Okay. Well, here we are. Another year, another conference. So welcome to the leadership team for Arcus. Very familiar faces. Terry Rosen, the CEO. Jen Jarrett, COO. Thanks for— And Pia. And Pia. Thank you. Hi, Pia. And I'm Yigal Nochomovitz. I'm a biotech analyst here at Citi. We've been covering Arcus now a long time, I think. Six years? I know it's since before the pandemic. I know that. So well, why don't we just start? Obviously, all the focus is on the renal cancer asset, although there's some optionality, obviously, in some of the other areas too, which we'll talk about. So maybe we can just start. Remind everyone, what do we know about CAS now? What are the key pieces of evidence that are supporting the advancement into the two phase IIIs, which you've announced? And Jen maybe can talk about those designs and the goals of those. But maybe, Terry, you want to start with the. Can I do a little bit of overview? Yeah, there you go. We're good now? It should be working. Okay. Okay, so as Yigal mentioned, a lot of focus for Arcus and about Arcus derives from Casdatifan. And I'll start by just sort of highlighting why is that, and we have a very broad portfolio. We have three programs in phase III involving multiple studies, but Casdatifan is probably the biggest value driver for Arcus, and that's for a number of reasons. The first is we own basically 100% of the rights to Casdatifan. Secondly, the molecule and the target have been validated both biologically, clinically, and then also commercially by Belzutifan, Merck's HIF-2 inhibitor. So that molecule is already at a run rate of $700 million in annual sales, and that's only in very late-line settings where it's used now. So that's the tip of the iceberg in terms of the opportunity. The third piece is that the Arcus molecule, as Yigal had alluded to, we've shown quite demonstrably that it has a better profile than that of Belzutifan. So if you couple the complete ownership with the high probability of technical success, the fact that we're entering phase III, and then together you put all of that, it gives us enormous strategic optionality for the entire company, and so having that program really becomes like the bedrock for everything else we're doing. What are the key high-level observations that would enable the differentiation that we talk about from the Merck molecule? We have roughly 120 patients' worth of data in the same setting later in line where the Merck molecule's been approved. On every endpoint, whether you look at what it's composed of four cohorts, each of 30 patients, whether you look at the individual cohorts or you combine all of those cohorts to look at the 120 patients, all of those cohorts are very pharmacologically relevant doses. That's why we did choose to look at them at the 120 patients. We also looked at the 30 patients to be sure that anyone else that wants to look at them, that you're not obfuscating anything. Because that also includes a cohort of 30 patients that's using the 100-mg tablet formulation. That's the go-forward phase III dose of our molecule. But whether you look at the rate of primary progression, which is roughly half of that of Merck, so between 15%-20% versus 35%, if you look at the response rate, which is about 50% better, 30-some-odd% versus 20%, or PFS, which is the important, that's the approvable endpoint, where we're more than double. So the Belzutifan PFS is on the order of 5.6 months. We're at a PFS that's over 12 months. And so we're more than double that of Merck. So whatever endpoint you look at, whether in the individual cohorts or in the combined data, Casdatifan looks better. We've also presented early data from what our fast-to-market strategy, that's in second line. It's, in general, talk about the design. But that's a study looking at second-line clear cell RCC. And it's basically CAS plus CABO versus CABO. We showed early data where we showed response rate data. With only roughly five months of follow-up, we had a confirmed response rate of 46%. Merck did a similar study with Belzutifan plus CABO. With two years of follow-up, there were 31% response rate. Next year, we'll be sharing data as we get to PFS, so we'll be able to compare there. So I think all of the data to date clinically point to a black-and-white differentiation between the two molecules. What I would emphasize for those like ourselves who like to see some scientific evidence that ties together with the clinical data to make those clinical data more compelling in terms of your conviction that they represent truth, where you can see dramatic differences between Casdatifan and Belzutifan is when you look at what's considered the gold standard biomarker for HIF-2 inhibition, and that's the suppression of erythropoietin production. So about 80% of your erythropoietin is under the control of HIF-2. So it's a very easy biomarker to measure. And what we've shown is not only do we have a much deeper or a deeper inhibition than that of Belzutifan, but Belzutifan loses that PD effect. These are data published by Merck after