Good evening, and welcome to the Repare Therapeutics conference call on its comprehensive phase I data from its first-in-human phase I RP-3500. All participants will be in a listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, questions. To ask a question, you may press star, then one on your touch-tone phone. To withdraw your question, please press star then two. Please note this event is being recorded. Steve Forte, Executive Vice President and Chief Financial Officer of Repare Therapeutics. Go ahead, Steve. Good evening, and thank you for joining us today for our review of the comprehensive results enabled by SNIPRx or TRESR study that was reported today at the 2022 AACR annual meeting. On today's call, Lloyd Segal begins with introductory comments. Dr. Tim Yap of the University of Texas MD Anderson Cancer Center will then provide a recap of the data he presented earlier today. Our Executive Vice President and Chief Medical Officer will provide some additional insights from actual patient case studies, and then Maria and Lloyd will make some concluding remarks. Lloyd, Maria, and Dr. Yap, along with Dr. Mike Zinda, our CSO, and myself, will be available for Q&A after the prepared remarks. Due to time constraints, we would kindly ask that you limit yourselves to one question and one follow-up during the Q&A. Before we begin, I would like to remind you that that we make during this call about the company's future expectations, plans, and prospects constitute forward-looking statements for the purposes of the Private Securities Litigation Reform Act. Forward-looking statements are based upon our current expectations and various assumptions and are subject to the usual risks and uncertainties associated with the company. Reasons why our results may differ materially from these forward-looking statements, and we refer you to our latest SEC filings where you will find a more detailed discussion of these risks and uncertainties. Forward-looking statements represent our views as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update and to do so even if our views change. As a reminder, the audio and slides from today's event will be made available on our website later today. I will now turn the call over to Lloyd. Thanks, Steve, and welcome to today's conference call. I'm pleased to have this opportunity to share additional data for RP-3500 from the TRESR phase I/II dose escalation. RP-3500 is a potent and selective oral small molecule inhibitor of ATR for the treatment of solid tumors with specific synthetic lethal genomic alterations. These data build upon the highly encouraging preliminary phase I monotherapy results from this first-in-human biomarker-driven phase I/II trial in patients, which were reported at the AACR meeting last October. With that, I'd like to introduce Dr. Timothy Yap of MD Anderson, our distinguished guest and principal investigator, joins us this evening to share a summary of the data he presented earlier today, as Steve noted. Repare is singularly focused on DDR synthetic with a highly differentiated pipeline of product candidates using our proprietary SNIPRx and STEP2 technologies. Our focus today, tonight, is to discuss our exciting monotherapy results. As highlighted here on the right, though, you can see that we expect to have some significant additional clinical milestones over the course of the year across the entire portfolio. While today's presentation focuses on the RP-3500 monotherapy TRESR trial data, this slide highlights the clinical data why we're so excited in the monotherapy potential of RP-3500. You'll get a sense of how this data will further inform our future development plans. With that, I would like now Dr. Timothy Yap to walk you through some of the data he presented earlier today at AACR. Dr. Yap will be available for Q&A following our formal results. Thank you very much, Lloyd. Great to be here, everybody. These are my disclosures. Next slide. Next. In our phase I and II TRESR trial, we included patients with solid tumors after failure or intolerance to standard therapy, deleterious STEP2 alterations. All patients also were required to have an ECOG performance status of zero to one, and listed there. You'll see, as listed, the primary endpoints to evaluate safety and tolerability, and also to establish overall response, clinical benefit rate, and progression-free survival. The key translational analyses included assessment of the anti-tumor activities to evaluate the impact of gene zygosity on clinical outcomes, to assess patient selection methods for ATM loss-of-function tumors. Next. Next slide, please. On this trial, we treated a total of 120 patients, male. The median age was 63 years. All patients had an ECOG performance status of zero to one. This was a very heavily pretreated lines of prior systemic therapy. 