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. For those of you joining on the webcast, if you want to ask a question, you can do so at any time. You can submit a question using the chat box feature at the bottom of your screen. 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. Approved for TTR polyneuropathy, 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 progresses?
You bet. Happy to. Maybe just before I talk about WAINUA, I could kind of give you a little bit of an update for people maybe that 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, well, it was approved at the end of December and launched in the 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. In addition to that, we also reported phase 2 data for our MASH drug targeting DGAT2, which was positive. In January, we reported positive phase 3 results for donidalorsen, our drug targeting HAE.
And we'll have more data on that reporting at a medical conference in midyear as well. But last year, we also had a banner year, right? QALSODY was approved, the first drug for SOD1 ALS patients. It was our second approved CNS disease medicine. We also reported positive results for 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 early next year, if the drug's 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 would 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 Ataxin-2. That's for the sporadic patient population, which is 90% of ALS patients. Those results we expect mid-year. And results from our phase 2 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. 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 usually 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. We'll report the royalties that we get that are in the mid-20% range on U.S. sales. We'll be reporting those on our quarterly reports. Other than that, there won't be too much more detail coming out. That's the way AstraZeneca handles stuff. We'll be going by their playbook on that one. Given that the market remains 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 in AstraZeneca are uniquely positioned to capitalize on finding and identifying and getting new patients on treatment with WAINUA.
Yeah, and to that point, Wade, for polyneuropathy specifically, where do you see the long-term commercial opportunity for WAINUA? Is it in the switch market, the treatment-naïve 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, 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 on treatment. And we see there's several guidelines and consensus recommendations for diagnosing and managing these patients that are available and continue to evolve. But patients still find it difficult and have a complex journey towards getting the help they need. Because the symptoms of ATTR polyneuropathy are kind of mirrored by other conditions sometimes. 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 diagnosis.
So we are out there as far as the switch versus naïve patient market, since there's less than 20% of patients that are on treatment right now, our main focus, we in 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 them accurately diagnosed, get them on treatment, because that's where the biggest market potential is in the long term for this market. We think that we've got in a great position together with AstraZeneca. We've been working in the TTR space for many years. AstraZeneca is uniquely positioned with its large commercial infrastructure. Especially as a lot of these patients are mixed phenotypes.
So they also present with cardiomyopathy symptoms and 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 have TTR polyneuropathy. So I think that the combined efforts of both companies put us in a good spot for finding these patients.
Yeah, and switching from the polyneuropathy to your ongoing program and cardiomyopathy, obviously the phase 3 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, this ATTR disease. It's the largest study in patients to date in this patient population with more than 1,400 patients enrolled. That's bigger than 2 times larger than the next closest trial in this patient population. It's specifically designed to demonstrate benefit in a broad population of patients, including patients on stabilizer or those that are naïve to stabilizer. Patients who have a mutation versus those who are a wild type. 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.
An MRI sub-study that's looking at it. It's a 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'll help patients and especially physicians who are treating these patients to know when's the best time to treat these patients, how best to treat them, and what benefit there may be in different sub-populations, patients on stabilizer, patients naïve, patients who are late-stage in disease, early-stage in disease, these different things.
The reason that we have this large study is 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, non-invasive 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 everybody that's 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. Now what we're seeing from recent studies and what we're seeing in patients coming into 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.
In terms of those subgroup analyses 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-naïve patients, those that are in background tafamidis? And maybe secondarily, do you think that you'd need to show a benefit in the monotherapy population versus the overall population to have a, let's say, commercial success or uptake?
Yeah. 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 capture the monotherapy effects in this patient population. And so we get the best of all worlds, you might say, because we can see, is there a benefit as a monotherapy, is there a benefit on top of tafamidis? And we can compare those different subgroups in our study. And we think with the size of our study, we've got the powering needed to, number one, hit the endpoint on the overall, but also see if there's at least interesting benefit trends in those subgroup analyses.
How are the blinded 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, we're blind to the blinded event rates we're tracking on a 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. 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 a 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 to end 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?
Yeah, 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 a silencer can have on this disease will be obviously read through to our work that we're doing as well. And I think that that's what's interesting is that I think if the HELIOS-B study, which is what we're talking about here, reads out positive, I think that further de-risks our study as well because that means that you can have a good effect with a 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 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?
