Good morning, everyone, and welcome to the ARC-20 phase 1b casdatifan data call. My name is Emily, and I will be coordinating your call today. After the presentation, there will be the opportunity for you to ask any questions by pressing star followed by the number one on your telephone keypad. I will now turn the call over to our host, Pia Eaves, Vice President of Investor Relations, to begin. Please go ahead. Good morning. Today, we issued a press release announcing data from our phase 1b ARC-20 clinical trial of casdatifan, or CAS, in ccRCC. The full release, along with today's slides, are available on the investors section of our website. These data were presented at the EORTC NCI-AACR conference earlier today by our lead investigator, Dr. Toni Choueiri of Dana-Farber Cancer Institute. Turning quickly to slide two, I'd like to remind you that on this call, management will make forward-looking statements which contain risks and uncertainties. These are outlined in our SEC filings, which we encourage you to review. I am joined today by our CEO, Terry Rosen, CMO, Dimitry Nuyten, and CCO, Eric Matthews. We are also joined by Dr. Rana McKay from the University of California, San Diego. As a specialist in renal cancer, she will speak to the current treatment paradigm for RCC and the significant unmet need that remains in this disease. For Q&A, we'll be joined by our President, Juan Jaen, and COO, Jennifer Jarrett. With that, I will turn it over to Terry. Thanks very much, Pia, and thank you all for joining us this morning. First off, I want to thank Dr. Toni Choueiri, who earlier today gave an outstanding presentation of the initial clinical data from our ARC-20 study evaluating casdatifan, our potential best-in-class HIF-2alpha inhibitor in clear cell RCC. Thank you so much, Toni, for the awesome presentation, and more importantly, for the great work that you and your colleagues do on behalf of patients. This large and robust data set includes efficacy data from our first two expansion cohorts. These included over sixty patients, all with clear cell RCC. We really couldn't be more excited about these data. They clearly demonstrate CAS's potential to play a meaningful role in the treatment of clear cell RCC. So let me get right into the new data and start with slide five of our presentation. This summarizes key elements of CAS's differentiated profile from that of belzutifan, the only approved HIF-2alpha inhibitor. Data from the 100-milligram cohort of ARC-20 showed a substantially reduced rate of primary progressive disease and a higher ORR relative to the results generated for belzutifan in the registrational study, LITESPARK-005. While the data for the 50-milligram cohort are even less mature than for the 100-milligram cohort, we believe these data clearly show that this dose, that's half of our planned go-forward dose, will also show differentiation relative to the profile of belzutifan. Median PFS has not been reached in either cohort, and you'll see later on this call that the swim lane and spider plot analyses suggest that the median PFS will in fact be higher than that of belzutifan. Note that I said the median has not been reached, not just that the median is immature. In addition, we observed a comparable safety profile, particularly with respect to grade three or greater hypoxia and anemia, the two primary on-target toxicities associated with HIF-2alpha inhibition. It's a very important part of the profile. We are also pursuing a differentiated combination strategy for CAS. Last month, we had a successful Type B meeting with the FDA, and we're now full steam ahead toward the initiation of PEAK-1. That's our first phase III trial for CAS. The PEAK-1 study will evaluate CAS plus cabo versus cabo in patients who have previously received anti-PD-1 therapy. It's a very simple design. We also recently announced a clinical collaboration with AstraZeneca to combine CAS with their anti-PD-1/anti-CTLA-4 bispecific antibody, volrustomig or volru. Importantly, Merck is not currently pursuing this particular combination with Bells, so by combining CAS with volru, we could have a potential best and first-in-class combination therapy. AstraZeneca will be operationalizing the study, makes a particularly resource-efficient way for us to pursue the opportunity. So turning to slide six, many of you have asked, "How can CAS achieve an improvement in efficacy measures without a higher incidence of AEs?" So I want to comment on the link between HIF-2 biology, on-target side effects, and antitumor activity. HIF-2alpha is a transcription factor, is involved in the regulation of literally hundreds of genes, each with its own dose-response sensitivity to HIF-2alpha inhibition. The easiest way to make this point is to compare the two on-target AEs that everyone is aware of, anemia and hypoxia. As we all know, robust HIF-2alpha inhibition leads to some level of anemia in the vast majority of patients, while hypoxia occurs far less frequently. That is because the pathways downstream of HIF-2alpha inhibition, driving these two AEs, are completely different. So the bottom line is that the pathways downstream of HIF-2alpha inhibition that drive antitumor activity are also different from the pathways that drive the on-target toxicities of anemia and hypoxia. And this is why we believe we can achieve greater antitumor activity without a higher incidence of on-target AEs. And frankly, the data now speak for themselves. It's no longer theoretical. Slide seven summarizes the HIF-2alpha inhibitor landscape. It's extremely sparse. In fact, we believe it's now just a two-horse race between us and Merck. Other than belzutifan and CAS, only two other HIF-2alpha inhibitors have been reported to be in clinical development in the U.S., and recent data presented suggest that neither molecule will have a competitive profile. This reflects the fact that because HIF-2alpha is a transcription factor, it's exceptionally difficult to design a good small molecule inhibitor against the target. In contrast, casdatifan has an ideal PK and PD profile and appears to prove efficacy without compromising safety, all with simple once-daily dosing regimen. There are multiple anti-PD-1s and TKIs approved and used today for RCC, and we believe that there will be appetite for multiple HIF-2alpha inhibitors. With our better molecule and corresponding development strategy, we're very well positioned to compete with the only other meaningful player, belzutifan, and to expand this already multi-billion-dollar market. So on slide eight, we highlight the differentiation of CAS's pharmacokinetic and pharmacodynamic profile underlying its clinical advantages. On the left, the black dotted line represents erythropoietin, and I'm going to be calling it EPO from now on. EPO suppression for belzutifan at its approved dose of 120 milligrams. And the purple line represents EPO suppression achieved with CAS at increasing doses. These data show that at 20 milligrams, that's one-fifth of our go-forward dose, we achieve the same pharmacodynamic activity as measured by EPO suppression as that of belzutifan at its approved dose. Therefore, with a 100-milligram dose of CAS, five times the PD equivalent of belzutifan, CAS is designed, and in fact, does hit HIF-2alpha far harder in the tumor. Second, as you can see on the right, unlike belzutifan, CAS does not have dose-limited pharmacokinetics. They're linear, they're dose proportional all the way up through a 200-milligram dose, the highest dose we've evaluated in our dose escalation study. At steady state, belzutifan does not achieve meaningfully higher drug exposure as the dose increases from 120 milligrams to 200 milligrams. So simply put, increasing the dose is not expected to