All right, welcome everyone to the 44th Annual JP Morgan Healthcare Conference. My name's Anupam Rama. I'm one of the Senior Biotech Analysts here at J.P. Morgan. I'm joined by my squad: Priyanka Grover, Joyce Zhou, and Rathi Pillai. Our next presenting company is IDEAYA, and presenting on behalf of the company, we have CEO Yujiro Hata. Thank you, Anupam, for the introduction, and thank you again to JP Morgan for allowing us to present at the 44th Annual Healthcare Conference at J.P. Morgan. Please note, we'll be making forward-looking statements today, and please refer to our SEC filings as appropriate. Since IDEAYA's founding 10 years ago, we've had several strategic guideposts that have led our organization, including first-in-class targets, predictive biomarkers, rational combinations, and early-stage disease. Those strategic focus areas have led us today to have four clinical pipeline focus areas that we'll cover during today's presentation. The first is darovasertib. This program is now in a registrational study, and we are guiding towards top-line results this quarter to enable our potential first accelerated approval filing in the United States. We believe darovasertib is truly a unique molecule and has the opportunity to potentially define this indication of uveal melanoma across both the neoadjuvant, adjuvant, and metastatic settings. Next is our focus in the area of ADCs DNA damage repair. For many of you that have known us for the last 10 years know that DNA damage repair has been one of the core scientific focus areas for the company, and we believe one of the greatest opportunities in the antibody-drug conjugate space is to identify combination opportunities to extend durability and ultimately survival. Next, third, is our focus on the area of MTAP deletion. For those that you may know, MTAP deletion is often co-deleted with another key tumor suppressor gene called CDKN2A, which is on the 9p21 chromosome. Unfortunately, today, there are no currently approved therapies for this biomarker-defined patient population, which represents roughly 15% of solid tumors. And I would say, alongside RAS, MTAP perhaps represents one of the largest patient selection biomarkers being pursued by the industry today. Lastly, is our focus to address what we believe is one of the greatest scientific challenges in the area of cancer, which is the challenge of tumor heterogeneity. If I were to highlight one program that really highlights our commitment to address tumor heterogeneity, it's our recent phase I molecule, IDE574, our dual KAT6/7 inhibitor, which, alongside another major pharma company, we have the opportunity to have another potential first-in-class agent in the clinic. What has fueled this productive pipeline and engine is a proven drug discovery engine, and I'll highlight just several key points on this slide. First is that we have internally discovered six clinical stage molecules across six potential first-in-class targets, including very difficult target classes such as helicases, polymerases, and glycohydrolases. In addition, we've also pioneered key selectivity profiles across very key paralogs and protein families, including kinases and lysine acetyltransferases, as an example, KAT6. What this has resulted in is what we believe is one of the deepest clinical precision medicine oncology pipelines in the biotech industry. We have currently nine clinical stage molecules that are advancing, as noted earlier, darovasertib, our most advanced program, and really the strategic premise of building this type of deep pipeline is really two areas. First is this will enable us to have wholly owned combinations across critical nodes of key pathways. Second is the ability to address multiple solid tumor indications of high immune need, including uveal melanoma, small cell lung cancer, colorectal cancer, breast cancer, among many others. Our lead indication is uveal melanoma. Uveal melanoma, unfortunately, is a rare but very aggressive form of cancer, and unfortunately for patients, this indication has one of the worst prognoses in terms of solid tumor indications. Survival typically ranges roughly 10-12 months, and as we can see here, the five-year survival rate is 15%-20%. Unfortunately for these patients, there are limited treatment options. The majority of these patients have no approved therapies available to them in the metastatic setting. There are no approved systemic therapies in either the neoadjuvant or adjuvant setting. The mechanism that our lead molecule, darovasertib, is targeting is in the G protein-coupled receptor protein family, specifically a key activating mutation of GNAQ and GNA11. What makes this indication quite fascinating scientifically is that essentially 95%+ of these patients have either a GNAQ or GNA11 activating mutation. So in this instance, the indication is the diagnostic. Darovasertib was specifically designed to block this PKC activation pathway that is turned on by this mutation of GNAQ and GNA11. As I noted in my introduction, our strategy