Welcome everyone. The Arcus Biosciences full year and fourth quarter 2025 earnings and results call will begin shortly. In the meantime, if you would like to pre-register to ask a question, please press Star followed by one on your telephone keypad. If you change your mind, please press Star followed by two. Hello everyone, thank you for joining the Arcus Biosciences full year and fourth quarter 2025 earnings and financial results call. My name is Claire, and I'll be coordinating your call today. During the presentation, you can register a question by pressing Star followed by one on your telephone keypad. If you change your mind, please press star followed by two on your telephone keypad. I will now hand over to Holli Kolkey from Arcus Biosciences to begin. Please go ahead. Good afternoon. Thank you for joining us on today's conference call to discuss Arcus's fourth quarter and full year 2025 financial results and pipeline updates. I will be filling in for Pia Eaves, our Head of IR, who is out on maternity leave. I would like to remind you that on this call, management will make forward-looking statements, including statements about our cash runway, our projected 2026 revenue, and our expected clinical development milestones and timelines. All statements other than historical facts reflect the current beliefs and expectations of management and involve risks and uncertainties that may cause our actual results to differ from those expressed. Those risks and uncertainties are described in our most recent annual report and Form 10-K that has been filed with the SEC. For today's call, please refer to our latest corporate presentation posted in the investor section of our website. This afternoon, you'll hear from several members of our management team. Now I'll turn the call over to our CEO, Terry Rosen, to begin. Thanks very much, Holly, and thank you everyone for joining us this afternoon. 2026 is going to be a transformative year for Arcus. As you know, we've been focused on establishing casdatifan as the unequivocal best-in-class HIF-2α inhibitor and the new standard of care for clear cell renal cell carcinoma. This year is gonna be another substantial year for data presentations, as well as the advancement and expansion of our Phase III clinical program for CAS. I want to emphasize, particularly those who are new to Arcus or casdatifan, that the advantages of casdatifan are well understood. That's all connect from the earliest days of its design and development. The advantages derived from dramatic differentiation of casdatifan's PK/PD profile. These are evident in the highly quantitative and reproducible differentiation on the primary biomarker for HIF-2α inhibition, EPO production, and the manifestation is improvement on all key efficacy measures. casdatifan hits the target harder, it hits it earlier. Just this week, we shared updated data from our 20 cohorts evaluating casdatifan monotherapy in late-line clear cell RCC. We're also thrilled that Dr. Toni Choueiri will be presenting his data this weekend at ASCO GU. We're gonna discuss these data in more detail today. Suffice it to say, the bottom line is that single-agent CAS continues to achieve unprecedented ORR and PFS in late-line clear cell RCC. It's not only relative to data for belzutifan, the only currently marketed HIF-2α inhibitor, but also relative to data for standard of care TKIs. This can be seen very clearly on slide seven of our corporate deck. Importantly, casdatifan achieves these outcomes without the debilitating toxicities associated with TKIs. In addition to the clinical data, the ASCO GU presentation will include biomarker data that further reinforce the confidence in the differentiation of casdatifan versus belzutifan. Also at ASCO GU, we're gonna see the detailed results from the phase three LITESPARK-011 study. This evaluated belzutifan plus lenvatinib versus cabozantinib in IO-experienced clear cell RCC. These data should be both validating and highly de-risking for our ongoing phase three PEAK-1 study, which is evaluating CAS plus cabo in a similar setting and with the same control arm. With both our own data and the belzutifan data being presented, this ASCO GU will be an extremely important event for the HIF-2α inhibitor class, firmly establishing it as a key standard of care in the treatment of RCC. We believe HIF-2α inhibitors will have a place in every line of treatment for RCC, CAS is extremely well-positioned to be the HIF-2α inhibitor of choice across all settings. As we will describe later, we believe the profile of CAS will enable a unique frontline regimen that will transform the patient journey in this setting and could translate into $ multi-billion commercial opportunities. Our first Phase III study for CAS, PEAK-1, is enrolling and is designed to get CAS approved and to patients as quickly as possible. This represents our fast-to-market strategy. There's already a high level of excitement driving enrollment in PEAK-1, the strength of our new ARC-20 data, coupled with the further validation of the HIF-2α inhibition in early line settings by the LITESPARK data, will amplify the enthusiasm for this study. By combining our best-in-class HIF-2α inhibitor with the most widely used TKI cabozantinib, we believe we'll capture a substantial share of the IO-experienced setting. I'd like to spend a few minutes on our frontline strategy because this is going to be a huge focus for us throughout 2026. Our frontline strategy is enabled by the consistently low rate of primary progression that's been observed with casdatifan across settings. This is shown very clearly on slide 20 of our corporate presentation. Primary progression reflects the proportion of patients whose disease progresses at or before the first scan. It's important for this rate to be as low as possible, particularly in early line treatment, because patients with primary progression do not get an opportunity to benefit from therapy. This is devastating for both patients and their doctors. In contrast to the low rates for CAS, belzutifan is associated with a very high rate of primary progression. 