about nine weeks on therapy. And we've shown that we still have robust inhibition of that erythropoietin production out past the year. So that's something that's very quantitative. It's very reproducible. And that dramatic differentiation is what underlies the clinical data differentiation. Another important aspect of those data, and we'll be sharing more on this early next year, but we've also been able now, with about 120 patients' worth of data, to show that the ability to suppress the production of erythropoietin, while erythropoietin doesn't drive the cancer, it's correlative. So the deeper you can suppress an individual's production of erythropoietin, the more favorable their outcome is, whether you look at response rate or whether you look at PFS. So we feel that's pretty compelling. Just to touch quickly on our other programs as an introduction. The other program that's in phase III is our anti-TIGIT program. That actually involves three different phase III studies. The reason we're so excited about that is the first one of those is going to read out in 2026. That's a study called STAR-221. It's in upper GI cancers. Not only is it going to read out, so that study enrolled about 1,050 patients. It was fully enrolled in June of 2024. But we just presented data from the phase II correlative of that, same dosing regimen, same patient population, where we showed OS on the order of greater than two years, whereas the standard of care in that setting, which is Nivo chemo, but you also see similar data for Tisle chemo or for Keytruda chemo, is about 12 to 13 months. So almost 2x the OS. So that'll be reading out later this year. Also, the second phase III study there, STAR-121, which is in the PD-L1 all-comer non-small cell lung cancer, probably the biggest part of Keytruda's market, 1,000-patient study that'll be fully enrolled at the end of this year, and we're running a phase III lung trial also in that where we're combining with durva and actually AstraZeneca is executing that. Third phase III program is with our CD73 inhibitor. We just, as of September, fully enrolled almost a year ahead of schedule in nine months, a study called PRISM1. That's quemli, our CD73 inhibitor, on top of gem/Abraxane, the standard of care there. So that was versus gem/Abraxane. That was fully enrolled in September. The readout there is OS. For gem/Abraxane, that's probably in the order of nine to 10 months. So that's not that far off. Finally, because we are an R&D-centric organization, we have a very substantial discovery organization. In our investor event that we just did in October, we highlighted a group of immunology programs that we've been quietly working on. And the first one of those, which is a H2 inhibitor, we expect to enter the clinic next year. The final piece is we're well capitalized. We sit currently with over $1 billion in cash. So everything that we're talking about, we're able to execute. And that cash covers well readouts for all of those programs, the initial phase III readouts, including that PIK1 study that's in clear cell RCC. Jen, you want to comment on the design of the. Yeah, is that what you want to go with? Sure. Okay. Yeah, of course. So the first phase III study that we have ongoing for CAS is combining CAS with CABO and comparing that combination to CABO and in IO-experienced clear cell RCC. So these are patients that got IO either in the adjuvant setting or in the frontline setting. So this is a very big patient population, a market opportunity. We're going right on top of the most widely used TKI in that setting, CABO. It's used about two and a half to one times more than Lenvima in that setting. So the reason that we liked using CABO is that clinicians are so comfortable using that. When you're dealing with TKIs, TKIs do have a fair amount of toxicities. And so choosing a TKI that clinicians are very comfortable using, very comfortable managing toxicity, and therefore keeping patients on drug is super, super important. And then CABO is also what we're using in the control arm. So using the same TKI in experimental arm and the control arm also just makes this a very clean study. And that is a key difference from the Merck study, which is similar, LITESPARK-011, where they use Lenva in the experimental arm. So they combine Belzutifan with Lenva. And then they're using CABO in the control arm. So I don't think they'll have any contribution to component issues, but there's a little bit of like, you know, if they show a benefit, which they seem to have shown with the combination, is some of that coming from Len? Is it from Belz? So we feel like we have a much cleaner study design. We expect that this- I wonder how the investigators liking that they're enrolling that fast because they like it. They like that design. It's easy. Yes. And that's exactly where I was going. And so investigators love the design. So our expectation is that this study will enroll very, very quickly. If you look at the typical RCC study, either frontline or second-line study, they tend to enroll 15 to 18 