My name is Maury Raycroft, and I'm one of the biotech analysts at Jefferies. It's with great pleasure that I'd like to welcome Yujiro Hata, the CEO of IDEAYA. Thanks so much for joining us today, Yujiro.
Thanks so much, Maury, and thank you to Jefferies for the invitation again this year. We look forward to the discussion, and great to be back here in London. Thank you.
And we're going to do fireside chat format. So maybe for those who are not familiar with the IDEAYA story, if you can give a one-minute intro to the company.
Sure. So IDEAYA Biosciences, we're a leading precision medicine oncology company. We have a significant focus on an emerging area of cancer biology called synthetic lethality. Today, we have five potential first-in-class programs in the clinic. Our most advanced is darovasertib, which is in a registrational trial for first-line metastatic uveal melanoma. We have a second program, IDE397, in phase II, targeting a very large patient selection biomarker called MTAP deletion. And we have several additional assets, Maury, as you know, in the precision medicine oncology space.
In addition to the five currently in the clinic, we are targeting three additional development candidates by the end of the year, which will hold an R&D day on Monday, December 16, which will provide an update on several of those. I did also want to mention, Maury, as of this morning, we'll be also sharing the news. We have been guiding towards a second MTAP deletion development candidate in a couple of weeks, since there's only a couple of weeks left in the year. That second target is around MTA-cooperative PRMT5. So that is part of the update we'll be providing today.
Got it. Okay, great intro and overview. And you mentioned the metastatic uveal melanoma study that's ongoing. Maybe talk about the enrollment for that study and where you're at with that.
Yeah, so that trial is going extremely well. I think the really high-level summary is the level of investigator enthusiasm we're seeing for that registrational trial is extremely high. Pretty much every single target enrollment that we've set for the program, we have exceeded, which is great. And as part of this recent earnings release, we did know we enrolled over 150 patients already in the study. As a reminder, the target enrollment for the first readout for potential accelerated approval, which is median progression-free survival, is roughly 230 patients. So we feel good about how that's tracking.
We will look to most likely provide more formal guidance as we turn the page to 2025. But Maury, as you know, most of our analysts are projecting a late 2026 commercial launch. To achieve that kind of timeline, we do anticipate a potential readout for median progression-free survival, which would be the primary endpoint for potential accelerated approval towards the end of next year. That's what we're continuing to track towards. Obviously, a lot of that is going to be driven by enrollment.
Got it. And anything else you want to say just around the drivers for getting to median PFS in the study? And maybe talk about just what information you're able to get from the study and what you're walled off from it.
Yeah, so it is a blinded study. So our randomization and the comparator arm has several key components there, including DTIC, which is a chemo, PD-1, PD-1 plus CTLA-4. Really, the quick summary here is we anticipate in that control arm, based on historicals, median progression-free survival has typically been reported in that two to three-month range. Maury, as you know, we presented at ESMO last year a median PFS that was just above seven months. So I think we have quite a bit of confidence, appreciate those are single-arm studies, but based on historicals, we feel very good about that. We did, as you know, had a Type C meeting with the FDA to get alignment with the FDA. That median progression-free survival was an acceptable endpoint for potential accelerated approval. We're obviously targeting on the enrollment side.
We've continued to also do further assessment of our phase II data set. So this is not the registrational trial, but the data set we present at ESMO. Probably one of the biggest questions we are getting is, have we had any luck on median overall survival from the combination, since that's not something we've reported? So I think stay tuned for that. We have been monitoring that data quite closely. So I would say here, don't be surprised if that's a data set we provide sometime next year.
Got it. So that's frontline median overall survival.
Correct. Yeah, correct. So caveat it with, it's a single-arm study. It's not randomized. But we all know that there's been a lot of data readouts on survival. And historically, in the frontline setting, they've been in that 12-13-month range. As we've said before, we have been targeting a plus six months for the full approval endpoint. So we have roughly 38 patients in the frontline setting. So we should hopefully get some reasonable view on that, which obviously will hopefully give us either less or more confidence, not just in the accelerated approval readout, but going into the full approval readout as well.
Got it. Okay, helpful. And what else can you say about powering assumptions for the ongoing pivotal study? And what PFS improvement do you need to show versus the expected approximate three months with investigator choice arm to get stat sig and gain accelerated approval?
