Good morning, good afternoon, and thank you for joining us today. My name is Malika, and I am an associate in JP Morgan's Healthcare Group. Before I introduce you to our presenters today, I want to call your attention to the blue button on your screen. This is where you'll submit questions that will be addressed during Q&A. With that, I am pleased to introduce you to Lloyd Segal, CEO, Steve Forte, CFO, Maria Koehler, Chief Medical Officer, and Michael Zinda, Chief Scientific Officer at Repare Therapeutics. I know that they are very excited to tell you about their story, so we turn it over to Lloyd and his team. Thank you, Malika, and thanks, special thanks to J.P. Morgan for including us, again this year in what I hope is the last virtual, JP Morgan in a very long time. Before I dive in, I'll call out the slide numbers that I'm on. I understand everybody can move the slides forward and ahead at their own pace. I call your attention to slide two and our safe harbor statement, particularly to the risks described therein. I'm on slide three, and before I get going, I'll just say I'm going to do this at a pretty brisk pace and then bring Mike, Maria, and Steve in for Q&A. I don't wanna cut that time short, so I'm gonna provide a high-level presentation, and then we'll dive back in, wherever the group wants to take us on Q&A. This sums us up nicely where we stand today. We are, as we sit here, the leading clinical-stage precision oncology biotech focused on synthetic lethality. That starts clinically with our two compounds currently in either phase I or phase I/II clinical trial. RP-3500 is a potential best-in-class inhibitor of ATR, and RP-6306 is a first-in-class inhibitor of PKMYT1. As I said, both are currently in the clinic, the former in phase I/II TRESR trial, which we'll get into in some detail, in both monotherapy and combinations. As is the PKMYT1 RP-6306 trial, in both monotherapy and combinations, we expect multiple data readouts on both those trials in 2022. Behind those, we have a robust pipeline of synthetic lethal-based therapeutics, and all of our compounds are wholly developed in-house and generally, as I'll describe, wholly owned by Repare and unpartnered. We have guided recently that our third homegrown clinical program, Pol theta, that compound will be entering IND-enabling studies in the first half of this year, which suggests we should be able to get into clinic either very late this year or in the first half of next. I think we're particularly proud and excited about the idea of having delivered, if we can, do this with Pol theta, three clinical compounds from our platform in about three and a half years. Everything we do at Repare is based on our proprietary genome-wide CRISPR-enabled platform. We call it SNIPRx. It does two things for us based on our very proprietary capabilities in genomic instability, DNA damage repair, and an approach on synthetic lethality. One, it enables novel target identification that we use both for our own account and in a very broad partnership we announced in 2020 with BMS, and differentiated patient selection insights, what we call our step two insights, once we are prosecuting our compounds, and we'll talk about that a bit today. At December 31, we finished 2021 with over $340 million in cash on our balance sheets. That includes the $100 million we raised in November, and we are very comfortably funded through 2023, keeping the pedal on the metal clinically in terms of our pipeline. I'm on slide four, and I just wanna point to a new and important member of our team. Phil Herman joined us January 1 from Y-mAbs. He has a long career as a commercial leader in oncology, starting at Pfizer. We're very excited to have Phil join us to bring commercial discipline insights as we start to chart out the commercial footprint of our programs as they move into phase II and beyond. I'm moving right to slide seven, and I'm just gonna quickly remind those of you who haven't seen this recently of our platform. On slide seven, what you see is our synthetic lethal SNIPRx programs to identify new targets and how we get to new small molecules. We always start with the patient's unique genetic lesion, so we're starting with our patient selection paradigm in mind. We have a proprietary set of CRISPR-based tools that are highly sensitive, and we find those targets, and we've proven that we can get to novel synthetic lethal targets from every campaign we've undertaken to date. On slide nine, though, we highlight something that's really different that we do, and once we have chemical matter against a target, we use the same platform to do effectively chemical synthetic lethal screens to look for the network of other synthetic lethal alterations that predict a response to inhibition of our target protein, in this illustration, ATR. As you'll see as we tell our story, this has become a very powerful differentiator for how we get at drug discovery. Slide ten, just briefly, we crafted a great collaboration