Thank you for standing by. This is the webcast operator. Welcome to the Repare Therapeutics conference call. Please note that this webcast is being recorded. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, press star then one on your telephone keypad. To withdraw from the question queue, please press star then two. Please note this event is being recorded. I would now like to turn the call over to Lloyd Segal, CEO. Lloyd, please go ahead. Good morning, and thank you for joining us today to focus on our two new pipeline programs that we expect to translate into the clinic in the very near term. I invite you to visit the investor section of our website to view the webcast slides and today's press release. Today, Mike Zinda, our CSO, and Phil Herman, Repare's Chief Commercial and Portfolio Development Officer, will walk you through the headlines and details on these programs, including key insights on the commercial opportunities we see and important preclinical data which underscore our belief in these two new differentiated and high-potential clinical programs. I'll finish with some concluding remarks, and we'll make ourselves available for Q&A, together with Maria Koehler, our Chief Medical Officer. Before we dive into our update, I'd like to remind you that we'll be making forward-looking statements during the call. Forward-looking statements are based upon our current expectations and various assumptions and are subject to the usual risks and uncertainties associated with companies in our industry and stage of development. There are a number of reasons why our results may differ materially from those forward-looking statements, and we refer you to our latest SEC filings, where you can find a more detailed discussion of these risks and uncertainties. In addition, any 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 these forward-looking statements in the future, we specifically disclaim any obligation to do so, even if our views change. As a reminder, a recording of today's event will be made available on our website later today. We're delighted to have the opportunity this morning to unveil two exciting programs that we aim to bring into phase I clinical trials next year, starting with RP-1664 in the first half of 2024 and then followed by RP-3467 in the second half of the year. Repare's first program to enter the clinic was camonsertib in the summer of 2020, followed by lunresertib in the spring of 2021. With the planned clinical entry of these two new programs in 2024, this represents a pace of roughly one IND per year. All of these have come from our discovery platform, which has been exceptionally productive in creating potential first and/or best-in-class clinical candidates. Phil and Mike will now walk you through these new programs in detail. Thank you, Lloyd. What's even more important than the expansion of our clinical portfolio is the scale of the unmet medical need across new opportunities we're introducing today. Let me start with RP-1664, a potential first-in-class oral PLK4 inhibitor, synthetically lethal, or SL, with TRIM37 amplification or overexpression, or TRIM37 high in solid tumors. We believe that PLK4 inhibition drives SL in TRIM37 high tumors, a characteristic of many tumor types, and very frequent in certain tumors, including breast cancers, non-small cell lung cancer, and neuroblastoma. Our extensive preclinical data points to the exciting promise of RP-1664 as a monotherapy drug candidate. With regards to the size of the unmet medical need, we estimate that there are roughly 60,000 patients annually across all tumors in the U.S. and the U.K. that could potentially benefit from this treatment. We expect to initiate a phase I study in first half of 2024. For RP-3467, we plan to initiate phase I trial in the second half of 2024. RP-3467 is a potential best-in-class inhibitor of DNA polymerase theta, or Pol theta, and we believe that RP-3467 works synergistically in combination with multiple other therapies, including PARP inhibition, ADCs, and RLTs, based on the data that Mike will share with you shortly. We're quite excited about this combination potential, as these modalities represent very significant and multi-billion-dollar oncology therapeutic markets. As you can see, these two programs are nice complements to our existing portfolio and position well to add meaningful value to growing Repare. Importantly, we believe that for both programs, we can get to early clinical answers efficiently and with careful, controlled spending. RP-1664 is our first-in-class, highly potent and selective inhibitor of PLK4. PLK4 is synthetically lethal with TRIM37 amplification or overexpression, or TRIM37 high, and routinely demonstrates monotherapy regressions preclinically. RP-1664 will be initially investigated in TRIM37 high solid tumors in a focused and capital-efficient phase I clinical study in first half of 2024. TRIM37 is elevated across roughly 63,000 patients with clear unmet medical need, including non-small cell lung cancer and breast cancer patients. In addition, more than 80% of high-risk neuroblastoma tumors have TRIM37 high, offering a unique opportunity to evaluate the PLK4 hypotheses in this population. Mike will now share more details on the rationale for targeting PLK4 and review the promising preclinical data for our RP-1664 program. ... Thanks, Phil. The