Good morning, everyone. Welcome to the first day of our Kenter Healthcare Conference. My name is Lee Walczak, a biotech analyst here at Kenter. Today, I'm very pleased to have the IDEAYA team with us today, Yujiro and Josh. Thank you very much for being here. By the way, congratulations on the Sevier deal yesterday. A very exciting time. I would say IDEAYA is probably, you know, shaping up to be one of the highest conviction names for us internally. I understand you guys have a lot of exciting, you know, updates coming up over the next six months, including a pivotal, you know, top line that's for Darovasertib. I think today will be a great opportunity for you guys to maybe set the stage for investors right before your R&D day, your 10th anniversary. That's very exciting. Maybe I'll just hand it over to you guys to give some quick intro remarks. For sure. First, thank you so much, Lee, for the kind introduction. Thank you to Kenter for the opportunity to participate this year. Lee, as you said, you know, we're thrilled to be here this time this year. Marks a very important milestone for the company. It's our 10-year anniversary. As you know, on Monday, September 8, we're going to be holding our 10-year anniversary R&D day. We have three clinical data updates that we're guiding for that event. We hope for all those people that can either dial in virtually or be there in person, we'll make sure it's definitely worth people's time. I would say a big picture here, Lee, as you know, we have seven programs that are either in the clinic or at IND stage. We announced our new asset in the clinic today in the PRMT5 space. We are planning to have nine programs in the clinic by the end of the year. I would say within that, I would focus on three core areas for us, and at least for this conversation. First is what we're doing with Darovasertib, obviously an agent that we have a lot of confidence in, that we believe has the opportunity to be the standard of care across the uveal melanoma patient journey. As you just mentioned, and I'm sure we'll talk about it here in a bit, we announced that what we think is a terrific partnership with Servier. We think they're going to be really fantastic partners for us to ensure we're able to get this therapy to patients worldwide. Beyond Darovasertib, the next two key focus areas for us will be in DLL3. We saw your terrific note. You were just talking to your colleague here a moment ago. We concur with a lot of the thesis of that note, which is our view that DLL3, we think, can be the next big antigen in the ADC arena. As you know, we'll have over 70 patients of data we'll be presenting here in the next couple of days. Finally, third is in MTAP deletion. Our perspective is that IDEAYA is the industry leader in the area of MTAP. We have multiple assets here, two that are either now in the clinic or IND stage. As you know, we have a third program we're targeting for the clinic next year. With that, maybe we'll open it up. I think maybe just on the last part with the IND engine, one of the key themes you will hear on Monday, September 8, is really our continued investment and advancement of our capabilities in artificial intelligence drug discovery. I think what makes us unique is our ability to integrate novel cancer biology with this capability in AI drug discovery. Our Chief Scientific Officer, Michael White, will be spending a bit of time on that. Hopefully, that will also generate a lot of enthusiasm. Okay, great. Clearly a lot on your plate this year. Maybe start with a survey, you know, deal that you guys did yesterday. I thought that was a pretty interesting one. That's for ex-U.S., right? It's for Darovasertib. Talk to us about, you know, the thought process behind that. Why is it a good deal for you guys long term? I'll let Josh take that. I think have him just cover kind of what our thinking here was, both commercially as well as sort of broader panel impact for the company. Josh? Yeah, so we're thrilled to have announced the Servier deal. Obviously, you know, we have a lot of respect for what they are as an organization and think they bring a lot to the table as we think about broadly commercializing Darovasertib. You know, we viewed the opportunity with Servier really from a couple of different lenses. One was just obviously the capital and the deal terms that it afforded us here in the near term. You know, we have a lot in the pipeline, as we've alluded to. We think this capital gives us a lot of flexibility to really focus in on those key areas that Yujiro alluded to and drive development there. Two, it's really focused in the U.S. W e're obviously an emerging biotech company. Having a strong partner, ex-U.S., gives us the ability to really focus in on sticking the launch here in the U.S. Some of the timing aspects around that relate to some of the pre-commercial