Q1 2026 Arcus Biosciences Inc Earnings Call

May 5, 2026

Speaker #1: Updates and financial results. After today's prepared remarks, we will host a question-and-answer session. Please limit yourself to one question and one follow-up. If you would like to ask a question, please press star 1 to raise your hand.

Speaker #1: To withdraw your question, press star 1 again and will now hand the conference over to Holli Kolkey, VP of Corporate Affairs. Holli, please go ahead.

Speaker #2: Good afternoon and thank you for joining us on today's conference call to discuss Arcus's first quarter 2026 financial results and pipeline updates. I'd like to remind you that on this call, management will make forward-looking statements, including statements about our development strategies and our expectations regarding the advantages and opportunities afforded by our investigational products, our clinical development milestones and timelines, our projected cash runway, and our financial outlook.

Operator: I will now hand the conference over to Holli Kolkey, VP of Corporate Affairs. Holli, please go ahead.

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.

Operator: I will now hand the conference over to Holli Kolkey, VP of Corporate Affairs. Holli, please go ahead.

Holli Kolkey: Good afternoon, and thank you for joining us on today's conference call to discuss Arcus Biosciences' Q1 2026 financial results and pipeline updates. I'd like to remind you that on this call, management will make forward-looking statements, including statements about our development strategies and our expectations regarding the advantages and opportunities afforded by our investigational products, our clinical development milestones and timelines, our projected cash runway, and our financial outlook. 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 quarterly report on Form 10-Q 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: Those risks and uncertainties are described in our most recent quarterly report on Form 10-Q 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 will hear from our CEO, Terry Rosen, Chief Medical Officer, Richard Markus, President Juan Jaen, and CFO Bob Goeltz. With that, I'd like to turn the call over to Terry.

Holli Kolkey: 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 quarterly report on Form 10-Q 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 #3: Thanks very much, Holli. And thanks, everyone, for joining us this afternoon. We're starting a new era for Arcus with full ownership of our lead program case data van, our phase three kidney cancer study peak one enrolling rapidly, a clear path to win in the front line, and a next-generation molecules for inflammation and immunology that can be advanced rapidly into and through development.

Speaker #3: And with that, the strategic optionality imparted by a rich portfolio of wholly owned molecules and programs. We are at an inflection in value creation for patients and shareholders that will continue to accelerate over the next 12 to 18 months.

Holli Kolkey: This afternoon, you will hear from our CEO, Terry Rosen, Chief Medical Officer, Richard Markus, President, Juan Heyen, and CFO, Bob Gelb. With that, I'd like to turn the call over to Terry.

Terry Rosen: Thanks very much, Holli, and thanks everyone for joining us this afternoon. We're starting a new era for Arcus with full ownership of our lead program, casdatifan, our Phase 3 kidney cancer study, PEAK-1, enrolling rapidly, a clear path to win in the front line, and a next generation of molecules for inflammation and immunology that can be advanced rapidly into and through development. With that, the strategic optionality imparted by a rich portfolio of wholly owned molecules and programs. We are at an inflection in value creation for patients and shareholders that will continue to accelerate over the next 12 to 18 months. Arcus has proven to be a highly productive company, creating and advancing a steady stream of potential best-in-class molecules for patients with cancer and inflammatory and autoimmune diseases.

Speaker #3: Arcus has proven to be a highly productive company creating and advancing a steady stream of potential best-in-class molecules for patients with cancer and inflammatory and autoimmune diseases.

Speaker #3: We believe that discovery is not a commodity and we've built exceptional small molecule medicinal chemistry and drug discovery capabilities. Our scientists utilize proven biology to create unmatched medicines designed to raise the standard of care.

Speaker #3: Since its inception, Arcus has advanced molecules from program initiation to I&D filing and has shortened 18 months and accelerated platform and signal seeking studies to move from proof of concept phase one studies to randomized phase two and registrational phase three trials in just a few years.

Terry Rosen: We are at an inflection in value creation for patients and shareholders that will continue to accelerate over the next 12 to 18 months. Arcus has proven to be a highly productive company, creating and advancing a steady stream of potential best-in-class molecules for patients with cancer and inflammatory and autoimmune diseases.

Speaker #3: Today, the company is laser-focused on case data van, which represents a market opportunity of more than $5 billion in kidney cancer alone. I want to stress that case data van's efficacy advantages are underpinned by much better molecular properties and a superior pharmacodynamic profile.

Terry Rosen: We believe that discovery is not a commodity, and we've built exceptional small molecule medicinal chemistry and drug discovery capabilities. Our scientists utilize proven biology to create unmatched medicines designed to raise the standard of care. Since its inception, Arcus has advanced molecules from program initiation to IND filing in as short as 18 months, an accelerated platform and signal-seeking studies to move from proof of concept phase 1 studies to randomized phase 2 and registrational phase 3 trials in just a few years. Today, the company is laser-focused on casdatifan, which represents a market opportunity of more than $5 billion in kidney cancer alone. I want to stress that casdatifan's efficacy advantages are underpinned by much better molecular properties and a superior pharmacodynamic profile. This profile reflects the key capabilities in Arcus that I described earlier.

Speaker #3: This profile reflects the key capabilities in Arcus that I described earlier. The simple fact is that case data van hits its target much harder and in a more sustained way than Belzuda van, as illustrated on slide six.

Speaker #3: This is a point we've emphasized since the data first emerged. These data are clear in their striking. We believe this fundamental differentiation between case data van and Belzuda van and the limitations of Belzuda van's pharmacodynamic profile and durability of effect are undoubtedly contributors to, if not the principal, driver of the outcome of Lightspark 012.

Terry Rosen: Today, the company is laser-focused on casdatifan, which represents a market opportunity of more than $5 billion in kidney cancer alone. I want to stress that casdatifan's efficacy advantages are underpinned by much better molecular properties and a superior pharmacodynamic profile. This profile reflects the key capabilities in Arcus that I described earlier.

Speaker #3: In the pharmacodynamic advantages of case data van, we'll continue to result in improved clinical outcomes across lines of therapy. I want to emphasize this point.

Terry Rosen: The simple fact is that casdatifan hits its target much harder and in a more sustained way than does belzutifan is illustrated on slide 6. This is a point we've emphasized since the data first emerged. These data are clear, and they're striking. We believe this fundamental differentiation between casdatifan and belzutifan and the limitations of belzutifan's pharmacodynamic profile and durability of effect are undoubtedly contributors to, if not the principal driver of, the outcome of LITESPARK-012. The pharmacodynamic advantages of casdatifan will continue to result in improved clinical outcomes across lines of therapy. I want to emphasize this point. This dramatic difference in profile has been evidenced since late last year. It is not esoteric. Its manifestations on clinical outcomes are dramatic and are at the core of our differentiation. No results to date are surprising. Our top priorities for 2026 are clear.

Speaker #3: This dramatic difference in profile has been evident since late last year. It is not esoteric. It's manifestations on clinical outcomes are dramatic and are at the core of our differentiation.

Speaker #3: No results to date are surprising. Our top priorities for 2026 are clear. One, complete enrollment for peak one, our second-line phase three study, and two, initiate a phase three study in the front line patient population.

Terry Rosen: The pharmacodynamic advantages of casdatifan will continue to result in improved clinical outcomes across lines of therapy. I want to emphasize this point. This dramatic difference in profile has been evidenced since late last year. It is not esoteric. Its manifestations on clinical outcomes are dramatic and are at the core of our differentiation. No results to date are surprising. Our top priorities for 2026 are clear.

Speaker #3: With the recent outcome of Lightspark 012, case data van has a clear path to consolidate a fragmented front line setting as the first tip to alpha inhibitor in this setting.

I want to stress the cast of efficacy, advantages are underpinned by much better, molecular properties in a superior phco Dynamic profile. This profile reflects the key capabilities in our case that I described earlier. The simple fact is that cast dense hits its Target much harder in an a more sense. Same way than those those who defend is Illustrated on slide 6. This is a point, we've emphasized since the data first emerged you did our clear in their striking, we believe this fundamental differentiation between test data and and belzan and the limitations of Belgium defense, pharmacodynamic profile and durability of effect are undoubtedly contributors to if not the principal driver of the outcome of light sparkle 012. And the pharmacodynamic advantages of kannadasan will continue to result in improved clinical outcomes across lines of their

I want to emphasize this point.

Speaker #3: Let me spend a moment on why case data van is at the center of everything we do. We believe case data van can transform the treatment paradigm and clear cell renal cell carcinoma and our development strategy is designed to generate evidence to secure CAS as a backbone therapy so that every patient has the opportunity to benefit from CAS across each line of therapy.

This dramatic difference in profile has been evidenced since late last year. It is not esoteric. Its manifestations on clinical outcomes are dramatic and are at the core of our differentiation. No results to date are surprising.

Terry Rosen: 1, complete enrollment for PEAK-1, our second-line Phase 3 study. 2, initiate a Phase 3 study in the front-line patient population. With the recent outcome of LITESPARK-012, casdatifan has a clear path to consolidate a fragmented front-line setting as the first HIF-2 alpha inhibitor in this setting. Let me spend a moment on why casdatifan is at the center of everything we do. We believe casdatifan can transform the treatment paradigm in clear cell renal cell carcinoma, and our development strategy is designed to generate evidence to secure CAS as a backbone therapy so that every patient has the opportunity to benefit from CAS across each line of therapy. PEAK-1 represents our path to market strategy.

Speaker #3: Peak one represents our fast-to-market strategy. This is designed to build on the clinician enthusiasm that we've seen for CAS as an experimental agent and to generate the data to support the approval of a foundational treatment for clear cell RCC as rapidly as possible.

Our top priorities for 2026 are clear 1. Complete enrollment for Peak 1. Our second line, phase 3 study and 2 initiate a phase 3. Study in the Frontline patient population with the recent outcome of Light, spark 012 cast data and has a clear path to consolidate a fragmented Frontline setting as the first tip to help inhibitor in this setting,

Speaker #3: Enrollment in peak one is accelerating and we're on track to complete enrollment by year-end 2026. We're confident that peak one will establish CAS plus CABO as the new standard of care in the I/O experience setting.

Terry Rosen: We believe casdatifan can transform the treatment paradigm in clear cell renal cell carcinoma, and our development strategy is designed to generate evidence to secure CAS as a backbone therapy so that every patient has the opportunity to benefit from CAS across each line of therapy. PEAK-1 represents our path to market strategy.

Speaker #3: The peak sales opportunity for CAS in this setting alone is more than $2 billion. At the same time, we are aggressively building a holistic strategy to embed CAS across the treatment paradigm.

We believe we can transform the treatment paradigm in clear cell renal cell carcinoma, and our development strategy is designed to generate evidence to secure CAS as a backbone therapy, so that every patient has the opportunity to benefit from CAS across each line of therapy.

Terry Rosen: This is designed to build on the clinician enthusiasm that we've seen for CAS as an experimental agent and to generate the data to support the approval of a foundational treatment for clear cell RCC as rapidly as possible. Enrollment in PEAK-1 is accelerating, and we're on track to complete enrollment by year-end 2026. We're confident that PEAK-1 will establish CAS plus cabo as the new standard of care in the IO experience setting. The peak sales opportunity for CAS in this setting alone is more than $2 billion. At the same time, we are aggressively building a holistic strategy to embed CAS across the treatment paradigm. We have been making tremendous progress in the frontline setting with multiple IO combinations now enrolling in ARC-20 and generating data in support of our first-line strategy. These approaches offer the greatest potential for long-term survival for patients.

Speaker #3: We have been making tremendous progress in the front line setting with multiple I/O combinations now enrolling in Arc 20 and generating data in support of our first line strategy.

Peak 1 represents our fast to Market strategy. This is designed to build on the clinician enthusiasm that we've seen for cases and experimental agent and to generate the data to support the approval of the foundational treatment for Clear. Cell RCC is rapidly as possible.