months. There's no directly competing studies right now, which is really nice. RCC is a much less competitive space than a lot of other oncology markets like lung. We're using a two-to-one randomization. So that means patients are twice as likely to get an experimental arm versus the control arm. So both patients and clinicians love that. And then the third thing that's important is that Belz is still not paid for in a lot of regions, including in Europe. So Europe is particularly enthusiastic about the study. I mean, there's a lot of enthusiasm everywhere. But because there's so much awareness around Belz in Europe, and it's used for VHL, but it's not paid for yet in RCC, the only way to get access to a HIF-2alpha inhibitor in RCC is to put them in a clinical study. So that's driving a lot of the enthusiasm for LITESPARK-011 in Europe. So we do think that study is going to roll very, very quickly. It is a PFS endpoint. So PFS for the control arm is probably around nine months or so. So that should also enable us to get to a readout very, very quickly. So we're calling this our fast-to-market opportunity. Did you give timeline for the? We haven't. I'd say our goal is to get the study completed enrollment by the end of next year, so that would be in that kind of 15-month window that is pretty consistent for other RCC studies, and then it's just going to come down to the event rate. What we do have on ct.gov right now is the primary completion date of April 2028. We definitely would love to beat that. Our goal is to beat that. Sounds like you have some buffer there. Yeah, we have a little buffer. So I think as we get closer to the data event, start to get a sense for what the event rate looks like, then I think we can provide more specific items. But obviously, the goal is to get to data as quickly as possible. So PFS is the critical. But is there an OS in there too? We're looking at OS as the key secondary endpoint. Is there a crossover? You don't do that. No, no, no crossover. So OS is the key secondary endpoint. We've had a discussion with the FDA. Very, very comfortable with PFS as the sole primary, which is what 80%-90% of the RCC studies have had. You're just going to go to the pre-specified number of PFS events. You don't have. It's fast. You don't want to put interims in. Right. So this is a very clean study. One thing we have said is there's no interim. So we're putting all of the alpha on that one PFS endpoint. So not taking any risk there. So very excited about that study. The next thing is frontline. So we have a collaboration with AstraZeneca to combine CAS with Volru, which is their anti-PD-1. One other thing, sorry. So on the IO experience versus the, so is it, do you have a ratio, or is it just you take who you take in that population, or? Right. So our sense is that just based on what we see with that CAS-CABO cohort, about 20% of patients enrolled in CAS-CABO cohort had gotten adjuvant Pembro. And that's pretty consistent with what we've seen in some other contemporary studies. We'll see what they got in LITESPARK-011. That'll be an interesting data point to see what percent of patients had previously been treated in the adjuvant setting. But our expectation, based on everything we know, is that about 20% of our patient population is adjuvant Pembro. And these patients, because most of these patients either progressed while they were getting adjuvant treatment or right after their adjuvant treatment completed, they're considered to be resistant to Pembro. And so that's why they're considered to look just like a patient that failed frontline anti-PD1 therapy in the metastatic setting. Okay, okay. When we look at, we talked about this too. So when we look at those different patient populations in the CAS-CABO cohort, so patients that got treated with Pembro in the adjuvant setting versus a patient that got treated in frontline metastatic patients, they performed very similarly. Okay, and one other thing before we get to Evolve, just maybe comment a little bit on the data that's supported that they play well together, CAS and CABO, just the safety. There's no issues there with the. Yeah, safety profile. Something else that we highlighted, the investor - or I'm sorry, the ASCO event where this was presented. Safety profile looks right. A lot of people actually look at the safety profile and think that it looks better than what you expect with CABO mono. So I don't know if there's anything to that, but the data looks really good. One of the things that we're keeping a close eye on, which is super important, is just the dose intensity. Because obviously, the goal is to keep patients on the highest dose possible of both drugs as long as possible. And the CAS dose intensity was like 95%. I think CABO was 90%. So that's something that clinicians have been very impressed by because a lot of times when you combine two active anti-cancer drugs, you will see added tox and say you'll have to dose reduce or take patients off one of those therapies. So it's a very, very positive sign that we've