for darovasertib is to position this molecule to be the new standard of care across the entire uveal melanoma patient journey, including neoadjuvant, adjuvant, and the metastatic first-line metastatic uveal melanoma setting. Alongside our strategy here, as we noted in our J.P. Morgan guidance on Sunday, we are targeting to have three randomized phase III trials initiated in the first half of this year. So why are we so excited about this compound and the opportunity that we have in front of us in metastatic uveal melanoma? We presented data last fall at the Society for Melanoma Research in Amsterdam, and we reported an overall response rate of approximately 35%, and as you can see here, a median duration response of nine months. To provide context, historical response rate has been reported at roughly mid-single-digit%, so clearly a marked improvement from what patients currently have available to them today. Beyond response rate, PFS and OS are obviously critical endpoints, and for those that are aware, PFS is the primary endpoint for accelerated approval, and OS is the primary endpoint for full approval. At SMR, we reported a PFS of seven months. Historical PFS, based on large meta-analysis, has ranged from two to three months, and overall survival, we reported an OS of over 21 months, and historical OS has sadly been in the 10 to 12-month range. This is the high-level design of our current randomized phase III study. Several pieces that I'll highlight here first. The 437 patients we need for full enrollment are now fully enrolled as of December, and as noted earlier, we are now on the precipice of being able to provide our top-line results to hopefully enable our first accelerated approval filing here in the U.S. In terms of investigators' choice, there are several therapies that will be on that arm, including checkpoint, PD-1 plus CTLA4, and the chemo DTIC. Beyond the metastatic uveal melanoma setting, we're very excited about the indication expansion opportunities that are in front of us that we believe will enable darovasertib to be a bona fide blockbuster opportunity. And front and center as part of that indication expansion opportunity is in the neoadjuvant uveal melanoma setting. For those that may have not followed this program very closely, we did receive Breakthrough Therapy Designation from the FDA in the spring of last year. We believe we're the only second company to receive Breakthrough Therapy Designation in the neoadjuvant setting in the area of oncology. So I think really punctuates the importance of the data that I'm going to share with you on this slide. As you can see on the left, the primary endpoint, there's two cohorts here, is enucleation, and as you can see at the bottom, over half of these patients that were scheduled to get their eye removed due to the ocular tumor, we were able to preserve their eye. Quite a remarkable result, and we believe the key data that really convinced the FDA to give us BTD designation in the enucleation setting specifically. Second, as you can see, over half of the patients, we saw 14-letter vision gain during the neoadjuvant treatment before the plaque procedure. Again, remarkable data that gives us confidence not just in the enucleation cohort, but the plaque therapy cohort as well. This is the high-level design of the randomized phase III study that we've launched in neoadjuvant melanoma. We launched this trial in the middle of last year, so now this study is fully up and running. We're going to be targeting to enroll a total of 450 patients, roughly 120 in the enucleation cohort, 330 in the plaque therapy cohort. As I noted earlier, the primary endpoint in the enucleation cohort will be eye preservation, and the plaque therapy cohort will be a 15-letter BCVA vision test, and there will be a pooled analysis across both cohorts on event-free survival while we demonstrate no detriment. This study, we also did recently guide as part of our JP Morgan guidance that we will target to complete enrollment of the study in the first half of 2027. Our hope here is assuming we have the ability to get accelerated approval in the metastatic setting by the time we are in that phase of hopefully commercialization, that the neoadjuvant phase III randomized study has the opportunity to hopefully be fully enrolled. Now we're going to transition from darovasertib to our next program that we've now guided our goal to have in a registrational study this year, and that's our DLL3 TOPO-ADC program, IDE849. As we know, the antibody-drug conjugate field has drawn significant attention in the oncology community, and we believe one of the greatest areas of unmet need that needs to be filled is how do we make ADCs more durable. We believe there are several key opportunities here, and we believe front and center as part of this is clinical combination opportunities with DNA damage repair small molecules. Within that, IDEAYA has been a research pioneer, has evaluated multiple mechanisms to achieve this goal, and we believe PARG, in specific PARG, with