Yeah, so I mean, several people have asked us what's the potential for the drug as a monotherapy for reimbursement versus 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, it doesn't 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 that they can put them on a second drug to see if they can provide additional benefit in this fatal disease. And the other thing is the monotherapy market is pretty large too. I mean, I don't want to put that down, right? Because 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. It's a pretty big market, so I think there's pretty good opportunity in both cases.
Great. Well, helpful overview of WAINUA, and a lot of programs to get to. We'll 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, 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. It's somewhere between 1-13 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 10-100 times higher than a normal person might have. So whereas you and I might have 70, 80, 90 mg/dL in our blood, FCS patients will have 2,000, 5,000, sometimes even as high as 10,000 or 11,000 mg/dL. And their blood's 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. These patients are at very high risk for acute pancreatitis along with other complications, abdominal pain, cognitive issues. They often refer to it as the FCS brain fog. I think with FCS patients, I think the stats are that more than 70%-80% of the patients have a history of pancreatitis. It's pretty severe. A lot of these patients are diagnosed pretty young, like when they're in their 20s. Some have had pancreatitis attacks as children. It's just a very severe disease. Of course, acute pancreatitis can be fatal. If you have one attack, you're three times more likely to have another attack. If you have two attacks, you're like 10 times more likely to have another, a third attack. It's just a downward spiral.
So you really want to get these patients on a therapy that can 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, get very substantial reductions in triglycerides, which are 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 two main pathways to clear triglycerides, lipoprotein lipase, LPL, and clearance mechanisms through the liver, 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.
So for these patients, we saw with olezarsen that we almost completely eliminated pancreatitis attacks in these patients. In the patients that were in the 50 and 80 mg dose cohorts, there was only one attack in each group, and in the placebo group, there were 11 attacks. And the first attack happened in the placebo group at 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 mg group, the first attack was months later, like 4 months or something later, 102 days. And in the 80 mg dose group, it was almost a year out before that attack happened. So there's a huge delay, not only a reduction, but a huge delay in time to first event in the study.
All of this shows for the first time, basically, that a drug that lowers triglycerides has an impact and benefit in acute pancreatitis. That's something that was recognized by the medical community because we had not one, but two New England Journal of Medicine papers published this weekend with a presentation of data from two of our studies and an editorial that accompanied those publications. It's something that the medical community has focused on.
We'll get into the olezarsen and what the read-throughs from the pancreatitis data mean for SHTG in just a second. 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 that you presented in the last day or two put you in a great position to capture the market and build a competitive profile?
Yeah, 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 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.
When you look at ApoC-III lowering, 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. So we're seeing very, very potent effects on the target, and that's translating to real effects on not just triglyceride, but in the 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, could you briefly touch on what each of those trials, the outline 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. So the design for the sHTG program is that we have two pivotal studies because that's what's required by regulators in a larger patient population. So CORE, they're called CORE and CORE2. And each of those is going to enroll somewhere around 400-500 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 200-500, 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 higher degree and in these lower triglyceride 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 CORE2. And those are 12-month studies. So we expect all of this data would come out here next year.
Yeah.
So that's planning CORE and CORE2. In SHTG patients, that's greater than 500 mg per deciliter as far as triglyceride levels.
Primary endpoint, there's trig reduction, but I'm curious if you can talk about the importance from a 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 acute 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 and are higher risk. But it's still pretty substantial, right? And the studies are about 10 times larger than the SHTG 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 studies, so we know that they're occurring.
Now, if we see the same kind of dynamic that we see with FCS patients as far as almost 80%-90% reduction in AP attacks, then we would expect that the majority of those attacks are happening in 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 more confidence that we're going to see some benefit in SHTG patients.
Confidence in the read-through to sHTG. Yeah. In terms of powering, 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, we didn't look to power it for reduction in acute pancreatitis, but if we have the same kind of magnitude and we have enough events, who knows what we could find, right, as far as that goes. So I think we can't promise that we're going to see stat sig because it obviously wasn't powered for that. But I think we're pretty confident we're going to see some sort of benefit.
Last question, last question on olezarsen. Obviously, two 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, a size that'd be fairly efficient for the FCS patient population. It's a small number of patients in the U.S. There's a fairly focused number of treaters.
We're pretty familiar with the KOLs in the space and the people who are treating these patients. It's going to be scaled according to that size and effort in that regard. 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, and we need to find them.