synthetic lethal, lethal relationship between PLK4 and TRIM37 was published by two distinct labs in the journal Nature in 2020. In short, the mitotic spindle is brought together by two redundant sets of proteins during the mitotic phase of the cell cycle, centrioles and the pericentriolar material, or PCM. PLK4 regulates centriole production, while TRIM37 regulates the PCM. Therefore, in tumor cells with high levels of TRIM37, the PCM is depleted, creating a synthetic lethal interaction with PLK4 inhibition that results in aberrant mitosis and ultimately cell death. Based on this data and on the patient opportunity Phil described, we initiated a drug discovery program that culminated in the identification of RP-1664. RP-1664 is a potent and selective inhibitor of PLK4, inhibiting the enzyme with an IC50 of 1 nM and inhibiting cell proliferation in the low double-digit nanomolar range across TRIM37-high cell lines. vitro selectivity assays were very promising, with no activity against the Aurora kinase family, which has been seen with previously published PLK4 inhibitors. RP-1664 has a favorable ADME profile and is being progressed towards the clinic in the first half of 2024. We tested RP-1664 in two distinct isogenic cell line pairs. On the left are MCF7 cells that have TRIM37 high. This, in this cell line, PLK4 inhibition kills the control cells because TRIM37 is high. When we deplete TRIM37 with shRNA, these cells become resistant to PLK4 inhibition. In the right panel, the RPE cells are either wild type for TRIM37 or engineered to overexpress TRIM37. Again, this drove a hypersensitivity to PLK4 inhibition when TRIM37 is high. We then investigated several different endpoints specific to PLK4 inhibition in cells to confirm the mechanism of action. We demonstrated that PLK4 is inactivated in the left panel, results in abnormal centriole number and aberrant mitoses in the middle panel, and ultimately activates p21, leading to tumor cell death in the right panel. We also tested a panel of cell lines that had normal levels of TRIM37 and compared them to cells with TRIM37 high. The majority of TRIM37 high cells were potently inhibited by PLK4 inhibition, whereas most of the wild-type cells were much less sensitive. We moved these findings into in vivo models to further test the TRIM37 hypothesis. RP-1664 was tested in three different breast and non-small cell lung cancer CDX or PDX models. We saw a clear dose response with robust monotherapy activity, ranging from stasis to regression in this set of models. Given the high prevalence of TRIM37 high in high-risk neuroblastoma, we tested RP-1664 in two different CDX models. We saw a clear dose response with both models demonstrating deep monotherapy regressions. Through a collaboration with the Children's Hospital of Philadelphia, we extended these findings into a larger set of neuroblastoma CDX and PDX models. Five out of six of these models led to deep, durable regressions, up to 6+ weeks of dosing. As we normally do, we also tested several intermittent schedules to understand their impact, if any, on efficacy. To do this work, we used a child formulation of RP-1664 to mimic the predicted human PK profile. In both models, we demonstrated that a range of schedules from three days on, four days off, to 14 days on, seven days off, resulted in similar efficacy pre-clinically. This data will be used to inform our dose schedule work in the clinic. To be able to assess PD clinically, we have developed assays to monitor key biomarkers downstream of PLK4 inhibition. These include abnormal centrioles, mitoses, and upregulation of p21. These assays will be used for the evaluation of tumor PD and potentially surrogate tissue during a phase I trial. A focused and capital-efficient phase I trial is designed to clinically test RP-1664. We'll start with a dose escalation in adult/adolescent solid tumor patients with TRIM37-high status and additional biomarkers of sensitivity to PLK4 inhibition. Following key dose and/or safety milestones, we plan a two-prong approach: a TRIM37-high expansion in adults with various tumors at RP2D, and for the second, testing RP-1664 in high-grade pediatric neuroblastoma and possibly other TRIM37-high pediatric tumors. We are in advanced discussions for potential clinical collaboration to execute these pediatric trials with a substantial cost offset to Repare without giving up commercial rights. In this later study, we will be able to also use a pediatric formulation to facilitate dosing of smaller children. These two studies, carefully designed in collaboration with both medical and pediatric oncologists, will give early insights into both the highly biomarker-enriched neuroblastoma opportunity and the TRIM37-high adult tumor opportunity. In summary, we believe the data for RP-1664 demonstrates highly promising preclinical efficacy for TRIM37-high tumors. The TRIM37-high opportunity addresses a significant population of greater than 63,000 patients with clear unmet medical need and the ability to move quickly into the biomarker-enriched neuroblastoma patient population. RP-1664 is a highly potent and selective PLK4 inhibitor that routinely drives robust regressions across the preclinical models tested by ourselves and by our collaborators. This is driving high excitement about the potential for RP-1664 as we move inefficient