Great attendance. Everyone looks very tired, so that's a good sign. Yeah. Nice to be, like, feeling like we have a lot of energy, and everyone else is, like, dragging. Hi, everyone, let's get started. We have Arcus joining us for the Fireside Chat. I'm Li Watsek, a biotech analyst here at Cantor, and we're thrilled to have Jennifer Jarrett, Chief Operating Officer, and Ike Ohakwe, Chief Commercial Officer, with us here today. I guess for our audience, we can start with a brief company overview, and I know, guys, you have a lot coming up, so maybe walk us through the catalysts as well. Yeah. So, maybe I'll focus on that latter part, the two catalysts that we have coming up, because I think it tells a lot about where the company is today, so first of all, it's really unusual to be sitting up here, the middle of September and still have two really exciting data sets that are coming before year-end, so just in the next two months or so. The first data set that's coming is from our ARC-20 studies, for our phase I/Ib study for casdatifan, which is our HIF-2 alpha inhibitor. The data will be presented at an oral plenary session at the Triple Meeting in Barcelona in just over a month. We're really excited that Toni Choueiri is gonna be the one presenting the data. He did a lot of the early clinical work for belzutifan, was the lead author in their publication, so he probably knows more about this class than anyone, so he will be the one presenting our data. As far as the data that we will be presenting, it's gonna be a lot. So we'll be presenting data from the 100 mg expansion cohort, which was the first expansion cohort that we enrolled. It's just over 30 patients. We'll be able to share data on primary progressive disease, on ORR. We will not have mature PFS, but we'll be able to say something about where PFS is headed. And there'll be a lot of tables and charts, so, you know, you'll see waterfall, spider plot, which I think looks probably the most interesting, swimmer lane, which also looks really interesting 'cause you start to get a sense for what the durability of response looks like. So I think that'll be really exciting. And then on top of the 100 mg expansion cohort, we'll also be presenting some data from the 50 mg expansion cohort, which was the expansion cohort that we enrolled after the 100 mg cohort. So that one will have less follow-up. The 100 mg cohort has about 10 months median follow-up. The 50 mg is only about 5 months median follow-up, but it's looking really interesting, so we thought it was worth showing everybody. And I think what'll be nice about that is we've seen a lot of examples in the oncology space, where you see one data set looks really interesting, and then you see a little bit of, the data, receding a little bit when you see the next set of data. And so I think seeing, like, two data sets back-to-back that look very similar should be very confidence-inspiring for people. So that is the first data set that's coming. The second data set that we expect to be presenting before year-end is for our TIGIT antibody, domvanalimab. This is an Fc-silent TIGIT antibody, so that is different than most of the other TIGIT antibodies that you hear about, such as the Merck TIGIT antibody, the Roche TIGIT antibody, the iTeos TIGIT antibody. Those are all Fc-enabled TIGIT antibodies. The data set that we'll be presenting is for our ARC-10 study, which was a phase III study that we were running. We decided to terminate it for strategic reasons, to focus instead on our study that was looking at dom plus zim plus chemo in all-comers lung, but what was nice about terminating the study early is, like, we now have another data set with randomized arms that is looking at dom plus zim versus zim versus chemo. It's a 100-patient data set in total. It was 40 patients dom/zim, 40 patients zim, 20 patients chemo, and we'll have about two years of follow-up, so with all of that follow-up, we'll obviously be able to show ORR, and we'll also be able to show PFS and OS, and we think the data lines up really nicely. We know that, as we keep saying, and I think you've said this as well- Yeah ... TIGIT is a show-me story, but, you know, we think for a show-me story, the data is gonna look really, really interesting to people. And we'll talk a little bit more about what's out there to give us, to continue to give us confidence in our TIGIT antibody. Okay. So I guess before we dive into your programs, which you have a lot, I have a strategic question for you. Obviously, when I look at your pipeline, I think there are two baskets, right? One is IO TIGIT, PD-1, and the other basket, you're looking at some small molecules. I think HIF-2 is a very interesting molecule. So how are you thinking about, you know, these two baskets? And then obviously, you're running some combinations as well. So just from a portfolio, I guess, perspective, where do you