ORIC Pharmaceuticals, Inc. ($ORIC)

Great. Good morning, everyone. Thanks for joining us here at the Goldman Sachs Global Healthcare Conference. And good morning on our second day of event ever who's joining us online as well. And we're thrilled to have the team from ORIC here this morning, and we'll just get right into it.

Maybe to start, there was some news last week, not from you guys but from Fulcrum, which was an update that has obviously been top of mind given the mechanism of action overlap. Maybe you could speak to the Fulcrum update on pociredir and any potential implications for your program in prostate cancer in Rinzimetostat?

Yes. Firstly, thanks for having us here at the conference. So I just got a conference. We're just talking about the long flight across the country. So at a high level, last week, Fulcrum announced the discontinuation of their PRC2 inhibitor, which they were studying in sickle cell disease. If you read the press release, the press release kind of states that the FDA's position is really based on 3 things. One is the risk benefit profile for sickle cell disease, which is obviously very different than it is for oncology. Two was the previously disclosed malignancies they saw in their preclinical tox work. And third was the ongoing secondary malignancies that tazemetostat is seeing in various indications as well. So obviously, that was -- people think that's a true to us. When we take a look at this, we think the implications are limited when we look at Rinzimetostat and again, that's really for 3 reasons. One is that we've dosed over 100 patients, both as a monotherapy and in combination with AR inhibitors. We have not seen any instances of secondary malignancies based on the [indiscernible] we've done, which is a 4-week tox 13-week tox in 2 species, which is a requirement for oncology, which is different from non-oncology. We have not seen a sign of malignancies as well. And third, I think most importantly is, as I said before, the risk profile for prostate cancer is very different than sickle cell disease. So that's, I think, first and foremost, when you think about any drug, it does come down to the risk benefit profile, taking into consideration therapeutic area, taking into consideration the overall patient population as well. We also went on to say that over the last 6 months, obviously, we've had a number of interactions with the FDA as we imminently look to start a Phase III study, and there's been no change to our base case plan. Now as you can imagine, with the news on tazemetostat, which I think happened in the first quarter, secondary malignancies was a topic that came up as well, but there was no delay or anything in our timing. And lastly, last week, we did announce that we have completed the end of Phase I meeting. The 3 objectives of that meeting were first was to finalize the protocol. The second was to confirm the dose selection that we picked for the Phase III study, which is 400 mg once a day of Rinzimetostat in combination with darolutamide. And third was to determine any other prerequisites that were required for the initiation of the Phase III study. So we did announce last week that the protocol is finalized, the dose is confirmed and there's nothing else kind of precluding us from starting that Phase III study. So we expect to start that study imminently. At the end of the day, I think our view is this all comes down to the risk-benefit profile of the drug. Even if you look at some of the prostate cancer drugs today like docetaxel, some of the PARP inhibitors, some of the radio ligands, there is some small percentage of patients that see these secondary malignancies. So again, it all just comes down to the risk-benefit profile, which, again, oncology is very, very different than sickle cell disease.

So maybe we could talk about a more relevant comp within the prostate cancer contact, which is mevrometostat. And could you just speak to like the mechanism of action, differences and distinctions between rinzi and mevro?

Yes. So going way back, I think PRC2 inhibitors, in general have been studied in prostate cancer for a number of years. I think the #1 issue has been the first-generation PRC2 inhibitors have been plagued with 4 drug properties or in vivo potency, very, very short half-lives, call it, 1 to 2 hours, and some of these also had SIP auto induction, where you actually saw a decrease in exposure with repeat dosing. We think mevrometostat call it a second-gen PRC2 inhibitor -- we think they've improved on a number of those. They've got good in vivo potency. They've increased the clinical half-life from about 1.5 let's call it 5 hours. -- and they don't appear to have the SIP auto induction issue. And as you can see, that has translated into a pretty profound benefit based on their randomized data they presented at ASCO GU in 2025. . What we bring to the table, I think, is we continue to have good in vivo efficacy we have a clinical half-life of 20 hours, and we think that could be a key differentiator for us because with these epigenetic modifiers, what you want to do is cover semen for 20, 24 hours, and we're able to do that with that. Now Pfizer's half-life being 5, 6 hours does require BID dosing. So you do have this kind of peak to trough. And our view and this view as well is that a lot of the on-target toxicities is Cmax driven. So we're able to prevent that is the once-a-day dosing.

