Thank you everyone for coming today. My name is Ruk Pyatt. I'm an executive director with the investment banking division at Morgan Stanley. Before we get started, I just need to read a quick disclosure. "For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative." We have the pleasure of hosting IDEAYA's management team today for the Fireside Chat. We have Yujiro and Paul from the company. Thank you for making the trip out here from California, which wasn't easy. We really appreciate your time here today. Maybe just to get us kicked off here, Yujiro, can you just start by taking us through IDEAYA's pipeline and your oncology platform? Sure. So first, Ruk, thank you so much for the kind introduction, and thank you to Morgan Stanley for inviting us this year again for the Fireside Chat. So IDEAYA was founded just over eight years ago, with a core focus to build a leading synthetic lethality-focused precision medicine oncology company. Today, we have four potential first-in-class clinical programs. Our most advanced program is Darovasertib. Here, the lead indication is metastatic uveal melanoma. We just launched into a first-line potential accelerated approval study in HLA-A*02 negative MUM. We also have a phase II company-sponsored trial in neoadjuvant as well as adjuvant uveal melanoma. Our second program, IDE397, this is targeting a very large patient selection biomarker called MTAP deletion, which is believed to represent roughly 15% of all solid tumors. Here, we have a significant focus on our monotherapy development. We're focused on very specific tumor types, including lung cancer. Also here, as you know, we have a very important partnership with Amgen, to do a clinical combination, with their MTA-cooperative PRMT5 inhibitor, AMG 193. For that combination, dosing for patients has just begun. Our third, first-in-class clinical program, which we did announce earlier today, preliminary clinical proof of concept, is IDE161. We're very excited, about the update this morning, where, as you saw, we did... We are seeing early evidence of tumor shrinkage and clinical efficacy, including a BRCA1/2 endometrial cancer patient, where we saw a partial response in the target lesion, at first scan. In the last month or so, we also announced, our fourth clinical program with GSK, now has entered the clinic with Pol Theta. And then lastly, which would represent our fifth first-in-class program, the Werner Helicase candidate nomination is on track, before the end of this year. Great. Thank you. We'll get into each of your pipeline assets to double-click on them. But as you kind of think about IDEAYA and this rich pipeline that you've built, and talk thinking about the platform, how would you characterize IDEAYA, and what's a core part of your story? Yeah, I think there are several key features, Ruk, for us, and hopefully, as you've seen, are growing and advancing first-in-class clinical pipeline. First and foremost, we believe we have a phenomenal organization, which is obviously made out of all of the employees in the company. And I would say one of the key aspects that we've meticulously built is a world-class drug discovery organization, and also, I would say, continued strength around a very capable clinical development organization. In addition, our platform in precision medicine oncology has demonstrated its ability to deliver multiple first-in-class programs into the clinic. And as you know, in many cases, these are extraordinarily challenging targets, including PARP, Pol Theta, MAT2A, and hopefully, as we'll be able to, you know, target here soon is Werner Helicase. Great. Thank you. Maybe let's dive into the lead program, which I think most people are very familiar with, with DARO and metastatic uveal melanoma. Now, you've previously presented really compelling data on DARO and Crizo combination trial, and now you're preparing for the registrational trial in HLA-negative subtype specifically. Now, can you walk us through the strategy on focusing on HLA-negative patients and any conversations you might have had with the regulatory agencies? Sure. So our strategy within metastatic uveal melanoma is to pursue a first-line accelerated approval study, specifically in HLA-A*02 negative. And there are really two primary reasons why we made that decision. First, we believe the HLA-A*02 negative population doesn't just represent the majority of the UM population, we believe it represents the vast majority of that patient population. Second, there is no FDA-approved therapy in HLA-A*02 negative. So with a combination of those two, both in terms of the fastest path to approval and the highest probability of success study we can run, we felt very good about that decision, and obviously, we had a very good conversation with the FDA, and pretty much received all the key aspects we hoped we would, to launch into this study, which has now just begun recently. Yeah. That's great that, you know, you're focusing on HLA-negative, which obviously is a larger, you know, opportunity. Is there a possibility that you will enroll additional HLA-positive patients for expansion cohorts in this trial? And as you think about that market, obviously, contenders there, how do you think about, you know, your place