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Great. Thanks for joining us. I'm Terrence Flynn, Morgan Stanley's U.S. Biopharma Analyst. For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com backslash research disclosers. If you have any questions, please reach out to your Morgan Stanley sales representative. With that, very pleased to be hosting Arvind this morning from the company of Randy Thiel, the company's CEO, and Andrew Syke, the company CFO. Thank you both for being here. Really appreciate it. I am looking forward to conversation. Maybe to kick it off, Randy, you've been in the 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, Terrence, 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 where we are right now, mainly because we've been around a little while, right? So 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. You know, and 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 one programs that we have, that we now have four of. And 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, 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, you know, we've got four programs in the Clinic. The first is a BCL-6 degrater 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 LARC-2. 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 SVMA. 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. And to round it out, we have an HBK1 degrader for use in immuno-oncology indications just starting in the clinic in this current quarter. And so no commitments on data yet, but starting the trial now, maybe we'd expect to add data in a year or so. So we've been pushing those programs forward, I think very effectively. We have made some important decisions, you know, 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. And if we don't feel like we're positioned to do that, that will be a place for someone else to jump in. And we'll talk a bit about that. You know, the last point I would make is from a capital perspective, our guidance is into the second half of 28. So we certainly have the capital we need to get through these important inflection points. So 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. And right now, it's really about moving those phase one programs to their inflection point 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 happened for the KRAS program earlier this year, we decided that would only move forward with a partner, whetherthat's the call, that's what we're thinking about. And 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 in phase one. 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 one company and not a company that is about to be a commercial breast cancer company. Okay, great, great. Perfect framing. Maybe let's just jump into the assets that you walk through here. I mean, 393 is your BCL6 degrader. Maybe just give us an update and kind of like you said, you know, data by year end, walk us through, you Know, the trial and maybe level set us on expectations in terms of what we should be focused on. Yeah. So ARV393 is a degrader for BCL-6. And BCL6 really, given our history, you know, I'd say our formative years in AR and ER as our first targets, BCL 6 was one of our first target that's certainly an undruggable. There had been BCL inhibitors moving through preclinical studies, none really that I know of made it to the clinic. And one reason for that is, and that makes BCL an ideal target for a protactigrator, is that deep degradation of BCL-6 is important. It's rapidly resynthesized. And BCL6, 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 BCL6. So the study that we're running is in subsets of NHL. We are rolling pretty broadly across both B-cell lymphomas like LBCL and T-cell lympomas 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 is transplant as an important modality, it's pretty crowded. If you're looking for oral therapies, it is not very crowded. If you are looking for BCL-6 targeted agents, it is not crowded. The way the space has evolved is to add on additional therapies to deepen and extend responses. That is what we would like to do with a BCL 6th grader. 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. So, 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. So 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 Lymphomas 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. And also just through the way the trial was run, we mentioned about a year ago that we'd seen responses in both T cell and B cell lymphomas. I think that unmet needs absolutely led to an enrollment of a disproportionate number of T cell patient versus what we would have expected. So we're 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. So we have an escalation ongoing with 393 as monotherapy, but we're also dosing with glufidamab in patients as well. And so that will allow us to disclose both 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. So we will be looking for initial signs of safety, of course. Obviously, we've been able to dose as we'd like to, so that's feeling pretty good about that. PK, PD, degradation of BCL-6, and, of coarse, some early signs of efficacy. Now, in an escalation study, especially where I've said we would not expect early doses to be efficacious, we'll keep the expectations a bit more modest there. But if you look over time what a patient in second-line AITL or diseases is getting, think of a 40% or so range of ORR. So that's what we'd be like to be seeing to make sure that we have good single-agent activity in these patients. And then clearly as we get to be dosing at a range that we'd prefer to be doseing at, we'd expect to continue to see improvement there. But that's how we think about the first set of data in the last part of the year. Okay, great. And just to remind us, is that like typical 3x3 design? It's a pretty typical design. Okay. And then have you said how many cohorts? I know you said it's more predominantly T-cell versus B-cell, but have you set how many cohort you've gotten through yet at this point? I think we've said, you know, assumed dozens of patients, but 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 done this, dosing at a range that we would expect to produce efficacious exposures, that's what we'll be most focused on. there certainly will be some patients that were dosed well below where we'd expect to see. Okay. And how much follow-up will you have on those initials? It'll vary. So patients that are dosed the highest will have the least follow-ups. Yeah. Okay. And is this a medical conference? Is this something like an ASH update, or this is a corporate update? We've said a medical congress. 