35% is monotherapy in its Phase III trial. The manifestation of this key differentiation is that in frontline RCC, belzutifan will likely always require combination with a TKI to keep primary progression low. In fact, Merck's Phase III study in the frontline setting is evaluating exactly that. Lenvima, Belz, Pembro, that's a pretty non-patient-friendly regimen in the context of quality of life. A TKI-free regimen, on the other hand, is much more desirable for both patients and clinicians. The most common feedback that we receive from investigators is that given casdatifan's profile, the use of a TKI can likely be put off for years. This offers a far better option for patients that would greatly improve their quality of life. Our frontline strategy is to develop casdatifan without a TKI and specifically with a backbone of casdatifan plus anti-PD-1, which we can build upon with a third non-TKI mechanism. We plan to execute on this strategy quickly and efficiently using our ARC-20 study. This is probably a good time to explain how we have and will continue to leverage ARC-20 to drive our development strategy for CAS. First, with four monotherapy cohorts and 121 patients of efficacy data in late-line clear cell RCC, ARC-20 enables us to clearly demonstrate that CAS has the best-in-class HIF-2α inhibitor profile. Second, with these four monotherapy cohorts, which were designed to satisfy Project Optimus, we've established that 100 mg once a day is the optimal going forward dose of casdatifan. The design allows us to rapidly and efficiently add and enroll cohorts to evaluate CAS and CAS-based combinations in other settings. We now have around 30 sites across four countries active in this study, and this drives efficiency. We first utilized this with the CAS plus cabo cohort, where we quickly generated data to support our first phase III study, PEAK1. We added three new cohorts, approximately 90 patients in total, to demonstrate the feasibility of using CAS without a TKI in early line settings. One of these cohorts is the CAS plus zim cohort, which is fully enrolled and for which we've already shared a primary progression rate of 9% for the first 23 of 30 patients. With the low rate of primary progression across all settings, we and our investigator advisors are convinced that the ideal frontline therapy is a TKI-sparing casdatifan regimen. We just started enrolling a new cohort to evaluate CAS with anti-PD-1 and anti-CTLA-4 to support the rapid initiation and execution of our first Phase III study in the frontline settings. Finally, while RCC is our top priority, we've generated exciting preclinical data for CAS in HCC and are evaluating opportunities to pursue HCC in a cost and resource-efficient manner. We spent a lot of time already on casdatifan, but I want to transition now to our immunology portfolio, where there's been a lot of and growing interest. We've leveraged the same small molecule capability that created casdatifan to build an emerging portfolio of inflammation and immunology programs. Two of these are expected to enter the clinic over the next 12 months. We are focused on addressing validated targets against which it has historically been difficult to create small molecule drugs that have optimal pharmaceutical properties. For this reason, we expect limited competition for our I&I programs, similar to what we're seeing with casdatifan. Our three most advanced molecules are an MRGPRX2 antagonist, a TNF inhibitor, and CCR6 antagonist. Later on this call, Juan will speak in more detail about the potential differentiation of our compounds relative to others. Before we go there, I'd like to turn the call over to Richard to review the new and updated casdatifan data that we'll be presenting at ASCO GU this coming weekend. Thank you, Terry. I'd like to start on slide nine of our corporate deck just to remind everyone about the design of our ARC-20 study. Today's data includes updated ORR and PFS based on a data cutoff date of January 30th from the four late line monotherapy cohorts highlighted on this slide. This is now the fourth time we are presenting data for single agent casdatifan in the setting. As you'll see on the next few slides, the efficacy data continue to improve with longer follow-up. Moving to slide 10, where we show the latest ORRs for the 100-milligram QD cohort, which is our going-forward dose and formulation. The confirmed ORR increased from 35% at the August data cut, now to 45%. The 45% ORR in this late line patient population is remarkable, in that it's twice that observed with belzutifan in LITESPARK-005. Similarly, the confirmed ORR for the pooled analysis improved from 31% to 35%, well above the range of ORRs that has been observed for belzutifan. On slide 12, we show the latest Kaplan-Meier curve for the 100-milligram cohort. You can see here that this 100-milligram cohort shows an impressive median PFS of 15.1 months after 17.8 months of median follow-up. There are some patients still on treatment who are censored before the median, but even in the highly unlikely scenario where all censored patients progress at their next scan, the median PFS for this cohort would still be 14.4 months. Let's move on to the next slide 13, and we show the latest Kaplan-Meier curve for the pooled analysis. The median PFS remained at 12.2 months. As you can see here, there are quite a lot of patients still on treatment beyond 12 months and even beyond 24 months. Overall, we are seeing PFS that is two to three times longer with CAS monotherapy than the 5.6 months observed for belzutifan in the same setting. These data clearly support the proposition that casdatifan is the best in class HIF-2α inhibitor. Our highest priority now is to maximize the potential of this molecule in clear cell renal cell carcinoma. Now I'd like to spend some time on our development plans, starting with our first Phase III study, PEAK-1, which is evaluating CAS plus CABO versus CABO in immunotherapy-experienced ccRCC. The trial design is shown on slide 19 of our corporate deck. PEAK-1 is actively enrolling. We are confident that the study will complete enrollment quickly. Additionally, PEAK-1 has a sole primary endpoint of PFS, which should enable a relatively short time to read out. This is a fast to market strategy that builds on top of standard of care, and based on all the data to date, we have high confidence that this study will establish CAS plus CABO as the new standard of care in IO-experienced clear cell RCC. Meanwhile, as Terry talked about earlier, our first-line strategy has the potential to transform the treatment paradigm for RCC. We're focused on the development of a TKI-free regimen that improves on the efficacy of IO-only therapy, and there are several opportunities for CAS to do this. The biggest limitation of anti-PD-1 plus anti-CTLA-4 therapy is that it has a relatively high rate of primary progression, that is, of 20%-25%. With CAS's low rate of primary progression and its orthogonal