and cost effectively into the clinic in the first half of 2024. Phil, will you now lead us into RP-3467? ... Thank you, Mike. We believe RP-3467 has the potential to be a best-in-class Pol theta inhibitor. What's really exciting is that RP-3467 has demonstrated compelling synergistic efficacy without added toxicity across a number of preclinical models when combined with multiple modalities. This is the case when RP-3467 is combined with PARP inhibitors, RLTs, and chemo ADCs. RP-3467 has the potential to add meaningful value to our portfolio, given the global market segment for these modalities, ranging from roughly $3 billion for PARP today, to $5 billion for ADCs, and up to $8 billion for RLTs. We have designed a capital-efficient phase I program to help us determine safety, optimize dosing, and guide us to the most impactful clinical combination. Thanks, Phil. DNA-damaging events occur within cells every day, and our cells evolve different pathways to deal with these events. One type of DNA damage, double-strand DNA breaks, can be particularly genotoxic to cells. Cells have evolved three main pathways to fix DNA double-strand breaks: non-homologous end joining, or NHEJ, homologous recombination, or HR, and microhomology-mediated end joining, or MMEJ. Pol theta is required for MMEJ in double-strand DNA break repair, and is the only known cellular mechanism to repair these breaks during mitosis. Because this mechanism is not the main approach a cell takes to repair DNA double-strand breaks, Pol theta inhibition is predicted to be highly tolerated. This is supported by its minimal expression in normal cells and Pol theta knockout data from mice, where no significant phenotype was observed. However, tumor cells that have elevated double-strand DNA breaks due to genetic alterations, like BRCA mutations, or are subject to double-strand DNA break-inducing therapies like PARP inhibitor, RLT, or some chemotherapy ADCs, can become dependent on Pol theta and MMEJ for survival. This explains the broad, broad set of potential therapeutic opportunities that Phil noted earlier. Pol theta is a unique multifunctional enzyme with both the DNA polymerase and DNA helicase domain. We and others have shown that both domains are necessary for cellular activity, and therefore inhibition of either domain should have a similar therapeutic effect. Early in our research, we used a structure-enabled drug discovery approach to find highly potent and selective inhibitors of both the polymerase and helicase domains of Pol theta. A key finding from these efforts was a huge cellular falloff in potency of the polymerase inhibitors from enzyme assays to cellular assays. This made driving SAR to find true drug-like molecules with potencies consistent with progressing into man a significant hurdle. We saw this both with our inhibitors as well as with those of others. However, when we tested our helicase inhibitors, we saw a normal falloff in the potency to cell assays. This allowed us to create what we now believe has the potential to be a best-in-class Pol theta inhibitor targeting the helicase enzyme. RP-3467 is a highly potent and selective inhibitor of Pol theta helicase. It inhibits the enzyme with an IC50 of less than 250 pM and inhibits cellular proliferation in the low single-digit nanomolar range across BRCA2 null cell lines with homologous recombination deficiency. There's no activity seen in a panel of helicases, and RP-3467 does not inhibit the Pol theta polymerase domain. It has a favorable ADME profile, was clean in Panlab s, and is moving to the clinic in the second half of 2024. Cell assays demonstrated RP-3467 blocks Pol theta-mediated DNA repair, with IC50s that correlate with the inhibition of cellular proliferation. When tested in an isogenic pair of cell lines, RP-3467 only inhibited cells that were BRCA2 null and had no effect on the BRCA2 wild type cells. This massive synthetic window is consistent with literature data demonstrating Pol theta loss is well-tolerated in normal cells. Finally, we demonstrated in vivo monotherapy efficacy in a BRCA2 null background, driving around 60% tumor growth inhibition. We believe RP-3467's greatest therapeutic opportunities are in combination with double-strand DNA-damaging agents. One of these approaches is PARP inhibitor, with the rationale outlined here. In BRCA-proficient normal cells, PARP inhibitors induce double-strand DNA breaks that are repaired by homologous recombination. However, when used to treat tumors with HR deficiencies, the cells become dependent on Pol theta-mediated MMEJ. Therefore, when you inhibit Pol theta and PARP together in tumors with a key set of HR deficiencies, you drive robust cell death. As a reminder, and to go a bit deeper into some of Phil's earlier numbers, the HR-deficient patient population where PARP inhibitor is registered represents approximately 25,000 patients across a range of tumors. We've broken this down to both first-line and PARP inhibitor-resistant populations to further highlight this opportunity. With the emergence of the potential best-in-class PARP-1 selective inhibitors in the clinic, we tested RP-3467 in combination with both PARP 1/2 and PARP-1 selective inhibitors. Both inhibitor classes synergized with RP-3467 in vitro. We tested the RP-3467 plus olaparib combination in vivo in BRCA2 null tumor