actually see the biggest opportunities? Yeah. So, you know, in terms of targets, we're actually pretty agnostic. So, you know- Right ... we're not an IO-focused company. We're not a oncology exclusively focused company. We're not a cell-intrinsic target company. So we've picked targets that we like and where we feel like there's suboptimal drugs against those targets. And so we did start more in the IO space, so our TIGIT program and then our Adenosine programs would all probably be put in that bucket. But our next wave of programs is gonna be more cell-intrinsic targets, so that's obviously the HIF-2 alpha program that you were referencing. The next program that I think you'll start to hear us talk more and more about is our AXL inhibitor. So that's another, really interesting target, for lung cancer. There's a few other molecules that are out there, but they lack, both potency and selectivity, so I think, we think we have a best-in-class molecule there. We have some other cell intrinsic targeted molecules that we're working on, that we'll be able to probably talk more about over the next year. And then you'll also see us start to expand a bit more into inflammation. We've always had experience at our company in the inflammation space. A lot of our research team came from ChemoCentryx, which was focused on the inflammation space, so there was just already a lot of in-house knowledge and expertise, so it was a really logical place for us to expand into. So I think also over the next twelve months, you'll start to hear more about some targets that we're working on, on the inflammation side. Mm-hmm. So it's nice because we do have our own drug discovery engine. We can sort of work on whatever we want, whatever we find interesting. But to your question, you know- Yeah ... you will see our portfolio diversify, continue to diversify over the next few years. Okay, maybe let's move on to the HIF-2 alpha, and Cas. Obviously, we've seen some competitor data at ESMO, so just want to get your thoughts on that and in terms of differentiation for Cas. Yeah, so there's two competitor data sets, which I think both for us, the read-through is very, very positive. We were definitely excited when we saw both those data sets because we think they created a lot of opportunity for us. The first data set was for NiKang molecule. So, as most of you probably know, there's one approved molecule today in the HIF-2 alpha space, that's Merck's Belzutifan. So obviously, that is a competitor. We thought there was another potential competitor with NiKang molecule. This was the first time that we'd seen data from their expansion cohorts and dose escalation. While the headline numbers actually looked pretty good, so they showed about a 24% confirmed ORR, nine months plus-ish, PFS, there was a lot of other sort of holes in the data that you could poke at. Probably the biggest issue was their half-life. So they saw about a 35-day half-life, so very similar to what Novartis saw. So obviously, that resulted in more grade 3 hypoxia, which is one of the on-target toxicities that you see with this mechanism. On top of that, they clearly had to play with a lot of different dosing regimens, so they're looking at different loading and maintenance doses, and based on their data and based on their commentary, it sounds like they still haven't figured out what the right dose is. And then third is, when you looked at their ORRs and really started to break down the numbers a bit, for their denominator for their ORR, they used an efficacy evaluable patient number, which was different than their ITT patient population number, and it wasn't very clear what was accounting for that difference. You know, the real ORR was probably different than the 24%. The primary takeaway for us on that was that NiKang is probably not gonna be much of a competitor in this space, and it really is just gonna be between us and Merck. We'll talk more about how we think we stack up relative to Merck in a bit. The other data set was Merck's LITESPARK-005. Most of the numbers looked the same, so primary progressive disease still around 33%-34%. That is definitely the biggest weakness any RCC specialist that you talk to will call that out right away. And what that means is- Mm ... 