that has gone very nicely, including some announcements last quarter, on opt-ins within this program. BMS crafted with us in, I think it was May 2020, a $65 million deal that has potential of as much as $3 billion in the long run. It's focused on targets that we developed through the platform that I just described. In this case, when BMS gets excited about a target, they do all the heavy lifting on small molecule development. On slide 11, what that results in is a pipeline that has now become quite a portfolio of opportunities. The top two, RP-3500 and RP-6306 already in the clinic. The third one down, as you see, Pol theta expected to enter the clinic with IND-enabling studies planned for the first half of this year. With the exception of a partnership we crafted essentially in Japan and certain regions in Asia, except for China, which we retained, we have 100% ownership of all of our programs, including our two most advanced clinical programs. We have eight additional synthetic lethal targets we're pursuing beyond Pol theta, and we're more excited than we've ever been about that early pipeline. On our own and with Bristol Myers Squibb, we have a pretty rich set of new synthetic precision oncology targets that we're pursuing. I'm gonna jump right to our ATR inhibitor, and I'm on slide 13. ATR is a fascinating and critical DNA damage repair protein with a central role in the regulation of replication stress. We have what we believe is a potential best-in-class inhibitor of ATR. I'm gonna go right to slide 15, and what you see in slide 15 is the power of our step two selection tools. On the left, you know, it's long been known that ATM is synthetically lethal with ATR inhibition. What we discovered is there are 16 potential additional genetic alterations that we think predict a response to an ATR inhibitor. That, as you see on the green bars to the left versus the purple horizontal bars to the right, very materially expands the population that we can address, drugs that we develop against. That is central to our view of how to develop drugs. I'm gonna go right to slide 18. In October, we did a first reveal of a dataset for our RP-3500 phase I portion of our trial, module one. What you see on slide 18 is our goal of getting a recommended phase II dose and schedule was in fact successful. We had a systematic approach to getting to this dose across a pretty large cross-section of patients. We're very satisfied with our conclusion that a single daily oral dose at 160 milligrams, three days on, four days off, was both well-tolerated and showing the kind of efficacy we wanted to show. On slide 19, I think it's important to note some previous experiences with the class of ATR inhibitors from other published works raised the issue of anemia in particular, but a range of other non-anemia related tox that was associated with ATR inhibitors. We were extremely pleased after evaluating two schedules at our dose, 76 patients on the three-four schedule. We saw anemia in the range of 15% for grade three, 0 grade four. Importantly, on the zeros that you see in the columns highlighted in green, really, you know, virtually no other tox or low levels of tox unrelated to anemia, just very rare. This really, we think, separates us from the field, at least to the extent that things have been published by others. I'm on slide 21, and I think this captures some of the early analysis we shared in October, which we'll follow up later this half. I think some things were striking about the data that we shared here in October at AACR-NCI-EORTC, which was presented by Dr. Timothy A. Yap. First and foremost, you know, we saw a really striking trend to stable disease patients who were not expected by virtue of being 4, 50, and 6 or plus 9 patients having stable disease, you know, in some cases, as you see here, well beyond 24 weeks. This is a trend we wanna watch. We saw real responses across a range of genetic alterations, and you see here, ATM, BRCA, CDK12, and the group in brown at the bottom, just a number of other alterations that we hope to continue to report on with more detail as we bring this data forward. On slide 22, I think you really see a summary of the overall patient benefit that we were seeing and that, Dr. Yap reported at our ANE presentation. First and foremost, almost half of the patients that were evaluable, that was 69 patients evaluable, showed a meaningful clinical benefit. That was across multiple step two genomic alterations. It was across schedules and after PARP inhibitor failure. We saw 12 responses by RECIST or other commonly accepted objective standards, including the PCWG3, GCIG. There were 14 patients with ongoing stable disease of over 16 weeks, and 8 patients under 16 weeks with early and significant decreases in tumor markers and tumor shrinkage. We were extremely pleased with what we saw here. On slide 23, I think we also started the process of highlighting the predictive nature of ctDNA in the trial, and we're including