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

Good day, everyone, and thank you for joining the 23rd Annual Needham Healthcare Conference. My name is Joey Stringer, and I'm one of the biotech analysts at Needham & Company. It's my pleasure to introduce our next presenting company, Ionis Pharmaceuticals. Joining us today from Ionis is Head of Investor Relations, Wade Walke. [Operator Instructions] So with that, we'll go ahead and get started. Wade, thank you so much for joining us today.

You bet. I'm glad to be here, and thank you so much for the invitation.

Now this past day or two, Ionis announced some new data from olezarsen and FCS. So we'll get to that in a little bit, but let's first start with the TTR program, WAINUA proof for TTR polyneuropathy, you partnered with AZ. Just curious if you could provide any color on what type of launch metrics either you or they could provide as the launch progressive -- as the launch progresses?

You bet, happy to. Maybe just before I talk about WAINUA, I could kind of give you a little bit of update for people maybe haven't been following us that closely recently or maybe even those that have, we have a lot going on. In addition to WAINUA, which was just approved and launched this year in January, it was approved at the end of December and launched in second half of January. We just reported Phase III data from our olezarsen program at ACC this weekend, which I mentioned, we'll get to a little bit later. And in addition to that, we also reported Phase II data for our MASH drug, targeting DGAT2, which was positive. And in January, we reported positive Phase III results for donidalorsen, our drug curing HAE, and we'll have more data on that reporting at a medical conference in the midyear as well. Last year, we also had a better year, right? We had -- QALSODY was approved, the first drug for SOD1-ALS patients. It was our second approved CNS disease medicine. We also reported positive results for our Angelman program and for our program targeting tau for Alzheimer's disease. And I think all of this really further demonstrates our leadership position in the neurology space, very exciting stuff going on. And just looking forward, we anticipate our first potential independent launch with olezarsen in early next year if the drug is approved with priority review by year-end. And we expect to file the NDA for donidalorsen later this year with potential approval next year. Donidalorsen will be our second independent commercial launch. So we're starting to see more and more of these drugs that we launch independently coming out of our pipeline. And we also expect to have some important mid-stage clinical trial results for our Angelman program and our ALS program targeting ATXN2 as for the sporadic patient population, which is 90% of ALS patients. Those results we expect mid-year. And results from our Phase II study in geographic atrophy with a drug targeting Factor B in the second half of this year. So just a lot of stuff going on, very exciting. We've really just -- the last several years, we've just been having one success after another, and so it's been an exciting time to be at Ionis. And all of this really sets us up nicely to deliver a steady cadence of new medicines to patients. Now turning back to WAINUA, which is what you ask me about. I can tell you the launch is off to a good start. AstraZeneca is responsible for booking product sales. So they'll be reporting the product sales on their earnings reports, and we'll report the royalties that we get that are in the mid-20% range on U.S. sales. So we're reporting those on our quarterly reports. Other than that, there won't be too much more detail coming out. That's the way AstraZeneca handle stuff, and so we'll be going by their playbook on that one. So -- and given that the market remained pretty much underserved and there's a large portion of patients that are currently not on treatment. As we see the market growing, we think, we and AstraZeneca are uniquely positioned to capitalize on finding and identifying and getting new patients on treatment with WAINUA.

Yes. And to that point Wade, for polyneuropathy specifically, where do you see long-term commercial opportunity for WAINUA. Is it in the switch market that treatment-naive patients? And then kind of as a follow-up to that, where do you think the field stands right now in terms of diagnosis rates for polyneuropathy specifically?

