You there. For our last session of the day, thanks so much to the team, IDEAYA Biosciences, for joining us. Maybe just quickly an introduction from both of you, and if you could, a brief overview, as it stands today and with respect to, like, what you see as value drivers of it. Sure. Well, first, thank you so much, Corinne, for the kind invitation to participate at your event this year. Yujiro Hata, founder and CEO. I can maybe let Darren do a quick introduction as well, and happy to go through a quick overview. Hi, I'm Darrin Beaupre. I'm the Chief Medical Officer at IDEAYA Biosciences. I've been with the company for about 7 or 8 months now. My background is I'm a medical oncologist, hematologist, PhD in cancer biology, started out at the Moffitt Cancer Center, but I've been in the industry 16 years, joined IDEAYA because of an amazing pipeline that you're going to hear about. Yeah, great transition, pipeline. IDEAYA Biosciences, we were founded 7.5 years ago. We're a leading precision medicine oncology company. We have a significant focus in the area of synthetic lethality. Today, we have three first-in-class programs in the clinic. Our most advanced program is darovasertib here, targeting a very specific genetic mutation called GNAQ, GNA11, which is very high prevalence in metastatic uveal melanoma. Here we've launched into a first-line accelerator approval study in the first-line setting of metastatic uveal melanoma. We've also launched a company-sponsored Phase II study in both neoadjuvant and adjuvant. Our second clinical program is IDE397. This is a first-in-class MAT2A inhibitor, targeting a very large patient selection biomarker called MTAP deletion, which is believed to represent roughly 15% of all solid tumors. Here are two core focus areas. We just announced the Phase II monotherapy expansion dose has been selected. Here we're targeting very specific tumor types, including lung cancer, gastric cancer, as well as bladder cancer. Also significant focus on our partnership with Amgen to combine with our MTA-cooperative PRMT5 inhibitor. Here, just a few weeks ago, we announced IND clearance, and there what we could say is that patient dosing will begin here very shortly. Our third first-in-class program is IDE161, which is a PARP inhibitor. Here, the patient selection biomarker is HRD. We have a significant focus in ER-positive, HER2-negative HRD breast cancer, which we believe represents 10%-14% of breast cancer. Then we have a very deep portfolio behind that. Pol Theta, another first-in-class program, that would be our fourth in the clinic. That IND should be happening also here very soon. All the technical aspects to file the IND is now behind us in terms of GLP toxicology studies. Now it's just about getting through pharma governance at GSK. Lastly, our fifth potential first-in-class clinical program would be Werner helicase, and that candidate nomination continues to be on track for this year. Great. Maybe let's start with darovasertib. You reported clinical data a couple of months ago from Phase II studies in both metastatic and neoadjuvant uveal melanoma, as you said. Maybe just, like, briefly review the data that you shared. Sure. Darrin, want to take that? Yeah. The Phase II data that we presented was really quite dramatic. Maybe I could set the stage for you. Talking about a disease that really doesn't have any effective therapies. Just as I talk about the data, maybe we could use some comparisons, which is. Uh-hmm. What we would consider standard of care. The kind of things that people use in metastatic uveal melanoma today are things like immunotherapy agents, like combinations with ipilimumab and nivolumab. Sometimes they use single agent pembrolizumab, for example, or in patients who are not eligible for immunotherapy, they give chemotherapy. That's sort of standard of care. What might a standard of care agent deliver in this patient population? You know, standard of care delivers, you know, a response rate of 5% or 10%, a progression-free survival of about 3 months. Really not terribly impressive. The other thing I want to emphasize is that when I make some comparisons relative to our data, keep in mind that the patient populations for which these other agents have been studied tend to be to patients with less tumor burden, less aggressive disease. They have lower LDH. They have lower amounts of extrahepatic disease. They have lower amounts of tumor burden. We're talking about even in the best of circumstances, where patients aren't really as bad off, those numbers are still pretty dismal. Of course, we presented data both in the first line and the relapse setting that really dwarfs that. You know, our overall response rate in treatment-naive patients was 45%, so an unprecedented overall response rate. Our progression-free survival, whether you're in first line or in relapse disease, is at least double what standard of care can deliver. That's really has set us up for the stage of doing this registration trial, where we will prove once and for all that what we have with the darovasertib combination is the most effective therapy in the uveal melanoma setting, where we'll be taking on standard of care, which could be either Ipi-Nivo, pembro, or chemotherapy head-to-head. Fortunately, after our