Morning, everyone, and thanks for joining us here at the Goldman Sachs Conference. I'm joined by Yujiro Hata, CEO of IDEAYA Biosciences, and we're thrilled to have you all, all with us. Maybe we can start with an overview of there's a lot going on. Maybe you can distill for us what you think of as some of the kind of key value drivers of IDEAYA, particularly over the next, let's call it 12 to 24 months.
Yeah, first, great to see you, Karin. Thank you to Goldman Sachs for the opportunity to participate again this year. So, IDEAYA Biosciences, we have six programs in the clinic. We're targeting to have nine by the end of the year. Our lead program is darovasertib. It's in a frontline, HLA-A2 negative, registrational trial in the indication of metastatic uveal melanoma. Here we have completed enrollment to enable potential accelerated approval, several months ago. We are guiding for our first top line results to hopefully enable accelerated approval. I think here that's definitely a significant focus area for us. Here the primary endpoint to enable that potential approval is median progression-free survival. Historical PFS here has been roughly two to three months.
As you know, Karin, we've reported PFS at a major medical conference a few years ago, where we observed PFS of roughly seven months. In addition, in the second half, we are guiding to a median overall survival update on this combination in the frontline setting, also in the second half. We anticipate that's gonna be either at a medical conference, or we'll do a concurrent as a manuscript, alongside those top line results for accelerator approval. In addition, we have several data catalysts for neoadjuvant indication. As you know, we got breakthrough therapy designation here a few months ago. We anticipate that will also be at two major medical conferences, including one in the second half of roughly 100 patients. A lot happening for darovasertib , moving very quickly. Maybe just quickly beyond that, I would start, sort of highlight two additional areas.
One, is in the MTAP deletion space. As you know, we're very active here with the lead MAT2A inhibitor in phase II. We also will have our own PRMT5 inhibitor in the clinic. We anticipate here very shortly.
Okay.
to enable a wholly owned combination before the end of the year here. I would say indication focus areas include lung cancer, pancreatic cancer, as well as others.
Okay.
Beyond that, I would probably say DLL3 Topo ADC is also front and center. This is now a phase I asset in the U.S. We've dosed, in aggregate, probably now north of 90 patients with a partner in Hungary and China. We are guiding towards a third quarter medical conference update of over 50 patients, including dose escalation as well as expansion. We did recently learn that we do have an oral presentation for that. That will be exciting to see. Beyond that, we have several other programs in the clinic, including Werner Helicase, Pol Theta, and we have other INDs that we're targeting by year end.
Okay. We'll run through a lot of that, I think, today, but we'll start with the darovasertib piece. Like you mentioned, we were looking to see potentially registrational data by year end. I guess, what are you looking to see in terms of progression-free survival for it to be kind of like worthy of that approval?
Yeah. Our hope here is that we do think the control arm is gonna be fairly stable in PFS based on historical data of two to three months. Ideally, we're above sort of that five and a half month range. We think we can hit that. We'll have the ability to hit our primary endpoint.
Okay. And remind us in terms of the phase I, II , what you saw there and how it informed sort of the phase II , III portion. Also, could you talk about any kind of baseline patient characteristic changes from one study to the next?
Yeah. So we've seen a PFS of, you know, roughly seven months, both in the frontline setting as well as the pretreated setting. In the hepatic only setting, we saw that PFS go to almost a year, 11 months. It's been fairly robust. And, you know, that was across roughly, you know, 40 some odd patients. In terms of the registrational study, you know, we don't think there's gonna be substantial changes here. We're obviously exclusively focused on the frontline setting for the registrational study, also in the HLA- A2 negative population. But, you know, we feel good about that endpoint and at least based on our historicals, you know, we're looking forward to this update by year end.
Okay. It's an event-driven study, so obviously timing's a little bit tricky to predict. How confident are you that you'll be able to get there by the end of the year?
