Q4 2025 Arcus Biosciences Inc Earnings Call

February 25, 2026

Speaker #1: Welcome, everyone, to 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 1 on your telephone keypad.

Operator: Welcome everyone. The Arcus Biosciences Full Year and Q4 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. Thank you. Hello everyone, thank you for joining the Arcus Biosciences Full Year and Q4 2025 Earnings and Financial Results Call. My name is Claire, 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.

Speaker #1: If you change your mind, please press star followed by 2. Thank you. Hello, everyone, and thank you for joining the Arcus Biosciences full-year and fourth-quarter 2025 earnings and financial results call.

Speaker #1: My name is Clare, and I'll be coordinating your call today. During the presentation, you can register a question by pressing star, followed by 1, on your telephone keypad.

Speaker #1: If you change your mind, please press star followed by 2 on your telephone keypad. I will now hand over to Holly Culkey from Arcus Biosciences to begin.

Speaker #1: Please go ahead.

Speaker #2: Good afternoon, and 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.

Holli Kolkey: Good afternoon, thank you for joining us on today's conference call to discuss Arcus's Q4 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.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: This afternoon, you'll hear from several members of our management team. So now, I'll turn the call over to our CEO, Terry Rosen, to begin.

Holli Kolkey: 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.

Speaker #3: 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 castatafan as the unequivocal best-in-class HIF-2 alpha inhibitor and the new standard of care for clear-cell renal cell carcinoma.

Terry Rosen: Thanks very much, Holly. 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 going to be another substantial year for data presentations, as well as the advancement and expansion of our Phase 3 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, and that's all connect from the earliest days of its design and development. The advantages derive from dramatic differentiation of casdatifan's PK/PD profile.

Speaker #3: And this year is going to be another substantial year for data presentations, as well as the advancement and expansion of our Phase III clinical program for CAS.

Speaker #3: I want to emphasize particularly those who are new to Arcus or castatafan that the advantages of castatafan are well understood. That's all connect from the earliest days of its design and development.

Speaker #3: The advantages derive from dramatic differentiation of castatafan's PK/PD profile. These are evident in the highly quantitative and reproducible differentiation on the primary biomarker for HIF-2 alpha inhibition, EPO production, and the manifestation is improvement on all key efficacy measures.

Terry Rosen: 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 ARC-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 going to discuss these data in more detail today, but 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 7 of our corporate deck.

Speaker #3: Castatafan hits a target harder. It hits it earlier. Just this week, we shared updated data from our 20 cohorts evaluating castatafan monotherapy in late-line clear-cell RCC.

Speaker #3: We're also thrilled that Dr. Tony Sciarri will be presenting his data this weekend at ASCO GU. We're going to discuss these data in more detail today, but 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.

Speaker #3: This not only relative to data for Belzutafan, the only currently marketed HIF2 alpha inhibitor, but also relative to data for standard of care TKIs.

Speaker #3: This can be seen very clearly on slide 7 of our corporate deck. Importantly, castatafan achieves these outcomes without the debilitating toxicities associated with TKIs.

Terry Rosen: 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 going to see the detailed results from the Phase 3 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 3 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.

Speaker #3: In addition to the clinical data, the ASCO GU presentation will include biomarker data that further reinforce the confidence in the differentiation of castatafan versus Belzutafan.

Speaker #3: Also, at ASCO GU, we're going to see the detailed results from the Phase III LIGHTSPARK 011 study. This evaluated belzutafan plus lenvatinib versus cabozantinib in I/O-experienced clear-cell RCC.

Speaker #3: These data should be both validating in highly de-risking for ongoing Phase III PIK1 study which is evaluating CAS plus CABO in a similar setting and with the same control arm.

Speaker #3: With both our own data and the Belzutafan data being presented, this ASCO GU will be an extremely important event for the HIF-2 alpha inhibitor class, firmly establishing it as a key standard of care in the treatment of RCC.

Speaker #3: We believe HIF-2 alpha inhibitors will have a place in every line of treatment for RCC, and CAS is extremely well positioned to be the HIF-2 alpha inhibitor of choice across all settings.

Terry Rosen: 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. In fact, 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 multibillion-dollar commercial opportunities. Our first Phase 3 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 is 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 the early line setting by the LITESPARK data, will amplify the enthusiasm for this study.

Speaker #3: In fact, as we will describe later, we believe the profile of CAS will enable a unique frontline regimen that will transform the patient's journey in the setting and could translate into multibillion-dollar commercial opportunities.

Speaker #3: Our first Phase III study for CAS PIK1 is enrolling in its design to get CAS approved and to patients as quickly as possible. This represents our fast-to-market strategy.

Speaker #3: There's already a high level of excitement driving enrollment in PIK1, and the strength of our new ARC-20 data, coupled with the further validation of the HIF-2 alpha inhibition in early-line settings by the LIGHTSPARK data, will amplify the enthusiasm for this study.

Speaker #3: So by combining our best-in-class HIF2 alpha inhibitor with the most widely used TKI, Cabozantinib, we believe we'll capture substantial share of the I/O experience setting.

Terry Rosen: 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. Now 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.

Speaker #3: Now, 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.

Speaker #3: Our frontline strategy is enabled by the consistently low rate of primary progression that's been observed with castatafan across settings. This is shown very clearly on slide 20 of our corporate presentation.

Speaker #3: 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.

Speaker #3: Particularly in early-line treatment, because patients with primary progression do not get an opportunity to benefit from therapy. There's a devastating for both patients and their doctors.

Speaker #3: In contrast to the low rates for CAS, Belzutafan is associated with a very high rate of primary progression—35% as monotherapy in its Phase III trial.

Terry Rosen: 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 3 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 3 study in the frontline setting is evaluating exactly that. Lemba, Bells, 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.

Speaker #3: The manifestation of this key differentiation is that in frontline RCC, Belzutafan will likely always require a combination with a TKI to keep primary progression low.

Speaker #3: In fact, Merck's Phase III study in the frontline setting is evaluating exactly that: Lenva, Bells, Pembrol. That's a pretty non–patient-friendly regimen in the context of quality of life.

Speaker #3: A TKI-free regimen, on the other hand, is much more desirable for both patients and clinicians. The most common feedback that we received from investigators is that, given castatafan's profile, the use of a TKI can likely be put off for years.

Speaker #3: This offers a far better option for patients that would greatly improve their quality of life. Therefore, our frontline strategy is to develop castatafan without a TKI and specifically with a backbone of castatafan plus anti-PD1, which we can build upon with a third non-TKI mechanism.

Terry Rosen: 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 milligrams once a day is the optimal going forward dose of casdatifan.

Speaker #3: 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.

Speaker #3: First, with four monotherapy cohorts in 121 patients of efficacy data in late-line clear-cell RCC, Arc20 enabled us to clearly demonstrate that CAS has the best-in-class HIF2 alpha inhibitor profile.

Speaker #3: Second, with these four monotherapy cohorts, which were designed to satisfy project optimists, we've established that 100 milligrams once a day is the optimal going-forward dose of castatafan.

Speaker #3: Finally, 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.

Terry Rosen: 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 3 study, PEAK-1. 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.

Speaker #3: We first utilized this with the CAS plus CABO cohort, where we quickly generated data to support our first Phase III study, PIK1. We then added three new cohorts, approximately 90 patients in total, to demonstrate the feasibility of using CAS without a TKI in early-line settings.

Speaker #3: 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.

Speaker #3: 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 castatafan regimen.

Speaker #3: And we just started enrolling a new cohort to evaluate CAS plus anti-PD1 and anti-CTLA4 to support the rapid initiation and execution of our first Phase III study in the frontline setting.

Terry Rosen: 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 and 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.

Speaker #3: Finally, while RCC is our top priority, we've generated exciting preclinical data for CAS in HCC and are evaluating opportunities in a cost- and resource-efficient manner. We spent a lot of time already on castatafan, but I want to transition now to our immunology portfolio, where there's been a lot of—and growing—interest.