improve target engagement or efficacy. That's the problem with absorption-limited pharmacokinetics. Slide nine shows some very important, hot-off-the-press pharmacodynamic data, which very tangibly illustrates these advantages of CAS that we believe are driving its improved efficacy profile relative to that of Belz. These are very new data. I think many of you haven't seen these data. They're actually included data from Merck. On the left, you'll see some recently published data showing EPO suppression over time for belzutifan, and by week 13, EPO suppression is minimal. It's almost non-existent. In contrast, on the right, we show the same analysis for CAS, and that CAS achieves approximately 60% suppression of EPO, very close to a maximal effect over a very sustained period of time. These data reinforce our confidence that CAS can have a differentiated efficacy profile over that of belzutifan and represent a very clear demonstration of the PK/PD advantages of CAS over Belz. These new data are both striking and compelling. I think this might actually be one of the most important slides in the deck. Slide 10 provides the punchline. While we recognize the caveats of cross-trial comparison, data from the 100 milligram expansion cohort, which is our planned go-forward dose of CAS, demonstrated differentiation on every available key efficacy measure compared to the published data for LITESPARK-005, specifically, primary progressive disease rate and ORR. Although median PFS has not been reached, it's clear from the data to date that CAS will exceed the 5.6 months median PFS for Belz. Further data maturity will determine by how much. Importantly, this is without any meaningful difference in safety, as you'll see in the last two columns. All of this was achieved despite a more advanced patient population and with shorter follow-up relative to that of LITESPARK-005, as well as other belzutifan studies. On slide 11, we show how the response rate could likely continue to improve as the data set matures. Specifically, this slide shows the bridge between our confirmed response rate and unconfirmed response rate. For the 100 milligram cohort, there are two pending responses. While not all pending responses will definitely confirm, every confirmed response would increase the confirmed ORR by just over 3%. Also, in both cohorts, there are a significant number of patients with stable disease, you know, that we always call still in play. Given the IO-like kinetics of this mechanism, we can certainly expect additional conversions to responses with more follow-up. And even more importantly, the stable disease patients in both the 50-milligram and 100-milligram cohorts are deriving meaningful clinical benefit, and they're going to contribute to median PFS. In summary, we have already exceeded the Belz-confirmed ORR in the 100 milligram cohort. In addition, the 50-milligram cohort, so the second expansion cohort, is on track to exceed the Belz benchmarks as well. On top of that, we believe the data suggests there's a pretty clear path to exceeding a 30% confirmed ORR as the data sets mature. Overall, these data demonstrate that casdatifan has the potential to change the standard of care, capture substantial market share, and further increase the RCC market by extending treatment duration. I'd now like to turn the call over to our guest, Dr. Rana McKay of the University of California, San Diego. Dr. McKay has significant experience in the treatment of clear cell RCC and the development of novel agents, including belzutifan. She will also be a member of our steering committee for PEAK-1. We're very lucky to have her today with us, and we're thrilled to have her involved with our program. Rana? Thank you so much, Terry, for that wonderful overview, and really happy to be here today with you all. Beginning on slide 13, the treatment landscape for patients with metastatic renal cell carcinoma has been largely evolving over the past several years, and combination immunotherapy regimens are now the frontline treatment standard for the majority of patients with advanced disease. For patients with intermediate and poor-risk disease, either IO-IO or IO-TKI are both life-prolonging options for these patients. For those individuals who have favorable risk disease, the standard practice is to offer combination therapy with IO-TKI or IO-IO, and in unique situations, TKI monotherapy. IO-based combination therapy has improved survival for patients with advanced disease. However, only a small subset, maybe 10% of patients, derive long-term benefit, and the bulk of individuals, 90% of patients, progress to lethal refractory disease. In the post first-line setting, treatment options largely include TKI monotherapy, the combination of TKI and mTOR inhibition, and most recently, belzutifan, the first HIF-2alpha inhibitor approved for this disease, introducing an agent with this novel mechanism of action for the first time in RCC. Unfortunately, in the later line settings, treatment options are palliative in nature, with the goal of improving survival, delaying progression, and maintaining quality of life. TKIs can be associated with significant toxicity, including chronic fatigue, diarrhea, rash, mucositis, weight loss, and other side effects and unfortunately, long-term durable benefit to any one of the given regimens is largely lacking. Now on slide 14, there remains a significant unmet need in the second line setting following IO combination treatment, given that IO-resistant RCC is a universally lethal disease. The current standard of care is largely TKI monotherapy with cabozantinib, based on original data from the phase 3 METEOR trial, which tested this agent post-VEGF TKI, and from the control arm of several phase 3 trials in the modern era, following receipt of frontline IO agents. The PFS is relatively short, ranging from seven to 11 months across these studies, and treatment resistance is inevitable. All patients develop progression due to either intrinsic or acquired resistance. This unmet need creates a significant opportunity to investigate combination treatment strategies that delay the time to progression, deepen responses, and reduce the rate of primary progression. Ideally, we can do this with combinatorial strategies that don't have overlapping toxicities and preserve quality of life. I'm very excited about a strategy that leverages the existing benefit of VEGF TKIs with the addition of a HIF-2 alpha inhibitor that has the potential to decrease resistance, deepen responses, delay progression, while also maintaining quality of life. Turning to the next slide, slide 15, the approval of belzutifan has provided an important new treatment option for patients who fail on anti-PD-1 and TKI therapies. belzutifan is a breakthrough therapy for patients with better-tolerated safety profile than those of TKIs. Specifically, no hypertension or other typical TKI-related toxicities, such as rash or diarrhea, that can have a meaningful impact on a patient's quality of life. Here we highlight the data from the LITESPARK-005, the registrational study leading to the approval of belzutifan in late-line clear cell RCC. These data established belzutifan monotherapy as a new standard of care in late-line clear cell RCC, but there is clearly opportunity for improvement. First, one of the greatest limitations of belzutifan is its very high rate of primary progressive disease. Specifically, 33.7% for belzutifan, compared to 21.5% for Everolimus. So one in three patients in the clinic who receive this agent will have no benefit to therapy, and there is no way to identify these patients upfront. This is a major limitation of belzutifan, and many patients are not able to go on to receive additional treatment after