Speaker #3: These approaches offer the greatest potential for long-term survival for patients. One of our key objectives today is to make very clear our integrated development strategy for case data van.

Speaker #3: It's actually quite straightforward and here's how we believe things will play out. In the first line, our bedrock therapy will be CAS, IPI, anti-PD1.

Enrollment in Peak 1 is accelerating. And we're on track to complete enrollment by year, end 2026. We're confident that D1 will establish Cash Plus Cabo as the new standard of care in the io experience setting.

Terry Rosen: At the same time, we are aggressively building a holistic strategy to embed CAS across the treatment paradigm. We have been making tremendous progress in the frontline setting with multiple IO combinations now enrolling in ARC-20 and generating data in support of our first-line strategy. These approaches offer the greatest potential for long-term survival for patients.

The peak sales opportunity for cash in this setting alone is more than 2 billion dollars.

Speaker #3: We believe that we can drive the 35% share of IPI/NIVO to a regimen with greater than 50% of the important first line market. While the I/O regimen of IPI/NIVO is the dominant therapy today, there's a segment of physicians that's always going to want to reach for TKI.

Speaker #3: Particularly for patients with a fast-growing bulky tumor. Therefore, we will also be developing a CAS combination inclusive of a TKI. A TKI with a well-established track record of both efficacy and safety that will allow the patient to have CAS/CABO as a subsequent regimen.

Terry Rosen: One of our key objectives today is to make very clear our integrated development strategy for casdatifan. It's actually quite straightforward, and here's how we believe things will play out. In the first line, our bedrock therapy will be cas ipi anti-PD-1. We believe that we can drive the 35% share of ipi-nivo to a regimen with greater than 50% of the important first-line market. The IO regimen of ipi-nivo is the dominant therapy today, there's a segment of physicians that's always gonna wanna reach for a TKI, particularly for patients with a fast-growing, bulky tumor. Therefore, we will also be developing a cas combination inclusive of a TKI, a TKI with a well-established track record of both efficacy and safety that will allow the patient to have cas cabo as a subsequent regimen.

At the same time we are aggressively building a holistic strategy to embed cast across the treatment Paradigm. We have been making tremendous progress in the Frontline setting with multiple IO combinations. Now enrolling in our 20 and generating data in support of our first line strategy, these approaches offer the greatest potential for long-term survival for patients.

1 of our key objectives today is to make very clear, our integrated development strategy for K status. It's actually quite straightforward and here's how we believe things will play out.

Speaker #3: Our second line treatment now enrolling its registrational trial peak one will be CAS/CABO. Building on these standard of care in this line, CABOSAT and NIV monotherapy.

In the first line, our BEDROCK therapy will be cast—hippocampal anti-PD1. We believe that we can drive the 35% share of ipilimumab/neo to a regimen with greater than 50% of the important first-line market.

Speaker #3: Finally, we will have a third line plus regimen CAS with another well-established TKI and we will be investigating this regimen in both Belzuda van, Naive, and Belzuda van experienced patients.

Terry Rosen: Therefore, we will also be developing a cas combination inclusive of a TKI, a TKI with a well-established track record of both efficacy and safety that will allow the patient to have cas cabo as a subsequent regimen.

Speaker #3: We think this is a very important kind of cool study. We also plan to explore novel CAS combinations in HCC, liver cancer. I would like to emphasize that all of the clinical development plans discussed today are accounted for within our existing budget and have no impact on the guidance and runway that we have provided.

While the IO regimen of IFP-Neo is the dominant therapy today, there's a segment of physicians that's always going to want to reach for TKI, particularly for patients with a fast-growing, bulky tumor. Therefore, we will also be developing a CAST combination inclusive of the TKI.

Terry Rosen: Our 2nd-line treatment, now enrolling its registrational trial PEAK-1, will be CAS cabo, building on the standard of care in this line, cabozantinib monotherapy. Finally, we will have a 3rd-line plus regimen, CAS with another well-established TKI, and we will be investigating this regimen in both belzutifan-naive and belzutifan-experienced patients. We think this is a very important, kind of cool study. We also plan to explore novel CAS combinations in HCC, liver cancer. I would like to emphasize that all of the clinical development plans discussed today are accounted for within our existing budget and have no impact on the guidance and runway that we have provided. We now control in all respects our early-stage pipeline, including our CCR6, CD89, and CD40 ligand programs, all of which are expected to port IND candidates in the next 6 to 18 months.

The TKI with the wellest-documented track record of both efficacy and safety that will allow the patient to have cast Cabo as a subsequent regimen.

Speaker #3: We now control in all respects our early-stage pipeline, including our CCR6, CD89, and CD40 ligand programs, all of which are expected to afford IND candidates in the next six to 18 months.

Our second line treatment now enrolling it's registrational trial. Peak 1 will be cast Kabul building on these standard of care in this line, tables that any monotherapy.

Speaker #3: So as we focus our resources capital, human, and otherwise on the late-stage development of case data van, the follow-on programs in our pipeline, our early, but also with clear early and capital-efficient clinical proof of concept opportunity and huge commercial potential.

Finally, we will have a third-line plus regimen cast with another well-established TKI, and we will be investigating this regimen in both Sudan-naive and Belgian-experienced patients. We think this is a very important, kind of cool study.

Terry Rosen: I would like to emphasize that all of the clinical development plans discussed today are accounted for within our existing budget and have no impact on the guidance and runway that we have provided. We now control in all respects our early-stage pipeline, including our CCR6, CD89, and CD40 ligand programs, all of which are expected to port IND candidates in the next 6 to 18 months.

We also plan to explore novel CAST combinations in ATC liver cancer.

Speaker #3: Therefore, we anticipate low spend and short timelines to get to proof of concept that will drive disproportionate value creation. Juan will discuss these programs in more detail later on in this call.

I would like to emphasize that all of the clinical development plans discussed today are accounted for within our existing budget, and have no impact on the guidance. And Runway that we have provided

Speaker #3: If you want to walk away with just one thing from today, it's that Arcus has complete control of its destiny. The core asset of the company is case data van and we have the strategy, data, and resources to transform the treatment of clear cell RCC and create a $5 billion plus drug.

Terry Rosen: As we focus our resources, capital, human, and otherwise, on the late-stage development of Casdatifan, the follow-on programs in our pipeline are early but also with clear, early, and capital-efficient clinical proof of concept opportunities and huge commercial potential. Therefore, we anticipate low spend and short timelines to get to proof of concept that will drive disproportionate value creation. Juan will discuss these programs in more detail later on in this call. If you want to walk away with just one thing from today, it's that ARC has complete control of its destiny. The core asset of the company is Casdatifan, and we have the strategy, data, and resources to transform the treatment of clear cell RCC and create a $5 billion plus drug. Bob will further elaborate on the enormous commercial opportunity here.

Speaker #3: Bob will further elaborate on the enormous commercial opportunity here. We also continue to leverage our demonstrated competitive advantage in small molecule drug discovery and increasingly scarce capability to generate wholly owned and unique development candidates the advancement of which further enhances our strategic optionality.

We now control in all respects, our early stage pipeline, including our ccr6 CD, 89 and cd40 Ligon programs, all of which are expected to forward, IND candidates in the next 6, to 18 months. So as we focus, our resources, Capital human. And otherwise on The Late stage development of cast data fan, the following programs in our pipeline are early. But also with clear early and capital efficient clinical proof of concept opportunity and a huge commercial potential.

Therefore we anticipate will spend and short timelines, to get the proof of concept that will drive disproportionate value creation.

1 will discuss these programs in more detail later on in this call.

Speaker #3: With that, I'd like to turn the call over to Richard to discuss our clinical programs.

Speaker #4: Thanks, Terry. I'd like to start with case data van. As Terry described, our development plan is designed to establish case data van as a foundational standard of care in clear cell RCC.

Terry Rosen: The core asset of the company is Casdatifan, and we have the strategy, data, and resources to transform the treatment of clear cell RCC and create a $5 billion plus drug. Bob will further elaborate on the enormous commercial opportunity here.

Speaker #4: So that all patients have the opportunity to benefit from treatment with a case data van-based regimen across multiple lines of therapy. At ASCO GU this year, we presented updated ORR and PFS from our four late line monotherapy cohorts of Arc 20.

If you want to walk away with just 1 Thing from today, is that Arcus has complete control of its Destiny. The core asset of the company has cast data in and we have the strategy data and resources to transform the treatment of clear cell RCC and creates a 5 billion plus drug.

Terry Rosen: We also continue to leverage our demonstrated competitive advantage in small molecule drug discovery and increasingly scarce capability to generate wholly owned and unique development candidates, the advancement of which further enhances our strategic optionality. With that, I'd like to turn the call over to Richard Markus to discuss our clinical programs.

Speaker #4: As you can see here, the FC data continued to improve with longer follow-up at each data presentation. Moving to slide 12, where we show the ORRs for the 100 milligram QD cohort.

Richard Markus: Thanks, Terry. I'd like to start with casdatifan. As Terry described, our development plan is designed to establish casdatifan as a foundational standard of care in clear cell RCC so that all patients have the opportunity to benefit from treatments with a casdatifan-based regimen across multiple lines of therapy. At ASCO GU this year, we presented updated ORR and PFS from our 4 late line monotherapy cohorts of ARC-20. As you can see here, the FC data continued to improve with longer follow-up at each data presentation. Moving to slide 12, where we show the ORRs for the 100 milligram QD cohort, which is the dose and formulation being used in our phase 2 studies, the confirmed ORR increased from 35% at the August data cut to 45%. A 45% ORR in this late line patient population is rather remarkable.

Bob will further elaborate on the enormous commercial opportunity. Here, we also continue to leverage our demonstrated competitive advantage in small molecule drug discovery and increasingly scarce capability to generate wholly owned and unique development candidates, the advancement of which further enhances our strategic optionality. With that, I'd like to turn the call over to Richard to discuss our clinical programs.

Speaker #4: Which is the dose and formulation being used in our phase three studies. The confirmed ORR increase from 35% at the August data cut to 45%.

Thanks, Terry. I'd like to start with 'cast out a fan.'

Speaker #4: A 45% ORR in this late line patient population is rather remarkable. It's twice that observed with Belzuda van and Lightspark 5 or any study in this patient population.

100% of care in clear cell RCC—said, all patients have the opportunity to benefit from treatment with a caspase-8 fan-based regimen across multiple lines of therapy.

Speaker #4: Similarly, the confirmed ORR for the pooled analysis improved from 31% to 35%. Well above the range of ORRs that have been observed with Belzuda van.

Pasco gu this year we presented updated or and PFS from our 4 late line monotherapy cohorts of our 20

Richard Markus: Moving to slide 12, where we show the ORRs for the 100 milligram QD cohort, which is the dose and formulation being used in our phase 2 studies, the confirmed ORR increased from 35% at the August data cut to 45%. A 45% ORR in this late line patient population is rather remarkable.

As you can see here, the FC data continued to improve with longer follow-up at each data presentation.

Speaker #4: On slide 13, we show the Kaplan-Meier curve for the 100 milligram cohort. As you can see here, that the 100 milligram cohort shows an impressive median PFS of 15.1 months after 17.9 months of median follow-up.

Speaker #4: On the next slide, we show the latest Kaplan-Meier curve for the pooled analysis. The median PFS remained at 12.2 months. So overall, we're seeing PFS that is 2 to 3 times longer with CAS monotherapy than the 5.6 months observed with Belzuda van in the same setting.

Moving to slide 12 where we show the OS for the 100.

Richard Markus: It's twice that observed with belzutifan in LITESPARK-005 or any study in this patient population. Similarly, the confirmed ORR for the pooled analysis improved from 31% to 35%, well above the range of ORRs that have been observed with belzutifan. On slide 13, we show the Kaplan-Meier curve for the 100 milligram cohort. As you can see here that the 100 milligram cohort shows an impressive median PFS of 15.1 months after 17.9 months of median follow-up. On the next slide, we show the latest Kaplan-Meier curve for the pooled analysis. The median PFS remained at 12.2 months. Overall, we're seeing PFS that is 2 to 3 times longer with casdatifan monotherapy than the 5.6 months observed with belzutifan in the same setting.

