To get started, welcome back, everyone, to the 2025 RBC Global Healthcare Conference. My name is Greg Renza, one of the biotech equity research analysts, and we're very pleased to have IDEAYA Biosciences with us today. Joining us from the company, of course, is the CEO, Yujiro Hata, as well as the new CFO, Josh Bleharski. Guys, it's great to have you. Thanks. Great, Greg. Thanks so much for the kind introduction, and thank you to RBC for the opportunity to participate again this year. Yeah, it's always great to see you guys. It's another eventful year for IDEAYA. Maybe, Yujiro, before we begin, we'll just have you provide a brief overview of IDEAYA, your lead asset, Darovasertib in uveal melanoma, and really what is a nicely emerging broader pipeline. Yeah, for sure, Greg. 2025, actually this year, is our 10-year anniversary. I would say as part of that, we think 2025 is set up to be perhaps one of our potentially most transformational years with Darovasertib, our lead program. Here, we're guiding towards a potential readout for our frontline metastatic uveal melanoma study in HLAA2 negative, which is going to be a randomized median progression-free survival readout by year-end. I think that is definitely front and center. In addition, we also have guided from our phase II single-arm study to also report our first median overall survival data. That will be patients that include both HLA-A2 negative as well as HLA-A2 positive. We anticipate this will be over 40+ patients' worth of data. In addition, we have two additional neoadjuvant uveal melanoma data guidance for this year, one that will be in the middle of the year, Plaque Therapy cohort, and that will be focused at a retinal conference. In the second half of the year, we'll have data on both the Plaque Therapy as well as the enucleation cohort at an oncology conference in the second half. As you can see, we have a lot of guidance that we've committed to for Darovasertib with four data readouts from now to the remainder of the year. In addition, we have several other activities across our pipeline, including an MTAP deletion. As you know, Greg, we have a potential first-in-class MAT2A inhibitor that's in phase II. We're doing evaluations of monotherapy in both lung and urothelial cancer. We have two focus areas on the combination side, one with Gilead's Trodelvy in urothelial cancer as well as lung cancer. We did recently announce a selection of a dose expansion. In addition, we have our own PRMT5 inhibitor that will be going into the clinic here very shortly, and we're targeting to enable that wholly owned clinical combination before the end of the year. Beyond that, we have a lot of other assets, including DLL3, our 180C. We have guided towards a medical conference update in the third quarter. We also have a phase I WRN inhibitor, which we recently had an oral presentation at AACR. We also have PARG, Pol Theta, also in phase I clinical trials. We're also guiding towards three more INDs from now to the end of the year, which would give us nine clinical programs. We are definitely firing on all cylinders, obviously a big focus on Darovasertib to hopefully get our first commercial product. I think for us, really the broader underlying theme is that we're trying to build one of the leading diversified pipelines in precision oncology. That's great. Yujiro, maybe for the first time in a long time, the latest addition to IDEAYA wasn't an asset or a program going into clinic, but it was Josh as the new CFO. Maybe Josh, question for you, just a few weeks in now, if I recall or have it right, Yujiro just ran through Darovasertib, the expanding pipeline, your nice resource position as well. Just walk us through what attracted you to IDEAYA and what some of the goals are as you come aboard. Yeah, yeah, thanks, Greg. I'm thrilled to be a part of the team at IDEAYA. It's a company that I've admired for many years from a distance. It was a company I was close to in my prior role. I felt like just given the depth of the pipeline that Yujiro just talked about, obviously the financial resources at the company and the period that we're entering into over the next several quarters, thinking about growth and maturation of the pipeline and even potentially thinking about a commercial launch, it was a really exciting time to come aboard and lend a hand. I think the team is phenomenal and first rate. I was thrilled to have an opportunity to come aboard. I think, Yujiro, thank you, thank you, Josh. I think, Yujiro, the attention on Daro for the rest of 2025, you spoke about the PFS data. Now, what is the status of Daro in metastatic uveal melanoma? The latest update, I think, suggests over 300 patients have been enrolled. Maybe just walk us through some of the details of what to expect