our clinical molecule IDE161, has the opportunity to be tested in the clinic and to test this hypothesis of enhancing the durability of the TOPO-ADC class. Through that, about a year and a half ago, we've been executing on a strategy to also bring internal potential first-in-class TOPO-ADCs into IDEAYA, and through that, we in-licensed IDE849, the DLL3 TOPO-ADC, and also another potential first-in-class bispecific B7H3 PTK7. As you can see below, in two models, one with our DLL3 ADC, the second with our bispecific ADC, we see very robust combination results that makes us very excited and confident about this opportunity to bring these two agents together to test this hypothesis about extending durability of this important class of therapies. This provides more detail scientifically. I will truncate this summary to the top right, but essentially we know that PARG enzymes specifically play a key role in the resolution of the DNA damage that's elicited by topoisomerase. We are essentially directly targeting this mechanism through PARG inhibition, and as we showed earlier, we not only have generated in vitro data, but we've also generated in vivo data across multiple preclinical models with multiple topoisomerase ADCs, including approved ADCs, and the result is consistent. We've been able to enhance the durability of multiple TOPO-ADCs in combination with IDE161. So now with DLL3, why are we and many companies focused in this area of DLL3? One of the main reasons is because one of the key applications in the area of small cell lung cancer. For those that may not be aware, small cell lung cancer represents roughly 15% of all lung cancers and perhaps continues to be one of the highest unmet need areas within lung cancer specifically. Unfortunately, survival is very short, and there are very few available therapies to these patients, and this is one of the key holes that we're targeting to fill. Beyond small cell lung cancer, we believe there will be broader opportunities, including within the neuroendocrine space, as well as indications such as melanoma. So this is data that we presented at the World Conference on Lung Cancer last September. I think this waterfall speaks for itself. This molecule is quite active. We reported a confirmed response rate in the second-line setting of roughly 70%, and as you can see, most of these bars are going down, and we also are seeing very deep responses as well. We also reported preliminary progression-free survival, and here we're reporting PFS just north of six months. And just to provide context, obviously cross-trial comparisons, a DLL3 T-cell engager that has been approved in the small cell lung cancer space has reported a response rate roughly in the 40s in a PFS of roughly four months. So we believe based on each of those measures, IDE849 is well positioned not only to be a potential first-in-class asset, but a leading asset in the broader DLL3 space. This slide summarizes our broad clinical development strategies. There are essentially several strategies that we're pursuing. One is in the small cell lung cancer space. Another is more broadly in the neuroendocrine tumor space. We did provide guidance on Sunday that our goal is to initiate our first registrational study for this program that we would target to be a monotherapy accelerated approval study. In addition, we'll be evaluating combinations, including with standard of care, which would largely include chemotherapy such as platinums, PD-L1, and of course, as I mentioned earlier, the PARG combination. Based on that data, we will also in the future look to pursue a front-line study in small cell lung cancer. Our first potential first-in-class TOPO-ADC pipeline has been growing. So now we have another phase I asset in IDE034, which is a first-in-class that we know the first of its kind bispecific that's now entered a clinic, which is a B7H3 PTK7. And why is this important? This is important for several reasons. First, the co-expression of these two antigens is very high in several key indications, including lung, CRC, breast, as well as several other solid tumor indications. Second, as you can see below, based on this specific bispecific antibody, we've seen superior efficacy versus the mono TOPO-ADC, specifically versus the B7H3s and PTK7, and we believe that's based on enhanced internalization of this bispecific ADC versus the monos. And as you can see below, we're seeing very robust regressions across each of these models. In addition, we will also be evaluating our IDE161 PARG combination as we will with DLL3 to build a portfolio of assets and opportunities across this area. We'll now shift gears to the third area of focus for us, which is in the area of MTAP deletion. As I noted in the introduction, why we're so excited and focused in this area of MTAP deletion, as I noted earlier, which is around this biology around chromosome 9p. As we know, one of the most common deletions of the tumor suppressor genes that are most common in cancer is both MTAP and CDKN2A. These two tumor