A 45% or in this late line. Patient. Population is rather remarkable it's twice that observed with P fan and light, spark 5, or any study in this patient population.

Speaker #4: And as is often discussed while the median is an important benchmark, it's not the only metric that's important. As you can see here and perhaps more impressive is the number of patients still on treatment beyond 18 months and even beyond 24 months.

Similarly, the confirmed or R for the P analysis. Improved from 31% to 35%.

Well, above the range of ours that have been observed with belzutifan.

On slide 13. We show the captain Meyer curve for the 100.

Speaker #4: These data clearly support the proposition that case data van is the best in class HIF2 alpha inhibitor. And our highest priority now is to maximize the potential of this molecule in CCRCC.

And you can see here that the 100 milligram cohort, shows an impressive median PFS of 15.1 months.

17.9 months of median, follow-up.

On the next slide, we show the latest Captain. Meer curve for the pool analysis.

Richard Markus: Overall, we're seeing PFS that is 2 to 3 times longer with casdatifan monotherapy than the 5.6 months observed with belzutifan in the same setting.

Speaker #4: Our first registrational trial which is in the second line setting is well underway. Enrollment in the ongoing phase three study peak one is accelerating.

Richard Markus: As is often discussed, while the median is an important benchmark, it's not the only metric that's important. As you can see here, and perhaps more impressive, is the number of patients still on treatment beyond 18 months and even beyond 24 months. These data clearly support the proposition that casdatifan is the best in class HIF-2 alpha inhibitor, and our highest priority now is to maximize the potential of this molecule in CCRCC. Our first registrational trial, which is in the second-line setting, is well underway. Enrollment in the ongoing Phase 3 study, PEAK-1, is accelerating, and we are on track to complete enrollment by year-end. We are confident that PEAK-1 will establish CAS plus cabo as a new standard of care in the IO experience setting.

The median PFS remained at 12.2 months. So overall, we're seeing PFS that is 2 to 3 times longer with cast monotherapy than the 5.6 months, observed with Belgium found in the same setting.

Speaker #4: And we are on track to complete enrollment by year-end. We are confident that peak one will establish CAS plus CABO as a new standard of care in the IO experience setting.

And, as often discussed, while the median is an important benchmark, it's not the only metric that's important.

Speaker #4: With a sole primary endpoint of PFS and a 2 to 1 randomization favoring the experimental arm, and CABO as the control arm, we believe peak one is optimized for both probability of success and speed to data.

As you can see here, and perhaps more impressive is the number of patients still on treatment Beyond 18 months and even Beyond 24 months,

These data clearly support the proposition that testan is the best-in-class history to Alpha inhibitor.

Speaker #4: I'd like to spend some time now on the front line setting. With the outcome of Merck's Lightspark 12 last month, CAS has the opportunity to be the first HIF2 alpha inhibitor option in the front line setting.

And our highest priority now is to maximize the potential of this molecule in ccrcc.

Richard Markus: Enrollment in the ongoing Phase 3 study, PEAK-1, is accelerating, and we are on track to complete enrollment by year-end. We are confident that PEAK-1 will establish CAS plus cabo as a new standard of care in the IO experience setting.

Speaker #4: Treatment in the front line is generally bifurcated into IO/IO or IPPI anti-PDX combination. This currently leads to the conceptual trade-off between longer time to response or higher primary progression but with the potential for durable responses and long-term survival with the IO/IO option or faster time to response and lower primary progression but with much more treatment-associated toxicity for the TTI anti-PDX options.

Our first registration of trial, which is in the second line. Setting is well underway. Enrollment in the ongoing phase 3 study peek 1 is accelerating

I'm on track to complete enrollment by year-end.

Richard Markus: With a sole primary endpoint of PFS and a 2-to-1 randomization favoring the experimental arm and cabo as the control arm, we believe PEAK-1 is optimized for both probability of success and speed to data. I'd like to spend some time now on the frontline setting. With the outcome of Merck's KEYNOTE-A18 last month, CAS has the opportunity to be the first TIGIT alpha inhibitor option in the frontline setting. Treatment in the frontline is generally bifurcated into IO/IO or a TKI anti-PD-1 combination. This currently leads to the conceptual trade-off between longer time to response or higher primary progression, but with the potential for durable responses and long-term survival with the IO/IO option, or a faster time to response and lower primary progression, but with much more treatment-associated toxicity for the TKI anti-PD-1 options.

We are confident that P1 will establish cast plus Cabo has a new standard of care in the io experience setting.

With a sole primary endpoint of PFS, and a 2, to 1, Rand failing, the experimental arm.

And Cabo as the control arm We Believe each 1 is optimized for both probability of success and speed to data.

Speaker #4: There's currently no treatment option that has the ability to both rapidly control disease and provide the best chance for long-term survival. While also having a favorable tolerability profile for long-term use.

Alex has been some time now on the front line setting,

With the outcome of Mercedes Light, spark 12. Last month cast has the opportunity to be the first, his 2 Alpha inhibitor options in the Frontline setting.

Speaker #4: We believe a CAS plus IO/IO combination in the front line setting has the potential to deliver on both of these fronts. We are enrolling several cohorts within the Arc 20 study evaluating CAS combinations in the front line setting.

Richard Markus: This currently leads to the conceptual trade-off between longer time to response or higher primary progression, but with the potential for durable responses and long-term survival with the IO/IO option, or a faster time to response and lower primary progression, but with much more treatment-associated toxicity for the TKI anti-PD-1 options.

Treatment in the front line is generally bifurcated into IO/IO or a PI anti-PD(x) combination.

Speaker #4: While the data are maturing, primary progressive disease rates have already been shown to be low. Just 7% or 2 out of 30 patients for the CAS plus Zimerlimab, our anti-PD1 cohort.

This currently leads to the conceptual trade-offs between longer time to response or higher primary progression. But with a potential for durable, responses and long-term survival with the ayo ayo option.

Richard Markus: There's currently no treatment option that has the ability to both rapidly control disease and provide the best chance for long-term survival while also having a favorable tolerability profile for long-term use. We believe a CAS plus IO/IO combination in the frontline setting has the potential to deliver on both of these fronts. We are enrolling several cohorts within the ARC-20 study evaluating CAS combinations in the frontline setting. While the data are maturing, primary progressive disease rates have already been shown to be low, just 7% or 2 out of 30 patients for the CAS plus zimberelimab, our anti-PD-1 cohort. This rate compares favorably to published rates for anti-PD-1 monotherapy or ipi-nivo in the first-line setting. In fact, it is close to the rate of a TKI-containing regimen, but without the need for the TKI. We're also enrolling a cohort evaluating CAS plus zim plus ipi.

Or a faster time to response and lower primary progression, but with much more treatment-associated toxicity for the TPI anti-PD(X) options.

Speaker #4: This rate compares favorably to published rates for anti-PD1 monotherapy or IPINIVO in the first line setting. And in fact, it is close to the rate of a TKI-containing regimen but without the need for the TKI.

There’s currently no treatment option that has the ability to both rapidly control disease and provide the best chance for long-term survival.

While also having a favorable tolerability profile for long-term use.

Speaker #4: We're also enrolling a cohort evaluating CAS plus ZIM plus IPI. Emerging data from these cohorts of Arc 20 will inform the first line registrational strategy with the goal of finalizing the phase three study protocol and beginning startup activities by the end of this year.

We believe a cast plus ayo ayo combination. In the Frontline setting has the potential to deliver on. Both of these fronts. We are enrolling several cohorts within the R20 study, evaluating cast combinations in the Frontline setting.

Speaker #4: In parallel, we will shortly begin to evaluate additional CAS plus TKI-containing regimens in the early and late line settings. Including in patients with prior Belzuda van experience.

Richard Markus: This rate compares favorably to published rates for anti-PD-1 monotherapy or ipi-nivo in the first-line setting. In fact, it is close to the rate of a TKI-containing regimen, but without the need for the TKI. We're also enrolling a cohort evaluating CAS plus zim plus ipi.

While the data are maturing, primary progressive disease rates have already been shown to be low—just 7%, or 2 out of 30 patients—for the CAS plus zimberelimab, our anti-TIGIT cohort.

Speaker #4: This effort contemplates the preference and in fact a strategic necessity to utilize alternative TKIs as patients advance from one line of therapy to the next.

And in fact, it is close to the rate of a TKI-containing regimen, but without the need for the TKI.

Speaker #4: Near term, we expect to have multiple data readouts for case data van in 2026. First, mature ORR data and initial PFS data for approximately 45 patients treated in the Arc 20 CAS plus CABO cohort in the IO experience setting will be presented at an investor event or at a medical conference.

Richard Markus: Emerging data from these cohorts of ARC-20 will inform the first-line registrational strategy with the goal of finalizing the Phase 3 study protocol and beginning start-up activities by the end of this year. In parallel, we will shortly begin to evaluate additional CAS plus TKI-containing regimens in the early and late-line settings, including in patients with prior belzutifan experience. This effort contemplates the preference and, in fact, the strategic necessity to utilize alternative TKIs as patients advance from one line of therapy to the next. Near term, we expect to have multiple data readouts for casdatifan in 2026. First, mature ORR data and initial PFS data for approximately 45 patients treated in the ARC-20 CAS plus cabo cohort in the IO experience setting will be presented at an investor event or at a medical conference, and all patients will have had at least 12 months of follow-up.

We also enrolling the cohort evaluating cast plasm, plus Ipsy.

Emerging data from these cohorts of R20 will inform the first line. Registrational strategy with the goal of finalizing the Phase 3 study protocols and beginning startup activities by the end of this year.

Speaker #4: And all patients will have had at least 12 months of follow-up. Second, we will share initial data from the Arc 20 cohorts evaluating CAS in early line settings.

2ki containing regimens in the early and late line settings including in patients with prior buildup and experience.

Speaker #4: Including the cohort evaluating CAS plus ZIM in the first line. We also expect updated data from late line monotherapy cohorts including overall survival. Before I hand it over to Juan, I'd like to quickly touch on Quemiclustat, our small molecule CD73 inhibitor.

this effort contemplates, the preference and in fact the Strategic necessity to utilize alternative tkis as patients Advanced from 1 line of therapy to the next

Richard Markus: First, mature ORR data and initial PFS data for approximately 45 patients treated in the ARC-20 CAS plus cabo cohort in the IO experience setting will be presented at an investor event or at a medical conference, and all patients will have had at least 12 months of follow-up.

Near-term. We expect to have multiple data readouts for testin in 2026.

Speaker #4: CD73 is highly expressed in pancreatic cancer and high CD73 expression is associated with significantly poor prognosis in several tumor types. In spite of this, as we recently published in Nature Medicine, in our phase two study, Arc 8, those patients with higher baseline levels of CD73 or adenosine activity were the ones with longer PFS and OS in response to Quemy treatment.

First mature or our data and initial. PFS data for a approximately 45 patients, treated in the are 20 cast plus Cabo course, in the io experience setting will be presented at an investor event or at a medical conference

Richard Markus: Second, we will share initial data from the ARC-20 cohorts evaluating CAS in early line settings, including the cohort evaluating CAS plus zim in the 1st line. We also expect updated data from late line monotherapy cohorts, including overall survival. Before I hand it over to Juan, I'd like to quickly touch on quemliclustat, our small molecule CD73 inhibitor. CD73 is highly expressed in pancreatic cancer. High CD73 expression is associated with significantly poor prognosis in several tumor types. In spite of this, as we recently published in Nature Medicine, in our Phase 2 study, ARCADE, those patients with higher baseline levels of CD73 or adenosine activity were the ones with longer PFS and OS in response to quemliclustat treatment. Pancreatic cancer is one of the most aggressive cancers with an average 5-year survival rate of just 13%.

