If you have any questions, please reach out to your Morgan Stanley sales representative. All right, great. I'm happy to welcome Lloyd Segal, CEO, Steve Forte, CFO, and Maria Koehler, Executive Vice President and Chief Medical Officer, with us today. Thank you very much. And just for everyone in the audience who's not familiar with the Repare story, maybe we can talk about, initially the platform, the technology, and highlight any key takeaways you'd like to start us off. First of all, thanks for having us here at Morgan Stanley. Great conference and great venue. We started Repare in 2016 with a very simple principle and concept based on a scientific approach called synthetic lethality. To make a very complicated story very simple, we start with a gene alteration that we know is present in some pretty aggressive tumors, and we try to find other targets that work in concert with that gene. When that gene is deleted, give a better chance of killing a tumor because there's a sort of network at play in how the deleted gene, when it's deleted out naturally in tumor in that individual, and the target, when those come together, you can really target a tumor elegantly. The proof of concept of this idea of synthetic lethality was PARP inhibitors. Where, in the case of PARP, you know, it was clear that you could select for patients driven by that very similar hypothesis. In eight-plus years since we built Repare, we have put into the clinic three, and very shortly, four clinical programs that are built around this idea of synthetic lethality. I think we've proven already with our clinical data, let alone our preclinical data, which have been, you know, quite compelling, that this approach works. Great. Just to double down a bit on, I guess, how you advance programs, any insight into preclinical development and why potentially you're targeting DNA damage repair mechanisms initially? Yeah. So, I mean, this idea of synthetic lethality is highly prevalent within DNA damage repair, where there's usually more than one, gene or gene product at work in driving, tumor growth. If I use actual examples from how we've developed our, our clinical drugs, I'll point to two, one in our lunresertib program and the other in our, our PLK4 program. In lunresertib, we started based on this idea of synthetic lethality with Cyclin E1 amplification mutations. And so we really drove our platform work, you know, starting in 2017, 2018, on this idea of finding a synthetic lethal pair for, you know, for, Cyclin E1 high mutations. And that's how we found lunresertib. We published it in a Nature paper, which was quite seminal. I think it was in 2021 or 2022. And, more importantly, we've since proven in the clinic that Cyclin E1 and two other genetic alterations that we identified preclinically, PPP2R1A and FBXW7, predict a human response to PKMYT1 inhibition with our lunresertib compound. So we've seen responses in all of those selected tumor types. And in our clinical approach with lunresertib, we only look at patients with those three alterations because in the paradigm of precision oncology that we embrace, we only want to enroll in our studies patients who we've demonstrated or likely respond to the drug. The second example, which is a little more recent for us, is PLK4. So, together with some external collaborators, we recognized that TRIM37 high alterations predicted a response to PLK4 inhibition. And so there, it was animal work that really drove us to the direction we've taken now clinically. So we did a collaboration based on that preclinical prediction that TRIM37 high alterations predicted a response to PLK4 inhibition. And in our animal work, together with the Children's Hospital of Philadelphia, CHOP, you know, leading pediatric hospital research institute, we showed better data than they've ever seen. We've shared a lot of that publicly, in the models of pediatric neuroblastoma, which we hope will translate very shortly into kids- Mm. -with pediatric neuroblastoma. So it was a great example of how our application of synthetic lethality, our platform and our approach, really streamlined our way into a specific, clinical program and patient selection paradigm. Great. And before we dive into the pipeline and progress the team's making, could you talk about any potential collaborations Repare has signed to identify these patients in the future and actually select? Because these could be potentially specific patients carrying mutations that are unique. Yeah, so- Companion diagnostics or anything like that. Yeah. So I mean, the beauty and the long-term dream there is that next-generation sequencing or NGS will become so ubiquitous that this won't matter. In the real world today, and with our regulator partners at the FDA, there is a much more routinized path forward. And so to ensure that we had a you know a clear proven partner in our requisite diagnostic path forward for our drugs, it's public that we've partnered with Foundation Medicine Inc, who we view as among the leaders. There are a couple of great emerging players, but they've been fantastic partners to us in terms of developing and proving out companion diagnostics, finding the right regulatory path forward, particularly with lunresertib, which is, we hope, in the lead to get there. As we succeed with our lunresertib programs, Foundation will be a partner there, and they are fantastic at what they do. Great. That's helpful. So starting off with lunresertib, excuse me, I think maybe we're having a fire drill test here, but I think it's just a test. Yeah, the lead program here- May I have your attention, please? Due to the testing of the elevator, car L will be out of service for next five minutes. Thank you for your understanding. I really wanted to use that elevator. We're gonna edit that out. So for lunresertib, in regards to... This is your most advanced program, could you introduce your evolving trials, and before moving on to the lunresertib combo with CAM, which I think most investors are focused on, how would you describe the current clinical program? The current clinical program