Yeah, no, great question, Maury. So we haven't given all the specifics around the powering and the hazard ratios, but let's just sort of put it this way. What we showed is an ability to double progression-free survival in our phase II data set. And that's basically the assumption we're taking that we should have the ability to hopefully double PFS. And as we mentioned for the OS, similar to what I mentioned earlier about roughly a plus six months benefit on OS. And that's how we powered the study. So based on kind of bigger picture and what we've seen, we do feel confident in both of those endpoints moving forward.
Got it. Okay. And one of the interesting things about the setting is that there's a drug approved already with the Immunicore drug, but it's for a distinct population with the HLA-A2 positive population. For Immunicore, they've reported a run rate of $320 million at their third quarter update. What's your view on the read-through from Immunicore launch, their trajectory, and what that means for your opportunity?
Yeah, look, we think the great part about the Kimmtrak launch is it provides us real figures on a novel tumor type where there was not anything approved prior, right, before a couple of years ago. And here for the listeners here, they reported the last quarter just over $80 million in revenue for the quarter, which was approximately 30% quarter-on-quarter growth. So continue to see very strong growth. We don't believe they've achieved their peak sales revenue. So on an annualized basis, that's over $300 million. Importantly, the segment that they're approved in, which is HLA-A2 positive, based on our statistics and data, we believe that's about one-third of the metastatic uveal melanoma population. Maury, as you know, we're doing the frontline registrational trial in the other portion, which we believe is two-thirds.
In addition, we do believe the drug is active in HLA-A2 positive, and we're going to continue to support that with additional phase II data that we'll be publishing. So that's sort of just pure annual incidence is going to be larger. We believe we're going to be relevant to both A2 negative as well as A2 positive. The last part is around duration. So Maury, as you know, duration directly impacts market potential. So if you are in that range of a PFS, that's in the range that we're talking about, we have historically seen our therapy given beyond progression, so roughly three-to-four months. So that puts you close to a year. And then importantly, based on the two-year PFS Kaplan-Meier curve that we published, we're seeing roughly a quarter of patients that are progression-free beyond two years.
And the reason why that's critical is because now you're exceeding that one-year mark, and now you're getting to the two-year mark, a portion of patients that are progression-free. So having this long tail, those annual incidence patients starts overlapping. And that's when you see oftentimes a well overachievement on potential total addressable market and peak sales opportunity. So that's our continued hope. And obviously, as we'll also see, hopefully an update that we'll be providing perhaps sometime next year, also just getting a lens on where we are on the survival piece as well.
Got it. Okay. And with timelines approaching for this opportunity, how do you think about building out a commercial sales team for this setting?
Yeah, timely question. As you probably said, we just recently announced the hiring of Stu Dorman from Gilead. We're thrilled to have him join us as Chief Commercial Officer. We'll be starting in a few weeks here. And Stu Dorman has really terrific experience, helped launch Trodelvy, was involved in the commercial efforts for Opdivo, really has the right skill sets to be our commercial hire. And for us, really, our key three themes as we move forward to 2025, which I think this is central, first is commercial readiness, second is continued clinical execution, and then finally, third is around targeted pipeline expansion.
And we're firing on all cylinders on that front here. We do anticipate with a fairly focused sales force, roughly just about 30 U.S. sales force, we believe we can cover the U.S. market, or at least our current thinking now is a commercial CRO type model for Europe. So we do think that this is absolutely an indication a company such as IDEAYA could take on and hopefully be successful in.
Got it. And relatively recently, you disclosed alignment on a neoadjuvant registrational study. Maybe talk about that study design and also the data that you've already reported here and how this informed your pivotal study design.
Yeah, so first, for the listeners that may not be aware, so neoadjuvant uveal melanoma, so now this would be a trial that will be executing on a target patient population that's in the pre-metastatic setting, and the reason why this is significant is we're talking what we believe is a much larger patient population, an annual incidence that would go up from roughly 4,000 to roughly 12,000 patients, again, predominantly in the U.S. and Europe, and most importantly, a patient population where there are no approved therapies. So again, significant high unmet need, we think substantially larger than the metastatic population. Here, there's two subgroups of patients that we're focused on. We had an oral presentation at ASCO this past year. One are patients that are on track to get their eye removed because their ocular tumor is of the size or location that would require removal.