Good questions. So in the ATTR polyneuropathy indication, it's -- there's still -- there's been a lot of work that's been done to diagnose and find these patients. But despite all of that, despite the new medicines that are out there, fewer than 20% of the estimated 40,000 patients worldwide are diagnosed and are on treatment. So -- and we see -- there's several guidelines and consensus recommendations for diagnosing in these patients that are available and continue to evolve, but patients still find it difficult and have a complex journey towards getting to the help they need because the symptoms of ATTR polyneuropathy are kind of mirrored by other conditions at times. So patients often require several visits to physicians before they receive a correct diagnosis. Our research shows that up to 40% of patients are misdiagnosed before they finally receive an accurate dose. So we are out there as far as the switch versus naive patient market since there's less than 20% of patients that are on treatment right now. Our main focus, we and AZ are focused on finding patients, getting new patients on treatment. Of course, if patients want to switch from the current therapy they're on, we'll let them. That's not a problem. But our main focus is really to try and find these patients get to accurately , get them on treatment because that's where the biggest market potential is in the long term for this market. And we think that we've got in a great position together with AstraZeneca. We've been working in the TTR space for many years, and AstraZeneca is uniquely positioned with its large commercial infrastructure and especially as a lot of these patients are mixed phenotypes. So they also present with cardiomyopathy symptoms and our end can be found in cardiomyopathy or cardiologist offices. And AstraZeneca, of course, has a large presence in cardiologist offices. So they're uniquely positioned to be able to help find these patients that also are TTR polyneuropathy. So I think the combined efforts of both companies are put us in a good spot for finding these patients.

Yes. And switching from the polyneuropathy to your ongoing program and cardiomyopathy, obviously , the Phase III CARDIO-TTRansform trial ongoing. Just briefly, can you outline the trial design there, and what are some of the key design elements that you think gives you confidence that you have the right approach here and are set up for success in the long term in this indication.

You bet. So CARDIO-TTRansform is our study that's looking specifically at patients with the cardiomyopathy form of ATTR disease. And it's the largest study in patients to date in this patient population with more than 1,400 patients enrolled. That's bigger than -- 2x larger than the next closest trial in this patient population. And it's specifically designed to demonstrate benefit in the broad population of patients, including patients on stabilizer or those that are naive to stabilizer and patients who are -- have a mutation versus those who are wild-type, and we've got several sub-studies as part of this program, 2 sub-studies. One, that's looking at using advanced imaging techniques to see how WAINUA treatment could affect changes in the heart itself, and MRI sub-study that's looking at scintigraphy study, I should say, that's looking to look at the changes in the TTR plaques, that build up in the heart as well. So we think we've got a well-powered study. We think it's looking at a lot of different interesting parameters that will help patients and especially physicians who are treating these patients to know when is the best time to treat these patients, how best to treat them, and what benefit there may be in different subpopulations, patients on stabilizer, patients naive, patients who are late stage in disease, early stage in disease, these different things. And reason that we have these large studies because we recognized several years ago along with the academic community, that there were a lot of changes going on in this patient population with new techniques to diagnose this disease, noninvasive techniques, including the scintigraphy technique as well as Pfizer's efforts with tafamidis to find and diagnose these patients, get them on treatment. These patients were getting diagnosed earlier. And so the patients coming into clinical studies were less severe. They were diagnosed earlier in their disease. And so because of that and because all of us -- everybody is doing studies in this patient population are conducting outcome studies. You have to recognize that as you get to a less severe patient population, you're having fewer events. And so you have to take that into account when you size and power your study, we realized that we needed to increase the size and duration of our study, and we did that a couple of years ago. And now what we're seeing from recent studies, and what we're seeing in patients commune our study is tracking with the assumptions that we have based on those updated powering assumptions. So we're pretty confident that we have the right study in this patient population.

And speaking in terms of the subgroup analysis you mentioned, can you talk a little bit more about what the important data from those subgroups that investors should focus on, including those that are the treatment-naive patients, those that are a background tafamidis? And maybe secondarily, do you think that you'd need to show a benefit in the market population versus the overall population to have a, let's say, commercial success or uptake?

Yes. Well, I mean, the way the study is designed, currently, it's looking at the overall population and the combined events hospitalization mortality in that patient population. And as a subgroup, as a secondary endpoint, it's looking at monotherapy. So we'll have that data in the study. Even if we are looking at the overall population, we'll still -- we'll capture the monotherapy effects in this patient population. And so we best of all worlds, you might say, because we can see, is there a benefit as a monotherapy? Is there a benefit on to be on tafamidis, and we can compare those different subgroups in war study. And we think with the size of our study, we've got the powering needed to number 1 hit the end point overall, but also see if there's interesting -- at least interesting benefit trends in those subgroups analysis.

How the blended event rates progressing, Wade? Any updates on when or if we could see an early readout from the trial?