Speaker #3: We've leveraged the same small-molecule capability that created Castatafan to build an emerging portfolio of inflammation and immunology programs. Two of these are expected to enter the clinic over the next 12 months.

Speaker #3: 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 INI programs similar to what we're seeing with castatafan.

Terry Rosen: 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 compound 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.

Speaker #3: Our three most advanced molecules are an MRGPRX2 antagonist, a TNF inhibitor, and a CCR6 antagonist. Later on this call, Juan will speak in more detail about the potential differentiation of our compounds relative to others.

Speaker #3: But before we go there, I'd like to turn the call over to Richard to review the new and updated castatafan data that will be presenting at ASCOGEO this coming weekend.

Speaker #1: Thank you, Terry. I'd like to start on slide 9 of our corporate deck, just to remind everyone about the design of our Arc20 study.

[Company Representative] (Arcus Biosciences): 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 cut-off date of 30 January from the four late line monotherapy cohorts highlighted on the 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. Now 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%. A 45% ORR in this late line patient population is remarkable. That is twice that observed with belzutifan in LITESPARK-005.

Richard Markus: 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 cut-off date of 30 January from the four late line monotherapy cohorts highlighted on the 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. Now 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%. A 45% ORR in this late line patient population is remarkable. That is twice that observed with belzutifan in LITESPARK-005.

Speaker #1: Today's data include updated ORR and PFS based on a data cutoff date of January 30th from the four late-line monotherapy cohorts highlighted on the slide.

Speaker #1: This is now the fourth time we are presenting data for single-agent castatafan in the setting, and as you'll see on the next few slides, the efficacy data continue to improve with longer follow-up.

Speaker #1: Now 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%.

Speaker #1: The 45% ORR in this late-line patient population is remarkable in that it's twice that observed with Belzudafen in Lightspark-5. Similarly, the confirmed ORR for the pooled analysis improved from 31% to 35%, well above the range of ORRs that have been observed for Belzudafen.

[Company Representative] (Arcus Biosciences): 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 the 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.

Richard Markus: 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 the 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.

Speaker #1: On slide 12, we show the latest Kaplan-Meier curve for the 100 milligram cohort. And 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.

Speaker #1: 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 the next scan, the median PFS for this cohort would still be 14.4 months.

Speaker #1: So let's move on to the next slide, slide 13, and we show the latest Kaplan-Meier curve for the pooled analysis. The median PFS remained at 12.2 months and, as you can see here, there are quite a lot of patients still on treatment beyond 12 months.

[Company Representative] (Arcus Biosciences): The median PFS remained at 12.2 months, and 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 2 to 3 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, and 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.

Richard Markus: The median PFS remained at 12.2 months, and 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 2 to 3 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, and 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.

Speaker #1: And even beyond 24 months. So overall, we are seeing PFS that is 2 to 3 times longer with CAS monotherapy than the 5.6 months observed for Belzudafen in the same setting.

Speaker #1: These data clearly support the proposition that Castatafan is the best-in-class HIF-2 alpha inhibitor. Our highest priority now is to maximize the potential of this molecule in clear cell renal cell carcinoma.

Speaker #1: So I'd now like to spend some time on our development plans. Starting with our first Phase III study, PIK1, which is evaluating CAS plus CABO versus CABO in immunotherapy-experienced ccRCC.

Speaker #1: The trial design is shown on slide 19 of our corporate deck. PIK1 is actively enrolling, and we are confident that the study will complete enrollment quickly.

[Company Representative] (Arcus Biosciences): PEAK-1 is actively enrolling, and 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 readout. This is a fast-to-market strategy that builds on top of standard of care. 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.

Richard Markus: PEAK-1 is actively enrolling, and 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 readout. This is a fast-to-market strategy that builds on top of standard of care. 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.

Speaker #1: Additionally, PIK1 has a sole primary endpoint of PFS, which should enable a relatively short time to readout. So this is a fast-to-market strategy that builds on top of standard of care.

Speaker #1: And based on all the data to date, we have high confidence that this study will establish CAS plus CABO as a new standard of care in IO-experienced clear-cell RCC.

Speaker #1: 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.

Speaker #1: And there are several opportunities for CAS to do this. First, the biggest limitation of anti-PD1 plus anti-CTLA4 therapy is that it has a relatively high rate of primary progression—that is, 20 to 25 percent.

[Company Representative] (Arcus Biosciences): First, 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% to 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. In fact, we have shown that patients who progress quickly on IO-based therapies have tumor markers that correlate with responsivity to CAS. Additionally, 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.

Richard Markus: First, 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% to 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. In fact, we have shown that patients who progress quickly on IO-based therapies have tumor markers that correlate with responsivity to CAS. Additionally, 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.

Speaker #1: The CAS has a low rate of primary progression, and its orthogonal mechanism gives us confidence that we can meaningfully improve upon the high rate of primary PD seen with IO-only therapy.

Speaker #1: In fact, we have shown that patients who progress quickly on IO-based therapies have tumor markers that correlate with responsivity to CAS. Additionally, median PFS for IO-only regimens in clear-cell RCC is relatively short, at about 12 months.

Speaker #1: So 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.

Speaker #1: These include our fully enrolled cohort evaluating CAS plus ZIM, which we believe will convincingly demonstrate the ability of CAS plus an anti-PD1 to form the backbone of our first-line regimen based on both safety and efficacy.

[Company Representative] (Arcus Biosciences): These include our fully enrolled cohort evaluating CAS plus zimberelimab, 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. Additionally, 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. We'll share more about this in coming months. Lastly, we continue to monitor data from the eVOLVE-RCC02 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.

Richard Markus: These include our fully enrolled cohort evaluating CAS plus zimberelimab, 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. Additionally, 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. We'll share more about this in coming months. Lastly, we continue to monitor data from the eVOLVE-RCC02 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.

Speaker #1: We plan to share data from this cohort in the second half of this year. Additionally, we just started a cohort to evaluate CAS in combination with anti-PD1 and anti-CTLA4.

Speaker #1: In addition to this cohort, we also plan to evaluate another TKI-free combination for CAS in the front-line setting, and we'll share more about this in coming months.

Speaker #1: Lastly, we continue to monitor data from the Evolve study evaluating CAS plus Vorustimig and anti-PD1 CTLA4 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 front-line setting.

Speaker #1: 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.

[Company Representative] (Arcus Biosciences): 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.

Richard Markus: 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.

Speaker #1: And 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 castatafan.

Speaker #2: Thanks, Richard. I'd like to start on slide 22. RCC represents a massive, multibillion-dollar market opportunity for castatafan. Sales for RCC drugs in just the major markets are over $10 billion annually today, in anticipation to grow to $13 billion by 2030.

Jen: Thanks, Richard. I'd like to start on slide 22. RCC represents a massive multibillion-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 two-horse race with just belzutifan and us with casdatifan. While market is slightly ahead of us, historical data has shown that in just a two-player market in oncology, second entrants have captured 42% when there is zero differentiation. Let me repeat that, this is when there is no differentiation.

Jen Jarrett: Thanks, Richard. I'd like to start on slide 22. RCC represents a massive multibillion-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 two-horse race with just belzutifan and us with casdatifan. While market is slightly ahead of us, historical data has shown that in just a two-player market in oncology, second entrants have captured 42% when there is zero differentiation. Let me repeat that, this is when there is no differentiation.

Speaker #2: As you can see here, historically, the market has been dominated by only two classes of therapies, IO and TKIs. And HIF2 alpha inhibition is the only new class of drugs on the horizon today.

Speaker #2: Importantly, as of today, the HIF-2 alpha inhibitor field is only a two-horse race, with just Belzudafen and us with castatafan. While the market's slightly ahead of us, historical data has shown that in just a two-player market in oncology, second entrants have captured 42% when there is zero differentiation.

Speaker #2: And let me repeat that. This is when there is no differentiation. With efficacy differentiation, as we are seeing with Casatafan, this share can be meaningfully higher. In oncology, analogs have shown that fast followers with differentiation share can be as high as 85%.

