Great. Thanks for joining us. I'm Terence Flynn, Morgan Stanley's U.S. biopharma analyst. For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. With that, very pleased to be hosting Arvinas this morning from the company of Randy Teel, the company's CEO, and Andrew Saik, the company's CFO. Thank you both for being here, really appreciate it. Looking forward to the conversation. Maybe to kick it off, Randy, you've been in this seat now for about six months. Just talk to us about your priorities. What are you most focused on these days as we enter the end of the year here? Yeah, thank you very much, Terence, and thanks for having us at the conference. Maybe also definitely talk about that as we go through the day or through the half hour. I want to talk a little bit about the company and where we are right now. Sure. Mainly because we've been around a little while, right? The company is now 13 years old and has certainly gone through some phases. We really have led the way in PROTAC discovery and development, and it's been really gratifying that just in the past few months, the first program that we invented is now in the market and serving patients. So it's off treating second line plus breast cancer patients, which is obviously pretty thrilling for all of us at the company to have discovered the technology and have the first drug out in the market. We have now shifted, as we'll talk a lot about, to our earlier stage pipeline. So we decided to not invest in the commercialization of that, but to focus our capital on the phase I programs that we have, that we now have four of. I think one important feature for investors looking at Arvinas these days is that we've been talking for a while about milestones and catalysts from that pipeline coming out in the future, and now the future is very rapidly approaching. So as we sit here in September and look out over the next year and a half, all four programs, including one that's just starting in the clinic this quarter, I would expect to have important data coming out. So just to set the scene a little bit, we've got four programs in the clinic. The first is a PROTAC BCL6 degrader for hematology indications and subsets of NHL. That program will have its first data by the end of the year. We've got a neurodegeneration program that degrades LRRK2 that will have some important biomarker data coming up at a conference next month. We just began a rare neuromuscular program for Kennedy's disease, also known as SBMA. Started that in the beginning of the year. It's been enrolling well, and we expect to have data in the first half of next year. To round it out, we have an HPK1 degrader for use in immuno-oncology indications just starting in the clinic in this current quarter. No commitments on data yet, but starting the trial now, maybe we'd expect to have data in a year or so. We've been pushing those programs forward, I think, very effectively. We have made some important decisions. To get to your point on priorities and prioritization, over the first six months of my tenure here, we've tried to be very focused. I've tried to lay down a very clear priority that where we invest, we're going to invest to win. If we don't feel like we're positioned to do that will be a place for someone else to jump in, and we'll talk a bit about that. The last point I would make is, from a capital perspective, our guidance is into the second half of 2028, so we certainly have the capital we need to get through these important inflection points. When it comes to my initial priorities, it has really been to look at the pipeline. I've been at the company for eight years, so it is not as if I've learned a great deal about the company in my first few months as CEO. I certainly continue to be impressed and amazed and proud of the team that we have and how well we've done at moving important programs into the clinic. Right now it's really about moving those phase I programs to their inflection points and seeing where the data are, where they end up, what makes sense as next steps for each program, whether that's to pile in and invest more, whether that's like happened for the KRAS program earlier this year, we decided that would only move forward with a partner, whether that's the call. That's what we're thinking about. Also making sure that we turn ourselves a bit from being a company that was on the precipice of being a commercial company to now being back to a company that's in phase I. Those companies look different. They operate differently, they feel differently, and it's been very important to me and the team that we ensure that we are acting like a young phase I company and not a company that is about to be a commercial breast cancer company. Okay, great. Perfect framing. Maybe let's just jump into the assets that you walk through here. I mean, ARV-393 is your PROTAC BCL6 degrader. Maybe just give us an update and kind of like you said, data by year-end, walk us through the trial and maybe level set us on expectations in terms of what we should be focused on. Yeah. ARV-393 is a degrader for BCL-6. BCL-6 really, given our