ctDNA to the greatest extent possible across our patient set in this trial. I think we only have time for one. I'll go to slide 26. In this case, this was a patient with castrate-resistant prostate cancer. To this point on ctDNA, what we saw was a late response here in week 16, but the ctDNA was already way down on week 6. This is the kind of response that we think ctDNA can be highly helpful in predicting as we continue to look at the data coming out of this trial. More important that we can believe that some of the anecdotes about later responses in ATR inhibition as a monotherapy are things that we're seeing more frequently in the data set. I'm gonna move right to 28 and wrap up on RP-3500 here and on the next slide. What you see here is the current landscape of the trial. The sort of purple or darker gray colored areas are the TRESR modules that we're currently focused on. The Module 1, which we already reported initial results on, we now have enrolled 120 patients. We have our RPTD, and we are, as we've guided to, turning to the module two portions of that trial, beginning in this half and over the next several quarters as we have data that we can bring to bear, thoughtful designs for our follow-on work. In addition, as you see on the bottom left of this slide, we have combinations with PARP inhibitors. The TRESR portion of the trial included talazoparib, Pfizer's PARP inhibitor. We also launched in August 2021, ATTACC, which includes RP-3500 plus olaparib and niraparib. Not both, RP-3500 plus olaparib, RP-3500 plus niraparib. Our goal is in the second half to try to bring together a data set that compares and contrasts what we've achieved in patients for all those combinations with PARPs. We'll also be starting a combination trial. Actually, we just started a combination in December with gemcitabine. We'll be starting a pediatric trial in this quarter, so a very busy time. To quickly summarize, you know, we think RP-3500 is a potent and potentially best in class, highly selective ATR inhibitor. TRESR is the largest biomarker selective trial testing ATR as a single agent. We saw RP-3500 was really well-tolerated and highly differentiated from the field based on this part of the profile. We saw meaningful clinical benefit, as I've outlined. We have an RPTD. We think the safety profile is really nicely set up. The biomarker data confirm multi-tumor proof of mechanism across several molecular backgrounds. We're gonna continue to report on that when we deliver our next report on module one. The early TRESR data provide a real nice view on our step two capabilities to predict other genetic alterations that can predict a response. Looking ahead to 2023, just in terms of the specific milestones, you know, in the TRESR module one, we'll fully report that out likely second quarter, the second part of the first half. We'll initiate that pediatric trial in this quarter. The talazoparib and the ATTACC combinations, we're looking at a readout targeting Q3. The gemcitabine should be probably a little later than that, a readout in the second half. With that, I'm gonna shift gears and look at PKMYT1. Again, just in the interest of time, I'm gonna race through this. Unlike ATR inhibition on slide 32, PKMYT1 is a first-in-class drug. PKMYT1 is a target, and I'm on slide 34. Came out of our step two, sorry, out of our CRISPR screens, our SNIPRx screens, as highly synthetic lethal with cyclin E1 overexpression. PKMYT1 on slide 35 is a WEE1 kinase family, but it's distinct from WEE1 in how it, where it's located and how it operates for the reasons described. On slide 36, as you can see, we developed 6306 as a highly potent and selective inhibitor of PKMYT1. We're not aware of anyone else who has developed a PKMYT1 inhibitor. It had a really nice preclinical profile, and we put it into the clinic. We're often asked how PKMYT1 is differentiated from WEE1, and slide 37, I think, highlights just the nature of how it's acting, how it's phosphorylating CDK1 differentially, not only in its mechanism, but it's acting in the cytoplasm and not really adjacent to where WEE1 is acting. You know, we think, and as we've described pretty comprehensively in our published papers, which you can access off our website, that it's a distinctive mechanism and target. On slide 38, what you see is, you know, we saw the massive difference in sensitivity when we compared WEE1 to PKMYT1 in our preclinical modeling. I'm gonna go right to slide 40 because I think this highlighted work that we previously published on RP-6306, our PKMYT1 inhibitor, as an effective and active compound in cyclin E1 amplified tumors. We see in preclinical in the xenograft models that we worked with, you know, a nice tumor growth inhibition and a really good justification to head to the clinic. One of the more fascinating data sets that Mike presented was also on slide 41. In looking at RP-6306 plus gemcitabine, we saw some very significant regression and no toxicity to speak of in that