discussion with the FDA in our Type C meeting, we've been able to come up with a seamless design that allows us to execute not only a Phase II portion that would allow the potential for an accelerated approval based on improvement in progression-free survival, but also continuing to enroll the study for the second primary co-primary endpoint of overall survival, which is a key endpoint for full approval. That really that's the information that set the stage for the registration trial. That's what we're lined up to do in the registration trial, and starting getting patients enrolled is imminent. Great. One of the highlights of the data, among many, was the efficacy in hepatic-only metastatic uveal melanoma. Can you talk to us about the implications of that population and the data you showed there? Yeah, there's a couple of things there. You know, number one is it's, it's a patient with perhaps disease only in the liver, so perhaps it's more like the population you might see that were in those other studies that I mentioned, that had patients who were less, had less extrahepatic disease, less tumor burden, right? Their disease wasn't advanced. That's key because if you look at our progression-free survival in that group, it was 11 months, which is really quite amazing. As you might expect, even higher than we saw in the all-comer population. Again, sets the stage well that progression-free survival is an endpoint that we really should hit in our registration trial. The other point is, as you know, there are liver-directed therapies out there, right? There are people who talk about giving high-dose chemotherapy in the liver and having to put a patient in the intensive care unit, maybe stay in the hospital overnight, et cetera. Big, big procedure. Here we can do just as well with a pill. There's no liver-directed therapy that's shown any data better than what we've had in terms of response, in terms of progression-free survival. Again, once again, I think we're showing with simple, you know, administration of oral medication, we can deliver as good, if not better, in many cases, anything out there. Right. You mentioned it, but I think the Phase II endpoint, the primary endpoint for registration, just help us understand how you selected it, and what you're powered to show? Progression-free, you know, when you do a randomized trial, progression-free survival and overall survival are the key endpoints in typical Phase III oncology trials. That's the first thing. Second thing is, really not too hard of a benchmark. You know, if we feel like if we double the progression-free survival, that would be a key for success as the first co-primary endpoint. With overall survival, you know, we're thinking, you know, if we improve overall survival by 6 months or more, we'll again, hit where we want to hit. Those are sort of benchmarks for where we'd like to be, and I think those would show a dramatic improvement relative to standard of care. Yeah, understood. What historical context can you provide us to help us think about the pace of enrollment in these registrational studies? Yeah, maybe I'll just quickly take that. Historically, in the past, we have enrolled at clips as high as 50 patients a month. Right now, for our Phase II study, we've been in a limited number of sites, so about 12, roughly 12 sites in the U.S. Now, for the U.S. sites, for the registrational trial, we're going to be multiples of that, and then also we'll be enrolling globally, in particular in Europe. We think enrollment will not be an issue based on our historical experience here. I'd only add to that from the perspective of, you know, meeting with investigators, a tremendous amount of enthusiasm for this study. In fact, you know, we're getting a lot of requests for compassionate use even so. Mm. There's really a high demand for the combinations. We don't see that enrollment's going to be an impediment. Yeah. One of the decisions you made is to restrict the registrational trial to HLA-A2 negative patients. Talk to us about that decision. Maybe we'll start there. Sure. Sure. Well, maybe I-- kind of getting at that question a little bit differently in that let me maybe lay out the strategy for how we want to get darovasertib and crizotinib in all the patients with uveal melanoma. You know, the way we've outlined our development program, it's not only the registration trial, but it's a multifaceted approach to make sure every patient with uveal melanoma has access to this combination. Of course, there's the registration trial, which will go after the HLA-A2 negative patient population. It was really the fastest and seamless way that we could get to a registration as quickly as possible, based on the fact that it gets complicated when you add in the HLA-A2 positives in terms of the control arm and the duration you have to wait in order to get the endpoints. That patient population will be covered. In addition, now, we're going into the neoadjuvant space with single agent darovasertib, and this will be HLA irrespective. It'll cover HLA positives, it'll cover HLA negatives. Again, here, we're doing a couple of very critical things for patients. One is saving the eye, a very, very critical and important thing to do for subjects, but also preserve vision. For those