You started to allude to this. But as you think about that differentiation, how would you expect to show up in like clinical benefit? And what maybe tie that into what you've actually seen in the clinical data you've produced today? .

Yes. That's a great segue. And I think what we expect that to see is in the safety side of things. And I think we have seen that. And as you know, we had a pretty comprehensive Q1 update. The Q1 update was really the objective of the Q1 update was really threefold. It's 1 to select the patient population that we were going to study the first Phase III and selected dose of rinzimetostat that we're going to move forward with and thirdly, to determine which AR inhibitor are we going to pick for the first Phase III study. As you know, we're studying both with apalutamide and with darolutamide. We did that. We selected a dose of 400 mgs of rinzimetostat, and we've decided to go with darolutamide for the first Phase III study. . So if you look at that data update, I think, first and foremost, the efficacy that we've shown on the PFS because that's ultimately the regulatory endpoint. It's a highly competitive to what renewed shown compared to mevrometostat. If you look at the landmark analysis at 5 months and we look it at 5 months because of the average follow-up we had, the median follow-up, I should say, was 5 months. We had a landmark analysis about 84%, which is right on top of what Pfizer showed at 5 months. both the ASCO GU data in 2025, I think it was about 80% and then ASCO GU 2026, it showed about 84%. So the differentiation really comes on the safety side. So we were able to show that competitive -- highly competitive efficacy with a differentiated safety profile. So if you look at the adverse event safety events versus Pfizer, you can see both in the frequency and the severity of events were significantly less. If you look at Grade 3 treatment-related adverse events, we had mid-single digits, I think, depending on which data set you look at, the 875 BID and the Fed or the 1250 in the fastest state, they had somewhere in the mid-30s to high 40s. So we think safety at the end of the day, will win out here. Obviously, you're dealing with older men that are on therapy for an extended period of time. So I think that's the key differentiator so far, what we've shown now could that translate into longer PFS longer term, we'll have to run that out to see what that looks like.

Right. One of the things that's come up in our conversations kind of subsequent to the data was this like nonspecific discontinuations in the Phase I trial. Maybe you could just contextualize that for us. and help us think about what you guys saw in your early Phase I update relative to apples-to-apples comparisons versus mevro or other basic cancer trials?

Yes, I think that's a good question. That's something that we've gotten a lot of questions about since our last data update. I think a couple of things. We addressed that in a few ways. I think, one, what we saw in our study is no different than what you typically see in other Phase I studies for prostate cancer. Just to remind people, it is a Phase I study, the primary endpoint is safety and PK. It's not an efficacy endpoint. I think that's kind of one. When you look at other Phase I studies in prostate cancer, there's been many that's been reported recently, including meets and some of the other T cell engagers and other things like that. It's very common that you have early kind of nonrelated discontinuation. So I think that's kind of one. In these early Phase I studies, you don't always have perfect clarity on exactly why there are discontinuations short of something definitive like a safety or an adverse event. And so patients can continue for a variety of reasons. Often, it's attributed to something like with dry consent or physicians' decision. What's a little bit unique in prostate cancer studies, you also have the phenomenon of increasing -- and so often patients can come off the study, especially in a Phase I study where the endpoint safety can come off early, not for radiographic progression, but just to move on to other studies or other therapies. And so that's something that you typically see in Phase I studies with prostate cancer, even though the prostate cancer guidelines discourage that. They encourage you to stay on [indiscernible] until radiographic progression, which is a key kind of regulatory endpoint. As we move forward, thinking about a Phase III study, a lot of times that resolves itself, usually because the primary endpoint is something efficacy in case of mevrometostat, it's radiorapic progression-free survival or overall survival patients, physicians are often blinded to PSA response to not have any bias in the study. And so you see that as kind of typical in the way the progression of clinical studies for prostate cancer trials are conducted.