background. This combination drove complete regressions across a broad range of doses from 0.3 mg/kg-10 mg/kg. These regressions were highly durable. As can be seen here, we followed the tumor for up to 90 days post-treatment, a finding that is rare with aggressive, rapidly growing preclinical models. This is driving significant excitement for the combination, where there is remarkably no body weight change versus olaparib alone. The main challenge seen clinically with PARP inhibitor combos is hematologic toxicity. Thus, we ran an experiment in mice to look for any signs of additive or synergistic tox in the heme compartment. This slide shows the outcome of combining 10 mg/kg, the high dose of RP-3467, with a formulated dose of olaparib that mimics the human exposure. The combo was extremely well-tolerated and showed no signs of any additive nor synergistic tox in the heme compartment. This is again consistent with the hypothesis that inhibition of POLθ alone or in combination will be uniquely well-tolerated. We extended the in vivo combination studies that I just showed you into PDX models with endogenous deleterious alterations in BRCA one or two. Again, the combination of RP-3467 plus olaparib resulted in complete regressions across these tumor models. In addition to the PARP inhibitor combinations, we are very interested in radiotherapy combinations. Radiotherapy drives double-strand DNA breaks and also offers an excellent opportunity for RP-3467 combination. Various forms of radiation drive double-strand DNA breaks in cancer cells and can be transferred into mitosis. POLθ's essential role in repairing these breaks provides a natural combination opportunity. We are initially focused on radioligand therapy combinations, given the clinical success of this space, driving a compelling commercial opportunity for RLTs of over $1 billion. With this opportunity in mind, we tested an RLT agent in combination with RP-3467. We found that this combination drove a statistically significant overall survival benefit of the combination versus a full dose of RLT in an HR-proficient background. This data is consistent with testing the combination based on the RLT patient selection approach. For example, the PSMA or FAP target ligand expression. Finally, we tested the potential of RP-3467 in combination with chemotherapies that result in double-strand DNA breaks. We studied both carboplatin and topoisomerase inhibitors, as used in several approved ADCs. In vitro, both combinations demonstrated synergy and supported in vivo testing. When tested in vivo, we demonstrated clear combination benefit with full clinically relevant doses of both chemotherapies. These responses were durable, and there was no added toxicity based on body weight of the combo versus either agent alone and is supportive of testing chemo ADC combination clinically. We plan to initiate a phase I dose-finding study in the second half of 2024. This phase I study is designed to enable potential phase I/II studies examining RP-3467 in combination with PARP inhibitors, RLT, and/or ADCs, for which we may consider clinical collaborations as appropriate. In summary, Polθ is a promising therapeutic target, in particular for combination studies with the three DNA-damaging therapies we discussed. We believe RP-3467 could be a best-in-class inhibitor, in our hands, has demonstrated compelling preclinical synergy in combination with PARP inhibitor. We've also demonstrated combination efficacy with both RLT and various chemotherapies in vivo. RP-3467 is extremely well-tolerated with all combination tested preclinically, and I'll conclude by adding that we expect to initiate a phase I study in the second half of 2024. Thanks, Mike and Phil. I hope it's now clear why we're excited, as we are, by the potential of RP-1664 for the treatment of TRIM37-high tumors and by the large potential of RP-3467, our Pol θ inhibitor, in combinations across a wide range of tumor types. Looking ahead now to upcoming milestones, we expect to advance 1664 into a phase I clinical trial in the first half of 2024, and the same for RP-3467 in the second half of the year. We also reiterate our prior guidance across the rest of the portfolio. We have a clear focus on clinical execution and are supported with a strong balance sheet that provides cash runway into 2026. This concludes our prepared remarks. I would like now to open the call for questions. Due to time constraints and to ensure equitable participation, we would kindly ask that you limit yourselves to one question and one follow-up during the Q&A, and that you limit your questions to RP-1664 and RP-3467. Operator? We will now begin the question-and-answer session. To ask a question, you may press star then one on your telephone keypad. If you're using a speakerphone, please pick up your handset before pressing the keys. To withdraw from the question queue, please press star then two. Our first question will come from Jeff Hung with Morgan Stanley. You may now go ahead. Thanks for taking my questions. There are multiple PLK4 inhibitors in development in tumors with TRIM37, but what differentiates RP-1664 from other PLK4 inhibitor candidates? And then I have a follow-up. Okay, so currently we believe there is one compound that's in the clinic, and then there is at least another compound we know from another competitor that's