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

Good afternoon, and welcome to the Ionis Pharmaceuticals Tominersen Update Conference Call. As a reminder, this call is being recorded. At this time, I would like to turn the call over to Mr. Wade Walke, Vice President, Investor Relations, to lead off the call. Please begin.

Thank you, Cole, and thank you, everyone, for joining us on today's call to discuss the tominersen development program. I encourage everyone to review the press release Ionis issued this afternoon, which can be found in the Investors section of the Ionis website. Today's call will begin with brief opening remarks from Brett Monia, Chief Executive Officer; followed by Q&A during which Brett will be joined by Frank Bennett, Chief Scientific Officer; Eric Swayze, Executive Vice President of Research; and Eugene Schneider, Chief Clinical Development Officer. Before we begin, I would like to remind everyone that we will be making forward-looking statements on today's call, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail. With that, I'll turn the call over to Brett.

Thanks, Wade. Hello, everyone, and thank you for joining us on today's call. I'll keep opening remarks brief so we can get right to your questions. As we and our partner, Roche, announced earlier today, Roche has decided to discontinue dosing in the Phase III GENERATION HD1 study of tominersen in patients with Huntington's disease. We understand that there are many questions about this news. We don't have a lot of answers at this point, but we'll do our best to answer your questions based on the information we do have. Roche's decision was based on the results of a preplanned review of data from the ongoing Phase III study, which was conducted by an unblinded independent data monitoring committee or iDMC. While no new or emerging safety signals were identified, the iDMC made this recommendation based on tominersen's potential benefit-risk profile. Roche will continue to follow participants from the Phase III study in order to assess additional safety and clinical data. In addition, dosing in the GEN-EXTEND open-label extension study will be paused while Roche reviews data from the tominersen program to inform on next steps. Dosing in the Phase I GEN-PEAK pharmacokinetic and pharmacodynamic study of tominersen as well as Roche's observational HD Natural History Study will continue. Roche plans to share its learnings and next steps for tominersen when full data from the pivotal program have been analyzed. We look forward to learning more when those results become available. I'd like to thank the patients and families who participated in the tominersen clinical program for their partnership, trust and dedication. While we are saddened by today's outcome, we remain committed to the HD community and focused on delivering treatments for this and other devastating neurological diseases. Although this is a disappointing setback for Ionis and the HD community, we are confident in the potential of our technology platform to address many neurological diseases, represented by our industry-leading neurological disease pipeline. And thanks to our strong financial position, we have the resources to advance multiple neurological disease programs, including several from within our wholly owned pipeline. And with that, I'll open the call for questions, but I do want to emphasize that we may not have answers to many of your questions at this time, but we'll do our best.

[Operator Instructions] Our first question today will come from Jason Gerberry with Bank of America.

I guess, Brett, just curious, how are you guys thinking about approaching the HD space going forward and commitment to advancing an ASO, irrespective of what Roche finds and how it communicates its future plans in the space? I guess it's an indirect way of asking, as you guys think about what's been learned so far, calling into question the relevance of huntingtin protein as target or the issues that have been talked about in terms of getting ASO deep into -- inside the brain, just kind of curious if you think an ASO approach is still appropriate and your commitment to that disease area.

Sure, Jason. Thanks for the question. We're going to learn so much from this study, and there's so much we don't know at this time. And again, we haven't -- we -- Ionis has not seen any of the Phase III data. And we're looking forward to getting an update from Roche on that one when they get through all and analyze all the data. And we'll learn so much from this once we do get that data, which I do think will help us point to directions that we want to go forward to treat Huntington's disease. So there's still much to learn. Unfortunately, we can't comment on this. We are -- we still are strong believers in the ASO approach. I mean we're targeting the root cause of this disease -- the cause of Huntington's disease by lowering the huntingtin protein. And there are other strategies that we can take on. And as far as being able to hit the regions of the brain that matter the most in Huntington's disease, maybe I'll ask Frank Bennett to comment on our confidence in our ability to be able to hit the huntingtin where it matters most and the ASO platform for targeting Huntington's disease as well as maybe potentially other thoughts on other strategies for targeting this disease. Frank?

Can you hear me?

Yes, we got you.