And all patients will have had at least 12 months of follow-up.

Second, we will share initial data from the R20 cohorts, evaluating casts in early line settings including the cohort evaluating cash flow of them in the first line.

Speaker #4: Pancreatic cancer is one of the most aggressive cancers with an average five-year survival rate of just 13%. In Prism 1, our phase three study, evaluating Quemly plus Gemcitabine and Nabla paclitaxel, versus Gemcitabine and Nab paclitaxel in the front line pancreatic setting, completed enrollment in September of 2025.

We also expect updated data from late line monotherapy cohorts, including overall survival.

Before I hand it over to Juan,

I'd like to quickly touch on cleanly crew staff. Our small molecule cd73 inhibitor.

Richard Markus: In spite of this, as we recently published in Nature Medicine, in our Phase 2 study, ARCADE, those patients with higher baseline levels of CD73 or adenosine activity were the ones with longer PFS and OS in response to quemliclustat treatment. Pancreatic cancer is one of the most aggressive cancers with an average 5-year survival rate of just 13%.

CD73 is highly expressed in pancreatic cancer, and high CD73 expression is associated with significantly poor prognosis in several tumor types.

Speaker #4: Results from this study are expected in the first half of 2027. And if positive, Prism 1 could represent the first transformative therapy for an all-comer first line patient population in 30 years.

In spite of this, as we recently published in nature medicine.

Speaker #4: There's no biomarker requirement and no known resistant mechanism. And data to date have indicated that the regimen was well tolerated. Finally, we recently announced that the phase three STAR121 study evaluating our anti-TIGIT, Donbanilimab plus ZIM and chemotherapy versus pembrolizumab plus chemotherapy as a first line treatment for metastatic non-small cell lung cancer will be discontinued due to futility.

And our Phase 2, study arcade, those patients with higher Baseline levels of cd73 or density. Activity, were the ones with longer PFS and Os in response to cleanly treatment

Richard Markus: In PRISM-1, our Phase 3 study evaluating quemliclustat plus gemcitabine and nab-paclitaxel versus gemcitabine and nab-paclitaxel in the frontline pancreatic setting completed enrollment in September of 2025. Results from this study are expected in the H1 of 2027, and if positive, PRISM-1 could represent the first transformative therapy for an all-comer first-line patient population in 30 years. There's no biomarker requirement and no known resistant mechanism, and data to date have indicated that the regimen was well tolerated. Finally, we recently announced that the Phase 3 STAR-121 study evaluating our anti-TIGIT domvanalimab plus zimberelimab and chemotherapy versus pembrolizumab plus chemotherapy as a first-line treatment for metastatic non-small cell lung cancer will be discontinued due to futility. While these are certainly not the results we expected, the study had one important positive outcome.

Pancreatic cancer is 1 of the most aggressive. Cancers with an average 5-year survival rate of just 13%.

In PRISM-1, our Phase 3 study evaluating domvanalimab plus gemcitabine and nab-paclitaxel.

Versus gemcitabine and nab-paclitaxel in the frontline, Adriatic study. Back the taxol in the frontline, Adriatic study.

Completed enrollment in September of 2025.

Speaker #4: While these are certainly not the results we expected, the study had one important positive outcome. In addition to the assessment of dominance trial, STAR121 also evaluated ZIM plus chemo as an exploratory endpoint.

Results from this study are expected in the first half of 2027 and if positive prism 1 could represent the first transformative therapy for an all Comer first line patient population in 30 years.

Speaker #4: ZIM plus chemo performed consistently with respect to overall survival as compared to pembrol plus chemo. These data are consistent with what was observed in numerous studies with ZIM.

Richard Markus: Finally, we recently announced that the Phase 3 STAR-121 study evaluating our anti-TIGIT domvanalimab plus zimberelimab and chemotherapy versus pembrolizumab plus chemotherapy as a first-line treatment for metastatic non-small cell lung cancer will be discontinued due to futility. While these are certainly not the results we expected, the study had one important positive outcome.

There's no biomarker requirement, and no known resistance mechanism. A day that dates have indicated that the rushman was well tolerated.

Finally, we recently announced that the phase 3 star 121 study.

Speaker #4: And this randomized data set provides valuable support for the utility of ZIM as an anti-PD1 combination partner for Arcus and its collaborators. And now I'd like to turn the call over to Juan to discuss our immunology and inflammation programs.

Evaluating our anti- digit. Don vanilla map plus Zim. And chemotherapy.

Versus pemberley zimat. Plus chemotherapy has a first line treatment for metastatic non small cell lung cancer.

We'll be discontinued due to futility.

Speaker #2: Thanks, Richard. Arcus has an exceptional small molecule discovery team that has demonstrated time and time again the ability to create highly effective drug candidates against difficult targets.

Richard Markus: In addition to the assessment of dom in this trial, STAR-121 also evaluated zim plus chemo as an exploratory endpoint. Zim plus chemo performed consistently with respect to overall survival as compared to pembro plus chemo. These data are consistent with what was observed in numerous studies with zim. This randomized data set provides valuable support for the utility of zim as an anti-PD-1 combination partner for Arcus and its collaborators. I'd now like to turn the call over to Juan to discuss our immunology and inflammation programs.

While these are certainly not the results we expected. The study had 1 important positive outcome, and in addition to the assessment of Dominus trial star, 121 also evaluated Zoom plus chemo, has an exploratory endpoint.

Speaker #2: We have been utilizing this expertise to create and develop drugs that have the potential to address very large markets in inflammation, allergy, and autoimmune diseases.

Z-Plus chemo performed consistently with respect to overall survival as compared to pembro plus chemo.

These data are consistent with what was observed in numerous studies with zoom.

Speaker #2: In-house expertise in immunology has been a core aspect of our discovery group since Arcus's funding having been key to many of our oncology programs.

And this randomized data set provides valuable support for the utility of Zim as an anti-PD1 combination partner for Arcus and its collaborators.

Speaker #2: Our team is addressing well-understood and validated mechanisms and has implemented a two-pronged strategy in immunology. First, we leverage our medicinal chemistry capabilities to design and create small molecule drugs that regulate key cytokines.

Juan Heyen: Thanks, Richard. Arcus has an exceptional small molecule discovery team that has demonstrated time and time again the ability to create highly effective drug candidates against difficult targets. We have been utilizing this expertise to create and develop drugs that have the potential to address very large markets in inflammation, allergy, and autoimmune diseases. In-house expertise in immunology has been a core aspect of our discovery group since Arcus' founding, having been key to many of our oncology programs. Our team is addressing well-understood and validated mechanisms and has implemented a two-pronged strategy in immunology. First, we leverage our medicinal chemistry capabilities to design and create small molecule drugs that regulate key cytokines therapeutically validated by existing biologics. Secondly, we target immune cell types that play key roles in human disease and have been historically understudied, such as mast cells and neutrophils.

Juan Jaen: Thanks, Richard. Arcus has an exceptional small molecule discovery team that has demonstrated time and time again the ability to create highly effective drug candidates against difficult targets. We have been utilizing this expertise to create and develop drugs that have the potential to address very large markets in inflammation, allergy, and autoimmune diseases. In-house expertise in immunology has been a core aspect of our discovery group since Arcus' founding, having been key to many of our oncology programs.

And now I'd like to turn the call over to Juan to discuss our immunology and information programs.

Thanks Richard.

Arcus has an exceptional small, molecule Discovery team that has demonstrated time and time again the ability to create

Highly effective drug candidates against difficult targets.

Speaker #2: Therapeutically validated by existing biologics. Secondly, we target immune cell types that play key roles in human disease and have been historically understudied such as mast cells and neutrophils.

We have been utilizing this expertise to create and develop drugs to have the potential to address very large markets.

Inflammation allergy and autoimmune diseases.

Speaker #2: Our first molecule in the immunology area to enter the clinic will be AV102, a highly selective orally bioavailable MRG PRX2 antagonist. In the coming weeks, we will be sharing its preclinical profile in an oral presentation at the Society for Investigative Dermatology.

Juan Jaen: Our team is addressing well-understood and validated mechanisms and has implemented a two-pronged strategy in immunology. First, we leverage our medicinal chemistry capabilities to design and create small molecule drugs that regulate key cytokines therapeutically validated by existing biologics. Secondly, we target immune cell types that play key roles in human disease and have been historically understudied, such as mast cells and neutrophils.

In health expertise in Immunology, has been a core aspect of our Discovery group since Marcus's funding having been key to many of our ecology programs.

Our team is addressing well-understood and validated mechanisms and has implemented a two-prong strategy in immunology.

Speaker #2: The presentation will highlight the ability of AV102 to fully block MRG PRX2 dependent activation and degranulation of mast cells. AV102 inhibits all common human MRG PRX2 variants.

First, we leverage our Medicinal Chemistry capabilities to design and create small molecule drugs, that regulate key Saito, therapeutically validated by existing biologics.

Juan Heyen: Our first molecule in the immunology area to enter the clinic will be AB102, a highly selective orally bioavailable MRGPRX2 antagonist. In the coming weeks, we will be sharing its preclinical profile in an oral presentation at the Society for Investigative Dermatology. The presentation will highlight the ability of AB102 to fully block MRGPRX2 dependent activation and degranulation of mast cells. AB102 inhibits all common human MRGPRX2 variants. We have optimized the potency of AB102 under physiological conditions, such as in human blood and serum. Due to its potency under these conditions, we believe that AB102 is a potential best-in-class once daily oral treatment for chronic spontaneous urticaria and other atopic conditions such as atopic dermatitis, and allergic asthma.

Juan Jaen: Our first molecule in the immunology area to enter the clinic will be AB102, a highly selective orally bioavailable MRGPRX2 antagonist. In the coming weeks, we will be sharing its preclinical profile in an oral presentation at the Society for Investigative Dermatology. The presentation will highlight the ability of AB102 to fully block MRGPRX2 dependent activation and degranulation of mast cells. AB102 inhibits all common human MRGPRX2 variants. We have optimized the potency of AB102 under physiological conditions, such as in human blood and serum.

Secondly, we target immune cell types that play key roles in human disease, and have been historically understudied such as mass cells and neutrofil.

Speaker #2: We have optimized the potency of AV102 under physiological conditions, such as in human blood and serum. Due to its potency under these conditions, we believe that AV102 is a potential best-in-class once-daily oral treatment for chronic spontaneous urticaria and other atopic conditions such as atopic dermatitis and allergic asthma.

The next would be av102 a highly selective orally by available mrgprx2 antagonist.

In the coming weeks, we will be sharing. Its clinical profile in an oral presentation at the society for investigative Dermatology.

Speaker #2: It is expected to enter the clinic in the third quarter of 2026 with TK data available shortly thereafter and potential for proof of concept data in early 2027.

The presentation will highlight the ability of AV102 to fully block MRGPRX2-dependent activation and degranulation of mast cells.

AB, 102 inhibits all common human mrgprx2 variants.

Speaker #2: In rapid succession, we have selected an oral small molecule TNF inhibitor drug candidate which is a potential treatment for rheumatoid arthritis, psoriasis, and inflammatory bowel disease.

Juan Jaen: Due to its potency under these conditions, we believe that AB102 is a potential best-in-class once daily oral treatment for chronic spontaneous urticaria and other atopic conditions such as atopic dermatitis, and allergic asthma.

We have optimized the potency of AV102 under physiological conditions, such as in human blood and serum.

Speaker #2: And an orally active small molecule CCR6 antagonist candidate. As a potential treatment for psoriasis. Both of these molecules are expected to enter the clinic in 2027.