Moving on to donidalorsen, another exciting program you guys have in late stage. He read out positive data in January from the phase III trial, met the primary endpoint, haven't yet disclosed the treatment effects, but maybe zooming out a little bit. There are multiple prophylactic therapies out there. Market leader is TAKHZYRO. How do you view the market opportunity for donidalorsen? Where do you think donidalorsen would fit into the treatment landscape?
Yeah, that's a good question. I mean, it is somewhat crowded space. TAKHZYRO is the market leader with a prophylactic treatment, which is the majority of patients in the U.S. are on prophylactic treatment. Outside the U.S., it's a different dynamic where I think most of the patients are on demand treatments. So there's a growth opportunity in the U.S. Inside the U.S., when we look at the opportunity there, TAKHZYRO does, I'd say, kind of set the standard. It does 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 switched 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 two 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 looked to go to Orladeyo. Now we've heard since then, there's a lot of patients that have been switching back from Orladeyo to TAKHZYRO because of the efficacy issues. The great thing about 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 two weeks or maybe every four weeks for some patients to donidalorsen, which you can dose every four weeks to eight weeks, right?
Probably the majority of patients, 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 delivered through an autoinjector that can 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 is have that simple injection, the convenience, the efficacy, kind of all wrapped into one.
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 a 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 four-week dosing, whereas that's TAKHZYRO's every two-week dosing, right?
2 weeks, yep.
Yeah. 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 making sure that we can keep them attack-free. How do we do that? What's their benefit with their prophylactic before switching? What does it look like after switching? And then doing a survey afterwards and asking them which drug they preferred. Did they prefer their previous one or did they prefer donidalorsen?
Kind of gathering all of that information will help physicians who, assuming that everything looks good and the drugs approve, that physicians will know how to switch patients from prophylactic treatment they're currently on onto donidalorsen safely and effectively. So that's something we think will be important. That's also data that we're going to present mid-year along with the phase III data.
Yeah, 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, very large patient population and are going after a larger physician base. But with prophylactic treatments for HAE in the US, especially, that's pretty concentrated prescriber-based. So the opportunity is pretty attractive for us, right? The majority of HAE patients in the US are treated by allergists and about 1,000 allergists or immunologists manage about 70% of the 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 figure that we'll probably have somewhere less than 100 customer-facing teams that include 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'll be a huge commercial lift. And just to set expectations, I know Takhzyro is selling, I think, somewhere around in the billion-dollar range. We don't project that we're going to be in that billion-dollar sales range. I mean, and we think the market is crowded and there's other players coming into the space. We're projecting that we'd 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 pretty attractive from the return on investment.
In the U.S., Wade, or is that in terms of 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 wanted to touch on Angelman syndrome 582 program that's partnered with Biogen. What I found interesting is that they've mentioned it several times and highlighted in their recent earnings presentation. So just quickly, can you detail this collaboration and any options that 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. There's a $70 million license fee that comes with that decision. That decision will come about mid-year after they have an opportunity to review the latest data that's come out of the study. So once they make that decision, then obviously, we'll let you know. It has similar sort of economics associated with it as, say, Spinraza, for example. If you go back and look at those economics, it's very similar, right? As far as the disease itself, unlike SMA, it's not a fatal neurological disease, right?
It's a developmental disorder and patients will live a normal lifespan, but they basically develop to the mental age of about a two-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 that's probably about somewhere around two to three times 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 that 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.
There's an antisense transcript, and we use antisense to degrade the antisense transcript. It's antisense against antisense, which I guess makes sense if you think about it. 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. It's got a good safety profile. We're investigating this to target UBE3A.
This is a disease that hasn't had a lot of clinical development work on it. We're kind of blazing new ground as far as identifying 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 make the decision on whether to advance it in phase III. If we do, what's the regulatory path?
Got it. And we're almost out of time, but I want to squeeze one or two more in on Angelman, Wade. We get this question. What differentiates Ionis's program and approach relative to competitors, specifically Ultragenyx? And then you've showed last fall some initial slow wave EEG delta data, some good response there. But what does that mean in terms of the additional phase 1-B readout in the middle of this year? What data can we see there and what are 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 acid chemistry, which we've steered away from, especially in the CNS, because it doesn't have as good of a safety profile 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 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 that's 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, is 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. 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 Bailey IV. We're looking at SAS-CGI and other things. So 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.
Yeah, I know 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.
Thanks, everyone, for joining on the webcast. Everyone, have a good day and a good rest of the conference.