2/3 of patients had prior platinum, a third of patients had prior platinum, a third of patients had prior PARP inhibitors, and 23% of patients had prior PD. Most common tumor types, as listed there, included ovarian, prostate, breast, and pancreatic cancers. The most common genotypes included ATM, BRCA1 and BRCA2, SETD2 mutations. Next slide, please. So this slide shows the treatment-related adverse events, and you can three days on, four days off schedule. Out of 95 patients treated to date, grade 3 anemia was observed in 24% of patients. Anemia events reported. Grade 3 decreased neutrophil counts were reported in 10.5% of patients. Grade 4 and 3 decreased platelet count in 5% of patients. Grade 4 in 1% of patients. Really, outside of these three key hematological parameters, we really did not see any Really highlighting and supporting the highly selective profile of RP-3500. Next slide, please. On this clinical trial, monotherapy results in terms of median duration of treatment, which is seen at eight months, but also responses in a whole range of solid breast, melanoma, head and neck squamous cell cancer, and also pancreatic cancer across different genotypes, including germline and somatic, germline RAD51C, SETD2 mutations, ATM, CDK12, BRCA2 mutations. Interestingly, cancers, all but one of these patients had a PARP inhibitor. All of these patients had prior platinum chemotherapy. You can see that recent patient population of ovarian cancer patients. Despite all of that, the responses were highly durable as shown there. On this trial in our ovarian cancer patients, we really observed clinically relevant benefit. That's the overall response was 25%. There's one complete response by RECIST criteria, one and three partial responses by RECIST and one SD. The clinical benefit rate was 75% and the median PFS was 35 weeks. You'll see that this is despite 90% PARP inhibitors and 85% who were platinum refractory or resistant. The clinical benefit was really seen across the different genotypes with the genotypes listed on the left if your eyesight's good enough. Certainly BRCA1, BRCA2 mutations and also HRD patients, SETD2 mutations and also CDK12 mutations. You'll see that on the graph the median PFS of 35 weeks. We also saw in this trial clinically relevant benefit in patients with BRCA1 and BRCA2 mutation cancers. This includes patients with ovarian, breast, head and neck squamous cell cancer and melanoma. The clinical benefit rate was 43% for this patient population and currently 50% for these post-PARP inhibitor treated BRCA-mutated ovarian cancer patients. Next slide, please. We also observed durable clinical benefit in patients with ATM loss of function tumors. Overall response 12%. There were three responders, prostate cancer, one with RECIST PR, a PR in a pancreatic cancer patient. 29% of patients received RP-3500 for at least six months. It was 44% for this patient population, and median PFS was 17 weeks. Next slide, please. The highlight is that the anti-tumor activity was largest in patients with biallelic loss of function. As many of you will know, you know, this is something that has been looked synthetically for therapies including ATR inhibitors, but really is not typically reported by routine clinical NGS assays. Certainly in this central NGS assay that was developed by Repare Therapeutics called SNIPRx, that not only looks at biallelic loss of function, it also looks at junctions. It was something used on this trial. What was found was that, as you can see in the bar chart on the right, the clinical benefit rate was significantly higher in the biallelic loss of function tumors versus the monoallelic loss of function tumors. You can see that trend as well for the ATM patients and the BRCA1 mutant. There was also a longer PFS for patients with biallelic loss versus the non-biallelic loss of function for all subjects. These data are very compelling. Further analyses in additional patients and also confirmation in larger prospective studies are required. To conclude, RP-3500 monotherapy is well-tolerated. The mechanism-based anemia observed responses and clinical benefit in different tumor types and also genomic alterations. The overall clinical benefit rate was 43%. 90% had received prior PARP inhibitors and 85% were platinum refractory or resistant. The overall response was 25%. The median PFS was 35 weeks. In patients with BRCA1 and two tumors previously treated with a PARP inhibitor, the clinical benefit rate was 48% and responses were in cancers including melanoma and head and neck squamous cell cancer. As mentioned, biallelic loss of function has the potential to enrich patients but most likely. Multiple clinical trials with RP-3500 alone or in combination are currently ongoing. Thank you very much. Next slide, please. Maria? Yeah. Thank you. This is Maria Koehler. I would like to now, when you have this opportunity, to hear Dr. Yap present a summary of his to share with you a few patient examples and talk to you about the significant learnings from this trial. I will first discuss three examples. I will finish with few cases of patients suffering from recurrent platinum resistant and PARP treated ovarian cancer. Here on slide 21 is this patient was presented by Dr. Yap earlier today, and we are glad to see that this patient had a RECIST response. We had very good hints with the decreasing tumor markers that started actually after two months of monotherapy. The 120 mg/d, three days on, four days off. This is important because this is not our recommendation, and this is yet another