Well, good afternoon. Thanks for joining us for the next session at the Bank of America Healthcare Conference. I am Tazeen Ahmad. I'm one of the senior SMID biotech analysts at the bank. It's my pleasure to have our next presenting company with me here on stage, Arvinas, and sitting next to me are, Ian Taylor, who is Chief Scientific Officer, as well as Randy Teel, who is Chief Business Officer, as well as interim CFO and Treasurer. Gentlemen, thanks for making the trip out last.
Thank you. Thanks for the invitation.
Maybe we'll start with Randy about the overview of the company. If you could give us a two-minute summary of the platform and what makes Arvinas differentiated, and then I'll ask you a question about a recent transaction.
Sure, sounds okay. And thanks again for hosting us. Yes, so Arvinas was founded about 11 years ago at this point. We make PROTAC protein degraders. I expect that most folks in the audience are well aware of that by now. We've moved to a point where we have our first pivotal data coming out in the latter half of this year. So our lead program is vepdegestrant, partnered with Pfizer, and our monotherapy second-line plus study has top-line data planned for the second half of the year. That's, that's probably the biggest thing coming this year. Hard to compete with that. Also, for that program, we'll also share some combination data with some other CDK4/6 inhibitors.
We recently, last December, shared data with vepdegestrant along with palbociclib, Pfizer's CDK4/6, but also have an ongoing study with abema and ribo as well, and so we'll share some of that data by the end of the year. That will tee us up for our first, you know, ever, submission for approval and hopefully get that in short order and turn us into a commercial company, which obviously would be a major milestone for us. At the same time, we are bringing along a number of other programs, at least 20 in the pipeline. With the recent deal that we'll talk about in a minute for ARV-766, the next two programs actually are just now starting in the clinic. So ARV-102 is a LRRK2 degrader in neuroscience.
As far as we know, that's the first PROTAC degrader intended for neuroscience or neurodegenerative disorders to enter the clinic, and that has just started dosing earlier this year. We'll certainly talk about that during this half hour. And then we also have a program called ARV-393, which is a BCL6 degrader relevant for both hematology, but also some potential solid tumor activity as well. Behind that, like I said, a number of other programs, both in neuroscience and in oncology. Those are the two major focus areas that we have. And we are well capitalized at this point, capital into 2027. I'll get that question out of the way right at the start. We usually wait till the end, but that's one we always get asked.
But a lot to talk about, so I'll let you move on to the next one.
Yeah. So as promised, I wanted to ask you about the deal that you signed with Novartis for ARV-766 and prostate cancer. Can you talk about how long those talks were in play and why it made sense to have Novartis be, you know, take over this program here and what it means for Arvinas in the future?
Yeah, absolutely. And business development for us has been a pretty constant activity, I mean, for the past 10 years. So we started out with target deals with Merck back in the day, Pfizer, Genentech, Bayer, along the way, you know, through 2018 or so, and then did the Pfizer deal for vepdegestrant in 2021, which was a co-co deal. I didn't mention that a moment ago. For vepdegestrant, it's a co-co, you know, 50/50 global cost and profit share. The Novartis deal for ARV-766 is quite different. It's an outlicense. That was just announced about a month ago. It's still in HSR review, so it still has to close, but that's an outlicense.
And the rationale there was, as we have gotten more and more data for vepdegestrant and continued to expand the development program, which we last talked about in December, we realized it would make sense. We had always known it would make sense to look for a partner. For ARV-766, which is an AR degrader, the market there is primarily in prostate cancer, and there are late line opportunities in CRPC, but the biggest opportunity was clearly always going to be in the castrate-sensitive space. Those are large, long trials, thousands of patients, and we felt like as we look ahead towards what I just talked about in terms of completing the trials with vepdegestrant, increasing them, multiple phase 3s ongoing, planning to build out the infrastructure to launch in the U.S.
While it's a 50/50 cost share with Pfizer, we book sales in the U.S., and Pfizer books sales outside the U.S. So we thought that for ARV-766 , it made much more sense to do an outlicense structure, where we'll let Novartis, who has a lot of capability in prostate cancer, a growing portfolio in prostate cancer, Pluvicto and some other therapies, makes sense to let them invest, take it to the earlier stages, and obviously, that patients can benefit from that. We can benefit from that while we are focused on bringing vepdegestrant to market, as well as bringing along the next generation of PROTAC degraders from our pipeline. So that was really the rationale there. We're excited about that. Lots to come from it.