You've guided us writing another update from the program this later this year. And maybe if you could just talk about the scope of update that you're going to provide? What kind of -- what kind of things should we be expecting there?

Yes. So we provided update in January of each year, which we do on a regular basis. And at that time, we specifically intentionally called it a program update to give us full optionality or flexibility on what we provide there. So that could be a number of things. That could be just an update on where we are at the first Phase III study, which we referred to as malais1. It could be our thoughts on a second Phase III study in prostate cancer could be potentially a third -- another study outside of prostate cancer or could be some additional data update as well. Now obviously, we're expecting the mevro 1 data update as well. So it could also be some color on the results of that study and anything we learned from that study as well. So that's kind of broad. Obviously, we'll provide additional details at a later point.

Within that range of things you just said, 1 of them is data in the post-therapy eye population. And so what do you think you need to have to be able to provide a robust update such that it would be worth sharing in the second half of the year in terms of patient numbers, et cetera?

Yes. Specifically on the post AR inhibitor population, I think, one, we're obviously excited by the data we've shown so far. I think when you look at radiographic progression-free survival, it looks fairly consistent to what we've seen in the postretirement in I think you asked a good question, what do we need to see to kind of move that 1 forward. I think, one, we want to see a little bit more patient, more patients responding the same way that we have in our initial bolus of data and then to, I think, a little bit longer duration is what we want to see. And so again, as Dominic said, similar to the post abiraterone patients, we had a median fall up of about 5 months. And so the 5-month PFS actually stands out pretty well compared to other therapies in the space at that landmark. So I think we want to see a few more months of duration to see if that holds. And I think that we would get pretty excited by that moving forward since there is a significant unmet need there.

Minus the benchmarks are for RPS lasted five months?

Yes. It's relatively similar to the post abiraterone setting and that you see a lot of patients, either 1 in clinical studies or 2 in the real world, getting AR switch. And so this would be the opposite. So instead of patients having received abiraterone and getting an AR inhibitor, this is kind of the vice versa, they're getting an air PI so the air switch would be abiraterone. And in that setting, there's been some recent Phase III studies that reported data, you typically see in about 3 months. And so the AR switching is typically shorter as patients do worse having seen an AR inhibitor switching to abiraterone. So I think that's 1 chemotherapy is about the same, so about 7 to 8 months. That is a 5-month landmark PFS and whereas we're tracking about 85%. And I think the other interesting benchmark there, it is a relatively small data set. It's a population that Pfizer has not been focused on with mevrometostat but they did report Phase I data in 1 of their earlier updates a couple of years ago in that setting. And there, they showed a 5-month landmark PFS in the high 60s. And so again, there's some separation there. Again, it's small data sets to compare. But I think what we're seeing so far is very encouraging.

You got it. All right. Let's talk about the registrational study [indiscernible]. Maybe first speak to the dose selection at 400 mgs -- and are you confident kind of with that selection and it sounds like you had these regulatory conversations that you've satisfied any sort of project documents or other requirements?

Yes. I think we disclosed this on the Q1 update. We did complete an extensive exposure response analysis has a number of different measures, looking at the correlation to exposure to both the efficacy and safety. And the key takeaway there is that from an efficacy standpoint, there was no statistical difference in the dose on the safety there was -- so that was the key driver. So this is actually the ideal scenario project optimist, right? You want to maintain the efficacy without pushing the dose too much from a safety standpoint. And as you pointed out, you did complete the end of study and the FDA was satisfied with the completion and the way we approach project Optimis. So 400 is our dose going forward. We feel good about it. and we'll have data in probably in early 2028 from the Phase III study.

One of the key strategic questions you answered update earlier this year was the decision on combination agent of darolutamide. Maybe you could talk about the advantages you saw partnering in that direction, both with respect to the drug and bear as a partner.