And then the second subgroup, which is around patients that are getting what's called plaque therapy. And this is basically a metal disc device that they stitch onto your eye. This emits radiation. And we believe most of the patients that we'll be studying in our study will lose their vision as part of that procedure. So the primary endpoints, which, from our FDA Type meeting with the FDA, now this is for full approval, for the enucleation cohort would be eye preservation. And then for the plaque therapy cohort would be some kind of visual acuity readout. I know there has been some conversation about we haven't provided that much information on the visual acuity. It was about 10 or so patients. What I wanted to report today is that data set has now grown.
We have over 20 patients on the vision piece for patients that have been on treatment over six months. We have now over 30 patients that we have now tracked for over four months. That's the data we've recently provided with the FDA. I think Maury, you and I talked about this. We are thinking about further paths to accelerate the registrational path for neoadjuvant. One of the ways you can do that is around regulatory status. There are your typical two options: either fast track designation or breakthrough therapy designation. All we can say is a meeting has occurred. We've provided that information. We have a fairly good sense of where the FDA sits on that, including on the vision piece. That's data that we're assembling.
We hope to be in a position to submit that briefing book by the end of the year. That will be another data set we will likely plan to share around middle of 2025. This will be a much larger data set than we provided before. Recall, middle of this year, it was about 35 patients, somewhat split between enucleation and plaque therapy. I know I'm throwing a lot at you here, Maury, but we should have over 75 patients in both of those groups with hopefully this sufficient follow-up. Our hope is we could present this data at a medical conference, and we should have hopefully a lot of milestones at that point, one including launching the study, the formal phase III registrational trial, this objective on this data readout, and then lastly, this regulatory piece that I mentioned to you earlier as well.
Got it. Yeah, really interesting update there. Maybe talk about the types of patients that you're going to enroll into this study. You mentioned the significant unmet need there too. What else should investors know about that? And then getting to this data update, middle of next year, the study is open label, right? So maybe just talk about a little bit more about the logistics there.
Yeah, so you're talking about for the neoadjuvant uveal melanoma side? Yeah, so here in terms of the patient population, Maury, I think for all of us that, for many of us that have been working in oncology for a long time, the neoadjuvant setting uveal melanoma, frankly, is one of the highest unmet medical needs out there. These are situations where treatments that are provided, there haven't been advancements in a long, long time, as we mentioned around eye removal, significant opportunity there to hopefully deliver patient benefit. Second, around the plaque therapy as well. I mean, these are procedures that have been utilized over the last several decades. And I think hopefully our therapy as a systemic agent, one that we believe is safe in that setting or sufficiently safe. And we clearly believe we're seeing activity.
The last piece I should have mentioned is the key secondary endpoint for both of those cohorts would be specifically around no detriment to event-free survival, which we believe based on the fact that we're active in the metastatic setting, we also feel good about that endpoint as well. So we hope that for all of these, in roughly a year, we can enroll this study plus or minus a quarter. So let's say four to five quarters and roughly two years from first patient enrolled, we believe we should at least be able to get to that first interim readout, which would put you towards the end of 2027.
Got it. Okay, all helpful. And let's move on and talk about MAT2A. So with this program, you're in the clinic with two combo studies, and you've shown great monotherapy data as well. Talk about where you're at with the combinations and what we could potentially see in the next update there.
Yeah, so we have two core focus combinations, Maury, as you know, that we're proceeding with. One is with AMG 193, which is Amgen's PRMT5 inhibitor. Here, the expansion focus will be in lung cancer, and we've guided currently right now is target expansion towards the end of the year, early next year. On that front of MTA-cooperative PRMT5, we continue to believe strongly in the mechanistic rationale and that we do believe in this pathway, hitting these two specific targets is the way you're going to deliver greater response rates as well as greater durability. Several companies, including us, have recently presented at medical conferences, including Amgen, including Bristol Myers, as well as us both at the triple meeting in Barcelona recently, as well as ESMO on monotherapy data. But ultimately, we feel to get into that earlier line setting, combinations are going to be critical.