Yes, I just want to make sure I'm coming through. So yes, as Brett mentioned, I think it's really early to speculate on next path forward for this program. We are committed to finding a treatment for Huntington's disease. And like Brett said, we were on target for the root cause of the disease. And based on all the data that we have available, we think we're hitting the regions of the brain that are important for the disease. And we'll learn a lot more as the data gets analyzed, and we may revise our thinking a bit. But right now, we're firmly committed to finding a therapy for Huntington's disease patients. And there are several options that we will consider once we have the data in hand.

And our next question will come from Yanan Zhu with Wells Fargo Securities.

So first of all, just wondering because it's a benefit -- risk-benefit evaluation, do you have a sense of whether this is from the efficacy perspective or the safety perspective that the iDMC made this decision? And have they seen any efficacy data? For example, I think the trial completed enrollment in -- last April and most of the efficacy endpoint looks like 2-year endpoints. So just wondering, how much efficacy data have they evaluated?

Yes. Good question, important question. So the iDMC assessed both safety and efficacy. It's very important to remember that this iDMC committee is a separate committee from Roche, right? It regularly reviews clinical data, including safety and risk versus benefit. And it's data that Roche does not have access to. It's the normal flow of the safety oversight committee. So they do look at both safety and efficacy. And this was a regularly scheduled, preplanned review of safety efficacy from the Phase III study in which they brought a recommendation to Roche on the [ potential benefit, risk tied ] to this decision by Roche. So it is safety and efficacy. We, again, have not seen any of the data. And based on that recommendation, Roche made the decision they did. I think that's about as much as I can say on -- oh, with respect to how much data they observed, again, we don't have those details. What we do know is that the Phase III study completed enrollment in April of last year. So you can do a little bit of guesstimation based on the amount of patients. I think it's 791 patients that -- a subset of them have been treated through the [ full -- in dorms ] 25 months and then moved into the open-label extension.

Got it. And then the next question is really about the read-through to other neurological disease programs. Do you think this is HTT specific? And in terms of another high-profile Phase III study with tofersen, do you think -- would this have any read-through to that program? And will your partner have some kind of a safety review of that program?

So we're very -- we're pleased that we were informed by Roche that the decision made by the iDMC was not based on any new emergent safety concerns for the program. And as I mentioned before, this iDMC meets regularly. So they're assessing safety and the risk-benefit profile all the time. So no new safety emergent concerns. Whether or not there's an on-target issue or not, again, we're going to have to go through all the data, understand what the mechanism is behind this. There's a lot of data to go through. And we'll have a better -- Roche will have a better sense of the data and draw conclusions at that time and will inform us of that. We see absolutely no read-through to our neurological disease platform. As a reminder, the -- SPINRAZA has now been in patients for more than 11,000 patients around the globe. Many of those patients have been treated for many, many years, very well tolerated. And in addition, our 6 or more clinical programs today in neurology are all proceeding on track with no issues. And in fact, tofersen has demonstrated encouraging signs of clinical benefit that makes us and Biogen looking very much forward to the Phase III results later this year. So we see no -- absolutely no read-through as to the mechanism, a relationship between on target or off target or if it's all efficacy and not related to safety. We're going to have to wait for the data to play out.

And our next question will come from Yaron Werber with Cowen.

This is Brendan on for Yaron. So just really quickly from us, first, obviously, this is more or less a question that's been raised plenty of times kind of prior to now about the functional endpoints here. But at this point, do you think that -- there's really a chance this could be due in any capacity maybe to the length of time at which the efficacy is evaluated and maybe how that might impact your thoughts on trial designs for kind of HD in general? And then just a second, really quickly, if you can tell us if this maybe impacts the timing or content of the actual data updates, either from the OLE studies or the Phase III data next year at all?

Sure. Maybe I'll ask Frank to comment on his thoughts about the study design and whether or not he feels the duration of treatment had any impact in this outcome. What I could tell you and remind you of is that this is the largest Huntington's trial ever conducted, and it was conducted on a wealth of information from natural history data and other data that it was designed based on, so we're feeling quite confident that this was a very well-designed study. But Frank, our CSO, is much closer to the partnership as well as the Phase III program, so I'll let him comment.

Yes. So again, I'm going to reiterate what we said before is that we haven't seen the data. So I think it would be inappropriate to make any comments regarding length of the study or what the data from the study means. We just haven't seen any data. So it's inappropriate for us to make comments regarding the trial design. So the -- that's really about -- all I can say right now is that until we get more data in, that will be very informative and help us figure out if there were some flaw in the design of the study going forward.