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 its performed, especially as the doses have increased. That being said, you know, going back to what I said about acting like a younger phase one company, we certainly over our history as a company have used both medical congresses and done our own releases and both are, you know, both are in play. We've said for this to expect a medical congress, but I'm much more worried about making sure we get the data out at the right time in the right way. Okay. Makes sense. And I guess in terms of the monotherapy versus combo. So 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 being monotherapy data next year? With combo. Combo data as well. both. Yeah, exactly. All right. Yeah. And importantly, the, you know, the patients treated with the glyphic, those are LBCL patients, BCL, B-cell lymphoma patients. And I think, you know, as we, if we look at the landscape, right, and you may be getting at this question, but as we think about development across LBCl and other B-cel lymphomas and across T-cel lymphomas, there's really an opportunity to think about what you do in the late line versus is what you do in the early line. As monotherapy, the opportunities are really in the late line. Those opportunities can come a bit quicker. You know, trial timelines are shorter. Responses for patients are often unfortunately shorter, and so it's a bit quicker to run those trials. And 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. But that being said, it's pretty clear that there's unmet need in the earlier lines as well, especially as combination therapies with bispecifics or even chemo in some settings. And those are also where there's a greater commercial opportunity. So as we think about a development path, it's going to include both. It won't necessarily be the case that everything has to be done in a sequence. You should expect some overlap so that even as we're moving in late lines, we're moving into earlier lines. And I think the Glow-Feed Combo is a great example of that where it isn't that there's no opportunity for a Glow Feed Combo in later lines of LPCL, but the opportunity certainly gets more attractive as we move earlier into second line and places like that. So we'll be looking across the whole treatment landscape for places where we think it's right to put a BCL-6 degree. Okay. Maybe just talk to us about the baseline characteristics of the monotherapy BCL cohort versus the combo cohort. Is it all late line, or does it differ because you have Glofi in one of the combo arms, so meaning those are going to be slightly earlier stage patients? Yes. Yes, on that front. But they're all in this setting pretty late line. Like I said, even though there is not a tremendous number of options that are oral and certainly not BCL-6 therapies approved, there are none. That being said, there aren't a lot of therapies in this space, and so patients that are going to be on a Phase I trial get to be pretty late-line. And what, again, you said 40% OR and T-cell, what's kind of the bar you're setting for the data mid-next year? So I think the easiest way to do that is to wait a little bit. So, like I said, BCL-6 was one of our first undruggables. So we were quite gratified to see that, as there are other players in a similar space, BMS being one of them, that they've had response rates over 50%. So 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 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. It's very hard to make these cross-trial comparisons. But I think it'll be easier to set a number of expectations when we get closer to those data. But we've been very gratified to see good response rates for BCL-16 graders in the clinic already. And anything in terms of just given the pathway, any predicted safety tolerability things that are on the watch list for the class as a whole that we should think about? So not really. And by class, if you mean class protectorators, definitely the answer is no. I just meant B-cell 6. Yeah, if we mean B-cel 6 degraders. As we did our GLP talks, the only thing that was prompted for us to be paying attention to was eosinophilia. Okay. Of course, in phase one, we'll be looking for everything. 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, and there will be opportunities to differentiate, whether that's deeper responses, whether that'S safety, whether that'Tolerability. It's a bit hard to speak too much when we're not sharing the data yet. But 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, a lot or preclinal models with many different combination agents, and we're 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. And then maybe just remind us, like, again, I know there's not any clinical data yet to do a cross-drug comparison to Bristol's BCL-6 integrator, but on a preclINICAL basis, what do you think differentiates your drug the most from their compound? Yeah, I think that there are some comparisons that we've done, and doing our best to suss out exactly which compound they're using is always a good exercise to do. We've done a couple things. One is that we built in some lenalidomide-like activity into our molecule that we don't 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. And 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. Okay. Makes sense. But if we were to see differentiation, you know, that could be a rationale. Yeah. And then, again, I guess, you know, a couple of questions on just the kind of next step. So would you guys, because again, B cells, the bigger market versus T cells, but let's say the data in, you know, 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 