Yeah, there's really two pieces, because it is an event-driven endpoint. You know, Karin, as you mentioned, first is about enrollment. So where are we relative to enrollment? The good news here, we've exceeded the target we needed, which was 250 patients. We've probably enrolled over 320 now. We'll be frankly almost done with the full OS approval enrollment, you know, hopefully by the end of the year. The second driver beyond enrollment is, as you mentioned, the timing of the events. It's blinded, but you know, those events are being tracked. We continue to track as we had expected, and at least so far we are on track to have those results by year end.
Okay. Assuming that the data is positive, how quickly would you expect to be able to file for approval, and what would the timelines be for kind of a launch then?
Yeah, we haven't given specific guidance on that yet. As we, I would say, as we get closer to those top line results and perhaps at the time of the top line results, being able to give more visibility on the timing of the NDA submission. I think here, we would just highlight we do have fast track designation, so we would get an expedited review on that. We are already beginning things to prepare for that NDA submission, including dialogue with the FDA in terms of, you know, all the nuts and bolts of what they would wanna see as part of that submission.
Okay. Obviously there's been some debate around the accelerated approval pathways that the FDA, in particular, we've seen in some lung cancer settings that overall survival being requested. I guess in light of that backdrop, how confident are you that an accelerated approval pathway will be available on these data?
Yeah, we feel quite confident about the endpoint for accelerated approval, medium progression-free survival. I think several things I would highlight. One is we did have an official Type C meeting with the FDA to get endorsement around these endpoints and the design. As long as we followed what the FDA asked us to, which was to do an integrated phase II, III study, where we would seek accelerated and full approval off of the same study, PFS for accelerated approval, OS for full approval. That's exactly what we've done. We feel very confident. Second is we've had multiple interactions with the FDA on this program, you know, since that conversation, including breakthrough therapy designation, and even more recent discussions with the FDA again, just around some specifics around the NDA filing, including areas such as real world evidence submission, et cetera.
So, so everything is on track.
Okay. You will have overall survival data from the phase I, II this year as well. I guess, how should we think about the right benchmarks for that, that endpoint?
Yeah, we are excited to give this OS update from the phase II study in the second half. We anticipate it is gonna be likely 44 patients or more. Here we believe historical OS in the treatment naive setting is roughly 12-13 months. In fact, you may know there was an updated presentation at ASCO from several investigators that noted the frontline median OS of roughly 10 months that was based on a certain meta-analysis where they were able to parse it out based on stage of treatment. We believe based on historicals that median OS in the control arm will likely come in about 12-13 months. Here we have powered the randomized phase III to ideally show an OS improvement of six months or greater. You would ideally want to be in the high teens or the 20 plus range for OS.
Okay. Understood. And then in terms of the uveal melanoma market opportunity, I guess, can you remind us how you see it across the HLA status? And what can you learn from sort of precedent launches in this space?
Yeah. I think first, we would highlight that, you know, our target focus for the frontline study is in the HLA-A2 negative market. I would say primarily based on our internal patient screening data and other data that we have externally. We do believe the majority of the population is HLA-A2 negative. Second, you know, Karin, as you know, I think we would just emphasize we believe our drug is equally active in the HLA-A2 negative as well as HLA-A2 positive based on its mechanism of action. That is why we are studying this agent in the neoadjuvant setting irrespective of HLA-A2 status. In terms of the commercial opportunity, we think the annual incidence, which is primarily an indication that is found in the U.S. and Europe, we believe is roughly 4,000-5,000 patients.
That prevalence number would be probably about double that, we anticipate. As you've noted, you know, there is another launch that has, there is a launch that has occurred here. You know, we've seen a robust revenue uptake. I know the last quarter they reported quarterly revenue, you know, of roughly almost $100 million for the quarter. I think that's encouraging to see.
One of the things that's driven the success of that launch, I think, has been duration of therapy, particularly people being treated kind of post-progression. As you think about that dynamic, would you expect to see something similar with, with darovasertib in this patient population?
Yeah, I think the success there are probably several things here, Karin. One is I think we're really seeing real time the benefit of getting front, frontline approval. You know, it is a rare tumor, but when you get frontline approval, you, you're gonna capture hopefully good market share.