work we have to do today. Third, ungating the adjuvant study, which we talked about in our release, being able to start that with Servier, sharing some of those costs is huge for us. I think the ability to ungate some of those studies in the adjuvant space, as well as the capital infusion that it gives us, and the ability to focus on our core areas of focus that Yujiro alluded to, are some of the reasons we thought this would be a good time to do it. The partner that we chose is an established, well-known name, ex-U.S. We're thrilled to have been able to get that done. OK, that makes a lot of sense. I guess we want to maybe move into the DLL3 ADC. Obviously, the data is coming up this weekend at World Conference on Lung Cancer. That's very exciting, over 70 patients of data. That could be very substantial. In my view, you guys got this asset last year from Henry. To me, that's probably one of the more underappreciated assets for you guys. As you mentioned, we did a deep dive into the DLL3 space. We think there is a lot of opportunity here for you guys to untap. Maybe for our audience, set the expectations for what we're going to see this weekend. What would be the bar for success? Yeah, sure. In terms of what you'll see, Lee, as you mentioned, there will be over 70 patients' worth of data. It will include both dose escalation as well as three expansion cohorts. In those expansion cohorts, there will be roughly 20-somewhat patients per expansion cohort. In summary, it's going to be a sizable data set from that perspective. What people should expect is an AE table and patient baseline characteristics. What I can tell you is the patient baseline characteristic, just bigger picture, and we publicly noted this in the past, which is roughly half of the patients are second line and the remainder are third, fourth plus line patients. In addition, on the efficacy side, what you should expect to see is a waterfall plot, obviously response rate type information. We will show a swimmer plot as well as some preliminary median progression-free survival data. The second line data is not sufficiently mature. I think we'll be able to provide a lot of information. In terms of what success looks like, I would say across all lines of treatment, and this would be targeting a confirmed response rate. We may not have a fully confirmed response rate, likely about a quarter or so patients are still too early. Ideally, if you could have a confirmed response rate in the 60% range across all lines, and then in the second line setting, can you have, you know, in the mid 60% and above a confirmed response rate. We think that would be a win. On the PFS side, Lee, as you know, in this indication, for example, IMDELLTRA got approval, accelerated approval in extension stage small cell, and they showed a PFS of four-somewhat months. What would get people excited, I would hope something in the 6 months+, would be clearly, at least we think, clear value from a durability perspective. OK, it sounds like response rate, you think the bar is probably in the 60% range across all lines. PFS, 6 months+ is probably a good outcome. For this data update, we probably wouldn't have PFS data, right? We'll have the swimmer lane, so we will have some sense of durability. No, we will show a PFS Kaplan-Meierkay. Okay. The all lines PFS will have preliminary data. The data is not very mature yet. Okay. For the second line, it's just too early. Okay. My comment around that PFS, sort of what would success look like, that would be not for second line, but across all lines. OK, got it. In terms of differentiation, obviously IMDELLTRA, which is TCMK, is approved here. You also got another DLL3 ADC, Zyla, that showed pretty strong data in the 60%-70% response rate. When you think about how you can position yourself and differentiate from these two assets, any points that you want to highlight in terms of maybe safety or efficacy side? Yeah, look, you know, I think Lee, here, as you know, the data is still relatively early, including from, you know, one of the peer companies that you mentioned. I would also emphasize that some of the response rate numbers that have been put out there are not confirmed response rates. As you know, from a regulatory perspective, that's frankly all that really matters. In particular, in an indication like small cell lung cancer, where, as you know, progression can be very quick, I think one just has to, at least I think, focus on the confirmed response rate numbers as the one that's going to matter. As it relates to, I think there, you know, I think Lee, what you're highlighting is there is another category of assets in DLL3, specifically around the T-cell engagers. I think there, what we can say is the data has been promising. As you know, and their approval study showed a response rate in the 40s. We talked about the PFS