Jen: With efficacy differentiation, as we are seeing with casdatifan, this year can be meaningfully higher, and oncology analogs have shown that fast followers with differentiation, share can be as high as 85%. Additionally, we are developing CAS 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 multibillion dollars in size.

Jen Jarrett: With efficacy differentiation, as we are seeing with casdatifan, this year can be meaningfully higher, and oncology analogs have shown that fast followers with differentiation, share can be as high as 85%. Additionally, we are developing CAS 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 multibillion dollars in size.

Speaker #2: Additionally, we are developing CAS with different combination partner sub-Belzudafen, which should drive even further differentiation. Turning to slide 23, the sole market in HIF-2 alpha inhibitor Belzudafen, which is currently approved only in late-line clear-cell RCC, is already generating annual run-rate sales of nearly $1 billion.

Speaker #2: While impressive, this is only scratching the surface in terms of market opportunity for a best-in-class HIF2 alpha inhibitor. For castatafan, 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 multibillion dollars in size.

Speaker #2: Specifically, our PIK1 study is targeting the IO-experienced setting, of which there are approximately 21,000 patients in the major markets alone, so more than twice the third-line patient population where Belz is approved today.

Jen: Specifically, our PEAK-1 study is targeting the IO experience setting, of which there are approximately 21,000 patients in the major markets alone, so more than twice the third-line patient population where Welireg 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 IO/IO and IO TKI regimens. Here we estimate peak sales potentially for CAS 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.

Jen Jarrett: Specifically, our PEAK-1 study is targeting the IO experience setting, of which there are approximately 21,000 patients in the major markets alone, so more than twice the third-line patient population where Welireg 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 IO/IO and IO TKI regimens. Here we estimate peak sales potentially for CAS 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.

Speaker #2: Additionally, with the duration of therapy at least double that of Belzudafen today, we expect a peak sales opportunity of $2.5 billion in the IO-experienced or PIK1 setting alone.

Speaker #2: In first-line, the opportunity is even greater. With our TKI-free strategy, we believe we can take meaningful share from both IO-IO and IO-TKI regimens. Here, we estimate peak sales potential for CAS of $3 billion or more.

Speaker #2: All in, castatafan could be a $5 billion drug in first and second-line RCC alone, and to be clear, this is a revenue opportunity to Arcus, not PAM or total addressable market.

Speaker #2: There's opportunity to expand that further with trials that support castatafan usage in other RCC settings, as well as potentially other tumor types like HCC, which Terry referenced earlier.

Jen: 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 Cherry 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 CAS in the front line. You can see here very clearly that the IO/IO regimen is preferred 3 times more than the IO TKI regimen as a combination partner for CAS for all the reasons we discussed earlier today.

Jen Jarrett: 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 Cherry 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 CAS in the front line. You can see here very clearly that the IO/IO regimen is preferred 3 times more than the IO TKI regimen as a combination partner for CAS for all the reasons we discussed earlier today.

Speaker #2: And as a reminder, we own all of the rights to castatafan, including economics, other than into PAN and certain other Southeast Asia countries, so nearly 100% of castatafan revenues would accrue to us.

Speaker #2: I'll end with one slide that supports our plans to focus on a TKI-free regimen in the front-line and up slide 24. Here we show market research that we recently conducted to determine the preferred combination partner for CAS in the front-line.

Speaker #2: You can see here very clearly that the IO-IO regimen is preferred three times more than the IO-TKI regimen as a combination partner for CAS, for all the reasons we discussed earlier today.

Speaker #2: I'd now like to turn the call over to Juan to discuss our immunology portfolio and workflow.

Jen: I'd now like to turn the call over to Juan to discuss our immunology portfolio in more detail.

Jen Jarrett: I'd now like to turn the call over to Juan to discuss our immunology portfolio in more detail.

Speaker #3: Thanks, Jen. I'm happy to describe such an emerging immunology portfolio. This is an area in which we have interest and in-house expertise since the founding of the company.

[Company Representative] (Arcus Biosciences): Thanks, Jen. I'm happy to describe such emerging immunology portfolio. This is an area in which we've had 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.

Juan Jaen: Thanks, Jen. I'm happy to describe such emerging immunology portfolio. This is an area in which we've had 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.

Speaker #3: This portfolio currently includes five programs that you can see in our slide deck. Reflecting the maturity of multiple years of research in compound optimization.

Speaker #3: 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.

Speaker #3: 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.

Speaker #3: We generally look for more than just the convenience of a neural drug. In fact, the value proposition for several of our programs includes an expectation of differentiated efficacy, safety, relative to the approved biologics.

Juan: 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-IL-4 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.

Juan Jaen: 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-IL-4 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.

Speaker #3: Our portfolio includes several programs as I mentioned before, five active ones, but today I will focus on our MRG PRX2 and TNF inhibitor programs, which are expected to be the first to reach the clinic.

Speaker #3: 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.

Speaker #3: While anti-IgE and anti-IL-4 receptor antibodies are marketed very successfully, for example, Dupixent alone is a $15 billion drug, there's still significant unmet medical need.

Speaker #3: While the market 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.

Juan: 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.

Juan Jaen: 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.

Speaker #3: 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.

Speaker #3: 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.

Speaker #3: 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.

Speaker #3: This could translate into a potentially improved therapeutic index and potential best-in-class profile. We expect our MRG PRX2 antagonist to enter the clinic later this year.

Juan: We expect our MRGPRX2 antagonist to enter the clinic later this year. We plan to start with a healthy volunteer Phase I study, and 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 of 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. However, 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.

Juan Jaen: We expect our MRGPRX2 antagonist to enter the clinic later this year. We plan to start with a healthy volunteer Phase I study, and 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 of 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. However, 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.

Speaker #3: We plan to start with a healthy volunteer phase one study to follow quickly with approval of concept study in chronic inducible urticaria. This program has the potential to generate proof of concept data within 9 to 12 months following entry into the clinic.

Speaker #3: 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.

Speaker #3: One of the challenges with today's TNF antibody therapies is that the day block TNF signaling at both receptor one and receptor two. However, blocking TNF receptor two can actually impact regulatory T cells and T cell repair resulting in a paradoxical inflammation as a side effect in some patients.

Speaker #3: Our approach is designed to selectively prevent TNF from activating TNF receptor one, while preserving TNF receptor two biology, which we expect to be an effective but safer alternative to the antibodies.

Juan: 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, and 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, and 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.

Juan Jaen: 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, and 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, and 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.

Speaker #3: Relative to the early competitor in the clinic, our molecule has been designed to have a better overall potency in human PK profile and we expect to be in the clinic with this program in late 2026 or early 2027.

Speaker #3: 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 and we are working to move these into the clinic as rapidly as possible.

Speaker #3: With that, I'd like now to hand it over to Bob to review our financials.

Speaker #4: 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.

Bob: Thanks, Juan. Our cash at the end of Q4 was $1 billion, as compared to $841 million as of the end of Q3. 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 Q4 of $33 million, which compares to $26 million for Q3. Our revenue is primarily driven by our collaboration with Gilead. Our R&D expenses for Q4 were $121 million, as compared to $141 million in Q3. G&A expenses were $26 million for Q4, compared to $27 million for Q3.

Bob Goeltz: Thanks, Juan. Our cash at the end of Q4 was $1 billion, as compared to $841 million as of the end of Q3. 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 Q4 of $33 million, which compares to $26 million for Q3. Our revenue is primarily driven by our collaboration with Gilead. Our R&D expenses for Q4 were $121 million, as compared to $141 million in Q3. G&A expenses were $26 million for Q4, compared to $27 million for Q3.

Speaker #4: 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.

Speaker #4: Our revenues 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.

Speaker #4: 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.

Bob: Total non-cash stock-based compensation was $15 million for Q4, compared to $14 million for Q3. Shifting gears to guidance for 2026, we expect to recognize GAAP revenue of $45 to 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.