You bet. So the event rates were -- blinded event rates were tracking regular basis, and they're tracking according to our plan. So that looks good so far. As far as when we could read out the study, we look at a couple of different things. And one is are the blinded event rates tracking according to plan or are they doing better or worse or whatever so that we can estimate when we'd want to end the study early. The other thing is that as other data comes in from other studies, we can incorporate that into our assumptions and take a look and see whether or not we could end the study early. So if we see significant benefit from, say, another silencer in the field, then we might be able to take that into account into our assumptions and decide whether or not we want it in the study early. But we have that flexibility built into the study so that we can do that or we can run it all the way to completion if we need to.

Kind of leads into my next question. I suppose it just depends on what the data look like. But obviously, competitive data readouts, how will that specifically influence your decision on the potential timing of the CARDIO-TTRansform readout?

Yes. So that's a great question. I think since we have a silencer and there's another company out there that has a silencer as well, we're both basically working in the same class. And so to see what kind of an impact the silencer can have on this disease, will be obviously read through to our work that we're doing as well. And I think that's what's interesting is that I think if this -- the HELIOS-B study, which is what we're talking about here, reads out positive, I think that derisks -- that further derisks our study as well because that there's -- you can have a good effect with the silencer class, and that means that we can build off of that information with our study as well.

And last one on WAINUA here. In terms of big picture obviously, a lot will depend on what the data look like. But can you talk about some of the discussions that you've had with physicians and that you've had around -- and thoughts around potential reimbursement for silencers, such as WAINUA for TTR cardiomyopathy versus oral stabilizers. What is your research telling you about the potential reimbursement dynamic?

Yes. So I mean several people have asked us what's the potential for the drug as a monotherapy for reimbursement, of course, it's like on top of tafamidis, which is an expensive drug. And the discussions we've had indicate that if you have data to show that there's a benefit, does it have to be stat-sig, but if there's a trend in benefit that you have a better chance of getting reimbursement for combination treatment because these patients on tafamidis, the majority of them continue to progress on tafamidis. So it does slow the progression of the disease, but it doesn't necessarily stop the progression of the disease, and it is a fatal disease. So when physicians are treating these patients and they see them progressing and they know that there's another treatment that could have some benefit, they're likely going to request that payers reimburse for that drug, so they can put them on a second drug to see if they can provide additional benefit in this fatal disease. And the monotherapy market is pretty large, too. I mean I don't want to put that down, right? Because as far as there's a lot of patients that are getting diagnosed, physicians may feel like if the stabilizer has a better impact on the disease, they may want to start them on that instead of a stabilizer for example, or if they're progressing, they may want to switch them from a stabilizer to a silencer first. So it just depends on what the data shows. And there's it's a pretty big market. So I think there's pretty good opportunity in both cases.

Great. Well, we'll overview WAINUA, and a lot of programs to get to -- switch gears to olezarsen. Certainly, top of mind is the recent FCS data that you put out. We'll touch on FCS as well as SHTG. But first, FCS, you gave a presentation Sunday morning and then a conference call this morning. A lot to unpack here, but first, give us a quick overview of the FCS indication, the unmet need there, and how you plan to position olezarsen, and then we'll get into some of the data.