and, you know, roughly four-somewhat months. Median duration response, I believe, was in that 9- 10 month range. They did see high, fairly high AEs, where, you know, roughly 60% SAEs, about half of patients that had cytokine-release syndrome, as well as a neurological tox called IPANS, for which they have black box warnings for both. You do have to be under initial hospital monitoring to get that agent. We do know if any indication is a community cancer, it's small cell lung cancer. We think if you can deliver greater efficacy in the form of response rate, greater PFS, and a greater safety profile, we have a clear opportunity, at least we believe, to really be the agent or the class of agents that could really be the backbone in small cell. Now, it will be about who has the best class of agent. Let's have this conversation in a few days, you know, with actual world data that's out there. You know, we feel good about this update. I think there will be a lot of eyes on this presentation when we present it in Barcelona here in the next couple of days. I think one sort of safety event that many investors are very focused on, especially associated with TOP1 payload, is LD, you know, risk. We've seen that maybe with some of your competitor molecules. How are you thinking about this risk associated with your molecule? I understand you talked about the linker system might be, you know, more stable, and you have some, you know, clinical evidence to support that. Maybe walk us through that. Yeah, so that's correct. In the ADC area, specifically TOP1 ADCs, and also in lung cancer, interstitial lung disease, or also known as ILDs, is definitely one of the AEs that you have to watch for. When you look at large meta-analyses that have been done in the ADC arena, you'll find that the typical AE rate for ILD in lung cancer studies with TOP1 ADCs is roughly about 10%. The highest indication where you see ILD is actually colorectal cancer, about roughly 15%. As we all know, Enhertu has about a 12% ILD rate, obviously a different indication. Their grade 5 ILD, I believe, is 0.9% from their approval study. Where you really have to focus is that grade 3 and higher ILD rate. In lung cancer in general, for example, even Keytruda, you do see roughly a mid-single-digit ILD rate in lung cancer as a PD-1 antibody. It is something that you're going to see. Where we're going to be focused as part of this update is what is the ILD rate we see, in particular, what's the grade 3 and higher ILD rate we see. Do we see any grade 5? Obviously, that is another one I think people will be focused on. I'll be more brief on this. What are the parameters that typically drive ILD rates for ADCs? This is based on historical published data that's out there. We talked about the indication as being a parameter. A second is DAR levels. DAR-8, not surprisingly, typically has more ILD than DAR-4, the payload. Importantly, another parameter that has been associated with higher ILD rates is how cleavable that linker is. That's where we do think we may have a differentiation opportunity from Zye. Our linker system is different. Ours is a tetrapeptide cleavable linker, which cleaves once it's internalized with lysosomal degradation by enzymes such as Cathepsin B. Zye is specifically engineered to be a tumor microenvironment linker, which is specifically designed not only to cleave once it's intracellularly, but extracellularly as well. They've already noted what doses they're pursuing. What we have publicly said is all of the expansion doses we're evaluating are at higher doses beyond what Zye explored from at least their public communications that we understood, which I believe is 1.6 fixed bucket. OK, great. I guess we're going to see the data this weekend. In terms of the development timeline, I think one thing is interesting. If we, you know, look at Zye, they're moving to phase two-three later this year. You guys just started the trial in the U.S. just recently. You seem very confident that you're actually not really lagging behind. Tell us why you are so confident and how much data from China you guys can leverage. Yeah, look, you know, fairly recently, we saw recent data. It was over 70+ patients, as you mentioned, from the peer company. That's exactly what we're going to be sharing in our update right here in a couple of days. Patient exposure has been or experienced over 100 patients at this point. As you noted, we got IND clearance in the U.S. several months ago. Our perspective is that this is not going to be one based on a few months. It's going to be one based on who has the right clinical development strategy. Obviously, who has the best-in-class profile. We're very focused right now on what that clinical development plan is. Lee, I won't be able to give you all of the specifics because I'd have a very upset Chief Medical Officer if I