in the market? Yeah, our view here, Ruk, is once everything is done, we should be covering every aspect of uveal melanoma, whether that's HLA-A*02 negative, positive, as well as in the neoadjuvant-adjuvant setting, which, as you know, we are pursuing agnostic of HLA-A*02 status, which I think will only further support this molecule's activity in HLA-A*02 positive. Specifically to your question, we are continuing to enroll patients in our ongoing phase II study, in HLA-A*02 positive. This assumes success in our A*02 negative trial, in our frontline trial, that if we do receive approval there, our plan would be to publish our A*02 positive data for potential compendial listing. Got it. Thank you. And also, congratulations on, you know, getting your neoadjuvant phase II trial up and running. How do you plan to leverage the neoadjuvant endpoints, such as reduction of radiation and eye preservation, to further demonstrate clinical efficacy? And what are some of the key updates that we could potentially anticipate? Yeah, I think the neoadjuvant indication is a really exciting opportunity for several different reasons. First is there are no FDA-approved therapies or systemic therapies in the neoadjuvant setting. Second, for that same reason, we believe the regulatory hurdle is potentially quite low. And based on the preliminary clinical efficacy we've seen, we believe we've seen a very strong signal for Darovasertib as a monotherapy to deliver value. Here, there's really two patient populations to be aware of. First, are patients with larger-sized tumors in the eye. Here we believe, these would be patients that would be, on track to get enucleation, and here the endpoint would be around a, eye preservation endpoint. From a registrational perspective, we believe there's a potential to have a first-line, single-arm accelerated approval design. The second cohort would be small to medium-sized tumors. This would likely be randomized against plaque, and there, at least our current thinking, is three potential endpoints. One would be radiation reduction, second being vision preservation, and potentially a third, response rate type, type endpoint. Got it. Thank you. And in terms of, you know, the registrational trials, I know you haven't really provided detailed guidance, you know, in terms of how the street or investors are thinking about, you know, the timeline, do you think there's a consensus on approximate timeline to approval? And, you know, as you think about that, what's your view on anticipated pace of enrollment for the registrational trial relative to your recent phase II experience? So yeah, first, Ruk, here, on the neoadjuvant/adjuvant side, you know, obviously, the neoadjuvant one is the time. The endpoints are gonna be much sooner in terms of the clinical readouts. Second, in particular, the enucleation cohort, we believe the regulatory hurdle may be quite low. So there are certain scenarios there, and if it is possible as a single-arm design, we have not provided that public guidance, but there are certain scenarios where we do think that could potentially come online commercially in fairly close proximity to what we're anticipating in our first-line metastatic trial. Here, I would say it's just too early. We need to generate more data and have a conversation with the FDA. But I would hope with, you know, 20-some-odd patients, as long as we see a clear signal, we can have that conversation. In terms of adjuvant therapy, those clinical endpoints could be longer, including relapse-free survival, that would likely be randomized against placebo. And then lastly, I think to your question around the, you know, the rapid rate of enrollment we've seen in our phase II study for metastatic uveal melanoma has been only with about roughly 12 sites in the U.S. We're gonna be about tripling to quadrupling that number in the US. We're obviously gonna have a very strong presence in Europe. So we don't anticipate that enrollment's gonna be a challenge here. Got it. So, even with site activation outside of Europe, that's, you know, we'll see updates from that? Yeah, correct. So I think once we have, you know, enrollment ongoing, we would anticipate giving some updates on where we are on with enrollment, but at least based on our phase II experience you know, we believe, enrollment should go quite rapidly. Yeah. Got it. Thank you. Before we switch gears to kind of what might be the getting interest from investors on 397, can you just talk a little bit about the activity that you've seen in dara relative to your competitors? Sure. So for IDE397, for those that may or may not know, is a first-in-class NOTCH2 inhibitor. Here, the patient selection biomarker being MTAP deletion. deletion. And here we have reported monotherapy efficacy, including multiple responses in several priority tumor types. So in particular, we've noted a confirmed partial response of -47% reduction of priority tumor type. We've not disclosed that tumor type. We also have recently noted a 33% reduction in a lung cancer patient as well. Here I would emphasize this was part of our phase II expansion monotherapy expansion, and here, the denominator is quite small, so we haven't been in many patients thus far. Then as you