from the liver so the drug -- the disease-closing protein never gets made, right, it never gets secreted. It doesn't get out there in time so there's no need to clean it up once it's in the circulation of doing damage. We believe that the silencing mechanism, because you're blocking the production of the toxic protein remember being made from the start, from the get-go, it will be more efficacious for this patient for any form of TTR amyloidosis. The polyneuropathy data supports that conclusion in which tafamidis was developed for polyneuropathy years back and actually didn't hit its primary endpoint. It wasn't approved in the United States, and whereas we have seen stunningly positive efficacy in the polyneuropathy indication. So we think that, that bodes well for the outcome for the cardiovascular cardiomyopathy indication. And that, coupled with the convenience of self-administration and the excellent safety we're seeing with eplontersen, we think it really represents a potential real breakthrough for patients suffering with heart due to -- suffering from heart failure due to TTR amyloidosis.

And in terms of potential combinations between different approaches here that are being developed, any thoughts?

I don't think there's any point -- there's any rationale for combining two silencers. They kind of do the same thing, but you can make a case for combining a silencer like eplontersen with a drug like tafamidis, right? And in fact, I think that's -- and that's what I think was -- more importantly was the market research that we and our partner AstraZeneca have done, shows that physicians are ready to treat patients already on tafamidis with a silencer to put it -- a silencer on top of those stabilizers. They know patients are continuing to progress, and they believe that silencers will provide additional benefit. And of course, that will have to be played out in the Phase III studies. So like I said, in the U.S., and that's with the case, that's what's evolving inside the U.S. too, tafamidis is the treatment of choice today, it's the only treatment for TTR cardiomyopathy. And physicians are eager to add a silence or on top of a stabilizer, because the mechanisms are complementary to each other. We've brought the production of 80%, 85% or so of the toxic protein. The remaining 15%, you can think of it being stabilized by a stabilizer to really clean it and get to 100% maybe or close to it. In our Phase -- very importantly, in our Phase III trial, we actually have both. We have a large segment of patients with -- on tafamidis that we're adding eplontersen on top of as well as a large segment of patients, the other half of the patients are on eplontersen alone. So we actually believe that we're going to have the richest data set to be able to actually show the benefits of eplontersen alone as well as eplontersen on top of a stabilizer, like tafamidis, we're seeing is very important, for patients, for physicians, for payers, for them to see all that data, the richest data set. We're conducting the largest Phase III trial ever done in this patient population, and that's one of the reasons why, is to be able to have that type of data. Depending on how the Phase III data plays out, how great -- or good or great the silencer efficacy ends up being, we also need to think about whether -- about newly-diagnosed patients in the future, right? Will a newly diagnosed patient automatically go on to tafamidis, which is the standard of care today because it's the only treatment option for patients? Or will they just go right to a silencer right off the get-go. That's to be determined, and that's going to be really data-driven, and we're looking forward to the data when it reads out.

Perfect. And maybe last question here on the diagnosis of these patients. You mentioned on the polyneuropathy side, that only about 20% of the patients are being diagnosed and treated. How about the cardiomyopathy? I know that it used to be similar, but after tafamidis approval, Pfizer improving the diagnosis rate of these patients, any thoughts here about the diagnosis and how your partnership with AstraZeneca can again potentially help here by reaching patients ex U.S.?

Diagnosis has improved in TTR cardiomyopathy really significantly over the last few years. And that is driven by several things, one of which is the fact that tafamidis is a drug. So you have a drug to actually treat and search for patients because once you diagnose them, you actually could do something about it, right, you actually have a treatment. But more than that, Pfizer, who commercializes tafamidis has done great work in drawing attention to this disease, right, patient -- or disease awareness. A disease that was really, really poorly diagnosed in the past is much more readily diagnosed today. And then thirdly is the fact that diagnostics has improved tremendously. Back when tafamidis was first developed, you had -- you actually had to take a biopsy and staying histologically for amyloid to confirm that you actually had TTR cardiomyopathy. Today, you can do it noninvasively using imaging techniques. So it's much, much easier to diagnose. Based on all of this, these patients are being diagnosed earlier in cardiomyopathy, and they're living -- they would not live longer than they normally would live based on their -- the time of their diagnosis, which is why -- one of the reasons why. Another reason why the size of our study is so important because our study has the sample size that we believe supports the powering that needs needed for a patient population that is being diagnosed earlier on in their journey through heart failure. So just another reason why we think we have the right trial design for this area of disease that has such a high unmet need.

Great. And just a reminder here for those who are attending virtually, you have any questions, please, if you can post it on the platform or email me and I'll make sure we address your question. So I think it's time to move to the next program, which may not be as big as ATTR and eplontersen but it's fully old and a lot of people I know are very excited about that. It's HAE, hereditary angioedema. So can you maybe give us an overview of the donidalorsen and the disease, the size of the disease and what is the current standard of care there that you are trying to compete with?