history, I'd say our formative years in AR and ER as our first targets, BCL-6 was one of our first targets that's certainly an undruggable. There had been BCL-6 inhibitors moving through preclinical studies, none really that I know of made it to the clinic. One reason for that is, and that makes BCL-6 an ideal target for a PROTAC degrader, is that deep degradation of BCL-6 is important. It's rapidly resynthesized. BCL-6, just for a little more stage setting, is an important factor in B-cell development, functions in germinal centers to allow B-cells to rapidly allow to develop into mature B-cells and allow some DNA mutation without apoptosis that's important for B-cell maturation. It should turn off after that. If it doesn't turn off, that's where you start to have problems with BCL-6. Yeah. The study that we're running is in subsets of NHL. We are enrolling pretty broadly across both B-cell lymphomas like LBCL and T-cell lymphomas like AITL. The landscape in that setting, which is an important context, is pretty crowded when it comes to other therapeutic modalities. If you're looking at antibodies, bispecifics, chemo, there's CAR T therapies, there's transplant as an important modality. It's pretty crowded. If you're looking for oral therapies it's not very crowded. If you're looking for BCL-6 target agents, it's not very crowded. The way that the space has typically evolved is to add on additional therapies to deepen and extend responses, and that's what we'd like to do with a BCL6 degrader. You made a point in your question about the conduct of that trial. We have been clear to say that, for a couple of factors, we began that trial dosing at levels that we did not expect to be efficacious. We've made it through a few rounds of enrollment in different cohorts at levels that, especially in B-cell lymphomas, we would expect to be below an efficacious range. As we get to that first data, what we've decided to do is focus the first data release, by the end of this year, more on the T-cell lymphoma patients, and then save a disclosure for B-cell lymphoma patients more for the middle of next year or so. That allows us to focus on a population with very high unmet need, which later line, second-line plus T-cell patients certainly are. Also, just through the way the trial was run, we mentioned about a year ago that we had seen responses in both T-cell and B-cell lymphomas. I think that unmet need absolutely led to an enrollment of a disproportionate number of T-cell patients versus what we would have expected. So we are going to focus on them first. The other thing that does is that as we get to the B-cell patient disclosure, more focused on those patients next summer, we also can discuss our ongoing combination therapy. We have an escalation ongoing with ARV-393 as monotherapy, but we are also dosing with glofitamab in patients as well. That will allow us to disclose both of those next year. So when it comes to this first data disclosure, there really is no specifically indicated therapy for second-line plus T-cell lymphoma patients. We will be looking for initial signs of safety, of course. Obviously, we have been able to dose as we would like to, so feeling pretty good about that. PK, PD, degradation of BCL-6, and of course, some early signs of efficacy. Now, in an escalation study, especially where I have said we would not expect early doses to be efficacious, we will keep the expectations a bit more modest there. But if you look over time what a patient in second-line AITL or disease is getting, think of the 40% or so range of ORR. So that is what we would like to be seeing to make sure that we have good single-agent activity in these patients. Then clearly, as we get to be dosing at a range that we would prefer to be dosing at, we would expect to continue to see improvement there. Yeah. But that is how we think about the first set of data in the last part of the year. Okay, great. Just remind us, is it typical 3 by 3 design? Yeah, it's a pretty typical design. Okay. Have you said how many cohorts? I know you said it's more predominantly T-cell versus B-cell, but have you said how many cohorts you've gotten through yet at this point? I think we've said assume dozens of patients. Okay. In terms of number of cohorts, haven't talked about it. Okay, got it. Okay. The important question I think will really be now that we are, and we've said this, dosing at a range that we would expect to produce efficacious exposures, that's what we'll be most focused on. Yeah. There certainly will be some patients that were dosed well below where we'd expect to see. Okay. How much follow-up will you have on those initial set of patients? It will vary. Okay. Yeah. Patients that are dosed the highest- Right. will have the least follow-up. Yeah. Okay. Is this a medical conference? Is this something like an ASH update, or this is a corporate update? We've said a medical congress. Yeah. I think as an aside, that's really important for us in terms of making sure that, especially in a space where there's multiple players and a lot of combination options, I think it's really