they progress on belzutifan. There is a tremendous opportunity to improve on this endpoint. Second, belzutifan showing an objective response rate of 21.9% after more than eighteen months of follow-up, and the existing efficacy demonstrated with CAS in treatment-refractory disease, there is the potential to achieve a higher response rate with casdatifan. Lastly, while belzutifan demonstrated a hazard ratio for PFS of 0.75 and a median PFS, the median PFS was only 5.6 months. We expect that by achieving a lower primary progression rate and improved objective response rate, casdatifan treatment should result in improved progression-free survival. My last slide, slide 16, highlights the segments of the first and second-line RCC market. As you can see, there's a laundry list of different agents available for physicians to choose per the guidelines. Despite all of these options, about one-third of patients are given cabozantinib monotherapy in the second-line setting. The CAS development plan targets this largest segment of the second-line treatment and has the opportunity to take share of other segments as well. Importantly, nearly 80% of patients will not have received cabozantinib in front line and are therefore eligible to receive CAS with cabo in later line settings. I want to also touch briefly on the phase 1b study, where AstraZeneca and Arcus are combining an anti-PD-1 CTLA-4 bispecific with casdatifan. Clinicians will embrace this regimen because of the potential to establish another TKI-free option in the front-line setting without substantially compromising quality of life. Nivo/ipi is a standard of care and preferred regimen in the front-line RCC setting, given established long-term durability, but its Achilles heel remains the relatively high rate of primary progression. Currently, one in five patients will have primary progressive disease. By combining CAS with a PD-1 CTLA-4 backbone, this weakness will be addressed without introducing overlapping toxicities that have been observed with other triplet regimens. The combination of CAS with cabo in second line and IO in front line has ignited enthusiasm in the oncology community, offering potentially potent synergy that overcomes the limitations of current standards while maintaining a manageable safety profile and the opportunity to redefine treatment paradigms and improve patient outcomes in RCC. I'll be here for the question and answer session, and we'll be happy to answer any questions then. I'm going to turn the call over to Dimitry. Thanks, Rayna. I'll first review the ARC-20 study design on slide 18. The dose escalation portion enrolled patients with any advanced solid tumor and was designed to assess safety, PK, and PD to identify the optimal dose to take forward. For the dose expansion portion in RCC patients, we started with 100 mg daily dosing, which is our planned go-forward dose for phase 3, and we have since enrolled both a 50 mg and 150 mg cohort to satisfy dose optimization requirements. For the 100 mg daily dose cohort, this was administered as 50 mg BID, or twice a day, because at the time, we only had 10 mg capsules available. We have since transitioned to 25 mg tablets, so going forward, patients will receive 100 mg QD, excuse me, or once a day. We have shown that the capsules and tablets are bioequivalent, and the exposure for 50 milligrams BID and 100 milligrams QD is similar. This data is in the appendix of our presentation. On this call, we will focus on the data from the first two expansion cohorts, the 100 milligram daily dose cohort and the 50 milligram cohort. On slide 19, we show the patient demographics, and here you can see that both the 100 milligram and 50 milligram cohorts enrolled heavily pretreated patient population. All patients had received prior treatment with an anti-PD-1 and at least one EGFR TKI, and more specifically, 27% in the 100 milligram cohort and 29% in the 50 milligram cohort had received four or more prior lines of therapy. As a reminder, in LITESPARK-005, only patients with one to three prior lines of therapy were allowed. In the subgroup analysis conducted both by Merck and Eisai for their respective studies, the response rates in patients who received more prior lines of therapy were lower. Turning now to the overall response rate for one hundred milligram cohort on slide 20. I'll start with the rate of primary progression, which was 18.8%. This compares very favorably to the 33.7% in LITESPARK-005. The rate of primary progression represents the patients whose disease progresses on or before the first scan. High rates of primary progression will negatively impact the early part of the Kaplan-Meier curve for progression-free survival and ultimately median progression-free survival and other landmark readouts. As Rana mentioned, primary progression was considered to be the largest weakness in the LITESPARK-005 data set. We have observed substantially better results relative to belzutifan for this important efficacy measure in both cohorts. The overall response rate is 34%, which includes one patient who responded after the data cutoff. Including this patient, there are two patients whose responses are pending confirmation, and there is one patient whose response did not confirm due to subsequent progression. The confirmed response rate is 25%. Even with only 11 months of median follow-up, this is numerically higher than what was observed for belzutifan in a similar patient population. As you will see in later slides, there are many patients with stable disease still on treatment, so there's plenty of opportunity for further improvement in the overall response rate with longer follow-up. The next slide, slide 21, includes the ORR table for the 50-milligram cohort, which has an even shorter follow-up of 8 months. Despite this, we are seeing an overall response rate of 25% and a confirmed response rate of 21%, with one response pending confirmation. This is already in line with LITESPARK-005. The disease control rates are above 80% for both cohorts, reflecting the low rate of primary progressive disease. As a side note, one of the patients who was assessed as having progressive disease in the 50-milligram cohort remained on study therapy because they were doing clinically well, despite the progression seen on the CT scan, and two scans or 12 weeks later, they had a documented 33% reduction in tumor volume. Per formal RECIST criteria, this patient is recorded as having progressive disease as best overall response, not as a responder, despite their longer-term benefit, and in our efficacy table, this is captured as a progressive disease patient. Note that there are slight differences between the efficacy evaluable population and the overall population for each cohort, with three non-evaluable patients in the 50-milligram cohort and one in the 100 milligram cohort. Three out of four patients were deemed ineligible for the study shortly after enrollment due to kidney function in two patients and hemoglobin in one patient. The fourth patient discontinued treatment before the first scan due to an unrelated AE of acute kidney injury. These patients were all on study for a short period of time. The one ineligible patient in the 100 milligram cohort discontinued just after the first scan, which showed stable disease with a 29% tumor volume reduction. The other three patients discontinued before they could complete their first scan. On slide 22, we provide some additional context for interpreting our overall response results. We have mentioned that we... Sorry. We have already mentioned the more heavily pretreated patient population and the shorter follow-up for ARC-20 relative to any belzutifan benchmark study. You can see that very clearly on this slide. Also, regardless