All right, let's kick off our next session. with me, Terry. Arcus Biosciences Company. Welcome. Thank you. Very exciting times this year. Before we go through the questions, which I have a lot, I'm going to turn it to you guys for opening remarks. Terry, take it away. Great. Let me just introduce Arcus to those of you out here who might not be as familiar with us. I'll be brief. The company was founded about 10 years ago. We've built ourselves around a very strong R&D capability, particularly discovery. That's reflected in the type of programs we choose. We focus on programs particularly with small molecules, where there's been great validation, but perhaps not a great molecule yet. I think that leads me to casdatifan, which is clearly our most valuable program right now. That kind of fits that paradigm, where we think we've demonstrated unequivocally that we have a better molecule than the one other molecule that's out there. That's belzutifan. It's Merck molecule. It's validated the program clinically. It's validated it commercially. We think we've shown a lot of data, and we have a lot more coming later this year that show not only do we have a better molecule, but it enables a better development strategy. As we sit here now, we look at casdatifan as a $5 billion-$10 billion opportunity commercially. Finally, while we talk less about it, next year, for example, 80% of our resources will be invested in casdatifan development. We've somewhat quietly built a very strong immunology and inflammation portfolio of molecules, and they all fit that same paradigm where there's strong validation. In this case, a lot of it coming from biologicals, where you have double-digit billion-dollar drugs even, but where there's something that could be addressed that might be a disadvantage of those programs with a small molecule. For example, we have an A2 antagonist that's heading into humans imminently. We'll have proof of concept for that probably early next year. We'll have PK data later this year. We have a TNFR1 antagonist in development. We have a STAT6 inhibitor, CCR6, small molecule inhibitor as well. A very robust I&I portfolio. That's moving along in parallel to the casdatifan development. Final point I would just make is our cash position is strong. We are funded into the second half of 2028 with everything we'll talk about today, and that gets us onto the other side of data from what's the first registrational trial that's ongoing and enrolling right now for casdatifan in the second line. I'll stop there. Yeah, fantastic take your questions. Yeah. A lot going on in the company. There's a lot of readouts. Can you walk us through the timing for some of these readouts, including the PDAC? What's going on in I&I program? I know that you guys started that phase III, the PEAK-1 study. What's the status for that? Maybe just give us a status on these programs and the timing for the readout. Sure. You mentioned PDAC. We have an ongoing, fully enrolled as of September of 2025, study in pancreatic cancer with our small molecule CD73 inhibitor, QUEMLY. We're anticipating that to read out with data in the earlier part of 2027. That's purely event driven. That's running QUEMLY, gemcitabine versus gemcitabine. You'll see when we talk about casdatifan, we like to go on top of standard of care, very clean study, very clean data readout, and that was driven by very strong phase II data. That's a 2027 readout. Casdatifan, the first registrational study, we started enrolling that basically at the beginning of this year. We expect it, and we're on track to be fully enrolled by the end of this year. When you think about that casdatifan plus cabozantinib versus cabozantinib, when you think about cabo as having a PFS on the order of 10 months or so, while we haven't given guidance to the readout, clearly that just doing the mathematics takes you, if it's fully enrolled at the end of this year, it takes you probably into the earlier part of 2028 for data. In terms of the I&I portfolio, the first program heading into the clinic, which is imminent, is our A2 antagonist, will generate PK data in healthy volunteers quickly. We'll do an icabinnet challenge. We'll have those data likely by early next year. With all the other data going on in the field, proof of concept, we'll likely be entering a urticaria study, catching up to others because we kind of are able to skip a step and go directly to the real study there. There's a steady cadence of INDs that will flow in that immunology program. All those molecules I mentioned, STAT6, CCR6, TNF receptor 1, are IND candidates in the next 6- 12+ months. I'll also just note on timing because it's probably the most important study that we'll be doing. We anticipate getting our frontline first registrational study in kidney cancer with casdatifan up and going by the end of this year, and that'll be looking at casdatifan anti-PD-1 ipi versus ipi/nivo. I'll just remind people that in the frontline, that's the most commonly used regimen right now, ipi/nivo. We'll talk a little bit more about our plans and the data we're generating in support of that as well. Okay, yeah. A lot of questions on that and others. The big data readout was obviously the one coming mid-year, I think you guys mentioned could be more closer to ESMO timing. Maybe just give us an idea of obviously that CAS combo combination, the update to that data, we're going to get that. Besides that, what other CAS data are we going to see along the