Juan Heyen: It is expected to enter the clinic in Q3 2026, with PK data available shortly thereafter and potential for proof of concept data in early 2027. In rapid succession, we have selected an oral small molecule TNF inhibitor drug candidate, which is a potential treatment for rheumatoid arthritis, psoriasis, and inflammatory bowel disease, and an orally active small molecule CCR6 antagonist candidate as a potential treatment for psoriasis. Both of these molecules are expected to enter the clinic in 2027. We are very excited about the potential for our I&I programs to provide improved options for patients, and we are working to advance these into the clinic as rapidly as possible. I'd now like to turn the call over to Bob to discuss the market opportunity for casdatifan and our financial results.

Juan Jaen: It is expected to enter the clinic in Q3 2026, with PK data available shortly thereafter and potential for proof of concept data in early 2027. In rapid succession, we have selected an oral small molecule TNF inhibitor drug candidate, which is a potential treatment for rheumatoid arthritis, psoriasis, and inflammatory bowel disease, and an orally active small molecule CCR6 antagonist candidate as a potential treatment for psoriasis. Both of these molecules are expected to enter the clinic in 2027.

Speaker #2: We are very excited about the potential for our II programs to provide improved options for patients, and we are working to advance these into the clinic as rapidly as possible.

Due to its potency under these conditions, we delete that AD102 is a potential testing class. Once daily oral treatment, for chronic, spontaneous urticaria, and other atopic conditions, such as atopic dermatitis and allergic asthma.

Speaker #2: I'd now like to turn the call over to Bob to discuss the market opportunity for Castatifan and our financial results.

It is expected to enter the clinic in the third quarter of 2026 with PK data, available shortly thereafter, and potential for proof of concept data in early 2027.

Speaker #3: Thanks, Juan. Before I get into the quarterly financials, I'd like to spend some time on the multibillion-dollar market opportunity in RCC for Castatifan. Sales for RCC drugs in just the major markets are anticipated to grow to $13 billion by 2030.

In Rapid succession. We have selected, an oral small, molecule tnf inhibitor drug candidate, which is a potential treatment for rheumatoid arthritis, psoriasis and inflammatory bowel disease.

Speaker #3: Historically, the market has been dominated by two classes of therapy, IO and TKIs. There have been a number of offerings in both classes which is why the market is fragmented.

Juan Jaen: We are very excited about the potential for our I&I programs to provide improved options for patients, and we are working to advance these into the clinic as rapidly as possible. I'd now like to turn the call over to Bob to discuss the market opportunity for casdatifan and our financial results.

And an orally active, small molecule ccr6, antagonist, candidate as a potential treatment for psoriasis, most of these molecules are expected to enter the clinic in 2027.

Speaker #3: In contrast, there are only two HIF2 alpha inhibitors on the horizon, and we believe our data have demonstrated clear advantages over our only competitor.

We are very excited about the potential for our II programs to provide improved options for patients, and we are working to advance these into the clinic as rapidly as possible.

Speaker #3: We have a clear path to consolidate the market and entrench Castatifan as the primary backbone therapy. The development plan that Terry and Richard described is designed to accomplish this objective.

Bob Gelb: Thanks, Juan. Before I get into the quarterly financials, I'd like to spend some time on the multi-billion dollar market opportunity in RCC for casdatifan. Sales for RCC drugs in just the major markets are anticipated to grow to $13 billion by 2030. Historically, the market has been dominated by two classes of therapy, IO and TKIs. There have been a number of offerings in both classes, which is why the market is fragmented. In contrast, there are only two HIF-2A inhibitors on the horizon, and we believe our data have demonstrated clear advantages over our only competitor. We have a clear path to consolidate the market and entrench casdatifan as the primary backbone therapy. The development plan that Terry and Richard described is designed to accomplish this objective.

Bob Goeltz: Thanks, Juan. Before I get into the quarterly financials, I'd like to spend some time on the multi-billion dollar market opportunity in RCC for casdatifan. Sales for RCC drugs in just the major markets are anticipated to grow to $13 billion by 2030. Historically, the market has been dominated by two classes of therapy, IO and TKIs. There have been a number of offerings in both classes, which is why the market is fragmented. In contrast, there are only two HIF-2A inhibitors on the horizon, and we believe our data have demonstrated clear advantages over our only competitor.

I'd now like to turn the call over to Bob to discuss the market opportunity for custody and and our financial results.

Speaker #3: If we look at the sales for the sole marketed HIF2 alpha inhibitor, Belzudifan, which is currently approved only in late-line clear-cell RCC, it is already generating annual run-rate sales of nearly $1 billion.

Thanks Juan before I get into the quarterly financials, I'd like to spend some time on the multi-billion dollar market opportunity in RCC, for CAD data events.

Salesforce RTC drugs, in just the major markets, are anticipated to grow to $13 billion by 2030.

Speaker #3: Only scratching the surface. With Castatifan, we are also targeting earlier line settings. The IO experienced population with peak 1 and the IO naive first-line population with our next pivotal study.

Speaker #3: These earlier line settings have larger patient populations and longer durations of therapy. Both of which contribute to a much larger market opportunity. Specifically, our peak 1 study targets approximately 20,000 patients in the major markets in the IO experienced setting.

Bob Goeltz: We have a clear path to consolidate the market and entrench casdatifan as the primary backbone therapy. The development plan that Terry and Richard described is designed to accomplish this objective.

Historically, the market has been dominated by 2 classes of therapy IO and tkis. There have been a number of offerings in both classes, which is why the market is fragmented in contrast. There are only 2 hip to Alpha Inhibitors on the horizon and we believe our data have demonstrated clear advantages over our only competitor.

Bob Gelb: If we look at the sales for the sole marketed HIF-2A inhibitor, belzutifan, which is currently approved only in late line clear cell RCC, is already generating annual run rate sales of nearly $1 billion, only scratching the surface. With casdatifan, we are also targeting earlier line settings, the IO experienced population with PEAK-1 and the IO naive first line population with our next pivotal study. These earlier line settings have larger patient populations and longer durations of therapy, both of which contribute to a much larger market opportunity. Specifically, our PEAK-1 study targets approximately 20,000 patients in the major markets in the IO experienced setting. We believe our commercial opportunity here exceeds $2 billion. In the first line, the opportunity is even greater.

Bob Goeltz: If we look at the sales for the sole marketed HIF-2A inhibitor, belzutifan, which is currently approved only in late line clear cell RCC, is already generating annual run rate sales of nearly $1 billion, only scratching the surface. With casdatifan, we are also targeting earlier line settings, the IO experienced population with PEAK-1 and the IO naive first line population with our next pivotal study. These earlier line settings have larger patient populations and longer durations of therapy, both of which contribute to a much larger market opportunity.

Speaker #3: We believe our commercial opportunity here exceeds $2 billion. In the first line, the opportunity is even greater. With the lack of HIF2 alpha inhibitor competition in the front line, our goal is to grow the IO/IO share from roughly a third of the market to more than half by adding CAS.

We have a clear path to consolidate the market and entrench C data. Fan, as the primary backbone therapy, the development plan, Mary and Richard described is designed to accomplish this objective. If we look at the sales for the sole Market, it is to Alpha inhibitor belud, which is currently approved only in late line. Clear, cell RCC, is already generating annual run rate, sales of nearly 1 billion dollars only scratching the surface

Speaker #3: In fact, our market research indicates that oncologists overwhelmingly prefer the promise of a CAS plus IO/IO over a TKI-containing regimen. As Richard mentioned, we also plan to investigate a regimen with IO and TKI in the front line to address the remainder of the market.

With cast data fan, we are also targeting early lines. The iio Experience population with Peak 1 and the io naive first line population with our next pivotal study.

Bob Goeltz: Specifically, our PEAK-1 study targets approximately 20,000 patients in the major markets in the IO experienced setting. We believe our commercial opportunity here exceeds $2 billion. In the first line, the opportunity is even greater.

These earlier lines settings, have larger patient, populations and longer durations of therapy both of which contribute to a much larger market opportunity.

Speaker #3: We believe the opportunity for Castatifan in the front line exceeds $4 billion. One point I'd really like to emphasize as we think about the commercial opportunity is duration of treatment.

Specifically our Peak 1 Study targets, approximately 20,000 patients in the major markets in the io experience setting.

We believe our commercial opportunity here exceeds 2 billion dollars.

Bob Gelb: With the lack of HIF-2A inhibitor competition in the front line, our goal is to grow the IO IO share from roughly a third of the market to more than half by adding Cas. In fact, our market research indicates that oncologists overwhelmingly prefer the promise of a Cas plus IO IO over a TKI-containing regimen. As Richard mentioned, we also plan to investigate a regimen with IO and TKI in the front line to address the remainder of the market. We believe the opportunity for Casdatifan in the front line exceeds $4 billion. One point I'd really like to emphasize as we think about the commercial opportunity is duration of treatment. We've seen impressive data in late line monotherapy, with many patients on therapy beyond 18 months.

Bob Goeltz: With the lack of HIF-2A inhibitor competition in the front line, our goal is to grow the IO IO share from roughly a third of the market to more than half by adding Cas. In fact, our market research indicates that oncologists overwhelmingly prefer the promise of a Cas plus IO IO over a TKI-containing regimen. As Richard mentioned, we also plan to investigate a regimen with IO and TKI in the front line to address the remainder of the market. We believe the opportunity for Casdatifan in the front line exceeds $4 billion.

Speaker #3: We've seen impressive data in late-line monotherapy with many patients on therapy beyond 18 months. We plan to share updated data later this year. As we think about earlier lines of therapy, we believe there is the potential for meaningful upside resulting from the durability of effect.

In the first line, the opportunity is even greater with the lack of hip to Alpha. Inhibitor competition in the front line, our goal is to grow the ayo ayo share from roughly, a third of the market.

To more than half by adding tasks.

Speaker #3: Conceptually, we think strong HIF2 alpha inhibition holds the promise of a long-term tail effect. All in, we think CAS has a peak sales opportunity of $5 to $10 billion.

In fact, our market research indicates that oncologists overwhelmingly prefer the promise of a CAST plus AYO-AYO over a TKI-containing regimen.

Speaker #3: As a reminder, we own all of the commercial rights to CAS other than in Japan, and certain other Southeast Asian countries held by our partner Taiho.

Bob Goeltz: One point I'd really like to emphasize as we think about the commercial opportunity is duration of treatment. We've seen impressive data in late line monotherapy, with many patients on therapy beyond 18 months.

As Richard mentioned, we also plan to investigate a regimen with IO and tki in the front line to address the remainder of the market. We believe the opportunity for Cas data fan in the front line exceeds 4. 0.

Speaker #3: Now let's turn to the financials. Arcus is well-positioned to advance its full pipeline with 876 million in cash at the end of the quarter.

Bob Gelb: We plan to share updated data later this year. As we think about earlier lines of therapy, we believe there is the potential for meaningful upside resulting from the durability of effect. Conceptually, we think strong HIF-2 alpha inhibition holds the promise of a long-term tail effect. All in, we think CAS has a peak sales opportunity of $5 to 10 billion. As a reminder, we own all of the commercial rights to CAS other than in Japan and certain other Southeast Asian countries held by our partner, Taiho. Now let's turn to the financials. Arcus is well-positioned to advance its full pipeline with $876 million in cash at the end of the quarter. We have cash runway until at least the H2 of 2028.

Bob Goeltz: We plan to share updated data later this year. As we think about earlier lines of therapy, we believe there is the potential for meaningful upside resulting from the durability of effect. Conceptually, we think strong HIF-2 alpha inhibition holds the promise of a long-term tail effect. All in, we think CAS has a peak sales opportunity of $5 to 10 billion. As a reminder, we own all of the commercial rights to CAS other than in Japan and certain other Southeast Asian countries held by our partner, Taiho. Now let's turn to the financials.

1 point. I'd really like to emphasize as we think about the commercial opportunity is duration of treatment. We've seen impressive data in late line, monotherapy, with many patients on therapy, Beyond 18 months,

Speaker #3: We have cash runway until at least the second half of 2028. We expect to end 2026 with approximately $600 million in cash. Indicative of the declining spend we expect over the year.