model. I think if I can just go past the why PKMYT1 in the clinic, what was really interesting is when we brought our step two screen to bear. Slide 42 is a phenomenal example of how our step two screens power our clinical work. What we did once we had RP-6306 as an advanced pre-clinical compound, we put it back into that step two screen, and we observed that FBXW7, you know, was predicting response. It was synthetic lethal with PKMYT1 inhibition. FBXW7 in slide 44, again, for that model, in this case it was a PDX model, showed a really nice response to RP-6306, as in a monotherapy setting. Again, really deep tumor growth inhibition. FBXW7 is particularly attractive to us on slide 45 because in particular, colorectal and lung squamous cell cancer, we see these FBXW7 alterations as very common in these very, very large addressable patient populations. With that, on slide 47, we went ahead and launched in April, May of last year, our RP-6306 clinical trial program. It's currently in dose escalation and schedule finding, but we were sufficiently advanced in that program for the reasons I just described, to launch in December our gemcitabine combination, which is already underway, and expect to launch in this quarter our fulvestrant combination. I think that speaks volumes to the comfort that we and our investigator partners had in the safety and tolerability of RP-6306 to date. We expect to get more precision around dose and schedule finding fairly shortly, at which point we'll get a lot more comfortable about projecting when and what we expect to share clinically. Sorry, in terms of disclosure. I'm gonna move pretty quickly to Q&A, so we can maybe just get to our key milestones on slide 51. As I mentioned, just to wrap up, we've got comprehensive module one data coming out in this half. We'll initiate pediatric phase I, initiate our phase II monotherapy. We'll start module two in this quarter. We'll probably disclose a richness of what that'll be about, and Maria will get a chance to talk to that shortly. Initial data for the combinations, as I said, in the second half, along with an RPTD for the GEM combinations. PKMYT1, we'll provide more color, but we expect our initial MYTHIC phase I monotherapy readouts in the second half of this year. The fulvestrant combination in this half. I think I mentioned earlier, we expect to initiate IND-enabling studies for a third clinical compound, Pol theta, in this half. I'm going to wrap there and invite the team in for Q&A, if we can pull folks in. I can see one question. Hang on. Okay, we have Mike, Maria, and Steve. Welcome, Mike, Maria, and Steve. Maybe we can address that one question in terms of what we think Maria will be disclosing in the RP-3500 initial data this year, the sort of full data set on module one. You're on mute. Sorry. This will be a set of 120 patients, and we have chosen the time of releasing the data based on the observation time. We wanted the patients, the 120 patients to have a sufficient number of months of follow-up. This will be a longer follow-up. This will be a larger set of patients than the one reported at the October meeting. We are also expecting to have some increased depth in the evaluation of the tumor and the ctDNA that you got a little bit of information in Lloyd's presentation. However, we will have the correlation about how does the biallelic versus monoallelic status of the alterations affect sensitivity to ATR inhibitor. We also will have a correlation between genomics and proteomics in some of the tumors, specifically in the ATM. Finally, as you know, we have a proprietary targeted panel, deeply sequenced tumors by NGS. We are going to present the correlation between the central review of the available tissue versus what was the enrollment criteria done by commercial assays, NGS assays. Those layers on top of obviously more patients for a significantly longer follow-up time. I think there should be an expectation of a richness of data that for us, most importantly informs our modular architecture and decision making. That's the whole idea. Thank you so much, Maria and Lloyd. One more follow-up question is related to RP-6306. What additional toxicity do you expect with addition of GEM to RP-6306? We did not characterize the toxicity profile of monotherapy, so it's very difficult to hypothesize anything with gemcitabine. We are pretty happy with the profile that we are observing now, which sort of is confirmatory of what we saw in the preclinical studies, which always is a good sign. However, how it will be tolerable in the context of our predicted very significant synergy with gemcitabine is very difficult to speculate. We will see the data shortly. We started enrollment. Thank you so much. On that topic, could you tell us a little more about the plan for disclosure regarding RP-6306? Generally, in disclosure for RP-6306, we're gonna wait till we get to the point where our dose and schedule finding is advanced to where we can more reasonably