We actually still have some data coming up for ARV-766 at ASCO in just a couple of weeks, so you can look for that there, but thereafter, it'll be certainly Novartis' program, pending closure to pursue.
Okay, thanks for that, Randy. I mean, how much, if any, of this timing revolves around the macro environment of interest rates and, you know, companies that are not revenue-generating are always under more scrutiny in this type of environment, and did you think that it could be more challenging to raise capital without having clarity on, on where interest rates are going in the nearer term?
No, I would have to say less so. We take a pretty long view, and like I said, we feel well capitalized, but we have a lot of plans. But that being said, I think the resource intensity of moving into the castrate-sensitive space and the trials that that would require in the coming years as we're commercializing vep, I think that's that is a bigger consideration. Not that we don't think about that, but it's that's a bigger consideration for us. And the deals, they take a while, right? These are conversations that that can go back years, as we keep potential partners updated on our progress. It definitely isn't overnight, so those have been going on longer than the-
... interest rate conversations.
Okay, good to know. So maybe let's pivot back to the pipeline, and Ian, maybe you can give us a summary of the data that was presented at this past San Antonio Breast Cancer Conference, because that was a big pivot point for share price, certainly for Arvinas. And you know, help us appreciate the importance of the data that was presented there, specific to vep plus palbo.
Sure. So, it was our phase Ib cohort of vepdegestrant plus palbo, very heavily pretreated patient population, so about 90% had prior CDK4/6, mostly palbo. About 80% had had prior fulvestrant, and about 80% had prior chemotherapy, 42%-ish in the metastatic setting. So basically, fourth line plus, very late line and, and, you know, after palbociclib in particular. And what we showed was a response rate of about 42%, clinical benefit rate of 63%, and, you know, really interestingly, a PFS of 11.1 months, which was, you know, by far the best data that's been seen, post CDK4/6. So having a CDK4/6 inhibitor after CDK4/6 inhibitor, there have been a number of studies where that, the data was very equivocal.
But we really believe that having a great de grader like vepdegestrant in combination with a CDK4/6 inhibitor and palbo, in this case, the synergy that we attacked, because the two pathways are overlapping, they're complementary, they, there's crosstalk, really came to the fore, and that's what drove the great efficacy in both ESR1 mutant patients as well as wild type. So that synergy really helped because in the monotherapy setting, you see better activity in the ESR1 mutants because it's really a signature for ER dependence of those tumors as opposed to wild type.
In the late line, there's a lot of non-ER-dependent mechanisms, but when you're hitting both pathways really hard with vepdegestrant against ER and palbo, that synergy really accelerated and increased the efficacy and, you know, really much higher than any of our comparator studies like PACE, MAINTAIN, et cetera. So we're really pleased, and it sets us up well for a registrational study down the line, as well as I think it portends for our first-line study as well, with combination, potentially a combination with palbociclib.
Yeah. How important was that efficacy in the wild type in trying to establish what the market opportunity could be?
Yeah, basically, you know, it could double it, I guess. I mean, Randy could probably speak to the actual size, but, you know, we're hoping with our monotherapy trial that we'll also have, we have-- it's a, it's a dual endpoint, so we'll have-
ESR1 mutants, as well as the intention to treat, which, but it's not powered for wild type specifically. Obviously, other therapies have had trouble getting a broad label. We think we have a really great chance for it, but to have that activity in wild type in the combination, really, you know, it acts as a hedge. If we don't get that label in the monotherapy, you know, we're in a really great shape to have it in the combo. You know, in that stage, probably a couple of years behind our monotherapy trial.
Right. So, the data was much better than people had anticipated, of course, but one area that was a topic of discussion was the rate of neutropenia that you saw. 11% of patients had that grade 4, but you were able to address that by , down- titrating palbo. Can you talk about what the feedback specifically to that has been with physicians and how that's going to influence your phase III trial design?
Yeah, sure. So, certainly in the combination with vepdegestrant and palbo, we did see an increase in exposure to palbo, about 50% over its mean exposure. Of course, you have to remember that the range of palbo exposure is ±30% anyway, so there's quite a bit of variation. We were about 50%, so a little bit higher. That did come with a higher rate of neutropenia, because there is a pretty steep exposure neutropenia relationship. So what was happening was that the investigators were doing what they always do with palbociclib, because neutropenia is a big problem, is they dosed down. So it went from 125 to 100 and in some cases to 75, and then whatever...