progressing towards the clinic. The compound that is in the clinic equally inhibits the Aurora kinases as well as PLK4 and does not demonstrate the same synthetic lethal window that you see with a truly PLK4-selective inhibitor. Okay, and then you talked about with RP-3467, what is your current thinking on combination potential with RP-1664? Is this limited by potential safety, previously seen with the class, and any thoughts on how safety might look with RP-1664, particularly neutropenia? Thanks. We think RP-1664 is a very compelling monotherapy opportunity currently. We are progressing different ideas around combinations, but we're not yet revealing those opportunities. Thank you. Our next question will come from Chris Shibutani with Goldman Sachs. You may now go ahead. Hi, everyone. This is Charlie on for Chris. Thanks for taking our questions and congrats on the progress. Just wondering, with the future combination of opportunities for 3467, wondering what the strategy is there. Are you looking to potentially partner with, a large cap pharma, company that could provide the PARP inhibitor or the radioligand opportunity for you to, to combine? And I have a follow-up. Thanks, Charlie. Great question. As always, we are on a constant mode of understanding the natural partners for all our assets. Our new programs give us two more arrows in our quiver, and I'll say both programs offer multiple opportunities to collaborate with pharma and biotech. I think particularly as you're pointing to, there's enormous potential to support the differentiation upfront of multiple emerging PARP-1 selective agents. I think there's clear evidence that Mike shared that support the ability of 3467 to improve efficacy and reduce AEs in RLT, which has become a highly competitive field. And there's clear opportunity to synergize with ADCs, again, potentially reducing AEs and improving efficacy. So I guess in short, across the board, this is a great opportunity to think about partnering. Great, thank you. And then, one more on 3467. Just wondering if at this time, you know, I know that previously you had another Pol theta candidate that was going to be progressed at the clinic, and you opted for 3467. Wondering if at this time you can kind of characterize what it was about 3467 that caused it to be progressed forward. Thank you so much. Yes. I think, when we looked at 2119 compared to 3467, really we just saw that routinely 3467 at extremely low doses was driving regressions across all the models and complete regressions. Whereas 2119, we saw that this varied between stasis and regression. So we think that this was a very unique molecule with both its potency and selectivity, that was really driving a differentiated phenotype in vivo, in really what we thought was necessary to drive the best-in-class potential opportunity. And that point, of our goal of having what we believe a best-in-class compound, given the really competitive dynamics around Pol theta, that we think are already in place and coming, our focus was really a best-in-class compound. We think we have a potential best-in-class compound here. Okay, that's great. Thank you all so much, and congrats again. Our next question will come from Marc Frahm with TD Cowen. You may now go ahead. Thanks for taking my questions, and congrats on getting all this data together for these molecules. Maybe for RP-1664, can you, Mike, walk through how you're defining TRIM5, TRIM37 high, and maybe how dose responsive is that synthetic lethality interaction that you're seeing in terms of the level of expression, or is it more of a threshold effect? Yeah, great question. So we're calling it TRIM37 high because we find that gains or amplifications or cells that had high expression that we were able to define using a number of preclinical parameters were all driving hypersensitivity to PLK4 inhibition. We'll be using these in different ways as we progress into the clinic. As for the kind of synthetic lethal therapeutic index that we saw, we were seeing somewhere between that five and 10-fold therapeutic index that we were looking at. And we're continuing to identify additional drivers of sensitivity in addition to just TRIM37 high. Should we expect some of those other synthetic lethal interactions to be part of the trial, like you've done with your other programs, or are they not ready for that quite yet? I think we'll be flexible to be able to include those into the trial, as we start to understand them better. Really, they're again driving that similar type of a mechanism of where there are additional alterations that could drive changes to the PCL. Good. Thank you. Our next question will come from Joe Catanzaro with Piper Sandler. You may now go ahead. Hey, everybody, thanks for the updates here. Two from me. Maybe first on Pol theta. Mike, I'm wondering if you know or can speculate why there was a meaningful discrepancy between cellular and biochemical potency for the polymerase inhibitors, and is maybe does that just indicate that the helicase function is maybe more relevant than the polymerase function within cellular contexts? Thanks, and I have one follow-up. Yeah. So, from the work that we did, looking at our own polymerase inhibitors across a range of different inhibitors, we found, as well as those that were in the literature, we find that all of them bind to an allosteric site within the polymerase, and that allosteric site is only available when the polymerase is bound to DNA. We feel that this was the reason is that you had to have a mass excess of the inhibitor to be able to bind that site and inhibit the polymerase before it started its action, where it bound to the DNA, and we believe that was the rationale for this large cellular fallout. ... 