Good afternoon, everyone, again. Welcome to the next session with ORIC. I'm Ami Fadia, Biotech Analyst here at Needham. A quick reminder to our listeners: you can send over questions for me to ask through the dashboard. With that, I wanted to welcome Jacob Chacko, who is the CEO of the company, to the session and also turn it over to him to make the presentation, and then we'll have some time at the end for Q&A. Sounds good. Ami, thank you for having us. We appreciate the time today. I'll spend about 30 minutes talking about the company and overview of the pipeline, and focus primarily on two of our programs, ORIC-114, which is a lung cancer-focused program, and then ORIC-944, which is focused on prostate cancer. I'll try to keep some time at the end for questions, Ami, from you or from anybody else who's listening in. I'll just start out with the usual disclaimers. I will be making forward-looking statements during the course of this presentation and would encourage you to take a look at our SEC filings for a more fulsome forward-looking statement disclosure package. Let me just take a second and tell you about ORIC and the mission of the company and really sort of what we think defines us and differentiates us from what is otherwise a quite crowded oncology space. ORIC stands for Overcoming Resistance In Cancer. In a nutshell, that is the mission of the company. We have been for many years now focused on various mechanisms of resistance within the cancer space, primarily focused on solid tumors, mostly on lung, prostate, and breast as our key areas of focus, and generally with a small molecule approach as opposed to antibodies or other modalities. Some of that hearkens to the team that we've built over the course of time, which I will touch on. We believe that we have built one of the most differentiated pipelines of programs, both first-in-class and best-in-class programs, going after various targets that are either, in some cases, totally unvalidated, novel, first-in-class type of opportunities for ORIC, and in other cases, validated targets, but ones where we think we have a better molecule, better approach, with better drug properties. We can kind of talk about philosophically how that's come together over time. We've always, since the inception of the company, deployed a precision oncology mentality, which is to say that we tend to gravitate towards targets that lend themselves to trials where we can take a patient-selected, biomarker-driven approach that generally leads, I think, to more comprehensive data sets and ones where you can prospectively select for patients where you're enriching for phase II and eventually phase III signal, and often leads to accelerated approval timelines and just faster timelines in general in the oncology space. Those are the kinds of targets that appeal to us quite a bit. Now, we've built the company with a dual-pronged strategy in terms of the pipeline. And what I mean by that is, since the inception of the company, we've had robust internal discovery capabilities, but we've actually paired that up with opportunistic business development in the case of two of our programs where we've in-licensed those programs. And those may be targets where someone else has had a more advanced approach or a better approach than what we had been able to come up with internally. And so that's been a unique way that we've built the pipeline. The team we've brought together has worked together for many, many years, both at ORIC and, in fact, even prior to ORIC, in many cases, at prior companies that have had a successful history of developing successful approved cancer therapeutics. Importantly, even in the current environment, I think it's important for us to note that we have a very strong balance sheet. We ended January of this year with over $350 million of cash on the balance sheet. That gives us runway to the end of 2026. That encompasses actually a pretty aggressive and robust set of clinical studies that we've planned for the pipeline. So that's a fully burdened cash number and cash runway that we're providing. Really, primarily over the coming quarters, there's a variety of different milestones and updates on the two lead programs, ORIC-944, like I said, which is the prostate-focused program, and ORIC-114, which is the lung-focused program. So I mentioned the team that we've brought together, and that team has worked together in multiple different contexts, either on the discovery research side, the clinical side, the BD, IR, and finance side. Really, that's what's defined the key areas of focus for the company that I mentioned to you earlier, which is small molecule drug development, primarily with focus on prostate, lung, and breast. Let's dive into the pipeline. Right here is what we think of as probably one of the more robust pipelines within small-cap oncology today. Either through our own data sets or through the data sets of competitors, we've achieved proof of concept in multiple of these programs. And specifically, I'm going to focus my commentary today on ORIC-114, which is a