with lunresertib contains several combinations. Those are the combination with camonsertib, which is our key data set that is going to be released sometimes in fourth quarter, most likely at the company event that will be after the main medical meetings. We are planning to release the data in two gynecological tumors, specifically ovarian cancer and endometrial. In addition, we performed a Phase I trial in combination with FOLFIRI, with lunresertib FOLFIRI. The reason for doing this is that FBXW7, one of our key alterations, is present in about 12% to 15% of colorectal cancer. This is a very aggressive tumor subset that is specifically not sensitive to immunotherapy and unmet need. And this combination was, data on this combination was released at ESMO GI about two months ago, showing a promising signal in colorectal cancer with FBXW7, as well as in some other tumors, but our major subset was colorectal cancer. So that's another possible way forward. Great, thank you. So now maybe we can dive into the MYTHIC trial. This is testing LUN plus CAM at the recommended Phase II dose in patients with platinum-resistant ovarian and endometrial cancer, and I believe you said that these data are expected in the fourth quarter. This will be a company presentation sometime around a medical meeting, is that correct? No, after the medical meeting. After the medical meeting. Yeah. Any additional guidance on whether it'll be earlier or later in the fourth quarter? Probably later. Later in the fourth quarter? Mm-hmm. Okay, great. So stepping back for a moment, just to level set expectations, can you provide an overview of the current treatment landscape and unmet needs? Sure. So, I will start with endometrial cancer because it's a very fast-evolving field. Endometrial cancer is an extremely aggressive disease, which actually is very important because the frequency of endometrial cancer over the last several years is growing by about percent or so a year. So this is a growing opportunity of high unmet need. The evolving landscape, the patients were treated just with chemotherapy, but since the success of immunotherapies, the immunotherapy, like ICIs, the immune checkpoint inhibitor, together with chemotherapy, are now approved in unselected patients with endometrial cancer. And this constitutes the standard of care with survival benefit in first- line endometrial cancer. So that is good for the women, but then there is absolutely nothing known to work, nothing is approved in the second- line after the chemo with ICI. So this is the completely opened field for the second-line endometrial cancer. And again, as you already heard, we are testing only the combination in these three alterations. Another very important feature is that about 70% of carcinosarcoma endometrial carcinosarcoma and about 70% of serous endometrial cancer, which is the most common endometrial cancer, is positive for our markers. So it is a substantial subset of this population. Further, and we are going to present details of what I'm going to tell you in a conference in late in September in Ovarian AACR conference. This population of the three markers constitutes in ovarian and in endometrial cancer, a very high risk, bad prognosis population. So we have a biomarker selected population of increasingly unmet need, even more unmet need than the overall population of endometrial cancer. So as I told you, in summary, we are trying to position ourselves as a opportunity in the selected 70% of patients in, after ICI and chemo. For ovarian cancer, the frequency of the markers is very different. Majority of the ovarian cancer patients with our markers have CCNE amplification. The frequency of PPP2R1A and FBXW7 is very low, single digits, like 1 to four, five percent. And the overall platinum-resistant population, again, a very unmet need population, is about 25% to 30%. So I don't... I think I answered your question. Very helpful. That was clear in regards to the treatment landscape or unmet need right now. So, focusing in on the MYTHIC trial, could you provide any initial data you've presented so far or challenges you faced? Of course, anemia being one of them, which basically from my understanding has been sorted out, but any additional details in that dynamic would be great. For the MYTHIC trial, the only data that we presented was about a year ago at the AACR meeting 2023, and at that time, this was initial dose escalation trial in any patient with any tumor, as long as the patients had the tumors had this alteration of interest. However, upon approaching the RP2D, the recommended Phase 2 dose, we had a couple of patients with gynecological malignancies, and this is not that we targeted the gynecological malignancies, we just happened to went to centers which has a lot of gynecological cancers, so we had an enrichment for gynecological malignancies. Among those patients, and we had about twenty-some patients, there were 10 patients treated at recommended dose. These were patients with endometrial or ovarian cancer, the 10 patients, and we found 50% response rate. Of course, this is not probably repeatable number, because this is a very small patient population. But this is a very appealing signal that we are now following, and this is the reason why our expansion that we will reveal in the later this year is in gynecological malignancy. Yeah, you, and I just want to make sure this doesn't go unanswered. You, you asked a question about anemia, and I think it's worth just stepping back. You know, we did see a higher signal in anemia in that very early set of patients at RP2D than we would have liked. But overall, today, where we sit, we just addressed that at the time and since in more than 80 patients, and we shared this data in the first quarter, with a just a single week dose holiday for any patients who were coming out to the trial under 11 hemoglobin. When we look now at our tolerability and safety profile compared to, as Maria described, I think wonderfully, like the chemotherapy alternatives, whether it's ADC or chemo alone, or in combination with pembro or an