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

Good morning, everyone. Thank you for joining the 21st 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. And joining us today from Ionis is EVP of Research, Eric Swayze. For those of you joining on the webcast, if you want to ask a question, please do so at any time. You can submit a question using the chat box at the bottom of your screen. With that, we'll go ahead and get started. Eric, thank you so much for joining us today.

Great. Thanks, Joey. I appreciate the opportunity to be on and talk about our company a bit.

So Ionis has been one of the leaders in developing RNA-targeted therapeutics for a long time. Just curious, can you give your perspective on sort of the past, the present and the future of Ionis' ASO approach?

I'd love to. And I'm thrilled to tackle such an open-ended and far-reaching question. So for those who know the company, we have been at this a long time. And I've personally been at it a long time and been here almost 30 years. So we started with what we call the big dream of making oligonucleotide drugs, which target RNA and modulate gene function with the ultimate goal of trying to make transformative medicines for patients where they had no therapies before. And really, we started this with kind of a blank slate and no road map and often little idea on how to do it or what we were doing. And many would say, and rightfully so, it's led to some fits and starts and failures. I would say that one thing that we've always done and we continue to do, and it's a theme at Ionis is focused on technology advancement, always trying to make the drugs better and the technology to modulate gene function by targeting RNA better. And we keep getting our technology better and get new chemistries and new mechanisms and move forward and always advance the technology. And I guess that kind of leads us -- that's the past, and that's led us to the present where we've realized that success with at least one commercial blockbuster in SPINRAZA, where it's transformed the care of SMA. And Biogen is looking to extend that SPINRAZA franchise, both looking at higher doses of SPINRAZA in DEVOTE, SPINRAZA on top of its competitor therapies, both Zolgensma with the RESPOND study and on top of risdiplam with the ASCEND study trying to really demonstrate that, that drug is -- has maximal efficacy and is the -- will remain the standard of care. We're also thinking about technology advancement, have just announced with Biogen a follow-on for SPINRAZA, which has a new backbone chemistry that we've employed. The goal here is to both increase potency to increase efficacy, which we think we can do it as backbone chemistry and then extend the duration. These compounds are very stable. And we think, hopefully, we can get to [ utility dosing ] with this type of follow-on. So that's an example of the technology. And if you start to look at then the other technology advancement we've had really is the LICA platform, which is in current late-stage drugs with our cardiovascular franchise, via the drugs like eplontersen, donidalorsen and olezarsen. They all use this LICA targeting platform, which gets us to a very nicely administered drugs monthly or potentially bimonthly with donidalorsen in a low-volume, convenient to use at home auto-injector. And we think this has really been transformative for the platform. And then if you look at the future, we're continuing to invest in the platform. We've got some -- we saw some questions later about some backbone chemistries that we're working on, which we think will further enhance therapeutic index. We have a broad platform that we call LICA, which is really tissue targeting, which is trying to direct the drugs where we want them to go, where they're needed and not where they're not. And we can talk about some of those platforms. And we're also looking at other mechanisms and other modalities. We view ourselves as an all-modality company who will try and find the best drug for modulating gene function. We have a chemistry platform that can support it, and we're actively looking for alternative and complementary technologies, which we hope to bring into the fold within the next little bit here.

Great. And sort of sticking with higher-level platform-type questions. Can you discuss the current challenges and really the potential future directions in ASO technology? What's the next frontier in this area of drug discovery?

Yes. So we focus on really 2 or 3 key points all the time and I hit on some of those. One is always looking to improve therapeutic index. And one of the key drivers of that is, of course, potency, right? If you lower the dose of our drugs, you give less to the patient and achieve the same or better effects, and lower drug almost always correlates with reduced side effects and a better overall profile. So we focused intently on that. We also -- one way to do that is with tissue targeting and what we call the LICA strategy, to direct the oligo where it goes. If you look at how that's worked with the liver LICA platform, it's improved potency 30-fold by directing the drug to the cell and tissue of interest, deliver on -- at a site. That allows us to dramatically lower the dose and also extend the dosing frequency. So that's led to our liver LICA platform. If you look at a drug like pelacarsen, which is now in the Phase III outcome trial for lowering Lp(a) with Novartis, the parent of that molecule was administered at 300 milligrams a week. We get better efficacy administering the LICA version at 80 milligrams a month. So we both dramatically reduced the dose, which allows us to reduce volume and extended the frequency. Just an example of how the LICA platform, targeting a tissue can improve potency. And I really think that's one of the key future goals of all oligonucleotide platforms is to solve the delivery challenge, right? And figure out how to make the drugs go where you want them, not just where they go. We know they went to liver. We followed that for a while. But even for a tissue that they naturally go to, targeting them there does better. And we've invested in looking at tissues such as the beta cell pancreas with the GLP-1 LICA platform that we've talked about and also are very enthusiastic about the transparent receptor targeting platform for muscle. So I think that's a huge new direction for the field and people who don't have good delivery strategies and good platforms for getting their drugs into the right place will kind of be stuck in the past.