brain-penetrant EGFR and HER2 exon 20 inhibitor, which we're developing in lung cancer in selected patient populations. And I'll talk more about why we're so excited about that program. But primarily, the differentiation there resides on the well-tolerated profile from a safety and tox perspective, and then importantly, the CNS activity of that compound. ORIC-944 is a PRC2 inhibitor, which we in-licensed from Mirati Therapeutics about four years ago, just after we went public. That program or that target is one that has significant de-risking from competitor data sets, namely Pfizer, which has presented some pretty compelling data for their PRC2 inhibitor in combination with enzalutamide in metastatic, castration-resistant prostate cancer. That program, that space, for those that know the target, folks are well familiar that essentially PRC2 inhibitors in the past, the first-gen compounds, have suffered from very bad drug properties, either short half-life or CYP autoinduction that leads to dose-dependent decreases in exposure or both of those aspects. In this case, with ORIC-944, we think that we've got a drug that the Mirati scientists came up with, a drug that really has quite a differentiated drug profile that ought to lead to better outcomes in the clinic, as good or better than what we have seen with competitor data sets thus far. Those are the two programs that we're most focused on right now. Really, from a big-picture perspective, the plan is to start pivotal studies for both of those programs in the second half of 2025. That's obviously just around the corner here, as you think about 5, 6 quarters from now, for us to be in multiple pivotal studies with multiple programs underway. The team is really in heads-down execution mode on those two programs. What I'll say at a very high level is we do have a third clinical program, which we had provided an update on at ASH of last year. That's ORIC-533, our small molecule orally available CD73 inhibitor, which we were developing initially as a single agent in multiple myeloma. It was the first CD73 inhibitor that has ever shown single-agent activity. And that's in a late-line multiple myeloma population. So obviously, a quite difficult clinical hurdle for that program to have shown that activity where it did. Now, despite it having shown that activity, we made the strategic decision that just given the heavy lift that we're going to have on ORIC-114 and ORIC-944 to get those two programs into pivotal studies by the second half of 2025, we've made the decision that for ORIC-533, the next stage of combo development ought to be undertaken by somebody else, hopefully by a future partner. There are some earlier-stage programs in the pipeline as well, namely ORIC-613, which is a PLK4 inhibitor, which uses a synthetic lethality pathway to be developed in patients with TRIM37 amplifications with breast cancer. We're not going to have enough time for me to probably get into any of that today. So why don't I just dive into the first two programs? So let's start on ORIC-114, which, as I mentioned, is a brain-penetrant EGFR and HER2 exon 20 inhibitor. Slide seven really covers for you the target product profile that we were aiming to hit that we think with the phase I data set that we presented at ESMO last year, we have already shown significant proof of concept in terms of being able to achieve this target product profile. Taking a step back, if you just look at the EGFR and the HER2 exon 20 space, it's a space that I think the first-order analysis from investors is that it's a crowded space because there's several compounds that are in late-stage clinical development going for this target. Amivantamab from Janssen is approved as the only approved EGFR exon 20 inhibitor today. The main issue with the space, though, as you look across the drugs that have been developed and have fallen by the wayside, or even the ones that are in late-stage clinical development, has been either one or two problems. In the case of almost every drug that's been developed, they don't have CNS activity. So they have not been developed to have blood-brain barrier penetration. They don't have good CNS activity. Those studies have excluded patients with active brain mets, meaning they have said that if you have brain mets, the only way you can come onto the study is by being treated for surgery or with surgery or radiation for those brain mets before you can come onto the study. That is a huge problem because 35%-50% of these patients at initial presentation have brain metastases. Every patient is going to eventually develop brain metastases if they're treated with a drug that is not brain-penetrant because that is just the natural evolution of these lung tumors in the TKI space. And so that has been a huge issue with the TPP that's been hit by the later-stage programs in the space. The second big issue has been safety and tolerability. And that comes in two different flavors. So one is EGFR wild-type related toxicity. So that would be things like rash or diarrhea, GI toxicities. Every drug in this space is