Sure. You bet. So just a little background on FCS. It's an ultra-rare disease, somewhere between 1 and 13 per million as far as prevalence goes. So there's maybe anywhere from hundreds to maybe a few thousand patients in the U.S., for example, as far as numbers go. And it's a very severe disease that's driven by extremely high triglyceride levels. These patients will have triglycerides that are 10 to 100x higher than a normal person might have. So whereas you and I might have 70, 80, 90 mg per deciliter in our blood, FCS patients will have 2,000, 5,000, sometimes even as high as 10,000 or 11,000 mg per deciliter. Their blood so full of triglycerides. It looks milky white. And if you set it aside for a minute in a vial, you just get this big layer of fat that rises to the top. It's pretty amazing that that's even possible when you think about it. And these patients are at very high risk for acute pancreatitis along with other complications, abdominal pain, cognitive issues, [indiscernible], the FCS brain fog. And I think in -- with FCS patients, I think the stats are that more than 70%, 80% of the patients have a history of pancreatitis. And so that's -- it's pretty severe, a lot of these patients diagnosed pretty young, like when they are in their 20s. Some even had pancreatitis attacks as children. And so it's just a very severe disease. Of course, acute pancreatitis can be fatal. If you have 1 attack, you're 3x more likely to have another attack. If you have 2 attacks, you're like 10x more likely to have another, a third attack, it's just a downward spiral. So you really want to get these patients on a therapeutic and lower their triglycerides and reduce that risk of pancreatitis. And the great news is that the data that we presented this weekend shows that olezarsen can do just that, very substantial reductions in triglycerides, which is very hard to do in FCS patients because they have these genetic mutations that limit their ability to break down triglycerides. So they have -- of the 2 main pathways to clear triglycerides lipoprotein lipase, LPL and clearance mechanisms to deliver, their LPL pathway is basically gone. And so they clear triglycerides extremely slowly. They can have a meal with some fat in it, and that fat will be in their blood for a week or so, whereas you and I will clear it in hours. And so for these patients, we saw with olezarsen that we almost completely eliminated pancreatitis attacks in these patients in the patients that were in their 50 and 60 -- 50- and 80-milligram dose cohorts. So there was only 1 attack in each group. And in the placebo group, there were 11 attacks. And the first attack happened in the placebo group like 9 days after randomization, and there was kind of a steady cadence of attacks throughout the placebo group during the study. And in the treated groups, in the 50-milligram group, the first attack was months later, like 4 months or something later, 102 days. And in the 80-milligram dose group, it was almost a year out before that attack happens. So there's a huge delay, not only reduction, but a huge delay in time to first event in the study. And all of this shows for the first time, basically that a drug that lowers triglycerides has an impact and benefit in acute pancreatitis. And that's something that was recognized by the medical community because we had not 1, but 2 New England Journal of Medicine papers published this weekend with a presentation of data from 2 of our studies and an editorial that accompanied those publications. So it's something that the medical community is focused on.

And we'll get into the olezarsen, and what the reduce from the pancreatitis data mean for SHTG in just a second, but one last question on the FCS indication. Just given the data that you have there's a competitor program out there. How do you think the data you presented in the last day or 2 put you in a great position to capture the market and the competitive profile.

Yes. I think we have a very competitive drug. If you do apples-to-apples comparisons, we actually see in similar patient populations, which is tricky because if you're comparing FCS patients to SHTG patients, then you're not doing the right kind of comparison, right? Because FCS patients have these genetic mutations that SHTG patients don't have. And so if you look at like -- we don't really have much data in any competitor with FCS data specifically. But if you look at SHTG data that we've looked at, we see triglyceride lowering in the greater than 80% reduction, which is fantastic. It's lower in FCS patients because, like I said, it's a harder patient population to move the needle on. But again, pancreatitis is the main issue there, and we certainly saw a very substantial effect on pancreatitis in that patient population. And when you look at APOCIII lowering, and you do -- and again, if you look at placebo-adjusted numbers, not just looking at adjustments from baseline, you see that our target reductions are in the 80% range plus, and so we're seeing very, very potent effects on the target, and that's translating to real effects on not just triglyceride, but in case of FCS patients, reductions in acute pancreatitis attacks.

That's a good segue into the SHTG indication, Wade. You've got several late-stage trials, Phase III trials ongoing, expect to read out data in 2025. Just want to, can you briefly touch on what each of those trials be outlined for those, and then we'll talk more on the primary endpoint and some of the key secondaries in the pancreatitis, what would be important there?

You bet. The design for SHTG program is that we have 2 pivotal studies because that's what's required by regulators in a larger patient population. So CORE -- they're called Core and Core 2. And each of those is going to enroll somewhere around 400 to 500 patients, one a little bit more than the other. But in total, somewhere around 800, 900 patients between the two of them. And then we have the ESSENCE study, which is a study to round out the exposure safety database that we need for the filing. And that's actually not in SHTG patients. That's in patients with triglycerides between 200 and 500, just to investigate that in a different patient population, but one that's obviously easier to enroll because you have even more patients, but they also have different aspects about their background conditions like they have a higher prevalence of type 2 diabetes, which is also seen in SHTG patients but often in a higher degree in these lower transit patients, and they can have cardiovascular disease and high BMI liver fat, that sort of thing. So it's one that helps the regulators get comfortable with the safety profile in a broader patient population. And so those studies -- ESSENCE is actually fully enrolled. It's got over 1,400 patients in it. And then we're close to fully enrolling CORE and CORE 2 and those are 12-month studies. So we expect all of this data would come out here next year. That's planning CORE and CORE 2 in SHTG patients, that's greater than 500 mg per deciliter as far as treatments with [ the doubles ].