patients who don't have to have their eyes removed, preserve their vision. Again, that'll be in the neoadjuvant approach, then in the adjuvant approach, also, what we want to do is prevent metastases. In terms of the pie, we've got the HLA-A2 negatives covered in the metastatic setting. We'd have HLA-A2 positives and negatives covered in the neoadjuvant/adjuvant setting in primary uveal melanoma. In addition, what we're looking to do is expand out a cohort, either in our current ongoing Phase II trial or in an additional Phase II trial, where we'll look specifically at the HLA-A2 positive patient population. If we play our cards right, our dream scenario is that all of this data is going to read out simultaneously with the registration trial. You know, one of the things that the investigators are most concerned about, we get this question nine and frequently: "What are the investigators, what's their biggest concern?" Their biggest concern is being able to have access to the combination. Can you imagine? One of them said: "You know, but you're not doing HLA positives in your registration trial. How am I going to get a patient on there?" We're going to have a Phase II trial for HLA-A2 positives in the metastatic setting. We're going to have a trial for HLA-A2 negatives in the metastatic setting. That'll be our registration trial. We're going to have access for those patients with primary uveal melanoma, irrespective of your HLA status. In fact, you know, we're telling investigators there's no facet of this disease that you can't address with our, with either our combination or our single agent, darovasertib, and that's what gets them excited. Yeah. Here, kind of talking to the competitive landscape, we recently saw the KIMMTRAK launch. What can we learn from that launch as we think about the market opportunity in uveal melanoma? I think the KIMMTRAK launch, current, as you know, has well exceeded consensus estimates right out of the gates. They're on an annual clip of, you know, getting towards a quarter billion, which is obviously great. I think a key piece to this also around the HLA-A2 negative versus positive. You know, I think folks have referenced that the A2 negative is the majority of the metastatic uveal melanoma population, but as you can appreciate, there's a big difference if that's 55% or 75%. Mm-hmm. Folks may have missed it, but there was a group at ASCO that published some data, and that group noted only a third was A2 positives. We have a much larger database, and that's data that we may end up putting out there in the public in the second half of the year. Here, what we can say is, at least based on our figures, we believe A2 negative is the large majority of the patient population. Just from pure incidence and numbers. Mm-hmm. I think that's really how we think about it. You know, of course, on the A2 positive side, as Darren said, we're not forgetting about that as well. We do have a comprehensive strategy that we'll be pursuing, obviously, assuming we get approval, in the first line, A2 negatives as well. Yeah, understood. Let's maybe spend a bit of time on the neoadjuvant/adjuvant setting. What have you seen to date for that population, and how are you thinking about trial design there? Yeah. you know, the data we've presented previously is, you know, quite exciting. We have, you know, up to nine patients who have disease in their eyes that can be measured, right? They either have primary uveal melanoma or metastatic uveal melanoma that happen to have disease in the eye that could be measured. Really, in every single one of those patients, we've seen evidence of tumor shrinkage. We also presented some information about a really interesting case out of Australia. There was a gentleman who was unfortunate enough to be blind in one eye to begin with. The patient had a retinal infarct due to peripheral vascular disease. you know, he was, you know, an elderly gentleman who started developing vision problems in the other eye, his so-called good eye. Mm. - which eventually progressed to a point where he was considered clinically blind. The thought from the patient was, "Well, you know, it's my good old peripheral vascular disease is back," He went to the doctor to be evaluated. Unfortunately, when the doctor looked in his eyes, he said, "It's not from your peripheral vascular disease, it's from a uveal melanoma." Unfortunately, in his case, the tumor was large enough where the only really reasonable option was eye removal. Instead, what happened was we were contacted by Dr. Shackleton, who was very interested in the compassionate use program that we had, was able to get therapy for this patient, and after several months of therapy, the patient went up to have as much as an 80% reduction in his tumor, and then now has been converted from an enucleation to brachytherapy. In addition, he's gone from clinically blind to now having what would be considered normal sight. It's an amazing case. We've seen other evidence that things like this are going to happen. What are we doing based on some of the compassionate use data? We also have an investigator-sponsored trial that's running, where we've presented the data and shown that every patient in that study has had some evidence of tumor shrinkage thus far. What