argument that we don't believe that we are sacrificing efficacy for good safety and very good efficacy. As you can see here, this patient on 120 mg/d is enjoying a very good quality of life. This lady is traveling to California, and this is a presentation of a 73-year-old patient with prostate cancer and ATM. As you can see, this patient started on five days on, two days off schedule, and we know that the schedule is now switched to 120 mg. The patient was on 120 mg, and the patient then switched to 120 mg. Again, it is one of our step-down doses. This is a patient very importantly with adrenal insufficiency that he has a tendency to get a lot of infections. So did this patient. The adrenal insufficiency was not very well controlled, and he had a lot of treatment interruptions. Despite that, as you can see, the tumor continues to go down, and on our last evaluation this year, his tumor size was 29.7%, so it's like within the error of the 30. We also see why FDA does not really love the PSA as endpoint because the flat PSA are inconsistent with the tumor size. The other point I wanted to make on this slide is please look on the left how fast the week 15, and there was a dramatic decrease in the ctDNA, and then it was sustained five weeks later. On this, thank you. On the next slide is my last patient on with the ATM loss of function. This is a patient who has germline ATM loss of function and had multiple bone lesions only and did not have measurable disease. Therefore, we do not. Patient was eligible based on elevated PSA. As you can see on the top of the slide, the PSA very quickly declined first on week 19 to more than 90% and achieved normal levels on week 19. The patient now is on study more than six months with normal PSA. As you can also see the ctDNA kinetics, we cannot measure germline in ctDNA, but the patient had additional alterations, which was TP53, and this went down significantly. Now next slide, in a patient with ovarian cancer. The patient had germline RAD51 alteration. This is another patient that presentation. This patient, RAD51 is a known alteration that is DNA damage. But it's also one of our STEP2 genes. As you can see, this patient received 160 mg, 3/4, however, one week off. This patient had a lower dose happens to be than the patient who than our. Proving that we are not sacrificing any efficacy for the toxicity. The patient did not require any changes in schedule and remains on therapy for 40 weeks ongoing with complete remission. Finally, my last slide is a patient. These are patients who we have several of with BRCA1 who had responses. This patient was very heavily pretreated, as you can see, which is not uncommon for patients with ovarian cancer. The patient had platinum agents and two PARP inhibitors and was 160 QD 3/4 and switched to 120 mg at week six. This patient continues to decrease thereafter about 48 weeks due to non-measurable new lesions. I will now, next slide, please, conclude what we learned from the TRESR study. Next slide. As mentioned by Dr. Yap, w e believe that we have very potentially best-in-class safety profile, which is confirmed now in much larger cohort. Several of the patients are on therapy close to a year or more than a year. It shows that anemia is non-cumulative, and we also did not see any new adverse events since our first announcement. We are showing that the potency, selectivity and differentiation is increasingly clear. This is a very large trial of 120 patients, so we had a great opportunity to comprehensively assess both dose and schedule. We felt that dose and schedule is one of the critical aspects for compounds that potentially have a small therapeutic window in tumors and molecular alterations, and this helps us, with these numbers of patients, to convince for further development. The proof of concept that we obtained in ovarian cancer was clearly demonstrated, and this is just you can read the statements that Dr. Yap showed with the very impressive progression-free survival of more than eight months, and in the very heavy decrease. It was in ovarian cancer in multiple genomic alterations. Finally, please do not forget about the further exploration of as other STEP2 alterations. We do believe that ATM is a very significant opportunity. ATM loss is in the Module 2, and all our learnings for proper selection, exclusion of the CHIP that Dr. Yap will help us to potentially look at the opportunity in this segment. We also need to learn a little bit more about, and this is why our Arm 3 in Module 2 is enrolling. This would be all, and I will now. Thank you, Maria. Before we open the call to your questions, I want to express our deep appreciation to Dr. Yap and all of our clinical collaborators and their patients and caregivers. I also want to acknowledge Maria and her team, outstanding leadership from Stephanie Guerrera, Biljana Bazdar-Vinovrski, Adrian Fretland, and Yi Xu, all of whom, with the collaboration of many others around them, have had a profound impact on delivering these ground. To sum up today, we've achieved early monotherapy proof of concept in ovarian cancer with a 25% OR and 75% CBR across multiple heavily pre-treated post-PARP platinum patient