And primary endpoint, there's trade reduction, but curious if you can talk about the importance from the clinical and also a commercial perspective on the key secondary endpoints, in particular, the acute pancreatitis rates.

You bet. So the regulators, particularly in the U.S., only really require triglyceride reductions as a primary endpoint for approvability. And obviously, we're tracking a pancreatitis in that study. It's lower in SHTG patients. The rate is lower in SHTG patients than it is in FCS patients who obviously have generally much higher triglyceride levels at a higher risk, but it's still pretty substantial, right? And the studies are like about 10x larger than the SHG or the FCS study. And so although we have a lower rate, we also have a much larger number of patients. And so we have the potential to have a significant number of events to track in these patients. And we are seeing -- I can't give you all the numbers, but we are seeing AP events in the study. So we know that they are correct. Now if we see the same kind of dynamic that we see with FCS patients as far as like almost 80%, 90% reduction in AP attacks, then we would expect that the majority of those attacks are happening in the placebo patients. And so we would potentially see a benefit in SHTG patients. Obviously, the data will tell. We'll have to see. But the FCS data, that does give us some more confidence that we're going to see some benefit in SHTG patients.

Confidence in the read-through to SHTG. In terms of powering, is the CORE -- are the CORE trials -- are they powered to show a static difference on AP reduction? Or how do you have those -- have you disclosed that?

We haven't really disclosed that, but I can tell you that it's powered to show the primary endpoint, which is triglyceride reduction. I don't think anybody thought that you could get the kind of magnitude of benefit that we saw in FCS patients with AP reduction. And so who knows what we'll see. I mean that -- we didn't look to power it for a reduction in acute pancreatitis, but with -- if we have the same kind of magnitude and we have enough events, knows what we could find, right? And as far as that goes. So I think we can't promise that we're going to see [indiscernible], because it obviously, it wasn't powered for that. But I think we're pretty confident we're going to see some sort of benefit.

And last question on olezarsen. Obviously, 2 indications here. Can you broadly outline what the commercial strategy would be for FCS and SHTG. How big of a footprint would you need?

Sure. So for FCS, it's an ultra-rare indication, and we'll scale the commercial effort appropriately for that. And we're looking at really focusing our efforts to really tailor the program to benefit FCS patients, physicians, caregivers and payers as well in that terms. And people often ask us, how are you going to price for FCS versus SHTG and we will start with a rare disease price for the drug when it comes out for FCS patients. And then when the drug gets approved for SHTG, we would drop the price to an appropriate price for that larger patient population. And so when we look at commercial size, it would be fairly efficient for the FCS patient population. It's a small number of patients in the U.S., there's fairly focused a number of treaters. We're pretty familiar with the KOLs in the space and the people who are treating these patients, and it's going to be scaled according to that size and effort in that regard. But we -- there is going to be some effort needed to find these patients. They're still not all identified yet, right? There's a lot of patients out there that have high triglycerides and are having symptoms and they don't know that they have FCS, even though it seems hard to believe, but they're still out there. We need to find them.

And moving on to donidalorsen. Another exciting program you guys have in late stage. She read out positive data in January from the Phase III trial met the primary endpoint. You haven't yet disclosed the treatment effect, but maybe zooming out a little bit, there are multiple lactic therapies out there, market leaders, TAKHZYRO. How do you view the market opportunity for donidalorsen? Where do you think doni would fit into the treatment landscape?