of what study you look at, a phase I or a phase III, the overall response rate for belzutifan has fallen in a very tight range of 19.1% to 21.9% for patients who received both prior anti-PD-1 and EGFR TKI, and both of our 50 and 100 milligram expansion cohorts already meet or exceed these benchmarks. Turning to slide 23, we show the waterfall plus, which demonstrates that the vast majority of patients on casdatifan experienced tumor reduction. We've also highlighted the patients who are still on treatment, of which there are several in each cohort. Slide 24 shows the spider plots, which illustrates the very durable disease control achieved with casdatifan. These are great spider plots, particularly for a drug administered a single agent in a late-line population. Duration of response is still extremely immature. In fact, all patients who responded, with one exception, maintained their response at time of the data cutoff. Insofar as the probability of future responders note, for example, the patient in the 50-milligram cohort hovering, slightly above the 30% reduction mark. It's also clear that patients with stable disease can do well with no growth in their target lesions over a prolonged period of time. The registrational endpoint is progression-free survival, and whether or not a patient reaches a 30% reduction is not relevant if that patient remains free of disease progression. Median progression-free survival has not been reached in either cohort. To be clear, this means that at the time of the data cutoff, more than 50% of patients in both cohorts had not progressed, or their disease had not progressed. But you can see on slide 25. Sorry, on slide 25, in our swimmer lanes, you can see you can get a good sense for the time on treatment. And you can also see the first patient here is going beyond one year of treatment. It is also notable we see very few progressions beyond 26 weeks. So once a patient reaches 26 weeks on treatment, they tend to do very well. We've also included a really interesting patient case on slide 26. This patient received pembro and lenva with the best overall response of stable disease, and her tumor progressed within six months. As a reminder, the overall response rate for this regimen is over 70%, 70%, and the median progression-free survival is 23 months. So her outcomes were clearly quite poor. However, after receiving her first dose of casdatifan in November 2023, her response was noted as early as six weeks later at her first scan. That response has been maintained for the last nine months and was ongoing at the time of the data cutoff. Finally, on slide 27, I'll briefly speak about the safety and tolerability. We have not seen any dose-limiting toxicities to date in ARC-20, up to and including the 150 milligram cohort. Evaluation of the 200 milligram cohort is ongoing. Anemia and hypoxia are the two on-target AEs that we are monitoring closely, and thus far, the incidence of these AEs has looked very similar to that of belzutifan in LITESPARK-005. To date, we have not seen grade four treatment-related AEs or treatment-related deaths, which is pretty remarkable for an anticancer therapy. And now on slide t28, we'll summarize these data for you. You can see we show a clear improvement on every efficacy measure that has been reported for belzutifan, and we achieved this without meaningful deterioration in safety. This is what gives me significant confidence that we have a drug with an extremely competitive profile and that we are very well-positioned in the HIF-2alpha field. You heard earlier on the call how Rana highlighted the primary PD rate being an incredibly important point for patients and physicians. Here we show, for two cohorts combined, that we have achieved a primary PD rate that is about half of what was reported for belzutifan. This is huge, and that brings me to our development program and how exactly we will capitalize on this excellent profile. On to slide number 30, you can see that the data we presented today are just the beginning, and we expect to present a steady cadence of results from our ARC-20 over the next 12 to 18 months. Specifically, in the first half of next year, we expect to present median progression-free survival results from the 150 milligram cohorts. We'll also share efficacy results from two other monotherapy cohorts and the safety data from CAS plus cabo combination cohort in the second half of next year, followed by early efficacy data from the combination in either late 2025 or early 2026. We believe all of these data further de-risk our phase three study, PEAK-1, which leads me to our late-stage development plan for casdatifan. You can see on slide 31, we are currently planning to take casdatifan forward into two settings. First, following IO treatment, and second, in IO-naive clear cell RCC patients. We recently had a successful meeting with the FDA for PEAK-1, and we are moving forward as rapidly as possible with the study initiation. In parallel, our clinical collaboration partner, AstraZeneca, is leading efforts on casdatifan plus Volru combination. Both of these concepts have been received extremely favorably by the clinical community, and we are very excited to get going with these trials. The design for PEAK-1 is shown in slide 32, which is expected to begin in the first half of next year. The design of PEAK-1 is simple, which should drive rapid study enrollment. Specifically, we are planning to enroll approximately 700 patients randomized 2:1 to casdatifan plus cabozantinib versus cabozantinib, the leading TKI prescribed for second-line clear cell RCC patients. The study population will include both patients who received an anti-PD-1 as adjuvant therapy and those who received an anti-PD-1 as part of their first-line regimen for metastatic disease, with or without a VEGF-R TKI. On slide 33, I want to highlight why we are excited about PEAK-1. As you know, CAS and cabo both have meaningful single-agent activity through independent mechanisms, and importantly, with minimal overlapping toxicity. There actually have been two studies from Merck showing that HIF-2alpha inhibition plus a VEGF-R TKI could improve upon TKI monotherapy. Though these studies are relatively small, the median PFS observed in these studies, 13.8 months for cabo plus Belz and 11.2 months for lenvatinib plus Belz, appear to be meaningfully longer than the median reported for TKI monotherapy. I'll end on slide 34, where we lay out our clinical strategy for casdatifan. To date, casdatifan has been administered to over 150 patients and 56 healthy volunteers. We will continue to expand the development program for CAS. As Terry and Rana talked about earlier, we are very excited about our clinical collaboration with AstraZeneca to combine CAS with their potentially best-in-class anti-PD-1 and CTLA-4 bispecific. Additionally, we are planning to initiate additional cohorts in our ARC-20 to evaluate casdatifan in certain clear cell RCC populations. We'll talk more about this in the coming months. We are also considering additional tumor types for the development of casdatifan. I'll now turn the call over to Eric to discuss the potential market opportunity. Thank you, Dimitry. So just quickly here, we've prepared an overview of the market opportunity for CAS in RCC on slide 36. You can see the different lines of therapy and the total market estimates for the U.S. So first, focusing on the IO-naive metastatic segment, we're projecting a market size of 12,200 patients. And just for background on that estimate, we use an annual incidence of 21,000 patients for all RCC histologies, of which 75% are clear cell. And we then take out prior adjuvant-treated patients who have had prior PD-1 adjuvant within 12 months, yielding