Sure.
Second is, really just highlights the unmet need, right? Unfortunately for these patients, survival in the setting is, you know, could be 10-12 months depending on whether you're a first or second, third line patient. Patients need better therapies here. On your question on duration, yes, duration I think is gonna be a part of the story. Here, what we can say is, as I mentioned, PFS of, you know, if you sort of ideally have in that seven to eight month range, we have seen patients get treated beyond progression. We also did report a two-year PFS Kaplan-Meier curve in the past, and we are seeing roughly a quarter of patients that are progression-free even beyond two years. We do think we will have the opportunity for a long tail for at least a subset of patients.
As you ramp kind of towards the registrational data, filing strategy, et cetera, can you talk about the commercial strategy, when we should expect some of those pieces to come into play and sort of like how you are framing out that commercial go-to-market?
Yeah. We are hard at work in building a commercial organization right now. We've, you know, brought on a Chief Commercial Officer. We've hired several additional VP level folks in commercial. We recently brought on a head of tech ops. We just recruited a head of medical affairs. We're going full force, in terms of U.S. commercialization. We will give more visibility on that timing as we get closer. I think really the next step would be around, as your earlier question, on the timing of the U.S. NDA submission. In addition, we'll be about how do we handle ex-U.S., in particular Europe. I think I would say our high level thinking, we have, you know, several possible scenarios, but that's also guidance that we'd like to give as what's our plan for the Europe regulatory and then ultimately commercialization.
At this time, I would say, our significant focus is to commercialize this ourselves in the U.S. We are having, I would say, a few different discussions with larger companies here, but that's our base plan right now. We also think we can do this ourselves in Europe as well.
Okay. Last year you kind of revealed some data and a registrational plan for darovasertib in the neoadjuvant setting. Maybe you can run through just briefly the key highlights of that data set and how it informs the registrational program.
Right. In terms of, sorry, for the neoadjuvant.
Neoadjuvant. Yeah.
Yeah. For the neoadjuvant, that's correct. We have two clinical data updates. We're targeting from now to the end of the year. One will be at a retinal conference in the third quarter. We anticipate that will likely be about 30 patients from the plaque bracket therapy cohort, and there the data will be focused on visual outcomes. The second, which will be a larger data set of about 100 patients, will have roughly half enucleation patients, the other half plaque bracket therapy. That data set will be largely the data we shared with the FDA when we got breakthrough therapy designation. I think it'll be important for the public to see that. We're excited about the data. I know, you know, the team is very excited about it.
I think hopefully it'll fill in some gaps, particularly around some of these vision endpoints that we had talked about earlier. Now it's about really getting the study up and running. You know, we're targeting to get that started here and hopefully dosing our first patient here fairly soon.
Okay. Maybe you could give us some historical context around eye preservation rate, which is one of the endpoints that you've shared on the neoadjuvant side. What have you shown and how does that compare to?
Yeah. Here the past data that's been presented, so people know we've given a company update on this and the enucleation cohort. Data was also presented as an oral presentation at ASCO in the past. Really the quick summary is we've seen the majority of patients we've treated, we've been able to preserve their eyes. Just so people are clear on what's happening, for basically roughly about, we think roughly a quarter of patients, because they have a tumor in their eye, unfortunately the standard of care procedures actually do eye removal. What we've shown is that in a portion of patients, in this case the majority of patients with darovasertib treatment, we were able to get them off of that enucleation track so they can avoid eye removal.
Based on our conversations with the FDA and what was in our briefing book, the target is to ideally have an eye preservation rate that's 10% or higher. We are well above that range, which is why we feel very good about this endpoint and which is also why we believe we got breakthrough therapy designation from the FDA.
Can you talk to us about what the phase III design looks like and some of the key number, number of patients, how long, et cetera?