mechanism, we believe we can meaningfully improve upon this high rate of primary PD seen with the IO-only therapy. We have shown that patients who progress quickly on IO-based therapies have tumor markers that correlate with responsivity to CAS. Median PFS for IO-only regimens in clear cell RCC is relatively short at about 12 months. Again, we believe we can meaningfully improve on this PFS. To determine the optimal go-forward TKI-free regimen, we are evaluating multiple CAS combinations in ARC-20. These include our fully enrolled cohort evaluating CAS plus Zim, which we believe will convincingly demonstrate the ability of CAS plus an anti-PD-1 to form the backbone of our first-line regimen based on both safety and efficacy. We plan to share data from this cohort in the second half of this year. We just started a cohort to evaluate CAS in combination with anti-PD-1 and anti-CTLA-4. In addition to this cohort, we also plan to evaluate another TKI-free combination for CAS in the frontline setting, and we'll share more about this in the coming months. We continue to monitor data from the eVOLVE study evaluating CAS plus volrustomig, an anti-PD-1 CTLA-4 bispecific that's in collaboration with AstraZeneca. The safety and early efficacy data from all of these cohorts will inform the design of our first Phase III study for CAS in the frontline setting. We have already started planning activities to enable us to initiate a Phase III study as soon as we have the relevant safety and efficacy data in hand. Our goal is to initiate a Phase III study at the end of this year. With that, I'd like to turn the call over to Jen to speak in more detail about the potential market opportunity for casdatifan. Thanks, Richard. I'd like to start on slide 22. RCC represents a massive multi-billion dollar market opportunity for casdatifan. Sales for RCC drugs in just some major markets are over $10 billion annually today, and is anticipated to grow to $13 billion by 2030. As you can see here, historically, the market has been dominated by only two classes of therapies, IO and TKIs. HIF-2α inhibition is the only new class of drugs on the horizon today. Importantly, as of today, the HIF-2α inhibitor field is only a 2-horse race with just belzutifan and us, with casdatifan. While market is slightly ahead of us, historical data has shown that in just a 2-player market in oncology, second entrants have captured 42% when there is 0 differentiation. Let me repeat that, this is when there is no differentiation. With efficacy differentiation, as we are seeing with casdatifan, this year can be meaningfully higher. Oncology analogs have shown that fast followers with differentiation share can be as high as 85%. Additionally, we are developing casdatifan with different combination partners than belzutifan, which should drive even further differentiation. Turning to slide 23, the sole marketed HIF-2α inhibitor, belzutifan, which is currently approved only in late-line clear cell RCC, is already generating annual run rate sales of nearly $1 billion. While impressive, this is only scratching the surface in terms of market opportunity for a best-in-class HIF-2α inhibitor. For casdatifan, we are focused on early line settings, which have larger patient populations and longer durations of therapy, both of which will contribute to a much larger market opportunity that is multi-billion dollars in size. Specifically, our PEAK-1 study is targeting the IO experience setting, of which there are approximately 21,000 patients in the major markets alone, somewhere than twice the third-line patient population, where BELZ is approved today. Additionally, with the duration of therapy at least double that of belzutifan today, we expect a peak sales opportunity of $2.5 billion in the IO experience or PEAK-1 setting alone. In first line, the opportunity is even greater. With our TKI-free strategy, we believe we can take meaningful share from both IOIO and IOTKI regimens. Here we estimate peak sales potentially for casdatifan of $3 billion or more. All in, casdatifan could be a $5 billion drug in first and second line RCC alone. To be clear, this is a revenue opportunity to Arcus, not TAM or total addressable market. There's opportunity to expand that further with trials that support casdatifan usage in other RCC settings, as well as potentially other tumor types like HCC, which Terry referenced earlier. As a reminder, we own all of the rights to casdatifan, including economics, other than in Japan and certain other Southeast Asian countries, so nearly 100% of casdatifan revenues would accrue to us. I'll end with one slide that supports our plans to focus on a TKI-free regimen in the front line, and that's slide 24. Here we show market research that we recently conducted to determine the preferred combination partner for casdatifan in the front line. You can see here very clearly that the IOIO regimen is preferred three t imes more than the IOTKI regimen as a combination partner for casdatifan, for all the reasons we discussed earlier today. I'd now like to turn the call over to Juan to discuss our immunology portfolio and what's next. Thanks, Jen. I'm happy to describe such emerging immunology portfolio. This is an area in which we have interest and in-house expertise since our the funding of the company. This portfolio currently includes five programs that you can see in our slide deck, reflecting the maturity of multiple years of research and compound optimization. Our strategy is simple and has been core to our approach since the very beginning of the company: to minimize biological risk by focusing on and building upon mechanisms with validated clinical activity. In general, we are focused on taking a small molecule approach to pathways where biologics have been highly successful. This is where we believe that we have an opportunity to create the most value. We generally look for more than just the convenience of an oral drug. In fact, the value proposition for several of our programs includes an expectation of differentiated efficacy, safety, relative to the approved biologics. Our portfolio includes several programs, as I mentioned before, five active ones, but today I will focus on our MRGPRX2 and TNF inhibitor programs, which are expected to be the first to reach the clinic. Firstly, regarding our X2 antagonist program, we plan to target both chronic urticaria as well as atopic dermatitis. X2, which has received a lot of attention in recent months, represents a novel and exciting target for the modulation of