1664, I, I think you mentioned earlier, there's been at least one taken through the, PLK4 inhibitor taken through the clinic. Yeah, I think it was dose-limited by, by neutropenia. Is it your expectation that the selectivity for 1664 can maybe improve upon that? And then, maybe relatedly, is there anything you've learned from camonsertib in managing myelosuppression there that you could apply early into 1664's dose escalation? Thanks. So I think the short answer is yes to all of the above. In that, we do believe that having more selectivity in just the PLK4 and not the Aurora kinase inhibitor, the Aurora kinases, really drove this differential sensitivity, giving a better therapeutic window when we move this progressive forward. Okay, thanks. I think the best summary is the only clinical compound out there is a really dirty compound. Our next question will come from Charles Zhu with Guggenheim Securities. You may now go ahead. Hey, guys. Good morning, and thanks for providing this update and for taking our question. Maybe just one clarifying question on your early clinical development for RP or planned clinical development for RP-1664. Could you talk a little bit about how you are, you know, provide some color around how you are planning to make this thing a little bit more, perhaps a little more capital efficient relative to what you have previously done with your current clinical stage assets? You know, which histologies will be in-house, which will be potentially partnered, and just given the prevalence of TRIM across all these different histologies, where you could, you know, narrow focus or maybe make some of those decisions. Thank you. Thanks for the question, Charles. I think you should expect us to provide more detail as we head into the clinic with this compound that we're not going to be sharing today. Again, it's pretty competitive space. But suffice to say that we are certain that we can be a lot narrower, laser-focused in how we conduct this phase I, relative to the imperatives that drove how we developed camonsertib and lunresertib in their very earliest clinical trials. And we are certain that this will allow us to get through a phase I with much less capital in total to get our answer than you would have seen in camonsertib and lunresertib. And I should emphasize again, in case this was lost, this is a monotherapy effort. We don't have to understand and aren't seeking to understand the combination potential of RP-1664, because this is a single agent monotherapy strategy. Got it. Great. Thank you. Our next question will come from David Martin with Bloom Burton. You may now go ahead. Yes, thanks for taking my questions, and congratulations on the progress. First question relates to one of the earlier ones. The amount of TRIM37 high that you're getting in the models, is that reflective of physiologic conditions in the human tumors? Yes. That's a simple answer. Okay. And I think the question was asked, but I wasn't sure on the answer. Like, are there levels of TRIM37 elevation where this synthetic lethal cuts out? And how high does the TRIM37 elevation have to be? Yeah. So yes, yes, there is. The exact levels, we have insights into that that we're not going to be currently sharing, but it has to be enough TRIM37 to degrade the PCM, right? So that's the key finding. So it's not like an RTK that's amplified. Again, it's just, you just need a little bit extra to be able to degrade that PCM and then result in a dependency. And the PCM- Okay, great. Just a reminder. Yep. Okay, thanks. So my second question, the other Pol theta programs that are in development now, can you remind us, are they inhibiting both the polymerase and the helicase? And if they are also inhibiting the polymerase, would that disadvantage them? So there are three inhibitors in the clinic, two from Artios that are both polymerase inhibitors, and a helicase inhibitor that IDEAYA and GSK are bringing forward. Unfortunately, this time we don't know what their clinical compounds are, so we've been unable to test them. Our decision to go after the helicase is really because that's where we were able to combine this ultra potency that we think is really necessary, along with the right drug-like properties, to be able to progress it to the clinic. Okay, thanks. That's it for me. This concludes our question and answer session. I would like to turn the conference back over to Lloyd Segal for any closing remarks. Thank you. Sorry. This concludes our prepared remarks. I would now like to open the... Sorry. Sorry Sorry about that, guys. Thank you everyone for your time today. Also, a special thank you goes to the entire Repare team for advancing our mission to be the leading precision oncology biotech, focused on novel synthetic lethality medicines that meaningfully improve the lives of people with cancer. We look forward to continuing to update you on our progress. I hope you have a great day. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.