suppressor genes are roughly 20,000 base pairs apart. Because of that, when MTAP is deleted, CDKN2A is almost always co-deleted. So why is this important? It's important for several reasons. First, this is very common in cancer, unfortunately. This occurs in roughly 15%-20% of lung cancer, roughly 20% of pancreatic cancer, and unfortunately for patients, there are no FDA-approved therapies for these MTAP deletion patients. There are three core strategies that we'll be pursuing here. First is around pursuing this interplay between the purine and pyrimidine pathway in folate, and this is what we're pursuing with Gilead around leveraging the topoisomerase DNA damage in connection with MAT2A. We're guiding with Gilead to provide a clinical data update at a major medical conference this year. Second is this combination with MAT2A and PRMT5. We are one of only two companies in the industry that have clinical stage molecules. This is continuing to leverage the biology and our expertise in the MTAP pathway, and here the primary focus will be in non-small cell lung cancer. Then finally, I would say it is an area that has become a growing focus and importance in the industry, which is the key question of what else is co-altered with MTAP. I highlighted CDKN2A as the most common co-alteration with MTAP, and the other most common alteration is RAS. We obviously know the focus of RAS specifically in indications such as pancreatic cancer, and roughly 90% of patients that have MTAP deletion in pancreatic cancer would also have a RAS alteration. Because of that, it creates a rational combination specifically in pancreatic cancer. So as you can imagine, if you're a pancreatic cancer patient, you have a RAS alteration, and you have an MTAP alteration, both alterations are known to cause cancer. Unless you're addressing both sets of biology, will you be able to deliver maximal response to those patients? We believe this is going to continue to be a very exciting field for the whole industry and definitely an area to watch for over the next several years. I covered most of this slide. I would just highlight here our focus with an MTAP deletion currently is in the area of urothelial cancer, lung cancer, and pancreatic cancer. This waterfall is data that we presented at R&D Day last September, and really the takeaway message here is we're seeing a response rate of roughly 40% in aggregate. The durability data is still immature. However, we can see we have several patients at the dose level two now that have extended beyond 200 days. In addition, as part of this in terms of a go/no-go decision, what we publicly communicated is we'd like to see a response rate north of 40%. We're still doing dose evaluation in non-small cell lung cancer, and we hope to be able to select an expansion dose in that indication over the next couple of quarters. Next is our phase I PRMT5 inhibitor, IDE892. Obviously, there are several molecules in the clinic against this target class. As I mentioned earlier, what differentiates us is we are one of very few companies that have wholly owned clinical assets that target both PRMT5 and MAT2A, and we believe both of these targets are foundational assets to hopefully deliver maximal value to patients with MTAP deletion solid tumors. As you can see, the monotherapy data preclinically demonstrates strong tumor regressions, and really what gets us excited about this is the ability for MAT2A to help address specifically acquired resistance mechanisms in the PRMT5 pathway. And as you can see, deep durable regressions we've been able to deliver through this combination. The last section that I'll walk through is our next generation molecules that are now both in phase I, which one is in Werner helicase with IDE275, and the second is IDE574, our dual KAT6/7 inhibitor. Due to time for now, I'll focus on the KAT6/7 program, which has recently entered phase I. For those that may have seen Pfizer just several days ago announce their first KAT6/7 molecule, just entered phase I this past Friday. Those may know Pfizer recently started a registrational study on a KAT6 selective molecule. We believe KAT6/7, which is specifically in the lysine acetyltransferase area of biology, specifically targeting a very important area of cancer biology called chromatin remodeling. We believe this target pathway has now been clinically validated, and we believe here the opportunity is to drive greater efficacy from what KAT6 has delivered through this dual inhibition of these paralogs of both KAT6 and KAT7. As you can see to the bottom right, we see significantly greater efficacy versus the KAT6 selective molecules. Here, we will most likely be focused clinically on the hormone receptor positive setting of breast cancer, as well as prostate cancer and other indications, including CRC and lung cancer. Within all of the assets that we're working on in the clinic, which now amazingly represents nine clinical stage programs, we believe KAT6/7 perhaps represents one of the largest clinical opportunities in terms