provide you that. All we can say is we're thinking through this very, very thoroughly. Clearly an opportunity in small cell. We believe clearly an opportunity for some type of monotherapy accelerator approval path. You'll hear more about how we're thinking about clinical combination strategies, including with immunotherapies, as well as with a key proprietary asset we have in the DNA damage repair arena called PARG ID161, which, as you know, we think has the ability to enhance the durability of this class of agents around TOP1 ADCs. I know I threw quite a lot at you there. Hopefully, several things to think about. For small cell lung, obviously, DLL3 is a very interesting antigen. It's validated. We've been getting questions from investors. There are other antigens out there, B7H3. I think they just got breakthrough designation. That's clearly moving forward. You see some other antigens like SEZ6 that could be very specific to small cell lung as well. How are you guys thinking about DLL3 versus some of the other antigens? Yeah, look, our perspective on this is that our view is DLL3 is the key antigen, or at least we think the most exciting antigen for small cell lung cancer. There are a couple of reasons for that. One is the level of upregulation of DLL3 versus some of these other antigens, specifically in small cell lung cancer. Perhaps the most important is really around what drives resistance to ADCs, right? As you know, there are really two areas of focus there. One is resistance around the payload mechanism. Second is around up or down regulation, specifically of that antigen that's related to that ADC. The reason why DLL3, I would say, historically has been such a big focus for pharma in small cell is because DLL3 is directly connected to a key transcription factor called ASCL1, which is directly involved in the survival in small cell lung cancer. It's directly tied to this key survival oncogene, which DLL3 is directly connected with. The small cell lung cancer cell should not be downregulating that antigen, right? The bet we're making, which is why we actually accessed, I mean, we at risk went to in-license this from Hungary. Just so you know, we were very, very well down the line before the first data came out from Zye. Hopefully, people appreciate we went in there, did our work. We think that should play out. Where that should play out versus these other antigens like B7-H3 is ultimately response rate and, of course, durability. SEZ6, we saw the recent abstract published at World Conference on Lung Cancer in Barcelona. All I'll say is ours was embargoed. Theirs was not. People can make that judgment of which data they're more excited about. That's a good point. I do want to move on to Darovasertib. Clearly, it's going to be a big year for this asset. Maybe start with the neoadjuvant setting. I think next Monday, you're going to share some vision loss data. I do think investors may struggle a little bit with how to put that into the right context. What can you say to guide investors towards what types of vision loss data we're going to see and how to interpret that data? Yes. Here also, when we talked about the Servier partnership, I would also note that as part of their diligence, they did review the data that's going to get presented here at R&D Day, as well as the ESMO oral presentation, as well as the OS data that's going to be shared at SMR here fairly soon. As it relates to the R&D Day presentation, what people should expect is 20- 30 patients in the plaque brachytherapy cohort with a specific focus on the visual outcomes data. Here, Lee, there will be more data than what people have seen in the past. That's really the bottom line. People will see a waterfall of ocular tumor shrinkage. I think a question should be how deep are those responses? How consistent are those tumor reductions in a larger denominator? Obviously, that's going to be very important. Next is what are we seeing as it relates to these visual prediction tools, whether that's the amount of radiation exposure. The connection is quite simple. More radiation means more vision loss. Second is what do we see as it relates to visual prediction data. That's where we're going to have Dr. Singh present from the Cleveland Clinic. As I'm sure you know, it's actually his software that was developed by the Cleveland Clinic specifically. He'll kind of walk through what that whole setup is. Lastly is data we have not shown before, which is what is the actual impact we see to vision during neoadjuvant treatment. As you know, Lee, a lot of the focus has been what is the impact of vision post plaque therapy. We have not actually talked about do we actually see improvement in vision during the neoadjuvant therapy. We think it'll be informative and hopefully will give people more comfort about that specific cohort and those endpoints. Our