different lines of treatment? How many patients should we expect to see with these various updates? Great. I think this is probably the most important question. In terms of data flow for this year, we've recognized basically with the failure of belzutifan in LITESPARK-012, the frontline is there for the taking, and we think it's with a great drug and also a great development strategy. We have ongoing studies or imminently starting studies that read on all lines of therapy. Our strategy is actually very simple. We want to make sure that every patient can experience and have the opportunity to get casdatifan, and basically that it becomes a backbone therapy across all lines of therapy for clear cell RCC. Let me just in that, and then I'll talk about the data that will support in the frontline, if you want to think about the brass ring in this whole area, that's thinking about ipi/nivo, which is used in about 35% of frontline patients. It has a limitation that's associated with its rate of primary progression, which is about 20%. If not for that, it would be used more. We think with what we've already shown with casdatifan, even on top of anti-PD-1, we can reduce that rate of primary progression, and we think that we can take that ipi/nivo from 35% to roughly 50%+ of the market. Now, with that said, the rest of that frontline is fragmented, that other 60% some odd is broken into multiple TKI inclusive regimens. While individually they're smaller and fragmented, as a whole, it's a big opportunity. We recognized, particularly as we had ad board discussions with both U.S. and European advisory boards, that we should have a TKI inclusive regimen available in addition to that IOIO cast. That covers the first line. The second line, as you mentioned, very straightforward. The most commonly used, the largest part of that market is monotherapy cabozantinib, and we have an ongoing study that's looking at cabozantinib plus casdatifan. Finally, in the later lines, we're going to be looking at another TKI. We'll announce that shortly, and we'll be combining that with casdatifan, running a randomized study versus the TKI alone. Importantly, we'll be doing that in belzutifan-experienced patients. We're killing a couple birds with two stones, generating the data to support the registrational study, but also showing that casdatifan works in experienced patients. Finally, we haven't talked about this much, I want to comment on this now, we'll be talking about it more as the year goes along. We've really used our monotherapy single agent late line study to demonstrate that dramatic difference between casdatifan and belzutifan. Obviously, you don't have to parse out other agents in the combination. We're reaching a point where we should have OS data later this year as well. I'll remind everybody that while in clear cell RCC, the approvable endpoint is PFS, it's been thought that a dramatic differentiation could be an OS benefit. We feel that later this year, the OS will be mature enough from that late line to demonstrate a benefit that we think will read through all lines of therapy. What will those data sets look like? First of all, we have the 120 patients of monotherapy, data that will update not only all the other parameters but a first look at OS. In the front line, we have an ongoing cohort that's generating the safety data that will support the Phase III study. That's looking at casdatifan plus our anti-PD-1 Zim plus Ipi. We've already spoken with the FDA. We know the amount of safety data that we'll need. Keep in mind when people talk about Ipi-Nivo as a regimen, that's actually you get four cycles of Ipi-Nivo and then you get Nivo. It's 12 weeks of Ipi-Nivo therapy. We'll have double-digit patients later this year that have had Ipi anti-PD-1 casdatifan that'll form that safety component. We've also been running a 30 patient, 31 patient cohort that looks at anti-PD-1 plus casdatifan. We reported in January of this year that there was only a 7% rate of primary progression. Keep in mind that KEYTRUDA alone in this setting would show 25%-30% rate of primary progression. Ipi-Nivo shows maybe 18%, 19%, 20%. With casdatifan anti-PD-1 alone, we're already addressing what is believed to be the most limiting factor with the use of that Ipi-Nivo. We'll show not only the rate of primary progression data, but you'll get a good look with probably about a nine months of median follow-up of the waterfall and the early ORR, you'll be able to squeeze together the Ipi anti-PD-1 cast plus the anti-PD-1 cast, that basically looks like the therapy that we think is most important. We'll have up and running our study with that late line casdatifan plus other TKI, we'll have roughly 40 some odd patient data set that's looking at casdatifan plus cabo in the second line setting. We may even have early data on OS for that. We'll certainly have Kaplan-Meier curves for that as well on PFS, we're going to make sure that we compare to all the other data sets that are out there, whether they be bel's cabo alone, or bel's lenvatinib. We think we'll be able to compare across lines of therapy in cohorts ranging from 30 to 40 to the 120 patients that have late line, very large data set of casdatifan later this year. Right. That's a lot. Let me just kind of list- Sure list up to you to make sure I capture everything. Obviously I think the casdatifan cabo in that second line plus, I think you've mentioned about 40 patients. That's the update from the previous- Correct