of addressable patient population. So we just covered, I think, quite a lot, and I hope my clock is correct that I have 15 minutes left here, so maybe that's with the Q&A portion. But we're here at the last slide. So hopefully you get a sense that IDEAYA is really now at a key precipice as we are getting very close to having our top-line results, as I noted earlier, to hopefully enable our first accelerated approval filing in the U.S. with darovasertib. Next, we're investing heavily on the next wave of growth. And here, as we talked about earlier, is our focus on extending the durability of TOPO-ADCs, our deep commitment in the area of MTAP deletion biology, and then lastly, with KAT6/7, we think one of the most exciting opportunities to address one of the key challenges, which is tumor heterogeneity. So with that, Anupam, thank you very much, and we're done with the prepared remarks. Thanks, Yujiro. I'll ask the first couple of questions, but if anybody in the audience has questions, feel free to raise your hand, and I can help get your question in. So I just wanted to quickly ask about the metastatic uveal melanoma study. Data's in 1Q. I'm assuming that you're looking at sort of blinded events, and you've looked at it recently enough to reiterate your guidance that the data will be in 1Q. Is that a fair statement? Yeah. So yeah, we're not providing specifics sort of where we are within that continuum. Anupam, as you appreciate, there are sort of several steps in the process, but really for now, our public guidance is around being able to provide those top-line results this quarter. And I wanted to ask a bit of a broader market question. What have you learned from the Kimmtrak launch here in the U.S. about uveal melanoma that you can apply to darovasertib here? Yeah. So are those two mics active? Yeah. Okay. Can I bring maybe Darrin and Stu to join me at the front? I think much better that our functional leaders are answering. Obviously, you're going in a different subtype. Yeah. But, you know. Yeah Go ahead, Stu. Stu Dorman, I'm the Chief Commercial Officer at IDEAYA. With regard to Kimmtrak and Immunocore, I mean, obviously, they've done very well in this market. What we've seen from them, though, is a market share that has really plateaued, and they've spoken openly about getting into the community, and there are challenges there, there are continued efforts to do that. We feel that we have a plan in place to be able to action on that ourselves in a way that will allow us, with the oral nature of the darovasertib and crizotinib combination, to enter that market quite a bit faster. Questions from the audience? Yeah. Yeah. Thank you so much for your wonderful presentation. It's a multi-combo story, and I'm just curious about how about the single-agent access strategy and what about the monotherapy data such as IDE161? Yeah. So for us, we're going to really follow the science and the biology. So we have several programs where monotherapy is going to be a focus, including for DLL3 IDE849, in addition to the KAT6/7 molecule. But for several of the programs, as you highlighted, combination is really front and center, including in the MTAP arena. Additional questions from the audience? Yujiro, you talked a lot about the combination potential just right now, right, and having the science drive you. What led you to 161 kind of reemerging back into the pipeline here as now potentially a backbone combination product for the company? When you look at the ADC arena, as we know, there have been several key mechanisms that have been pursued, including microtubule mechanisms, obviously topoisomerase, which would land you in the area of biology around DNA damage repair. For us, our view is topoisomerase obviously is a critical payload mechanism. If you're really trying to think through what are the right combinations from a scientific perspective, ideally you're focusing in the general biology area of DNA damage repair. That leads you down a pathway of several different targets, including PARG, Pol theta. We know PARP1 is also another that people are interrogating, and that's really what led us to this area. Within those set of targets, based on the data that we've generated, we believe PARG is one of the most promising to extend the durability. Hopefully, we'll now be the first company in the industry to test this hypothesis in patients, and we anticipate we'll be able to test this hypothesis across multiple clinical stage TOPO-ADCs. Yep. How much myeloid toxicity do you see? Oh, sure. How much myeloid toxicity do you see with these DNA damage inhibitors on their own? I ask because obviously the main issue with the topoisomerase payload that you have for Trodelvy is significant neutropenia. Do you risk making that neutropenia significantly worse by adding another drug that has hematological toxicity in its profile? Yeah. Obviously, it's all going to be about what you do in the clinic, and that's the whole point of dose optimization. So I don't know, Darrin, if you have any comments? The