Our continued focus here is on the MAT2A PRMT5, which is also why today we're this morning sharing that we have our own MTA-cooperative PRMT5 inhibitor. We do believe that has a best-in-class profile, and we hope to be able to announce that development candidate here in the next several weeks. Beyond that, as you know, we're in a Trodelvy combination in urothelial cancer. This is really to leverage the basic research and science that we did around the role of chemotherapy in combination with MAT2A that we believe we can leverage specifically in the indication urothelial cancer. So just so this is clear for listeners, really our objective with Trodelvy is to utilize that topo payload, but to have the ADC be able to deliver that chemotherapy topo payload in a more differentiated pharmacology through the ADC format. So that's really the thesis we're trying to answer.
We believe if we can deliver that safely, we do anticipate we should see more efficacy there. I think both will be exciting. Hopefully, there will be an expansion phase by the end of the year as well. We have other combinations here, Maury. We are considering. We're probably having another half a dozen discussions ongoing in parallel. I would say another area of interest is around standard of care combination. PD-1 is an obvious one. There's some data that we have as it relates to specifically PD-1 and IDE397. That is data that we may also plan to share at the upcoming R&D day.
Got it. And with the Trodelvy combo, maybe starting at that point, I guess where is that at right now? And could you have a data update from that picture potentially?
Yeah, no, so we're excited about this combo. For us, you may have known that we did share some early glimpse of data in Barcelona a couple of weeks ago where we had now reported a partial response in a urothelial cancer patient, and we did note in earnings that that patient did confirm that response also got deeper as well, which was nice to see. We have about a dozen scans we're getting that we believe is at roughly a therapeutic dose range for the cohort.
We've already dose escalated. We think we'll be likely done with the dose escalation by the end of the year, and we should be in a position to expand. In terms of guidance, we'll be working most likely through formal guidance as we get into January. But do we hope that we should be in a position to share that data sometime next year? I think that should be hopefully a viable objective.
Okay, and can you also say anything additional about the Amgen combo as well and when we could see data from that?
Yeah, I would say they're really the next core focus, and some of this is more in Amgen's, obviously, as they're running the trial, but for us, really the next key milestone is around the expansion, so there are public guidances, our hope for expansion by the end of the year to early next year, and that's continued focus for that one. I think at that point, the hope would be once you have expansion data at the right dose in the right tumor type, and here, Maury, we would just emphasize again that tumor type absolutely does matter. All of our preclinical data, our clinical data supports that comment, and that's why for us, the expansion with Amgen is the critical data set.
Got it. And relative to the monotherapy updates that we've seen from the PRMT5 drugs, what do you want to see with the combination? What more can you do with combo?
Yeah, I think here it's pretty simple, Maury. I mean, our expectations for both combos is we want to see higher response rates and greater durability. And I think as it relates to the durability part in particular, what we're trying to address through some of these combinations is around both resistance mechanisms and bypass mechanisms. And you're going to see this as a continued theme from us and what we've executed across our portfolio, including, as you know, with PKC and c-MET and uveal melanoma, with Pol Theta in part, with GSK, and of course, PRMT5 and MAT2A. It's all around trying to address bypass resistance mechanisms to hopefully deliver both higher response rates as well as greater durability.
Based on our assessment of this pathway, we're quite convinced that this is going to be the way you're going to be able to hopefully deliver that greater efficacy is through these rational combinations, of which this is one, obviously, combination that we're interrogating. There, hopefully at R&D day, we will be able to give a deeper dive into the science and why we continue to believe this piece around combinations is going to be critical.
Got it. And what else can you say about your new PRMT5 that's wholly owned at this point?
Yeah, look, it's a program that we've been working on for quite some time. We've been doing basic research and chemistry on this for well over five years. We've always set a very high bar, Maury, as you know, with any candidate that we select or anticipate targeting to select here very shortly. We do believe it has a best-in-class profile, both in terms of pure potency, selectivity. And then lastly, I think what's exciting about this asset is that this is fit for purpose to be able to combine it with IDE397. So as you know, sometimes when you put various molecules together, it may or may not be the most optimal. In this case, we were able to specifically select the candidate with this objective in mind. So we're excited to hopefully provide this update on that candidate nomination here shortly.
And our target would be hopefully to get that into the clinic sometime middle of next year. And so we hope we'll be one of the first companies to hopefully have a potential wholly owned combination in the MTAP space. And hopefully here, Maury, my main sort of message I would say, and hopefully this demonstrates our conviction around this mechanistic combination. From our perspective, we want to double down. We believe wholly owning this combination, having that flexibility is going to be important.