Yes, yes. Again, it's the largest study ever conducted in these patients, and there's going to be a wealth of data to go through and to learn from. As far as data updates, we received no new information from Roche that -- whether they've changed any of their plans for data presentations on the open-label extension, et cetera, this year. So we'll have to wait to hear from Roche on that.

Yes. And just to say it, I think the Roche team is focused on working with physicians and patients right at the moment. So being polite, we don't want to get in the way of that communication. We'll find out more later.

And our next question will come from Tyler Van Buren with Piper Sandler.

So I guess with respect to how we move forward, if they continue to analyze all the data and decide to shut the program down, do you get, I guess, the asset and all rights related to the approach or the technology back from the partnership? Does it just dissolve? And with -- is there any meaningful financial implications with respect to below the revenue line in the P&L? Did you guys have a meaningful level of spend for this program? Can you help us understand that?

Yes. Thanks, Tyler. So there's no change in our guidance for the year. As a reminder, Roche fully absorbs all the operating expenses for this Phase III trial. And really, the top line revenue that we are expecting from a successful Phase III and approval for tominersen was really pushed out a number of years. So no significant financial impact on -- in the near term, of course. And of course, our financial strength allows us to take this on and be able to still invest in everything we want to invest in and need to invest in to keep us delivering on the drugs that we see coming forward to the market. And as far as the logistics of the deal, sure, I mean, if Roche were to ever decide to abandon the program entirely, yes, it would come back to Ionis, but we're far from that. I mean we're just going through the data, and we're looking forward to learning a great deal from this study and determine what the best course of action is with Roche once we get through that data.

And our next question will come from Yale Jen with Laidlaw & Company.

Just a few quick questions. The first one is that -- if this decision has anything to do with the futility? Or that's not the case?

Yes. Futility -- this was not a futility analysis. Maybe I could talk -- ask Eugene to comment on what went in the -- sort of the process that went in, how this is different than a futility analysis.

Sure. So our best understanding is that this was a different type of analysis. This was a scheduled, regular iDMC review of all available safety and efficacy data. Futility analysis is a different type of analysis. It's focused primarily on efficacy. It has very specific goals and thresholds in mind and statistical thresholds for proceeding. So this was different from a futility analysis, yes.

And again, this is a prescheduled, preplanned review that has been happening throughout the Phase III program on safety and risk benefit, which includes efficacy, of course.

Okay. Great. Maybe just a quick follow-up here, which is that the Roche stopped enrolling patients or continue the dosing patients. Does that fully mean that, that program is terminated? Or there's -- the other possibility has been not fully explored yet?

So what it means is that dosing in the Phase III study and in the open-label extension study has ceased. And it does not mean that the program is done. Roche will have to go through all the data and draw their conclusions once they get through all the data because there's a lot they can learn from this study. So no, it does not mean that. But what it means that -- I mean, literally, that the dosing has halted.

And in the open label, they paused dosing, evaluating the data. And they're continuing to follow up the patients in the Phase III study for continuing safety measures and also for continuing clinical outcome measures.

And our next question will come from Luca Issi with RBC.

Obviously, you haven't seen the data, so I know the comments can be limited here. But maybe for either Frank or Eric, just a high-level question. How should we think about the fundamental hypothesis that knocking down mutant huntingtin can actually drive a benefit for patients? Should we start questioning that hypothesis? Or do you think that hypothesis is still valid and it's just a matter of maybe enrolling the right patient's population or maybe finding a better molecule or maybe optimizing the duration of therapy? How should we think about that?

Yes. Good question. Frank, do you want to take that?

Yes. So right now, I think it's really premature to come to any conclusion regarding -- whether lowering huntingtin is going to benefit patients. We just -- we don't know enough. And I know that's frustrating. I'm still firmly convinced that, that is the right strategy for treating this disease. And until we get into the data and identify is this a too-advanced patient population or other parameters, we just won't know that answer. There is nothing in the literature that would suggest that lowering the huntingtin protein won't benefit patients, and so this is very perplexing and disappointing to us. And just -- we have as many questions as you do in that regard.

Anything to add to that, Eric?

Not much. I mean I agree with Frank, it's a hard hypothesis to walk away from because it's a dominantly inherited genetic disease and the cause is so well-known. And so we were on target, and we're lowering the cause of the disease. And it is a tough hypothesis to walk away from. And it's a complex disease. So hopefully, we'll learn a lot from the data and can help inform us and Roche in the field in how to go forward and get therapies available for patients.