That neutropenia then came down more into the range of where it historically is with palbo. You know, at the lower levels, basically, the neutropenia was basically down where it should be. Only three patients stopped dosing entirely because of neutropenia.
out of the 46 that we had in the study. So basically, to answer your question, the KOLs, the investigators, Erika Hamilton at San Antonio, basically said that the neutropenia was easily managed because this is what they do with palbociclib all the time. They just dose down to drop the neutropenia. So it's really not much different than what they're used to. And so, I think that will be informative going forward. For our Phase III study, we do have a study lead- in, where we're comparing 100 mg and 75 mg in combo with vepdegestrant, and we'll see what that is the best dose there in terms of PK, neutropenia, and just tolerability in general.
Yeah. So for some who are trying to understand what the risks are, for example, you're looking at the 75 and 100, but, but what about the 125 mg? You know, some have hypothesized that at least some of the efficacy can be attributable to that early exposure to palbo. And do you risk having lower efficacy when, when you move into phase III?
Yeah, we don't, we don't think so. First of all, there's really no exposure-efficacy relationship with palbo. That's been shown. You can look it up in the, the FDA documents, the summary basis of approval, and that was looked at. They saw a, a exposure, a neutropenia relationship, and we saw it as well, but there's been no exposure-efficacy relationship. Also, the, the dose interruptions due to neutropenia happened very quickly within the first cycle, like 30 days. And then dose reduction happened within, like, 37 days on median, and then the median time to response was about 110 days. And then also, subsequently, patients that were dose reduced actually had a longer duration of therapy than patients who stayed at 125. So the, the time that they were on the higher exposure getting neutropenia was very, very transient.
They stayed on drug and had response at the lower doses much longer. So it's really almost impossible to believe that that transient increase drove the type of efficacy where eventually, again, we talked about 11 months PFS. Obviously, we'll see when the study lead- in, we're gonna be testing 100, 75 to start with. We won't have a lot of efficacy data with that. It's mostly PK and safety to pick the go-forward dose. But we're very confident that it's, the efficacy was not because of the boost in exposure.
Okay. And then in terms of timelines for phase III, can you walk us through that for this program?
The phase III for the combination first line.
Yes. So basically, we're in discussions with Pfizer whether that Phase III will be a combination with palbo or their CDK4-
Right
-compound, which we've started a combination study with that. And we'll have data toward the end of the year. And then we'll be making a data-driven decision with Pfizer on what combination we'll bring forward in that first-line study. It'll be, you know, not the most straightforward of decisions, quite frankly, just because we're not gonna have as much data with the CDK4 combo as we have with palbo. But we know what to expect in terms of safety, what we need to see, and we know what kind of range we want to see with efficacy. So, it's just gonna be an apples to oranges comparison just because the amount of data that we will have for both.
Yeah. I guess a more cynical investor would say, well, palbo was going off IP for-
Yeah
-for Pfizer, and so Pfizer would be motivated to try to really move forward with the CDK4. But from Arvinas's standpoint, mechanistically, can you talk about what advantages the CDK4 could present relative to palbo?
Yeah, I mean, I think, right. Certainly, Pfizer has incentive to do CDK4 for the reasons you stated. I think mechanistically, you know, they're both certainly driving the cyclin pathway. From a biological standpoint, you know, obviously, CDK4/6 has CDK4 component. CDK4 is thought to be maybe the bigger driver of efficacy, certainly more of safety, because their neutropenia rates with that compound are much, much lower. So instead of 60% Grade 3,4, it's more like 15%. So any potential increase in exposure we might see there would be much more tolerated. We wouldn't have to presumably see the type of dose reductions that had to be done with palbo. Again, that's standard with palbo. So, and we'll see. They've shown good efficacy with their compound so far.
And we've shown preclinically that that combination works really well, the PROTAC ER with CDK4, actually better than the CDK4/6 palbo, preclinically in both wild-type estrogen receptor models as well as ESR1 mutants. So, I mean, that's preclinical data, but all of it kind of adds up to say that if we did go forward with that combination, it would be a very strong combination.
Where do you think the main opportunity would be, first line over time or second line?
Well, I think, so kind of separate. So we think the palbo combination, which we're also in second line, we're also considering including abema and/or ribo as well. So sort of have a physician's choice. But in the first line, it's either gonna be palbo or CDK4.