33%-34% of your patients are progressing basically out of the gate, so on or before your first scan. These are patients that never get a chance to benefit from treatment, and that's obviously gonna be a drag on PFS and OS. Their ORR was, you know, pretty much unchanged, their, you know, almost 22%. PFS was also unchanged, five and a half months. These are all numbers that we think are beatable. And then on OS, they were not stat sig. It was not the primary endpoint of the study, so it doesn't change anything from an approvability standpoint in the U.S., or likely how the drug is gonna be used here. But as soon as the clinicians that we worked saw that number, they were all pinging us and saying: "Look, this is, like, a huge opportunity for you guys. We think you guys have a better drug, and this is just another example of where we think that you can show better data than Merck." So we thought both those data sets played very much into our favor. So maybe let's just talk a little bit about the benchmark here. Mm-hmm. Obviously, you're thinking, you know, Merck's data sort of set a very good bar for you guys. So, you talked a little bit about, you know, ORR and the primary disease, you know, rate. Maybe just touch on that, and why do you think... Or what do you need to show to be able to say, "Okay, we're best in class? So there's three efficacy measures that matter. First is Primary Progressive Disease. We're gonna know what that number is. It is not gonna change when we present it, because you know that at the very first scan. For both the 50 mg and the 100 mg, when we present that data, those numbers are what they are. The second number is ORR. That number is maturing, but we're not gonna be at a completely mature number because you do see some responses associated with HIF-2 alpha inhibition that change over time. But as we've been saying, our confirmed ORR for the 100 mg dose already looks better than Bel's. And then last is PFS. We will not have a mature number, as I said earlier, but I think we'll be able to give people a sense for where we're trending, and that number is gonna be trending better than where Belzutifan is. And then on top of that, as we've been saying, our goal is to have a drug with better efficacy and comparable safety. What's nice about this mechanism, it's actually really well-tolerated. That is, like, one of the first things that any clinician you talk to will say about HIF-2 alpha inhibition, is just these patients that are coming off of years of TKIs, and they go on Belzutifan, and they think it's a dream compared to what they've been experiencing. So we want to basically replicate the safety profile that we've seen with Belzutifan. So you'll see some on-target anemia and hypoxia, so we're keeping a close eye on those. But, you know, right now, we look very, very similar to the data that's been generated by Merck. So you sort of picked the 100 mg dose, but you're also sort of looking at, you know, patients at a lower dose and a higher dose. So is that mostly to satisfy Project Optimus? ... That was exactly what it was. So at our first FDA meeting, we talked to the FDA about what would we need to satisfy Project Optimus, and where we came out is that we would enroll a cohort at a lower dose and then a higher dose, then 100 mg. That's how we got to 50-150 mg. The sequences, you know, we did the 100 mg obviously first, and then we did the 50 mg, and then we enrolled the 150 mg after the 50 mg. So, we're actually, you know, maybe a little bit ahead of the game, on dose optimization, given where we are. But that's exactly why we did this cohort. But what is nice is, you know, we're now gonna have 90-plus patient data set. So it's gonna be a very substantial data set at the end of the day, and it should allow us next year to continue to be able to present data from this study. So we're not gonna just see the Triple Meeting data set, and then you won't hear from us until we get phase three data, but there's gonna be a lot of other data that's generated from this study that we can present on at future conferences. And you decided to go into combination with TKI. Talk to us about why you picked Cabo, and then maybe the phase three trial design for PIK3CA. Yeah, sure. I mean, we just opened the Cabo cohort in the phase 1. I think Cabo is the market-leading TKI, sort of across the board in the community setting, as well as the easiest to use, easiest to dose. So, we think that's, like, the clear, obvious choice from a phase 3 design standpoint. Makes it a very simple design of Cabo plus, minus Cas. Right now, there's not a lot in second-line RCC as far as enrollment, so we think the enrollment will go very quickly. So it just kind of brings the whole sort of best in profile from the molecule standpoint into a differentiated combination, right? So there's multiple TKIs that get used in RCC, and they all have a place. We think we'll have the best combination with CABO, and clearly, that will stack up relative to Belz with Len, and, it'll be sort of a two, two combination sort of choice there. So you also want to go after, you know, frontline, perhaps with another partner. Maybe talk a little bit about some of the options that you guys are looking at. Yeah, we can't say a whole lot about it. Yeah. Other than to say, like, we have a first-line strategy. Yeah. We'll be able to talk more about it- Hopefully by the Triple Meeting. in the future, so yeah- Yeah. So we think it's different, but unfortunately, we can't say more than that today. Yeah. Okay, maybe, Eric, you