Greetings and welcome to Monte Rosa Therapeutics' Conference Call to discuss the company's interim clinical results from the ongoing phase I/II study of MRT-2359. At this time, all participants are in listen-only mode. A question-and-answer session will follow the formal presentation. As a reminder, this conference call is being recorded. It is now my pleasure to introduce Andrew Funderburk, Senior Vice President of Investor Relations and Strategic Finance at Monte Rosa. Thank you, Andrew. You may begin. Thank you, Operator. Good morning, everyone, and thank you for joining our conference call today to discuss the interim clinical results from the ongoing phase I/II study of our GSPT1-directed molecular glue degrader, MRT-2359, in heavily-pretreated metastatic castration-resistant prostate cancer patients. With us on today's call are Markus Warmuth, Chief Executive Officer, and Filip Janku, Chief Medical Officer. We have also posted slides to our website that will accompany today's call. Before we begin, I would like to remind everyone that any statements we make or information presented on this call that are not historical facts are forward-looking statements that are based on our current beliefs, plans, and expectations, and are made pursuant to the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. Please refer to our annual report and other filings that we make with the SEC for our risk factors and other information. With that, I'll turn the call over to Markus. Thank you, Andrew, and thank you, everyone, for joining us this morning. It's a pleasure to provide you today with an update for our MRT-2359 program in metastatic castration-resistant prostate cancer, or CRPC. Our Chief Medical Officer, Filip Janku, will walk you through a more detailed summary of the clinical trial results in just a bit. However, let me provide a quick overview of the key results from the study right here. In the small phase II expansion arm of MRT-2359 in combination with enzalutamide, we observed compelling clinical activity in heavily-pretreated metastatic CRPC patients, in particular in the subset with androgen receptor or AR mutations. In the four AR mutant patients enrolled in the study, treatment with MRT-2359 in combination with enzalutamide led to a PSA response in four of the four patients, so we are seeing a 100% PSA response rate in the subset, although it is still a small sample set, of course. Two patients experienced PSA 90 responses, and two additional patients had PSA 50 responses. Also, two of the four patients had a RECIST partial response, and the other two patients had stable disease, leading to a disease control rate of 100% in the AR mutant setting. In this AR mutant subset, two patients remained on therapy for 10 cycles or longer, and three or four patients remained on drug as of the data cutoff on December 3rd. Furthermore, five additional patients without AR mutations had stable disease per RECIST, several associated with tumor size reductions, resulting in a disease control rate of 64%, so including the AR mutant subset, nine patients across the full set of 14 available patients either had a PR or stable disease. The combination of MRT-2359 with enzalutamide was well tolerated, with mild or moderate manageable GI adverse events being the most frequent toxicities. We believe this safety data compares favorably with other therapies currently in development for metastatic CRPC. Also, the data support the potential of MRT-2359 in metastatic CRPC patients with AR mutations. Tumors of up to 30% of metastatic CRPC patients in later lines of therapy carry an AR mutation, representing a substantial market opportunity. We believe there could be additional potential in earlier line settings, in particular in patients naïve to 2nd generation AR inhibitors or in combination with other agents, including radioligand therapies. Before we dive deeper into the clinical data, let's now briefly review the Therapeutic Rationale for MRT-2359 in metastatic CRPC. MRT-2359 is a molecular glue degrader of GSPT1, a protein critical for the control of translation of several oncoproteins, including MYC. It's previously shown that in tumor cells, degradation of GSPT1 can trigger synthetic lethality, in particular in the context of high expression of MYC. In addition, as shown on slide five, MYC is known to promote multiple aspects of prostate cancer biology, including activation of the E2F and AR transcriptional programs, and has been shown to drive resistance to various therapeutic agents, including AR inhibitors and radioligand therapies. MRT-2359 reduces expression levels of MYC and other key oncoproteins and pathways secondary to loss of GSPT1 and inhibition of translation, thereby leading to growth inhibition and cell death, and hence has the potential to treat metastatic CRPC. Our preclinical studies, which we will review shortly, confirmed that prostate cancer cell lines and xenograft models were highly