And more on the platform here, how did this MsPA technology, these modifications -- can you talk about the potential clinical benefits or the therapeutic rationale for the MsPA backbone modification? And does this require any additional technological -- excuse me, I should say, manufacturing challenges over traditional or the LICA technology, I should say?

Yes. I guess I'll start with the benefits and remind me if I forget about the manufacturing issues. So the key -- the MsPA chemistry really allows us to do things that we have never been able to do before. And actually it's one of my first projects when I joined the company as a medicinal chemist was make a backbone that allows us to remove some of the phosphorothioates. And the phosphorothioate is a backbone that's broadly used in oligonucleotides because it stabilizes the linkages. The native phosphodiester backbone is too -- really too unstable in most cases to be used in animals. And we use phosphorothioate extensively. It has a lot of benefits. It has some nonspecific protein binding to things like albumin that allow the drugs to be distributed throughout the body and get into tissues. But this nonspecific protein mining can also lead to side effects, such as immune stimulation, which is a side effect that's dogged lots of oligonucleotide therapeutics throughout the years. And the MsPA Backbone can give us -- it gives us another tool to minimize phosphorothioate content and really play with the phosphorothioate content and tune in to exactly what we want. And it does this because it doesn't have the nonspecific protein-binding characteristics that phosphorothioate does but is more stable than phosphorothioate. So we can use that to tune the drug to do exactly what we want. We can dial down the PS content if we need. We can couple that with a LICA strategy to then direct the drug to the tissue we want it to go to. And we can do all of these while increasing stability, which then increases duration. And we published some of these results not too long ago where we showed that we were able to extend, for example, using the MsPA backbone of a single stranded oligonucleotide to match the duration of effect of the standard SAR RNA designs in the liver, for example. So I think it's a really versatile tool and we're pretty enthusiastic about it. We have that backbone in essentially every new lead identification exercise that we're pursuing across the company, and expect it to be showing up in our drugs very soon in the not-too-distant future. And hopefully, the profile we've observed in preclinical species will translate into humans, and we can continue to evolve and improve upon the platform over time. And then with regard to manufacturing, what we change in the manufacturing process is just a different reagent. And so it uses the same starting materials of the monomers that go into making up the drug. We changed the reagent that adds the chemical to the phosphorus. So it's actually conceptually a fairly small tweak in the manufacturing process. It's very similar in scope. There's, of course, challenges. Anytime you introduce a new chemical, you've got to find the sources for it and figure out how to use it and optimize yields. And translate the research manufacturing successes that we've had. It's quite easy to make in the research environment to a GMP environment, but we're pretty good at that, and we're confident that we'll be able to do that without undue delays and bringing it forward.

Great. Now you have a significant pipeline, of course, over many disease areas. Can you talk just general corporate strategy here in terms of Ionis' plan to sort of partner programs versus keeping them in-house. How does that strategy look sort of going forward here?

Well, first, I should just highlight that we have had a change in global strategy. We used to -- and historically have had a model where all of our drugs would be partnered, and we would never commercialize our own drugs. And we have changed that in the last couple of years and are focused on building an expert commercial organization really to maximize the value that we can get for our drugs to both patients and to shareholders. [ I don't ] think we can get much better revenue growth through commercializing some of our drugs. The productivity of the technology platform makes it such that we cannot or do not want to commercialize all our drugs. And so we actually -- we had an Investor Day last year where we spent a lot of time talking about our commercial plans and our commercial strategy and how we want to build that. And can I ask about how we make these decisions? And I say, well, first, we've been working internally on some franchise spaces, both in the cardiovascular space, where we have a lot of drugs in our pipeline; and also the neurology space, where we are building upon the success of SPINRAZA and the ability of our drugs to work with local administration to the central nervous system, and we think they work very well. And so drugs that fit into those 2 spaces will fit well together within a commercial structure. And so -- if those leg up, if you will. In terms of Ionis' commercialization. We're also focusing our commercialization efforts in the U.S. market, find some partners via multiple models for the global market. And then really lastly, we always look at each drug uniquely and determine how it fits in overall, and is it a nice rare or smaller disease market that we could tackle with the young commercial organization? Is it a huge cardiovascular market? Like something like pelacarsen that I mentioned earlier that we partnered with Novartis, where there's millions and millions of patients with high Lp(a)-driven cardiovascular disease. It's a large cardiovascular market. If the hypothesis that lowering Lp(a) can reduce cardiovascular -- improve cardiovascular outcomes, and these patients holds true with our Phase III study, it will be a massive market. And so you want to have to -- someone like Novartis to go sell that drug into the broader patient population. So we kind of look at all of those things together and make decisions about what fits from our new emerging commercial structure well and what we think will be the best value for patients.