And our next question will come from Jessica Fye with JPMorgan.

First one is, what was the dose used in the Phase III study?

It was 120 milligrams. And it was dosed either every 2 months or every 4 months.

Okay. Great. And what is this -- what do you think about the -- maybe pursuing an allele-specific approach in Huntington's from here?

Yes. Frank, what do you think?

I think that's on the table. That's always been on the table with Roche. We sort of pioneered the development of allele-selective Huntington reduction. At the time we made the decision to go forward with tominersen, the -- we decided to use a non-allele approach mainly because we wanted to treat the entire Huntington's disease patient population. And we saw no evidence for adverse effects from lowering total huntingtin. But again, as we get time to analyze the data and carefully consider the options, that is an option that we have available to us.

And our next question will come from Vincent Chen with Bernstein.

I just have a couple of quick ones. Well, first, simply, when I look at the clinical trials [ I've got listed ], it looks like the majority of the functional endpoints and imaging endpoints as well are collected at baseline and then -- at week 101, with the exception of the Montreal Cognitive Assessment. I was wondering, can I ask you what efficacy endpoints are collected at points in between these -- or in between the baseline and sort of that week 101?

I'm not sure any of us have those details. But Frank would have -- would be the best choice if he did. Frank?

Yes. I mean there's periodic -- I'm not sure what's in the ClinicalTrials.gov posting, so I don't want to comment about that. But this is a clinical study to look at efficacy. And so there's a number of different efficacy endpoints, a whole smattering of them that are collected frequently throughout the study. And so it's not just at week 101. It's -- I think what maybe you're referring to is that's what the data would be compared to. So it's baseline versus week 101 comparison as an endpoint for the study. But there -- the full spectrum of clinical data is collected on a periodic basis throughout the study.

I see. That's very helpful. And I guess maybe one -- or just -- this is a bit of a speculation question, I realize you don't have the data yet. But I'm just kind of curious, in your eyes, if you think about why a drug might be -- why it might be difficult to show efficacy in this trial, in this indication, what would you think is the most likely cause? Is it a matter of sort of maybe the degree of knockdown that's needed in Huntington's being higher than what have been expected preclinically? Or could be a matter of just sort of distribution, where you need to get within the brain? Or could it be a matter of need to treat patients much earlier in the course of the disease or to treat for a much longer time and with more patients to sort of discern a slowing of disease progression?

Yes. So I think all of those are on the table. And until we see data, we -- I don't know which one's most likely. I think they're all possibilities that we need to consider with the program.

And our next question will come from Paul Matteis with Stifel.

Great. I was -- I wanted to kind of revisit the question surrounding biodistribution. I guess you talked about how this is a genetic disease. It's almost 100% penetrant, and you are really confident in the target. I guess why isn't then biodistribution and getting enough drugs in the deep brain one of the plausible conclusions of what could have gone wrong here? And I guess if that is at all on the right track, have you thought about direct delivery as a potential approach for a future study, like with a port or something like that?

Yes, Paul, thanks. We haven't ruled anything out. I mean we have not ruled that out that maybe we didn't get enough biodistribution, enough knockdown in certain regions of the brain. It was 1 of the 3 things that were highlighted in the previous question that Frank said, those are all on the table. But our -- we have a wealth of preclinical data that supports the conclusion that we are getting substantial and sufficient reductions in mutant huntingtin, where we need to get them done for the benefit of patients. That's preclinical data. We're going to have to [ cull ] through all the data in the Phase III study and all the studies to drove -- expand on those conclusions, but that's where we are. We haven't ruled that out. Frank, do you want to add anything to that?

No, I think that's right. I think you answered it. As -- I think there are a lot of questions and hypothesis that are on the table. And as I said, right now, I think it'd be premature to speculate which one is most probable at this point. They're all things that we're considering.

And do you want to comment on local delivery?

Yes. So again, if that's the direction that it looks like we would want to go based on the data, that's definitely on the table, something to consider. There are a number of strategies that have been done. [ As -- Paula knows this ], I fundamentally don't think that direct delivery into the striatum is going to be effective in treating this disease. So I won't rule it out, but it's not high on my list of possibilities to go.

And our next question will come from Mani Foroohar with SVB Leerink.