kind of how do you weigh like that development path like going for just t cell versus going for t and b cell together i see the t and v cell a little bit like the the question around what line are you going after which is that the t cell population 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, which is certainly a possibility. That being said, the unmet need is pretty remarkable, right? In later line LBCL patients, there are treatments that patients are getting out to the third, fourth line. Once you hit second line in AITL, there's, 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 BCL. I'd hate to say that one patient's need is greater Than others, but I think there's 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-cel only. I think we'll be active in both yeah okay okay got it um and then i'm assuming that again you know this one seems like more likely of a partner opportunity just given the scale especially you know b-cell lymphomas large market seems like again if you're competing against bristol much easier to do that with a partner by your side is there something that again i know you obviously stay dependent but is there somebody i'm missing like why you would keep this versus partner or do some kind 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. It is very clear that looking at the landscape for NHL, that combinations are going to be important. The gate that we've got to get through first is strong monotherapy activity and combinability. We've chosen to go with Glowfee first, but that is not where we would expect to end. We would expect it to begin at a combination. Now, 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? And I mean I'll use 806 as a good example. We love 806. The results were great. It's going to come out late. It was an infusion as opposed to an oral. It was in a very competitive space. We felt like that was a space where a partner could do better. Somebody who's got more skin in the game in the overall RAS market wants to be in that space. For us, it would have been a new entry. We would have Been late. It would have Be tough. BCL6 is different. We're tied for the lead. There's three of us. We're pretty much neck and neck. We know where to go with it. There's lots of large pharma with interest in helping us with combination studies. That could take many different forms, right? It doesn't have to be an out-license. It could be partnership. It Could be letting them run one line of therapy. We run another. And Randy mentioned there's also an AITL opportunity, which we could easily handle ourselves, right. We'd look for an accelerated pathway with the agency, that could be a quicker to market, a couple hundred million dollar revenue stream, very biotech friendly. So there's different ways to look at this, but we need to let the data mature a little bit to pick our path. Yeah. Okay, great. Maybe just moving on to 102, which is your LERC2 degrader for Parkinson's. You mentioned ready some biomarker data next month. So again, I guess maybe just frame for us where that's going to be and what the relevant benchmark is. Right. Yeah. So the LARC2 degrader is ARV102. And the intention is to develop that program for both PSP, which is progressive supernatal palsy, and then ultimately Parkinson's disease as well. And right now where we are is we've completed two phase one 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 ADPD. And then as Terrence, as you said, we'll have another a bit next month as well at MDS. And what we showed back in March, ADPD, 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's 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 therapy. It's a slowly progressing disease, as you all know. But 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 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. So we thought that was pretty exciting. We clearly, you know, 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 ocular motor 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 you know, companies are looking at doing to try to get a preview of disease-related changes that will happen later on. So, what we will be showing is data that describes, after only 28 days, you know 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 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. And so 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. And is that, is it, so is it versus some kind of baseline level or how do you? Yeah. Think about it as a patient is going to decline at some rate. And then hopefully with the addition of ARV-102 that we're able to slow the change in that rate. Okay. And again, it's only after 28 days. So expectations are, should not be high there, but it's a really interesting new approach that we think will have some promise going forward. Yeah. Okay. So then 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 in the future. Probably a good time to jump into that. So we are looking at starting the next trials for ARV-102 in 2027, which was a change in plan that we announced a couple months ago. And just so everyone's on the same page, what happened there is we had been planning to move from the Phase 1 trial that we did in Europe and then move into two additional trials, a Phase 1B 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. It was a please-don't-start kind of hold. And they asked us to send the completed chronic tox data before we started that. So this is going back a couple of months. We said we would finish that study and submit it. We've now done that. And so 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 1b to harmonize some of the studies that we were doing in the path forward. So 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 with a clear path. And then when we complete these discussions with the agencies, we'll identify what the new path is, any changes to what we 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. But 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? I mean, it sounds like more chronotox data. We have not. No, we haven't. It was really a, you know, we had done a pre-IND meeting a year and a half, couple