going to have some degree of EGFR wild-type related tox. Just by definition of trying to hit EGFR exon 20, there will be some activity on wild type. But you really want to minimize that activity so that you get really as minimal toxicity profile on the GI tox, the diarrhea, and the rash as is possible. What you've seen with some drugs that have come before, so in the case of mobocertinib from Takeda, you've seen quite a bit of GI tox, diarrhea that really was probably quite problematic for that drug eventually. And that drug has now been withdrawn, even though it had an accelerated approval. And then in the case of poziotinib from Spectrum, it had quite a bit of rash. And so the skin toxicities really probably led to the downfall of that drug in terms of its future development. Now, the profile of ORIC-114 has minimized that EGFR wild-type related tox. And we can kind of talk you through some of the phase I data that demonstrates that. Importantly, though, I mentioned there's two flavors of toxicity that we care about here. And the second flavor is one that you don't hear a lot because quite a few of the programs in the space have dirty kinome trees and so therefore have quite a bit of off-target toxicity. So you will see things like elevated ALT, elevated AST, bilirubin increases, CPK increases, anemia. These are the kind of toxicities that are off-target toxicities that are present in the profile of many of the other competitors in the space because of the dirty kinome trees and the off-target hits that they have in their kinome trees. And 114, again, does not have that liability because of an exquisitely clean kinome panel for this program. Now, slide eight demonstrates for you the importance of having CNS activity. So I mentioned mobocertinib earlier. You can see that actually the same pattern with amivantamab, the approved EGFR exon 20 inhibitor, that when you really dig down into the data and look at the performance of patients with versus without brain metastases, patients treated with these other drugs that are not brain-penetrant have dramatically different outcomes when they either have or don't have brain metastases and are brought onto the trials. And so that's been reflected in many, many other targets in targeted therapy within lung cancer. In ALK, it's probably been best studied. And you can see in alectinib, which is far and away the market share leader within the ALK lung space, the benefits of a drug that is brain-penetrant where you don't see those dramatically different outcomes for patients with versus without brain metastases. And so that's why it is so critical to have a brain-penetrant compound. Now, slide 9 shows you the design of the trial for ORIC-114. We're right now sort of right around the middle of this slide in terms of where we are in development, which is that we're closing in on the end of dose escalation. What we've announced is that in the first half of this year, we anticipate choosing two provisional recommended phase II doses to satisfy the needs of Project Optimus from the FDA. We would then seek to optimize across those two doses and dose expansion cohorts and then be in a position that by the second half of 2025, we'd be able to start one or more pivotal studies just depending on the competitive signal that we see in the three populations of interest, which are EGFR exon 20, HER2 exon 20, and then finally, atypical mutations of EGFR. Importantly, and unlike the competition in this space, we are allowing patients onto the study whose brain mets have not been treated with surgery or radiation. So like I said, every other drug in the space in their early-stage studies, in their phase I, phase II studies, excluded patients with brain metastases unless they had been treated with surgery or radiation. And we are not having that exclusion here because we feel so passionately and we're so confident about the brain penetrance capability of this drug. Slide 10 is a busy chart, but it tries to highlight for you the dynamics that I just mentioned, which is as you look across the competitive landscape, what you'll see is if you focus on a couple of different lines, one is whether or not prior exon 20 inhibitors were allowed in those studies. You can see for the vast majority of drugs, other than BluePrint, which has now been discontinued, they did not allow prior exon 20 inhibitors to be enrolled in those patients who had had a prior exon 20 inhibitor to be enrolled in those studies. Then the other couple of rows down from that, you see untreated CNS mets allowed or disallowed. Again, other than BluePrint, which has now been discontinued, you can see every other drug in the space did not allow patients with untreated CNS mets to come onto their study. So we enrolled a dramatically different patient population than anybody had enrolled prior to our data set. Namely, that was 80%+ of the patients had a prior exon 20 directed therapy before coming onto our study. And 86% of the patients had had CNS metastases at baseline coming onto the study. So just a dramatically different patient population. And