We plan to share updated data later this year.

As we think about earlier lines of therapy, we believe there's the potential for Meaningful upside resulting from the durability of effect.

Speaker #3: As Terry outlined, Arcus is entering a new era with more control over our pipeline investments. While we are building a plan to take full advantage of the Castatifan opportunity, we are also sequencing these investments such that any significant growth in overall spend will be largely incurred after a peak 1 readout.

Conceptually we think strong have 2 Alpha inhibition holds the promise of a long-term tail effect.

As a reminder, we own all of the commercial rights to cast other than in Japan and certain other Southeast Asian countries held by our partner Tayo.

Bob Goeltz: Arcus is well-positioned to advance its full pipeline with $876 million in cash at the end of the quarter. We have cash runway until at least the H2 of 2028.

Speaker #3: As a result of the wind-down of DOM and reduced spend on Quenly, together with broader spend management, we expect to significantly reduce our overall R&D spend in 2026 and 2027 compared to 2025.

Now, let's turn to the financials Arcus is well positioned to advance its full Pipeline with 876 million in cash. At the end of the quarter.

Bob Gelb: We expect to end 2026 with approximately $600 million in cash, indicative of the declining spend we expect over the year. As Terry outlined, Arcus is entering a new era with more control over our pipeline investments. While we are building a plan to take full advantage of the casdatifan opportunity, we are also sequencing these investments such that any significant growth in overall spend will be largely incurred after a PEAK-1 readout. As a result of the wind down of Dom and reduced spend on Quemly, together with broader spend management, we expect to significantly reduce our overall R&D spend in 2026 and 2027 compared to 2025. For example, as our late-stage efforts have become focused on casdatifan, we have decreased our headcount by approximately 10%. Let me transition to the financials for the quarter.

Bob Goeltz: We expect to end 2026 with approximately $600 million in cash, indicative of the declining spend we expect over the year. As Terry outlined, Arcus is entering a new era with more control over our pipeline investments. While we are building a plan to take full advantage of the casdatifan opportunity, we are also sequencing these investments such that any significant growth in overall spend will be largely incurred after a PEAK-1 readout.

Speaker #3: For example, as our late-stage efforts have become focused on Castatifan, we have decreased our headcount by approximately 10%. Let me transition to the financials for the quarter.

We have cash Runway until at least the second half of 2028. We expect to end 2026 with approximately 600 million in cash and indicative of the decline in spend, we expect over the year.

As Terry outlined Arcus is entering a new era with more control over our pipeline Investments.

Speaker #3: For our P&L, we recognize gap revenue for the first quarter of $17 million. Our revenue continues to be primarily driven by our collaboration agreements.

Speaker #3: We continue to expect to recognize gap revenue of $50 to $65 million for the full year of 2026. Our R&D expenses for the first quarter are stated net of reimbursements and were $122 million, and included non-recurring workforce costs.

Bob Goeltz: As a result of the wind down of Dom and reduced spend on Quemly, together with broader spend management, we expect to significantly reduce our overall R&D spend in 2026 and 2027 compared to 2025. For example, as our late-stage efforts have become focused on casdatifan, we have decreased our headcount by approximately 10%. Let me transition to the financials for the quarter.

While we are building a plan to take full advantage of the cast out ofan opportunity. We are also sequencing these Investments such as any significant growth in overall, spend will be largely incurred after a peak 1 read out.

Speaker #3: Our actions to reduce headcount have lowered our ongoing cost structure which we expect will result in reduced R&D expense and future periods. The discontinuation of STAR 121 and the broader reduction in our DOM-related investment will contribute to a meaningful decrease in R&D expenses as the year goes on.

As a result of the wind down of Dom and reduced spend on quenley together with broader spend management. We expect a significantly reduce our overall R&D. Spend in 2026 and 2027 compared to 2025.

For example.

As our late stage efforts have become focused on CAD data fans, we have decreased our headcount by approximately 10%.

Bob Gelb: For our P&L, we recognize GAAP revenue for Q1 of $17 million. Our revenue continues to be primarily driven by our collaboration agreements. We continue to expect to recognize GAAP revenue of $50 to 65 million for the full year of 2026. Our R&D expenses for Q1 are stated net of reimbursements and were $122 million and included non-recurring workforce costs. Our actions to reduce headcount have lowered our ongoing cost structure, which we expect will result in reduced R&D expense in future periods. The discontinuation of STAR-121 and the broader reduction in our Dom-related investment will contribute to a meaningful decrease in R&D expenses as the year goes on. By 2027, we expect more than 80% of our portfolio spend will be directed toward CAS development.

Bob Goeltz: For our P&L, we recognize GAAP revenue for Q1 of $17 million. Our revenue continues to be primarily driven by our collaboration agreements. We continue to expect to recognize GAAP revenue of $50 to 65 million for the full year of 2026. Our R&D expenses for Q1 are stated net of reimbursements and were $122 million and included non-recurring workforce costs. Our actions to reduce headcount have lowered our ongoing cost structure, which we expect will result in reduced R&D expense in future periods.

Let me transition to the financials for the quarter.

Speaker #3: By 2027, we expect more than 80% of our portfolio spend will be directed toward CAS development. DNA expenses were $29 million for the first quarter.

For our P&L, we recognize GAAP revenue for the first quarter of $17 million.

Our Revenue continues to be primarily driven by our collaboration agreements.

We continue to expect to recognize gaap revenue of 50 to 65 million for the full year 2026.

Speaker #3: Total non-cash stock-based compensation was $19 million for the first quarter. For more details regarding our financial results, please refer to our earnings press release from earlier today and our 10-Q.

Our R&D expenses for the first quarter are stated net of reimbursements and we're 122 million and included non-recurring Workforce costs,

Speaker #3: I will now turn it back to Terry.

Speaker #2: Thanks, Bob. That was awesome. Let me close by summarizing the key themes for the remainder of 2026. Castatifan is our number one priority and this year will be another transformative year for data and, importantly, development as we advance towards commercialization.

Bob Goeltz: The discontinuation of STAR-121 and the broader reduction in our Dom-related investment will contribute to a meaningful decrease in R&D expenses as the year goes on. By 2027, we expect more than 80% of our portfolio spend will be directed toward CAS development.

Our actions to reduce head count. Have lowered our ongoing cost structure which we expect will result in reduced R&D expense in future periods.

The discontinuation of star 121 and the broader reduction in our Dom related investment, will contribute to a meaningful decrease in R&D expenses as the year goes on.

Speaker #2: We expect multiple data sets: CAS plus CABO data, initial first-line data and overall survival data from late-line monotherapy cohorts, all of which will further reinforce Castatifan's best-in-class profile and support our registrational strategy.

By 2027, we expect more than 80% of our portfolio. Spend will be directed towards cast development.

Bob Gelb: G&A expenses were $29 million for Q1. Total non-cash stock-based compensation was $19 million for Q1. For more details regarding our financial results, please refer to our earnings press release from earlier today and our 10-Q. I will now turn it back to Terry.

Bob Goeltz: G&A expenses were $29 million for Q1. Total non-cash stock-based compensation was $19 million for Q1. For more details regarding our financial results, please refer to our earnings press release from earlier today and our 10-Q. I will now turn it back to Terry.

GNA expenses are 29 million for the first quarter.

Total non-cash stock-based compensation was $19 million for the first quarter.

Speaker #2: Peak 1 enrollment continues to accelerate and we're targeting full enrollment by year-end. All of the clinical development plans for Castatifan that were discussed today are accounted for within our existing budgets and have no impact on our guidance or runway.

Terry Rosen: Thanks, Bob. That was awesome. Let me close by summarizing the key themes for the remainder of 2026. casdatifan is our number one priority. This year will be another transformative year for data and importantly, development, as we advance towards commercialization. We expect multiple datasets, CAS plus cabo data, initial first line data, and overall survival data from late line monotherapy cohorts, all of which will further reinforce casdatifan's best-in-class profile and support our registrational strategy. PEAK-1 enrollment continues to accelerate. We're targeting full enrollment by year-end. All of the clinical development plans for casdatifan that were discussed today are accounted for within our existing budgets and have no impact on our guidance or runway. Beyond casdatifan, our PRISM-1 Phase 3 trial for quemliclustat pancreatic cancer is fully enrolled and on track for a readout in H1 2027.

For more details regarding our financial results, please refer to our earnings press release from earlier today, and our 10 Q, I will now turn it back to Terry. Thanks Bob, that was awesome. Let me close by summarizing the key themes for the remainder of 2026.

Speaker #2: Beyond Castatifan, our Prism 1 phase 3 trial for Quenly pancreatic cancer is fully enrolled and on track for a readout in the first half of 2027.

Speaker #2: Juan shared the exciting progress on our INI portfolio with AB102 expected to enter the clinic in the third quarter and our TNF inhibitor and CCR6 antagonist following shortly thereafter.

Just the other fan is our number 1 priority and this year will be another transformative year for data. And importantly development, as we advance towards commercialization, we expect multiple data sets, cashless Cabo data, initial first line data and overall survival data from weight line. Monotherapy cohorts, all of which will further reinforce cast data fans, best-in-class, profiles, and support, our registration of strategy.

Speaker #2: With 876 million in cash and investments and runway into the second half of 2028, we're well-positioned to execute on all of these priorities and create significant value for patients and shareholders.

Terry Rosen: All of the clinical development plans for casdatifan that were discussed today are accounted for within our existing budgets and have no impact on our guidance or runway. Beyond casdatifan, our PRISM-1 Phase 3 trial for quemliclustat pancreatic cancer is fully enrolled and on track for a readout in H1 2027.

Speaker #2: We're moving into a new era for Arcus with full ownership of our lead program Castatifan and a clear strategy to win and transform the front-line setting.

Peak 1 enrollments to accelerate and we're targeting full enrollment by year at all of the clinical development plans, for kids data and that were discussed today, our accounted for within our existing budget, and have no impact on our guides or Runway

Speaker #2: While rapidly advancing the next generation of wholly owned molecules for inflammation and immunology. We have no doubt that we will be generating disproportionate value for patients and shareholders over the coming 12 to 18 months.

Terry Rosen: Juan shared the exciting progress on our I&I portfolio, with AB102 expected to enter the clinic in Q3 and our TNF inhibitor and CCR6 antagonist following shortly thereafter. With $876 million in cash and investments and runway into H2 2028, we're well-positioned to execute on all these priorities and create significant value for patients and shareholders. We're moving into a new era for Arcus with full ownership of our lead program, casdatifan, and a clear strategy to win and transform the frontline setting while rapidly advancing the next generation of wholly owned molecules for inflammation and immunology. We have no doubt that we will be generating disproportionate value for patients and shareholders over the coming 12 to 18 months. Thank you all for joining us.

Speaker #2: Thank you all for joining us. We appreciate your interest in continued support of Arcus and we will now open the call for questions.

Beyond CAST data events, our PRISM 1, Phase 3 trial for QUADLIE and pancreatic cancers is fully enrolled and on track for a readout in the first half of 2027. Juan shared the exciting progress on our INI portfolio, with AV102 expected to enter the clinic in the third quarter and our TNF inhibitor and CCR6 antagonist following shortly thereafter.

Speaker #3: We will now begin the question and answer session. Please will let yourself to one question and one follow-up. If you would like to ask a question, please press STAR 1 to raise your hand.

with 876 million in cash and Investments and Runway into the second half of 2028. We're well positioned to execute on all these priorities and create significant value for patients and shareholders.

Speaker #3: To withdraw your question, press STAR 1 again. We ask that you pick up your handset when asking a question to follow for optimum sound quality.

Speaker #3: If you are muted locally, please remember to unmute your device. Please stand by while we compile the Q&A roster. Your first question comes from the line of Diana Graybosch with Learink Partners.