ICI, we have an incredibly competitive profile that represents just a phenomenal potential alternative to chemo. Great. And based on any KOL feedback you've received, what do you think physicians are thinking about when they see the anemia has been worked out, you have the drug holiday? How's the overall feedback in that regard? So the physicians really like the combination because, as you know, the landscape consists of, in both of those diseases, with chemo plus minus, ICI in endometrial cancer. But once this is done, the next step is also chemo. And the chemo can be either the sort of old chemo, single agent that everybody was using for years, or an alternative of chemo, which is also chemo, which is the ADCs, which are tested, okay? So while the IV-given therapy is definitely a opportunity for these patients after the first or second line, physicians and patients are looking for something else as well. And in the mind of the physicians, they always want to give the right patient the right drug. The testing, which with increasing number of patients are tested now for either NGS or some other options, the testing allows to isolate the patients, let's say, with CCNE or FBXW7, that is, or PPP, that actually is on all the routine panels. So if the physician orders a Foundation or Tempus or Caris or whatever, this, they see this marker, so the obvious reflex is to look for something that is suitable for the patient and not chemo. Okay, that's helpful. So now diving a bit deeper into the MYTHIC readout coming in the end of the fourth quarter, second half of the fourth quarter. Can we set expectations in regards to what you're expecting to see or what the benchmark is in platinum-resistant ovarian cancer first, and then we can move on to the next one? Yes, taking those in turn, in platinum-resistant ovarian cancer, we're looking for a response rate around 30% or better, and we think it's gonna take five to six months PFS to have a compelling bar and a compelling offering. In terms of endometrial, and the bar is lower, as Maria described, we think, you know, we think the something on the order of 20% response rate is gonna matter a lot or better, and a similar five to six-month PFS. Okay. And I've noticed in your most recent deck, or it goes back maybe a couple months, you call out chemo, Bev, single agent chemo, mirvetuximab. Why include these different benchmarks, and where do you think this falls in the treatment dynamic? Just like you mentioned, all these drugs, because all these drugs are existing in the armamentarium of treatment that the physicians can choose from. And now, for example, Mirva is a great drug, which is approved, however, only in patients who have tumors with very high folate expression. So if you have a patient without folate expression, Mirva is not the drug for those populations, which is great because this is the concept of the right drug for right patient. Completely fortunately, the overlap between our markers and the folate receptor is pretty minimal, about maybe 10% to 15%, so this is not going to be a competing population. Regarding bevacizumab, this is again, an old proven solution for patients, but usually, the bevacizumab is given to patients already in the first- line. It is approved in first- line, including maintenance, and those patients already got the bevacizumab. What we know, for example, from the update from the Mirva trial is that if the patients got the bevacizumab, the response to Mirva and the PFS with Mirva is very worse than, for those patients who did not get bevacizumab. So again, we are learning from all these trials that the population of patients keeps being divided into this small subset of different unmet needs. And what other drugs did you ask? And then just single-agent chemo. Yeah, and single-agent chemo. Single-agent chemo is the old solution. However, the success in platinum resistance specifically is pretty miserable with a response rate of about 15% to 16%, and PFS in the range of four months. So this is something that the physician give to the patients because they need to be treated. However, it is not something that anybody is particularly proud of. So we're anticipating falling somewhere close to the chemo Bev ORR response rate? Well, the benchmark Lloyd mentioned are about 30% for ovarian cancer in platinum-resistant ovarian cancer, with the PFS in the range of, you know, six or so months. And for endometrial cancer, that is definitely less chemotherapy sensitive than ovarian cancer. And in addition, please do not forget that the population, our subset, is worse prognosis, so we really cannot use the reported percentages that are reported for all comers in ovarian or endometrial cancer. Because if you look. And the other problem that we have in some way is that nobody knows what the true response rate is. We just have data which we'll present in this meeting that I mentioned in later September, that the prognosis in these patients with standard of care is much worse, significantly much worse than with the PFS with several zeros. Just to specify, much worse for those with our biomarkers. Yeah, the patients that we are approaching to for our therapy, right? It's the prognosis is worse versus the overall population. So, we are truly addressing the very high unmet need, where the percentage of responses to single-agent chemo is probably much lower than the 15%, and we are targeting doubling it. And considering the worst prognosis, we will probably, hopefully, triple it. Again, that's the goal. Okay. And moving on a bit to the potential market opportunity down the line, how would you guide investors to the potential upside if those were approved in both ovarian and endometrial? Is Mirvetuximab potentially a benchmark to look at or something to think about, or how overall would you approach that? This is a fire by safety director. ... Sorry. The testing of the fire alarm system has been concluded. We apologize for any inconvenience. Thank you. May I have your attention please? The fire and life safety director, the testing of the fire alarm system has been