one that was a high bar in which to show activity, but in which we showed pretty significant activity. So you see on slide 11, the waterfall plot in EGFR exon 20. You can see at the top the annotations for what prior therapies the patients had had. And you can see just how pretreated these patients were. In fact, almost all of them had received amivantamab, which, like I said, is the only approved EGFR exon 20 inhibitor today. You can see despite the fact with all that prior treatment and despite the fact that so many of these patients had CNS mets at baseline, as you can see in the annotations at the bottom, we still saw multiple RECIST PRs that were confirmed, multiple patients who were ongoing at the time of this data update, which was at ESMO last year. And then importantly, in the bottommost row, you actually see multiple examples of patients where CNS lesions had been resolved. Now, one of the most profound examples of the CNS activity of the drug was this patient vignette highlighted on slide 12. This was a 55-year-old lady who had EGFR exon 20, non-small cell lung cancer, who had previously been treated with chemotherapy, progressed, then was treated with amivantamab, and actually did quite well on amivantamab. She was on amivantamab for almost a year in response and eventually progressed exactly where you think she'd progressed with the drug that is not brain-penetrant, which is with four small lesions in the brain. So she had progression in her brain. She would not have qualified for any other drug in the space, any other trial in the space because of the exclusions that they have in their inclusion exclusion criteria because she had had a prior exon 20 inhibitor and she had brain mets that had not been treated with surgery or radiation. She did qualify for our study because of our more loose inclusion criteria that we allow and came onto the study and pretty quickly had a complete response in the lungs and a complete response in the brain. And at the time of ESMO, had been on study for nine cycles and ongoing. And as you can see from the tox profile, the worst tox that she was having was of a grade 2 nature. So really helped typify exactly why we think that this drug has best-in-class potential in the space. Now, beyond EGFR exon 20, we also enrolled a population of patients with HER2 exon 20 and in fact, even had more responses in the HER2 exon 20 population, as you can see from the waterfall plot on slide 13. And again, saw shrinkage of CNS lesions and evidence of that in this population as well. Now, the third population I mentioned, which we had not even started enrolling at the time of ESMO last year, is atypical mutations in EGFR. And that's a population that has attracted a lot of recent attention, I think primarily because it has been underserved in terms of drugs in the space. Right now, what gets used for this population is afatinib, which every clinician will tell you is a pretty suboptimal drug, especially from the perspective of toxicity. We are actually more potent, again, with ORIC-114 against the atypical EGFR mutations than we are against EGFR exon 20. And so you can see here some preclinical work that verifies that. Again, this is a third population of interest to us and one that we're starting to enroll right now. And so big picture of the roadmap for this program is to enroll the three different populations of interest that I mentioned to you over the next year or so as we do dose optimization work. And all of that's in anticipation of starting 1, 2, or 3 single-arm accelerated approval studies in the second half of 2025. This would be the classic TKI playbook with quite rapid timelines where we could potentially be submitting NDAs for one or more of those populations in the second half of 2027. So let me just jump in quickly into just a quick piece on the commercial side, and then let's go over to ORIC-944 before we take some questions on me. So ORIC-114, one of the knocks of the targeted therapies, especially recently, has been some of the disappointing commercial launches of certain of the drugs and certain of the targets. What I'd say is that this particular space has been in the EGFR exon 20 has been tested for far longer than some of the other targets, basically as long as there's been EGFR inhibitors, people have been testing for these mutations. You can see as you start to add up the size of some of these populations of interest for us, they're actually larger than RET. They're larger than ALK when you add up a few of these different populations. Commercially, this should be quite different than the dynamic that you've seen that's preceded. Now, let's just jump into ORIC-944 for a few minutes, and then we'll open it up for questions. Now, ORIC-944, as I mentioned, is a PRC2 inhibitor that we acquired from Mirati about four years back. Again, stepping back, what's been the problem with this space has been drugs that have had really poor drug properties. And that's come in one of two flavors, which has been either short half-life or CYP autoinduction or both issues. In the case of