the number you see there for a total addressable market of 12,200 patients in the U.S. Then, for the top seven major markets globally, we estimate this number to be about 22,000 patients. These newly diagnosed IO-naive metastatic patients typically remain on treatment for about 18 months. All of this then translates into a global market opportunity of well over $3 billion. As you saw earlier, the anti-CTLA-4 PD-1 share of this market is already substantial, and it's growing in the U.S. and globally... largely due to the potential for incredibly durable responses. In the U.S., just recently, this regimen was added into the NCCN guidelines as a preferred regimen for favorable-risk patients, expanding its utility. Yet, as you can see here, the benchmarks for ORR and PFS with this approach could still be improved dramatically, which is the opportunity for combining with CAS. There have been attempts, as you know, to combine TKIs with PD-1/PD-L1, but these efforts have faced tolerability challenges that have impacted delivery of the regimen. Whereas we believe with CAS's safety profile, as you've seen, and its potential for driving early sustained responses, CAS plus Volru could prove to be a winning combination for this newly diagnosed metastatic RCC population. Next is what we call the post-IO population, comprised mostly of second-line patients, but increasingly including first-line patients who have seen prior adjuvant. We estimate this population will be about 11,300 patients in the US, almost equivalent to the IO-naive population. Approximately 20,000 patients in total for the G7 major markets. Median treatment duration in this population is currently 7 to 11 months, the former, if they received a TKI in frontline, or the latter if they've only received prior immunotherapy. The opportunity for CAS CABO here as the potential best-in-class HIF-2 TKI combination is clearly very attractive to patients and investigators, and we're hearing tremendous interest in rapidly bringing this regimen forward with the PEAK-1 study. As you saw earlier, the market of available treatments here is really fragmented, with CABOs the most predominantly used TKI consistently across regions. So in building upon CABO, we believe CAS CABO will consolidate a market-leading position in this indication, taking share from other TKIs and everolimus, yielding a market opportunity of well over $2 billion a year. So that brings us to the late line segment, and these are patients who have already cycled through two or more lines of therapy, where median PFS is unfortunately only about five months. This is where belzutifan is currently approved. Today, Arcus is focused on the earlier post-io and io-naive settings and combinations, and we are evaluating a range of additional subpopulations in RCC. So just zooming out now, the overall RCC market is already very large, with TKIs generating over $5 billion in annual sales combined. Following Bells' U.S. label expansion into RCC in December of last year, there was an immediate and dramatic doubling of U.S. scripts, now generating well over $500 million in annualized run rate. Keep in mind, this inflection was driven by new scripts in the late line monotherapy setting, where again, PFS is only about five months. By moving differentiated HIF-2 combinations into earlier lines of treatment, we have the opportunity to help a larger number of patients with extremely durable responses and manageable safety, enabling patients to benefit from continuing on effective treatment significantly longer. So I'll now turn the call back over to Terry. Oh, so I'll finish by saying thank you all for joining us today. We're obviously thrilled with these data, most importantly with the opportunity we have to change the standard of care for RCC and make meaningful difference for patients. I'll now open the call to questions. Thank you. As a reminder, if you would like to ask a question today, you can do so now by pressing star, followed by the number one on your telephone keypad. If you change your mind or you feel like your question has already been answered, you can press star followed by two to remove yourself from the queue. Our first question comes from the line of Peter Lawson with Barclays. Please go ahead, Peter. Great. Thank you. Thanks for the update. Really appreciate it. I guess first question, which is beyond kind of thoughts on where you think PFS could eventually land, you know, based upon what you've seen for the disease control rate and kind of the reduction in fast progressors, and kind of your thoughts on what you think its best correlation is there for PFS, if it's, you know, disease control rate or PRs. Thank you. Thanks, Peter. You know, I don't want to get ahead of ourselves. If you can look at the swim lanes yourself, as you know, we're out in the 100-milligram cohort at roughly 11 months of follow-up. We still haven't hit the median. We think we're going to be substantially better than that 5.7 months of PFS that were reported for belzutifan. And in fact, we plan to report these data sometime as early as possible next year. So we think we're going to be clearly better, but we don't want to throw a number out there yet. You can do your own estimating. Gotcha. Okay, thank you. And then, a timeline for completing the phase three, kind of your estimate there and kind of when you think you could be on the market. So we haven't shared that yet. We'll give a little bit more color on that, but we expect it to enroll very rapidly. So you know, the enthusiasm for the study has been high. We're moving full speed to get it going by the first half of next year. And we have no more to really say about that, but I'll just offer Jen or Dimitry opportunity if they want to jump in and give any more color on that. No, thank you. Cover it well. Thanks, Terry. No, I... Go ahead, Dimitry. Yeah, no, I was going to say the same thing. I think most importantly, as I highlighted, study design is very straightforward. There's a lot of enthusiasm, and we, let's say we hope to get started, the first half of 2025. Gotcha. Okay, perfect. Thank you so much. I'll jump back in the queue. Thanks, Peter. Our next question comes from Daina Graybosch with Leerink Partners. Daina, please go ahead. Hi. Thanks for the questions. Congratulations on the data. I'm gonna do one detailed science and one commercial question, but start with the science. So, Terry, on the comparison of the long-term pharmacodynamic data, I guess what gives you confidence that the waning trend in EPO that you showed was observed with belzutifan is also relevant for the downstream HIF-2 alpha pathways that drive hypoxia and the tumor shrinkage? So what we would comment is more illustrative of the point. I'm gonna make a couple points on that. So the first thing to realize is what we've said all along. belzutifan at its clinically used dose is basically just approaching, maybe not exactly at the maximal effect on EPO suppression. And what you can see is that there's a feedback mechanism. We could get more into that at a later point. That clearly makes the HIF-2, at least in the kidney, less responsive to that. So you're essentially seeing almost no effect. Now, as we've always said, and we're not gonna change our story, that EPO suppression is not directly related to what's going on in the tumor. But you basically have no margin for error if any type of mechanism that kicks in that might make your molecule less potent on HIF-2 or if there's greater expression in the tumor, etc., you're gonna see a waning effect. And given that we're at five X starting relative to that PD effect, we have a big buffer, and that's certainly the explanation why we're not seeing anything falling off. I think it's a big concern if I