Bob Goeltz: Total non-cash stock-based compensation was $15 million for Q4, compared to $14 million for Q3. Shifting gears to guidance for 2026, we expect to recognize GAAP revenue of $45 to 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.

Speaker #4: Shifting gears to guidance for 2026, we expect to recognize gap revenue of $45 to $55 million for the full year 2026. As we discussed on prior calls, we expect operating expenses to decrease meaningfully in 2026 as compared to 2025.

Speaker #4: 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.

Speaker #4: 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.

Speaker #4: 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.

Bob: For more details regarding our financial results, please refer to our earnings press release from earlier today and our Form 10-K. I'll now turn it back over to Terry.

Bob Goeltz: For more details regarding our financial results, please refer to our earnings press release from earlier today and our Form 10-K. I'll now turn it back over to Terry.

Speaker #5: Thanks very much, Bob. I'm going to end on slide 33. Spent 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 KISS DataFan data.

Juan: Thanks very much, Bob. I'm gonna hand-

Terry Rosen: Thanks very much, Bob. I'm gonna hand-

Terry Rosen: ... 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 gonna be another huge year for casdatifan data. Those data are both going to reinforce the confidence in its best-of-class profile and provide greater clarity on our first-line development strategy. Later this year, we'll have at least 2 additional data presentations for casdatifan. First, we'll be presenting updated data for the casdatifan plus cabo 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 zimberelimab cohort of ARC-20.

Speaker #5: Those data are both going to reinforce the confidence in its best-of-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 KISS.

Speaker #5: First, we'll be presenting updated data for the KISS Plus Cabo 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, so the aim here is to be able to provide a relatively mature and meaningful data set, including Kaplan-Meier curves.

Speaker #5: Also later this year, we'll share new data from the KISS DataFan Plus Zim cohort of ARC 20. This is intended to demonstrate the safety and early efficacy of the combination and to establish KISS Plus anti-PD1 as the backbone for our first-line combination.

Terry Rosen: This is intended to demonstrate the safety and early efficacy of the combination and to establish CAS 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 3 study for casdatifan, our goal is to complete enrollment by year-end. We're adding first-line combination cohorts to ARC-20 to determine the optimal regimen for our first Phase 3 study in the first frontline setting. This will enable us to initiate our second Phase 3 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.

Speaker #5: There's also a lot happening on the development front. For Peak One, our first Phase 3 study for KISS DataFan, our goal is to complete enrollment by year-end.

Speaker #5: Also, we're adding first-line combination cohorts to ARC 20 to determine the optimal regimen for our first-phase three study in the frontline setting and this will enable us to initiate our second-phase three study for KISS DataFan at the end of this year.

Speaker #5: 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.

Speaker #5: We appreciate your interest, your continued support of Arcus, and we're happy to open the call for questions.

Speaker #1: 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 two.

Operator: Thank you. To ask a question, please press star followed by 1 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.

Speaker #1: When preparing to ask your question, please ensure your device is unmuted locally. Our first question comes from Salemside from Mizuho. Your line is now open.

Speaker #1: Please go ahead.

Speaker #6: 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.

Salim Syed: Great. Thanks for the question, guys, and congrats on the data at ASCO GU. Just one from us. 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.

Speaker #6: 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 I/O benchmarks here as you move away from TKI-based regimens?

Speaker #6: And just second to that, any thoughts here on what you would like to see in terms of improvement from those benchmarks? Thanks so much.

Speaker #5: Sure. So that's a good question, and I think as we move into this TKI-sparing regimen, the focus should really go to Ipi/Nivo. So there's a lot of data out there on Ipi/Nivo.

Terry Rosen: 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% to 25%. Second, it has a relatively short PFS. It's on the order of 12 months or so.

Speaker #5: Those of you who were at ASCO last year know that there were even basically a decade of follow-up. And the reason is Ipinevo is the number one therapy that is utilized in the frontline and it's roughly in a third to 35 percent of patients.

Speaker #5: And 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.

Speaker #5: And that's on the order of 20% to 25%. Second, it has a relatively short PFS—it's on the order of 12 months or so.

Speaker #5: So I think those numbers become very clear simple lines to put in the sand where obviously we want to demonstrate meaningful improvement. And I would emphasize that's all going to start with that rate of primary progression and we believe it's exciting that we've even shown with anti-PD1 alone we're looking at potentially single-digit rate of primary progression and we'll have more to say on that later this year.

Terry Rosen: 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. 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.

Speaker #5: But I think those form a good place to start the conversation around benchmark.

Speaker #7: Yeah. I just would like a specific study to look at or checkmate Q14, which was the registrational study for Ipinevo and frontline RCC. And then the other study to look at that had an Ipinevo arm with cosmic 313, an interestingly the key efficacy measure.

Jen: Yeah, just with like a specific study. Like out our CheckMate-214, which was a registrational study for Ipi/nivo and frontliner ccRCC, 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.

Jen Jarrett: Yeah, just with like a specific study. Like out our CheckMate-214, which was a registrational study for Ipi/nivo and frontliner ccRCC, 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.

Speaker #7: So rate of PD, PFSOS, etc. We're all very, very similar across those two studies.

Speaker #6: Okay. Super helpful. Thanks so much, guys.

Salim Syed: Okay, super helpful. Thanks so much, guys.

Speaker #5: Thank you.

Terry Rosen: Thank you.

Speaker #1: Thank you. Our next question comes from Leigh Wetzick from Canta. Your line is now open. Please go ahead.

Operator: Thank you. Our next question comes from Li Watsek from Cantor. Your line is now open. Please go ahead.

Speaker #8: Hey, this is Daniel Brander on for Leigh. Congrats on the data update as well from our end. We're just curious to hear where you're at with the VolruPlus KAS run-in in the frontline study that's being operationalized by AstraZeneca.

Daniel Vonder: Hey, this is Daniel Vonder on for Li. Congrats on the data update as well from our end. We're just curious to hear where you're at with the volrustomig CAS run-in in the frontline study that's being operationalized by AstraZeneca. I know you had mentioned that it was paused and that you're looking at the data, any more color about when it might open again, if it's gonna open again?

Daniel Bronder: Hey, this is Daniel Vonder on for Li. Congrats on the data update as well from our end. We're just curious to hear where you're at with the volrustomig CAS run-in in the frontline study that's being operationalized by AstraZeneca. I know you had mentioned that it was paused and that you're looking at the data, any more color about when it might open again, if it's gonna open again?

Speaker #8: I know you had mentioned that it was paused and that you're looking at the data, but any more color about when it might open again, if it's going to open again?

Speaker #5: Yeah. So thanks. So what the question is referring to is the collaboration that we have with AstraZeneca that's looking at combination of KISS DataFan and their bispecific anti-PD1, anti-CTLA4 antibody.

Terry Rosen: Yeah. Thanks. That 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, anti-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 VORU. They also saw continued use of casdatifan. Actually, we're learning quite a bit about that access, anti-PD-1, anti-CTLA-4, combined with casdatifan, and, you know, it's looking good. We haven't since that dose down, we haven't seen any additional immune-AEs. I'll remind you, those look very VORU, very anti-CTLA-4 like. We haven't seen those since there's been the dosing down.

Speaker #5: 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.

Speaker #5: They also saw continued use of KISS DataFan. So actually, we're learning quite a bit about that access, anti-PD-1, anti-CTLA-4, combined with KISS DataFan. And no, it's looking good.

Speaker #5: So we haven't since that dose down, we haven't seen any additional immune AEs. And I'll remind you, those look very Volru, very anti-CTLA4-like. We haven't seen those since there's been the dosing down.

Speaker #5: I also think one important thing is, we didn't see any primary progression there. So, even though it's small and things are looking in the direction that we find and expected to be the case.

Terry Rosen: 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 3. 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.

Speaker #5: And at this point, I 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 three, but the thing to be knocked off the pedestal going in is that we recognize that Ipi anti-PD1 combined with KAS is what anything would need to be.