Okay. Now, but I guess some folks, I think, would maybe appreciate some color on how you're breaking out the opportunities-
Okay
First line versus second line, understanding that you're still trying to determine what the combos are gonna be in the first and second-line therapies. And maybe, Randy, you have some thoughts?
Yeah, I can, I can do that a bit. And also one more piece on the, the palbo combo data is that we had the data in December, but we also have a, a presentation just actually in two days at, at ESMO Breast, which will be updated data with another six months of follow-on from what we saw in December. So, look for that as well. So I think that sequence is important, right? So second-line mono comes first. There, the question that we get a lot is around ESR1 mutant versus wild type, so we can definitely talk about that.
Consider it another couple of years, and then the second-line combo comes along behind that, which is with palbo plus potentially other CDK4/6 inhibitors, like Ian just said, and then the first-line combo coming another 2 or 3 years beyond that, which again is, as Ian just said, palbo or CDK4.
Yeah.
So across those three, you know, in terms of how we think about it, in terms of commercial opportunity, they get from narrower to broader, which is a good thing for a small company like us, just starting on our first commercial launch. You know, we would estimate something in the few hundred million to maybe $500 million for the revenues for the second-line mono, depending on that mutant versus wild type question. That could push towards $1 billion for the second-line combo opportunity and obviously much larger than that for the first-line combo, which is dependent on a lot of factors, multiple years away, like what the competition looks like at that point, what other programs are brought forward in first-line combination as well.
But we really think that sets us up, you know, through the end of the decade, really, to have our first three launches all from VEP, while the rest of the pipeline begins to mature. So it really is a sequential, you know, stepwise growth pattern for us.
If the decision is made in front line to pursue combo with CDK4, does that change the timeline to when first-line combo would reach market?
Yeah, I think it, it could push out a little bit, but I think that would be, you know, well taken. That, that would be fine. And I think it's important as we talk about that, the trade-off, we will have a lot more data by the end of the year for VEP and palbo than we ever will for, for CDK4, right? And that's just, that's just a fact. We'll have to live with that. If we had to push off a little bit to wait, as we've talked about, it's obviously Pfizer has a strong push for CDK4. We are certainly not against that. They're both great options.
As Arvinas, without the involvement of Pfizer, what do you think about palbo versus ribo, in general?
In terms of?
Doctor preference.
Oh, well, and I think, certainly it's, it seems clear that ribo is becoming the more preferred-
-agent, probably because it has the overall survival label. From a mechanistic standpoint, at least, again, preclinically, we've done combinations with all three.
Yeah.
They basically look equivalent. And mechanistically, that makes sense. And I think also, you know, as ribo moves earlier, potentially even to adjuvant, there is a growing, I guess, recognition. There's not a lot of data, but I think it's coming, that if you switch CDK 4/6 inhibitors, as you go from one line to another, you actually can get benefit CDK after CDK. I think that's what the MAINTAIN study showed. Our data is kind of opposite of that because we had, it was basically palbo after palbo. But I think, if with our strong data with palbo, you know, I think, why wouldn't a physician use it if we have, you know, with such long PFS?
Especially if it's a switch after Ribo, then I think, you know, even more so.
In terms of just degraders being combined or your degrader being combined with ribo, how do you think that would be received by physicians relative to palbo?
Well, we have an umbrella study going on where we have-
We're combining with both ribo and abema.
Yep.
Basically, again, a PK safety study, not so much in efficacy. So we'll have data in terms of how well it's combined, whether we see any minor DDIs. So I think, you know, again, because of the mechanism and, you know, the agents, they're different, but they're, you know, kind of the same in general. I think there'll be a lot of enthusiasm to compare vepdegestrant, really as the partner of choice with anything. CDK, ribo, abema, palbo. We're also, in our umbrella study, we have a CDK7 inhibitor combination. We've got an everolimus combination ongoing. There's been talk about having PI3K or AKT combinations. So that's really our strategy to really set it up so that it's the partner of choice for any other-
Sure
-mechanism.
Okay, so let's talk about VERITAC-3, and what to expect there.
Well, VERITAC-3, again, that's our first-line study.
Again, it really depends on what agent we're going to combine with.
Yeah.
Palbo or CDK4. So, again, that'll be a data-driven decision that we get you probably the end of this year-
Yep.
Maybe beginning of next.