saw those data that you have that waning effect with belzutifan, and we think you know that certainly could bode well for the durability endpoints, whether they're PFS and in fact even OS as we start to move beyond what we've already seen with belzutifan. Juan wants to jump in here and say something. I think a critical observation here is that prior to seeing our data, you could have postulated that the kidneys found a different way of making EPO, so some other regulatory pathways kicked in. When you see that CAS is able to continue to suppress it, that tells you that the compensatory mechanism involves some enhanced version of HIF-2alpha activity, whether it's more protein or it's been modified in some manner, that there's more HIF-2alpha activity that the standard dose of Belz is no longer able to suppress, whereas CAS is able to suppress. Whether the same HIF-2alpha involving compensation happens in the tumor, you know, the clinical data is starting to speak to that point. But I think that it's HIF-2alpha dependence, it's really, really critical. Got it. My second question is on zanzalintinib. You used to have a combo, I think, that Exelixis was running. You didn't talk about that any longer, and I wonder if you can comment on that in light of the collaboration deal between Exelixis and Merck. So, why don't we bring Jen into the conversation? Jen, do you want to handle that question? Yeah. So, we did have a clinical collaboration with Exelixis. So you're right, we were combining CAS with CABO. That was a study called STELLAR-009. We announced in early September, that we were not going to continue with that study. As you know, we'd announced a few months before that, that we were prioritizing CAS plus CABO, which is the ongoing expansion cohort that we have in ARC-20. We think both are great TKIs, but we just felt like there was more familiarity out there, with CABO, given that it's the clear standard of care, as you heard from Rana, in the setting that we're pursuing. So we both felt like there weren't a lot of strategic reasons for us to continue with STELLAR-009 and that we would both move on, that we would focus on ARC-20 and PEAK-1. Exelixis, as you pointed out, did do the clinical collaboration with Merck. There weren't a lot of details in the release other than to say they're going to be doing a phase 1b. I'd assume that phase 1b is gonna be preceding the two phase 3 studies that they also referenced in that release. But obviously, we don't know details like you guys. But I would say that, you know, we continue to feel very, very good about our lead combination of CAS plus CABO and love the idea that we're going right on top of the standard of care. And to the point on enrollment, which we're really optimizing for, we believe this is a study that's gonna roll very, very quickly and is a very simple study for investigators to get their hands around. Thank you. Thanks, Dana. The next question comes from Jonathan Miller with Evercore ISI. Please go ahead. Hi, guys. Thanks for taking the question, and congrats on the data. Let's start with a dose response question. I think, Terry, Jen, you've been saying for a while you don't expect to see a major dose response between these two dosing arms. When I look at the waterfall charts, it does look to me like I'm seeing deeper responses from the 100-milligram cohort, although the headline ORR is obviously in the same ballpark. Can you talk a little bit about how responses are evolving over time and where you might look for a dose response if there was one to be observed in the course of time? Yeah, thanks. Thanks, John. So first off, if you look at the rate of primary progression, you know, they're basically the same. You know, numerically, the 50 milligram looks a little better. We are seeing, you know, kinetics that, you know, particularly anecdotally, that we hear we might be seeing things a little earlier. We also, though, as we may have talked about publicly already, we've seen, you know, patients respond as even at 14 months. Keeping in mind, the Merck data, they actually saw, you know, 60% of their responses occurred within six months, and then 20% more each of the next six-month period. So at between six and 12 months, and then another 20% between 12 and 18. I think it's hard to speculate at this point, on any differences between those two arms. I'll remind everybody that the 50-milligram cohort is really hitting the target hard. It's two and a half, the PD equivalent of the belzutifan dose. That obviously changed the standard of care, and so we're two and a half fold that, and then you've got the 100 that's, double that. So I think the place where we might see some difference would be on durability, and that'll simply take time to see. So whether we actually see some PFS differences between the 50 and the 100. But we feel that both of those doses are basically on the upper part of, you know, a conceptual dose response curve towards the top of the inflection, if not on the flat part. By and large, I would actually say I think the 100-milligram dose, you're squeezing all of the water out of the rock of HIF-2alpha inhibition that you can get. So that's how we handicap it right now. Jonathan, one other data point that I just wanted to point out in the presentation, where you did see a bit of a difference between 100 mg and 50 mg, was the time to response. That was quite a bit shorter for 100 mg. We'll see, you know, some of these later responses come in, if that changes that difference that you see, but that was something that sort of stood out as being a bit different about the 100 mg dose relative to the 50 mg dose. Okay, makes sense. And then maybe as a follow-up, I'd love to ask about, the, how you expect the IO combos to develop here. Obviously, the bispecific phase one is in Astra's hands for operationalization. But, how do you, you know, how do you report on, on Astra's speed there, their enthusiasm for these combos there, and your plans on IO combo regimens, potentially beyond Astra's bispecific? You showed, for instance, on your slide, Merck is planning their own PD one, plus HIF-2, plus TKI, triplet combos, et cetera. So I'll ask Jen to answer that, and Rana, if you want to add anything on to anything that Jen might say, that'd be awesome as well. Sure. Yeah, I can't say a ton yet, but you know, we have a strategy sort of similar to what you're suggesting, that is not directly competitive with the combination that's in development today. So we do like the idea of combining with IO up front, and I think you'll see us do that, but probably today, can't say more than that. And I will just say that AZ, you know, is very excited about the collaboration. We've obviously had a very long relationship with them. Interestingly, the team that we worked with on the study that we're now planning to do with them is the same team that we worked with on PACA, the study that we're doing with them for our TIGIT antibody. So we know them well, and we're really excited to get that study up and running. Rana, maybe you want to add something? Yeah. Happy to chime a little bit about the reference to the triplet with Merck. That is building on the backbone of pembrolizumab plus lenvatinib. So it is adding belzutifan to that backbone. And you know, I think the idea of having a TKI-sparing option in the frontline setting is dramatic. And we know from data from subsequent multiple studies now that IO post IO really does not work, and when you give IPI in later line settings, you are not able to maximize on the durability of that agent. The CR rate is zero, response rate maybe at best 10%-15% when that's used later. So I think multiple studies have demonstrated that in the upfront setting, like, maximizing that benefit of IO