sensitive to MRT-2359. While androgen receptor inhibitors have been a highly successful class of drugs in CRPC, many tumors do develop resistance. We believe that rationally combining MRT-2359 with 2nd generation androgen receptor inhibitors could help to retain potency against CRPC, including in tumors that have acquired androgen receptor mutations. Turning to slide six, we identified prostate cancer as a promising candidate indication for MRT-2359 early on in our discovery and preclinical work through an unbiased pharmacogenomic screen across hundreds of cancer cell lines spanning multiple tumor lineages. Supporting the Therapeutic Rationale I mentioned on the prior slide, our data demonstrate that prostate cancer cell lines co-expressing high levels of MYC and AR show much greater sensitivity to MRT-2359 than prostate cancer cells low or negative for MYC or AR. On slide seven, we show through global proteomics analysis that MRT-2359 not only reduces growth of MYC and AR-positive prostate cancer cells, but also significantly modulates the AR pathway, including AR itself, as well as the E2F pathway and its key member Cyclin D1, likely through modulation of MYC and its downstream signaling program. Importantly, MRT-2359 as a single agent was more effective than enzalutamide in reducing AR activity in the cell lines tested. Consistent with the pharmacogenomic screening and in vitro validation studies, MRT-2359 demonstrated encouraging single agent as well as combination efficacy with enzalutamide across a number of prostate cancer cell line-derived xenograft or CDX models, as shown in slide eight. These models include LNCaP, a cell line characterized by high-level expression of an AR mutation, as well as VCAP, a cell line presenting an amplification of AR, and low-level expression of the constitutively active V7 isoform. In both models, MRT-2359 in combination with enzalutamide drove significant tumor regressions and substantially outperformed enzalutamide alone. Since MYC can promote expression of DNA repair genes, potentially blunting response to radioligand therapy, we also tested the potential of MRT-2359 to improve activity through suppression of radiotherapy resistance-causing genes. More specifically, we assessed MRT-2359 in combination with a PSMA-based radioligand therapy, as shown on the right graph, where single agent treatments drove stasis at best. Combination treatments led to significant regression, suggesting a high degree of synergy between MRT-2359 and the PSMA-based radioligand, so in summary, MRT-2359 combined well with other AR inhibitors and with radioligand therapy to improve preclinical efficacy across CDX models spanning multiple AR alterations. This data corroborates the potential of MRT-2359 to benefit patients with metastatic CRPC across multiple lines of treatment. I now turn the call over to Filip to review the clinical trial design and study results in more detail. Thank you, Markus. Slide 10 outlines the design of our phase I/II clinical study. We conducted robust dose exploration in the monotherapy arms to confirm multiple safe dose levels and determine our recommended phase II dose of 0.5 mg daily on a 21-day on-drug, seven-day off-drug schedule. Results of the dose escalation have been disclosed previously. Based on the data Markus just highlighted, we initiated a phase II expansion cohort in heavily-pretreated metastatic castration-resistant prostate cancer. As of the December 3rd data cutoff, we enrolled 20 patients required to have RECIST-measurable disease for all patients entering the trial. This is a more stringent requirement than is typical for prostate cancer studies, which results in enrollment of a more severe and often more heavily- pretreated patient population with extensive metastatic disease. However, we believe this is important to be able to assess the clinical activity of the drug in this early study. Let's turn to slide 11. For our metastatic CRPC expansion cohort, we applied a multi-pronged approach to characterize tumors on a molecular level, including determination of key androgen receptor alterations for all patients enrolled. To do so, we employed RNA and DNA sequencing of tumor biopsies and molecular testing of circulating tumor DNA and circulating tumor cells to detect AR alterations, such as AR mutations and splice variants. We also verified non-neuroendocrine biology through RNA sequencing, which allowed us to exclude from the efficacy analysis tumors that had transformed to primarily neuroendocrine status. Slide 12 outlines the patient demographics, clinical characteristics, and prior therapies of metastatic CRPC patients in this study. Notably, the patients in this study were more heavily-pretreated than in comparable studies, of which we used the phase I study for the combination of mevrometostat with enzalutamide as a relevant benchmark. In our studies, 75% of patients had been previously treated with 2nd generation androgen