can touch on the commercial opportunities here for the combination. Sure, yeah. There's the two big ones that are sort of most clear are what we call the post-IO setting. So we'll have a lot of second line, as well as the post-adjuvant patients who have seen Pembro. And so that's the sort of Cas plus Cabo opportunity, and we think that's about a $2 billion opportunity. And then frontline is about 2x that. There's clearly opportunities to do differentiated combinations in frontline that Merck's not doing, and so between those two, I think we've got some pretty straightforward market opportunities there. And when you think about bringing something to market in RCC, physicians are used to changing from, you know, one TKI to another. The things that we're talking about in terms of primary PD, sort of early responses, faster time to response, those are things that really resonate with the community physician and, you know, clearly, the safety profile is not gonna be different. So I think that's what sets up for a pretty attractive opportunity for the molecule. In terms of your collaboration with Gilead, obviously, they have an opt-in option here. So when would that occur, and what are some of the, I guess, different scenarios that could play out here? So they. The opt-in trigger is based on us having a certain amount of data with a certain amount of follow-up. We should hit that point around the end of the year, so that's about when they would need to make their opt-in decision. So, you know, we're calling it end of the year, early next year. If they decide to opt in, we would get a $150 million opt-in, opt-in payment, and, they would then start cost-sharing for 50% of the cost of all the study. We retain a co-promote right in the U.S., so we would be, selling the drug with them, if it was approved. We share the profits in the U.S., and then outside the U.S., we get a high teens royalty that tiers up to, a 20% plus royalty, on ex-U.S. sales. Like, very attractive economics. Okay, so if Gilead decides not to opt in- Yeah. So would you guys, you know, sort of trying to do it all by yourself, or would you- Yeah, that's... I mean, I think we would- Oh, yeah ... probably either re-partner it with someone else or just go it alone. And what's nice about clinical collaborations, you know, which is obviously what we're planning for the first line, and that's in the works, is you get a lot of the benefits of partnering, but without some of the drawbacks because you have the cost-sharing, and so not everything is on your dime. The other company may be running the study. You don't have to add a bunch of people to run the study for you. And then on the positive side, you get to continue to control your molecule, and you get all of the downstream economics and rights. So one path could be, you know, this clinical collaboration strategy, and then another could be partnering, re-partnering, if someone were to offer us something that we thought was really awesome. You know, I'd say there is interest, and so we'll see if we get there. But I think Gilead's also interested in the molecule, so we'll see how it all plays out. We're very good with any direction this goes in. We know they like the molecule a lot, they're interested, and so we'll see what happens. Now, let's switch to TIGIT. Obviously, there's SKYSCRAPER-06, and then there's some interesting data coming out of ESMO. So just want to get your thoughts on why you think TIGIT is still a very good target? ... I mean, we could talk about both SKY sechs as well as the iTeos's data. I think what's really played out is that the Fc-active TIGITs have a challenge with toxicity. Whether you're looking at SKY sechs trying to combine with chemo or what you saw with iTeos's, where, you know, really interesting, clear, like, activity on the response rate side, but it came with a lot of toxicity. And I think across the board, that Fc story has really played out. We saw some really good data from AstraZeneca in gastric, actually, and their bispecific TIGIT is Fc-silent. Their ORRs and PFS are clearly above the benchmark in the gastric space. So from that standpoint, it's nice to see another Fc-silent TIGIT demonstrating clear activity as we have. And so, you know, seeing AZ really lean in on that program is definitely encouraging. And so in terms of the ARC-10 data you're gonna share later this year, I guess, what do you hope to accomplish with that data set? Obviously, this study is discontinued, so are you just trying to show, okay, we got a good, you know, TIGIT, good PD-1, and then therefore, it gives us more confidence for our study? That's, yeah, exactly it. Yeah. And so, to extend, there's lingering questions like, is Zim as good as pembro? The Zim numbers in ARC-10, like very, very similar to KEYNOTE-042, you know, probably couldn't get more similar. So it answered that question, and then, you