And you have these 3 late-stage programs, eplontersen, olezarsen and donidalorsen. Do you see these as the key drivers for near or even medium-term commercial or top line contribution to Ionis?

Well, yes, I certainly do. I think it's pretty straightforward that those late-stage drugs with readouts coming out very soon will be key for Ionis. I mean first, there's eplontersen, where we have 2 trials going on, both in peripheral neuropathy, which is scheduled to read out its interim in the not-too-distant future here this year, that will turn over a card. And then that same drug is in the largest cardiomyopathy outcome trial where we're going to have data in 2024. And we'll get to take a look at how the drug performs in the cardiomyopathy patient population. Of course, it's the same mechanism lowering TTR in the liver and present -- preventing accumulation of amyloid deposits. So we're very hopeful that the neuropathy successes and the precursor of this molecule is TEGSEDI, it's on the market for polyneuropathy, and eplontersen is a variant of that. It uses LICA that reduces dose and extends dosing frequency. So we're hopeful that, that data will be replicated in our soon-to-be reported study and that the cardiomyopathies trial will work out, and we can talk about that later. Olezarsen, we think -- we're very excited about that program. This is a drug which lowers triglycerides by inhibiting APOC3. It is really -- inhibiting APOC3 is the best way to lower triglycerides. It's very genetically validated. We've shown with the precursor molecule to that, WAYLIVRA, which is commercialized in Europe, that we can lower triglycerides. And olezarsen is a liver-targeted LICA variant of WAYLIVRA. And again, monthly dosing. We have that in 2 trials: one will read out in 2024, is the readout of the FCS trial. This is a rare indication of high triglycerides with people extremely high trigs, like 1,500 or 2,000 and where they really are in dire need of dramatic triglyceride lowering. And that's a 60-patient, I believe, trial where the endpoint is triglyceride lowering. We also have started a trial in a larger indication, which is severe high triglycerides, which is classified by the FDA as greater than 500. And again, the patient population there, the outlay of the approval endpoint is just lowering triglycerides in this patient population, and that's about 450 patients. And then you also mentioned donidalorsen, which is for hereditary angioedema. Here, it's a rarer market. A little bit crowded in the commercial space, but what we were very impressed by was the performance of the drug in our Phase II study, where we felt it could have potentially be the best in class in terms of preventing attack rates and both -- and also increasing -- having a very rapid onset in terms of decreasing the attack rates once patients were put on the drug. And there, there's a trial going on that got started last year with every month dosing or every other month dosing, well this drug has shown a nice ability to keep the targets abreast. And so we're looking at every other month dosing to try and give that option for patients with less frequent injections. Certainly, key value drivers, I think.

Now let's dive into some of the programs in a little bit more detail, starting with eplontersen. You have a recent partnership with AstraZeneca. Can you first, describe the commercial -- excuse me, the market opportunity here and outline the recent partnership with AZ? And what are the economics to Ionis?