receptor inhibitors, 80% with chemotherapy, and 55% with Pluvicto. All these are substantially higher than in the mevrometostat study. In addition, as previously mentioned, our study required the presence of RECIST measurable disease, while the mevrometostat study, like many other CRPC studies, included a high percentage of patients with bone disease only, a patient subset with generally more favorable outcomes. Of the 20 patients enrolled, as of the data cutoff, 14 patients were evaluable for efficacy. Two patients were non-evaluable due to early consent withdrawal, one patient due to early clinical progression, and three were excluded based on molecular profiling showing neuroendocrine differentiation. Slide 13 highlights the safety and tolerability profile of MRT-2359 in combination with enzalutamide. The combination was well tolerated, and the safety profile was favorable when compared with other drugs emerging as combination agents for metastatic CRPC, including EZH2 inhibitors. The most frequent AEs for MRT-2359 plus enzalutamide were mild or moderate gastrointestinal symptoms, which were manageable and did not limit use of the therapy. Slide 14 shows the waterfall plot for PSA responses and frequently used early marker of therapeutic efficacy in prostate cancer. Of note, of the 14 evaluable patients, four had AR mutations, and all four of these achieved a PSA response. This includes two PSA 90 responses and two PSA 50 responses. Three of the four patients remain on treatment today, suggesting a significant therapeutic potential of MRT-2359 in this setting. The PSA response rate in the overall population was 29%, a rate comparable, if not superior, to the mevrometostat plus enzalutamide combination. Slide 15 shows the RECIST waterfall and swimmer plots for our 14 evaluable patients. As you can see, two of the four AR mutant patients achieved a RECIST response, one confirmed and one unconfirmed, and the other two showed a stable disease, resulting in a disease control rate of 100% in this setting. As shown in the swimmer plot on the right, treatment effects in these heavily-pretreated patients were durable in a portion of patients. In the AR mutant subset, two patients remained on therapy for 10 cycles, and three or four patients remained on drug as of the data cutoff on December 3rd. Overall, MRT-2359 plus enzalutamide resulted in two RECIST responses and seven patients with stable disease per RECIST, several of which showed reduction in target lesion size. The disease control rate across the available population was 64%. A total of five patients remained on therapy as of the data cutoff. Slide 16 provides additional data on the four patients with AR mutations where the MRT-2359 enzalutamide combination led to robust and durable PSA and RECIST responses. Looking at these patients in isolation, we see that all patients previously received abiraterone, two of four previously received enzalutamide, and three of four received both chemotherapy and Pluvicto. Importantly, consistent with the 100% PSA response rate and 100% disease control rate in this subset, mutant allele frequency in ctDNA and total circulating tumor cell counts were also significantly decreased in three or four patients, with data pending for the fourth patient. Let's move to slide 17. In an effort to identify signaling pathways that correlate with response and tumor size reductions, we performed an unbiased analysis for significantly activated or suppressed pathways in pretreatment biopsies. Consistent with our therapeutic hypothesis, we found MYC, E2F, and AR signaling among the top upregulated pathways correlating with magnitude of tumor size reductions, results confirming clinically what we had seen in the preclinical experiments described by Markus and validating MRT-2359's proposed therapeutic mechanism. Having shown the association of tumor size reductions with MYC, E2F, and AR signaling levels, we next assessed whether combination treatment could suppress signaling through these pathways. Encouragingly and consistent with preclinical observations, we noted a significant decrease in pathway output through these oncoproteins, such as in the example we show here, demonstrating reduced E2F signaling in five of six post-treatment biopsies. I'd like to now share two individual patient case studies that demonstrate clear drug activity. Slide 18 is a case study of a patient with an AR H875Y mutation. This patient had been previously treated with several therapeutics that span multiple mechanisms of action, including chemotherapy, radioligand therapy, and an investigational bispecific. Despite a high number of prior treatments, MRT-2359 in combination with enzalutamide led to a robust response that correlated with rapid and sustained decreases in blood PSA and AR H875Y allele frequency in ctDNA. While PSA values started to rebound around month eight, there was continued decrease in the size of tumor target lesions, a finding