important for us to get word out about the trial, what's ongoing, how it's done, how it's performed, especially as the doses have increased. Right. That being said, going back to what I said about acting like a younger phase I company, we certainly, over our history as a company, have used both medical congresses and done our own releases, and both are in play. Okay. We've said for this to expect a medical congress. Okay. I'm much more worried about making sure we get the data out at the right time in the right way. Okay, makes sense. I guess in terms of the monotherapy versus combo, again, T-cell monotherapy is the approach, but in B-cell, it sounds like combo. The data update next year, it sounds like it's going to be both monotherapy, but also some combo data with glofitamab initially, or is it only going to be monotherapy data next year? With combo. Combo data as well. They have both? Yeah. Okay. Exactly. All right. Yeah. Importantly, the patients treated with the glofitamab combo, those are LBCL patients. Yeah. B-cell lymphoma patients. I think if we look at the landscape, right? You may be getting at this question, but as we think about development across LBCL and other B-cell lymphomas and across T-cell lymphomas, there is really an opportunity to think about what you do in the late line versus what you do. Right. in the early line. Yeah. As monotherapy, the opportunities are really in the late line. Those opportunities can come a bit quicker. Trial timelines are shorter, responses for patients are often unfortunately shorter, and so it is a bit quicker to run those trials. We do think that those are important for demonstrating efficacy, allowing the sort of inflation of the number of combination trials that we can run to show that individual contribution of components. That being said, it is pretty clear that there is unmet need in the earlier lines as well, especially as combination therapies with bispecifics or even chemo in some settings. Those are also where there is a greater commercial opportunity. Yeah. As we think about a development path, it is going to include both. It will not necessarily be the case that everything has to be done in a sequence. You should expect some overlap so that even as we are moving late lines, we are moving into earlier lines. I think the glofitamab combo is a great example of that, where it is not that there is no opportunity for a glofitamab combo in later lines of LBCL, but the opportunity certainly gets more attractive as we move earlier into second line and places like that. We will be looking across the whole treatment landscape for places where we think it is right to put a PROTAC BCL6 degrader. Okay. Maybe just talk to us about the baseline characteristics of the monotherapy B-cell cohort versus the combo cohort. Is it all late-line, or does it differ because you have glofitamab in one of the combo arms, so meaning those are going to be slightly earlier-stage patients? Yes. Yeah. Yes on that front. They are all in the setting pretty late-line. Yeah. Like I said, even though there is not a tremendous number of options that are oral, certainly not BCL-6 therapies approved, there are none. That being said, there are a lot of therapies in this space, so patients that are going to be on a phase I trial get to be pretty late-line. Yeah. Yeah. What, again, you said 40% ORR in T-cell. What is the bar you are setting for the data mid next year? I think the easiest way to do that is to wait a little bit. Like I said, BCL-6 was one of our first undruggables. We were quite gratified to see that as there are other players in a similar space, Bristol Myers Squibb being one of them- Yeah. that they've had response rates over 50%. Right. I think that as we look at what a combination or a B-cell target looks like, we're going to actually have to look at how the landscape is evolving. There's those therapies, and that's on the course of a year away, and I think there's a few data disclosures in between- Okay. that will help inform that. But right now, over 50%. Of course, you've always got to look at the patients that you are cross-referencing. Yeah. It's very hard to make these cross-trial comparisons, but I think it'll be easier to set a number expectations as we get closer to that, those data. But we've been very gratified to see good response rates for PROTAC BCL6 degraders in the clinic already. Okay. Anything in terms of just given the pathway, any predicted safety tolerability things that are on the watchlist for the class as a whole that we should think about? Not really. By class, if you mean class PROTAC BCL6 degraders, definitely the answer is no. Yeah. I just meant PROTAC BCL6. Yeah. If you mean PROTAC BCL6 degraders. Yeah. As we did our GLP tox, the only thing that was prompted for us to be paying attention to was eosinophilia. Okay. Of course, in phase I, we'll be looking for everything. Yeah. As we've looked at the other degraders that have shared some clinical data, I wouldn't say that there is a commonality between them. I don't think we've seen that. They've also been still early releases, so