are we doing in order to get us to a point where we can have a discussion with the FDA to talk about a registration plan? We're executing on a Phase II trial, where we've actually initiated our first few sites, getting ready to enroll imminently there again. What we have is a 2-arm study. In 1 arm, we're talking about patients whose tumors are so large that their eyes have to be removed. What we're asking the investigators, instead of taking out that eye, go ahead and give 6 months of neoadjuvant darovasertib, shrink that eye down, and let's convert them to plaque brachytherapy. The objective here will be, can we shrink the tumor, number 1? Can we preserve the eye for 2? Can we maintain some vision for 3? Also, that arm is going to be followed by adjuvant darovasertib in order to prevent liver metastases, which ultimately is what leads to the patient's demise. Save the eye is one thing, that's good, we also want to save the patient, right? Which is prevent those metastases. That's what's going on in the enucleation arm. It turns out, at least in the US, that's a smaller fraction of the patients with primary uveal melanoma. Maybe 20% of patients have their eyes removed. A larger proportion are allowed to get plaque brachytherapy because they're caught early enough to have mid-sized to small-sized tumors. Haven't forgotten about those because although they're fortunate enough to not have their eye removed, that's the good news. The bad news is, once they get their radiation therapy, they go blind, clinically blind, typically, that's actually a bad outcome. What we want to do is, by giving neoadjuvant darovasertib in that patient population, reduce the amount of radiation significantly so that they can get a plaque brachytherapy with less radiation, where their eye and their vision is preserved down the road. Again, that's the short-term endpoints, which are easily manageable. The longer-term endpoint, again, would be to give that adjuvant therapy to prevent metastases. The beautiful thing about the neoadjuvant part is it can read out fairly quickly. You know, within six months, you could have enough patients where you could start thinking about what would be my plan. Maybe you could have a discussion with the FDA, and it could be that we could actually just expand out the study that's running to enough patients to allow us to talk about a registration path like an accelerated approval. You can imagine what kind of enthusiasm we'll have from patients, what kind of, sort of a momentum we're going to have from investigators. If you can say, "Well, when a patient with uveal melanoma walks in your door, and they have eye-localized disease, your first thing should be not, where do I find the radiation oncologist? It should be, where's my prescription pad, so I can write a prescription for darovasertib?" We're seeing really terrific results, and we want to get this to patients as quickly as we can, so that's sort of the path that we're taking. How do you think about the commercial opportunity in the neoadjuvant and adjuvant setting? Can you just bring that out for us? Yeah, sure. Kurt, I think the opportunity in the neoadjuvant and adjuvant setting from a commercial market is much larger than the metastatic setting. We think it's multiples larger. And basically, the way we get to that number are several aspects. One is just purely annual incidence. The metastatic setting is reported about 4,000-5,000 patients. The primary uveal melanoma, and the annual incidence is at least double that. Next, when you look at total prevalence, is also much larger. In metastatic uveal melanoma, you know, it's probably in that 15,000 range in terms of total prevalence. In the primary uveal melanoma setting, that number actually is much higher. It's about $100,000. That's based on the various calculated OS rates in the pre-metastatic setting, since the OS rates are much higher there. Of course, here, because there's nothing approved from a market perspective, when there's nothing approved in that, in that pre-metastatic setting, you don't just think about it as new patients diagnosed per year. It's all the patients that are alive that would need to get on some therapy, right? There could be that opportunity to really get that initial much larger bolus of patients- Mm-hmm. -based on total prevalence. The last part of the calculation that would help you understand the market size is really around treatment duration. As Darren noted, for neoadjuvant, at least protocol now is treat up to a maximal benefit of six months. Mm-hmm. That could go longer. In the adjuvant setting, also up to 6 months, but again. Yeah ... you could imagine you could treat up to the point of relapse, so that could be several years in certain situations. Under any circumstance, we would, we believe the treatment duration in the pre-metastatic setting should be multiples of the metastatic setting. Great. Before we move on, is there any other setting where you'd consider exploring Daro without crizotinib or any other combination? I would say our primary focus right now, is in the uveal melanoma space. With that said, there's probably two areas in particular. One is where GNAQ/GNA11 is also prevalent, and there I would say it's skin melanoma, sort of in that mid-single digit, percent