Speaker #5: So I think our intent is that study that arm is open now. I want to emphasize that it's open in our 20 it will enroll fast.

Terry Rosen: I want to emphasize that it's open in our 20. It will enroll fast. We'll get the data that we need, and that'll inform what we do in our Phase 3 study.

Speaker #5: We'll get the data that we need and that'll inform what we do in our phase three study.

Speaker #1: Thank you.

Jane: Thank you.

Daniel Bronder: Thank you.

Speaker #3: Thank you. Our next question. Comes from Dana Greybush from Leigh Rink Partners. Your line is now open. Please go ahead.

Operator: Thank you. Our next question comes from Daina Graybosch, from SVB Leerink. Your line is now open. Please go ahead.

Speaker #9: Hey, everyone. You’ve got Bill on for Dana. Thanks for the question and congrats on all the data—it looks really great. So, in your biomarker analyses, you mentioned that the deeper EPA reductions were correlated.

Bill: Everyone, you got Bill 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.

[Analyst] (Leerink Partners): Everyone, you got Bill 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.

Speaker #9: Is this due to higher baseline EPO? And I guess in other words, did patients generally reach a similar I guess numeric EPO level after treatment?

Speaker #9: I got one follow-up.

Speaker #5: So I'll let one give you some comments on that.

Terry Rosen: I'll let Juan give you some comments on that.

Speaker #9: Yeah. So 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 we have data to support that those reflect the extent of HIF2 alpha activity in those tumors.

Juan: 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.

Juan Jaen: 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.

Speaker #9: The tumors that have a stronger HIF2 alpha signal tend to present with higher EPO levels. And those also tend to be the patients that display the deepest and more sustained reductions.

Speaker #9: Got it. And when you're looking at these biomarkers, did you also look at ZGF and other genes that might also be downstream of HIF2?

Bill: 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?

[Analyst] (Leerink Partners): 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?

Speaker #5: Yes. And there are other soluble peripheral markers that will be disclosing later this year that are regulated by HIF2 alpha and are well known to be each one of them independently negative prognostics.

Juan: Yes, and that 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.

Juan Jaen: Yes, and that 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.

Speaker #5: In this setting, 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.

Terry Rosen: 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-2α 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, there is benefit.

Speaker #5: But in this particular case, there's no sense that we would ever think about having or needing a selection criteria based on the biomarker because what I'll remind you is that probably 80-plus percent to 90-some-odd percent of patients with clear cell RCC have some level of HIF2 as a driver.

Speaker #5: So when we report on the these type of data, what you're actually seeing is while there's correlation, even those patients with lower levels are there is benefit.

Speaker #5: So we get a pretty continuous spectrum of benefit throughout those patients as opposed to some sort of binary cutoff that you might be seeking.

Terry Rosen: We get a pretty continuous spectrum of benefit throughout those patients as opposed to some sort of binary cutoff that you might be seeking.

Speaker #9: Got it. Thank you.

Bill: Got it. Thank you.

[Analyst] (Leerink Partners): Got it. Thank you.

Speaker #5: Thank you.

Terry Rosen: Thank you.

Speaker #3: Thank you. Our next question comes from Richard Law from Goldman Sachs. Your line is now open. Please go ahead.

Operator: Thank you. Our next question comes from Richard Law from Goldman Sachs. Your line is now open. Please go ahead.

Speaker #10: Hi. This is Jane on for Rich. Congrats on the progress. So we have two questions about the upcoming presentation at ASCODU this weekend. So first, Merck will present detailed results of thousand-plus Lenva in the phase three light spark 11, which may set the bar in second line.

Jane: 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 2 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 zanzalintinib in the Phase 1b KEYNOTE-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.

[Analyst] (Goldman Sachs): 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 2 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 zanzalintinib in the Phase 1b KEYNOTE-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.

Speaker #10: So what are your thoughts and expectations for light spark 11? And my second question is so Merck is also running a study of bowels plus Zenza in the phase one B2.

Speaker #10: He may care U03. So they have a poster about the TIP poster this weekend. So what's your view on this combo strategy versus CAS plus Cabo?

Speaker #10: Thank you.

Speaker #5: So let me start with expectations around light spark 011. From everything that Merck put out, they obviously said that the study was successful and any body language that you might infer we think the data are going to look quite good.

Terry Rosen: 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, and 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-2α inhibitor, and we're going on top of what is the standard of care CABO, insofar as TKI versus Lenva, and we have the same control arm.

Speaker #5: And we're excited about that. We think a couple of things. First off, it's really providing important validation for the field. And in an earlier line setting, and we feel great knowing that we have a better HIF2 inhibitor and we're going on top of what is the standard of care Cabo insofar as TKI versus Lenva.

Speaker #5: And we have the same control arm. So from our perspective, obviously, we have no knowledge of anything quantitative, but we expect good data and the better the Merck data honestly the better we feel it'll be better for patients.

Terry Rosen: From our perspective, obviously, we have no knowledge of anything quantitative, but we expect good data. The better the Merck data, honestly, the better we feel be better for patients and be better for Arcus, 'cause we think we're gonna outperform them with both of the molecules in our combination. The second part, when I say 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, and we think the LITESPARK data will help us very much.

Speaker #5: It'll 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 say there's two important things is all of our investigators have emphasized this point, which we recognize.

Speaker #5: We have a lot of tailwinds in terms of enrolling. Peak one. But for a number of reasons, the positive data that they'll present is going to really help us to drive enrollment.

Speaker #5: As I mentioned, we're looking to be fully enrolled by the end of this year, and we think the light spark data will help us very much.

Speaker #5: 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. But we just simply don't see Zanza as being a key changer at least in clear cell RCC at this point.

Terry Rosen: I'll make a couple of comments on zanzalintinib, and I'll see if Jen or Richard want to add anything more on top of it. We just simply don't see zanzalintinib as being a key changer, at least in clear cell renal cell carcinoma at this point. You know, we think cabozantinib 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 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 cabozantinib is the TKI of choice.

Speaker #5: So we think Cabo is the clear standard of care. It's not only is it a have a great profile, but the reality is it's very entrenched.

Speaker #5: So 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. So we think Cabo is the TKI of of choice.

Jen: Just one note on Keymaker US review you were asking for. The presentation is just a TIP from the Keymaker study, which, you know, is just a phase 1b/2 platform study. There's no data that's gonna be presented for Bell Zanza. It's just a Trials in Progress poster.

Jen Jarrett: Just one note on Keymaker US review you were asking for. The presentation is just a TIP from the Keymaker study, which, you know, is just a phase 1b/2 platform study. There's no data that's gonna be presented for Bell Zanza. It's just a Trials in Progress poster.

Speaker #10: Just one note on key maker US or VH you were asking for. The presentation is just a tip from the key maker study, which is just a phase one B2 platform study.

Speaker #10: So there's no data that's going to be presented for Bell's Zanza. It's just a trial in progress poster.

Speaker #3: Right. Yes, it's a TIP poster. Thank you so much. This is super helpful.

Jane: Right, yes, it's a TIP poster. Thank you so much. This is super helpful.

[Analyst] (Goldman Sachs): Right, yes, it's a TIP poster. Thank you so much. This is super helpful.

Speaker #5: Thank you.

Terry Rosen: Thank you.

Speaker #3: Thank you. Our next question comes from Ashvika. Do you want to weigh in from Truist? Your line is now open. Please go ahead.

Operator: Thank you. Our next question comes from Asthika Goonewardene from Truist. Your line is now open. Please go ahead.

Speaker #11: Hi. Good afternoon, everyone. This is Carby on for ASCO from Truist. Thank you for the questions. Just want to first question on ARC20 monotherapy.

Kavi: Hi, good afternoon, everyone. This is Kavi on for Asthika from Truist. Thank you for the questions. Just wanna 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?

[Analyst] (Truist Securities): Hi, good afternoon, everyone. This is Kavi on for Asthika from Truist. Thank you for the questions. Just wanna 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?