tazemetostat, for example, which was developed by Epizyme, it's a drug with a three-hour half-life. It's got CYP autoinduction, so there's actually dose-dependent decreases in exposure. What we like about this program is the Mirati scientists were really optimizing for coming up with a drug that had best-in-class drug properties, and we think that they've been able to do it. Now, PRC2 is a complex that people don't immediately know because I think a lot of people know it by the name of the first-gen inhibitors, which are really targeted at one subunit of the complex, which is EZH2, the catalytic subunit. The Mirati scientists focused on developing several EZH2 inhibitors as well as several EED inhibitors and putting them all up against a high-bar target candidate profile to see which one had the best drug properties and the best in vivo properties. And it happened to be this EED inhibitor that is now ORIC-944 that won out. So I love that it was a very empirically driven decision in terms of focusing on EED inhibition. Now, PRC2 inhibitors have been studied for many years in prostate cancer, primarily because the biological rationale is so strong. Essentially, what happens is the next-gen AR modulators, which would be enzalutamide, apalutamide, and daralutamide, have done quite well for patients in the prostate space. But eventually, those tumors, as you can see in the cartoon, evolve to become AR-independent. And so in that process of becoming AR-independent, the next-gen AR modulators lose their efficacy, and eventually, the tumors become resistant. What is thought to happen with the PRC2 inhibitor is that you're actually applying pressure to keep the tumor in a more luminal state and one that continues to be AR-dependent. And so there has always been this theory that if you combine a PRC2 inhibitor with an AR modulator, you ought to be able to get some synergy of the two. Now, Pfizer and now we preclinically have shown some pretty compelling in vitro analyses that demonstrate that synergy. So essentially, these are cell growth assays that have been conducted with varying exposure levels of either the PRC2 inhibitor or an AR modulator, in this case, enzalutamide. And essentially, what you're looking for is that the cell growth inhibition that you see with drug A plus the cell growth inhibition you see with drug B alone adds up to far more when you put the two of them together. And that's the synergy potential you're looking for. And essentially, without getting into all the nitty-gritty of the weeds here on these synergy analyses, 10 or more is a synergistic score. And so you can see using various synergy models, in the case of ORIC-944, we are above 10 in the Bliss, the Loewe, and the HSA synergy models. In the case of Pfizer, in combo with enzalutamide, you can see that they're above 10 in two of the three and pretty spot-on with 10 in the third model. So in other words, there is synergy in vitro when you look at the combo of a PRC2 inhibitor, whether that's an EZH2 inhibitor like Pfizer or an EED inhibitor like ORIC-944 in combo with an AR modulator. Now, slide 22 shows you the schema for the phase I study. Importantly, the properties on the right-hand side of slide 22 are what we were trying to optimize for, which was really better drug properties in the name of longer half-life and no CYP autoinduction, as well as good PD markers from the perspective of target engagement and obviously a well-tolerated profile from the perspective of safety and tox. So slide 23 shows you on the left-hand side the half-life. You can see Pfizer obviously seems to have solved the CYP autoinduction issue in the sense that they don't have CYP autoinduction, but their half-life does seem to be short at 4 hours or less. Tazemetostat obviously has both of the issues I mentioned to you, which is it's got CYP autoinduction properties, and it also has a short half-life. In the case of ORIC-944, what we've said is we don't see evidence of CYP autoinduction, and we see a half-life of about 20 hours clinically. So obviously, that differentiates quite nicely from the competitors that have come before. On slide 24, we look at target engagement, and this is very similar to data that Pfizer has shown with the target engagement of their own compound. You can see when you look at H3K27 trimethylation and look at inhibition levels, we're able to max out this assay at quite low doses, just as Pfizer does with theirs. I think the one big difference when you compare the two side by side is in our case, each of those dots is an individual patient. So you can see very little interpatient variability. It's really quite a tight band, and that's far less interpatient variability than we see with Pfizer or with the competitor compounds. Then finally, this is in vivo work, but it's the best we can do at this point just in terms of the side-by-side comparisons of the two compounds. And this is hot off the press. A couple of days ago, it was presented at AACR. You can see on slide 25, both molecules, the Pfizer molecule as well as ORIC 944, have good activity in