there. Yeah, so in terms of from an enrollment perspective, Greg, as you mentioned, we've already exceeded the patients we need for the randomized PFS readout. We're sort of well north of that. We're now hopefully going to target to finish off enrollment for the study, including for the full randomized OS readout for full approval. We anticipate that should be by the end of the year. Based on the progression events that we're tracking and based on the target enrollment that we've already achieved, that's what gives us the ability to guide towards a potential PFS readout, hopefully by year-end. Okay. And then just the assumptions on the PFS data, what would be considered approvable on an accelerated pathway? Yeah, so for me, we haven't specifically mentioned a specific hazard ratio here, but as you know, Greg, historical PFS based on several different studies have been in roughly that two to three-month range. We believe as long as we're north of five and a half months, we're going to be in good shape. As you know, at ESMO back in 2023, we had an oral presentation where we reported a PFS of approximately seven months. We feel confident about this endpoint for Accelerated Approval. Obviously, we're running the randomized study and everything is hopefully set up to have the results and consistent results that we've had in the past. You mentioned an OS update with the phase I and phase II. That could really de-risk to us the phase III OS readout. Maybe remind us how we should be thinking of that, what investors should look for, and how it sort of ties into that enrollment that you mentioned on the registration trial with the OS. Yeah, so I think, Greg, at least from our perspective, there have been large meta-analyses run in the metastatic uveal melanoma space, both Rantala and Kujala, which I think are two studies that people have looked at in the past. Where they're in the treatment-naive setting, historical OS, largely from checkpoint inhibitors and other agents there, have been in that 12-13 month range. For us, that's the bogey. Our objective and the way the study was powered is that we can achieve an OS that's ideally six months or greater. That would put you ideally towards the high teens or in the 20+ range. That's the objective. We do appreciate, we do think this is going to be an important update from our phase II study, appreciating it's a single-arm design. However, we have not reported survival on this combination to date. We do think it'll be informative. Granted, it is single-arm, it's 40+ patients, but we do think it'll be an important data point. Of course, this is all about getting a drug on market, right? Both you and Josh mentioned commercialization at the top of our discussion. Maybe walk us through what you view as the initial opportunity with a potential Accelerated Approval and then how that fares with a full approval. Yeah, so for the potential Accelerated Approval, our focus is going to be the HLA-A2 negative population. I think here, based on our clinical trial results as well as national bone marrow registries, we do think the majority of the population is HLA-A2 negative. I think that's the first where we'll start. We are seeking frontline approval based on this randomized study off of the randomized PFS readout. With that said, we want to emphasize that we are also still very focused on the HLA-A2 positive population. There, we're taking two approaches. First, we're going to roll something in that range of about 70+ patients in our existing phase II study and submit that as part of our NDA submission as real-world evidence that our agent is active in the HLA-A2 positive setting. In addition, Greg, as you know, we're launching a registrational study in the neoadjuvant setting irrespective of HLA-A2 status. That's the first part. As part of the NDA submission, we'll have that dialogue with the FDA to see how that goes. Our base case is Compendia, and this would hopefully enable us to get pricing and reimbursement in the US in the HLA-A2 positive setting. Our plan there would be to do it concurrent with that NDA submission that we'd be targeting for *A2 negative, assuming obviously we hit our top line results. Some of the questions we get is just on the potential for running a head-to-head with KIMMTRAK in the HLA-A2 positive. Is that something that you foresee or would be a reasonable potential step? Yeah, and also, Greg, I know just to your previous question, globally, we believe MUM HLA-A2 negative-positive is roughly 4,000-5,000 patient annual incidence. Okay, great. Mentioned that as well. In terms of the HTAC KIMMTRAK, at least at this time, our belief is the answer is no. Here for the A2 negative trial, we'll submit real-world evidence. In the A2 positive, we have patients in the frontline