Yes. I think at the end of the day, we think both apalutamide and darolutamide are both great drugs. I think what we said to date has really been no drastic difference between the 2 agents combining with apalutamide that I think at the end of the day, and we know this, right? We know enzalutamide and apalutamide are SIP inducers, and when you're combining it with our drug as well as mevrometostat, you have this kind of SIP interaction, the SIP DDI which decreases the dose or the , I should say, of our drug and mevrometostat as well, which requires you to increase the dose. And I think that's why Pfizer is required to push your dose as well. So that's a big difference, I think, when you look at the difference between going with darolutamide and avelumab. Again, we think they're both great drugs. We just think from a differentiation standpoint, -- this further differentiates us from Pfizer in the first Phase III study. Now to be clear, the decision to proceed with the first Phase III study darolutamide does not preclude us from using a different AR inhibitor in the second Phase III study in prostate cancer that we choose to go. So I think that was the key driver. They're both great drugs. And if you ask a number of KOLs, I think they stack rank the 3R inhibitors. They say, the cleanest from an efficacy standpoint, I think most people would say they're generally the same. I think from a safety standpoint, first, they say darolutamide is the safest drug of the 3. And if you look at some of the darolutamide, I just kind of rehash history here, but enzalutamide was launched back in 2012, apalutamide team 7 years at 2018 and darolutamide came a year after that. And darolutamide a run rate, call it, $3 billion, $3.5 billion and they're growing at 50% to 60%. So they're kind of 1 of the leaders in the space and they're growing exponentially there. So I think that's another factor we think about. Obviously, we're going to hitch our wagon to the key driver there. And the further differentiation on safety here, we think the better it is for us for this indication.

Okay. you mentioned that you've reached FDA I guess what can you share about the parameters and the registrational program that you're going to start here in the near term? .

Yes. So I think -- obviously, we don't go in intimate detail on our FDA interactions, but at a high level, -- the study design is a 600-patient study, 300 in the treatment arm, 300 in the control arm. The dose selected as we said, it's 400 of rinzimetostat plus the approved dose tide the control arm will be a physician's choice of AR inhibitor docetaxel. And again, the primary endpoint will be regranted PFS. Now we're expecting to start that study imminently. We think it will take about 15-ish 15, 16 months to enroll that study, and we could have top line data as early as early 2028. .

Okay. What would you expect the mix of docetaxel versus AR inhibitor to be based on real world utilization trends?

. I think generally speaking, we'd say the range is close to 50-50, maybe it's 40-60 on the extremes. But depending on which KOL you speak to, there's definitely a preference that each KOL has on what they like to do in some of that baby regional or their experience with the drug as well. So I think, yes, I think that's generally role. Now if you look at Pfizer, I think they're generally assuming -- it appears they're kind of assuming that similar split between AR inhibitor and docetaxel as well. .

Right. All right. That's a great transition to NESPRO1 data, which is away from you all, technically, but is a catalyst for the cost this year. Maybe just remind us briefly of the trial design relative to the Phase III that you guys are taking forward.

Yes. To be honest with you, we've obviously done our own independent work around our stats and our trial design. And it is very similar to mevro 1. And just to remind everybody that, again, it's 600 patients, they're using 5 BID in the fed state of mevrometostat plus the approved dose of enzalutamide versus the control on, which again is physician's choice between docetaxel dilute -- that study is powered to show a hazard ratio, I think about 0.66 or 65. They're assuming the control arm does 6.75. And if you do rough math, it appears you're assuming around 6 months for enzalutamide and about, call it, 7-ish months for docetaxel. So if you assume a 50-50 split between the 2 agents, you get to this blend of 6.75 in the control arm. For the treatment arm, they're assuming 10.2%. And as you know, they showed about 14 months at ASCO GU in 2025 in their randomized data set and the more recent updated as 2026 issued about 14 months. So they're assuming some level of degradation. So we think that study is well powered. We think that study has a chance of being positive as well.

It's pretty common to assume some level of degradation from early studies in the later studies in oncology. But I guess, how would you guys think about that level of 14 months to 10 months in transition from a solar study to a later stage trial. .

Yes. I think generally speaking, I'd say that maybe a little bit on the conservative side based on -- we've seen multiple data sets that they presented where they've confirmed the 14 months. But again, we think it's an appropriately powered study. And even if they're able to show 10 months, I think 10 months in that setting is a big win for the class for Pfizer and directly through to us. if you look at other agents in the space, Provia, for example, in a pre-chemo patient population is probably close to 10 months. So this as you guys know that in this study design, you're looking at metastatic CRPC patients. These are patients that had abiraterone, and they could have seen up to 1 round of chemo as well. So in theory, these are more heavily pretreated patients than the [indiscernible] pre-chemo patient population. .