Sure, happy to. We're very excited about donidalorsen. This is a drug to prevent the attacks that are associated with hereditary angioedema, Hereditary angioedema or HAE is a genetic disease that results in extensive, massive swelling of certain tissue beds, including the larynx, which can cause suffocation. The other thing about this disease is that the onset of an attack, a severe attack, which is disfiguring and it's so incredibly debilitating, you could be in a hospital and can be fatal, is unpredictable. It can happen any time. It can happen at work. It can happen at a celebration event or anything like that. It's unpredictable, and it's genetic, as I mentioned. Today, there -- for prophylactic treatment, which means to prevent the attacks from happening, the standard of care is a drug by Takeda called TAKHZYRO. TAKHZYRO greatly -- was a breakthrough, it greatly reduces the percentage of attacks in this patient population. However, patients are still getting attacks. It reduces about 75% or so. It's also not the most -- best tolerated drug that's out there today. It's a subcu drug, which requires, I think, two injections, large volume. This can be painful. And patient -- and it's every -- really most patients are on it every two weeks with this injection. So patients want better efficacy, better tolerability, better convenience. And donidalorsen is set up to address all three of those based on a lot of data, Phase II data, now long-term open-label extension data for two years of treatment after the Phase II study, which we showed 95% mean reductions in HAE attacks. So a big improvement in attacks with once per month that was seen. So we've got the convenience box checked with the potential for every two months dosing, which is in our current trial design, one month and two months options, flexibility in dosing with a simple painless auto-injector low-volume self-administration once every month or two. So that's the profile that we're excited about. We think we have -- that this is going to be a preference for many patients suffering with HAE. The other thing, Kostas, is that in the U.S., most patients are on TAKHZYRO or prophylactic treatment like that. The other question then is how do you get the patients to switch? Well, we actually are running a switch study right now, in which patients that are on a drug like TAKHZYRO or other prophylactic treatments that are even less efficacious than TAKHZYRO are being offered to come on to donidalorsen in a switch study, and then to see how they feel about the drug. Well, we were very pleased to see that we were able to enroll that study, which is around 60 -- more than 60 patients, enroll it fairly quickly, showing that patients want other options. They like the profile that they have seen with donidalorsen. We're also very pleased by the fact that patients are staying on donidalorsen for long periods of time extensively. The dropout rate has been very low. So they prefer -- appear to be preferring donidalorsen. And then thirdly, we're going to be able to have the data to be able to show how an allergist, which are the doctors that are principally see these patients, when they come to us and say, okay, you convinced me, how do I do it? How do I switch without putting the patients at risk for an attack? Well, we're going to be able to actually have the data showing that, how you wean them off of one prophylactic treatment and we protect them with donidalorsen without attacks happening, no gap in protection. So we'll actually be able to show that data as well. So that's donidalorsen. The Phase III data we're expecting in the first half of 2024. And if anywhere near as positive as Phase II data is, we'll file next year as well for approval in the United States.

That's perfect. And then maybe we can move to the next program, which is, again, wholly-owned, olezarsen. As you mentioned, you recently had some positive data from FCS. Can you describe a little bit the dynamics there in FCS then severe -- hypertriglyceridemia that you are currently evaluating the drug in? And what are your expectations there? Because I know these are -- you are targeting a condition that is currently not well understood or currently not well treated. Especially in FCS, there is pretty much nothing, no option for these patients. In hypertriglyceridemia, there are some options, but definitely far away from being perfect. So if you can give us an overview of the dynamics there and how do you expect your drug to address the unmet need in this space.

Yes. Wholly-owned drug, we're planning to bring to market ourselves. This will represent our first independent commercial launch. We've been reliant on partners throughout our history. This will be our first independent launch. This drug, olezarsen, is -- was designed to manage severely elevated triglycerides in individuals. Triglycerides are a lipid, think about it like cholesterol. But it's a different type of lipid, which causes different problems, not really adverse sclerosis like it does in -- like cholesterol does, but it causes patients to be at a severe risk of pancreatic failure, acute pancreatitis events that can be fatal, that can put them into ICU for extended periods of time and is recurring. So once you have one pancreatitis event, the chances are you're going to have another one and another one, any one of which could be fatal. They have other problems too, metabolic problems, disturbances, stomach pains, but that's the current principal thing we're trying to fix, protect patients from. There's two forms: a genetic rare form called FCS, and then a very large population in the United States alone that has made to be more than 3 million people with nongenetic severely-elevated triglycerides. We reported -- we're developing olezarsen. The rare population, FCS, we completed the Phase III study this year, and we reported the results in September, I think it was, where not only did we demonstrate substantial reductions in triglycerides that were highly statistically significant, we also showed substantial reductions in acute pancreatitis events in patients treated with olezarsen, which was truly remarkable. There are no treatments in the United States marketed today for FCS. So we're excited about these results, and we plan to file for FCS or approval early next year in the U.S. and outside the U.S. And then for the broad indication, SHTG, severe hypertriglyceridemia with no known genetic cause, millions of people in the United States again, these are individuals with triglycerides above 500, usually in the 1,000. Normal triglycerides are like less than 100. Similar to FCS and the elevations of triglycerides, there are no good treatment options for SHTG either. Most patients are -- they are attempted to be managed with fish oils or fibrates, they're not very effective, mild reductions in triglycerides. Olezarsen is designed to show that in multiples, multiple reductions in triglycerides, well beyond that of current treatments. And that's what we saw in the FCS. Then we expect that to replicate at least in the SHTG population. So this is a big market opportunity, a big unmet need, millions of people. And that Phase III study is enrolling patients now, and we expect results in early 2025.

Perfect. Thank you so much. With that, I'd like to thank you so much again for joining us, Brett. I think it's a very exciting time for the company. You have three key catalysts coming up, as you mentioned, the PDUFA date in December. Then you have the HAE readout in the first half, and then in the second half or early 2025, you have the olezarsen readout, which are three very important catalysts in addition to other things that obviously will be going on. But these are, I think, things that investors are closely watching. And just to mention that the stock year-to-date has been doing very well. It's up 37%, 38% compared to XBI, which is down about 5% year-to-date, so this is a great outcome. So I think it's a very interesting time for the company and a very distinct stock to watch as we head into 2024. Thanks, everyone, for attending our event today. Thank you, again, Brett, for joining us. Great to have you, and we look forward to watching your progress.

Great. Thank you very much, Kostas. I really appreciate it. Take care.

Thank you. Bye, everyone.

Bye.