been able to keep patients on either full doses or close to full doses of both drugs throughout their treatment. Okay, and then Evolve. Yeah, Evolve. So Evolve is a clinical collaboration that we're doing with AstraZeneca in the frontline setting where we're combining CAS with their anti-PD-1, CTLA-4 bispecific. Anti-PD-1, CTLA-4 is a very widely used regimen in the frontline setting. So that was what we loved about this collaboration was an opportunity to create, kind of build on IOIO in the frontline setting and add additional efficacy without the added toxicity and to avoid TKIs in the frontline setting, which is what people really like about using anti-PD-1, CTLA-4 versus anti-PD-1 plus TKI, which is the alternative. So we started this study a few months ago. It enrolled very, very quickly. We decided to pause enrollment and see how the patients already on treatment were doing because we saw some immune-mediated AEs, not unexpected AEs, just based on the fact that we were combining anti-PD-1, CTLA-4. So we're tracking those patients now. Then we'll make some decisions probably late this year as to whether or not we want to modify the dosing regimen for Volru and then likely keep going there. So that's one. How far did you get with the enrollment, or did you? We didn't say. You know what I would say is it enrolled quicker than we thought. but whatever you saw on this AE, this was what you would have expected with. It definitely was not something that we would not have expected. It is a very classic. If you look at like. What was the—I mean, then it wasn't a. Yeah. So I think it's just based on the incidents. We just wanted to be careful and conservative given these are novel, novel drugs. And so we just decided we have a decent number of patients on therapy. Let's pause, not enroll additional patients, see how these patients do, and then probably modify how Volru is being given. And if you look across their phase III studies, their phase III studies are all using slightly different dosing regimens of Volru. So this wasn't totally unexpected. So we'll see how these patients do, probably make a decision on tweaking the dosing of Volru. And then we can keep going here. In the meantime, we are adding some other cohorts to ARC-20 to look at CAS with other regimens. So Opdivo will be one of those. And second half of next year, we'll make a decision on which of these regimens. Wait, you said Opdivo separately? I didn't hear that. It'd be with Opdivo. Oh, so it's triple. Yes. So Opdivo plus CAS. So this will be in ARC-20. One of the nice things about ARC-20, the way we set that up is it's very easy to stick additional cohorts in there and evaluate other combinations. And so we're taking advantage of that and just decided to be safe, let's just see what CAS, Opdivo looks like. And we'll probably look at some other things in the study as well, which we haven't talked about yet. And then second half of next year, we'll be in a position to start a phase III study in the frontline setting and what we think is the best combination. You should think of that as, and this was like an intent all along, somewhat of a bake-off. So Jen didn't mention, but one cohort that we already have that's almost fully enrolled is we have anti-PD1 plus CAS. And the idea there was CAS was looking as good or better than TKI alone. And then top of it had better AE. So a big concept that Jen alluded to, but I want to highlight is the whole TKI-free strategy. That's something that's feeding into what the investigators are quite enthusiastic about. And it's an opportunity. It's rare that you get, call it dropped in your lap, an anti-cancer mechanism that essentially has AEs but no toxicity. So HIF2 inhibition. I've had investigators tell us that patients who've experienced TKI and they go on a HIF2 inhibitor, they basically never want to go on TKI again. They think it's like a vacation. So you can imagine, and we're talking about the CTLA-4 PD-1 plus CAS, PD-1 plus CAS, you could imagine that you could get two, three, four, five, six years of therapy that's robust, and then they'll get their TKI in the next regimen as opposed to giving them the TKI in the frontline. Are you giving serious consideration to just do PD-1 CAS? It's certainly in the mix. Why the CTLA-4 is a tough target? Because, well, the interesting thing with, and this is why we feel we should explore, and it's why we not only, it was our intent all along to not only investigate with Volru, but Ipi anti-PD-1 as well, because it does turn out the reason that's used in about 35%. So it's the most used regimen in frontline, and it's the highest probability to get a cure. So it has the most risk, as you said. CTLA-4 is a tough therapy. It's just, yeah. So it'll be part of the bake-off. It's interesting because the KOLs are saying, "No TKI. Let's keep it a nice, very well tolerated." But then you would think that to be intellectually consistent, you're like, "Well, we don't want to do CTLA-4 either. I had that same intellectual argument with myself. And I think the thing