disclosure that you guys already gave. The mono update as well to the 120 making that- 120 patients that later line, 2nd line setting for mono- 3rd line plus The 3rd line plus for casdatifan. You also mentioned there's two, the front line regimens, the PD-1 plus casdatifan- Correct how many patients should we- That's just over 30. About 30 patients. Then there's another casdatifan PD-1 and ipilimumab. Right Also in the front line. How many? That'll be about 30. Yeah. I think so we'll have the 31 patients for the casdatifan zimberelimab. The median follow-up will probably be in the 8- 10 month range. Yeah. We'll have like an early look at efficacy there, whereas like Terry was saying, the casdatifan zim ipi cohort will have double-digit number of patients that will have made it through the 12 weeks with the ipi containing portion. That's going to be mostly a read on the ability to tolerate that triplet. Right. The safety. Yeah. Okay. I remember in the past you also mentioned a monotherapy cohort in the frontline for that favorable risk group. Is that also going to be part of it? We have that whether or not we update on it. We're trying to be very focused on what we're doing insofar as the data we're generating that supports the registrational studies. We have those data, we'll probably comment on them, as you said, it sounds like a lot and we're trying to make it simple, not confusing, in the sense that those cohorts essentially read on rates of primary progression, which look really good, but they're not really adding to the dataset that support those registrational studies. Whether we mix that in or do it at a different point is TBD. Got it. Okay. You guys also mentioned that there was another TKI-free regimen that you were exploring. Oh. Later on we saw this PR on this bispecific from Bristol Myers Squibb. Is that the one that you guys are- That- Is there another one? What Rich is referring to is we just announced a collaboration with BMS, where basically that BMS BioNTech bispecific VEGF, PD-L1 bispecific, we're combining two arms of their platform study that BMS is executing. We're very excited about that. I think it's a high priority for them. That is another part of our strategy. It's very compartmentalized, so nothing else we're doing is dependent on that. That is going to be starting pretty soon. I think Bob kind of has described that nicely as it's kind of in between TKI sparing and IOIO, where you have that VEGF component there. I should also say, though, that's part of a strategy in and of itself. It's a sub-strategy. You'll see us announcing additional collaborations. We've set expectations that we would have more than one, and they're basically going to cover three different important aspects to us. One, we're working with a partner, for example, like BMS. They have such strong experience, expertise, and commitment in clear cell RCC. For a number of reasons, they're a great partner. They've got their platform study up and running. There'll be another study where you'll see that we also weave in an HCC component, which is, again, a very smart place for those bispecifics to go, and it's a very smart place for casdatifan to go. Then there'll be a third, where we'll actually be the one executing the study. While we value the strategic elements of these collaborations, we also like the idea that within ARC-20, we know we'll get one done very fast. And if one of these other partners can beat us- Great, we feel like we'll execute very efficiently. We're covering strategic partners, HCC as well as RCC, couple of interesting combinations, a study where we will execute it ourselves. I see. Okay. Do you believe that there's still a debate if CAS is the better HIF-2 alpha compared to belzutifan? Because one argument is that in the mono and the combo data that you guys have generated so far, it's still early, right? Small sample sizes. There's no control arm. What is giving you confidence that CAS is better? Yeah. I don't think there's much of a debate, and certainly when we talk to people, that's not something out of all the questions that people raise, and I'll explain why. First of all, we have such a huge amount of data as single agent. The 120-patient monotherapy, that's actually a fairly large end. Keep in mind that involves over 40 sites. We've got the multiple different settings, combinations, et cetera, where we generated data. I think the most compelling data, though, if you first just take the clinical efficacy data, we're so much better than belzutifan on every endpoint, whether it's ORR, PFS, our durability, our rate of primary progression. To me, within a very sho rt period of time, you're going to see a publication in as high impact journal that there is, that ties together the basic biology and science of HIF-2 and casdatifan, the biomarker data, and the clinical efficacy. That'll all be out there. The piece that's intrinsic in that that gives the most confidence, and to me, it enhances that confidence by orders of magnitude, is that you've got the biomarker correlative data from monotherapy patients that shows dramatic, and I state that, I'll emphasize with all caps, dramatic differentiation from belzutifan. Keep in mind, everything's rooted in this is highly reproducible and has nothing to do with patient population. You have a dramatic PK/PD difference between the molecules, and that's not something that has to do with patient demographics. We did our initial work even in healthy