mast cell activity. While anti-IgE and anti-IL4 receptor antibodies are marketed very successfully, for example, Dupixent alone is a $15 billion drug, there's still significant unmet medical need. While with the marketed antibodies, a substantial percentage of patients don't respond well to treatment. I want to emphasize that targeting mast cells is a validated approach in allergic conditions such as chronic urticaria, and allergic asthma. A small molecule approach that targets a novel pathway for mast cell degranulation could represent a differentiated mechanism of action to address the existing clinical need, both in chronic urticaria as well as atopic dermatitis, relative to the available biologics. Our candidate molecule has been specifically designed to improve both on the potency and pharmacokinetics side of the equation, relative to the early small molecule entrants into the clinic. In fact, we believe that our required clinical exposure in patients, obviously, will be dramatically lower than those required for the leading small molecule currently being evaluated in clinical trials. This could translate into a potentially improved therapeutic index and potential best-in-class profile. We expect our MRGPRX2 antagonist to enter the clinic later this year. We plan to start with a healthy volunteer Phase I study, to follow quickly with a proof of concept study in chronic inducible urticaria. This program has the potential to generate proof of concept data within nine to 12 months following entry into the clinic. Our TNF inhibitor program also represents another significant opportunity. Anti-TNF antibodies are amongst the most successful drugs ever developed. With our small molecule approach, we have the potential to develop a Humira in a pill. One of the challenges with today's TNF antibody therapies is that they block TNF signaling at both receptor 1 and receptor 2. Blocking TNF receptor 2 can actually impact regulatory T cells and tissue repair, resulting in a paradoxical inflammation as a side effect in some patients. Our approach is designed to selectively prevent TNF from activating TNF receptor 1, while preserving TNF receptor 2 biology, which we expect to be an effective but safer alternative to the antibodies. Relative to the early competitor in the clinic, our molecule has been designed to have a better overall potency and human PK profile. We expect to be in the clinic with this program in late 2026 or early 2027. Similarly to the X2 program, the TNF program also has the potential to generate proof of concept data fairly quickly. We are very excited about the potential for our immunology programs to provide improved options for patients. We are working to move these into the clinic as rapidly as possible. With that, I'd like now to hand it over to Bob to review our financials. Thanks, Juan. Our cash at the end of the fourth quarter was $1 billion, as compared to $841 million as of the end of the third quarter. Our cash position was bolstered by proceeds from our $288 million financing in November. Turning to our financial results for the quarter, we recognized GAAP revenue for the fourth quarter of $33 million, which compares to $26 million for the third quarter. Our revenue is primarily driven by our collaboration with Gilead. Our R&D expenses for the fourth quarter were $121 million, as compared to $141 million in the third quarter. G&A expenses were $26 million for the fourth quarter, compared to $27 million for the third quarter. Total non-cash stock-based compensation was $15 million for the fourth quarter, compared to $14 million for the third quarter. Shifting gears to guidance for 2026, we expect to recognize GAAP revenue of $45 million-$55 million for the full year of 2026. As we discussed on prior calls, we expect operating expenses to decrease meaningfully in 2026 as compared to 2025. The magnitude of this decrease will be in part determined by the results of the futility analysis for STAR-121, which will be conducted in the next couple of months. Accordingly, we expect to provide more detailed R&D expense guidance in connection with our Q1 call. We expect our cash and investments will enable us to fund operations until at least the second half of 2028. For more details regarding our financial results, please refer to our earnings press release from earlier today and our 10-K. I'll now turn it back over to Terry. Thanks very much, Bob. I'm going to end on slide 33, spend a bit of time on our upcoming news flow for 2026. As I mentioned at the beginning of the call, this is going to be another huge year for casdatifan data. Those data are both going to reinforce the confidence in its best-in-class profile and provide greater clarity on our first-line development strategy. Later this year, we'll have at least two additional data presentations for casdatifan. First, we'll be presenting updated data for the casdatifan plus cabozantinib cohort. We'll do that either at an investor event or medical meeting, by which time we'll have a minimum of 12 months follow-up on all patients. The aim here is to be able to provide a relatively mature and meaningful data set, including Kaplan-Meier curves. Also, later this year, we'll share new data from the casdatifan plus Zim cohort of ARC-20. This is intended to demonstrate the safety and early efficacy of the combination, and to establish casdatifan plus anti-PD-1 as the backbone for our first-line combination. There's also a lot happening on the development front. For PEAK-1, our first Phase III study for casdatifan, our goal is to complete enrollment by year-end. Also, we're adding first line combination cohorts to ARC-20 to determine the optimal regimen for our first Phase III study in the first frontline setting, and this will enable us to initiate our second Phase III study for casdatifan at the end of this year. We also expect to advance our two lead programs targeting inflammation and autoimmune disease into the clinic by early next year. With that, I'd like to thank everybody for joining us. We appreciate your interest, your continued support of Arcus, and we're happy to open the call for questions. Thank you. To ask a question, please press star followed by one on your telephone keypad now. If you change your mind, please press star followed by 2. When preparing to ask your question, please ensure your device is unmuted locally. Our first question comes from Salim Syed from Mizuho. Your line is now open. Please go ahead. Great. Thanks for the question, guys, and congrats on the data at ASCO GU. Just