Speaker #11: The last update had ORR somewhere in the 30% range, and now you're showing improvement in the mid-40s. So, how much of that was due to deepening responses, and at what time point were you seeing responses start to deepen?

Speaker #5: So it's definitely all due to deepening of response. And I like the question because it does go back. We share a lot of data, and we share almost in real time.

Terry Rosen: 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. 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.

Speaker #5: And so, on one of the slides we've included, we've shown how those data have evolved over time. But we also pointed out in 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.

Speaker #5: So, 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.

Speaker #5: So 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 generality in terms of where those responses may occur.

Terry Rosen: 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. There's no generalities in terms of where those responses may occur. What I would emphasize in, 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.

Speaker #5: And what I would emphasize to your question on deepening, even when we've seen patients that have generated their initial response out past a year, it's meaningful.

Speaker #5: So it isn't just that they were at a 29.6% tumor reduction and they went to 31%. These are genuine deepening of response. And the way we interpret it is that I think people aren't used to looking at oncology mechanisms that have a relatively benign safety profile.

Speaker #5: And what I mean by that is they're not poisoning you while they're reducing the size of your tumor. So once these patients become stabilized and they become healthier and they become stronger, all those things kick in, including their own immune system, to help.

Terry Rosen: 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.

Speaker #5: And so that's why you may see patients that all of a sudden deepen. It may have not even always been a gradual deepening. They start to deepen later on.

Speaker #5: And you do have for this mechanism what looks very IO-like in terms of the tail. So patients that do well and they do well for a long time, and 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.

Terry Rosen: That's one of the reasons we feel, and I think justified by the data, that the market is 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 as single agent in the late line, out past two years. We think that the front line, you know, is gonna be something where you can have patients going three, four, five years. That gets to the whole TKI-sparing strategy, that you're not just pushing off that TKI for a matter of months, but you're gonna dramatically change the opportunity for that patient that first presents, insofar as not having to go for TKI until many years later.

Speaker #5: And we've had a lot of patients even at a single agent in the late line out past two years. We think that the front line is going to be something where you can have patients going three, four, five years and that gets the whole TKI sparing strategy that 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.

Speaker #5: And so far as not having to go for TKI until many years later, but 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 at the outset to get the tumor under control, but they can get that years into their therapy.

Terry Rosen: 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.

Speaker #11: Got it. Thank you so much. If I may, I'm just going to squeeze in one more question.

Kavi: Got it. Thank you so much. If I may, I'm just gonna squeeze in one more.

[Analyst] (Truist Securities): Got it. Thank you so much. If I may, I'm just gonna squeeze in one more.

Terry Rosen: Thank you.

Kavi: question.

[Analyst] (Truist Securities): question.

Speaker #5: Thank you.

Speaker #11: Sure. Okay. Thank you. So you have said that STAR 121 will have a fertility analysis in the coming months. So if you choose to discontinue a STAR 121 based on a result, what is the clinical impact and what is the impact on your R&D spend?

Terry Rosen: Sure.

Kavi: 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?

[Analyst] (Truist Securities): 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?

Speaker #5: So the clinical impact is we're already anticipating from an operational standpoint that that likely will occur, but we may see something that tells us to keep going.

Terry Rosen: The clinical impact is we're already anticipating from an operational standpoint, that that likely will occur, but 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.

Speaker #5: Impact-wise, operationally, is fairly minimal. Because the study is basically fully enrolled. So that impact operationally would be that you wouldn't be doing all that work leading up to the registration.

Speaker #5: I'll let Bob comment on how we think about sort of the expense part of that whole thing.

Speaker #12: Yeah, I mean, the vast majority of the expense that we see, especially for any of our late-stage clinical trials, really is incurred primarily through the enrollment cycle.

[Company Representative] (Arcus Biosciences): Yeah, 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. You know, when you get to the latter parts of the trial and you've presumably seen that decrease in expense as an example for 221 and 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.

Bob Goeltz: Yeah, 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. You know, when you get to the latter parts of the trial and you've presumably seen that decrease in expense as an example for 221 and 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.

Speaker #12: And as the primary portion of patient treatment is occurring, so when you get to the latter parts of the trial and you presumably seen that decrease in expense as an example for 221 and 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.

Speaker #11: Got it. That's helpful. Thank you so much.

Kavi: Got it. That's helpful. Thank you so much.

[Analyst] (Truist Securities): Got it. That's helpful. Thank you so much.

Speaker #5: Thank you.

Terry Rosen: Thank you.

Operator: Our next question comes from Yigal Nochomovitz from Citigroup. Your line is now open. Please go ahead.

Speaker #13: Next question comes from Eagle Nokomovich from Citigroup. Your line is now open. Please go ahead.

Speaker #14: Yeah. Hi. Thanks. I just want to probe a little bit more in terms of the frontline strategy. So you've indicated that CASN plus ZIM will be the backbone of this strategy.

Yigal Nochomovitz: I just want to probe a little bit more in terms of the frontline strategy. You've indicated that CAS plus zimberelimab 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 question, you didn't put in the question on CAS plus zimberelimab, you put the triple. I'm just wondering, is the interpretation there that, you know, your base case is really to do PD-1 CTLA-4 CAS, and that's where it's gonna shake out?

Speaker #14: And then the question, of course, is whether the CTLA4 comes into the mix. So with that in mind, I'm just curious when you asked the oncologist as you showed us this new market data, in that question, you didn't put in the question on CAS plus ZIM.

Speaker #14: You put the triple. So I'm just wondering is the interpretation there that you're a base case is really to do PD-1, CTLA4, CAS, and that's where it's going to shake out?

Yigal Nochomovitz: Is there some reasonable potential that it could end up just being what you've identified as the backbone, CAS plus zimberelimab?

Speaker #14: Or is there some reasonable potential that it could end up just being what you've identified as the backbone, CAS plus ZIM?

Yigal Nochomovitz: Is there some reasonable potential that it could end up just being what you've identified as the backbone, CAS plus zimberelimab?

Terry Rosen: I'll let Jen start on that. We'll see if I add anything on top of what she says.

Speaker #5: I would jump start on that and see if I add anything on top of what she said.

Speaker #13: I will. But anyway, yeah, I mean, I think you actually described it really well that right now our base case assumption is that it would be CAS plus CAS plus ZIM or CAS plus anti-PD-1 really as the backbone and that we would likely build on that.

Jen: I will. Anyway, yeah, I think you actually described it really well, that right now our base case assumption is that it would be CAS plus ipilimumab. Right now we're thinking of CAS plus zimberelimab or CAS plus anti-PD-1/CTLA-4 as the backbone, and that we would likely build on that. You know, we'll keep looking at the CAS plus zimberelimab data to see how it looks over time. Yeah, certainly base case right now is CAS plus ipilimumab, and as we talked about today, that cohort is actually now enrolling. You know, 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 ipilimumab has a relatively high rate of primary progression.

Jen Jarrett: I will. Anyway, yeah, I think you actually described it really well, that right now our base case assumption is that it would be CAS plus ipilimumab. Right now we're thinking of CAS plus zimberelimab or CAS plus anti-PD-1/CTLA-4 as the backbone, and that we would likely build on that. You know, we'll keep looking at the CAS plus zimberelimab data to see how it looks over time. Yeah, certainly base case right now is CAS plus ipilimumab, and as we talked about today, that cohort is actually now enrolling. You know, 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 ipilimumab has a relatively high rate of primary progression.

Speaker #13: We'll keep looking at the CAS plus ZIM data to see how it looks over time. But yeah, certainly base case right now is CAS plus Ibinivo.

Speaker #13: And as we talked about today, that cohort is actually now enrolling and 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.

Speaker #13: And so it's also nice about this combination as Terry was talking about earlier, because Ibinivo has a relatively high rate of primary progression if we see early on at the first scan that that rate of primary progression is coming down, that gives us a very early read on efficacy, which is nice to have.

Jen: If we see early on, you know, at the first scan, that that rate of primary progression is coming down, that gives us a very early read on efficacy, which is nice to have.