know, obviously, we're just in the beginning processes of launching the combination study with Amgen. So at least I think personally, I think what we're seeing is an early clinical signal in the MTA-cooperative PRMT5 side as well as on the MAT2A side, which I do think bodes well for validation of this pathway. Right. And I think there's been just very clear, resounding excitement from investors around PRMT5 pathway, especially in reaction to what folks saw recently from Amgen, Mirati. Now, can you just walk us through the importance of this pathway from your perspective and the potential market opportunity? Sure. So the importance of this pathway is that when you look at various synthetic lethal screens in the cancer genome, one of the top hits that does come out is in the area MTAP deletion, specifically, with two targets, one being MAT2A, and the other being PRMT5. Within that, MTAP deletion is perhaps one of the largest patient selection biomarkers that are being pursued today in oncology. It's at least 2 times the size of KRAS G12C, if not larger. And then lastly, in terms of the mechanism of action of how both MAT2A and PRMT5 cause cancer cell death, has a similar mechanism, specifically around alternative and RNA splicing. Got it. And, to keep things a little bit interesting, what's your perspective on some of the data that we have seen recently from some of your competitors? You know, frankly, that's sort of what we were expecting. So, you know, we obviously had visibility in our data. You know, we've been collaborating with Amgen as well for a while. So it did not come as a surprise, frankly, at all to us. But that's exactly what we were expecting. And how do you think about the opportunity here for you? And, you know, obviously there are, you know, like Tango, you know, is also, in the space. But how do you think about the opportunity here for you and IDEAYA, and also maybe around your partnership with Amgen going forward? Yeah, at least our, our view here is we believe IDEAYA is extremely well-positioned, in the field of MTAP deletion, relative to our peers. We believe, strongly that the way we're gonna drive the greatest patient benefit, irrespective of MAT2A or PRMT5, is through a rational combination. That is our perspective based on extensive preclinical analysis that we have done, and we believe we are strategically aligned with Amgen, on our, on our view, on that as well. I would say bigger picture, I, I do think this is an extraordinary, opportunity, for all of the companies in the area. You know, I think at the end, Ruk, it's gonna be about, you know, how do they ensure, in terms of having the highest probability of success clinical trial, that you're in the right tumor setting and you're enabling the most optimal combinations. And at least our, our view today, with our work that we're doing with Amgen, we have quite a head start. Yep. And it really makes a lot of sense, you know, from the complementary nature of MAT2A and PRMT5. But now, how do you think about the potential monotherapy opportunity? Yeah. So I think we've been very consistent on our communication on this topic. Our view is, based on all of the data we've seen preclinically, in this pathway of MTAP deletion, that the way we're gonna deliver the most maximal benefit to patients will be through a rational combination. We've done extensive evaluation here. We've looked at over 100 different unique combinations, and clearly what comes to the top is the MAT2A, MTA-cooperative PRMT5. And also when you look at the various resistant mechanisms, compensatory pathways in MTAP deletion, we believe not only to deliver a better response rate or a broader response rate, ultimately, this is gonna be the best opportunity to deliver durability as well. Got it. Thank you. Now, maybe you can tell us a little bit more around 161 and the PARP opportunity, including today's update. Yeah. So I think today's update is quite significant, not just for IDEAYA, but we believe for the broader field of synthetic lethality and DNA damage repair. Today's update this morning is the first time anyone's ever presented preliminary clinical proof of concept as it relates to efficacy on PARP. And as you know, we're very early in dose escalation. We've only had a handful of scans. We've also only had first scans on patients, and even within that, what we've noted publicly today is that we've seen multiple patients with tumor shrinkage. We specifically highlighted this BRCA1, BRCA2 endometrial cancer patient, where at the first scan, we saw a partial response in the target lesion. We saw a complete response in the non-target lesion, and the CA125 tumor marker, we saw reduced by almost 90% in six weeks. And we know that in ovarian cancer, where that marker has been most well studied, a deep and rapid response of that marker has been correlated with ultimately OS. So we think all of those pieces together, at least our key takeaway here is, it does appear we have quite an active molecule, as a single agent. Got it. Obviously, you know, those optimization efforts are ongoing. You know, what are some of the clinical updates that we could potentially expect from the IDE161 program? Yeah, so we did, based on this update today, now provide new