settings. We'll also have patients that are pretreated as well. We have seen in many cases durable responses post-KIMMTRAK treatment as well. We think whether it's before or after KIMMTRAK, we know the agent is generally quite active in that situation. Also for Compendia as well, we would not plan to do, obviously need to do a head-to-head study. You mentioned some of the patient numbers. You also alluded to some pricing and not asking for price guidance, but it is a question that certainly comes up, especially with Crizotinib as a combination. What analogs do you think about when it comes to the combination and how you can harness the potential value of Daro + Criz? Yeah, so look, you know I think, Greg, our view is that we don't believe obviously the pricing in this setting so far, we have really one comp to go by, is based on the fact that it's a large molecule. I think here it's a rare cancer. Unfortunately, for patients in the A2 negative setting in particular, there are no approved therapies. Patients are typically surviving for less than a year. It is not a great situation. We think there's a relevant comp out there. Hopefully, as we get closer, we'll have more visibility. We do think that it is really the key price comp that we're at least worth thinking about right now. That's great. That's great. Let's talk neoadjuvant. You mentioned upcoming clinical updates, MIN-24 later in the second half of 2025. Just help us, Yujiro, frame some of the expectations, the insights that we should be gaining from these updates and even the potential read-through to the phase III pivotals that I think you plan to begin in the first half. Yeah. Greg, as you know, we're extremely excited about the neoadjuvant opportunity. Recently, we got FDA Breakthrough Therapy Designation in the neoadjuvant setting, at least that we believe we're only the second company to get a Breakthrough Therapy Designation, both in the neoadjuvant setting and in oncology. I think that's really hopefully a sentiment in terms of enthusiasm around the dataset that we've provided to the FDA as part of that BTD submission. In terms of what to expect on the upcoming data, I would say I think our enucleation data in general, in terms of what the bogey is, which is we guided towards an eye preservation rate north of 10%. Right now, we're at an eye preservation rate, which is north of 50%. I think we are well north of the number we need to achieve. I believe where we need more data, which we have not shared publicly today, which is around the eye preservation, sorry, the vision preservation data. This is specifically around the 15-letter vision test. Here, there's two datasets people should expect. One is around simulated visual prediction data because, as you know, actual vision data will take about 18-20 more months to mature. So we're going to need to wait longer for that. Second is actual vision outcomes on neoadjuvant treatment. What we observe, which I think in many cases was a surprise to us, but a positive surprise is that we were seeing a subset of patients where we actually saw visual improvement on neoadjuvant treatment prior to Plaque Brachytherapy. That's data that we have not shared in the past and we'll also be sharing as well. Visual prediction data. Second is actually outcomes on treatment during the actual neoadjuvant treatment phase. Since, as you know, the main focus in the past has been post-plaque therapy and then as you follow vision post that Plaque Therapy. That's great. That's great. Maybe, Yujiro, put some numbers around the neoadjuvant population, how that has really broadened the opportunity. Yeah, so we think that population is going to be substantially larger than the metastatic population. As I mentioned earlier, in the metastatic setting, we think 4,000-5,000 patients. We believe the pre-metastatic setting will be at least double that amount. Next, which I think is a number we're still working through, is what is the total prevalence as well. As you can imagine, Greg, because in the pre-metastatic setting, survival is much longer, you're going to have a much larger pool of patients that represent total prevalence. We should be able to penetrate, of course, annual incidence, but also some portion of that total prevalence. We do think there could be potentially significant upside by actually also targeting that prevalence pool. Yeah. I think historically, epidemiology and getting a handle on numbers has maybe been a challenge. It's an evolving eye on the market. Maybe just walk us through some of the inputs to that, why it has been challenging, why sort of the global collection is really a work in progress. Yeah. Uveal melanoma predominantly occurs because we believe it's based on an active invading mutation of gene GNAQ that largely