Got it. Okay, really helpful. And let's move on to your other phase I programs, including Werner, PARG, and Pol Theta. For Werner Helicase, what are you looking for in potential competitor updates from Novartis and Roche? So you've got two big competitors in the space when it comes to efficacy and safety in 2025. And can you de-risk the target? And how could that de-risk the target and inform your strategy?
Yeah, no, thanks, Maury, for asking about Werner Helicase. As you know, we feel this is a very important precision medicine oncology target. From our perspective, we believe it is one of the most important precision oncology targets that have been discovered and characterized in the last 10 years, and the primary reason for that is around the compelling biological validation of Werner Helicase, specifically in the biomarker setting of high microsatellite instability, which, as we know, is very prevalent in cancer. It's roughly a third of endometrial cancer, roughly 20% of colorectal cancer, as well as CRC. Not only is that synthetic lethal interaction extraordinarily robust, for those that may or may not be aware, Werner Helicase is a non-essential gene, which means you knock this gene out, normal cells survive.
In many ways, it's what we, I think, always hope for as a sector and what kind of these next generation precision medicine oncology targets can represent. Now, within that context, as you said, we have competition. I think we're in good company here. Novartis and Roche are both in early phase I studies. We are the first biotech company to be now in phase I with our Werner Helicase inhibitor. Importantly, we do believe we have a key differentiating features of our molecule that we are planning to present with GSK at an upcoming medical conference. Hopefully we'll be able to share more on that front. We do anticipate, at least based on what we understand and have heard, that there may be the first set of Werner Helicase clinical data provided publicly perhaps sometime next year.
Got it. And let's briefly talk about PARG as well. Just provide a status update on that program. And could we potentially see an update by the end of this year for PARG?
Yeah, so for PARG, the guidance that we provided is expansion target by the end of the year. So here we've been continued to do dose optimization. We feel we are narrowing on what that expansion dose will be. So that's our guidance. We feel good that we'll be able to hit that objective. The others, hopefully we'll be announcing an FPI with Merck and Keytruda and endometrial cancer. And this here is not specific to HRD. So this is in high microsatellite instability as well as microsatellite stable. And we also have supporting data on that that we may very well likely share at R&D day as well. Here, once we start that expansion, that will really be the data focus here. Expect us to focus on a single, most likely specific tumor type as part of that expansion.
And then lastly, as you know, Maury, one of the areas we're excited about PARG is the ability to combine it with a topo ADC class. So as you know, the bispecific ADC, we recently nominated the candidate around B7-H3 PTK7. So look for that continued theme from us around leveraging the PARG mechanism specifically to enhance the activity and in particular durability of the topoisomerase ADC class. And we believe that we can unlock that opportunity. That is a very significant opportunity in terms of both patient need as well as broader commercial market opportunity.
Got it. So I think we're pretty much out of time. Maybe provide a status update on Pol Theta and then talk about what investors should expect at the R&D day and just key catalysts that investors should be focused on going forward.
Yeah, so in terms of Pol Theta, that dose escalation is going well. We do anticipate hopefully being able to provide them some guidance with obviously the okay from GSK of when that expansion should happen. That would trigger a $10 million milestone payment. And there also we anticipate look for GSK to start the combinations with niraparib, fairly close proximity to initiation of that expansion phase. In terms of R&D day, Maury, I would say for us, we're continuing to refine the agenda, but I would say several key topics look for us. One is to continue to address why we're excited about the darovasertib neoadjuvant uveal melanoma opportunity. I think here perhaps also look for us to have several KOLs with us to hear from them directly about why we think this is such an exciting opportunity.
The next is what I sort of mentioned in the very beginning. Really, our three focus areas are around commercial readiness, continued clinical execution, and pipeline expansion, and then I would say last is going to be around our pipeline expansion, so here we will talk about existing clinical molecules, our upcoming candidates, and our hope here is to really dive into the deep science, why we believe we are the key biology and research leader in a lot of these key pathways and new biomarker areas, so I think it should be a great event and hopefully will showcase our scientific leadership and our commitment to continue to build a diversified pipeline moving forward.
Got it. Thanks so much for joining us, Yujiro.
Okay, thank you, Maury.