guidance that this half we are providing—planning to provide clinical program updates. We did not specify whether that would include a clinical efficacy update, but we wanted to note that it could include a clinical efficacy update, but we want to be able to sort of reserve that right. And obviously, if we did provide that update, you know, we did provide investors and analysts a heads up that that may be coming. Yep, got it. Now, are you, you know, given kind of a lot of good progress that you've made in identifying rational combination, you know, approaches, have you thought about potential combination approaches that may be sensible for PARP? Yeah, absolutely. I'm, I'm really happy you asked that question. In fact, I would say this has probably been one of the most important strategic priorities for the company. Hopefully, as our investors and analysts have seen, we do have a capability here. We enabled the first MTA-cooperative PRMT5 inhibitor matched with a combination with Amgen, and we believe there's similar opportunities for PARP. Here I would just highlight two pieces. First, our combination strategy is focused on getting us outside of the area of HRD. And then second, we believe these market opportunities is successful has the opportunity to be frankly really significant commercial market opportunities. So I, I you know I would say stay tuned, more news to come there. But obviously, first great to demonstrate early POC as a monotherapy, I think should just give us more combination as we pursue some of these combination strategies. Got it. Thank you. And it's, you know, you have a new update every, almost every month or every other month, so there's a lot to cover. Now, you know, also congratulations on the Pol Theta IND clearance. Do you have any color on potential endpoints that'll, you know, demonstrate signs of efficacy? And also, as you think about the different indications, are there any specific tumors that you plan on targeting? Yeah. So we haven't until the protocol publishes on ClinicalTrials.gov, which hopefully should be publishing soon. I can't share that at this point, but I may be taking one step back. Really, the strategic premise of Pol Theta is to specifically address the issue around PARP resistance, and we know that a large predominance of those patients has what's called BRCA reversions, which has been associated with a genetic signature related to microhomology end joining. And we know that Pol Theta specifically is the Achilles heel of microhomology end joining. So here, I think ultimately, Ruk, I think the hope is with this combination we can really enhance the efficacy of PARP with the hope to really hit these more long-term time to event endpoints like OS, which, as we know, has been somewhat of a challenge in that area, as we've seen in the last year. Got it. Thank you. Now, maybe, Paul, could you maybe talk... Obviously, good to have all these updates coming out, you know, in kind of like a bolus, you know, every couple of months. But as you think about, you know, the capital intensity and maybe also talk a little bit about the business model in terms of how, you know, you have so many programs to prosecute and push through the clinic, how, how are you thinking about the capital strategy for IDEAYA? Yeah, I think, we've been, since early on in the company, had an integrated strategy across the business and the science to enable multiple programs advancing into the clinic while we continue to into invest in research. And as you know, we've been relatively capital efficient, since day one, including, you know, even our lead program, Darovasertib, the MTAP-deletion program, IDE397, and the PARP program, IDE161, where we've noted that each of these are wholly owned by the company as they advance into the clinic. But we've still been able to, leverage partnerships to help with capital efficiency. So with Darovasertib, we have a partnership with Pfizer. We're getting drug supply, crizotinib, essentially for free, throughout the program and now, and, and have that supply lined up for the registrational trial. So that's really important. And, while it may not cost Pfizer too much, it does save us tens of millions of dollars. On IDE397, as was noted, we have a what we believe will be the definitive clinical study in the combination with AMG 193. This is a 50/50 cost share with Amgen. Even though they're the sponsor of the trial, we do co-own all the data. We co-own any intellectual property rights. We have a joint operating committee with them, so it's a very much integrated clinical effort. But we don't have to pay any of their internal costs. It is just sharing external costs. So again, it's capital efficient on that program. PARG, you know, we are holding this program. We've not partnered it at all yet, but we are thinking about combinations. We've not said too much about what the structure could look like, but you can add in something like Amgen, for example. Yeah. Beyond that, you know, we're well positioned from cash perspective. We have $510 million of cash. We've indicated in our operating plan, that does enable us to fund our operations into 2027, with a long cash runway. Importantly, that supports the Darovasertib registrational clinical