predict, you know, timing of when we'll have a sufficient N of patients, you know, on the recommended dose and schedule. That will be a 2022 event, but right now, I think we'll hold off until we get there to providing more specific guidance. Thank you. Another follow-up question on RP-6306 is what is the difference in the RP-6306 dose between the single module and the GEM combo module? These are two very different trials. These are not modules. We specifically designed the program so that we are establishing just simple dose and schedule for the specific alterations for monotherapy. It is a reasonably small trial. It's listed in clinicaltrials.gov as 60 patients trial only. However, the combination trials that are also listed in clinicaltrials.gov are larger, but these are completely different trials rather than modules. They have each about 100 patients. Thank you. How long is the combo trial projected to be, and do you see a role for RP-6306 as a maintenance drug? How long is it depending, obviously, you know, I don't want to be trivial here. Depending on the toxicity, we believe that it will be probably this, and I don't want to speculate, but we will release the data at the very end of the year. Let's call it a year. We just started literally in December, and this is when we release the data, release the fact that we started. The second question was? The second question was, do you see it as a role, as a main Okay. A role as a maintenance drug, yeah. Right. You know, again, it's too early to predict. It could be a maintenance drug, but it could be also a very good partner to chemotherapy or other modalities. Again, we listed in the presentation that we are planning to start other modalities beyond chemotherapy. Finally, it could be just a simple, a single agent drug in the specific genomic alterations. We are not at the stage where we are at the doses that we can claim efficacy, so it's too early to speculate. Thank you. Could you talk to us a little bit more about your early-stage pipeline and your partnership with BMS? Yeah. You know, we're thrilled with the engagement and frankly the partnership that we've had from the whole team at BMS, from our executive connections there to the team that's managing evaluation of the targets that we're generating. We did disclose in the last quarter that BMS has opted into two targets and are, you know, while the payments themselves were not really material. We like to think they represented important signs of progress. You know, they didn't have to opt into anything. They had to like what they saw. You know, we think that's a great partnership, and we have just been blown away by the level of engagement and thoughtfulness that team at BMS has engaged in our early-stage targets. In terms of the pipeline beyond that, I made a comment earlier that we're more excited than we've ever been about our pipeline, and that happens to be true. It's no secret that we have been working to crack the code on Pol theta since we formed as a company in 2016. We're really pleased to be on the precipice of getting that one into the clinic in the near term. There are several behind that we haven't talked to the street about that we're equally, if not even more excited about. I think those of you who followed us for a long time know that our style and our approach is more around what we did with PKMYT1. Just to remind you, last April, no one had ever heard of PKMYT1. We never named the target. In one day we presented a comprehensive set of evidence validating the target, the mechanism. By the way, we were in the clinic with a novel compound three weeks later. That's kinda how we like to do things with evidence and data to justify both the use of our new compounds in precious patients and the allocation of capital. I think these things go together. I hope at one point the street can look at our track record of continuing to deliver a mix of both compounds against targets with some precedence and completely novel work like our PKMYT1 work. Count on us to continue to deliver programs into the clinic at some impressive cadence. Between Mike's team, who have just done an incredible job of discovering and developing every compound that we're working with, to the work that Maria and her team and our collaborators did to develop RP-3500 and RP-6306 through the clinical stages they're at now. I am incredibly proud of what this team has accomplished, and I'd put them up against anyone on that front. Thank you. We have enjoyed hearing about Repare Therapeutics. Thank you for all the amazing work that you have been doing. We don't see any further questions from the audience, so do you have any parting thoughts for us? I think this is a seminal year for us. We have more clinical catalysts ahead of us in 2022 and 2023, and we're with $340 million in the balance sheet, we're extremely well funded to deliver on multiple catalysts in the near term. Exciting times for us, and we look forward to seeing you all again soon.