concluded. We apologize for any inconvenience. Thank you. Sorry about that. So the population of patients we are calculating the second- line endometrial cancer, which is, as I told you, a growing population of patients because of the epidemiology of endometrial cancer, which is related to obesity and other things that makes the tumor more common. And the opportunity is for oral drugs that have a relevantly safer to more, a better tolerability, and do not require that many frequent checks. Like, for example, Mirva has black box, as we know, and it's IV therapy for which the patients have to come, and has its own toxicity. And it's nothing wrong about Mirva, it's actually a extremely successful drug in the market, despite the little flaws that they have. As I said, we are planning to position our drugs along Mirva, because it's not an overlapping population. The percentage of patients is approximately the same in ovarian cancer as with Mirva, maybe a little less, you know, like 25 versus the 40% or 30%. So the market is pretty substantial, and we believe that the next step for an oral well-tolerated therapy is definitely to go early in line, not only to the platinum- resistant, but to an earlier, maybe maintenance therapy or after chemo. Yeah. For endometrial cancer, this is a much more wider open space, and the population is growing, and the markers cover a very significant percentage. Yeah. Great. Last question on MYTHIC. If these data are positive, do you plan on initiating a pivotal study in 2025? And then just any thoughts on accelerated approval? We are definitely thinking about it, but it all depends on data, so we'll see the data. And the second, on the conversation that we are planning to have with the FDA, and we hopefully will be able to talk a little bit more about it later this year. Okay, great. And then before moving on to financials, Repare has a lot going on. Are there any other milestones you'd like to highlight that could occur either this year or 2025? I'm thinking about the camonsertib monotherapy data in non-small cell lung cancer. Yeah. I think this year, you know, upcoming, there's some really important milestones, which are, getting Pol theta going in the clinic, which is imminent, and for which we have not changed guidance, which would give us our fourth, clinical entry. And then next year, readouts, you know, we hope early in the year on our WEE1 lunresertib combination and our camonsertib monotherapy, in non-small cell lung cancer with the ATM selected population. I think those are the ones that people are looking for. Great. So now moving on to financials. Recently, you announced a strategic reprioritization, which will materialize into approximately $15 million in annual savings, extending your runway into the second half of 2026. Could you just walk us through what led to this decision and how it'll impact your R&D efforts? This was a straight-up capital allocation decision, and in this market where it's clearly the highest bar I've seen in my years in this industry, with four compounds in the clinic before year end, it was hard to justify R&D, even though it's a phenomenal R&D that's enabled that amazing clinical portfolio we're prosecuting. To do R&D for INDs in 2026 and 2027, it just didn't feel right from a capital allocation point of view. It was tough. The intellectual decision for that capital allocation decision was easy. The hard part was amazing people who enabled our success are no longer with us, and we let go of on the order of 24% to 25% of our team. But that was all in research, about $30 million over two years, redirected to our clinical future. So as, the kinds of opportunities that Maria just described, a potential registration opportunity, a potential prosecution of Pol theta or PLK4, we have much more capital freedom now. Great. And if investors were to ask, "Does this have any read-through to your clinical programs? Are there any implications there?" How would you respond? I think that, as Lloyd said, really what we ended up doing is looking at what are the clearest nearest term value inflection points for us and reprioritized our strategy accordingly. ... and so as even within the questions you've asked us, a big focus on lunresertib-camonsertib. As we look at maybe if you think of this in terms of capital allocation, the strategy now is really focused around where we think our capital should be allocated. It starts with lunresertib-camonsertib, and then works its way down the rest of our portfolio. So lunresertib-camonsertib sort of we're getting the lion's share of that capital. We have a very efficient strategy going forward for Pol theta and for PLK4. And then beyond that, well, we've reprioritized our efforts accordingly on all our preclinical development. Great. And so last question. You're making a lot of progress. You're transitioning into potentially a later-stage clinical company. What do you think investors are missing, or maybe you'd like to highlight as a focus beyond the MYTHIC trial? I think the understandable love of ADCs, which are emerging, and I want to be clear, emerging because they're great drugs. Even if they're just better chemo, they're still great drugs. Combined with, you know, what I see as the sort of unintended consequence of IRA, you know, with everybody focused on biologics, great alternatives to chemo are being overlooked. And I tell investors all the time, "Talk to a patient. Talk to a woman as their second- or third- line of ovarian and endometrial cancer." I think that's part of what's being overlooked. And I think the other thing that's being overlooked is, you know, in that same context, is that there's an Elahera-like opportunity. You had a great question earlier. You know, we're tracking at this stage of development, I think, to be an Elahera analog in a non-overlapping, same part of the same broader population. It wasn't appreciated then, let's remember, for Elahera when it was coming out of Phase I, so it's not surprising that it's not appreciated today, but we'll change that with data. Great. Well, thank you very much.