effort, as well as early potential commercialization activities there. For other programs, it funds through meaningful data catalysts. So as we continue to provide these updates and generate momentum on some of these earlier programs, you know, I think in the success scenario, we will need to raise more money, but we have a good balance sheet to work from for now. Yeah. Great. Thank you. In terms of some of the key milestones, I think we kind of talked about all most of those earlier, but maybe just to summarize, what are some of the key updates that investors should pay attention to from your perspective in the next six to 12 months? Yeah, sure. So I think, you know, start with Darovasertib. We've launched in the registrational trial. The sites are up and running. We're expanding the number of sites. We've talked about the enrollment there. I think we've noted, based on the publication of the ESMO titles, that there will be an oral presentation at ESMO, presented by one of our investigators, that's going to talk around ctDNA data from our phase II clinical trial, and we'll likely correlate that with the already reported clinical efficacy. So I think that's important, because, you know, ctDNA is an area where it can help you to identify patients earlier, it can help you to see responses earlier or potential responses earlier. So I think it's just a really important update. Beyond the ctDNA data, that's all we can associate with ESMO because we're limited by the rules. But we have guided towards some other program updates before the end of this year, including an important metric, which is the prevalence within metastatic uveal melanoma, the prevalence of HLA-negative relative to HLA positive. We have our own data set. I don't think that a broad data set has yet been published that is metastatic uveal melanoma specific, so that'll be an important one. So publicly, it's not just the majority, we think it's the, the vast majority, but we're going to provide the underpinnings, for that. Then we may also share, a subset of data from our phase II trial, showing a breakout of HLA-A*02:01 negative versus HLA-A*02:01 positive in terms of efficacy. So that's daro on registrational. On the neoadjuvant setting for Darovasertib, kind of phase II monotherapy, that's a company-sponsored initiative. We recently announced first patient in. We've been guiding that, in parallel. We also have an investigator-sponsored trial, which has been running in Australia. So we've been guiding before the end of this year, to provide an update from that IST clinical efficacy update. That's important. And then moving on between, after that, IDE397 and the combination with Amgen. Amgen has guided that they'll present their monotherapy data on AMG 193 in a medical setting this year. So that, that'll be an important update for the space generally. Obviously, we'll continue to inform our, our combination efforts with them. I think we just, we just talked about PARG having potential program updates before the end of the year. And then on, on our fourth program, first patient in, would be the sort of next expected update on Pol Theta data. We just recently announced with GSK that we're, that we cleared the IND, so that, that would be an update that could be coming soon. And then Werner, we're guiding towards development candidates, so, nomination before the end of the year. So a number of important updates coming still before the end of this year. Got it. Great. I think we have about a minute left. Can you talk about your vision for the company? You know, I think you have been able to succeed in proving out the synthetic lethal narrative where others had struggled. But now, I think what you're turning into is really a broad oncology precision platform, with some of your own, not only, chemistry work, but also, there's... I know that there's a machine learning component as well. You know, fast forward, like, what's your ambition and vision for IDEAYA? Sure. Yeah, I mean, I think first and foremost, Ruk, I mean, I do think we have a real opportunity to build the next leading precision medicine oncology company. We have a very strong foundation to do that with five potential first-in-class programs, all of which we believe have blockbuster potential. I think the foundation here is, from our perspective, we have a phenomenal organization. We are doing cutting-edge science. In many cases, we are, you know, breaking the ground in new pathways and biologies and biomarkers, and that's what you're going to see us continue to do. We successfully leverage pharma relationships, from Pfizer to GSK to Amgen, and I would say the interest there has never been higher. Although you know, I founded this company over eight years ago, I think we're just at the start of the journey. Got it. And, yeah, I think we're about time, but thank you again for making time to come trek your way to New York, for the conference. You know, your assets, each asset, I think, are, you know, really strong and solid enough to, create a company. So you effectively have, you know, five companies and a platform behind it. Good luck with your meetings today, and, and we'll stay in touch. Thank you. Great. Thank you so much for the opportunity today. Yeah. Thank you.