setting. We believe this provides a strong rationale for phase II trials. As Maria just noted, we'll be giving consideration to the pattern of long-term benefit in ATM loss-of-function tumors with a CBR of 44%. As many have hypothesized, we've demonstrated that tumor response in these patients takes time, so a year. As Maria pointed out with her example of biallelic loss, proper diagnosis and selection of patients is also important in ATM loss of function. It's going to be an area of focus for us. We've all seen efficacy in multiple tumors, including prostate and pancreas, where several of our STEP 2 genes are represented. This too will be an area of ongoing focus for us. In this longer-term data, we are now able to demonstrate a highly differentiated and well-tolerated safety profile, effectively unchanged with our longer-term dosing at a dose. This concludes our prepared remarks. I would now like to open the floor to Q&A. I think it's the operator who's got questions for us. The first question will come from Jeff Hung with- Thanks for taking the questions. The first is for Dr. Yap. I know you mentioned that the anemia is well controlled in the monotherapy setting and it's non-cumulative, but how do you think about grade 3 anemia in combination with PARPs? Is there any reason to believe that it may exacerbate anemia with PARPs? Maria, I don't. Therapies, though, right? I don't think we've discussed any. Yeah. Jeff, we haven't disclosed any data from the combination study. I'm not sure it's a great place to dive into that today. My follow-up is for either the company or Dr. Yap on the analysis and PFS or best overall response. While you do see a long-term clinical benefit in tumors with ATM loss of function, can you provide some thoughts on why the conclusions appear to be so different in ATM loss? And do you think that selection based on IHC has any impact on PFS? Thanks. I think there are multiple points. I think it's a very interesting area. As you mentioned, you know, the elimusertib study assessed as an exploratory endpoint assay and nothing else will actually predict for response. The answer was in that exploratory retrospective study correlation with the benefit. What we have shown, well, what we have been studying separately, this has got nothing to do with. In a separate academic study at MD Anderson that we've been doing, we've actually now determined the combination of both mutation data and also, you know, immunohistochemistry data, because to clarify if your ATM mutation is a VUS or whether it's actually functionally relevant. You know, I was presenting that slide, that was purely to assess the ATM IHC loss assay by itself. You know, I think what it does tell us is that you need the IHC data as well. In a major symposium session I presented today, just talking about an easy way to think about how we best select for patients with ATM alterations that might be meaningful. I called it ABCD way of further that you're getting the right patients on, and not just letting any patient with an ATM mutation on, because there are, you know, plenty of VUSs which are variants of unknown. There are ones that are meaningful, which are the deleterious ones, and then there are even benign ones. That's A, is really important that you get that right. B, if you have a biallelic loss of function alteration, it's important versus, say, a monoallelic loss of function. C is patients who, you know, probably should have been excluded from this trial, who did not benefit from RP-3500 because they basically had an age-related clonal hematopoiesis or CHIP, which is nothing to do with cancer. It's not tumor derived. It's just part of our own aging process. D is, you know, do the IHC to add to your refinement of your biomarker, right? I wanna stress again that durability was there. I really do think that with these ATR inhibitors, and this is the same thing with elimusertib, that the duration with it, and we've shown some examples in the trial on patients treated, that they do take a long time to respond. They are responding and going down, a lot of significant reductions in molecular responses. It might be one of those drugs that just takes time, and it leaves these with impressive duration of therapy. As we think about how we get these drugs to registration, you know, you really want progression-free survival. You really wanna prolong survival ultimately. That's where you will get that with, you know, a significant improvement response. You know, Gordon Mills in his session yesterday actually said that we should rethink how we're actually assessing many of these tumors. Tumor response rate does not give you the full picture of patient benefit. We have to think about how we assess these patients in early phase trials. It's not all about these drugs. You know, if we did overall response with, say, CDK4/6 inhibitors, those would never get to registration, you know. We have multiple CDK4/6. You know, what it does tell us is how the drug trials will probably need to be planned and designed in the future to actually get to registration ultimately. Thank you. Thanks, Dr. Yap. Thanks, Jeff. Next question. The next question will come from Chris Shibutani. Please