Jen Jarrett: If we see early on, you know, at the first scan, that that rate of primary progression is coming down, that gives us a very early read on efficacy, which is nice to have.

Speaker #5: So what I'll add, Eagle, in this actually it's questions come up from investors and it's a topic also with investigators. So the data that we've seen thus far and obviously we just there early and we showed you the primary progression.

Terry Rosen: What I'll add, Igal. This actually, it's come, 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, obviously we just there early and we showed you the primary progression, but it's a good start. The question sometimes does come up in the context of 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 this comes up, even though it wasn't a formal part of that analysis that Jen did.

Speaker #5: But it's a good start. And the question sometimes does come up in the context of CAS Datafence, how much value does the anti-CTLA4 bring?

Speaker #5: So obviously we're going to have an early data set but the way we look at it is if you think about it in 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 CAS, if you could bring that into the front line, from a patient standpoint, that would just be awesome.

Terry Rosen: 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 front line 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 wanna get too cute.

Speaker #5: I mean, to not have to go with anti-CTLA4 and not have to go with TKI would be it comes up sometimes like a vacation.

Speaker #5: So we are going to 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.

Speaker #5: We don't want to get too cute. So if that anti-PD-1, anti-PD-1, anti-CTLA4, each on top of CAS, looks similar or maybe like anti-PD-1 potentially, could be there.

Terry Rosen: if that anti-PD-1, anti-CTLA-4, each on top of CAS, 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 CAS versus anti-PD-1 CAS versus Ipi/Nivo. We're not going to get too cute and outsmart ourselves just based on early data. if it should, we're gonna give anti-PD-1 CAS its shot at the limelight, if possible, because it would be great for patients.

Speaker #5: We're still more likely than not to go for a three-arm study where we would have anti-PD-1, anti-CTLA-4, CAS versus anti-PD-1, CAS versus Ibinivo. So we're not going to get too cute and outsmart ourselves just based on early data.

Speaker #5: But if it should, we're going to give anti-PD-1, CAS, it's shot at the limelight if possible because it would be great for patients.

Speaker #13: Thank you. Next question. Next question. Comes from Jonathan Miller from Evercore. Your line is now open. Please go ahead.

Operator: Thank you. Our next question comes from Jonathan Miller from Evercore. Your line is now open. Please go ahead.

Speaker #15: Claire?

Jen: Claire?

Speaker #13: Hi. Yes. Next question comes from Jonathan Miller from Evercore.

Operator: Hi. Yes. Question? Our next question comes from Jonathan Miller from Evercore.

Operator: Our next question comes from Jonathan Miller from Evercore.

Jonathan Miller: Hey, guys. I'm not sure if you can hear me, but hopefully you can. I was gonna ask on the first line study as well.

Speaker #16: Hey, guys. Not sure if you can hear me, but hopefully you can. I was going to ask on the first-line study as well. I don't know if you can hear me.

Jonathan Miller: Hey, guys. I'm not sure if you can hear me, but hopefully you can. I was gonna ask on the first line study as well.

Terry Rosen: Hey, John.

Jonathan Miller: Can you hear me?

Jen: Um-

Terry Rosen: John, apologies. We're having technical diff--. Can you hear us? You went out for a minute, so we didn't get the beginning of whatever question that was.

Terry Rosen: [crosstalk] John, apologies. We're having technical diff--. Can you hear us? You went out for a minute, so we didn't get the beginning of whatever question that was.

Speaker #17: John, we're having technical can you hear us?

Speaker #5: You went out for a minute, so we didn't get the beginning of whatever question that was. And I know John's voice. Is it?

Jonathan Miller: Oh, so sorry, guys. Thank you.

Terry Rosen: John's voice. Is it?

Speaker #16: Yeah. If you can hear me now, I'll just follow up on your question first. If I can just follow up on your question on the first-line setting.

Jonathan Miller: Yeah. If you can hear me now, I'll just follow up on what you all said on the first-

Terry Rosen: Sure, sure. Yeah. Okay.

Jonathan Miller: If I could just follow up on you all speaking in the first line setting. You know, you say at least 1 Phase 3 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 3 decision. I just want to get a sense for, broadly speaking, how many first line Phase 3 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 CAS belongs in all lines of therapy?

Speaker #16: You say at least one Phase 3 starting this year. You're adding an additional undisclosed combo to ARC-20 in the first-line setting this year. The Ibinivo combo is open.

Speaker #16: 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 three decision.

Speaker #16: So I just want to get a sense for broadly speaking, how many first-line phase threes 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 CAS belongs in all lines of therapy?

Jonathan Miller: What are your current thoughts on partnering in RCC and beyond for CAS, and whether that unlocks additional bandwidth to do some of these late-stage designs?

Speaker #16: And what are your current thoughts on partnering in RCC and beyond for CAS, and whether that unlocks additional bandwidth to do some of these late-stage designs?

Jonathan Miller: What are your current thoughts on partnering in RCC and beyond for CAS, and whether that unlocks additional bandwidth to do some of these late-stage designs?

Speaker #5: Yeah. So I'm just going to kind of briefly and then turn it over to Jen to give a more fulsome answer on all of that.

Terry Rosen: Yeah. I'm just gonna comment 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 collaborations. At this point, we feel we love that we basically own 100% of the casdatifan rights other than in Japan and a few other South Asian, Southeast Asian countries. As you know, that gives us an enormous strategic optionality.

Speaker #5: But I'll address the partnering part. From a partnering perspective, all you should expect to potentially see—and you probably will see—are clinical collaborations. So at this point, we feel we love that we basically own 100% of the CAS Datafence rights, other than in Japan and a few other Southeast Asian countries.

Speaker #5: 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 CAS Datafence is a relatively rare beast, we feel like we're in a good position to do some smart clinical collaborations under good terms.

Terry Rosen: With that said, there are other mechanisms and settings that make sense, 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 3 we might do, how they're sequencing, when we'll disclose some data, et cetera, because we will obviously, you know, we won't make a decision without sort of giving a sense of what drove that decision. Go ahead, Jen.

Speaker #5: I'll let Jen comment more broadly, though, on the number of Phase 3s we might do, how they're sequencing, when we'll disclose some data, etc.

Speaker #5: Because we will obviously we won't make a decision without sort of giving a sense of what drove that decision. Go ahead, Jen.

Speaker #15: Yeah, so just on the Phase 3 front—so obviously, we have PICK1 that's enrolling. Our plan is to start one other Phase 3 study around year-end.

Jen: Yeah. Yeah, just on the Phase 3 front, obviously, we have take 1 that's enrolling. Our plan is to start 1 other Phase 3 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 CAS plus anti-PD-1, plus CTLA-4. You could probably make an assumption that, you know, that first Phase 3 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 CAS plus anti-PD-1, plus another mechanism, probably something that wouldn't be a big surprise to a lot of people.

Jen Jarrett: Yeah. Yeah, just on the Phase 3 front, obviously, we have take 1 that's enrolling. Our plan is to start 1 other Phase 3 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 CAS plus anti-PD-1, plus CTLA-4. You could probably make an assumption that, you know, that first Phase 3 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 CAS plus anti-PD-1, plus another mechanism, probably something that wouldn't be a big surprise to a lot of people.

Speaker #15: That would be in the front-line setting and informed by this new cohort that we're adding that you referred to, John, so the cohort that's looking at CAS plus anti-PD-1 plus CTLA4.

Speaker #15: So you could probably make an assumption that that first phase three study would be looking at that triplet versus Ibinivo. So that would probably be our base case assumption today.

Speaker #15: We'll probably also add, as you were pointing out, another combination to ARC-20 to look at CAS plus anti-PD-1 plus another mechanism—probably something that wouldn't be a big surprise to a lot of people.

Speaker #15: I'd say, as far as whether we took that into a Phase 3, it's very TBD right now. I think, right now, that first Phase 3 in the frontline setting that I mentioned is our top priority and what we'd really be focusing on from a resource perspective.