one from us, and I appreciate all the color around the first line strategy. Just the numbers that you provided here on PD and PFS, are there any particular trials that you guys are looking at, just so we can start to think about the right IO benchmarks here as you move away from TKI-based regimens? Just second to that, any thoughts here on what you would like to see in terms of improvement from those benchmarks? Thanks so much. Sure. That's a good question, and I think as we move into this TKI-sparing regimen, the focus should really go to Ipi-Nivo. There's a lot of data out there on Ipi-Nivo. Those of you who were at ASCO last year know that there were even, like, basically a decade of follow-up. The reason is Ipi-Nivo is the number one therapy that is utilized in the front line, and it's roughly in a third to 35% of patients. One of the reasons it is growing, but one of the reasons that it isn't used even more is the rate of primary progression, and that's on the order of 20%-25%. Second, it has a relatively short PFS. It's on the order of 12 months or so. I think those numbers become very clear, simple, lines to put in the sand, where obviously we want to demonstrate meaningful improvement. I would emphasize, you know, that's all gonna start with that rate of primary progression, and, you know, we believe it's exciting that we've even shown with anti-PD-1 alone, we're looking at potentially single-digit rate of primary progression, and we'll have more to say on that later this year. I think those form a good place to start the conversation around benchmark. Just like the specific studies, so like at our CheckMate 214, which was a registrational study for Ipi/Nivo and front-line RCC, and then the other study to look at that had an Ipi/Nivo arm was COSMIC-313. Interestingly, the key efficacy measures, so rate of PD, PFS, OS, et cetera, you know, were all very, very similar across those two studies. Okay, super helpful. Thanks so much, guys. Thank you. Thank you. Our next question comes from Li Watsek from Cantor. Your line is now open. Please go ahead. Hey, this is Daniel Bronder for Li Watsek. Congrats on the data update as well from our end. We're just curious to hear where you're at with the volrustomig plus casdatifan run-in in the frontline study that's being operationalized by AstraZeneca. I know you had mentioned that it was paused as you're looking at the data, but any more color about when it might open again, if it's gonna open again? Thanks. The question is referring to is the collaboration that we have with AstraZeneca that's looking at a combination of casdatifan and their bispecific anti-PD-1/CTLA-4 antibody. As you stated, that study was paused, but the patients on the study continued. They were dosed down in terms of the dose of Volru. They also saw continued use of casdatifan. Actually, we're learning quite a bit about that access, anti-PD-1/CTLA-4, combined with casdatifan, and no, it's looking good. Since that dose down, we haven't seen any additional immunities, and I'll remind you, those look very Volru, very anti-CTLA-4 like. We haven't seen those since there's been the dosing down. I also think one important thing is we didn't see any primary progression there. It's a very, even though it's small and things were looking in the direction that we, you know, find and expected to be the case. At this point, I can't say anything further on plans. We're discussing those with AstraZeneca in real time. I think, though, it's important to recognize that from a probability standpoint, while we continue to learn from this study, and anything we do, will inform what we do in Phase III. The thing to be knocked off the pedestal going in is that we recognize that IPI anti-PD-1 combined with CAS is what anything would need to be. I think, our intent is that study, that arm is open now. I want to emphasize that it's open in ARC-20. It will enroll fast. We'll get the data that we need. That'll inform what we do in our phase three study. Thank you. Thank you. Our next question comes from Daina Graybosch from Leerink Partners. Your line is now open. Please go ahead. Everyone, you got go on for Daina. Thanks for the question, and congrats on all the data. It looks really great. In your biomarker analyses, you mentioned that the deeper EPO reductions were correlated responses. Is this due to higher baseline EPO? I guess in other words, did patients generally reach a similar, I guess, numeric EPO level after treatment? I got one follow-up. I'll let Juan give you some comments on that. Yeah. There's a what I would describe as a soft correlation between baseline levels being higher and the extent of reduction. Both of those we interpret it like, we have data to support that those reflect the extent of HIF-2α activity in those tumors. The tumors that have a stronger HIF-2α signal tend to present with higher EPO levels, and those also tend to be the patients that display the deepest and more sustained reductions. Got it. when you're looking at these, biomarkers, did you also look at VEGF and other genes that might also be downstream of HIF-2? Yes, there are other, soluble peripheral markers that we'll be disclosing later this year. They are regulated by HIF-2α and are well known to be each one of them independently negative prognostics in this setting. You know, one thing I would emphasize also about the biomarker work that I think is important for people to recognize, this is most important in just sort of supporting the overall understanding in tie to mechanism of the activity. In this particular case, there's no sense that we would ever think about having or needing a selection criteria based on the biomarker. What I'll remind you is that probably 80% plus or 90% some odd of patients with clear cell RCC have some level of HIF-2 as a driver. When we report on these type of data, what you're actually seeing is while there's correlation, even those patients with lower levels are, there is benefit. We get a pretty continuous spectrum of benefit throughout those patients as opposed to some sort of binary cutoff that you might be seeking. Got it. Thank you. Thank you. Thank you. Our next question comes from Richard Law from Goldman Sachs. Your line is now open. Please go ahead. Hi, this is Jane on for Rich. Congrats on the progress. We have two questions about the upcoming presentation at ASCO GU this weekend. First, Merck will present detailed results of belzutifan plus lenvatinib in the Phase III LITESPARK-011, which may set the bar in second line. What are your thoughts