that's going to be a place to watch it evolve. I do think it's worth pointing out, as we think about eventual differentiation from competitors here, it's a big space, especially as you move forward in combination. I don't think it's a winner-take-all kind of space. I think that the way we develop and how we develop and the speed which we develop is going to be very important. There will be opportunities to differentiate, whether that's deeper responses, whether that's safety, whether that's tolerability. It's a bit hard to speak too much when we're- Yeah. not sharing the data yet. I think overall combinability, being able to combine well with a broad set of other therapies in the NHL space will, I think, be a very strong indicator of success, which is one reason that we were quite pleased. We put out a lot of preclinical data. Yeah. A lot of preclinical models with many different combination agents, and we are really happy with what we both saw in terms of tumor regressions and inhibition, but also just the combinability and tolerability of those in the preclinical models, of course. Okay. Maybe just remind us, again, I know there is not any clinical data yet to do a cross-trial comparison to Bristol Myers Squibb's BCL6 degrader, but on a preclinical basis, what do you think differentiates your drug the most from their compound? Yeah, I think that there is some comparisons that we have done, and doing our best to suss out exactly which compound they are using is always a good exercise to do. Yeah. We did a couple things. One is that we built in some lenalidomide-like activity into our molecule that we do not believe that they did, which could allow for some stronger potency that you might otherwise need to get from adding on another agent. So that is a possible benefit. There were some differences that we have seen, again, cross-trial, cross preclinical trial comparisons of looking at tumor regressions versus inhibitions that do make us think that we may have an edge there. It could play out. Those will really have to come to bear in the clinic, of course. Yeah. Okay. Makes sense. But if we were to see differentiation, that could be a rationale. Yep. Then, again, I guess a couple of questions on just the next steps. Because again, B-cell is a bigger market versus T-cell, but let's say the data in T-cells proves more promising. Would that be something that you'd go forward with, or would you necessarily want it to be active in both settings? How do you weigh that development path, going for just T-cell versus going for T-cell and B-cell together? I see the T-cell and B-cell a little bit like the question around what line are you going after? Yeah. Which is that the T-cell patient population is much smaller. Right. Right? The second-line plus population is smaller. It gets more commercially attractive as you move into first line. Right. That being said, the unmet need is pretty remarkable. Okay. In later-line LBCL patients, there are treatments that patients are getting out to the third to fourth line. Yeah. Once you hit second line in AITL, I think I said there's no specifically indicated therapy, and you're essentially getting a salvage. You're getting whatever the physician feels might best work for you. So there's a very high unmet need in later-line T-cell patients that I think if I could say is greater than LBCL, I'd hate to say that one patient's need is greater than another's, but I think there's Right. a bigger dearth of treatments in that space, even if it's smaller. On the LBCL side, there's opportunity up and down the landscape. So I certainly think that we would not, let's say, be T-cell only. I think we'll be active in both. Yeah. Okay. Got it. And then I'm assuming that, again, this one seems like more likely of a partner opportunity, just given the scale, especially B-cell lymphomas Large market. Seems like, again, if you're competing against Bristol Myers Squibb, much easier to do that with a partner by your side. Is there something that, again, I know you obviously it's data-dependent, but is there something I'm missing, like why you would keep this versus partner or do some kind of collaboration? Well, maybe I'll make one point and then invite Andrew to jump in, too. Look, as I said at the start, we need to find the places that we're going to focus. Yeah. It is very clear that looking at the landscape for NHL, that combinations are going to be important. Right. Yeah. The gate that we've got to get through first is strong monotherapy activity and combinability. We've chosen to go with glofitamab first, but that is not where we would expect to end. We would expect to begin other combinations. As we get there and we gain conviction and investors gain conviction, if we think it's the right thing to bring in partners, certainly we will look at that. But I also think that there's a lot of work to do here on our own before we get there. But Andrew, any other comments on partnering? Yeah, no. I mean, with regard to partnering, it's important that we keep an asset or two for ourselves and our shareholders where we think we can win, right? I