volunteers. When you look at the biomarker data, and that's very well defined, that suppression of erythropoietin production, not only do you see a deeper inhibition by casdatifan than you do with belzutifan, but the time course is what's really dramatic. This is Merck's own data and our data, and these are, again, not sort of dependent on patient characteristics, or you don't need to randomize to do this. You go do another 50,000 patients, and they're still going to look the same. I think the piece that not only do we see that dramatic difference in durability of effect, but we've also demonstrated that the ability to suppress erythropoietin production is correlative with clinical outcome. If you combine all those factors, the fact that you're seeing better clinical efficacy and you've shown that your suppression of erythropoietin production is deeper and longer, and you've shown the correlation of ability to suppress that production. You've got too many dots connecting to not have strong confidence in that differentiation of the molecules. I see. Okay. You guys laid out earlier your vision for CAS in that 1L to 3L plus setting. Basically, it would dominate that entire treatment paradigm. Looking at that, what is your partnership strategy in general for CAS? You guys have traditionally been very friendly to partnerships. You have a lot of ongoing partnerships. For CAS itself, how are you guys thinking about that partnership strategy, or is there one? Yeah, let me state that, I'll see if Bob wants to add anything to that. What's nice, because this is a two-horse race, there's only two molecules out there. Belzutifan, Merck is developing that. We think we have a better molecule. We think strategics that might want to combine or collaborate with us recognize that as well. We're in a position where the collaboration strategy is do things like what you've just seen, where we're combining with something that makes a whole lot of sense, and both companies maintain the rights to their own molecule. We have every intent of commercializing casdatifan and not partnering anything that relates to the commercial rights. Is there anything else you would add? That was Yeah, underlining the latter part for sure. I think we view whole ownership of casdatifan as providing a ton of strategic optionality. We think that the molecule is very attractive from a clinical collaboration perspective. Right. That enables us in a very capital efficient way to go places that we wouldn't be able to go. Right by ourselves. I'd almost take that's how I think we should want people to think about looking at the entire portfolio. With casdatifan, we own 100%. There's no reason to want to give up any of that. Right. We think we can manage the commercialization. Even in the I&I, basically, the only program right now where there's even option rights is that our TNFR1 program, Gilead maintains an option to that we think we'll probably get to a decision on that by the latter part of this year. A2, CCR6, STAT6, actually CD40 ligand, CD89 antibody, those are all wholly owned Arcus programs, and that gives us another angle of strategic optionality to complement what we're doing with casdatifan. Fantastic. We have a couple more minutes left. There's still a lot for me to go through. It's just a very interesting time for you guys. Let's go into that second line setting, right? You guys have data coming out for that cas cabo data. Merck read out the LITESPARK-011 in that second line setting as well for the bel's lenva combination, and achieved a hazard ratio of 0.7 and then about 15 months of PFS against cabo's 11 months. You guys already showed that 15 months for that monotherapy cohort as well in that later line setting. What do you think is meaningfully better compared to that 15 months for bel's that would clearly show that the strategy that you guys have with that cas cabo is a more superior approach versus lenva and bel's? Yeah, we think we're going to be able to illustrate that by sharing Kaplan-Meier curve. We're not going to put out some number that is. As you know, median PFS gets criticized as for what it means because it's a single point, particularly for a program where durability is driving hazard ratio. It's also going to drive the commercial aspects of this. I think also when you think about the Merck study, it's a fairly different study in terms of the design. We're both running against cabo, which we think is great because that hazard ratio will let you compare directly. When you think about the Merck study, they had to exclude both lenva-experienced patients as well as cabo-experienced patients. We don't have that limitation because we're running cabo as the control. Yeah We can include lenvatinib patients as well as IO patients. What you'll see from us that I think will give you very strong confidence is Kaplan-Meier curves. We'll compare to all the corresponding Kaplan-Meier curves from the other combinations that you mentioned. As I mentioned before, we may even have some initial reads on OS, which for us, you know, is sort of like, well, this field hasn't been around long enough with HIF-2 inhibition. We feel that could be the Holy Grail from a commercial standpoint, because while OS hasn't been a required registrational endpoint, it's a huge point of differentiation, and I think it also reflects on that durability where we'll have an opportunity to maybe show advantages to their paradigm. Got it. Keep in mind, Merck has essentially had