Yeah. So basically, really the two key pieces is one is enrollment target. So there's two cohorts. One will be enucleation, the second will be plaque bracket therapy. The enucleation cohort will be 120 patients. The plaque bracket therapy cohort will be 400 patients. It'll be randomized two to one, from treatment to control arm. The primary endpoint for enucleation will be eye preservation rate, which we just talked about, the threshold of 10% on a 95% confidence interval. For the plaque bracket therapy, it's gonna be a 15 letter vision test and it's gonna be the comparison between the treatment and control arm. And we wanna show a benefit between 15%-20%. That's how it's been powered. If we achieve that, including needing to demonstrate no detriment in event-free survival, then we would get full approval. So there are two independent cohorts.
We also have the ability to submit the enucleation cohort earlier if that data is mature earlier. If we do, we think that could accelerate at least the enucleation submission by probably about half a year.
Okay. Will you also need to have the event-free survival data included in that enucleation population, or is that contingent on both groups?
Yes, that we would need the event-free survival data to submit, including the enucleation data early. We would need the EFS data. And also I think an important point, we would need the EFS data sufficiently mature, not just in the enucleation cohort, but across both cohorts.
Right. Okay. So can you talk to us about how long you expect it to take to start to accrue event-free survival data sufficient to meet this bar, which is no detriment in EFS?
Yeah. We think the timing is gonna be roughly two years from first patient enrolled to get EFS. We don't believe we're gonna need all of the events, roughly about 35%. It's because this no detriment threshold, you know, is statistically lower than needing to show superiority or non-inferiority. Second is we are studying the high metastatic risk population. If you model that, basically our biostats team believes that we'll have that first interim read for no detriment to EFS, two years from first patient enrolled.
Okay. Can you talk about the data, like the studies that you have ongoing? Have you been monitoring event-free survival and does that factor into some of the biostatistical modeling that you're doing?
Yeah. So the short answer, it's still early for EFS, and the neoadjuvant phase II study, not the registrational study. You know, we have had patients on for probably in that six to 12 months. You know, I think we just need longer, probably a year or so longer. The numbers that I provided to you is mainly about when we anticipate those patients will get metastatic disease or, sorry, recurrence in the control arm based on data. And based on the past data, we anticipate in the high risk population in approximately three years, half of those patients in the control arm should have gotten recurrence.
Okay. In terms of the high metastatic risk patient population, how is that population defined? And do you expect that that definition will be in any way kind of restrictive on your label ultimately?
Yeah. Maybe the second part on the label, you know, I think there it will be a discussion with the FDA. You know, obviously our hope, we would be able to get a broader label, but I think ultimately that would be a conversation with the FDA. That topic did come up as part of our FDA dialogue. They understand why we're focusing on the high risk population, primarily because that would enable a faster readout on EFS. In terms of how metastatic risk is categorized in this population, it's primarily genetic. There are different genetic genes and sort of gene expression profiling tests people go through, including what's called the Castle assay, which pretty much most all uveal melanoma patients now go through, which categorize their metastatic risk in basically four distinct categories.
Okay. Triangulating all of this together, what's the kind of timeline we should anticipate getting the registrational data on, and what kind of launch timeline does that set up?
Yeah. So for the metastatic population, we haven't given that specific. That would top line results, obviously end of this year. Hope, you know, we'll be able to submit that NDA obviously next year. We'll get more specificity then. For the neoadjuvant here, I would say kind of big picture, we think it'll take probably about five quarters to enroll the study. And then you're gonna have a sequence of three data sets that are gonna come in some sequential fashion. We think the first data set from the neoadjuvant full approval study, the first will be around the enucleation data. We think we'll have that largely within a year, something in that timeframe. The second data set will be around this no detriment to EFS. And as we talked about, there we think that will be the second readout with two years from first patient enrolled.
The last will be around the vision from the plaque therapy cohort. That, we anticipate, will be roughly 18 months for the first interim readout from last patient enrolled.
Okay. Maybe we can move on to the pipeline. Lots of stuff in development. Maybe you can start by highlighting the key data events this year, which are some of the things you're focused on.