Economics -- I think I'll probably defer you to one of our financial people for the actual economics to Ionis. Certainly -- the TTR neuropathy market is quite attractive, and it's attractive to many. There's a fair amount of competition in the space. And that's one reason we really like the AZ partnership. There AZ has a focus, especially in the cardiovascular market, and we think will be an excellent partner to help commercialize that drug. And we think we got a pretty good deal with AZ. They're a long-standing partner. They know our technology. They know the technology well, they know how to market and sell in the cardiovascular space. And if you look at how they've done with, for example, Crestor in the past, selling into the statin market, they did a great job. So we're enthusiastic about the AZ partnership. They're enthusiastic about the drug in both the polyneuropathy space as well as the cardiomyopathy space. Polyneuropathy, smaller, rarer patient population, but there's still a lot of patients. I think there's 40,000 hereditary ATTR patients worldwide or something like that, and there's estimates of 10 times that many cardiomyopathy ATTR patients. So it's a pretty sizable market, we think, as well as our competitors. And many analysts agree with us, that we think it will support multiple drugs with multiple mechanisms and that it's a really nice looking commercial market with drugs that can really help these patients that -- while there are approved drugs like tafamidis, there's still, we think, a great unmet medical need. And I'll also say that we're bullish on the TTR reducing mechanism versus stabilizing what's there. We think -- and a personal bias, I guess, from being in this field so long, reducing proteins that are pathological and toxic to me is an intuitively nice strategy for treating these diseases. You just take the bad actor away. And so we're hopeful that, that will turn out to be the best strategy. That being said, we also like our study design for the cardiomyopathy patient population, where we're running the largest trial in cardiomyopathy patients with 750 patients treated for 120 weeks, I think, an event-driven trial on the standard of care. And so we're allowing about -- we think we'll have about 50% usage of tafamidis in the trial. We think that's the way the drug will be used in the real-world population because tafamidis is out there and it's approved and it's been shown to give a benefit. And we powered our trial such that we can ask does eplontersen on top of tafamidis make a difference over tafamidis alone? Does eplontersen on its own make a difference over tafamidis alone or versus placebo? And we think those are great science questions to ask and hopefully, we'll get the results we want from our trial.

Got it. And you touched on both the cardiomyopathy and the polyneuropathy programs for eplontersen. Just curious to your thoughts on what profile do you think is going to be most critical to drive adoption in each of these indications? You mentioned that there's a thinking out there that both of these markets can -- are large enough to have more than one approved therapy. What's going to sort of drive adoption? What does the profile look like, a competitive profile look like in these indications?

Yes. I mean, well, certainly, if one drug had demonstrated in the clinical trial superior efficacy, and we don't know what's going to happen, we've got to turn over those cards. That would certainly be a differentiator in the marketplace. I always think efficacy is a key determinant, right? If you have a disease, especially a fatal one, you want a drug that has been shown to work the best. But we haven't turned over those cards yet. We do think our trial is positioned nicely to ask that question on top of the standard of care and really demonstrate improvement in cardiovascular outcomes. And we also are very comfortable, and as is AZ, with the presentation of the product. We plan to have a product presentation, as I mentioned earlier, in a low-volume subcu auto-injector device that's taken monthly at home by patients. And our market research that our commercial team has done says that's a very favorable view to physicians and patients and a good product presentation. So we're -- we think it will be a good competitor if the trials support the -- what we hope the data will show. So...

And sticking with one last question on the eplontersen program here. Now that you have the Phase III cardiomyopathy trial ongoing, there's been a lot of discussion around the 6-minute walk test primary endpoint and some competitor data. In your view, what sort of went wrong with the BridgeBio Phase III result missing that primary endpoint? What are the key differences for the cardio TTR transform trial that gives you confidence that Ionis could have a positive outcome for that trial?

Yes. I know there's a lot of talk about that trial. I really think the key is we're looking at cardiovascular events. So the gold standard in cardiovascular diseases is outcomes. And so we're looking at events, not a secondary measure like -- or like a 6-minute walk and how fast you walk. But how many events you have. And I think that it's a much harder endpoint and we should get the data we need. And one thing to note is that because it's an event-driven trial, we and AZ can monitor the events. And if we aren't seeing events that we need, we can take action and adjust accordingly as opposed to measuring something like the 6-minute walk. So I don't really know what happened wrong in their trial. Obviously, they would have better information than we do, and other speculation about the disease is being a little bit better managed and so some patients are being earlier and maybe they didn't have all TTR cardiomyopathy patients in their trial. It's hard to tell. But we're confident that we've got the right patient population in our trial and we can monitor the events, and we'll see how we do. And I also think our mechanism of lowering, as I've said earlier -- biased again. But I think the mechanism of lowering a TTR is a little bit better than stabilizing it.

Got it. Switching to the olezarsen program. Can you -- you touched on it earlier, but have a Phase III -- 2 Phase III programs going on there. Can you describe each of these indications in a little bit more detail and what you think the commercial opportunity is in each of those?