Terry Rosen: We have no doubt that we will be generating disproportionate value for patients and shareholders over the coming 12 to 18 months. Thank you all for joining us.

We're moving into a new era for our kids, with full ownership of our lead program kit data plan and a clear strategy to win and transform the Frontline setting. While rapidly advancing the next generation of wholly owned molecules for inflammation and Immunology. We have no doubt that we will be generating disproportionate value for patients and shareholders. Over the coming 12 to 18 months,

Terry Rosen: We appreciate your interest and continued support of Arcus, and we will now open the call for questions.

Speaker #3: Diana, your line is now open.

Thank you all for joining us. We appreciate your interest and continued support of our efforts, and we will now open the call for questions.

Speaker #2: Hi, David. Did you change your name?

Operator: We will now begin the question and answer session. Please limit yourself to one question and one follow-up. If you would like to ask a question, please press star one to raise your hand. To withdraw your question, press star one again. We ask that you pick up your handset when asking a question to follow for optimum sound quality. If you are muted locally, please remember to unmute your device. Please stand by while we compile the Q&A roster. Your first question comes from the line of Diana Grabosch with Leerink Partners. Diana, your line is now open.

Speaker #4: Yeah. No, not yet, but that's okay. Tell us about the CAS TKI front-line combo. Specifically, we all know Merck failed with that triplet mechanistically with Bell's Lenva Pembro.

You will now begin the question and answer session, please. When let yourself to 1 question and 1 follow up. If you would like to ask a question, please press star 1 to raise your hand to withdraw. Your question, press star 1 again.

Speaker #4: And that's the LightSpark 12. We have to press release; we don't know the detailed data. What could you see in that detailed data that would give you more confidence in CAS TKI IO, and what could you see in the Merck data that would give you less confidence in the TKI combo strategy?

You are muted locally. Please remember to unmute your device.

Please stand by while we compile the Q&A roster.

Your first question comes from the line of Diana. Grey Bosch with leerink Partners. Diana. Your line is now open.

Speaker #2: Thanks, Dada. I think we'll see what their data say, but I think the data that are out there tell us a lot already. So if you consider what we discussed at the beginning, that pharmacodynamic difference between Castatifan and Belzutafan, not only the depth of response but particularly the durability, and you think of that as a surrogate for its anti-tumor activity and a direct measure of its ability to inhibit HIF2.

Bob Gelb: Hi, Diana. Did you change your name?

Terry Rosen: Hi, Diana. Did you change your name?

Diana Grabosch: Wow, some real surprises today. Yeah. No, not yet, but that's okay. Tell us about the CAS TKI frontline combo. Specifically, we all know Merck failed with that triplet mechanistically with Bells, Lenva, Pembro, and that's the LITESPARK-012. We have the press release. We don't know the detailed data. What could you see in that detailed data that would give you more confidence in CAS TKI IO, and what could you see in the Merck data that would give you less confidence?

Diana Graybosch: Wow, some real surprises today. Yeah. No, not yet, but that's okay. Tell us about the CAS TKI frontline combo. Specifically, we all know Merck failed with that triplet mechanistically with Bells, Lenva, Pembro, and that's the LITESPARK-012. We have the press release. We don't know the detailed data. What could you see in that detailed data that would give you more confidence in CAS TKI IO, and what could you see in the Merck data that would give you less confidence?

Today.

No, not yet, but that's okay. Uh,

Tell us about the cast. Tki Frontline combo, specifically, we all know Mercedes with that triplet mechanistically with bells, lamba pembro. And that's the light, spark 12. We have the press release. We don't know the detailed data. What could you see in that detail data that would give you more confidence?

Diana Grabosch: The TKI combo strategy.

Diana Graybosch: The TKI combo strategy.

Speaker #2: I think what you can reconcile very easily is even in the absence of the data from the study itself, if you think about LightSpark 011 versus LightSpark 012, the duration of the treatment that you're talking about, when you think about PFS, roughly for the two different studies, is almost two X.

In cast, eki IO. And what could you see in the Merc data? That would give you less confidence.

In the tki combo strategy.

Terry Rosen: Thanks, Dana. I think we'll see what their data say, but I think the data that are out there tell us a lot already. If you consider what we discussed at the beginning, that pharmacodynamic difference between casdatifan and belzutifan, not only the depth of response, but particularly the durability. You think of that as a surrogate for its antitumor activity and a direct measure of its ability to inhibit HIF-2. I think what you can reconcile very easily is even in the absence of the data from the study itself, if you think about LITESPARK-011 versus LITESPARK-012, the duration of the treatment that you're talking about when you think about PFS roughly for the two different studies is almost 2x.

Speaker #2: So if you recognize that Belzutafan is whatever that surrogate for HIF2 inhibition directly relates to an inhibition of the tumor, it's clearly losing that effect with time and dramatically.

Great data. I think, um, we'll see what their data say. But I think the data that are out there, um, tell us a lot already. So, uh, if you, uh, consider what we discussed at the beginning, that, um, pharmacodynamic difference, between uh, cast data fan and belza fan. Uh, not only is the depth of response, but particularly the durability and you think of that as a surrogate for um, it says like tumor activity

Speaker #2: So you see at least on erythropoietin production on the average, you've lost that effect within 9 to 13 weeks. So when you think about it in the second-line population, the percentage of time where it's bringing benefit is X, and then in the front line, it's much less.

Terry Rosen: If you recognize that belzutifan is whatever that surrogate for HIF-2 inhibition directly relates to inhibition of the tumor, it's clearly losing that effect with time and dramatically. You see, at least on erythropoietin production, on the average, you've lost that effect within, you know, 9 to 13 weeks. When you think about it, in the second line population, the percentage of time where it's bringing benefit is X, in the front line it's much less. On top of that, if you think about the regimen, it, you know, it's pretty toxic regimen. Even pembro-lenva had about 37% rate of discontinuation. We know that the triplet was, you know, pretty unfavorable from a, you know, patient perspective.

In a direct measure of its ability to inhibit hif 2. I think what you can, um, reconcile very easily is even in the absence of the data from the study itself. If you think about, um, light spark 011 versus Light, spark 012, uh, the duration of the treatment that you're talking about, when you think about PFS roughly for the the 2 different, um, studies is almost 2X

Speaker #2: Then on top of that, if you think about the regimen, it's pretty toxic regimen. So even Pembro Lenva had about a 37% rate of discontinuation.

Speaker #2: We know that the triplet was pretty unfavorable from a patient perspective. So if you think about basically you're having diminishing effect of the HIF2 inhibitor on top of a much longer duration of an arm that has more AEs than the control arm, so you're basically getting paying a price but getting less benefit.

Speaker #2: So it's not surprising that you would end up with a hazard ratio that might not be too favorable. For us, we're going to select a TKI that we think has a very favorable relative to the group of TKIs out there profile.

So if you recognize that belzutifan uh is whatever that um surrogate for H tuna Vision directly relates to um an inhibition in the tumor. It's clearly losing that effect with time and dramatically. So you see at least on arithmetic production uh, on the average you've lost, um, that effect within, um, you know, 9 to 13 weeks. So, when you think about it in the second line population, the percentage of time where it's bringing benefits is X, and then in the front line, it's much less than on top of that. If you think about the regimen, it's you know, it's pretty toxic regimen. So even uh, pemro Lena had about a 37% rate of discontinuation, we know that the trip it was, you know,

Terry Rosen: If you think about basically you're having diminishing effect of the HIF-2 inhibitor on top of a much longer duration of an arm that has more AEs than the control arm. You're basically getting, you know, paying a price but getting less benefit. It's not surprising that you would end up with a hazard ratio that might not be too favorable. For us, we're gonna select a TKI that we think, you know, has a very favorable relative to the TKIs out there profile. The most important feature will be that we have a HIF-2 inhibitor that has its robust effect, and the durability of that effect is essentially the same on day 1 as it is on, you know, day, you know, 730.

Speaker #2: But the most important feature will be that we have a HIF2 inhibitor that has its robust effect in the durability of that effect is essentially the same on day one as it is on day 730.

Uh, pretty unfavorable from a, you know, patient, um uh uh perspective. So if you think about basically, you're having diminished diminishing effect of the H2 inhibitor,

Speaker #3: Got it. Thank you very much.

Speaker #2: Thanks, Dana.

Speaker #3: Your next question comes from the line of Jonathan Miller with Evercore. Jonathan, your line is now open.

Speaker #5: Hi, guys. Thanks for taking my question and congrats on all the progress. I guess looking at a very broad CAS development plan here with a lot of combinations and across first, second, third-line settings, one thing that's notably absent is any approach in the adjuvant setting, which obviously we know Merck is going after.

On top of a much longer duration of uh an arm that has more ease than the control arm. So you're basically getting, you know, paying a price but getting less benefit. So it's not surprising that you would end up with a A Hazard ratio uh, that that might not be too favorable for us. We're we're going to select a tki that we think you know has a very favorable relative to the K is out there um profile. But the most important feature will be that we have a hip 2 inhibitor that has its robust. Uh, effect in the durability of that effect is essentially the same on day 1 as it is on, you know, day, you know, 730.

Speaker #5: So I'd love to hear your updated thoughts on adjuvant and why that's missing from the current development plan. And then related to that, I guess, or the flip side of that is relatively recently, as recently as relatively recently, you were talking about a more conservative approach to late-stage development for CAS, at least with respect to the number of phase three trials you would want to start.

Diana Grabosch: Got it. Thank you very much.

Diana Graybosch: Got it. Thank you very much.

Terry Rosen: Thanks, Dana.

Got it. Thank you very much.

Thanks Pam.

Operator: Your next question comes from the line of Jonathan Miller with Evercore. Jonathan, your line is now open.

Jonathan Miller: Hi guys. Thanks for taking my question and congrats on all the progress. I guess looking at a very broad cas development plan here with a lot of combinations and across first, second, third line settings, one thing that's notably absent is any approach in the adjuvant setting, which obviously we know Merck is going after. I'd love to hear your updated thoughts on adjuvant and why that's missing from the current development plan. Related to that, I guess, or the flip side of that is relatively recently, as recently as relatively recently, you were talking about a more conservative approach to late stage development for cas, at least with respect to the number of phase 3 trials you would wanna start.

Your next question comes from the line of Jonathan Miller with Evercore. Jonathan, your line is now open.

Speaker #5: You were considering going after partnerships to ameliorate the cost of late-stage development. Obviously, there's been a bit of a shift there, but Terry and Bob, I heard you say we don't expect to see any impact on runway or the ability to prosecute all these different programs.

Speaker #5: So I'd love to get a little bit more granularity on the sequencing that you're talking about and when you would start these TKI containing and potential novel combo development efforts to enable you to pursue all of these different approaches without running up against the bandwidth limitations.

Jonathan Miller: Related to that, I guess, or the flip side of that is relatively recently, as recently as relatively recently, you were talking about a more conservative approach to late stage development for cas, at least with respect to the number of phase 3 trials you would wanna start.

Jonathan Miller: You were considering going after partnerships to ameliorate the cost of late-stage development. Obviously there's been a bit of a shift there, but Terry and Bob, I heard you say, we don't expect to see any impact on runway or the ability to prosecute all these different programs. I'd love to get a little bit more granularity on the sequencing that you're talking about and when you would start these TKI-containing and potential novel combo development efforts to enable you to pursue all of these different approaches without running up against the bandwidth limitations. Thanks.

Speaker #5: Thanks.

Speaker #2: Thanks a lot. Thanks, John. And I'll let Bob handle that, and then I may have a few comments to add.

Speaker #6: Yeah. In terms of the adjuvant setting, I think for us, it comes down to two simple things. One is the size of the opportunity and probably more importantly is the need.

Speaker #6: So when you think about that particular setting, we think that it's around 12,000 patients or so that get therapy in the adjuvant setting. It's only the high-risk patients, with resection.