prevalence, and then also mucosal melanoma, which is, higher in Asia and has been as reported as high as about 10%, in terms of GNAQ/GNA11 prevalence. The other, you may recall, we were evaluating the possibility of a crizotinib combination, specifically in HCC, 'cause we'll be targeting, liver cancer there as well. At this point, we've decided to really prioritize uveal melanoma. Yeah ... and more focus on the patient journey and target now the adjuvant than the neoadjuvant setting. Makes sense. Maybe we'll shift gears here to talk about the development candidates you've developed in-house. Before we go into the specific assets, could you just give us a sense for your discovery capabilities and, you know, the suite of capabilities you have at IDEAYA? I mean, yeah, I think over the last 7.5 years, from our view, you know, we've built, we feel we've built just a world-class organization when it comes to capabilities around functional genomics, and that entails both target and biomarker discovery, which has generated several of our key programs, including targets that I think a lot of folks know today in precision medicine oncology, such as Werner helicase, which, you know, we've been in partnership with GSK for several years. In addition, we've built a world-class capabilities as it relates to drug discovery. Here, we feel very, very confident that we could go head-to-head with any company, including pharmaceutical companies, to try to really pursue, frankly, any target in the synthetic lethality precision medicine oncology space. Here I would just highlight, we have, as you know, multiple helicases where we have either picked the candidate or is about to go into the clinic through an IND filing, in this case, Pol Theta helicase and Werner helicase, which I think is really the first time a biotech or pharma company has delivered back-to-back helicases in the area of precision oncology. For those that may know, helicases are known as notoriously very difficult targets to drug. Here, this will continue to fuel our future pipeline. Lastly, I would say, continue to hear more from us as it relates to our investment in data informatics, in particular in the area of AI machine learning, as applied to both target biomarker discovery, as well as drug discovery, in particular, lead optimization. Okay. Let's talk maybe first about IDE397. First, it's a MAT2A inhibitor being developed in patients with MTAP deletion. Could you briefly just refresh us on the mechanistic rationale for that program? Sure. Darren, you want to take that? What we're talking about, tumors that are MTAP deficient, right? That makes up about 15% of all cancers, right? When you have an MTAP deficiency, what happens is basically MTA accumulates in the tumor cell. When that occurs, it's sort of a partial inhibitor. What's nice is when you come along with a MAT2A inhibitor in that environment, what you do is you deplete out the cofactor from PRMT5, called SAM, and by doing so, you create a synthetic lethality that occurs, that causes the tumor cells to die, the tumor cells that have MTAP deficiency. That's sort of the premise behind where the MAT2A inhibitor comes in. Where PRMT5 comes in is it's, you know, it's a methyltransferase that's involved in regulating alternative splicing, and it's also can be inhibited by agents out there called MTA-cooperative PRMT5 inhibitors. A MTAP-deficient tumor is really a nice environment for a MTA-cooperative PRMT5 inhibitor to work because the MTA levels are high, so it allows that PRMT5 inhibitor to be highly effective. You come along and then further get rid of SAM, which is one of the cofactors involved with PRMT5, you know, a methyl donor, what you create is an environment really where there's really no escape of the tumors. That sort of sets the stage for why we want to do this combination. We have preclinical data that shows that when you combine the two agents, they are more effective than either agent alone. When you combine the two agents, you have a more dramatic impact on splicing than either agent alone. When you look at in vivo models with the combination, you see significant antitumor activity, potentially even cures, where the tumors regress, can't be found. We take the drugs away, the tumors don't come back. Really, the preclinical data is quite spectacular. What we're doing is a two-pronged attack clinically to address the question. Number one is we have our dose escalation, which is just completed, and you probably heard in the press release, we've started to move on to our dose expansion. We're fortunate enough to see a patient benefit from therapy with one of our key tumors. With tumor shrinkage, we've had a number of patients with tumor shrinkage, but an official partial response as well, so we're excited about the opportunity for monotherapy of our MAT2A inhibitor. That's not the focus. That's really to gain more safety data, understand the tumor types that we want to be in, and see what kind of potential we have as a monotherapy. Clearly, the preclinical data suggests that the combination will have dramatic, a dramatic impact, one that's unlikely to have been seen before by any of the PRMT5 inhibitors out there. We're forging forward a collaboration we have with Amgen to do a combination