Yes, sure. So as I mentioned earlier, the first is a disease called FCS. There's a 3,000 to 5,000 patients with FCS worldwide. And again, this is a genetic high triglyceride disease, and the patients just -- the key is they have really high triglycerides. It's not like your doctor says, oh geez, you should eat a little better. They've got trigs of 1,500 or something that puts them at risk for things like pancreatitis. They have to get their trigs down. So it's a logical place for the drug. It's where we ran the trials for the predecessor, WAYLIVRA. And this trial. And scheduled readout -- I think I misspoke, it's in 2023, the BALANCE study is scheduled to readout in FCS. Obviously, a more rare disease, and we're planning to commercialize that ourselves. We also have started another trial, and this is for this indication of severe hypertriglyceridemia. This is triglycerides over 500, still very high, but not as bad as the FCS patients. This is a broader indication. We think there's maybe 3 million to 5 million patients, I believe, is the number on that in the United States alone. So it's a reasonable market, pretty big market. Obviously, it then requires a bigger trial. So we've started the CORE study, which is 450 patients, 12 months on treatment. Again, the primary endpoint is triglyceride lowering. So we're happy with the triglyceride lowering endpoint and are looking forward to hopefully demonstrating that our drug can address those patients as well. And again, a lot more patients there, broader marketplace, very attractive commercial profile, and this is a drug that we're planning on holding onto ourselves in the U.S. and commercializing ourselves.

And another late-stage program, donidalorsen in HAE. You already talked about that market, there are multiple players there. How does donidalorsen -- how do you see that fitting into the treatment landscape? And you recently initiated the Phase III OASIS trial late last year. When can we see initial results from that? And what do you think the bar for success is on the monthly attack rate?

Yes. So I mean, so -- absolutely right. The OASIS trial initiated. We anticipate data in 2024. This is 80 patients or so, 24 weeks. And as I mentioned, we have both monthly subcu dosing, again, low volume once a month at home or by monthly, same dose, just extending the dosing frequency. And that was driven by the Phase I data where we saw a very nice duration where the target suppression at 2 months post the last dose was essentially the same as that as 1 month. So hopefully, that will be borne out in the trial and give patients an option. What we're looking for is in terms of attack rate is really an extension of the Phase II data, which, as I said, we found quite impressive. Really dramatic reduction in attack rate and dramatic rapid reduction in attack rate. These patients, they have -- they're hereditary angioedema patients. The attacks are terrifying. They can be life-threatening and they -- minimizing attacks and reducing attack frequency is the name of the game. So we think the most efficacious product in the marketplace will have a very strong competitive position. And the reason we're enthusiastic about donidalorsen is the Phase II data would suggest that it could be a best efficacy in the marketplace as opposed to the convenience play. So definitely, we're seeking great efficacy. We hope to demonstrate it. And we also think that we can get that efficacy with a product presentation that is going to be better for patients. Less frequent injections and lower volume injections that caused less injection site reactions than the current standard of care. So that's what we're looking for in that drug. And hopefully, our Phase III will bear that out. This is another drug that we're looking to commercialize ourselves at Ionis.

Got it. Now you plan to release some additional Phase II results this year. What are some of the key metrics that we should look for when these additional data are released? And then in terms of the open-label extension trial, when can we expect to see some additional results from the OLE -- the Phase II OLE?

So which Phase IIs?

Excuse me, this is for donidalorsen.

Yes. So we just published a paper on that in the New England Journal. And I think the -- I have to check and get back to you on the -- I think the second half is when we're looking at the OLE data. And it will be traditional OLE data, which is longer treatment, and we'll get a look at some of the every 2-month dosing, I believe, from that open label.

Got it. So additional durability and safety, tolerability [ of that kind ]?

But obviously, the key is the Phase III outcome in 2024.

And moving down to some mid-stage programs. You had some initial data from the anti-PCSK9 program recently, some Phase IIb data. Can you put these results into context in terms of how they fit into the broader competitive market for this indication? And what's sort of the clinical development path forward?

Yes. So as far as clinical development path, I mean, obviously, with a PCSK9 inhibitor for the broad cardiovascular market, you'd need a pretty big Phase III program and an outcome program. And this program is partnered with AstraZeneca. Again, we talked about their cardiovascular heft, so it's a good partner to have in the cardiovascular space. What we presented at AAC just recently was Phase IIb data from the ETESIAN study, where -- had a beautiful clear dose response for PCSK9 and LDL lowering and it extended upon our earlier observations that this drug appears to have potential best-in-class efficacy profile again in terms of both PCSK9 lowering and also resulting in lower -- and better LDL lowering than some of the antibodies and even other RNA therapeutics that are ahead of us in the competitive landscape. So again, it's an efficacy play. We think that if you've got high LDL and are not a target, you want a drug that gets you as low as you want to go, and it's clearly been shown that lower LDL leads to better outcomes in the cardiovascular space. So that's the ultimate goal of this program. And this molecule looks like it's pretty good and pretty good in the space. So we look forward to more data from some of the Phase IIb trials from -- that AZ is running and their plans for how they're going to advance that drug later this year, hopefully.