occurs in the Caucasian population, in particular patients historically from European descent. A lot of the population resides in North America, U.S., Canada, Europe, and Australia. I think that's the first part, Greg. I think there are some specifics around the specific genetics that I believe is the cause of uveal melanoma. I would say within that, because there have not been any approved therapies in the pre-metastatic setting, and now there's only one in the metastatic, it is a new area that we're sort of uncovering what the opportunity is. In the U.S., American Cancer Society does report annual incidence every year for the last 10-some-odd years. I think that's great. In Europe, there are countries such as Cancer Research UK that has been reporting sort of annual incidents as well. Hopefully, we'll get a better and better handle of that over time. The numbers that I mentioned to you, at least from an annual incidence perspective, we feel we have a pretty good handle on. That's great. Maybe on the neo, the phase III, walk us through the timeline for that pivotal readout in each population, enucleation and the Plaque Brachy. How long would you anticipate even obtaining that secondary endpoint of no detriment to event-free survival? Yeah, no, for sure. Here, Greg, you want to think about the registrational study in the neoadjuvant setting as two patient cohorts. First, our patients that are going to get enucleated here, we're targeting to enroll 120 patients. The primary endpoint for that cohort is eye preservation, as I mentioned earlier, with 15% eye preservation rate with a 95% confidence interval. There, as long as we're north of roughly 15%, we think we'll be in good shape. The secondary endpoint for that cohort is event-free survival. Here, I would highlight it is no detriment to event-free survival versus a higher bar such as superiority or non-inferiority. In this case, what we discussed with the FDA around no detriment would be overlapping confidence intervals. There isn't a specific hazard ratio target here. All we need to demonstrate is this no detriment based on overlapping KM curves. We do believe that's relatively a low bar based on past EFS type readouts that FDA has required. This is for full approval. The second cohort would be Plaque Therapy. This would be around this 15-letter vision test. The way you want to think about it is it's going to be basically looking at the difference between the treatment and control arm. Ideally, there we show a vision improvement between 15%-20%. The cohort enrollment will be 400 patients. Similar to the enucleation cohort, the secondary endpoint will be no detriment to EFS. In terms of the timelines for that, we anticipate between four to five quarters, we'll be able to enroll that study. That sounds fast, but just to mention that we enrolled roughly 100 patients with 20 sites in about a year. We're going to 5x the number of sites. We believe in roughly five quarters, we should be able to enroll that study. In terms of the readout, the eye preservation readout will be first. Typically, we know in about 6-12 months, so that'll be the fastest. We anticipate the second will be around event-free survival, which we anticipate will be roughly two years from first patient enrolled. The last one around the vision preservation, we anticipate the first interim read will be 18 months after last patient enrolled. That'll be the sequence. It'll be eye preservation, EFS, and then the vision test. The last part I'll mention importantly, after further dialogue with the FDA, they are going to allow us to submit the enucleation cohort for regulatory review earlier as long as the EFS data is sufficiently mature across both cohorts. That we think will enable probably about a six-month earlier submission for regulatory review of the enucleation cohort while we wait for the vision from the Plaque Therapy to further mature. That's fantastic. Covered a lot on Darovasertib, and there's still more to come in the last few minutes. Maybe we will do some quick hits on the rest of the pipeline. With respect to DLL3, the ADC, let's talk IDE849. Licensing was disclosed late last year. Just remind us of the broader strategy of this asset. Why are you so excited about it? And maybe just the confidence that you're essentially not behind others in the space. It is a rather active space. Yeah, yeah, for sure. DLL3, TOPO ADC, this asset is in phase I. Greg, here, I think the quick summary is we believe we have a very active monotherapy agent. I know there's information on our corporate deck where we're seeing a clear monotherapy signal. We're seeing partial responses, confirmed responses. At least what's been reported on our corporate deck is 70+% response rate. That's not all confirmed responses, just