Yeah. I would say, after darovasertib, we have guidance now on four clinical data readouts from now to the end of the year. That is gonna be quite active. I'd probably say next most near term is on DLL3, our Topo ADC program. This is a potential first-in-class asset and then potential best-in-class asset. We are studying right now in small cell lung cancer. We have interest in other tumor types like neuroendocrine tumors as well as others. We did recently guide that we're gonna have a clinical data update at a major medical conference. We're happy to report that we did recently learn it's been accepted as an oral presentation. It will likely be north of 50 patients. We'll include escalation as well as several expansion doses.
We know one of our peer companies here, it looks like they're targeting an expansion dose of approximately 1.6 mg per kg based on at least what we understood. We can't say here that we have dose escalated well beyond that dose, and are exploring expansion doses as well beyond that dose. I think that's a good thing. Just quickly here, you know, I know on our corporate presentation, you know, we're seeing about a 70% response rate. That's not a fully confirmed response rate. I think those are the questions we'd like to see. You know, what is the response rate? What kind of durability and AE profile? I would say that that's a, you know, I think a significant focus and I'm happy to talk about others. If any questions on that.
Maybe we'll start with that and then I'll circle back to other pipeline. You mentioned this data is coming later this year. In terms of number of patients, you also talked about that, but how should we think about the bar for efficacy in this patient population and in this indication?
Yeah. I mean, I think what we can say is, you know, we're seeing a very active monotherapy signal for this program. You know, there are several categorical therapies that you have to think about when you think about small cell lung cancer, including the DLL3 T cell engagers. You know, I think there you saw about a 35-40% response rate, you know, pretty good durability. They've gotten accelerated approval in the extensive stage setting. I think they're moving into the second line and then also looking at frontline studies. The other assets are probably the B7H3 ADCs. I think there, you're seeing a bit of a higher response rate, but probably more in that 40-50% range. At least we think with DLL3 Topo ADC, you know, we are seeing a higher response rate.
As you know, in this indication in particular, it's a big part of this is about durability. We think that's really what's critical in ensuring we have an adverse event profile that's competitive. I would say on its face right now, I think it's looking more encouraging than the T cell engagers, as well as the B7H3 ADCs. You know, we just have to see how that holds up as we go into larger patient populations. The last piece I will mention on this, Karin, is, you know, we do have a key proprietary asset that we think we can differentiate from our competitors. This is around the clinical combination with the DNA damage repair agent we have, called PARG, P-A-R-G 161.
Based on a lot of the clinical data we've generated, we believe this specific mechanism has the potential to enhance the durability of topoisomerase-based payload. That's going to be a central focus for us. We hope to dose our first patient on that by the end of the year.
Okay. Maybe this is related to that last part of your answer, but most of your programs are small molecules. This is an ADC. How did you come to get this asset and how do you think about including an ADC in part of your portfolio? Why is it right for this target? Maybe you can just talk about some of those.
Yeah. We have two large molecule antibody-drug conjugates in our pipeline. Our first is DLL3. We also have a bispecific B7H3 /PTK7 that's undergoing IND-enabling studies, and that IND will get filed this year. For us, Karin, you know, the reason why we're in the antibody-drug conjugate space is because of our long heritage, which is now about a decade in the DNA damage repair small molecule space. You know, we are an industry leader there from PARP to Pol Theta to Werner Helicase. We bring tremendous know-how in the area of DNA damage repair small molecules. We believe one of the greatest areas of unmet medical need in the ADC arena is around combinations, in particular combinations to try to enhance durability. 'Cause I think, as you know, one of the areas where ADCs have performed well is around response rate.
I do think durability is something that's really front and center. There are probably not a lot of great ways to do combinations. We think DDR small molecules is definitely one of the ways that that can be generated. We're thinking about this long term. Our plan is to be hopefully an industry leader in this area of DDR small molecules with ADCs. It's been a strategic objective of ours to wholly own these assets.
Okay. You mentioned that you partnered in the DLL3 ADC. Would that be your anticipation around ADCs as you enlicense them or will you develop competencies in terms of discovery on that kind of?