Okay.
and then we'll hopefully-
Well, I guess what level of data would you tell us?
Oh, what level of data would we tell you? I don't know. Maybe that's a question for Randy. I'm not sure.
Important to consider that that is a safety lead-in, and it's part of the ongoing phase III trial. I think the most important information-
Right.
that we'll probably want to share is the first line combo going to be with palbo?
Yeah.
Or CDK4? And if it's with palbo, what's the dose?
Right.
Is it 75 or is it 100? That's probably the most important information to know. But as far as, you know, breaking out data or pulling data out of an ongoing phase III trial, that'll be a discussion that we and Pfizer have to have to-
Okay.
decide exactly what we would share.
Right. So you'll say what you're gonna do, but not necessarily clear on what level of data we should expect to see?
Yeah, and I think you can probably extrapolate from that. If it ends up being a palbo combo for the first line combo, you should expect we'll, you know, feel the need to share a lot more information than if we're gonna make for CDK4.
Okay. And then in terms of monotherapy, pivotal study results, time, can you reiterate the timetable for that? That's coming.
Second half of the year.
Yeah. So let's assume it's around about end of year, around about San Antonio Breast.
Yeah, think things could be interesting, right? Because we won't be able to predict that. It's an event rate-driven-
Right
you know, endpoint. And so if we are planning to go out and have data with the TACTIVE-U, the umbrella trial, and at some conference in December or otherwise, we won't be able to predict what happens there. So, either way, I think we are poised for a lot of information over the next, you know, year or so.
Yeah.
If I really fast-forward to a year from now, we've shown the top-line data. We've gotten a look at, you know, the ESR1 mutant versus wild type question. We've shared combo data. We've made that choice about what's moving forward for the first-line phase III trial.
I think the world looks a lot clearer. You know, I think it... We admit it's a lot to keep track of right now. It looks a lot clearer a year from now, exactly what the plan is going to be.
Right.
A lot to come.
For the rest of this year, what would you say is your biggest catalyst, then?
Top-line data for VERITAC-2.
Right. And let's say it happens to be at around December timeframe. What would be good data? Not just statistically significant necessarily, but what's clinically meaningful?
Yeah, so I think, VERITAC-2, it's a little bit different than VERITAC in that we have no prior fulvestrant, no prior chemo.
Yep.
We're requiring that patients have at least six months of prior endocrine therapy. That's really to eliminate as much as we can, patients that have primary endocrine resistance. And so that means that the fulvestrant arm, which is our comparator, will do a little bit better than you saw from the EMERALD study, which is around two months. You know, we're estimating it could be four to five months.
But again, our data so far has been in late line, and we also expect to see a better benefit because the tumors are more ER dependent with those inclusion criteria. So you know, what would be clinically meaningful would be, you know, somewhere maybe double that. Some of it will be. A bar may be set when the EMBER-3 data reads out at some point this year.
But, you know, certainly our statistics are powered for, you know, less than doubling. But, you know, in the end, that becomes an FDA decision at the end. But we expect a pretty nice efficacy based on the data we've seen so far in very late-line patients.
Right... is there any concern that the comparator arm could perform better than you anticipated?
Well, I mean, that's always a possibility, right, in clinical trials. I think that, based on the historical data in that range that I stated is about right. I mean, maybe there's been one or two studies at most, where there's been an outlier, but it's fulvestrant has been pretty, pretty standardly performing, in history. So again, that's why you run the trial, to see, but, we're not too concerned about that.
Okay. So, we'll regroup after we see that data at year-end on, on that program. But I also did want to touch upon your BCL6 as well as your LRRK2 PROTAC programs. Can you give us a sense of why the company feels excited about those particular programs and what the next catalyst for those could be?
Yeah. So I'll start with LRRK2. BCL6 is in the same category of what I'm generally going to say. It's a perfect PROTAC target. LRRK2 is a kinase, but it also has a GTPase function, a scaffolding function as part of its activity. And so, therefore, just targeting the kinase activity of the protein only takes care of part of the story. And by degrading it, you remove that GTPase function, you remove the scaffolding function. And there's actually preclinical data that suggests when you use siRNA to knock down the protein, you actually get a better benefit than just a kinase inhibitor in terms of synuclein spreading or a behavioral defect in a mouse model.