CMO, Dr. Singh, will give their perspective. We're also happy to facilitate that analyst Q&A as well. That's very exciting if you can show vision improvement. I know you guys are also going to present at ESMO as well, perhaps seeing more patients. Is there any sort of new information that we should expect from that update relative to the R&D day? Yeah, that's correct. The ESMO presentation will have more patients. It's going to be roughly 100 patients. The reason why that number is larger at ESMO is that about 50 of those patients are from the enucleation cohort, maybe slightly more than that. That's data that we're not going to share at R&D Day because we're going to share that as a proffered paper presentation at ESMAO. Also, just as a reminder to everybody, for those that may or may not know, we did get breakthrough therapy designation specifically in the neoadjuvant setting in the spring. That data will be the data we're going to share at ESMO, which is largely the data we had shared with the FDA when we got the BTD designation. I think closing that loop will be important. For your ongoing phase three trial in the neoadjuvant setting, maybe update us on the enrollment progress and anything you can say in terms of the top line readout. What we can say is the clinical trial protocol has published on clinicaltrials.gov. Sites are being activated as we speak, and we're going through the screening process right now. We will give more guidance on that, Lee, as enrollment continues to pick up. Everything is on track as we had planned and have guided to date. Okay. Let's switch to the metastatic setting. I think at our oncology day earlier this year, the doctors are really enthusiastic about Darovasertib, calling it potentially to be transformative for these patients. We share that excitement. Now you have the pivotal sort of PFS interim data coming. I think you maybe pushed the timeline a little bit. Before it was year-end, and now it goes to year-end or Q1 2026. Maybe tell us a little bit what was driven that. Sure. As you know, there are two parameters, Lee, that are going to impact that PFS timing readout. One is enrollment, and second is the timing of the events as a time-to-event endpoint. Enrollment is done, right? We're finished with enrollment for the accelerated approval portion, and we believe we'll be on track to finish enrollment for the full approval OS portion as well by year-end. That adjustment has been made just based on how the events are tracking, which, as you appreciate, is not necessarily a bad thing. It seems like it's about events. Obviously, you know, that's sort of a dynamic thing. Exactly. OK. Maybe just talk about, you know, how confident then you will be able to hit the PFS at the interim. Would you be able to share some OS when you do the PFS analysis? Yeah, for the PFS, we know the number of events, which we have not specifically said to have the readout for PFS, just so that's clear. That's not an interim. That's just going to be the full analysis for PFS. They will look, as you mentioned, at OS at that time point. However, we do believe the data is going to be too immature to have a sense of where we are with OS. We will give guidance on when we think OS will likely come, you know, once we have this PFS readout. I think recently we're seeing the FDA seems to be very focused on contribution of components. Given your testing doublet, how confident that you guys are that the FDA will not raise this issue? I know you guys have done quite a bit of work here. Yeah, Lee, we feel very confident about contribution of components based on the discussions we've had with the FDA, including published data, as well as dose optimization data we shared with the FDA. On the published data portion, as you may know, there is published data with c-MET inhibitors, including crizotinib and cabo, specifically in uveal melanoma patients. It's not a large data set. It's in that 30 - 40 patient range. What we can tell you, the response rate was close to 0%. Next is data we have not published. I think ultimately, we may share it in the future, where we did do fairly extensive dose optimization as required by the FDA, where we essentially kept the crizotinib dose static at the current dose that we're utilizing. We dosed down Daro, and we demonstrated as we did that, we essentially lost activity. With the combination of that information, the FDA specifically did not require us to have crizotinib as a control arm. Okay. For the OS data update later this year, I know we talked about you think the right benchmark is perhaps 12- 13 months. You wanted to maybe add six months on top. We're probably looking at, you know, high teens, 18- 19 months. We also heard from some investors, maybe they want to see, you know, 20+ months, just given, you know, it's a single arm, right, understandably. Maybe tell