know, you'll also see that Dom plus Zim is definitely better than Zim across every efficacy measure. So we think it'll just inspire, you know, more confidence in TIGIT. There's already a lot of confidence in TIGIT. It's kinda, so there's a little bit of a disconnect between what you see in the gastric community and the lung community. I think, you know, in the lung community, probably a little bit more scarring that's taken place because of SKY-01 and SKY-06. But, like, the gastric community is super, super excited about TIGIT. I mean, our study STAR-221, our phase III for our TIGIT antibody enrolled, you know, probably half the time that we thought it would. I mean, it was enrolling by the end, a hundred plus patients a month. Just a huge amount of interest. There continues to be a lot of interest. I think as Eric was saying with the AZ data set in gastric, I think that's just gonna generate more interest. Lung, we get. You know, but for everyone, it's a little bit more of a wait and see, but we hope that this data set will be another data set that says, "Hey, you know, maybe Fc-silent TIGIT antibody is the way to go," and there clearly seems to be a benefit in lung. I guess for the front line set of all-comer setting, obviously, we've seen some nice data from Summit. So want to get your thoughts there, and what do you think the bar should be front line? So what we've said. For, and Eric can talk about the Summit data set. But when we looked at their median PFS. You know, seemed like people like the median PFS. Their stock is up a lot. I think people will like our median PFS for dom plus Zim a lot, and dom plus Zim, unlike their combination or their bispecific, also does not seem to have, you know, if, you know, maybe no added toxicity or very, very little, versus they obviously saw a lot of added toxicity with their bispecific. So we think our data set will stack up very, very nicely compared to theirs. I think- Yeah ... for ARC-10, we will have OS, right? With a lot of follow-up, almost two years of follow-up. So yeah, I mean, with the Summit data, it's an interesting PFS signal. We've seen a lot with VEGF, where PFS looks great, but then OS deteriorates quite a bit. So I think that's the big question that's still lingering there. So I guess for the ARC-9 GI study that you guys are running, and I think it's very encouraging that you can roll the study so quickly. Maybe just remind us what you hope to show from the phase III and in terms of the timeline for the top-line data. So the only guidance we've given is it could be in the second half of two thousand and twenty-five. That's the earliest, which, you know, isn't that far away. As we get closer, we'll be able to narrow down the guidance a bit, but right now, you know, we're saying potentially two thousand, second half of two thousand and twenty-five. And because, you know, it is event-based, you know, there's some chance that it comes in a bit later than that. Maybe Eric can speak to the market opportunity here, especially in the Western population. Sure, yeah. I mean, as you know, this is a first-to-market opportunity in gastric. First Fc-silent TIGIT, but also really the first phase III that will read out an all-comer gastric. I think we're really excited about the data that we've already seen from EDGE-Gastric showing in the high population. I mean, clear differentiation versus nivo/chemo's benchmarks. That's about a $2 billion opportunity just in the highs, which is about half the population. And then if you think about the just all-comer, where we're also seeing good activity in the phase II, that would sort of take it well above $3 billion. So, I mean, from a straightforward launch standpoint, there's not a lot of competition. You've seen Claudin 18.2 will, you know, will be in the market, but we've got a much better overall profile from both the safety and activity standpoint, and so I think, you know, it's really a nice opportunity to bring, you know, domzim into the marketplace without that sort of noise of what's going on in lung, so that's gonna be a great first, you know, approach, and then we'll have the lung, you know, phase III data read out actually, like, while we're launching, so. Maybe lastly, let's talk a little bit about CD73 and adenosine. You've shared some pretty nice data in pancreatic cancer and colorectal. Maybe just talk about what you shared at ASCO and what is sort of the plan there. Yeah, so starting with pancreatic cancer, so we're developing Quemli, which is our small molecule CD73 inhibitor with gemcitabine in first-line Panc. You know, obviously terrible, terrible disease. Not a lot out there that has worked. If you look at the benchmarks for gemcitabine, for overall survival, it's about nine to 11 months, and that has not moved in many, many years. The data that we presented at ASCO GI showed just over 15 months OS for that for the patient