Yes. And you have multiple Phase II readouts this year. We'll touch on a few more here. Cimdelirsen, Phase II results are expected in second half of this year. Can you describe the indication that's in development here and kind of the unmet need?

Yes. So this is a drug for acromegaly. And another rare disease, but where there is some competition in the space, but there really is nothing that fixes these patients or -- we still think there's a large unmet medical need in the acromegaly space. So this is, again, a LICA medicine targeted to the hepatocyte. So it fits the same monthly dosing profile that we've talked about in the other medicines. And the drug is designed to inhibit the production of growth hormone receptor, specifically in the liver, which we believe will decrease growth hormone signaling and growth hormone signaling drives the production of IGF-1, which is one of the key drivers of the disease of acromegaly. And we think that by interrupting the signaling access, we can lower IGF-1 in the plasma, and also keep it sustained and keep it lowered and so prevent IGF-1 excursions which you can see from other medicines that don't do what our drugs do, which is when we intervene in a pathway because of the duration of effect, our drugs knock the target down and they keep it suppressed over time. So you don't have excursions. And so hopefully, knocking down IGF-1, normalizing IGF-1 is the name of the game, but we have any reductions in IGF-1 are beneficial to these patients. So that's what we're trying to do is demonstrate that we can lower IGF-1, lower it enough to make a difference in the patients. And there's both a monotherapy trial, which we're going to have data for as well as some more open-label data from our combination trials.

And Eric, you mentioned the IGF-1, what -- you said that any sort of change in that would sort of be beneficial to patients. But is there a level or a change which is considered clinically meaningful or kind of a change that you're looking for in this initial Phase II trial?

Yes. Well, the ultimate goal, as I said, is normalization, to get it back into the normal range. As to how much of a change would be clinically meaningful? I think we've got to run the experiment to ask that. If we don't get normalization, we get lowering of IGF-1. Does it make a benefit to the patient on clinical endpoints? We have to wait for the trial data to really answer that. But ultimately, what we'd like to do is normalize it.

Yes. What are some other mid-stage programs that Ionis is most excited about? I know you have several, but your favorites or your top ones here.

Yes. So we didn't talk about our angiotensinogen program. We'll have some Phase II data on that in treatment-resistant hypertension later this year. This is a drug that interacts and intervenes in the RAS pathway at the level of the liver again. So it's a liver-targeted LICA, reduces angiotensinogen and we can intervene in the RAS pathway, lower blood pressure while sparing the kidney. So it's a very interesting approach, and we have previous data supporting our view that, that can lower blood pressure on, top of the multitude of medicines that are out there to -- that lower blood pressure, but there's still treatment-resistant patients that aren't met. Other drugs that I have a personal excitement about are some of our neurology programs, which are mid-stage. We have previously results -- released some data of Biogen on our MAPT program, we're looking forward to getting a IIb started there. This is a -- to me, it's the only program out there right now that can really address the tau hypothesis in Alzheimer's disease, where tau is present in the CSF and increasing in the CSF, concomitant with the onset of dementia. There's known that pathological aggregates of tau are intracellular and so we really don't see antibodies as being able to attack that, whereas we're turning off production, reducing all forms of tau. And the Phase I data -- Ib data that we had with Biogen really demonstrated robust engagement of all forms of MAPT with a drug that looks like it has a very extended dosing frequency. When we dosed in the patients, when it came back and were redosed to the open-label extension up to 6 to 14 months after the cessation of dosing for the patients in the higher dose cohorts, it was still flat. So their tau levels haven't recovered. So it looks like that's a very durable drug. And looking to get some studies going. We also have 2 drugs for Parkinson's disease, partnered with Biogen. A little bit earlier stage, but targeting LRRK2 and also alpha-synuclein. So again, pathogenic proteins in the disease. And we've got a study started in Angelman syndrome, where we have a drug that lowers an antisense transcript. This then allows reactivation of the gene that is causing Angelman syndrome in these patients. And I hope to get some data on that program, probably not this year but hopefully next year, exciting earlier-stage neurology program.

Great, fantastic, Eric. We're out of time for this session, but I want to thank everyone for joining us on the webcast. And thanks again, Eric, for participating. I hope everyone has a good day.

Great. Appreciate it.