in line with the mechanism of action of MRT-2359 that also depends on modulating non-AR pathways like MYC and the E2F pathway, as described by Markus earlier. On slide 19, we want to highlight the treatment journey of a second AR mutant patient. At baseline, this patient harbored the AR L702H mutation. This patient was also heavily-pretreated, having received chemotherapy, enzalutamide, Provenge, and several other therapies. Despite these treatments and the advanced stage of disease, the patient responded favorably to the MRT-2359 enzalutamide combination. PSA and mutant allele frequency in ctDNA significantly decreased by month three, correlating with a decrease in some of target lesions. Interestingly, and similar to what we had shown for the patient in the previous slide, although PSA began to rebound slowly during the course of treatment, tumor regression, as assessed by RECIST, was maintained. Again, we believe this supports that MRT-2359, at least in part, works through an AR pathway-independent mechanism. This patient remained on treatment as of the December 3rd data cutoff. Let's now discuss next steps for the program. Moving to slide 21. Based on the highly encouraging data we just shared, we are planning to conduct a signal-confirming phase II study of MRT-2359 in combination with a 2nd generation AR inhibitor in AR mutant patients. The study will allow the efficient further evaluation of MRT-2359 in metastatic CRPC by using a Simon's 2-Stage Design. We plan to initiate the study in 2026. The study is expected to enroll up to 25 patients with metastatic CRPC and AR mutations, and the main endpoints will be PSA response, RECIST response, duration of response, radiographic progression-free survival, and safety. There is also potential to expand the study into additional patient subsets, including patients naïve to 2nd generation AR inhibitors should the activity in the AR mutant patient population confirm. Data from the study have the potential to confirm MRT-2359's clinical activity in relevant patient groups, further determine a role for MRT-2359 in the treatment landscape of metastatic CRPC, and position the program for advancement into registrational studies. With that, I'll turn the call back over to Markus for his concluding remarks. Thank you, Filip. We're very encouraged by the data generated in our CRPC expansion cohort of MRT-2359 in its phase I/II study. We've demonstrated compelling clinical activity in a well-defined, high unmet need population of CRPC patients, namely those with AR mutations. This population represents up to 30% of 2nd line or later metastatic CRPC. Combination regimen was well tolerated and compares favorably to competing approaches. We're also pleased to announce that we expect to present updated data from this phase I/II study at the ASCO Genitourinary Cancers Symposium in February of next year. Looking ahead, we plan to initiate a signal-confirming phase II study of MRT-2359 in combination with a 2nd generation AR inhibitor in 2026. The study will initially focus on metastatic CRPC patients with AR mutations in AR, and we are exploring the potential to expand into earlier AR inhibitor-naïve settings should the signal in AR mutant patients confirm. Finally, on slide 24, I'd like to highlight the great progress we're making with our other pipeline programs. Our VAV1-directed MGD program, MRT-6160 licensed to Novartis, is progressing towards initiation of multiple phase II studies in immune-mediated diseases. Monte Rosa is eligible for milestone payments beginning upon initiation of phase II studies. VAV1 is a previously undruggable target that functions as a key signaling protein downstream of both the T and B cell receptor. Our phase I study results and extensive preclinical work support the potential of MRT-6160 to treat multiple immune-mediated conditions, and we're thrilled to have Novartis's extensive development capabilities driving this program forward. Next, the ongoing phase I study of our NEK7-directed MGD, MRT-8102, is proceeding more quickly than we originally anticipated. We now expect to present interim phase I data in early 2026. As a reminder, the ongoing phase I study includes single ascending dose and multiple ascending dose cohorts in healthy volunteers, as well as a part three cohort designed to evaluate potential early proof of concept in subjects at increased cardiovascular disease risk. We believe that degrading NEK7 with MRT-8102 represents an innovative approach to treat cardiovascular and other diseases linked to NLRP3, IL-1β, and IL-6 dysregulation. We think that MRT-8102 could potentially show a differentiated profile based on its potency, its selectivity, and prolonged pharmacodynamic effects. We are also making great progress with our preclinical pipeline, and we plan to provide updates on that next year. So, in summary, we could not be more excited about our pipeline programs and what's in store for 2026. With that, I would