Yeah. I know that was the second part of your question. I apologize. Yeah. We licensed DLL3 as part of a partnership with Hengrui Pharma. You, I'm sure you know, they're the largest pharmaceutical company in China, a major player in the ADC arena. We're thrilled to be working with them. They are trying to get this commercialized, that asset in China. They're very much investing and pushing that program forward hard. We do have a second partnership we did in China as well. I do think in the near term that will likely be our approach and strategy. As you know, Karin, our pipeline's quite full with what we have. We think with PARG, with our two ADCs, the second, which will be clinical stage two, we'll have our hands full for quite some time.
Okay. Sounds good. Maybe we should speak on 161 since you mentioned it. Other than the combination that you've got ongoing, what sort of updates should we anticipate for 161 from here? And sort of like what is the nature of that update that you wanna be able to share?
Yeah. I would say for PARG ID-161, and, you know, I would say this is probably a decision we made several quarters ago. The focus for that program is gonna be largely now focused on combinations with topo ADCs. I think if in terms of data updates, that's gonna be our focus. We know a lot of companies are trying to trail us in this target space. You know, we obviously wanna be also just thoughtful about data disclosure. I think the main updates we're gonna focus on is all around the combination with our clinical assets in the topo ADC arena.
Okay. Speaking of combinations, one of the areas you spoke to earlier was MAT2A. You've obviously got monotherapy studies in lung and bladder cancer as well as some combination work that you plan to kick off. Maybe on the monotherapy piece, what are some of the benchmarks for success on the monotherapy and how are you looking to use that data to inform your combination?
Yep. I would say high level, big picture in MTAP deletion, our perspective is, we think the path in this segment is gonna be all around rational combinations and who's the one that can enable those rational combinations first, and who's gonna be able to prioritize the right tumor types. We talked about some of them earlier, including lung cancer.
Yeah.
potentially pancreatic cancer as well as others. What we've seen with MAT2A IDE397 phase II, clearly now positioned as first in class, and it is a response rate of roughly 30%, in tumor types like urothelial cancer as well as lung cancer. There we have two combination strategies that we're pushing forward. One is in our partnership with Gilead on Trodelvy. As you know, we're looking at MTAP deletion urothelial cancer. We just picked an expansion dose. We're probably gonna pick another expansion dose here fairly soon. We also expanded that partnership with Gilead to also now include lung cancer. Their frequency is large. MTAP urothelial is probably about a third of patients biomarker, and in lung cancer it's probably 15%-20%. The second combination focus is with PRMT5. And, you know, as you know, this has been our focus to enable our own wholly own combination.
We do think we have a potential best-in-class PRMT5 inhibitor. I don't think we'll have the time today to go through all the reasons why.
Sure.
We're happy to do that at a later point in time. This for us is a high conviction combination. We think out of all the combinations different companies are focused on in MTAP, we continue to believe that MAT2A PRMT5 is the high conviction combination to run, in particular for lung cancer. We would expect to see higher responses, greater durability. As you know, Karin, we have a third target program that we're gonna target for IND next year in MTAP. We have not disclosed that target, but we think once all of that occurs, we will be the de facto leader in the MTAP deletion space, which we believe will be the broadest clinical pipeline in MTAP.
Okay. Maybe you can talk to us about kind of like where you get that conviction and how you expect the two MAT2A and PRMT5 to work together. Do you anticipate this being additive or synergistic, and sort of what is the underpinning of that confidence?
Yeah. We've done extensive preclinical evaluation in the MTAP arena across many, many targets, across the various clinical assets. We think this is one of the few combinations that's not additive but truly synergistic. We think through this mechanistic combination, we have the potential to intercept several key resistant mechanisms for PRMT5 in particular. You know, we do see much greater durability, preclinically. And you know, we presented that in multiple peer-reviewed settings, including at this year's ADCR. We sort of had a broad.
Yeah.
Publications that went out on this. And we know that, you know, just from the big pharma area, there's a lot of interest in this combination. I think a lot of people are gonna be waiting for us to generate our data.