and expectations for LITESPARK-011? My second question is, Merck is also running a study of belzutifan plus lenvatinib in the Phase Ib/2 KEYMAKER-U02A. They have a poster about a TIP poster this weekend. What's your view on this combo strategy versus casdatifan plus cabozantinib? Thank you. Let me start with expectations around LITESPARK-011. From everything that Merck put out, you know, they obviously said that the study was successful and any body language that you might infer, we think, you know, the data are gonna look quite good. We're excited about that. We think a couple things. First off, it's really providing important validation for the field in an earlier line setting, and we feel great knowing that we have a better HIF-2 inhibitor, and we're going on top of what is the standard of care Cabo and so far as TKI versus Lenva, and we have the same control arm. From our perspective, obviously, we have no-... knowledge of anything quantitative. We expect good data. The better the Merck data, honestly, the better we feel be better for patients and be better for Arcus, because we think we're going to outperform them, with both of the molecules in our combination. The second part, when I said there's two important things, is all of our investigators, have emphasized this point, which we recognize. We have a lot of tailwinds in terms of enrolling, PEAK-1, but for a number of reasons, the positive data, that they'll present is gonna really help us to drive enrollment. As I mentioned, we're looking to be fully enrolled by the end of this year. We think the LITESPARK data, will help us, very much. I'll make a couple of comments on Zanza, and I'll see if Jen or Richard want to add anything more on top of it. We just simply don't see Zanza as being a key changer, at least in clear cell RCC at this point. You know, we think cabo is the clear standard of care. It's not only is it a, you know, have a great profile, but the reality is it's very entrenched. It's, it's used a lot. Clinicians know how to use it, they know how to deal with the AEs, they're very comfortable with it. You know, we think cabo is the TKI of choice. Just one note on KEYMAKER-U02 review that you were asking for. The presentation is just a TIP from the KEYMAKER-U02 study, which, you know, is just a Phase Ib/2 platform study. There's no data that's gonna be presented for belzutifan. It's just a trial in progress poster. Right, yes, it's a TIP poster. Thank you so much, this is super helpful. Thank you. Thank you. Our next question comes from Asthika Goonewardene from Truist. Your line is now open. Please go ahead. Hi, good afternoon, everyone. This is Karmi on for Asthika from Truist. Thank you for the questions. just on a first question on ARC-20 monotherapy, the last update had ORR somewhere in the 30% range, and now you're showing improvement in the mid-40s. How much of that was due to deepening responses, and at what time point were you seeing responses start to deepen? It's definitely all due to deepening of response. I like the question because it does go back. We share a lot of data, and we share almost in real time, and so one of the slides, you know, we've included, we've shown how those data have evolved over time. We also pointed out at the earliest time point, how with this mechanism and also the safety profile, it's very clear that responses can occur even out past a year. The responses occur at all sorts of different time points. The stable disease patients also continue to do very well. The question about DOR hasn't come up, but what I can say is we're not close to a DOR. Patients, once they can get past that initial scan, do very well, and that's why we're seeing the PFS we're talking about, but there's no generalities in terms of where those responses may occur. What I would emphasize and, you know, to your question on deepening, even when we've seen patients that have generated their initial response out past a year, it's meaningful. It isn't just that, you know, they were at a, you know, 29.6% tumor reduction, and they went to 31%. These are genuine deepening of response. The way we interpret it is that, you know, I think people aren't used to looking at oncology mechanisms that have a relatively benign safety profile. What I mean by that is they're not, you know, poisoning you while they're reducing the size of your tumor. Once these patients become stabilized and they become healthier and they become stronger, all those things kick in, including their own immune system, to, you know, help. That's why you may see patients that all of a sudden, you know, deepen. It may have not even always been a gradual deepening. They start to deepen later on. You do have for this mechanism, what looks very IO-like in terms of the tail. Patients that do well, do well, and they do well for a long time. That's one of the reasons we feel, and I think justified by the data, that the market, it's not only going to be driven by the number of patients, but by the durability of the treatment. We've had a lot of patients, even a single agent in the late line, out past two years. We think that the front line, you know, is going to be something where you can have patients going three, four, five years, and that gets to the whole TKI sparing strategy. You're not just pushing off that TKI for a matter of months, but you're going to dramatically change the opportunity for that patient that first presents insofar as not having to go for TKI until many years later. They'll still ultimately get whatever benefit you might get from the TKI, but you just flip around the paradigm of no longer requiring that, you know, at the outset to get the tumor under control, but they can get that years into their therapy. Got it. Thank you so much. If I may, I'm just going to squeeze in one more- Thank you. -question, oh. Sure. Okay, thank you. You have said that STAR-121 will have a fertility analysis in the coming months. If you choose to discontinue STAR-121 based on the results, what is the clinical impact, and what is the impact on your R&D spend? The clinical impact is we're already anticipating from an operational standpoint, that that likely will occur. We may see something that tells us to keep going. Impact-wise, operationally is fairly minimal because the study is basically fully enrolled. That impact operationally would be that, you know, you won't be doing all that work leading up to the registration. I'll let Bob comment on how we think about, you know, sort of the expense part of that whole thing. I mean, the