us, you know, where do you think the bar, you know, should be? Yeah, I know, look, we appreciate the question, Lee. As you know, this is our favorite question to answer. Our guidance on this has been very consistent over the last several years, which, you know, we believe the control arm, based on, you know, large meta-analysis, will come out at roughly 12-1 3 months in the control arm. Our phase two-three randomized registrational study with OS full approval has been powered where we want to demonstrate a six months or greater benefit in OS. That would get you to the range, Lee, that you mentioned. We think if we deliver that, you know, we should hit our OS endpoint. I think the good news on this upcoming update that we'll have at the medical conference at the Society of Melanoma Research, which this year will take place in Amsterdam, I think the good news is we'll answer this question here very shortly in October. I know we're looking forward to provide that update. It'll be roughly 40+ patients in the frontline setting. Again, single arm, but we think will be a valuable data set to hopefully just give more color on this specific question. OK. Maybe let's move on to MAT2A. I think there are two things here, right? I think next week, you're going to present some data in bladder cancer. Talk to us what the bar should be. Also, I think this morning, PRMT5, you guys moving to the clinic. That's clearly very exciting. We're seeing, for instance, B1 is moving here. Talk to us about how you can sort of differentiate. Yeah, as you noted, Lee, we're very focused on this mechanistic combination between PRMT5 and MAT2A. We're thrilled to get our asset, the PRMT5, now an IND has been filed. We think it has a best-in-class profile. We'll talk about that at this upcoming R&D day. We do think in the MTAP area, this is all going to be about who enables the right combinations and the right indications. This one is front and center for us. As you know, within that, lung cancer is our number one priority, so we'll have a significant focus there. In terms of some of these other companies, I would just highlight two things. One is our TPPs are different than at least what we've publicly heard from others. I'm not sure we're going to have all the time to get into that today. Second is, recall here, Lee, we do have experience in the clinic, so we have a lot of information that we think we can bring to bear. We already know what dose we will need to be utilizing with ID397. We think we're the one company that really has the know-how here that we think will give us, really put us in a really good spot as it relates to at least leading this specific combination. Okay. With Trodelvy, I think maybe just quick, you asked about, you know, what does a win look like? I think here, you know, the bar is going to be high. I would say ideally, we're seeing a 40+% confirmed response rate. Ideally, median duration of response is six months or greater. Just a reminder for those that may not know, Trodelvy, there's been some real-world evidence data published about 98 patients. Later line setting at urothelial for Trodelvy post EV, the response rate is about 11%. For those patients, overall survival is actually six months. Progression-free survival, I believe, is about two months. As you can see, just a really, really tough situation. If you can deliver that kind of response rate I mentioned, clearly, you should have a path forward. Maybe just to tie everything together, obviously, you guys are very well financed, especially after the deal yesterday. You have pretty long cash runway into 2030. You also have a lot of things on your plate. What would be the top two or three sort of priorities for you guys over the next year? Sure. Josh. I think, as you're hearing here, we really are focused on kind of our top three assets. So Darovasertib, MAT2A, and DLL3. That's where I think we'll focus the bulk of our attention and our resources in the near term. I think appropriately, we're well funded to execute on those things. The earlier things in the pipeline, we'll keep you updated as we have data. We don't want you to forget about those altogether. In the interest of focusing people on those assets in the near term, I'd say that's it. Okay. I wish we had another hour. Yeah. Thank you both for the chat. I am really looking forward to the R&D day next week. Definitely. Thank you so much, Lee. Thank you, Josh. Yes. Maybe hard questions. Only hard questions. Hey, everyone. Thanks and welcome to our next session with IDEAYA Biosciences. My name is Lee Walczak, a biotech analyst here at Kenter. I'm very pleased to have the team from IDEAYA with us today, Jason and Harrison. Thank you very much for being with us. IDEAYA is probably known to be a C-47 story. I think the company has evolved quite a bit. You've added EGFR ADC. That's a very exciting asset.