go ahead. Hi, good evening. This is CJ on for Chris. Really exciting data to see in the ovarian cohort ATM selection. I think Dr. Yap just kind of walked through the four criteria. Are you able to integrate that into the Module 2, or can you help describe Module 2 for either ATM or to, you know, maybe get a better sense of the ovarian signal? So maybe I can- Maria? Thank you very much for the question. I think that the data in ovarian cancer are a very pleasant surprise. We are seeing several requests from the community of oncologists to progress this concept. Talking to FDA, we would not like to comment on it before we are talking to regulatory authorities. The answer regarding the ATM, as Tim mentioned, it is a subset that definitely has it. We have several patients who are on study. Remember, the study started only in July 2020, and we have a lot of patients here who have ATM loss. Those patients don't necessarily have a tumor shrinkage that is reaching the RECIST criteria shrinking. The ctDNA that we showed is documenting that the shrinking is due to anti. If we believe that, there is an effect of the drug in the ATM population, we just need to do a little the type of ATM. We have couple of ideas in specific tumors, whether this will be pan-tumor alteration or it will be couple of selected tumors. The worst thing that we can do is across all tumors and all alterations. Nobody does it. There is no precedent of doing this, so I don't think that we should do it for ATM. I do believe that we will explore further both ovarian cancer reasonably quickly, and we also will explore in selected tumors as start to start with. There is multiple other opportunities for monotherapy and obviously the combination. Great. Thank you. Next question. The next question will come from Joe Catanzaro with Piper Sandler. Please- Joe, congrats on the data today. I guess we have just a couple questions. Again, following up with this signal in ovarian cancer, is there any consideration for specific cohort? If so, would you restrict that to BRCA or full STEP2 lesions? I guess we're just wondering if there's any consideration to cast an even wider biomarker net with? We definitely do not have any reason to restrict it to BRCA. Our original report indeed had the enrichment for longer observation. We have a patient who had a confirmed partial remission with SETD2 gene. We have the complete remission in RAD51. There is no reason to restrict it only to BRCA1. That's part of the answer. The second is, we do believe patients were very heavily pretreated. All of them had platinum, as mentioned. Some of them had a very quick progression on PARP. Looking a little bit more into the data. However, we do not think that, you know, and what is important, nothing approved or nothing proposed in the patients who received PARP in ovarian cancer. That is for us, with the type of data that we have, and everybody is pretty impressed with the progression-free survival of eight months-plus. Whereas in this population, poorly evaluated, is probably around four months. At least with the PARP after PARP or Cisplatin, et cetera. Or even the one and the PFS that we obtained, albeit in 22 patients total, is pretty competitive and gives us a reasonable direction to discuss it further. Great. Our next question. The next question will come from Marc Frahm with Cowen. Thanks for taking my questions. Maybe just to follow up on that last point of yours, Maria. Given that the post-PARP ovarian, you might require PFS, I mean, should investors expect that means a randomized trial is likely necessary, or do you think there is a single arm path here? To avoid details of our registrational strategy. I don't want to comment on it. What I can, we had several discussions with gynecological oncology community, and we have several, probably both of those opportunities, single arm trial and randomized trial, and we need to just to make the right decision. However, it is a pleasure that we have enough data to be able to go forward. You know, in the richness of opportunities in front of us, you know, we will read out our PARP combination data. You know, we wanna move forward. This year, we'll be able to determine which of those options makes the most sense to create the most value for our patients in the long- Just for Dr. Yap, just on the kind of differences that are emerging on the AE profiles, could maybe just contextualize what some of those differences in hematologic really means for kind of patient quality of life or, you know, the impact on, you know, your and your clinic staff's ability to kind of manage patients in the clinic? Yeah. Significant. You know, I think more and more patients are trying to move away from chemotherapy options, and therapies are really where the entire field is heading, as you know. You know, and so the better the therapeutic profile, ultimately, the outcomes will be for patients. Yeah, it's extremely important. Okay. Sure. Did you have a follow-up, Marc, or does that cover it? No, I'm okay. Thank you. The next question will come from Charles Xu. Good evening, everyone, and thanks for taking the time to do this event and for taking my questions. With respect to patient