is critical. So I think the linkage to a combination that includes CTLA-4 inhibition in frontline is huge, and sparing the TKI is also, an excellent strategy, and, and that is not being done. Thank you. That makes sense. Thanks so much for the call. Thanks, Jonathan. Our next question comes from Li Watsek with Cantor Fitzgerald. Please go ahead. Hey, guys. Congrats on the data. A couple of questions from me. First, can you maybe just talk about your confidence level for an OS benefit for the PEAK-1 study, given what we have seen from the LITESPARK-005 study? So I'll comment that, first off, the approval endpoint here is PFS. I think we nonetheless feel certainly there's an opportunity to make progress on OS. So based upon how hard we're hitting the target, the effect on rate of primary progression, you're obviously putting more patients in play. Durability is looking good. And to the discussion we had earlier, we do think that there may have been some loss with belzutifan. Obviously, erythropoietin is one gene, but it's, you know, it's the canary for everything else that's going on. That's why it's the biomarker. And those new data were surprising to us, but we clearly see that we're maintaining near maximal inhibition. Keep in mind, if you look at the time course on that slide, that effect was kicking in with belzutifan at somewhere like between nine to 13 weeks, and our data were already out at roughly 36 weeks. So we feel good about hitting the target hard, hitting it long. We're seeing good durability. As Dimitry mentioned, once you get patients out past 26 weeks, they just, you know, continue to do well. We've seen even responses kick in late. So we'll see how OS plays out, but clearly, we, you know, we have no concrete data on that at this point, but everything would point towards an opportunity there. Li, just a reminder on the design. Okay. You know, LITESPARK-005 was obviously looking at Bel versus TKI mono with several alignments. You know, our study, PEAK-1, is looking at CAS plus cabo versus cabo. So yeah, the study designs are also pretty different. But, you know, we're going on top of the standard of care and then comparing to that exact same standard of care. Okay, got it, and then just follow up on your frontline strategy. Obviously, you have a lot of options for the combinations, and then you're looking at, you know, combo with AZ price as well, so it's not a normal combo, so I guess just curious, what factors are important for you to nail down the frontline path, and then for the AZ combo, just wondering about the timing of the data and status of the gating step for your frontline phase three. So I'll comment on the AZ part. We've agreed with AZ to not really get into any details yet. We're going to share a lot more once it shows up on ClinicalTrials.gov. That's primarily for competitive reasons, not surprisingly. I don't know if Jen, if you want to add anything else on the front line right now or, you know, the rest of the strategy. Yeah, I think that's probably all we can say. So just, stay tuned, I guess, is all I would add. Rana, is there anything you'd like to add about frontline? You made some key points about the TKI-sparing regimens, but I don't know if you had anything else you'd want to say there. Now, absolutely. I mean, I think the issue with, or the reason to have a TKI-sparing regimen is I think we're just not seeing from the data the long-term durability when combined with IO-TKI. You know, five years ago, when people were in the clinic, we could rarely say that somebody with metastatic disease could potentially be cured of their disease, but now with the introduction of immunotherapy combinations, that's really changed, and I think it's largely been due to the combination of nivolumab plus ipilimumab and building on that nivo-ipi backbone, but as I stated, you know, you take a chance with that regimen because of the fact that not everybody responds up front, and you actually end up losing at least 20. You know, from the clinical trials, it's, like I said, one in five, but likely in clinical practice, it's much higher than that, who get nivo-ipi. So I think there's huge appetite for building upon that. And what's so great about a HIF-2 alpha inhibitor, and particularly CAS, is just the side effect profile and tolerability and getting away from the TKI, being able to overcome the primary PD, the depth of response. So I think there's just incredible enthusiasm around that that would be largely embraced by the oncologic community, improve long-term outcomes for patients. One thing I'd add to what Rana said, so she talked about the clinical aspect of it. The thing that people forget, and I think this is another part of the excitement behind adding CAS to that, you know, bispecific, essentially CTLA-4 PD-1 inhibition, is that over 90% of clear cell RCC has some HIF-2 driver component. So in terms of that rate of primary progression, putting that on top of the IO is really, you know, scientifically as well as clinically sensible. Our next question comes from Asthika Goonewardene with Truist Securities. Please go ahead. Hi, good morning, guys. Thanks for taking my questions and congrats on the update here. Maybe I'll start with a question for Dr. McKay. Dr. McKay, in this study, c ould you tell us then what proportion of the patients have prior cabo or lenba? And I'm wondering that because with the LITESPARK-013 study, it showed that prior exposure to either of these agents seems to make the patient harder to treat with belzutifan. Did you and colleagues see the same? So I would say that in the later line setting, the bulk of patients will have been exposed to a TKI. I think that's the nature of treating renal cell carcinoma. I mean, of course, in somebody who's TKI naive, we're going to see higher responses the first time they're exposed to that TKI agent. So I think with the PEAK-1 strategy and, you know, this study in specific, I think when we see that, there's gonna be a subset of patients that have never received an IO or never received a TKI regimen. But that's essentially the nature of refractory RCC, is that the bulk of patients will have been exposed to a TKI. I don't know if that answered your question. No, Dr. McKay, what I meant was, that have you seen a difference in response to casdatifan, if the patient had had prior cabozantinib or lenvatinib versus axitinib or some of the other VEGF inhibitors? I see what you're saying. I don't know that we actually have that granularity, quite honestly. You know, it would be certainly interesting, you know, to tease that out, but I don't think we necessarily have, you know, granularity around that. Every single patient was exposed to a VEGF TKI, and I think the newer generation, you know, agents are certainly being used. You know, I would say that earlier in the disease course, when the disease has not been exposed to VEGF TKIs, you know, and is really driven by the alteration in VHL, I think selectively and potently, like, targeting that alteration, I think can have, you know, that's where you're gonna make a lot more strides. I think, in later line, where the disease is more refractory, that's actually where you probably need those off-target effects of those other TKIs. Yeah, and we- Got it. Okay. We're talking here among ourselves, so we, you know, most of these patients, if not all of them, did get both prior Lenba and Cabo. I'm talking to someone on our clinical team right here. And, and just so you know, you know, we are submitting some data for presentation for next year, where we... You know, I'm not sure we'll look at this exact sub-analysis, but we're gonna look at some different sub-analyses that I think will answer some interesting questions. So just wanted to put that