like to open the call for questions, handing it back to the operator. Thank you. If you'd like to ask a question, please press star one one. If your question has been answered and you'd like to remove yourself from the queue, please press star one one again. Our first question comes from Edward Tenthoff with Piper Sandler. Your line is open. Great. Thank you, and congratulations on these compelling results. I wanted to get a sense, when it comes to this new phase II that you're talking about, is the plan to use one of the next-gen androgen receptor inhibitors, or is it going to be more of a physician's choice? And in that case, would this be something where you would sort of stratify based on companion drug that's chosen? Thank you. Thanks, Ted, for the question. I think the simple answer today is that it's currently under discussion. I think it's quite possible that we'll be focusing on one particular 2nd gen androgen receptor inhibitor, but we're still also discussing, contemplating any advantages of making that a physician's choice. And so, long story short, probably more details to be provided as we get closer to initiating that trial. Great. Thank you very much, and congrats. Looking forward to the data on the rest of the pipeline early in the new year. Sounds great. Yeah, thanks, Ted. Thank you. Our next question comes from Marc Frahm with TD Cowen. Your line is open. Marc Frahm with TD Cowen, your line is open. Can you hear me now? Yes. Yeah, okay. Thanks for taking the question, and congrats on the data this morning. But maybe one quick clarifying question. You mentioned a couple of early discontinuations that obviously aren't evaluable because they did stop quickly. Did any of those patients meet the subset criteria of having AR mutations? And then looking forward to the trial you're going to be starting, you have required prior ARi use. And then also, what other prior therapies might you require before enrolling in that trial just to make it a homogeneous patient population? Yeah, thanks for the question, Marc. I'll start at a high level. So first, on the non-evaluable patients, let me point out, obviously, none of the neuroendocrine had an androgen receptor mutation. We obviously decided to include those simply because we had experience with neuroendocrine in our monotherapy dose escalation. As you might remember, sadly, we weren't able to see any relevant MYC expression in those tumors, and that was basically confirmed in the three cases we excluded. I'll let actually Filip comment on the other three cases. The other cases were essentially patients who were not available for the reasons which were often technical. Two of them were not available because they actually decided to withdraw the consent, which were more for the logistical reasons. One patient was actually not available because it was an early progression after several days on therapy. In fact, that patient already started to progress relatively rapidly, even in the screening period. The patient was still technically eligible to start the therapy, but I think it was pretty much a situation which was really hard to salvage at that point. That essentially summarizes that. Marc, could you repeat the second part of your question? The second was about the modifier I trial. Just what type of prior treatments are you going to require or not require prior AR inhibitor use or other things like Pluvicto? Just in terms of what type of patient population you're aiming to enroll. Yeah, I'll let Filip answer that question too. Yeah, very happy to work. Yeah. So So I mean, as you know, the AR mutations are more frequent in patients who are more heavily-pretreated, and we are not necessarily seeing signals being limited by the number of prior therapies as many of our patients, as I just pointed out in my clinical presentation, that these patients were actually heavily-pretreated. So we are actually looking into that. We haven't decided on the specifics at this point, and there will be more specifics to share in the months to come, but we're not going to be very picky as far as prior therapies are concerned. Okay. Thanks a lot, and congrats again. Thank you. Our next question comes from Clara Dong with Jefferies. Your line is open. Hi, good morning. Thanks for taking our question, and congrats on the data. So two questions for me. Maybe just quickly walk us through the rationale of selection of 0.5 mg RP2D, and what level of GSPT1 degradation did you see that those compared to? Maybe a higher dose? And then you've described this too as a signal-confirming trial. So under what kind of circumstances would this trial evolve into a registrational study if there's any possibility, and if there are minimal PSA response that you believe is necessary for MRT-2359 to justify that intent? Thank you. Great. Thanks, Clara, for the question. And so I'll try to address your first question. I'll let Filip answer on your more detailed question on the