Okay. I think the other maybe small point to mention as well as Pfizer is using approved dosing regimen and formulation in their Phase III. So they are switching from the 1250 BID in a fasted state into the 875 Fed. And I think the data they've shown on that, obviously, 1 way more tolerable than their original regimen that they used in their Phase II randomized -- and then two, the data they presented earlier this year and ASCO GU, the efficacy seems like it's tracking a little bit better as well. The PSA response is a little bit better. The PFS hasn't been reached yet. And so there's actually potential for that it could exceed in the earlier Phase I study, they also 17.1 months. And I think, as Dominic said, I think we believe if it is a positive study, that should be very commercially relevant when you look at the benchmarks. There are not many therapies in prostate cancer that have beaten the chemotherapy control. So I think that's 1 really interesting thing that, that is the standard to actually be. And so if they are able to do that, that would be fairly significant. The only other benchmark out there is Pluvicto that is doing very successful competing well against docetaxel. That has an RPFS about 9 months. And so we think if Pfizer can post results in the 10 months is kind of what they're assuming. -- with an oral therapy that's relatively generally well tolerated, we think that would be very successful for the program and the class.

Great. Is there anything that you might take into consideration on seeing your data that could inform Phase III kind of at the margin in your own design? .

That may be difficult. Obviously, we don't know when the mevro 1 data will be released. I think the guidance is mid-'26 or second half '26, which basically means the rest of the year. I mean we're early June, so we don't know when that's coming. As I said before, we're imminently starting the Phase III study. So it may be highly unlikely that we'd be able to kind of read into that. The other thing I'd say is that Pfizer typically will present top line data, just telling you the study is positive and maybe very little color around that. So we won't know the details about that as well. So I mean, realistically, it may be very difficult to kind of see what -- get any color on what they've disclosed other than what the study hits or not. .

Okay. Maybe you just talk about like a world in which, obviously, your base case is that it succeeds on efficacy, and it looks reasonable from a profile perspective. Is there a world in which the trial disappoints but you guys still feel confident in rinzimetostat? And what would that look like? .

Yes. We kind of think about it in 4 buckets. One is there's a big win where they just kind of knock it out of the park. Two is where they barely win Three is where they barely miss and 4 is where they're really totally dismiss which I'd say for based on the data that we've seen based on the powering of their Phase III study, we think is kind of off the table. -- in the middle 2, I think it's interesting because we really would need to understand why they barely made it or why they barely missed. Again, we think the key differentiator for us to date based on the data that we presented really comes in the form of safety, right? Better safety on better compliance, you maybe you get longer duration as well. So I think that's the key point. Now again, when Pfizer presents that detailed information, we'll be telling, they obviously have 3 studies ongoing for 1, 2 and 3. So we'll have to just see obviously what they present when they get this top line data update.

Okay. Maybe you could talk about the market opportunity and the sort of indication that you selected? And could you provide like a high-level view of what you think the opportunity is there? .

Yes. So we -- I mean, I think 1 to start off it. We think it's a very significant commercial opportunity. Again, we're kind of going into patients that have previously failed an RPI specifically abiraterone. One thing to point out, if you look at the kind of prescriptions in the U.S., Abiraterone right now is tracking about 50% of prescriptions in the RPI market. So there's very significant abiraterone use in the U.S. global as well. And so we think there are a lot of patients that have failed abiraterone roughly half the market. And I think there's pretty good statistics out there that kind of cite 35,000 to 40,000 metastatic prostate cancer patients, a majority of them have had seen a prior ARPI, potentially up to half of those would have seen abiraterone is their ARPI of choice. And again, 1 of the benefits with the PRC2 inhibitor, what we're starting to see with our data and the mevrometostat data is you have the potential for really long duration of therapy with mevrometostat in a randomized Phase II a 4.3-month PFS. If you kind of add those numbers together, using kind of typical pricing for an ARPI, you can easily get to a plus year opportunity just in the U.S., just in the post abiraterone setting. Again, if we were to move forward in a post AR inhibitor setting, that would be essentially about the same market size, again, just in the U.S. alone. So it's a very substantial market opportunity with a very significant unmet need.