only other thing I'd add is it depends on your schedule too. If you can deliver your DNA damaging agent in a way that's less myelotoxic, then putting the two together may not be as problematic as you think. And we think we've been able to do that with 161. I would also just remind folks, I think there is obviously also an opportunity you may not need full dose for both agents, right? So that's something that we'll have to test in the clinic ultimately. And the ADC matters. That's why we pick the ADC that we have with 161. We have specific delivery of payload to the tumor. We don't get that off-target cost. Could you just repeat that for the audience? Yeah. I think the only point our CSO in the back row is making, not every ADC is created equal, right? So that's sort of a general question. You obviously have quite a wide range of myelosuppression even across the ADC class, whether it's the linker, whether it's the payload, whether it's the antigen. But for Trodelvy, since this is the combination you're exploring. Trodelvy is with 397. Okay. I stand corrected. Yeah. Thank you. That's okay. Maybe while we're on 397 and Trodelvy, I think in your comments you said you wanted a certain response rate to kind of move forward. Is that right? Yeah. I would say for the Trodelvy IDE397, I would say ideally we're seeing a response rate that's north of 40%. Obviously, equally important, perhaps more important, will be around the durability. I think the good news is two things. We're seeing this phenomenon where we're seeing the drop in that spider plot fairly quickly and dramatically that we haven't seen before. So I think that's encouraging, and second, we're now starting to see these patients followed up, and that's why I mentioned we now have several that are up to 200 days. I even heard recently around we even have a patient past 500 days. So I think that's encouraging, and so we just need more data, more follow-up. But obviously, we can deliver that kind of response rate with good durability. We should have some path forward. And then on the safety side for that combination of 397 and Trodelvy, remind us you're testing different doses and lower doses of Trodelvy, hoping to navigate that therapeutic window, yeah? Yeah. So for the combination, I think we're in good shape. I mean, and maybe Darrin wants you to answer this question. We are testing or have been testing more than one dose level, but we think we found an optimal opportunity with the full dose of 397 and a reduced dose of Trodelvy of 7.5 mg per kilogram. It seems to have the best safety profile. It seems to have the best efficacy profile. That's where we sit today. We feel very comfortable with that. We still have to do some work within non-small cell lung cancer. There's the potential to maybe increase the dose there. We'll have to look at that, but we think we have a dose that's well tolerated, and I think the efficacy is very promising, especially if you think about the patients in that cohort that we've studied that have had EV-P in the past, and for TMB and pembro, they tend to not do as well with Trodelvy or other agents after that kind of therapy. And we think we're showing a highly respectable response rate in the patient population like that. So we're really excited about the opportunity here. But as Yujiro points out, we just need a bigger N, and we need more time to see how durable it is. And so far, the durability looks encouraging, but we just need more time. Questions from the audience? Yeah, right there. We see a lot of companies now moving in the direction of the dual payload approaches. And here, obviously, you're focusing on a systemic DDR rather than as a payload in combination with a TOPO-1 and a dual payload. Could you speak perhaps to a little bit of the advantages of using it as a systemic therapy combination rather than as a dual payload? Yeah. No, thanks for the question. At the end of the day, the concepts are the same, right? You're essentially trying to deliver two mechanisms to enhance durability. I would say kind of the pros and cons, I'll give the very shortened version. I think with dual payloads, a lot of it is, at least I believe, around can you drive additivity versus synergy, right? And a lot of that is going to be driven by the art of the DAR of each payload. Unfortunately, once you set that DAR, it's fixed in the clinic, right? And that's the advantage I believe you have with a systemic agent, right? Because ultimately, you're delivering two ultimately different payloads and essentially trying to deliver that same result, but you don't have a set DAR, right? So obviously, both of the payloads in the instance of the dual payload are being delivered by an antibody. So I think that's probably the advantage there. So it's an area obviously we would have interest in because we have obviously already two novel small molecule mechanisms. PAR would be an obvious second payload to consider. Any final questions from the audience? Thank you, Yujiro and team. Great. Thank you, Anupam. Thank you.