comes, I mean, it's interesting. Jen's pointed this out to a couple of people. The last ASCO, they were literally, BMS gave a presentation. It was like the nine-year follow-up on Opdivo. So you can get some dramatic cures. So you do have that. I would love to see if you gave me the choice. I think I'd rather see anti-PD-1, HIF-2 push the TKI out further. But if you could pull something off where HIF-2 basically lowered the rate of primary progression and enhanced the efficacy of CTLA-4 PD-1, that would be the—we want it now. When will you have resolution? Second half of next year. So the idea, we're treating this all as a bake-off, and everything's been working. If you sort of think of it as a retrosynthesis, we're working backwards to have the data to inform that. And AstraZeneca is paying for, obviously. Yeah, we have a SAG, but obviously, yeah, there is a big cost-sharing component to all this. And then if it's just the PD-1, you're going to use Opdivo? What are you going to do? Yeah, we have a cost-sharing component, but yeah, we'll say a lot more, I think, early next year about exactly what we're planning on doing. Our data set, I will foreshadow today. The study that's out there on clinicaltrials.gov is ZIM plus CAS. It's almost fully enrolled. The early data look good. Oh, okay. So for the purposes of this bake-off, you're using yours? Yes. Right. But that wouldn't. Right. And it may be different. And so we will have an Ipi anti-PD-1, and we haven't decided if it'll be Nivo, ZIM, or an arm of each. Okay. Okay. So that's important. Got that. Exactly. You know. And then that'll coincide pretty much with potentially almost having the. Oh, sorry. No, we're a year off. Sorry. It'll be 2027. One's the fast to market. The others capture that frontline. But that frontline durability, we think that really could be something that you've got patients four or five years. I mean, keep in mind, so this is a data point we like to point out. In our late-line monotherapy cohorts, the one that's the furthest along, 40% or so of the patients were still on study after two years starting treatment. So you're getting that durability even in the late line. That's what drives the concept of why for someone to take that TKI early in their therapy, push that into the later line of therapy, and let them have quality of life. What is the KOL you had, the lady from—what was her view on which way to go for the frontline? Did she have a view or she was— She liked IOIO. She liked IOIO. Yeah. TKI experience is important. And going back to your. Right. Brenda, like with whether to do the triple, like whether to do the bispecific or the— I don't think she's—I mean, she's involved with the bispecific study. I don't think she has a strong view, I think, like either would work. I think she's definitely excited about the Volru combination. We're still excited about the Volru combination. So we'll see where things go and chart these other options. And the important thing is having options and make an educated decision. The individual antibodies give you a different flexibility when you turn off the CTLA-4. So we'll see how that plays out. Right. Okay. Anything else you want to highlight on CAS? I mean, we covered a lot of territory there. No. Any other, I mean, any other updates from what you've already shown? I mean, we saw the update recently, and you've shown the combo data. You've shown the different doses. We know the dose going forward. You've done the dose exploration. Right. I think the update would be what we expect for next year very succinctly. Early in the year, we'll update on those monotherapy cohorts. We'll see a further refined durability, PFS. We'll talk more about the biomarker correlation between erythropoietin suppression and clinical outcomes. Roughly in the middle of the year, we'll update on the durability of the CAS CABO cohorts. And then in the second half, we'll share the data from the bake-off. You'll see what drives our selection of at least one phase III study with the intent to start that by the end of next year. Okay. Now, the one that sort of obviously everyone has written off, but I think is very interesting. Yes. So what's your view here? I mean, STAR-221, I mean, you have basically a very good setup, right? Yes. So I'll describe it. So STAR-221 is our first anti-TIGIT trial that we'll read out next year. We at AstraZeneca are the only ones who have utilized an Fc silent configuration for the anti-TIGIT. We have a molecule Domvanalimab, they have a bispecific that has Fc silent. Between the two of us, we've had five readouts today. Which is their Fc silent? It's the. The bispecific. It's that one. Same one. Yeah. Okay. They're running 11 phase III studies with it, including in the SKY-01 population. They started it after the failure of Genentech. But our data, we showed OS in the exact population that's the STAR-221 population in OS of just over two years where the standard of care, which is Nivo, chemo, but you have the same data for Tevimbra chemo and the same data for Keytruda chemo, is