Yes. And again, it sounds like you're as you share this market. So how do you think about kind of share .

Yes, again, we think the TAM is $3.5 billion in the U.S. If you just get some road map, based on number of patients and duration and using some average price. When you look at the ex U.S. market, if you look at prostate cancer, it's probably 90% or 100% of the U.S. market. So overall, we think worldwide, that could be close to a $7 billion opportunity. I think when we think of market share I kind of look at it 2 ways. One is you have the perfect analogy with darolutamide, right? You have a drug that came out 7 years after anlutamide. The only difference is really on the safety front. -- and that's doing $3.5 billion, and that's growing 50% per year. I think the other thing is we've done, actually, Matt, and our Head of Commercial, have kind of done an independent market research with the party. And based on that market research, if you just kind of put the profiles of our drug versus mevro and the only differentiation is safety, we should -- so safety does matter here is the point, and we think that could be a huge differentiator especially as you kind of move to a to earlier lines of therapy like castrate-sensitive prostate cancer, where patients are not on drug for months but they're on drugs for 4 years or so.

Great. Maybe we can pivot for the last couple of minutes here to the EGFR program. It's specifically designed for potency against exon 20 and a typical mutations in that drug. -- is ORIC-114, and I know there's a new name, but this will be easier for me to say. So let's start with how the agent is theoretically differentiated versus the range of other EGFR program.

Sure. Yes, we call it inozertinib. -- is kind of the new name. And so yes, preclinically, the molecule, I think a couple of things was designed specifically for exon 20. So oil screened and designed for that. I think that's 1 differentiator. That is not true for most of the EGFR exon 20 inhibitors today. And then two, also prospectively designed to be brain-penetrant. And so we thought that, that is a key feature preclinically that was missing in the marketplace. I think there's been a number of companies a number of therapies that have been going after EGFR exon 24. While we always felt the landscape was missing like a truly good brain penetrant drug, which is extremely relevant in lung cancer. . As you see from studies and other prevalence reports that at least 1/3 of patients will actually present with baseline brain mets at diagnosis or the time they enter clinical studies and a majority of them will actually progress with brain lesions over the course of their therapy. And so what we've seen with other targeted therapies for the other oncogenic drivers is that you really need a brain penetrant drug to be very successful to have very long duration of therapy. And so we think that, that is kind of the key differentiator. That was early preclinical data and how it was designed. We have presented clinical data now where we're actually seeing that. And so those were the things that we really wanted to see in the clinic. And so I think 1 that we look at the potency and selectivity, which is what it was designed for. And we're actually seeing that in the clinic. From a safety perspective, some kind of toxicities, where we've seen none of the off targets that other therapies have such as cardiotoxicity and QTC prolongation, CPK elevations, liver enzyme elevations, things like that. We haven't seen any of that. So I think that's 1 very good. Two, we're enrolling an extremely pretreated patient population. We're allowing extremely broad enrollment criteria for CNS criteria. And so 1 of the distinguishing features is that we allow patients to come into our study with so-called active brain metastases. And so they do not have to have been treated. They can come with full active CNS metastases. That's very different from other studies that will restrict patients from having brain metastases at all. Some studies allow it, but they have to be treated with things like radiation. And so that's kind of key. And what we have seen from our early data, we're actually seeing really dramatic relaunches in those patients. And so we think Again, that is the different feature that we have presented so far. We think that, that will translate into kind of long duration of therapy that has the potential to do that. And so we're excited to kind of continue to update folks with the progress of that program.

Great. You did share an update in December and you, I think, anticipate sharing another update kind of midyear this year. Maybe you could talk about the data to date and the scope of the update we could affect.