Okay. If that synergy plays out, it'll be most evident in the duration that you see relative, or will it be obvious as well with the response rate?
I think it should be both.
Okay.
Yeah. It should be, should be response, but in particular durability.
Okay. Maybe you can speak to the Werner Helicase. We've learned some things about competitor programs this year. Maybe you can elucidate the differentiating features of your own Werner Helicase program and how you expect that to kind of translate in the clinic.
Yeah. I think Werner Helicase is another potential first-in-class program for us. We think now the target has been clinically validated. You know, we've seen responses here as a single agent. Here, just so people are aware, the patient selection biomarker is high microsatellite instability, which is prevalent in several key cancers, including gynecological cancers like endometrial and ovarian. Also, it is prevalent in CRC, roughly 20%, as well as gastric cancer. Definitely a large area, an area of high unmet medical need. In terms of drug discovery approaches, there are several clinical stage assets, including our own, that primarily come in one of two buckets. One is either covalent inhibitors or non-covalent inhibitors. We and GSK, when we were picking our clinical molecule, we had both series that we're advancing forward. We had a very good covalent inhibitor as well.
I think ultimately we believe non-covalent is the way to go for this target. A lot of it is around where these inhibitors bind to the D1, D2 domain of the binding pocket and around key susceptible point mutations that you have to be just very cognizant to, to ensure you get sufficient activity.
Mm-hmm.
You may know one of the, you know, big really concerns in the area of MSI high is it's inherently a very high tumor mutational setting. You have to be very cognizant about point mutations, in particular around cysteine point mutations. There has been past data around covalent inhibitors and cysteine point mutations causing resistance. We know that from RAS, EGFR, and BTK inhibitors. We think non-covalent's the way to go. When you look at the clinical landscape, at least ours binds uniquely to that pocket of Werner, unlike other molecules in the clinic today.
Okay. We're running close on time, but I did wanna ask you about the KAT6 inhibitor you revealed on stage here last year.
Yeah.
Maybe you can just provide a little color on the features of this and how it compares to other programs in the clinic.
Yeah. I think, look, KAT6 has now become front and center. We know Pfizer had some really exciting data at ASCO just recently, you know, where they're, you know, with in combination with fulvestrant, saw roughly about a 35% response rate. And importantly, you know, in a very tough patient population, they saw a median duration response north of 15 months, which is quite impressive. Here we have what we think is a first-in-class differentiated profile. This will be first of its kind in the clinic if we can get that into the clinic. The IND is targeted for this year, which is a selective dual KAT6/7 inhibitor.
We won't have time to go into all the specifics, but we do believe KAT6/7 is essentially a paralog where the ability to hit both should drive greater efficacy, hopefully higher response rates, greater durability than what we've seen with KAT6 alone. In addition, we believe with this dual inhibitor mechanism, we hope to be able to remove fulvestrant, which would be obviously a huge achievement. Second is that we can expand this beyond indications like breast cancer into big indications like lung cancer.
Okay.
Definitely one to watch.
Okay. I think you've got something like three INDs planned for this year. I guess as you think about the discovery capabilities, is that the right cadence for the business in terms of bringing new assets into the clinic as we look into the future?
I don't wanna put too much pressure on our CSO, but yeah, I mean, I think ideally we're in that cadence of an IND a year. I think this year, you know, we happen to have a lot of productivity, we've already filed another IND. So it would be four INDs this year.
Okay.
which is definitely a record for us. Yeah, I think a cadence of one IND per year is where we wanna be.
Okay. In terms of cash runway, what is the current guidance and what are the clinical activities embedded within that?
Yeah. This past quarter, we reported just over $1 billion of cash. You know, we're in a very strong financial position. We did recently update our cash-out guidance from 2028 into 2029. You know, we've got a very strong runway and we've got a lot to invest in right now.
Okay. Great. I think that brings us close enough to time and is a good way to end. Thank you so much for joining us.
Yeah.
Yujiro, thanks to everyone who joined us here and online.
Great. Thanks so much, Karin. Thank you for the time.