this C4-2 prostate model, but in fact, show synergy when you put daralutamide in the mix with those molecules. In particular, in the case of ORIC 944 with daralutamide, where you see the most profound growth inhibition is with ORIC 944 and daralutamide more so than the combo of Pfizer's compound with daralutamide. So we're now, what we've said is in the first half of this year, you can see on slide 26, the design as we think about the next year or year and a half playing out, which is first half of this year, we plan to combine ORIC 944 with one or more AR inhibitors to do some dose-finding work. All of that is in anticipation of starting pivotal studies in the second half of 2025. Just given the time we've got on me, I think I've already sort of given the headlines on ORIC-533. So I'll just suffice it to say here with ORIC-533, we were pleased to see single-agent activity with this small molecule CD73 inhibitor in myeloma. The next step here is to wrap up dose escalation, which will be in the next month or two, after which we'll start looking for a partner to take this forward into various combination studies, most likely with the BCMA directed therapy or an anti-CD38 directed therapy. And so stay tuned for further updates on that program. With that, why don't we dive into the pipeline and any questions that you or the audience have? Okay. Great. Thanks, Jacob, for the presentation. Maybe I can ask you start with a question on ORIC-114. You've shown some very nice response rate data here. Can you talk about how you see that translating into durability over time? And what could kind of a pivotal trial look like in terms of the endpoints that you would need to see? Yeah. I think of it in multiple different hierarchies. I mean, so I think right now we've shown, I think, impressive efficacy from a response rate perspective in a heavily pretreated population. I think the next thing that we need to show is in a less pretreated population, so call it a second-line population that's had chemo but has not yet had an exon 20 or a HER2 exon 20 directed therapy, what does the response rate look like? In that population, good in this space, good response rates for either the approved drug amivantamab or the leading clinical stage drugs has been about a 40% ORR with there's a decent amount of tox, but manageable tox, especially from the perspective of wild-type toxicities. And then there's been a lack of CNS activity. So that's kind of the next thing we want to see is in that less treated population that is second-line, naive to an exon 20 inhibitor, do we have competitive response rates? And do we continue to see good CNS activity? I would argue that we probably ought to, just given what we've seen in a more heavily pretreated population. And then I think the next step after that would be the durability piece that you mentioned. So you just want to have patients on for long enough that you can really start to comment thoughtfully on durability. So I don't think that that's probably a second-order piece for us in terms of just the future de-risking of the program. But getting to the pivotal designs, really, this would be the playbook that you've seen time and time again since we ran it at Ignyta with entrectinib in ROS1 lung, which is single-arm accelerated approval trial design. Because of the CNS activity of the drug, that path would be open to us despite any amivantamab or others having full approval in front of us. And it would be relatively small study sizes as you think about these single-arm accelerated approval trial designs, which is why I said that we would look to start those in second half of 2025, and we'd be hoping to submit NDAs in 2027, so literally two years later. Now, FDA has been sticklers about having confirmatory trials well underway, and we've already started thinking about what the confirmatory trial might look like. I think every drug in this space has done one of two flavors, which is either a head-to-head versus chemotherapy or combining chemotherapy and then comparing to chemotherapy. So those are both obviously viable options that we could think about, but we could also think about something more creative, for example, combining with amivantamab. So amivantamab is a bispecific antibody, does not have brain activity, does not have brain penetrance, so it lacks that CNS activity. And so you could think of sort of an HER2 tucatinib strategy if you think about the analogy here of 114 combined with amivantamab, for example, as the treatment arm in a future confirmatory trial. That might be one possibility here that would be quite creative compared to what's come before. Given kind of the brain penetrance feature of 114, what type of sort of the safety efficacy trade-off do you think is acceptable, especially as we think about the current standard of care and also perhaps if you could comment on the Mariposa 2 data and how that sort of impacts how you think about where 114 could play in the treatment paradigm? Yeah. So there used to be a debate 5, 6 years ago amongst lung KOLs about whether you wanted a lung TKI