modifier trial. So for your question around PKPD and degradation, in this expansion arm, we actually decided to not determine levels of degradation of GSPT1. We had obviously done this extensively in our monotherapy dose escalation. And as you remember, we saw what we wanted to see during the dose escalation, like around 60%-70% degradation. In the expansion arm, and you know how precious these biopsies are, in particular the paired biopsies, we really wanted to focus on more functional interrogation of what's going on in those tumors pre and post-treatment. And so we were quite fortunate and happy that at the end of the day, we had in the order of six to seven paired biopsies and actually plenty of fresh biopsies from screening. And so no degradation data, but we believe the RNA-Seq data that we provided today obviously is clear functional evidence that not only are we degrading GSPT1 in that setting, but we are having the functional consequence on the pathways we want to have a functional consequence on, in particular, of course, MYC and the E2F pathway that are obviously closely connected. Handing it to Filip to answer the more specific questions on the modifier trial. Can you actually give me the second part of the question? The audio was a little bit harder to hear here. I was asking for a phase II trial. Under what kind of circumstances would this trial evolve into for registrational intent? So if I quote it correctly, this trial is kind of signal-confirming, right? So essentially, at the moment, we have four AR mutant patient populations. I mean, we have four patients. Obviously, the data look extremely encouraging, but I think with four patients, it's not really enough to commit to the registrational efforts. I think the modifier trial will have up to 25 patients. I mean, it might sound like a relatively small sample size, but also the activity in the existing study, which we just presented, is actually quite high. So in order to confirm the activity, you don't essentially need the massive amount of patients. If the level of signal is actually confirmed in the 25 patients, then we can actually then decide on the next steps, which ultimately should result in the registration. I don't necessarily want to get into much details. I mean, that will obviously include discussions with the relevant regulatory agencies, but essentially, both classical pathways, including the accelerated pathways, have been actually done in prostate cancer, especially in therapies when the molecular selection was used. Thank you for your color. Thank you. Our next question comes from Robert Driscoll with Wedbush Securities. Your line is open. Great. Thanks, guys. Good morning, and congrats on the data. Maybe just a quick clarification question. I just wondered if you looked at AR amplification status in the patients evaluated here, just given the preclinical data, and then the potential for including amplified patients in the next study, acknowledging that might be a little bit more difficult to define those patients. Okay. Thanks, Rob. I'm not sure if I completely understood your question, but I'll try. Then maybe I'm sorry. We were actually split into rooms between Boston and Basel today, so we're trying to coordinate our answers and hand it to Filip later. But I'm assuming your question was on amplifications, which I think you're pointing out correctly, that they were really underrepresented in our patient subset. That obviously also depends a little bit on where you set the cutoff. We used at least four copies to call something amplified. I think that's a prudent approach, and we literally saw no amplification. I think that's a little unfortunate and weird. We do actually think that this combination will work well also in the amplified setting, even then in the presence of AR-V7. There's certainly an opportunity, and we've tried to allude to this in our presentation. There's certainly an opportunity to expand into these types of other molecular subsets, in particular then in an earlier line setting. Filip, anything to add there? Things that I didn't catch in the question? No, I don't think so, Markus. You summarized that well. Yeah. Got it. That's super helpful. Maybe just one more sanity question. Just wondering how closely correlated the MYC, E2F, AR pathways are in the earlier stage patients, just thinking about rationale for going into those early stage patients maybe one day. It's an excellent question. I mean, everything we know today suggests that MYC is still very high also in the early setting. That's at least what we're concluding from RNA-Seq datasets, be it from TCGA-like subsets, but also from real-world samples. Obviously, I can't conclude yet on the functional interaction, right? That's to be determined. You probably saw in our slides that we had a few 2nd gen AR inhibitor naïve patients in the trial, and it's fair to say that those did extremely well as compared to the overall population. So