about 13 months. So almost 2x the OS. We've also had a very positive readout in a randomized study in PD-L1 all-comer non-small cell lung trial. So this study, which is event-driven, it enrolled 1,050 patients. It was fully enrolled as of June of 2024. It's going to read out sometime in 2026. And we think this will be the first time that you'll see a phase III readout for an Fc silent anti-TIGIT. All of our data to date have only pointed to positive. So from an investor standpoint, I think we have literally zero built into our value from that. Just remind everyone that just the trial design exam. Oh, you want to tell the trial design? Yeah. Just go through that. The hierarchical readout. Yeah. So it's pretty simple, which is also not like another simple study design, which is also what we tend to do is like going on top of standard of care and using standard of care in the control arm. So we're looking at dom, ZIM plus chemo versus Nivo plus chemo. So Nivo plus chemo is by far and away the most widely used standard of care in the frontline gastric setting. We're enrolling all-comer frontline gastric with the exception of HER2-positive patients. I'm sorry, HER2-positive patients. I know Jazz just had a positive readout. That patient population is not included in the study. For the primary endpoints, we're using just OS, which is really the gold standard from the FDA perspective. And we're using dual primary endpoints. So one primary endpoint is looking at the entire patient population, so ITT. And then the other is looking at just the top five, which is essentially your PDL1 high patients. And that's about 48% of the STAR-221 patient population. So it's still a big percentage. It's not like we're looking at a sliver in that other endpoint. And so we can win on either of those to have a successful study. If you win on just one of those endpoints, let's say you win on the PDL1 high or top greater than five patient population, you can then recycle the alpha into the ITT patient population. So it's a very simple study design. You do that one first? That's like hierarchical? No. They're tested at the same time, and so that's why. ITT and the top five. And the top five. Yeah. Those get tested at the same time. If you hit on one but not the other, you can then recycle alpha from one of the endpoints to the other endpoint. But if you hit on the top five, wouldn't it be weird not to hit on the ITT? I don't know. Not necessarily, just because we think most of the benefit is probably going to be in the PD-L1 positive. So either PD-L1 greater than one or PD-L1 greater than five patient population. So I think if we were to predict today, we'd say that's the patient population that's most likely to benefit. So that's why we did it like we did. But we think there's some chance, especially since the greater than ones is like 80% of the patient population. There's still a decent chance we get hit on ITT as well. So we'll see. As Terry said, no one's giving us any value for it, which is fine. We've got another asset, Casdatifan, which people are very excited about and giving value. Do you know? No, the reason we don't know is because it's event rate. And the thing that for those, we're not being cute about it, but to give a sense of how it looks, we've actually shared Kaplan-Meier curves from a randomized data set in the high PD-L1 lung patient population. And what you have there is anti-PD-1 with an OS of about two plus years, just what you would expect. In the anti-TIGIT arm of that, anti-TIGIT plus anti-PD-1, the hazard ratio was 0.64. But if you look at the Kaplan-Meier curve, you'll understand when you see how flat it is that that event rate. What study was this? That was the ARC-10 study. We stopped that early in favor of. So you're saying you need a lot, even if the hazard, I mean, you can have a good hazard ratio, but you still have not a lot of events if you have good. Exactly, so the thing is that until you hit your event rate can really fall off. You're tracking the pooled event rate. We know the pool event rate. You never said how many are the triggered? No, and we don't ever comment on the stat plan. But we can't make a call as to when we would want to give guidance that's going to read out in what part of 2026. Maybe as we get into early 2026, as soon as we can, we will. Okay. And then, can you go through the argument about the Fc silent and the fact that what you said, but just to re-say it? The whole thing about the immunity. I want to explain this clearly because it's going to finally matter. So an Fc silent antibody cannot have effector function. An Fc enabled may, but not necessarily have it. It turns out in the case of anti-TIGIT that you actually see very strong effector function with an Fc enabled antibody. What is effector function? Effector function means that the antibody not only binds to the cell, but potentially it kills the cell. And so what's driving that most likely is your peripheral T regulatory cells, which are basically keeping your immune system in check. They're your peacekeepers