Sure. I can cover the data, and then I think Tom can kind of point you to what to expect going forward. So I think a couple of the things that we've shared is we are really prioritizing first-line patients. And so we initially started enrolling patients that were previously treated. Now we're really focused on the first-line patients, both in the EGFR exon 20 side and the atypical side. What we've seen, just from a high level so far, I think the efficacy in terms of initial ORR seems to be as good, if not better, than what other therapies have reported. And both in terms of EGFRx288typicals, the safety profile as well looks as good or better than anything else. And so I think we feel extremely excited by that. . And then I think the 1 thing that is extremely differentiated is what we've seen on the CNS side. So again, in both of those patient populations, that's the first line EGFR exon 20 and the atypicals, we enrolled patients with active CNS mets. -- patients had measurable CNS mets. And in both of those populations, we had 10 CNS ORR in those patients with measurable disease. That has been something that has not been reported yet. And so we think, again, that 1 speaks to the differentiation and I think leaves us hopeful that we'll see a long-term duration of benefit there. Other companies that have reported data actually on the exon 20 side, most of them actually do not see a benefit in patients with CNS metastases, which is why a lot of times those are excluded from clinical studies. And so we're seeing activity in patients that aren't even allowed to be enrolled in other states. We saw a couple of updates at ASCO. There's a company [indiscernible] reported data with sunvenertinib. They had extremely restrictive CNS criteria. But when you look at the data, they actually had no benefit in patients that actually had CNS metastases, even though they were required to be treated. And so that was kind of the third study. We've seen that with others as well, is that there's just no benefit with some of the other therapies out there. Patients have any sort of history with CNS disease.

And I'll take the second part. So we have a pretty comprehensive update in the second half of the year. This will be at the 80 mg dose, which is kind of the recommended dose we're going forward with. So in first-line EGFR exon 20 is a monotherapy, we'll have 20 to 25 patients worth of data in first-line EGFR atypical of another 20 to 25 patients of data, and then we'll have about 20 patients or so in exon 201st line with combination with amivantamab as well. So it's a pretty comprehensive update we'd expect to see there. It's obviously systemic response rate. CMS response rate, safety tolerability and a look on durability as well. When we think about the benchmarks in each of those respective areas, we think more or less, it's that 60% plus from a systemic response rate. .

Okay. Maybe briefly, you could touch on what you see as the market opportunity or the size of the market in this population, particularly given the competitive landscape? .

Sure. Yes. I think when we think about this space, it's a smaller opportunity in terms of patients wise than prostate cancer, but there is the potential for really long duration of treatment. What's been pretty well characterized is both of the EGFR populations we're targeting. Exon 20 people typically cite about 2%, maybe a little bit higher on a cancer and that will get you several thousand patients in the U.S., about 4,000 patients. The atypical side seems to be a little bit bigger. I think it's commonly excited about 3% of lung cancer. And so that, again, that will get you kind of another 6,000 patients. So with about 10,000 patients the potential for long duration of therapy, typical drug pricing, you can easily get to multibillion dollars just in the U.S. for both of those as a TAM. The 1 thing that's a little bit different with targeted therapies in our view is you really want to have a best-in-class therapy. It is rare that you see market kind of split evenly in targeted therapies. So again, we want to have a best-in-class profile, if that is true. That's a very substantial commercial opportunity for both of those populations we're targeting. Again, if you add both of them together, it's about 5% of lung cancer that is kind of in the ballpark of an ALK market, and we've seen that market in the U.S. is about globally is about $4 billion to $5 billion split between kind of the 2 leading therapies there.

Okay. maybe in our final minute here, you could talk about cash runway and the clinical activities that are embedded in that guidance.

Yes. So we ended the first quarter with $420 million in cash and investments. That gives us cash runway into the second half of 2028. that does assume, obviously, the Phase III study for rinsimetostat, MLAs 1 that we're starting imminently. That also assumes us starting a Phase III study for inozertinib in early that's fully burdened in there. I think the other key takeaways as I said before, we're expecting top line data from the first Phase III study with rinzi in early 2028. So we've got cash runway well past that going into the second half of 2028. So we feel we're well capitalized at this point in time.

Beautiful. Well, it's great having you. Thanks for the conversation today. And thanks everyone joined us. And with that, we can turn it out.

Thanks.

Thank you. Great job.