I would say, at this point, no concern going into an earlier line, and no longer seeing that correlation effect. Again, I'm almost repeating myself. Earlier line means more AR dependent, probably means higher MYC expression and higher dependence on the MYC, E2F pathway as well. Got it. Makes sense. Thanks a lot, guys, and congrats again. Thank you. Okay. Thanks. Our next question comes from Derek Archila with Wells Fargo. Your line is open. Good morning. This is Hao calling in for Derek Archilla. Thank you for the question. For 2359, what's your strategic thinking on the program in terms of do you prefer a partnership or would you advance the program by yourself? Excellent question. And so again, we're super excited about where we are today with those results. Small sample set, but certainly compelling and very consistent in the AR mutant setting. We're very prepared to actually move ahead here with the modifier trial. We're obviously trying to keep the size of that next signal-confirming trial reasonably small. Don't misinterpret this, right? Once that signal confirms, obviously, we're ready to move beyond that set. I think we've been fairly pragmatic many times around our pipeline. If there's an opportunity to team up with someone to develop MRT-2359 in prostate cancer more quickly and broader, we will certainly have those discussions with strategics. Very helpful. Thank you. Thank you. Our next question comes from Michael Schmidt with Guggenheim. Your line is open. Hey, guys. Good morning. Thanks for taking my questions. Just to follow up on the activity limited or enhanced in patients with AR mutations. I guess, at the end of the day, do you see potential for this mechanism to also work in AR wild-type patients, perhaps those that are earlier stage? And then have you looked at correlation with MYC expression levels, and does that correlation exist into the MYC expression at baseline? And then lastly, on the phase II study, I guess, what type of data would support advancement to phase III? Thanks so much. Great questions, and I'll try to address the first two questions. I will then hand it to Filip for the third one. Again, I think what we're seeing here is that these LBD mutant patients obviously remain very dependent on AR and MYC signaling, and our RNA-Seq analysis in some ways has confirmed that. That doesn't mean it's not going to work in the wild-type setting. I think as we move into earlier line settings, where even wild-type obviously has a strong dependence on the AR signaling pathway and strong co-dependence on MYC, this will continue to work. Not a PR, but I'd like to point out that one patient who's wild-type and has now been on treatment for, I think, at least 10 cycles, if not longer. So to be tested, but all the data we have clinically and preclinically would suggest that this will work in AR wild-type, as long as AR is still very strongly on. As for correlation with MYC, there's a really great correlation. I mean, we obviously had to limit what we're showing in the slide, but it's really great correlation of clinical activity based on obviously resistant tumor shrinkages. With MYC, with MYC pathway activity, MYC per se not, but we've always said this is how active is MYC and not how much is around. Really great correlation with the MYC signature, really great correlation with the E2F signature, which is downstream. Really great correlation also with a combined MYC E2F signature. And so, as pointed out, really focusing here on the RNA-Seq pathway analysis in those paired biopsies has helped us big time to be convinced about the mechanism of action and confirming that this is actually truly related to addressing that MYC, E2F pathway. Filip, do you want to answer the other question? I think you kind of answered most of that. Michael, was there anything else? The last part of the question, which I'm not sure about. Yeah. I guess Yeah. I guess for the phase II, is there a particular PSA or RECIST response rate you're looking to see at a minimum? Yeah. It depends on the population, right? So I mean, if you are in the AR mutant stage, I mean, there are data from the comparable population with the AR degraders. I think that would be a good benchmark to look at for the PSA responses. I think we are definitely comparing favorably to that, I mean, at least at this point with the small number of patients. When it comes to a different population, which Markus was actually a little bit touching on, in which we potentially might have opportunities beyond the AR mutations, I think the good benchmark would be some other combo studies, such as the combinations of the EZH2 inhibitors. I believe even in that setting, when we look at the overall data, we actually compare comparably, if not favorably. Powerful. Thank you. Thank you. Our next question comes from Brian Cheng with JP Morgan. Your line is open. Yes. Thanks for taking our questions this morning. Can you speak to the durability of