trial, which we've just announced that the IND has been filed, where those patients will be coming on study imminently to really test the combination. You know, it looks like preclinically, even at the initial dose level, where we're beginning work with both compounds, really, lower doses than are what are needed from each agent alone are sufficient to have this antitumor activity. Even early on, we could see some dramatic effects. We're excited to get this study going. We're working with a great collaboration partner, Amgen, and that study's off and running, and we're really excited about the potential. I'll say one last thing about this. People have been talking about what's going on with the PRMT5 inhibitors. Well, what's been the problem? Well, we've always said this: If you don't have the right indication, selection marker, combination partner, you're not going to see what you want to see. We're doing all of this with Amgen. The key is you have to have the right tumors, because not all MTAP tumors are made the same. If you talk to experts in the field, they'll tell you that this is the mother of all clinical studies, because really, if we can't make a huge dent in cancer with this combination, we really have to wonder where we sit with the PRMT5 inhibitors. It doesn't make any sense anymore to study it any further. This is the experiment that's going to tell the entire field in oncology what's going on with this, with this pathway. That's why we're so enthusiastic about it. You could probably tell our CMO is quite excited about this. I appreciate it. You got through, like, all of my questions. Oh, good. Okay. Maybe briefly before we move on, in terms of therapeutic index and particularly in combination, what have you seen and what are some of the preclinical models showing? Yeah, yeah. It kind of goes back to the point I made, which is a very good question because that's obviously where sort of the PRMT5 inhibitors have stumbled. You know, we've seen at doses that would be considered subtherapeutic for both agents, when you put them together, you see magic. You see really dramatic impacts on splicing. We think that at doses that are going to be very, very well tolerated and certainly were in animals, we'll be able to deliver the maximum antitumor effect with minimal toxicity. Of course, we have to do the study to prove that, but that's why we're so enthused. Yeah, in terms of the clinical study, I guess, what should we think about in terms of timelines for next updates? I know part of it is not in your control, but what can you share? Sure, I can take that one. In terms of for specific guidance, currently, we have not provided that guidance at this point yet. We're obviously now pushing forward on the monotherapy expansion, based on the dose that we've selected. Here, I would just emphasize we're very much in the early innings. When we were doing our dose escalation, you know, 90+% of those patients were not in our priority tumor type. Now we're starting to see the priority tumor types, and as we just noted, we saw an early partial response. That's going to be the focus. As we get more data, we'll discuss that internally, in terms of potential updates on that one. Here, as Darren noted, the emphasis, at least right now, is really around our combination strategy. Here, I think the next steps, for the public will be, the clinical protocol should be publishing, we believe, here very soon on ClinicalTrials.gov. Folks will find out several key aspects of the trial, including the size of the trial and enrollment. Here, all we can tell you is that it's a substantial enrollment target that the parties are pursuing. Here, our view is that the parties are looking for a definitive answer from the combination. Second, is the trial is focused on a very specific tumor type, which also I think is a positive benefit. We should be able to hopefully identify a signal much faster through that type of strategy. Once I would say enrollment continues, and obviously, if we do see an early signal, you know, hopefully we'll have better visibility on potential timing of data updates there. Yeah, great. maybe moving on to 161. It's a PARP inhibitor. You introduced it earlier this year. You're already in the clinic. like, what's driving all the enthusiasm there? Darren was just at ASCO. I had a lot of conversation on this program. Yeah -with investigators, so. Yeah, I spoke to Tim Yap, who's sort of leading the charge here for this program. He's someone who's been working in the HRD space for some time. It's an interesting discussion we had. We talked about how the seas are parting here for the PARP inhibitors, and sort of they've lost their sort of luster and how, you know, they really haven't really delivered the promise that people hoped they would. They're toxic, they're difficult to combine with other agents, hard to get into earlier lines of therapy. They're losing favor, they're losing their labels. You know, our PARG inhibitor is really well-positioned to come into an open space to really make a dramatic impact. The focus is initially on HRD patients with homologous recombination deficiency, we see in our vision and our long-term vision that there is potential to go outside that patient population. Suffice it to say, I think, you know, we