vast majority of the expense that we see for, especially any of our late-stage clinical trials, really is incurred, primarily through, you know, the enrollment cycle, and as the primary portion of patient treatment is occurring. When you get to the latter parts of the trial and you've presumably seen that decrease in expense as an example for STAR-221 and STAR-121 and other studies, when we get to the latter part of the life cycle of trials, the expense starts to drop off pretty markedly. Got it. That's helpful. Thank you so much. Thank you. Our next question comes from Yigal Nochomovitz from Citigroup. Your line is now open. Please go ahead. Yeah, hi. Thanks. I just want to probe a little bit more in terms of the frontline strategy. You've indicated that casdatifan plus Zim will be the backbone of this strategy, and then the question, of course, is whether, you know, the CTLA-4 comes into the mix. With that in mind, I'm just curious, when you asked the oncologist, as you showed us this new market data, in that, in that question, you didn't put in the question on casdatifan plus Zim, you put the triple. I'm just wondering, is that, is the interpretation there that, you know, your base case is really to do PD-1 CTLA-4 casdatifan, and that's where it's gonna shake out? Is there some reasonable potential that it could end up just being what you've identified as the backbone, casdatifan plus Zim? I'll let Jen start on that and see if I add anything on top of what she says. I will. Anyway, I mean, I think you actually described it really well, that right now our base case assumption is that it would be casdatifan plus Ipi/Nivo. Right now, we're thinking of casdatifan plus Zim or casdatifan plus anti-PD-1/LA as the backbone, and that we would likely build on that. We'll keep looking at the casdatifan plus Zim data, again, see how it looks over time. Yeah, certainly base case right now is casdatifan plus Ipi/Nivo, and as we talked about today, that cohort is actually now enrolling. The idea is to generate safety data very, very quickly and, again, an early look at efficacy by looking at the rate of primary progression. What's also nice about this combination, as Terry was talking about earlier, because Ipi/Nivo has a relatively high rate of primary progression, if we see early on, you know, at the first scan, that rate of primary progression is coming down, that gives us a very early read on efficacy, which is nice to have. What I'll add, Yigal, and this actually, you know, the question's come up from investors, and it's a topic also with investigators. The data that we've seen thus far, and obviously we just they're early, and we showed you the primary progression, but it's a, it's a good start. The question sometimes does come up in the context of casdatifan, how much value does the anti-CTLA-4 bring? Obviously, we're gonna have an early data set, but the way we look at it is if you think about it, and this comes up, even though it wasn't a formal part of that analysis that Jen did. When you talk with investigators, including some of those who are aware of the anti-PD-1 early data, more specifically, as you could imagine, anti-PD-1 plus casdatifan, if you could bring that into the frontline from a patient standpoint, that would just be awesome. I mean, to not have to go with anti-CTLA-4 and not have to go with TKI would be like, it comes up sometimes like a vacation. We are gonna pay a lot of attention to that. With that said, I'd like to also put the other conservative part of this that we think is important. We don't want to get too cute. If that anti-PD-1, anti-CTLA-4, each on top of casdatifan looks similar or maybe like the anti-PD-1 potentially could be there, we're still more likely than not to go for a three-arm study where we would have anti-PD-1, anti-CTLA-4 casdatifan versus anti-PD-1 casdatifan versus Ipi/Nivo. We're not going to get too cute and outsmart ourselves, just based on early data. If it should, we're going to give anti-PD-1 casdatifan its shot at the limelight, if possible, because it would be great for patients. Thank you. Our next question comes from Jonathan Miller from Evercore. Your line is now open. Please go ahead. Claire? Hi. Yes. Question. Our next question comes from Jonathan Miller from Evercore. Hey, guys. I'm not sure if you can hear me, but hopefully you can. I was going to ask on the, the first line study as well. Hey, John. Can you hear me? Uh- John, apologies. We're having technical diff--. Can you hear us? You went out for a minute, we didn't get the beginning of whatever question that was. Oh, thank you. John's voice. Is it? Yeah. If you can hear me now, I'll just follow up on your question on the first- Yeah. Okay. Let me just follow up on you guys' question on the first-line setting. you know, you say at least 1 Phase III starting this year. You're adding an additional undisclosed combo to ARC-20 in the first-line setting this year. The Ipi/Nivo combo is open. You just said it was sort of your base case, but you haven't committed to showing data for us ahead of making that Phase III decision. I just want to get a sense for, broadly speaking, how many first-line Phase III are you thinking about in aggregate eventually? What are your plans for the adjuvant setting, which I noticed you didn't mention, except saying that casdatifan belongs in all lines of therapy. What are your current thoughts on partnering, in RCC and beyond for casdatifan, and whether that unlocks additional bandwidth to do some of these late-stage designs? ng to kind of briefly and then turn it over to Jen to give a more fulsome answer on all that. I'll address the partnering part. From a partnering, all you should expect to potentially see, and you probably will see, are like clinical collaboration. At this point, we feel we love that we basically own a 100% of the casdatifan rights other than in Japan and a few other Southeast Asian countries. As you know, that gives us an enormous strategic optionality. With that said, there are other mechanisms and settings that make sense, and since, the, you know, casdatifan is a relatively rare beast, we feel like we're in a good position to do some smart clinical collaborations, you know, under good terms. I'll let Jen comment more broadly, though, on, you know, the number of Phase III we might do, how they're sequencing, when we'll disclose some data, ets, et cetera. We won't make a decision without sort of giving a sense of what drove that decision. Go ahead, Jen. Yeah. You know, just on the Phase III front, obviously, we