to be brain penetrant or not because what if you have CNS toxicities that come with being brain penetrant? I think you'd be hard-pressed today to find a single KOL in the lung space that would tell you they don't want a brain penetrant drug. I think they all want a drug that's brain penetrant. And the reason for that is unless your target is in the brain, is relevant to toxicities. For example, TRK in the brain can lead to some CNS toxicities, but that's not the case in the case of EGFR exon 20, for example. So with a clean brain penetrant EGFR exon 20 inhibitor, you would not expect to see CNS toxicities. You can see from our phase I profile that that exactly validates what I just mentioned. Then as we think about the broader data sets, I think probably more than Mariposa, it's probably the Papillon data set that we were most focused on from Janssen. Papillon was, of course, their confirmatory study where Janssen paired amivantamab with chemo and showed that it was better than chemo in terms of efficacy and in terms of durability. But again, if you look at the subgroup analyses that they published, so one thing that's to be clear on is in the Papillon study, Janssen excluded patients with active brain mets. So if you had brain mets and you were coming on the study, you had to have been treated with surgery or radiation before coming onto the study, just like all these other non-brain penetrant compounds have done. But when you look in the New England Journal of Medicine article that was published with Papillon, you'll see that the patients with versus without brain mets, even after that cherry-picking of the patients so that you could not have had an active brain met coming onto the study, the ones with versus without brain mets had dramatically different outcomes on the study because that, again, happens when you have these non-brain penetrant compounds. I guess just a sort of tangential question on ORIC-114. I mean, there is sort of a huge unmet need for drugs that are brain penetrant, and I think you're sort of targeting a sliver of the patient population here with exon 20 and the atypical EGFR mutations. What can you learn from this particular molecule to sort of broaden your portfolio beyond 114? Within the lung space? Within the lung space. Yeah. So with 114, I mean, it's really the three populations that I mentioned to you, which is EGFR exon 20, HER2 exon 20, and then the atypical EGFR mutations. Those are the three primary populations we're focused on. Any one of those would be commercially attractive. There's thousands of patients with high unmet need. Whether you have brain mets or not, you want a brain penetrant compound for those targets. And so those are very attractive to us. And especially as you start to stack some of those populations, like I said, it gets to be larger than the size of the ALK population, which is obviously already a $2 billion-plus market today. So from a commercially attractive point of view, any one of those populations would be enough. But like I said, we think there's ample evidence we've already generated that probably one or more of those populations are the ones that we'll focus on. Even beyond that, though, you can look at HER2 amplifications, for example, in breast cancer, which is another small population that we're looking at in expansion cohort studies to look beyond lung cancer to see whether there's ways to expand 114 even beyond these base case populations that I mentioned. Got it. Okay. I had one question on ORIC-944. The plan for phase I studies to evaluate biomarker levels that can help capture dose dependency. How does the biomarker reduction correlate with response rate in prostate cancer? Yeah. So we've looked at the H3K27 trimethylation inhibition that I showed in monocytes. You can see that we bottom out the assay at quite low dose levels. We've also looked at the same biomarker, so namely H3K27 trimethylation in skin punch biopsies, for example, where you see much more of a step function decrease as we continue down from the lower doses to the higher doses. And then ultimately, everything right around sort of vectors to the 600 mg QD level as the level where we get exposures that correlate with the activity we saw in in vivo models, and then also to where we bottom out the target engagement for H3K27 trimethylation. So the go-forward dose that we'll be using here in the combo studies to start is 600 mg daily. The competition I mentioned with Pfizer seems to kind of get to the same level of activity at about 2.5 g of drug per day, so 2,500 mg per day divided up across two different doses. So we think that ought to be to our advantage to have the same or better activity as what they're able to do with a fraction of the dose. Okay. That's all the questions I have for you. I don't think I've received any other questions, so I think it's a good time to close the session. I wanted to thank you for taking the time to present today and share with us the story. Thanks to all our listeners for joining also. Terrific. Thanks for having us. We appreciate it, Ami. Thank you.