mean, I'll use ARV-806 as a good example. We loved ARV-806. The results were great. It's going to come out late. It was an infusion as opposed to an oral. It's in a very competitive space. We felt like that was a space where a partner could do better. Right? Somebody who's got more skin in the game in the overall RAS market wants to be in that space. For us, it would've been a new entry, we would've been late, it would've been tough. Right? Right. BCL-6 is different, right? We are tied for the lead. There are three of us, we are pretty much neck and neck. We know where to go with it. There are lots of large pharma with interest in helping us with combination studies. That could take many different forms, right? It does not have to be an out-license, it could be partnership, it could be letting them run one line of therapy, we run another. Randy mentioned, there is also an AITL opportunity which we could easily handle ourselves, right? We would look for an accelerated pathway with the agency that could be a quicker to market, couple hundred million dollar revenue stream, very biotech friendly. There are different ways to look at this. Okay. We need to let the data mature a little bit to pick our path. Yeah. Okay, great. Maybe just moving on to ARV-102, which is your LRRK2 degrader for Parkinson's. You mentioned, Randy, some biomarker data next month. Again, I guess maybe just frame for us where that is going to be and what the relevant benchmark is. Right. Yeah. The LRRK2 degrader is ARV-102, and the intention is to develop that program for both PSP, which is progressive supranuclear palsy, and then ultimately Parkinson's disease as well. Right now where we are is we have completed two phase I studies in Europe. So we did one in healthy volunteers, one in patients with Parkinson's. The first data from that came out earlier this year at AD/PD, and then as Terence, as you said, we will have another a bit next month as well at MDS. What we showed back in March, AD/PD, was some pretty unprecedented movement in biomarkers. Now, these are patients or healthy volunteers that are only being treated for 28 days. So for a disease like Parkinson's, which we went into, it is certainly a lot easier to enroll Parkinson's patients than rare disease patients. After treatment with 28 days, we would not expect to see changes in disease there. It's a slowly progressing disease, as you all know. What we did show is that some biomarkers relevant for the endolysosomal function, which is critical for the degradation of proteins like tau and synuclein, which are ultimately what aggregate and cause diseases like Alzheimer's and Parkinson's. What we're able to show is that even after 14 days of treatment, we were able to induce strong reductions in those biomarkers in ways that LRRK2 inhibitors had been unable to ever show. We thought that was pretty exciting. There's a big step down the road of actually showing that degrading LRRK2 can benefit and change the course of disease. That's not where we are. The data that we'll show next month includes a couple other measures. I think the really interesting one is an oculomotor measure. Essentially the way that works is if a patient has Parkinson's, their ability for their eyes to track an object will decline slowly over time. That is now a test that companies are looking at doing to try to get a preview of disease-related changes that will happen later on. What we will be showing is data that describes after only 28 days, that we may be able to see some changes in those biomarkers. Now, obviously, it will later have to be shown whether changes like that will eventually predict changes in the course of disease. But it's a really interesting piece of data to look at, and I think it's a really important illustration of how we, and we'll talk about this when we get to SBMA as well, of how we are very interested in using biomarkers to accelerate our ability to help patients identify that they have disease and identify patients for treatment and get to faster approvals over time as well and run better trials. We'll also be looking at additional biomarkers as well, which we'll talk about next month. The eye movement one is the one that's, I think, really easy to understand. Is it versus some kind of baseline level or like how do you? Exactly. Yeah. Think about it as a patient is going to decline at some rate. Yeah. Hopefully with the addition of ARV-102, we are able to slow the change in that rate. Okay. What- Again, it is only up to 28 days. Yeah. Right. Expectations should not be high there. Okay. But it's a really interesting new approach that we think will have some promise going forward. Yeah. Okay. How do you gauge clinical meaningfulness given the newness of this scale, I guess? It's going to have to evolve with the trials that we are running- Right. in the future. Probably a good time to jump into that. Yeah, sure. We are looking at starting the next trials for ARV-102 in 2027. Okay. which was a change in plan that we announced a couple of months ago. Just so everyone's on the same page, what happened there is we had been