population that we enrolled, so that's a very dramatic improvement. We actually did a synthetic control analysis, which was kind of interesting, where we worked with an outside group to do a match control analysis. So matching our patients up with patients that were in other phase 3 studies to come up with, like, a synthetic version of a control arm. In that control arm, they came up with about nine and a half months, so obviously very different than what we saw with our fifteenth plus months, so we're super excited about this study. I know, you know, a little bit jury's out on adenosine, but we're excited. The investigator community is very excited about the study. They're telling us, like: "Be prepared for this to enroll in record time." It's hard to believe, but sometimes enrolling a study too fast can be hard on a company, because you need to have a lot of drug, and they're like: "It's gonna roll way faster than you guys think. Sure. The other- Taiho opted in. Yeah, the new news was that Taiho opted in about two months ago, which is great for the program. That resulted in an upfront payment to us. There's also some near-term milestone payments that they'll be making to us, associated with starting the phase threes. Gemcitabine is very, very widely used in Japan. It is the standard of care. Outside there, it's a little bit more of a mix between FOLFIRINOX and gemcitabine, so it's great to have them on board for that reason. We think they'll be a really significant contributor from an enrollment standpoint, and they pay for all of the costs of the study in Japan, so it also helps us from that perspective. We are excited about that program. For Etrima, as a reminder, we just presented data at ASCO, the headline from that data set, and this was looking at Etrima plus FOLFOX plus Bev plus PD-1 in third line colorectal cancer. Usually you're looking at sort of eight-nine months overall survival in that patient population. We showed 20 months, which is something that's never been seen before in that patient population. So we're continuing to work with Gilead on next steps for that program. And one thing I just call out, we do have a an abstract that'll be presented a little later this year from ARC-9, but basically showing that high CD73 levels was associated with better OS, which is, you know, exactly what you'd wanna see, given that CD73 is what generates adenosine, and we're blocking adenosine. So, you know, we think that'll just be more validation that we seem to be doing biologically what you would expect. Just last question from me. Can you just remind us of the near-term milestones from your partners? Yeah. So, this one, so the opt-in payments, you mean, or? Yeah. Decisions? I just want to add from... You also have pretty comprehensive collaboration with them. Yeah. So, the three companies that we're mostly partnered with are, Gilead, obviously. So they have opted into Dom, Zim, Etrima, and Quemli, and they have an opt-in right to everything else in our portfolio for a certain period of time. The next thing that they would have an opt-in right to or the opt-in trigger would happen is for Cas, the HIF-2 alpha inhibitor. But that's obviously the big- Yes ... partnership, and we work with them very, very, very closely. There's probably 500 people, I would guess, at their company, maybe more, that are involved in our products, 'cause, you know, they're involved from a CMC perspective, a regulatory perspective, development perspective. So everyone there knows Arcus. Any time I run into someone in the Bay Area that's from Gilead, and I say I'm Arcus, they know who I am, immediately. The second partner that we work with is Taiho. So Taiho has an opt-in right to Japan and certain other countries in Southeast Asia, to our portfolio. That actually ends sooner, so I think the last product they get an opt-in right to is our CD39 antibody. They have opted in so far to Dom, Zim, and Etrima, and Quemli. So the next opt-in decision, like Gilead, will be for CAS. So they have a bit more time too than Gilead, as we saw with Quemli. So, you know, it could be like another year or two before they make their decision on Quemli. And then the third company that we work a lot with is AstraZeneca. So we were partnered with them on PAC-8. That is a phase three study for Dom in stage three lung that they are operationalizing. That's been going on now for about three years. So because of that study, we've been working pretty closely with them as well and have a good relationship with them, and they pay for about half the cost of that study, which is also nice. Great. Let's see if there is any questions from the audience. Eleven seconds to spare, and we also, you know, we have over $1 billion in cash, so we continue to be- Yeah ... really well-funded, and going back to the partnerships, between the upfront payments, milestones, cost sharing, it helps a lot. So-