Condolences on a tough out for you guys and definitely for patients. Let's review like -- I want to revisit a couple of questions. One on the allele-specific approach. You guys have commented that you previously done extensive work over the years. Could you clarify if you've specifically looked at allele-specific constructs and approaches to Huntington's disease, i.e., might you have some amount of data in hand for a construct should you agree -- decide to pursue that approach? And then secondarily, a minor one on the financials. Is there an intangible asset or any other carrying value on your balance sheet related to this program? So should the worst happen and Roche decides to terminate the program completely, although we're certainly far from that, would there be an accounting effect, will be a write-down impairment, et cetera? Just for accounting purposes.

I'll let Eric take the -- take a stab at the allele-specific approach and what our experience has been there.

Yes. Sure. So yes, we have had extensive experience in allele-specific reduction of mutant huntingtin. This is a collaboration that was started with Michael Hayden's group at UBC and trying to look at a variety of SNPs in the Huntington gene and lower them selectively. And we did that using a series of chemistries that we have that gave us 50- to 100-fold allele selectivity for several of the key SNPs. So -- and as Frank alluded to earlier, we have talked about this concept with Roche, and Roche is aware of it, and we've considered this concept and chose to advance the total Huntington lowering because the data we had suggested that it was just as good as allele-selective approach, and it would treat all Huntington's patients. But we have lots of experience. So we have things that are reasonably far along.

And we've published on it, right?

Yes. It's been extensively published in [ clinic asset research ] and other papers.

There's probably a dozen papers that we've published on that topic.

And Mani, there's no accounting effect. There's no write-down implications. The answer to your financial question was no -- is no.

And our next question will come from Gena Wang with Barclays.

I wanted to ask about risk benefit. Can you give a little bit more color exactly what kind of risk they are looking for? And also for the benefit, are you comparing -- basically, how do you look at the benefit? Is that the UHDRS and how that compares to the natural history or baseline? Is there a threshold they will be looking for?

Again, Gena, we don't have the details of the data. We don't have any of the data, I should say, on what was assessed as measures of risk or measures of benefit in that study. Maybe Eugene could talk a little bit about his thoughts on what an iDMC might look like -- look at in the risk-benefit analysis. But honestly, we really don't know. We don't know what their criteria were that they used.

I don't really want to speculate. I don't think it's my place. It's all outlined in the charter, which the iDMC is governed by. We don't know what they're looking at, yes.

And again, Gena, we're very -- this is sad day for patients, and we're very disappointed. We are encouraged that the decision wasn't based on any new emergent safety concerns. So that's one silver lining in this. And I guess I'll just stop there.

Okay. Then another related question is when the data come back, when Roche shared the data, how would you interpret the data that's, say, due to knocking down not enough versus -- so that you need to -- you can dose higher? Or would that be due to certain penetration to the brain was not enough? I think it kind of echo the previous questions, but like how would you interpret the data to understand what is the right approach to the next step?

Well, I mean, again, I'll ask Frank to comment a little bit, too, but we don't know exactly what we're going to see -- what Roche is going to see when they go through all the data. It's going to be a lot of data. And what we do know is that the reductions in mutant huntingtin that we observed in the CSF that we believe -- we have a lot of data that, that's very predictive of what's happening in the CNS was very durable and beyond the level that is predicted to show efficacy. I don't think we're going to get much more Huntington reduction data from that. And I should say, I should qualify, it's very important and what I just referred to is open-label extension data from our Phase II study. We don't have any data from the Phase III study. So that will be a key measurement. That will be a key piece of data that we're going to be looking forward to see when Roche goes through the data and gets the data and reviews it with us. But as for other pieces of data that will help us decide on what the best next steps are, it's hard to say. I don't know, Frank, do you have other thoughts?

No. It will be all the clinical data. There's additional biomarker data that's being collected. There's wearable data that is being collected on the patients. So there's a wealth of data. And it will be a data-driven decision as far as what is the best path forward. Without seeing the data and knowing what it is, it's really hard to speculate what would be the path forward.

And our next question will come from Esther Rajavelu with UBS.

Can you maybe share your thoughts on how long do you think Roche could take for this review? And what are some of the parameters that would be looked at to determine next steps? What's the threshold to either move us forward or to put a stop to the program altogether?