of your immune system are loaded with TIGIT. And about 80% of them are getting whacked by the Fc enabled anti-TIGITs. Why is that important? Well, it causes immune AEs. Go look left and right with either the Merck molecule vibosto or tirago, the Genentech molecule. What you'll see left and right is that the immune AEs are dramatically higher in the study arm. Now, the thing is it doesn't just cause immune AEs, but then that causes the patients in the study arm sometimes to have to go off of therapy. So you lose efficacy as well. With the Fc silent anti-TIGIT, and by the way, this effect is even more profound in the presence of chemotherapy. With the Fc silent anti-TIGIT, the mechanism, it's very elegant. It was worked out by Genentech. The blocking mechanism leads to none of that. So your safety profile, when you do anti-TIGIT, anti-PD-1 chemo versus anti-PD-1 chemo, the AEs look almost identical as if the anti-TIGIT wasn't there. So you're getting this blocking effect, which is central to the mechanism of basically activating the immune system selectively in the tumor to a very safe mechanism. And that's the big difference. So sometimes when I try to frame this, give people a metaphor in their mind, the Fc-enabled anti-TIGITs are almost like you should think of them as an ADC that targets peripheral T regs and blows them up. So you're getting this collateral activity that is non-beneficial and in fact detrimental to your anti-cancer activity because I'm giving you these AEs. And that's the big difference. Both we and AstraZeneca have seen similar data sets where the safety profile enables the study arm to not lose out because of AEs. I wonder if any enterprising academic ever took the data or someone at AstraZeneca or somewhere or one of the and took the data and imputed out all the stoppages for all the AEs and tried to see if they could recover like an actual therapeutic because that would be a good proof point for your saying. One thing that was interesting - I mean, this wasn't quite making the point - but AZ did present some data, I think maybe at ASCO. And so they have a bispecific, PD-1 TIGIT bispecific. And so what they did is they looked at the bispecific with their Fc silent TIGIT, and then they created another bispecific with an Fc active TIGIT antibody. And they showed exactly what Terry was referring to of T reg depletion, most importantly, maybe T cell depletion. So that was kind of an interesting experiment that they showed, but it made that point, I think, very specifically like why you want to block TIGIT and not target TIGIT-containing or expressing cells. Okay. Anyway, so this is a. Oh, yeah. So this is. So this is a silent catalyst here, which is like. Silent catalyst. You want to know. No one ever comes in. By the way, the synergy on the catalyst is that if that hits, the PD-L1 all-comer non-small cell lung trial, it won't be that, "Oh, based on those good data, now we're going to start this." So that's probably the biggest component of Keytruda's market. The 1,000-patient study with dom will be fully enrolled by the end of this year. So you're going to go from something that the world looks at as probability of technical success is zero from an investor standpoint, not from our standpoint, to immediately overnight, I think, particularly since we have the data and the PD-L1 highs that look quite compelling. So you combine that with a chemo regimen from the upper GI cancer. Don't forget, you're treating biology. You're not treating organs. And so when you combine the lung data we have with a potentially positive STAR-221 readout, I think there'll be the probability that people start to ascribe to that lung trial being positive, which is a huge market will be dramatic. But we're at this point, we don't want to twist anyone's arm. We're comfortable with. They don't come next year. I mean, that's still running. Oh, yeah. Yeah. Oh, yeah. Yeah. We haven't heard much about it. Because it just will be fully enrolled in the industry. Okay, so if STAR-221 hits, that will become very topical. Yes. Of course, it doesn't, whatever. But if it hits, then when would you have that? When would you be able to say something like an endpoint on the lung trial? That's like 20 later? That's later, yeah. Keep in mind standard of care is probably two years though. Oh, wait, one more thing. Why did you do the reason you did Nivo and you did your PD-1? Oh, that's standard of care. No, I know that, but why didn't you? You You didn't want to do Nivo in the active arm. You wanted to use your. We wanted to use our antibody. Just because of. Because it's a lot cheaper. Just cheaper. Cheaper settings. And then we're pricing not on top of whatever Nivo is priced at. We can figure out how we want to price dom plus zim. Okay. Cool. Well, that was fun. All right. That was awesome. Thank you for sitting down. We didn't even get to quemliclustat. Oh, you talked about it at the beginning. Yeah. Okay. So thanks so much. Thanks, everybody, for checking in on us. Appreciate it. You guys. All right. You're welcome.