planning to move from the phase I trial that we did in Europe, then move into two additional trials. A phase I-B in the U.S. and a registrational type study that was more global. We filed the IND with the FDA, and they put us on a clinical hold and said, "Don't start." We hadn't started yet. Yeah. It was a please don't start kind of hold. They asked us to send the completed chronic tox data before we started that. This is going back a couple of months. Yeah. We said we would finish that study and submit it. We've now done that. Okay. We're now interacting with the FDA on a path forward there. The silver lining of that, which is clearly a pushback, is that we're now simultaneously having discussions with the FDA and with the EMA and with the PMDA in Japan, which I think gives us an opportunity that we wouldn't have had if we'd moved right ahead with the phase I-B to harmonize some of the studies that we're doing in the path forward. Yeah. Until those discussions are done, what we've said is we're going to push the start of the trial to 2027, which I realize is a bit vague, but we can narrow that down as we come up- Yeah. with a clear path. Okay. Then when we complete these discussions with the agencies, we'll identify what the new path is, any changes to what we've said before, and whether or not we'll continue with that same general design, which I'll describe as smaller trial first, bigger trial, or whether we might try to go with a single trial. Yeah. We'll talk about that as we get through those discussions. Okay. Have you provided any more details on what the nature of the FDA request was? It sounds like more chronic tox data. We have not. Yeah. No, we haven't. We had done a pre-IND meeting a year and a half, couple of years ago. Yeah. And got the indication that going with the end life portion alone would be sufficient. Okay. They said that they'd like to see the full chronic tox data. Of course, I think any time you send data to an agency, they're going to have some questions. So we're responding to questions and- Okay. working through the responses. Yeah. Has it been generally consistent in terms of the personnel at the FDA that you've been interacting with since the initial, this year-and-a-half period that you talked about, or have there been turnover among the personnel? I think you can assume there's been turnover. Yeah. Okay. Yeah. I don't mean to imply that that- Yeah. is causing anything. Okay. Certainly there has been changes. Yeah. The team that we're working with now is not necessarily the same group that we've worked with before. Okay. Understood. I know the trial is, you got into 2027, but are you hoping to have the FDA hold resolved by the end of this year, or is that also a 2027 event? For me, the FDA hold is clearly important. Yeah. Right. What's even more important is coming up with a plan for what the next steps for the program are- Okay. that we can be clear across geographies. Yeah. Because I think given the data that we've seen, the conviction that we have, we want to move this forward rapidly and aggressively. Okay. To do that, I actually think we may be better served by having a trial that we can harmonize across the world and not just focus on the FDA. I don't have specific guidance for resolving a hold. Yeah. But I think as we get through the conversations with all the agencies in the next few months, we'll have an update. Okay. And sorry, just to be clear, because you talked about Parkinson's, but PSP. if you do go the registration path, is that Parkinson's or PSP? It's PSP. It's PSP. No. Okay. Got it. The next step is PSP. Okay. PSP. And some important features there. Yeah. PSP is a much more rapidly progressing disease. Yeah. Unfortunately, patients who are diagnosed with PSP often pass away within five or seven years. On the rating scale that physicians use to grade the disease, patients can be decreasing by 10 points a year. The benefit to that for running a trial is that it can happen on a much faster timeframe. Yeah. A Parkinson's trial is going to be longer. We think it makes sense, to Andrew's point on biotech activity and friendliness- Right. It makes sense to start with PSP. Yeah. Of course, we'll talk about PD as well, but PSP is the place that we would identify for the next trials. Okay. Great. Maybe just in the last few minutes here, ARV-027, this is for Kennedy's disease. Again, maybe just talk to us about the disease first because it's one that, again, rare disease, I think not a lot of people are familiar with. Right. I'm assuming there's a lot of unmet need, but then mechanism of your drug and how it could address the disease. Yeah, absolutely. So this program, ARV-027, is for Kennedy's disease, also known as spinal and bulbar muscular atrophy or SBMA, and it is a pretty devastating muscle wasting disease. It's a neuromuscular disease. And what essentially happens is in men, and it's almost always in men, what happens is you have a mutated form of androgen receptor called polyglutamine repeat androgen receptor, and it forms aggregates in muscle cells and leads to the muscle essentially wasting