We've received no -- we would love to know. We received no information on the timing on when Roche will feel comfortable that they've reviewed enough data that they'll share. I'll emphasize, we have a very good, strong relationship with Roche. And I'm sure that as they've done in the past, they will engage us regularly going forward, but there's no time line for that, nor is there anything that we could say on the threshold that we'll make -- that will be a decision point for us to go one direction or another because we don't know what we're looking for yet. There's a lot of data. There's patient population data. There's all kinds of data that we're going to be going through. And we're just going to have to be patient and go through it all and come to our conclusions. And again, when I say "our," I'm really focused on Roche. They're taking the lead on this.

Got it. So would you have -- would you be reviewing the data concurrently with them? Or would they sort of give you their conclusions?

We are not -- we -- reviewing the data concurrently with them. But they have been good partners in the past. They update us regularly. And I assume and expect them to be good partners going forward.

Got it. And then one last question. Can you remind us how much wild-type huntingtin is knocked down along with mutant?

Well, we haven't measured that specific -- we have an assay for mutant huntingtins. In preclinical models, the reduction was essentially the same between mutant and wild-type, which is what we'd expect from the mechanism.

And our next question will come from David Lebowitz with Morgan Stanley.

Just speculating going forward, how would you think you might approach antisense for Huntington's to potentially increase the efficacy of the approach?

Thanks for the question, David. Frank, you -- would you like to speculate again? We don't know what parameter -- what dial we'd want to turn if indeed this decision was -- we draw the conclusion after this analysis that we were short on efficacy. But maybe, I don't know, Frank, do you want to comment on that? You want to speculate?

Yes. Again, there are a number of different variables that we could look at that were already discussed. So potency of the drug, we have ways -- we're continually making improvements to the platform technology. And so it's possible to find more potent drugs, allele-selective strategies, delivery to different regions of the brain, treating patients earlier in their disease. I can -- there's a very long laundry list of things that could be done. But without knowing the data, I think that we're just unable to give you guidance which direction we're likely to go at this stage.

The good thing, David, that we have, of course, is -- the good thing that we have, of course, is a rich toolbox and a wealth of experience in this space that once we do -- if we do hone down on some hypothesis as to why we came up short, we're going to have a lot of tools available to us to pursue.

And our next question will come from Salveen Richter with Goldman Sachs.

Can you help us understand, prior to this announcement, what you understood about the therapeutic window and the prior safety issues that were playing out, including neurofilament light, and so how you were assessing that benefit-risk threshold at that time?

Sure, Salveen. Frank, would you like to take that?

Yes. So the 2 pieces of data that have been reported regarding safety tolerability all came from the original Phase I/II study. And in the 3 months' duration, all the adverse events appeared to be procedure-related adverse events. There -- to my knowledge, there were known adverse events that were associated with -- or possibly related to the drug. In the longer-term extension study, again, we looked at 2 different dosing paradigms, monthly and every 2 months. And if you just look at the overall safety profile because of the -- in part, the adverse events were related to the procedure. The fewer procedures, the fewer number of adverse events. But there were some signs in the monthly study that weren't associated with clinical outcome or clinical presentation, the bigger laboratory changes that were occurring, and they were changes that we were paying very close attention to. So one was the neurofilament light, where we saw a transient increase that peaked around 4 to 5 months after dosing was initiated and then it came back down towards baseline. That was more prevalent in the monthly dosing versus the bimonthly dosing. In fact, the bimonthly dosing was a fairly minor increase. We saw an increase in cells in the CSF that was more prevalent than the monthly dosing. And then CSF protein was another observation that was observed. So none of those observations were correlated with any kind of clinical adverse events. They were laboratory changes that we were very -- closely paying attention to. And there are changes that Roche was paying attention to in the Phase III study as well as their medical monitoring board.

And this will conclude our question-and-answer session. I'd like to turn the conference back over to Brett Monia for any closing remarks.

Sure. Thanks. And as I said at the outset of today's call, the Ionis team is extremely disappointed by this news and saddened for the patients and the families who've been waiting for the first disease modifying therapy for Huntington's disease. However, this setback doesn't change our commitment to the HD community and are pursuing a treatment for this devastating disease. More broadly, we remain confident in the ability of our antisense platform to transform the lives of patients with severe neurological diseases across the board. Looking ahead, we'll continue to execute on our commitments to these patients just as we always have. Thanks for joining us on today's call, and have a good afternoon.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect your lines at this time.