years ago, and got the indication that going with the in-life portion alone would be sufficient. And they said that they'd like to see the full chronotux data. And, 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 working through the response. Yeah. And has it been generally consistent in terms of the personnel at the FDA that you've been interacting with since the initial, you know, whatever, this year and a half period that you talked about? Or has there been turnover? I think you can assume there's been turnover. Yeah. I'm not, I don't mean to imply that that is causing anything, but certainly there has been changes. And the team that we're working with now is not necessarily the same group that we've worked with before. Okay. Okay. Understood. And is it, I know the trial is, you know, you got into 27, but are you hoping to have the FDA hold resolved, like, by the end of this year? Or is that that's also a 27 event? I think, so for me, the FDA Hold is clearly important. Right. What's even more important is coming up with a plan for what the next steps for the program are that we can be clear across geographies. Because I think given the data that we've seen the conviction that we have, we want to move this forward rapidly and aggressively. 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. So I don't have specific guidance for resolving a hold, 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 just, sorry, just to be clear, because you talk about Parkinson's, but PSP, that if you do go the registration path, is that Parkinson's? No, the next step is PSP, and there are some important features there. PSP is a much more rapidly progressing disease. Unfortunately, patients who are diagnosed with PSP often pass away within five or seven years. So on the rating scales 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 time frame. So a Parkinson's trial is going to be longer. So we think it makes sense, to Andrew's point on biotech activity and friendliness, it makes since to start with PSP. And, of course, we'll talk about PD as well, but PSP is the place that we would identify for the next trials. Okay. Okay, great. Maybe just in the last few minutes here, 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. what 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 vulvar 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 polyqar 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 a aggregate protein inside the muscle cell 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 is the target, which we think is the clearest and simplest way to attack the disease. We have been in a phase one 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 one study, some patients of SPMA. So the idea would be that if we're able to show that we can get a protactic grader 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, you know, indirect driver of disease, we're degrading the actual protein that's causing the disease. And so I feel like there will be an unusually high, you know, link between the phase one data here and eventual success in a way that is not always clear in neurological diseases where there hasn't been proof or evidence that affecting that target will change the course of time. Yeah. And just remind me how you guys have been working on AR, like you said, from the time of the IPO, ER, AR. So again, how does this drug differ from some of your earlier AR degraders? Yeah. So we've had a couple of AR degradors. This would actually be our third in the clinic. And folks might remember that we out-licensed one of them to Novartis a couple years ago. That's Lux degalutamide, an AR degrader. ARV-027 is a bit different. It also degrades AR and poly-QAR. are. What's different about O27 is its ability to get into muscle. So we've designed it and selected it very much for its ability of getting into muscle, which is where the important degradation needs to occur. So, we do get asked that for contractual reasons as well. We can't take O27 into prostate cancer. Novartis can't takes LUX into SPMA. If they did, it wouldn't work very well because of the muscle penetrance and so on, but just to be clear about that. But yeah, it's really our third AR degrader, which another reason that we're excited about this. Arvinas knows something about AR degraders for sure, so good opportunity. And then just, so to measure this AR degradation, this is a biopsy measurement? Yes, muscle biopsies. And then I guess the question is just what level of change is needed? Like how do you know what that threshold, I know this from the AR, ER degradation, there's always this debate about how much degradation do you need to drive a clinical benefit? So here, you know, how do you judge how much is enough, I guess? Yeah, it's interesting that it's a very similar target, not quite what it's polyglutamine AR versus AR, but very similar, but that operate in very different ways. So in prostate cancer, we're degrading AR, which of course is not the, which can be a driver of disease, but prostate cancer is not caused by the aggregation of AR. Here we're actually degrading the disease driver. So we think that probably 50% is a good target. We get asked a lot about, you know, what would the potential side effects be right now? 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've come to 50% is that in a preclinical mouse model where mice are expressing polyglutamate AR and exhibit a downward decline in muscle, grip strength, endurance, things like that, if we treat and reduce poly-QAR by about 50%, we not only see a stoppage of the decline of disease, we actually see full improvement by some measures. So mice that have been treated with 027 go back to wild-type levels of endurance. I'm not predicting anything about what happens in patients, but if we can see that with only 50% degradation, that's really the target. There's really no need to go higher than that, so that's what we will be aiming at in the clinic. Okay, great. Well, I think we're up against time, but I appreciate it and looking forward to all the data. Thank you very much, Terrence. Thanks, Randy. Thanks, Andrew. Thanks, everyone.