to highlight that. We know that there's going to be a peer company of ours that's going to be having an oral presentation at ASCO here shortly. We will also have our medical conference presentation in the third quarter. What people should anticipate is 40+ patients, including both in the escalation as well as multiple expansion doses. We do believe that we are neck to neck in this field with at least DLL3, TOPO ADC. Really here, we think the key determinant in terms of where we are relative to our peers is how far are we to select our move-forward expansion dose. That's sort of the quick summary. The fortunate news also, as part of our IND submission to the U.S. FDA, as part of the FDA feedback we received, they are enabling us to have our U.S. starting dose at one of the expansion doses that our partner HUTCHMED is currently evaluating. That, we believe, at least accelerates the escalation process by at least half a year. We will be quickly moving into both what we think could be a potential registrational accelerator approval study as monotherapy in the extensive stage small cell lung cancer setting. The second area I would see a big focus is going to be the frontline study there. I can quickly sort of summarize there. Historical standard of care on the frontline small cell setting is platinum doublet. Typically, cisplatin or carboplatin plus etoposide, which is a TOPO2 mechanism, followed by PD-L1 in the maintenance phase. Here, what we would likely do is combine with most likely cisplatin or carboplatin, most likely cisplatin since that's more commonly used, remove etoposide from the equation, replace with the ADC. In the maintenance phase, do PD-L1 randomized versus PD-L1 plus our ADC. That would likely be the strategy. We're still talking to investigators. I think there, that's where we've seen the enthusiasm to remove etoposide from the equation and replace that with our ADC. That's a study. We'll need to first start with dose optimization with PD-L1. Those efforts are already beginning in terms of that planning. That is why, as we said, obviously, the big opportunity here in small cell is the frontline study. We are not behind there from that situation. The last piece I will mention is HUTCHMED, our partner. They are obviously a major pharmaceutical company in China. They are pushing this very hard to get this hopefully approved in China. We will be looking at this as a global trial and also sharing our data together as we think about global submissions. That is all part of our agreement. Obviously, a big part of our strategy also will be around this PARG IDE161 combination, which our hope is that that can also enhance the durability. Beyond small cell, just really quick, we are also thinking about neuroendocrine tumors. We also know that DLL3 is upregulated in other solid tumors, including non-small cell lung cancer as well as melanoma. Great. The mono, you mentioned you're at the in-house PARG 161, the combination potential there. A great deal of white space with a deal done late last year. Fantastic. We're winding down on time. Maybe what I'll do, Yujiro, is when it comes to the MAT2A, your own in-house PRMT5, there was some Werner data. We've got poll theta. Maybe just walk us through some of your favorites to help the investors who are sifting through the pipeline and trying to understand how to prioritize. Where should folks be looking for the rest of the pipeline beyond what we just discussed? Yeah, no, great, Greg. Yeah, I would say I would maybe kind of focus on three quick areas, and I'll try to be as fast as I can. In the MTAP area, Greg, as you know, I mean, for us, the high convection combination is around the MAT2A PRMT5 combo. This has been a long time in works in terms of enabling our wholly owned combination. We do believe we have a potential best-in-class PRMT5 inhibitor. We won't have time to go through that today. Our IND and PRMT5 will get filed here relatively soon. Our goal is to enable the clinical combination by the end of the year. That is going to be front and center for us. On Werner, we think here we do have a target that's clearly showing monotherapy activity, durable responses, a therapeutic window. I think we told a very compelling story at AACR why we believe we have a potential best-in-class inhibitor based on its unique binding mode. Lastly, it is our view that we have a true platform of drug discovery that is going to continue to deliver more agents in the future beyond Werner, beyond Pol Theta, KAT6/7. We just talked about PRMT5. As Josh is very well aware, we have a lot more programs coming ahead as well. Great. We'll leave it there. Lots to look forward to in 2025 and beyond. Yujiro Hata, Josh, thanks so much. Great. Thanks, Greg. Thank you for the opportunity. All right.