come in sort of in a pathway that's been validated. Our mechanism of action is a bit different. What we've seen preclinically is we can work in tumor cells that are sensitive to PARP inhibitors, we can work in tumor cells that are insensitive to PARP inhibitors, and we can work in tumor cells that, you know, are a little bit surprising from where a PARP inhibitor would stand. Now HRD, there's a lot of unmet medical need in this space. We know the PARP inhibitors were, you know, approved in prostate cancer, breast, and ovarian cancer. Okay, we understand that, but there are a lot of other tumors where homologous recombination deficiency can be found that don't have a drug that can be effective. In our trial, which just initiated, we're going through the dose escalation now. We're going through that rather rapidly. We're going to be enrolling patients with homologous recombination deficiency, irrespective of their tumor type, to get a sense of where we stand in the HRD space. As we expand out, we're going to focus on some tumor areas where we've seen some really exciting preclinical data. These are patients with ER-positive breast cancer who have homologous recombination deficiency. We've seen some really exciting preclinical data there. Ovarian cancer patients, about 50% of those will have HRD. We'll be looking at those. In addition, we'll have a basket study that will allow us to cut across a number of different tumors with homologous recombination deficiency. I'd finish by just emphasizing there are a number of biomarkers that we're looking at that may be predictive of a response that take us outside of HRD. In addition, we have the opportunity, with some really novel combinations to make some impacts there as well. You may want to say a little bit more about that, Eijiro. Yeah, no, I think there's a lot of interest on the pharma side on this program. We've been trying to focus that interest on combinations. Yeah. We've already signed a few agreements there. This is for preclinical characterization. You know, these would be, frankly, massive markets if successful, and I think our investors and analysts would be very, very excited to hear what they are. That's coming in the future. Just the last piece I would add is the clinical trial execution has been going great. As you know, Craig, we cleared the first cohort. We're now in the second cohort. We've already started dosing patients there. Everything looks as-. Yeah ... as we had hoped. Every spot in the 2nd cohort is already spoken for. We already have a wait list beyond that. All we can also say from a PK perspective, it's exactly what we would hope it would be from cohort 1. Yeah. The shape of the curve is also kind of as what we had hoped. Yeah, it's firing on all cylinders, and clearly, this program is becoming that third leg of that stool, and obviously the fourth being everything we talked about with the platform. Yeah. We haven't even touched on them. We only have 2 minutes left. Sure. The helicase programs that are partnered with GSK, I guess, can you give us just, like, a brief flavor of what you're excited about there? Yeah, look, I think GSK has been a wonderful partner to us for both of these programs. We're, you know, extremely appreciative. I know they were here just earlier presenting earlier this week. You know, here it's really about, I think both programs really represent what we're about, which is going after first-in-class opportunities. You know, we believe each of these programs have blockbuster potential. Obviously, Pol Theta, I think significant opportunity in combination with PARP. We know a lot of data out there as it relates to the mechanism of resistance with BRCA versions. We feel fairly confident Pol Theta will help with that. Lastly, Werner helicase. There's no more robust synthetically interaction in the cancer genome than Werner helicase with high microsatellite instability. Here we think clearly an opportunity in combination with checkpoint. We hope to be in the first wave of programs in the clinic, and we feel we have an excellent molecule moving forward. Yeah. You've talked about a bunch of things happening, including partnerships, et cetera. How do you think about allocating capital across your discovery programs, as well as the clinical stage candidates and where partnerships might kind of help fill in the gaps? Sure. You know, we've always taken a hybrid approach to enable us to do more, right? I think the advantage with our partnership with GSK, program 4 and 5, I mean, collectively, they will be paying for 90% of the cost of those two programs. As these go into the clinic, that enables us to do more. I think we'll continue to do that. For us, we, you know, we want to continue to invest as much as we can, both in our research as well as clinical development, and continue to also push for the next wave of programs coming into the clinic. There's more that the public doesn't know about that we're very excited about, and obviously now we're pushing forward into a registrational trial to try to get that, our lead program on the market. Amazing. Well, thanks so much for joining us, to the team from IDEAYA, to everyone who joined us for this week at the conference, both here and via webcast. Great. Thank you so much. Thank you.