on people's radar screens. Yeah, and this is one important things. So there's one important thing to add here. So in PEAK-1, we will be stratifying by prior TKI or not. So it's a post-IO study, and we'll accept patients who have gotten PD-1 alone in the adjuvant setting and double IO regimen up front or a IO VEGF TKI regimen. And because of all the things that Dr. McKay just said, it's important that those two groups of patients might have different benefit in the later line setting. That's why we are stratifying that in our phase 3 trial. Got it. And then, Cabo has some known toxicities, which are managed by dosing down and pausing therapy. So for the combo, what overlapping toxicities are you most concerned with, and how do you anticipate managing the dosing of these drugs? Would you kind of dose down independently or sort of both together in PEAK-1? Yeah. So, I'll high level say that they're very orthogonal. The HIF-2alpha inhibitors primarily have that they're very clean molecules. They have on-target anemia that's well managed and the occasional hypoxia. And I'll let Rana talk about more generally any thoughts on that. Yeah. No, I, I think they're very distinct, though. The toxicities are really not overlapping. You know, the thing that we see with HIF-2 alpha inhibition is largely anemia and hypoxia, which are not the things that we dose reduce for cabo. You know, the cabo's adverse toxicities are around you know, diarrhea or rash, and you know, rarely is it a dose reduction because of cytopenias. So I think they're actually very distinct, and I think there can be dose modification parameters for each of the agents independent of one another. Thanks, guys. Last one: When's the next update to the ARC-20 data here? Have you submitted abstracts to any conferences? Sorry if I missed that. Juan, why don't you comment on that? Yeah. So we have submitted an abstract, and you know, it would be for a presentation next year. You know, as I said, one of the things that would be in the abstract is some analysis of different subpopulations. As Terry mentioned earlier, we also expect to have median PFS by then and then probably also some biomarker analysis. That will probably be the first next thing that you see on our ARC-20. Then also next year, most likely data from the other expansion cohorts, so the 150-mg and the other 100-mg expansion cohort that we just finished enrolling, as well as safety data from the CAS plus cabo combination cohort. A lot coming next year. Great, guys. Thank you so much. Looking forward to it. Thank you. The next question comes from Yigal Nochomovitz with Citigroup. Please go ahead. Hi, thanks very much. I wanted to just kind of come back to the debate around the dose, a hundred versus fifty. Just curious, how much of the fifty milligram data did you have when you settled on the decision of a hundred milligram for the PEAK-1 trial? Because, you know, now looking at the data and to Dimitry's point around the PFS calculation, the spider plots would suggest potentially a very similar PFS for fifty versus a hundred. And then if you look obviously at the EPO suppression, they're very similar. And then in the appendix, I think you have a PK chart, which shows basically complete overlap in terms of PK for both doses. So I'm just curious, you know, how you're thinking about that. Maybe Dr. McKay can comment as well. Have you shown this new 50 milligram data to the FDA? Do they need to weigh in on this in terms of the choice of 100 versus 50, or is the 100 locked in for PEAK-1? Just get a little more color because it does seem like they're really much more similar than different, if taking all the factors into consideration. Thank you. Thanks, Yigal, so I'll tell you that we're very confident in the 100, and as a matter of fact, the data set that you're looking at was in fact shared with the FDA. FDA is very comfortable with that as well, and big driver is we're hitting the target harder. There is PK difference, and one of the key features is that there's essentially no difference in the safety. So it also allows us to be able to dose down, but the data that you see were shared with the FDA. We, you know, we talked about Project Optimus. We obviously have 150 milligram cohort that's moving along as well. And I'll let Rana add anything that she might want to that, but I just would punctuate it with, we feel really good about the 100 milligram data, and the FDA was also supportive of that. Yeah, I mean, I think that just thinking about the FDA's initiative with Project Optimus, you know, the 100-milligram dose is not actually associated with worsening of quality of life, substantially increased toxicity. We're getting you know, potentially deeper responses, higher response rate. You know, I think the numbers are small, of course, but I think the opportunity also to allow for multiple dose reductions if somebody need it. You know, when you start at a lower level, you don't really have much lower that you can go for any given patient, and then you can't maintain durable long-term on treatment strategy. And thinking about the mechanism of these agents and sort of time to best response, you know, you want to be able to do that for patients. So I think that, you know, from the data that is shared, I think the 100 mg dose certainly makes significant rationale to move forward for phase 3 testing. Oh, okay. That certainly makes a lot of sense. And then just one other question. Just on the AZ collab with Volru, just can you remind us, is that exclusive, or could Merck also try that strategy? And why don't you take that one? Yeah. I mean, Merck has a PD-1 CTLA-4. It is not approved yet. I don't see them doing something until they had an approval, but it is something that they could be thinking about. So I think we feel good about where we are in getting that study up and running, and excited to be working with AZ again and feel like that they have a best-in-class bispecific. Keep in mind, you know, they're the only other company that we know of with, you know, either PD-1 and CTLA-4 or in bispecific, that has presented data in RCC. So that was data that was presented at ESMO. If anybody's interested, we can send it to them. I think it's also in our investor deck, but that was one of the reasons why we really liked the idea of going with AZ, is because we feel like they have, maybe the most advanced molecule in that tumor type. Oh, just one other quick one. Do you have any intention to go into or do some work in the non-clear cell, or are the conclusions that you've-- you're gonna generate in clear cell gonna basically translate across? Maybe Eric can comment too. Dimitry, do you want to make any comments about... go ahead, please. Yeah. So, I mean, in order for HIF-2alpha targeting to work, you need the VHL component, which is a very dominant component in clear cell and not in non-clear cell. So to go into non-clear cell, that would not make sense. And there are, of course, other, let's say, things that are mentioned, the rhabdoid or sarcomatoid subtypes, which are actually clear cell RCC tumors but have a component. And those patients we do allow. It's too early to say what the efficacy is in that particular subset, so it's a limited number of patients. But in order for HIF-2alpha to work, you do need that primary clear cell RCC component. So that, that's, I say, it is the majority of, Okay ... patients with RCC, but that's the inclusion for the trial based on a scientific rationale. All right. Thank you. Those are all the questions we have time for today, and so this concludes today's call. Thank you, everyone, for your questions and for your participation. Thank you, everybody. You may now disconnect your lines. Thank you. Thanks, everyone. Thanks, Rana.