inclusion in genotypes, maybe we're seeing some hints of this, you know, with the enrichment of signal in ovarian cancer. How are you thinking about, you know, potential longer-term enrichment of camonsertib? And obviously you also want to discuss this with the FDA, but, you know, come that time, how much data do you think you may have, not only from your phase I, but also across, you know, some of your expansion cohorts come to clearer paths forward? Thanks. You know, how I look at this, it is, you know, despite the fact that our colleagues in Bayer have a different safety profile, they did first of three responders in prostate cancer. We did see several responders in prostate cancer as well. We are looking very carefully. Actually, the responders from the Bayer ATR are helping us with some of our decisions because it's patients with prostate cancer, and some of this, as you know, had the CHIP, so they really don't count and, you know, situations like that. We do believe that the plan is. I again don't want to talk about the plan in detail. However, we do believe that while the opportunity in ovarian cancer is sort of pretty obvious, there are also prostate cancer and such as pancreatic cancer. In addition, we will do a little bit more selection than we need to do in ovarian cancer. We are very excited about it, and we have a thousand ideas that we need to sort of pin down. Remember, this is a phase I study with you now, with very fast accrual in the module two, where we are looking specifically at germline alterations, and we are looking at genes because we see a couple of specific genomic alterations that we did not reveal in this presentation that sort of look more interesting of opportunity. This turns out to be a really good data set. Thanks, Charles. Next question. The next question will come from Ben Burnett with Stifel. Please go ahead. Hey, thank you very much for taking our question. You stressed the importance of biallelic versus monoallelic ATM mutated cancers. I guess, do we know how common biallelic ATM mutated cancers are? I don't have a paper to quote or cite, but I would think 50%. Ben, it's Lloyd. As we explore that path forward and the application of our learnings, which are, you know, enriching for biallelic patients, you know, we're gonna explore just, you know, what that means from a commercial point of view, from a practicality. Today, as we sit here, harder to find those biallelic patients because of the tools that Dr. Yap and Maria described, but it's becoming, and that's part of the analysis, the, if you will, the commercial and patient finding analysis that we'll be doing before we go back to the regulator. Right. I often talk about the biallelic concepts for you, okay? If we go back to PARP, original olaparib, ovarian cancer, it was germline BRCA only. Why? Because germline BRCA is 90% that time. Then we started to go to, let's say, bladder cancer with PARP inhibitors, and almost nobody responded. Bladder cancer, BRCA alterations, so almost never biallelic. The concept of biallelic is just a fancy way in tumors, which sort of now became more fancy to just do an assay for that. But in the biallelic, now what happened after the approval of germline ovarian cancer, and by the way, germline BRCA in breast cancer, AstraZeneca and others started to look at somatic alterations that are much less frequent biallelic. Guess what? These patients also biallelic. However, there is definitely benefit. When you look at the evolution of the trials, the prostate somatic and germline, because we learned or the companies learned to sort of broaden it, not to omit the patients who migration to 50%+ PD-1 expression versus 1%+, right? I mean, 50% responds better, but you would not, or not let you because there is some benefit. It is all about really enrichment versus selection. That's why decision to make, because if there is a non-toxic good drug, probably everybody wants it, even if the chance of responding is less, like a medium, to give it to the right patient still. Great. This is important. Yeah, we have a few more questions to get, so if we can move along. Who's next up? Our next question will come from Zhi-Kang Xu with Berenberg. Question, congrats on the data update. Maybe two quick questions for Dr. Yap. If you look at the responses on the prostate cancer cases here, obviously we see some activity, some durable responses, but none of the patients actually received PARP as approved here. How do you think the clinical relevance here, does it really reflect the clinical practice? Some. I actually think there was a mixture of patients. I don't think they were all PARP inhibitor-naïve. You don't think it was purely PARP inhibitor-naïve prostate cancer patients, for sure, because, you know. That is correct. Right. Okay. Yeah. They were probably PARP inhibitors exposed already. But anyway, you know, it's kind of, to me, it doesn't matter because by the post-PARP ovarian cohort of patients, you know, and I would actually think that, you know, alongside breast cancers, these are the areas of unmet need. I would say BRCA-mutated pancreas as well, right? Where you already have these hereditary breast PARP inhibitors already approved, you know. Especially ovarian, you know, every patient probably will see, with ovarian cancer, will see a PARP inhibitor. And now, we have nothing for these patients apart from chemotherapy that's approved. We need a more rational approach for these patients, and we don't have that. Great. Just a quick follow-up. We see a lot of the strong activity here in ovarian, but for breast it is less, I guess. What do you think is playing a role here? Is it more of the biology of different tumor types or for the patients given the, you know, their relatively small data set. You probably see on the slide. I mean, these patients. This is a very advanced cancer patient population. If you look at the approved treatment from memory, it was down at, I think 20%-odd, right? 