Yes. That's a good question. I mean, it is somewhat crowded space. TAKHZYRO is the market leader with a prophylactic treatment, which is a majority of patients in the U.S. on prophylactic treatment outside the U.S., it's different dynamic where I think most of the patients are on on-demand treatments. So there's a growth opportunity in U.S. Inside the U.S., when we look at the opportunity there, there's -- TAKHZYRO does -- I'd say, it does -- kind of set the standard as a really good job on efficacy, but it still has some other issues that patients are looking for something better, right? You could tell that because when ORLADEYO, the oral drug came on the market. it had much weaker efficacy than TAKHZYRO, but a lot of patients switch because they were looking for something different. And I think that's because TAKHZYRO has a pretty extensive administration. Most patients are on injections every 2 weeks. We've heard that they're fairly large volume and that they're painful. And so patients are looking for something that maybe is better tolerated in that regard when they look to go to ORLADEYO. Now we've heard since then, there's a lot of patients that have been switching back to ORLADEYO to TAKHZYRO because of the efficacy issues. The great thing about done at donidalorsen is that we kind of have all of these things wrapped up into a single package, right? So we can shift the paradigm of an injection every 2 weeks or maybe every 4 weeks for some patients to donidalorsen, which you can dose every 4 weeks to 8 weeks, right? Probably the majority of the patient -- probably everybody will start on every 4 weeks, but then you might be able to shift some patients to every 8 weeks, depending on how well controlled they are. And then we have a drug that is in a small volume being delivered through an auto-injector that be self-administered. So you've got a simple injection, you've got something that is less frequently dosed and could have all of the benefits of prophylactic treatment that you find kind of like in a couple of different drugs all in a single drug. So that's where we think that we might have the opportunity to fit in the market. It's have that simple injection, the convenience, the efficacy kind of all wrapped into one.

And now you plan to announce additional data middle of this year. What's the bar for success on the monthly attack rates? I think closest injectable prophylactic competitors have reduction around 87%. Is that really the bar for success here? And are there any other endpoints that will be important for the uptake in the switching dynamic?

Sure. I think obviously, getting something in the ballpark of that efficacy, something in the 80% range is going to be important for efficacy, but you also got to remember that we can achieve that with every 4-week dosing. Whereas that's TAKHZYRO every 2-week dosing. Yes. So I mean -- so just right there, you've got a benefit even if you can achieve something on par, you've already got a benefit because you've got less frequent dosing, right? The other thing, too, that we're looking at is we're one of the first ones to do it's called a SWITCH study, and we're taking patients that are on their current prophylactic treatment and switching them to donidalorsen and then looking -- making sure that we can keep them tag-free, how do we do that? What's their benefit with their prophylactic before switching? What does it look like after switching? And then asking them -- doing a survey afterward and asking them, which drug they preferred. Did they prefer their previous one, or did they prone donidalorsen and kind of gathering all of that information will help physicians, who -- assuming that everything looks good, and the drug is approved that physicians will know how to switch patients from prophylactic treatment that are currently on onto donidalorsen safely and effectively. And so that's something we think will be important. And that's also data that we're going to present midyear along with the Phase III data.

Yes. Certainly looking forward to that data. And last question on donidalorsen. HAE in the U.S., it's a little bit different from your broad cardiovascular CNS type focus. What's the commercial plan here? Will you need a large infrastructure build? And what gives you confidence that you can execute commercially in this indication?

That's a good question. For us, we see it as a fairly easy commercial lift. It's not like olezarsen and SHTG, where you've got a very large patient population and are going after a larger physician base, but with prophylactic treatments for HAE in the U.S., especially that's pretty concentrated prescriber base. So the opportunity is pretty attractive for us, right? The majority of HAE patients in the U.S. are treated by allergists and about 1,000 allergists or immunologists manage about 70% of HAE patients. So as a result, we expect that we'll have a fairly efficient field team that we can use to get to physicians and patients in this market. We figured that we'll probably have somewhere less than 100 customer-facing team that includes field sales reps that are focused on the top allergists, immunologists, the prescribers, and we'll have patient education managers supporting donidalorsen patients out there as well. So all of that in, we don't think it will be a huge commercial lift. And just to set expectations, I know TAKHZYRO is selling, I think, somewhere around in the $1 billion range. We don't project that we're going to be in that $1 billion sales range. I mean, we think the market is crowded, and there's other players coming in the space. we're projecting that we probably get somewhere at peak sales of maybe $500 million for that drug. So even though it's not necessarily a blockbuster drug, it's also proactive from the return on investment.