away. It progresses slowly over time. It happens nearly always in men because it's an X-linked disease. The AR is on the X chromosome. Men only have one, so if there's an issue there, that's where you're likely to get this disease. And the way that the drug works is very simple. It degrades AR. It degrades polyQ-AR. Men with this disease only have polyQ-AR because they only have one copy of the gene, and so it's actually a pretty simple cause and effect, we think, where you have an aggregate protein inside the muscle cell. Yeah. We're hoping to degrade it and see a benefit. As you implied, very high unmet need. There are no approved therapies in this space in the U.S. anyway. No other therapies that we know of going after AR as the target, which we think is the clearest and simplest way to attack the disease. We have been in a phase I trial since the beginning of the year. We've completed a single ascending dose portion in healthy volunteers. We're now in a multiple dose portion with healthy volunteers, and the goal there is to identify a dose to move forward in, even at the tail end of this phase I study, some patients with SBMA. The idea would be that if we're able to show that we can get a PROTAC BCL6 degrader to be orally bioavailable, get into muscle, degrade AR in muscle, that will be a very strong indication that we can degrade the actual disease-causing protein in patients with the disease. So excited about that, and I have to, as an aside note, as we've introduced this program this year, it's gotten a pretty strong reception really because of the simplicity. This is not some upstream factor or some indirect driver of disease. We're degrading the actual protein that's causing the disease. I feel like there will be an unusually high link between the phase I data here and eventual success in a way that is not always clear in neurological diseases. Yeah. Where there hasn't been proof or evidence that affecting that target will change the course of disease. Yeah. Just remind me how you guys have been working on AR, like you said, from the time of the IPO, ER, AR. Again, how does this drug differ from some of your earlier AR degraders? Yeah. We have had a couple of AR degraders. This would actually be our third in the clinic. And folks might remember that we out-licensed one of them to Novartis a couple of years ago. Yeah. That is luxdegalutamide, an AR degrader. ARV-027 is a bit different. Okay. It also degrades AR and polyQ-AR. Yeah. What is different about ARV-027 is its ability to get into muscle. Okay. We've designed it and selected it very much for its ability to get into muscle, which is where the important degradation needs to occur. We do get asked that. Yeah. For contractual reasons as well, we can't take ARV-027 into prostate cancer. Yeah. Novartis can't take luxdegalutamide into SBMA. If they did, it wouldn't work very well because of the muscle penetrance and so on. Just to be clear about that. Okay. It's really our third AR degrader, which is another reason that we're excited about this. Arvinas knows something about AR degraders for sure. Yeah. Okay. Good opportunity. To measure this AR degradation, this is a biopsy measurement? Yeah. Okay. Muscle biopsies. Then I guess the question is just what level of change is needed? How do you know what that threshold? I know this from the AR, ER degradation. Yeah. There is always a debate about how much degradation do you need to drive a clinical benefit. Here, how do you judge how much is enough, I guess? Yeah. It is interesting that it is a very similar target. Yeah. Not quite, it is polyglutamine AR versus AR, but very similar, but that operate in very different ways. Okay. In prostate cancer, we are degrading AR, which can be a driver of disease, but prostate cancer is not caused by the aggregation of AR. Here, we are actually degrading the disease driver. Yeah. We think that probably 50% is a good target. Okay. We get asked a lot about what would the potential side effects be. But remember that the men that have this disease will already exhibit some of the effects that you might expect from an AR degrader. And so it might be expected that if you degrade all of it, you could make it worse, but in general, we would expect less effect from treating with the drug. The reason we have come to 50% is that in a preclinical mouse model, where mice are expressing polyglutamine AR and exhibit a downward decline in muscle grip strength, endurance, things like that, if we treat and reduce polyQ-AR by about 50%, we not only see the stoppage of the decline of disease, we actually see full improvement by some measures. So mice that have been treated with ARV-027 go back to wild-type levels of endurance. I am not predicting anything about what happens in patients, but if we can see that with only 50% degradation, that is really the target. There is really no need to go higher than that, so that is what we will be aiming at in the clinic. Okay. Great. Well, I think we're up against time, but appreciate it and looking forward to all the data. Thank you very much, Terence. Thanks, Randy. Thanks, Andrew.