response here you're seeing with 2359? Specifically, going back to your swimmer plot on slide 15, can you give a bit more color on the reason why the PR patient in the AR mutant cohort dropped out around month 10? Thank you. Yeah. Filip, do you want to address that question? Yeah. Yeah. Yeah. Very happy to. So we kind of pointed out during the presentation, and this patient actually started to have increased rebound in the blood PSA levels, which started around month 8. That being said, the RECIST response actually continues to be maintained, even after completion of the cycle 10, when the patient was taken off. So I mean, our understanding from the side is that the patient was actually taken off because of the rising PSA, even though the RECIST response was maintained. It was somewhat disappointing for us because we I mean, who knows now, but I mean, there was a potential probably for maintaining the RECIST control for another while, which I guess we would not know. But I think this kind of a slight disconnect between the PSA and the RECIST response actually might be potentially caused by that the 2359 actually addresses the multiple mechanisms, not only the AR dependency. Got it. And you spoke to the potential to combine with radioligand in your preclinical work. How do you think about building that out in your signal finding study moving forward? [crosstalk] No, go ahead, Filip. In the signal finding study, we don't plan to combine it with the radioligand. This is what was the question. However, the preclinical data, which Markus showed, are exciting, and I will let Markus to continue. Yeah. I mean, as Filip pointed out, not part yet of that planned modifier trial. That said, we're super excited about what we are seeing preclinically. Obviously, there's a few more things to check around safety. But again, so far, so good. If you're familiar with our data and you looked at the slides, you probably realized that we're using MRT-2359 at a very, very low dose here. There's a more detailed study coming. We didn't necessarily use it at a low dose because we were concerned about toxicity. Again, it was really more anticipating a high degree of synergy and trying to see where the lower limit of efficacy is. So at that dose, 1.5 mg per kg, again, no tox concerns, but a little bit more work to do. And obviously, we would need to have discussions with companies in that space on how to operationalize a trial. Great. Thank you. Our next question comes from Oliver McCammon with LifeSci Capital. Your line is open. Congrats on the data, and thanks for taking my questions. Just two for me. We've seen a number of readouts in a heavily-pretreated CRPC setting over the past couple of years. I know we discussed it a bit, but can you help contextualize some of these PSA results today within that broader development landscape? And then my second question is, curious on why some of these AR mutations seem to perform better on PSA changes than the AR-V7 splice variants. Thanks again. A couple of things, and I'll actually start with your last question, right? Yes. Clearly, the LBD or AR mutant subset did better than the AR-V7s. Interestingly, and I pointed this out early in the call, none of these AR-V7s had AR amplifications, which is quite typical and usually points to AR-V7 really having a functional impact. Also worth mentioning that in this AR-V7 subset, the actual average PSA value was on the low side. So long story short, we think we were a little unfortunate there to have mostly AR-V7s that were non-amplified and no longer that dependent on the AR signaling pathway. And our RNA-Seq data at baseline, in some ways, sort of confirmed that. In regards to other studies and benchmarking, we do think this compares very favorably to studies that have looked into AR mutant subset more specifically. Obviously, it's a bit I'm comparing apples to oranges to other agents like combinations with EZH2 or PRC complex inhibitors simply because they weren't necessarily that focused on molecular characterization of the tumors. But most of all, a lot of these actually were not requiring mature diseases, right? So we're essentially dealing with a less pretreated earlier stage population. One of the companies that I'm sure you're very familiar with, and I'm not mentioning names, but are solely focused on an androgen receptor inhibitor, AR-naïve subset, and so very hard, obviously, to compare those results to ours, so again, in the AR mutant subset, we do think we compare extremely well to some of the other next-generation AR inhibitors or differentiated approaches. Thank you again. Thank you. I'm sure no further questions at this time. I'd like to turn the call back over to Markus for any closing remarks. Sounds great, and so since there's no additional questions, I'd really like to close the call. Thanks, everyone, for participation, and have a great day. Thank you. This does conclude the program. You may now disconnect. Good day.