three opportunities now and has not shown yet an OS advantage. Okay, got it. You mentioned too, you're not that concerned about PFS. However, the market is going to be very concerned about PFS. If they should not be concerned about PFS, people like numbers. They like one number that they can easily compare things to. How will you think about it? Is that hazard ratio that people should be more focusing on than PFS? What's that one number for you? To me, absolutely it is the hazard ratio, and I think from while you'll be able to look at those curves, you'll be able to extrapolate to how you think that looks. I also think people can pick whatever number they want. We're not going to twist anybody's arm out of a particular number, we feel it would be silly to sit here now and pull a number out of the air that we think represents some sort of a milestone on any of our endpoints. Even when you look at our late line data, what we would emphasize is the shape of our curve, and we talk about it all the time. The number of patients, even stable disease patients that are out past two years of therapy, that's really going to drive both the utilization the commercial opportunity. We recognize that people will look at the number. We think our numbers will be good, but we're not going to We can get asked as much as people want. We're not going to look to throw out any single number for any single endpoint nor an ORR, you name it. We're not just going to throw a random number out, especially when we don't know the data yet. Right. Okay, got it. For this year or ESMO to work more ESMO timing readout, can you walk through what are the endpoints that you would show? I think you talk about the Kaplan-Meier curve. There's about 40 patients or so. What other endpoint should we see, the DOR? I think you mentioned potentially OS, but maybe just walk through all that. Some pieces of that will be a little bit more mature than others for sure. I think Terry said the Kaplan-Meier curve for PFS is probably the piece that we would most underscore in terms of telling us the most about the future of the program. I think we'll have various landmark numbers. You'll look at that time course of what's happening with patients over time. We do think that especially just given the pharmacodynamic profile of casdatifan, we think the tail effect for the program or for that molecule could look really good. Landmark numbers will be important in addition to just a median. I think as Terry also mentioned, the less mature pieces, but the pieces that we may begin to look at would be OS and then duration of response as you mentioned. I see. Okay, got it. How do we know that this data is going to be reliable just given that there's no control for this? Is there any reason to believe that this number could be somewhat inflated and then once you go start that phase III larger study that it's a different number? Yeah. It's interesting. Ironically, in this particular setting, you saw a little bit of the opposite effect with the belzutifan data. Actually, the other piece of it is actually ex-U.S. sites performed from an actual efficacy perspective with the belzutifan program slightly better than the U.S. sites. Some of the dogma that folks have around deterioration of data in U.S. versus ex-U.S. hasn't played out in their pivotal program for belzutifan. We think we have a pretty representative footprint at U.S., ex-U.S. ARC-20 is a big platform, if you will, with over 40 sites and we think there's a good representation there. I think we feel as good as about as you could for a study of that size. I think the data are so robust and there's so many different studies all pointing to the same answer that. Of course, your question is like it's one of those questions that can never be answered. You haven't run the thousand-patient study. No one's run the thousand-patient study before they've run the thousand-patient study. I don't think you could have a better, more comprehensive data set that goes from biological profile, PK, PD, clinical efficacy, large number of sites, large number of settings as opposed to so many times where data doesn't hold up is when someone comes in with 20 patients worth of data and there's nothing to calibrate it against. The other thing that we've shown and we had the same questions early in the monotherapy. Everything you're asking now when we had the same questions with the monotherapy data and what we've shown consistently and we actually always put the slide in and we'll do it again, the data have gotten better with time as opposed to degrading. I think it's a hallmark of this mechanism where you have something that's. Keep in mind, 85% to 90%+ of patients have HIF-2 as a driver. Every time when someone would ask a question about how do you think if whether it would hold up or not, it would almost be the opposite that would be the shock because you're going after something that's fundamentally a part of this tumor setting and you're hitting it robustly. I think if anything, the Merck data with a relatively modestly good HIF-2 inhibitor have so validated the target and the idea that you would have a molecule that's hitting the target so much harder and not have it manifest itself would be more the shock than the other otherwise. Fantastic. We're well over time. Thank you so much. Thank you. Very exciting stuff. I think next year we have to book you guys for two fireside chats. Thanks for giving us a extra three minutes. We appreciate it.