24% even of response rate. Again, I go back to what I was saying, endpoint. Is response rate really an accurate parameter to judge is to prolong patients' life. Just because there was a response rate or no response rate, that's not gonna decide durability of response. These patients have co-mutations, which could certainly contribute to resistance as well, and that needs to be figured out. I think the data are very promising. I think we have one. Thanks. Thanks, Zhi-Kang. I think we have one more call from Tim Chang with Northland Securities. Please go ahead. Hi. Thanks. Just a quick question for Dr. Yap. Doc, the other elimusertib data yesterday, and obviously, just looking at their slides. The profiles are different, but could you just comment on the differences with the treatment-related adverse events? It does look like the rate is. Indeed. I mean, from memory, it was about, I think, 60% grade 3 anemia rates, you know, with three days on, four days off schedule. Yeah, I, you know, that was. Yeah. I mean, Tim Chang, if I can rescue Dr. Yap, I mean, it's a little unfair to ask him to contrast this. He of Bayer in developing their drug, which was a different protocol, a different patient set, and a very different set of investigators. You know, I think this is one of those that have been presented in the past 24 hours really speak for themselves. I think we'll point out today, we feel very comfortable with that. We understand where the limited data we're seeing is. I think the thing that we should probably mention, you know, most pointedly is I think and Dr. Yap talked about at length, fits nicely within any imaginable target product profile, and you know, comparable to. We're just very comfortable that we've sort of put to bed the discussion about dose, safety, and tolerability, and we can move forward and hope opportunities are to help patients, in terms of efficacy. That's the discussion going forward. We have time for one more question. That question will come from David Martin with Bloom Burton, and please go ahead, sir. Yes. First off, I had a question. The ATR inhibitors, had they failed those PARP inhibitors or had they not failed? Depending on the definition of failure is not that well established like the years and years of working on the. Some of the patients were treated with PARP for a while, and some recurred after PARP, after very. If you are using the definition of platinum resistance or refractoriness, there was a mixture of these patients. I warn you that we don't understand. Do not think that we should define the PARP resistance refractoriness and sensitivity the same way. This was a mix of patients. I do realize that the hematologic toxicities of RP- 3500 do look lower than the other ATR inhibitor. Anemia is still something nonetheless that is a major risk for the drug going forward, or is it manageable? You know, if you look at the olaparib, anemia, it's the same. In fact, I think it's actually higher of the other PARP inhibitors. I think talazoparib especially, but the first generation, you know, the approved. Let me rephrase it. The four approved PARP inhibitors right now, talazoparib, niraparib, olaparib, rucaparib, anemia at that level, and it is not an issue. Dave, I'll add that you recall that has a phenomenal set of tools, including a nomogram that has not been yet used in future studies that we believe can bring downward pressure on those numbers, and make things more manageable for the oncologists. You know, just give them tools to really manage this. As Dr. Yap pointed out in his talk, the fact that beyond the anemia, which certainly falls within the range of other products, including PARPs, you know, we're not seeing these on or off target that would have us concerned. We think the profile is beautiful. I'm mindful of the time and that people have other meetings to get on to. I'd like to really extend our gratitude to Dr. Yap for his participation and continued clinical leadership. I would also like to thank all the patients, their families, physicians, caregivers once again today. A special thank you to the entire Repare team, their hard work and dedication in advancing our mission to be the leading precision oncology biotech focused on novel synthetic. This concludes our call. Thanks for taking the time with us on a late on a busy evening at AACR. Good night, everybody. Thank you for attending today's presentation. You may now disconnect.