have PEAK-1 that's enrolling. Our plan is to start one other Phase III study, around year-end. That would be in the frontline setting and informed by this new cohort that we're adding, that you referred to, John, the cohort that's looking at casdatifan plus anti-PD-1, plus CTLA-4. You could probably make an assumption that, you know, that first Phase III study would be looking at that triplet versus Ipi/Nivo. That would probably be our base case assumption today. We'll probably also add, as you were pointing out, another combination to ARC-20, to look at casdatifan plus anti-PD-1, plus another mechanism, probably something that wouldn't be a big surprise to a lot of people. You know, I'd say as far as whether we took that into a phase III is very TBD right now. You know, I think right now, that first phase III in the frontline setting that I mentioned is our top priority and what we'd really be focusing on from a resource perspective. We're also interested in generating some other data with that other combination as well. On the adjuvant setting, we'll see what the LITESPARK-022 data looks like. I think right now we probably view that as, you know, lower priority relative to certainly frontline and maybe some other things we might do with casdatifan, including HCC, just given it's not a huge market. You know, patients are on treatment for 12 months max. It's a very high bar from a safety perspective in the adjuvant setting, just because these patients are doing pretty well and feeling well. A lot of times they don't want to be on therapy, they come off therapy. Like I said, we'll see their data. We're always evaluating it. We'll continue to evaluate, and it's something that we might consider for the future. I think the way, and obviously, as the year goes along, we'll continue to share and probably into next year, we'll be sharing. Like, our view is that HIF-2 inhibition is gonna be used in every line, in every setting of clear cell RCC. Our ultimate development strategy, you know, whether it's supportive studies, etc., is gonna look like we're gonna make sure we've covered everything with time. From a prioritization standpoint, it's PEAK-1, frontline, potentially another one next year, then we'll be surrounding those with other studies that make sense so that we're leaving no stone unturned in being able to be used and reimbursed, etc., in every line of therapy. Yeah, we're continuing to look at, you know, as you were pointing out, clinical collaborations for that other new frontline option that we're thinking about. You know, not everything is on our dime, it's not all our resources, etc. That's important to us as well. Great. If I could just squeeze in one more before we run out of time. On MRGPRX2, you've mentioned a couple of times the potential for a safety delta on the basis of better potency and lower dosing. Are there specific safety signals that we should be looking at when we think about initial data here? How much data from the initial cohorts, especially in healthy volunteers, will you need to be able to put some bookends around what that potential safety delta might look like? Right. I'm always saying that outside of oncology, you're always one dose away from complete disaster. The answer is that a well-run, healthy volunteer study will give you some comfort, but, you know, you're always accumulating additional data. The default thing to always look out for, and I think that some of our competitors in the space sort of generate a little bit of a hint of this, when you're dealing with a very high exposure of any xenobiotic, you need to look at liver function, okay? You can actually, as our competitors have seen, if you go too high, you will actually start to see the liver complaining. We think that we'll be able to put way more daylight between our, the amount of our drug required to elicit this similar pharmacology and levels where the liver is gonna start to complain. Thank you. Our next question, our last question, sorry, comes from Emily Bodnar, from H.C. Wainwright. Your line is now open. Please go ahead. Hi, thanks for squeezing me in and taking the questions. It'd be great if you can kind of give us some updated expectations for the casdatifan plus combo data later this year, given now you have pretty mature monotherapy data with median PFS of at least 12 months. How are you kind of thinking about data for the full 45 patient data set? Thanks. Hello? There seems to be a connection issue. We'll be right back in just a moment. Emily, could you please repeat your question? Yeah, do you hear me? Yes. Thank you, Emily. Okay. Yeah, I was gonna ask if you could give us some more updated expectations for your casdatifan plus combo data later this year, given you now have pretty mature monotherapy PFS of over 12 months. How are you kind of thinking about what the combo could look like in earlier line patients in that full 45 patient data set? Thanks. Go ahead, Jen. Yeah. As Terry Rosen said, when we present the data, the goal is to have 12 months minimum follow-up on everybody so that, we may not have a PFS, but, you know, be able to look at a Kaplan-Meier curve and, you know, at least make some educated guesses as far as where PFS could shape out or shape up. As you know, for CAS mono PFS, we're seeing a range of 12-15 months. You know, we'll see what CAS combo shows. You know, right now, we obviously believe very, very strongly that we can beat combo alone because, CAS mono alone looks better than combo. You know, we'll build on both what CAS mono looks like and what combo mono looks like. Yeah, so we're excited to get this data out and, you know, we think like the LITESPARK-011 data, it will also be very de-risking for the PEAK-1 study. The other nice thing about LITESPARK-011, just may be obvious, but it'll give a good, call it contemporary look at what combo alone looks like because that's the control arm. To the extent that I'm thinking about, you know, benchmarks. Yeah, and what gives us obviously a lot of confidence in the casdatifan plus combo data and the PFS is, like I said, you know, just what we're seeing with casdatifan mono, you know, and the fact that, you know, casdatifan mono looks better than combo mono, and, you know, we think, you know, may even look better than belzutifan plus lenvatinib. We'll see what the LITESPARK-011 data shows. Great. Thank you. Thank you. We currently have no further questions, and therefore, concludes today's call. Thank you all for joining. You may now disconnect your lines. Thank you, Claire. Goodbye.