In the U.S., Wade, or is that in terms of what -- how you're thinking peak sales opportunity or...

That's peak sales global.

Global. Got it. Okay. Well, we've got a couple of minutes left and several programs to get to, not enough time, but I wanted to touch on Angelman syndrome 582, program that's partnered with Biogen, what fun -- interesting is that they mentioned it several times and highlighted in their recent earnings presentation. So just quickly, can you detail this collaboration? And any options that the Biogen has on it? And then maybe just high level on the indication itself.

You bet. So this is a program that is part of the Biogen collaboration. That means that they have an option to license this program. And there's a $70 million license fee that comes with that decision, and that decision will come about midyear after they have an opportunity to review the latest data that's coming out of the study. And so once they make that decision, then obviously, we'll let you know. And it has similar sort of economics associated with it as, say, SPINRAZA, for example. So if you go back and look at those economics, it's very similar, right? And as far as the disease itself, it's -- unlike SMA, it's not a fatal neurological disease, right? It's a developmental disorder in patients, who will live a normal life span, but they basically -- they developed to the age -- the mental age of about a 2-year old and then they stay there the rest of their life. So it's very hard on families, especially when you think about the fact that these patients will often outlive their parents and caretakers and they'll have to have other things set up in order to take care of them. So it's a patient population, it's probably about somewhere around 2 to 3x the size of SMA patient population. And it's obviously a severe need in these patients. We target the cause of this disease, which is they're lacking UBE3A protein in these patients. And it's kind of a complicated mechanism because they have mutations where they lose one, but there's also this alternate copy that gets repressed. And so there's an antisense transcript, and we use antisense to block -- to degrade antisense transcript. So it's antisense against antisense, which I guess makes sense if you think about it. And so in this patient population, we're using our proven chemistry, the same chemistry that we're using in SPINRAZA and QALSODY and tau, all of these other programs that we've had a lot of experience with what's got a good safety profile, and we're investigating this to target UBE3A. And this is a disease that hasn't had a lot of clinical development work on it. So there's -- we're kind of blazing new ground as far as I get ways to find. If the drug is showing improvement, what's the regulatory approvable endpoint for a Phase III study. A lot of the stuff work is going on with the current study to try and nail all of it down so that we can decide -- make the decision on whether to advance it in Phase III. And if we do, what's the regulatory path.

Got it. And we're almost out of time, but I want to squeeze 1 or 2 more in on Angelman way to get this question, what differentiates Ionis' program and approach it relative to patterspecifically Ultragenyx. And then you showed last fall, some initial Soave EET delta data, some good response there. But what does that mean in terms of the additional Phase Ib readout in the middle of this year? What data can we see there? And what are your expectations on that?

You bet. So as far as the difference goes, it's basically chemistry and our expertise, right? So the chemistry we're using, like I said, is the same chemistry we've been using for all of our CNS drugs, the Ultragenyx chemistry uses LNA locked nucleic chemistry, which we've steered away from, especially in the CNS because it doesn't have as good of a safety profile that we've in our experience. And so we like our chemistry basically. It looks good not only in efficacy, but it's got a good safety profile, and we've had -- to date, we've seen good safety findings with the drug so far, and we haven't seen any issues. As far as things to look for in the data is coming out, I mean, we're looking at a lot of different things. You mentioned EEG, which is something we saw positive signs on last year when we reported at the FAST meeting. EEG is an encouraging data as an interesting biomarker. But I have to caution it hasn't been validated in the same way that, say, NFL has for ALS, for example, and it was over a pretty short period of time. It was only over a few months. So we're looking at a lot of different clinical measures that I think are going to be more important for the regulatory pathway in this. We're looking at the Bayley-4. We're looking at SAS-CGI and other things. So it's -- I think it's going to be somewhere in those clinical parameters that are going to be the most interesting things to look at when the data comes out.

Yes. A lot of investors looking forward to that one. Well, we're out of time for this session. Thank you so much, Wade, for participating. Very helpful discussion.

You bet. I'm glad to be here. Thanks for the invite.

And thanks, everyone, for joining on the webcast. Everyone, have a good day and a good rest of the conference.