Jen: You know, I'd say as far as whether we took that into a Phase 3 is very TBD right now. You know, I think right now that first Phase 3 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. You know, 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 CAS, including HCC. Just given it's not a huge market, you know, patients are on treatment for 12 months max.

Jen Jarrett: You know, I'd say as far as whether we took that into a Phase 3 is very TBD right now. You know, I think right now that first Phase 3 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. You know, 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 CAS, including HCC. Just given it's not a huge market, you know, patients are on treatment for 12 months max.

Speaker #15: But we're also interested in generating some other data with that other combination as well. And then on the adjuvant setting, we'll see what the Lifespark 022 data looks like and I think right now we probably view that as lower priority relative to certainly front-line and maybe some other things we might do with CAS, including HCC, just given it's not a huge market.

Speaker #15: 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.

Jen: 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.

Jen Jarrett: 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.

Speaker #15: So a lot of times they don't want to be on therapy. They come off therapy. So like I said, we'll see their data. We're always evaluating it.

Speaker #15: We'll continue to evaluate and if something that we might consider for the future.

Speaker #5: I think the way and obviously it's your goals along, we'll continue to share and probably into next year we'll be sharing our view is that HIF2 inhibition is going to be used in every line, in every setting of clear cell RCC.

Terry Rosen: I think the way, 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-2α inhibition is going to be used in every line, in every setting, of clear cell RCC. Our ultimate development strategy, you know, whether it's supportive studies, et cetera, is going to look like we're going to make sure we've covered everything with time. From a prioritization standpoint, it's PEAK-1, front-line, potentially another one next year, and 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, et cetera, in every line of therapy.

Speaker #5: And our ultimate development strategy whether it's supportive studies, etc., is going to look like we're going to make sure we've covered everything with time.

Speaker #5: But from a prioritization standpoint, it's pick one front-line potentially another one next year and 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.

Speaker #5: in every line of therapy.

Speaker #15: Yeah. I'd recommend to look at what you were pointing out, clinical collaborations for that other or new front-line option that we're thinking about. So not everything is on our dime.

Jen: 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, et cetera. That's important to us as well.

Jen Jarrett: 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, et cetera. That's important to us as well.

Speaker #15: It's not all our resources, etc. So that's important to us as well.

Speaker #16: Great. And if I could just squeeze in one more before we run out of time. On PRX2, you've mentioned a couple of times the potential for a safety delta on the basis of better potency and lower dosing.

Jonathan Miller: 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?

Speaker #16: But are there specific safety signals that we should be looking at when we think about initial data here? And 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?

Speaker #5: Right. So I'm always saying that outside of oncology, you're always one dose away from complete disaster. So the answer is that a well-run, healthy volunteer study will give you some comfort, but you're always accumulating additional data.

Juan: 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, it, 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 functions. Okay? You can actually, as our competitors have seen, if you go too high, you will actually start to see the liver complaining.

Juan Jaen: 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, it, 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 functions. Okay? You can actually, as our competitors have seen, if you go too high, you will actually start to see the liver complaining.

Speaker #5: The thing that the whole 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.

Speaker #5: Okay? And so you can go you can actually ask our competitors have seen, if you go too high, you will actually start to see the liver complaining.

Speaker #5: And so we think that we think there will be able to put way more daylight between the amount of our drug required to elicit a similar pharmacology and levels where the liver is going to start to complain.

Juan: 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 going to start to complain.

Juan Jaen: 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 going to start to complain.

Speaker #17: Thank you. Our next question. Our last question, sorry, comes from Emily Bodnar from HC Wainwright. Your line is now open. Please go ahead.

Operator: 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.

Speaker #18: 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 CAS plus combo data.

Emily Bodnar: 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 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?

Speaker #18: 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 dataset?

Speaker #18: Thanks. Hello?

Operator: There seems to be a connection issue. We'll be right back in just a mo-. Emily, could you please repeat your question?

Speaker #17: There seems to be a connection issue. We'll be right back in just a moment.

Speaker #18: Don't.

Speaker #17: Emily, could you please repeat your question?

Speaker #18: Yeah. Do you hear me?

Emily Bodnar: Yeah. Do you hear me?

Speaker #5: Yes. Thank you, Emily.

Terry Rosen: Yes, thank you, Emily.

Speaker #18: Okay, yeah. I was going to ask if you could give us some more updated expectations for your CAS-plus combo data later this year, given you now have pretty mature monotherapy PFS of over 12 months.

Emily Bodnar: Yeah, I was going to ask if you could give us some more updated expectations for your casdatifan 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.

Speaker #18: So, how are you kind of thinking about what the combo could look like in earlier-line patients, in that full 45-patient dataset? Thanks.

Speaker #5: Go ahead, Jim.

Terry Rosen: Go ahead, Jen.

Speaker #15: Yeah. So is Terry 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 it'll be able to look at a Kaplan-Meyer curve and at least make some educated guesses as far as where PFS could shape out.

Jen: As Terry 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 CABO mono PFS, we're seeing a range of 12 to 15 months. You know, we'll see what CABO mono shows. You know, right now, we obviously believe very, very strongly that we can beat CABO alone because CAS mono alone looks better than CABO. You know, we'll build on both what CAS mono looks like and what CABO mono looks like.

Jen Jarrett: As Terry 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 CABO mono PFS, we're seeing a range of 12 to 15 months. You know, we'll see what CABO mono shows. You know, right now, we obviously believe very, very strongly that we can beat CABO alone because CAS mono alone looks better than CABO. You know, we'll build on both what CAS mono looks like and what CABO mono looks like.

Speaker #15: Or shape up. And so, as you know, for CAS mono, PFS, we're seeing a range of 12 to 15 months. So we'll see what CAS combo shows.

Speaker #15: And right now, we obviously believe very, very strongly that we can beat combo alone because CAS mono alone looks better than combo. And so we'll build on both what CAS mono looks like and what combo mono looks like.

Speaker #15: So yeah, we're excited to get those data out, and we think the Lifespark011 data will also be very de-risking for the PEAK-01 study.

Jen: Yeah, 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.

Jen Jarrett: Yeah, 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.

Speaker #5: The other nice thing about Lifespark011, just maybe obvious, but it'll give a good—call it—contemporary look at what combo alone looks like, because that's the control arm.

Terry Rosen: The other nice thing about LITESPARK-011, this may be obvious, but it'll give a good, a contemporary look at what CABO alone looks like, because that's the control arm. To the extent that I'm thinking about, you know, benchmarks.

Speaker #5: So, to the extent that thinking about benchmarks?

Speaker #15: Yeah. And what gives us obviously a lot of confidence in the Cas plus combo data and the PFS is, like I said, just what we're seeing with Cas mono and the fact that Cas mono looks better.

Jen: Yeah, what gives us obviously a lot of confidence in the CAS plus CABO data and the PFS is, like I said, you know, just what we're seeing with CAS mono, you know, and the fact that, you know, CAS mono looks better than CABO mono, and, you know, we think, you know, may even look better than Bell plus Len. We'll see what the LITESPARK-011 data shows.

Jen Jarrett: Yeah, what gives us obviously a lot of confidence in the CAS plus CABO data and the PFS is, like I said, you know, just what we're seeing with CAS mono, you know, and the fact that, you know, CAS mono looks better than CABO mono, and, you know, we think, you know, may even look better than Bell plus Len. We'll see what the LITESPARK-011 data shows.

Speaker #15: The combo mono—and we think it may even look better than Bell's plus Lam. You'll see what the Lifespark011 data shows.

Speaker #18: Great. Thank you.

Emily Bodnar: Great. Thank you.

Speaker #17: Thank you. We currently have no further questions and therefore conclude today's call. Thank you all for joining. You may now disconnect your lines.

Operator: 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.

Speaker #5: Thank you, Claire.

Terry Rosen: Thank you, Claire.

Operator: Goodbye.

Q4 2025 Arcus Biosciences Inc Earnings Call

Request a DemoDemo

RCUS

Arcus Biosciences

Earnings