And LRRK2 is genetically tied to Parkinson's disease, also progressive supranuclear palsy, overexpression, increased kinase activity, all correlate with disease progression and severity. So really, we believe that by degrading it, knocking it down, at least 50%, in the brain with our orally bioavailable PROTAC, will then have a benefit in terms of lysosomal function, decreasing in Parkinson's disease, synuclein, or in PSP tau. So for all those reasons, it's a great PROTAC target. It's genetically tied to the diseases in terms of its activity, and there's preclinical data to support that you'll have a disease-modifying effect. BCL6, very similar. Great PROTAC target. It's a transcription factor, transcription repressor, been very much under-drugged by inhibitors. We've shown great degradation in vitro and in vivo in DLBCL models, also other models of non-Hodgkin's lymphoma.
The duration of activity of the PROTAC is really important because, because it is a transcription factor, you need to keep it down. We've degraded basically 100% for multiple days after dosing, and that's important because it's a very high resynthesis protein. Within two hours, if you wash it out, the protein comes back. So again, an inhibitor would have a really hard time having full target coverage for that long. But with the degrader and the duration of activity, it's, it leads to basically tumor regressions in many different types of models. We've tested probably a dozen different models in the NHL space and seen, tumor stasis or regressions in pretty much all. Now we're looking at combinations.
Okay. On the point of LRRK2, because it's CNS-focused-
Yep.
How are you thinking about where you think Arvinas wants to develop it to before potentially, and I don't want to put words in your mouth, considering partnering, because those are, you know, expensive, time-consuming, large studies, and maybe Arvinas does want to keep it, but wanted to hear your thoughts.
Yeah, we've been pretty consistent with our neuroscience strategy, that there's some indications, right, LRRK2 for progressive supranuclear palsy, more aggressive disease, smaller study, we could potentially do that by ourselves. But when we get into Parkinson's disease or Alzheimer's disease for our tau program, we've always talked about needing a partner for, for that. Those are really huge studies, very expensive, and we've really never thought that we'd do those on our own. So that strategy remains intact, I think.
How attractive is it to be pursuing these targets like tau? Because there are so many companies pursuing that target, not with degraders per se, but, you know, many different mechanisms are being looked at.
Yeah.
Why is it a good use of your cash to want to explore looking at tau, for example?
Yeah, and I think... Listen, we really believe in our mechanism. It is differentiated from the ways that these other modalities have been gone after with antibodies or ASOs, obviously, have some liabilities in terms of delivery, brain penetration. So, you know, obviously, high unmet medical need. It's high risk as well. But we think that the PROTAC is probably the best way to actually try to drug these targets. They've-- It's been an underserved market and probably just not drugged in the best way. And so that if we can have an effect, decrease these proteins, maybe not requiring 100%, we think we can have a significant benefit where it's not seen before. I think our first test of that will be with LRRK2 in the CNS space, the neural space.
But obviously, tau is a big driver in Alzheimer's disease. Synuclein, a big driver in Parkinson's disease. So these are huge opportunities, and we just think that the, it's a great time to test the PROTAC mechanism, in those spaces.
Maybe last question for Randy. On the LRRK, specifically, are you getting inbounds on strategic interest in the molecule and in programs, specifically in CNS?
Yeah, for sure. So I joined Arvinas in 2018, and at that point, we had had, you know, multiple-year conversations ongoing with potential partners in oncology, and that has continued. So both in oncology and neuroscience, we do a pretty good job of keeping folks updated on where we are, what the plans are, because as Ian said, and there's a pattern here, right? With ER, with AR, with LRRK2, there may be populations that we can go after as a small company, but they've also got some really large value-driving indications that would just be really difficult for us. So we've always kept folks updated, and there's always been interest.
So you're doing the early-stage work, but is there a point in time where you think it's ideal to turn it over to someone else?
I think maybe the bright line for LRRK2 would be Parkinson's, you know, phase 2, things like that.
But we're not there yet.
Yeah.
The healthy volunteer studies will tell us a lot. You know, we're not far from finding out whether we can deliver a PROTAC orally and degrade LRRK2 in the CSF. So there's some major, I think, value-driving milestones to come that will really show what a PROTAC can do in neuroscience, and that's probably the right point to think more clearly about that.
Okay, perfect. With that, we are out of time, so I want to say thank you to you both for spending the last 30 minutes with me. Thanks, everybody, for coming into the room and listening to the presentation, and hope everybody has a great rest of the session. Thanks.
Thank you again.
Thank you.