Speaker #6: And their treatments capped at a year. And so when you actually do the math on that, we actually think that the opportunity certainly from a revenue perspective is probably certainly smaller than the second-line and probably even smaller than what could be a third-line regimen with an alternate TKI as we described.

Terry Rosen: Thanks a lot. Thanks, John. I'll let Bob handle that and then I may have a few comments to add.

Usually is relatively recently you were talking about a more conservative approach to late late stage development for cash, at least, with respect to the number of phase, 3 trials, you would want to start. You were considering going after Partnerships to amilyar the cost of late stage development, and obviously there's been a bit of a shift there. But Terry, and Bob, I heard you say, uh, we don't expect to see any impact on Runway or the ability to prosecute all these, uh, different, uh, uh, programs. So I'd love to get a little bit more granularity on the sequencing that you're talking about. And when you would start these tki containing, uh, and potential novel combo, uh, development, uh efforts, uh, to enable you to pursue all of these different approaches, uh, without running up against the bandwidth limitations. Thanks.

Bob Gelb: Yeah, in terms of the adjuvant setting, I think for us it comes down to two simple things. One is, you know, the size of the opportunity and probably more importantly is the need. When you think about that particular setting, we think that it's around 12,000 patients or so that get therapy in the adjuvant setting. It's only the high-risk patients with resection, and their treatment's capped at a year. When you actually do the math on that, we actually think that the opportunity, certainly from a revenue perspective, is probably certainly smaller than the second line and probably even smaller than what could be a third-line regimen with an alternate TKI as we described.

Bob Goeltz: Yeah, in terms of the adjuvant setting, I think for us it comes down to two simple things. One is, you know, the size of the opportunity and probably more importantly is the need. When you think about that particular setting, we think that it's around 12,000 patients or so that get therapy in the adjuvant setting. It's only the high-risk patients with resection, and their treatment's capped at a year. When you actually do the math on that, we actually think that the opportunity, certainly from a revenue perspective, is probably certainly smaller than the second line and probably even smaller than what could be a third-line regimen with an alternate TKI as we described.

Speaker #6: I think the other important part is we've had a chance to talk to physicians after seeing the LightSpark 12 data. And the bar to add another therapy on top of Pembro is considered quite high.

Speaker #6: In fact, most physicians told us that they actually wouldn't add Belzutafan to the regimen even in light of the LightSpark 12 data. So we actually think it'll be a minority of patients that ultimately will receive Belzutafan in that setting.

Thanks a lot. Thanks John and uh uh Bob will handle that and then I may have a few comments to add. Yeah. In terms of as you been setting, I think for us it comes down to 2 simple. Um, things 1 is, you know, the size of the opportunity and probably more importantly is the need. Um, so when you think about that, that particular setting, we think that it's around 12,00 patients or so that get therapy in the adjuvant setting, uh, it's only the high-risk patients, um, with reception and their treatment is capped at a year. Um, and so when

Speaker #6: So it's prioritization. And frankly, the other settings and first, second, and third line are higher on the list for us. And so that's sort of why we've made the decision that we have from an adjuvant perspective.

Bob Gelb: I think the other important part is we've had a chance to talk to physicians after seeing the LITESPARK-012 data. The bar to add another therapy on top of pembrolizumab is considered quite high. In fact, most physicians told us that they actually wouldn't add belzutifan to the regimen even in light of the LITESPARK-012 data. We actually think it'll be a minority of patients that ultimately will receive belzutifan in that setting. You know, it's prioritization and frankly, the other settings in first, second, and third line are higher on the list for us. That's sort of why we've made the decision that we have from an adjuvant perspective. In terms of the sequencing of the spend, as we highlighted, we have PEAK-1 up and enrolling right now.

Bob Goeltz: I think the other important part is we've had a chance to talk to physicians after seeing the LITESPARK-012 data. The bar to add another therapy on top of pembrolizumab is considered quite high. In fact, most physicians told us that they actually wouldn't add belzutifan to the regimen even in light of the LITESPARK-012 data. We actually think it'll be a minority of patients that ultimately will receive belzutifan in that setting. You know, it's prioritization and frankly, the other settings in first, second, and third line are higher on the list for us. That's sort of why we've made the decision that we have from an adjuvant perspective. In terms of the sequencing of the spend, as we highlighted, we have PEAK-1 up and enrolling right now.

Speaker #6: In terms of the sequencing of the spend, as we highlighted, we have peak one up and enrolling right now. Our goal is to have the study enrolled by the end of the year.

When you actually do the math on that, we actually think that the opportunity certainly from a revenue perspective is probably certainly smaller than the second line and probably even smaller than what could be a third line regimen with uh an alternate tki as we described. I think the other important part is we've had a chance to talk to Physicians after seeing the light spark 12 data and

Speaker #6: The work towards launching these additional phase three studies would have us in a position to sort of move those studies forward as early as late this year, into next year with obviously probably our highest priority being that front-line combination with IPPY and anti-PD1.

Speaker #6: But the other studies will be shortly on the heels. But if you think about just sort of the general investment profile for the studies, we'll be through the bolus of study startup for peak one.

Speaker #6: And the cost profile for peak one will be starting to decrease as we get into the second half of next year. So we kind of feel like that it's going to be a nice portfolio effect that when we think about these other studies, kicking in really from a spend perspective in late 2027 and into 2028, we sort of see a generally steady spend profile through the peak one readout like we described.

The bar to add another uh therapy. On top of pembro is considered quite high. In fact, most Physicians told us that they actually wouldn't add belza fan uh to the regimen even in light of the light, spark 12 data. So we actually think it'll be a minority of, uh, patients that ultimately will receive Belden in that setting. So, you know, it's it's prioritization and and frankly, the other settings in first second, and third line are higher on the list for us. And and so that's sort of why we've made the decision that we have from an agent perspective. In terms of the sequencing of the spend

as we highlighted, we have, um,

Bob Gelb: Our goal is to have the study enrolled by the end of the year. The work towards launching these additional Phase 3 studies, you know, would have us in a position to sort of move those studies forward, you know, as early as late this year into next year, with obviously probably our highest priority being that frontline combination with ipi and anti-PD-1. The other studies will be shortly on the heels. If you think about just sort of the general investment profile for the studies, we'll be through the bolus of study startup for PEAK-1, and the cost profile for PEAK-1, you know, will be starting to decrease as we get into H2 of next year.

Bob Goeltz: Our goal is to have the study enrolled by the end of the year. The work towards launching these additional Phase 3 studies, you know, would have us in a position to sort of move those studies forward, you know, as early as late this year into next year, with obviously probably our highest priority being that frontline combination with ipi and anti-PD-1. The other studies will be shortly on the heels. If you think about just sort of the general investment profile for the studies, we'll be through the bolus of study startup for PEAK-1, and the cost profile for PEAK-1, you know, will be starting to decrease as we get into H2 of next year.

Speaker #2: And John, and I'll Bob kind of gave you the line of the spend along with the studies. And I'll give you a little bit more granularity on how we literally see the trials themselves playing out.

Peak 1 up and enrolling. Right now, our goal is to have the study enrolled by the end of the year. Uh the work towards launching these additional phase 3 studies, you know, would have us in a position to to sort of move those studies forward. You know, as early as late this year into next year with obviously probably our highest priority being that front line combination with ipy and anti-pd1. Um, but the other studies

Speaker #2: So the first study, obviously peak one, that's enrolling, as Bob said, it'll be fully enrolled by the end of this year. And then we'll be waiting for readout.

Bob Gelb: We kind of feel like that it's gonna be a nice portfolio effect that when we think about these other studies kicking in, really from a spend perspective in late 2027 and into 2028, we sort of see a generally steady spend profile through the PEAK-1 readout like we described.

Bob Goeltz: We kind of feel like that it's gonna be a nice portfolio effect that when we think about these other studies kicking in, really from a spend perspective in late 2027 and into 2028, we sort of see a generally steady spend profile through the PEAK-1 readout like we described.

Speaker #2: We're going full speed ahead and expect that IPPY, anti-PD1 CAS, as we've been talking about for some time, to be getting up and going by the end of this year.

Terry Rosen: Hey, John, Bob kind of gave you the line of the spend along with the studies. I'll give you a little bit more granularity on how we literally see the trials themselves playing out. The first study, obviously PEAK-1, that's enrolling. As Bob said, it'll be fully enrolled by the end of this year. We'll be waiting for readout. We're going full speed ahead. We expect that ipi anti-PD-1 casdatifan, as we've been talking about for some time, to be getting up and going by the end of this year. We'll see where the TKI inclusive regimen comes in.

Speaker #2: We'll see where the TKI inclusive regimen comes in. Without getting into all the detail now, we'll be sorting through whether that's actually two studies two registrational studies or a three-arm study is also a possibility.

Speaker #2: And then finally, in the later-line study that we talk about, we'll start off in ARC20. And as you know, those are relatively small cohorts that enroll very efficiently.

Will be shortly on the heels. But if you think about just sort of the general investment profile for the studies, will be through the bolus of study startup for Peak 1 and the cost profile for Peak 1. You know, will be starting to decrease as we get into the second half of next year. So we kind of feel like that. It's a, it's going to be a nice portfolio effect that when we think about these other studies kicking in. Um, really from a spend perspective in late 27 and into 28, we sort of see a generally steady spend profile through the peak 1 read, like, we described. Hey, John and I'll, I'll, I'll Bob kind of gave you the line of the spend along with the studies. And I, I'll give you a little bit more granularity on how we literally see the, uh, trials themselves playing out. So, uh, the the first um, uh study. Well obviously Peak 1 that's enrolling, as Bob said, it'll be fully enrolled, um, by the end of this year.

Speaker #2: But the other point that I think will be very important within those studies, and we'll get to answers quickly, is that we'll be looking at that combination in the third-line plus in Belzutafan naive patients as well.

Terry Rosen: You know, without getting into all the detail now, we'll be sorting through whether that's actually 2 studies, 2 registrational studies or a 3-arm study is also a possibility. Finally, in the later line study that we talk about, we'll start off in ARC-20, and as you know, those are a relatively small cohort that enroll very efficiently. The other point that I think will be very important within those studies, and we'll get the answers quickly, is that we'll be looking at that combination in the 3rd line plus in belzutifan naive patients as well. I think that'll establish It's a cool study, and I think it's gonna establish something.

Speaker #2: And I think that'll establish it's a cool study, and I think it's going to establish something yes, I'm sorry, Bell's experience in addition to Bell's naive thank you, Juan.

And then we'll be waiting for read out. Uh, we're going Full Speed Ahead, um, and expect that it be, uh, anti- pd1 Cass as we've been talking about for some time, uh, to be getting up and going by the end of this year. Um, we'll see where the uh, tki um uh, inclusive regimen comes in. There's, you know, without getting into all the detail, now we'll be sorting through whether there's that's actually 2 stud.

Speaker #2: And I think that'll nail something that we think we know the answer to, but we'll have those data even this year.

Speaker #5: Excellent. Thank you so much.

Speaker #2: Thanks, John.

Speaker #1: Our next question comes from the line. Of Lee Watsek with Dancers. Lee, your line is now open.

Speaker #3: Hey, guys. Congrats on the progress. I guess just one question only. ARC20 update is especially from the triplet cohort. Sounds like you guys are enrolling the combination with them plus IPPY.

Juan Heyen: Bel's experience.

Juan Jaen: Bel's experience.

Terry Rosen: I'm sorry. bel's experience in addition to bel's naive. Thank you, Juan. I think that'll nail something that we think we know the answer to, but we'll have those, you know, data even this year.

Speaker #3: Can you clarify if we're going to see the initial data from this cohort this year? And what data points would you want to see to enable a phase three front-line trial?

Studies and we'll get the answers quickly is that we'll be looking at um that combination in the third line plus uh in Bel naive, uh patients as well. And I think that'll establish a cool study and I think it's going to establish something else experience. Well, yes, the I'm sorry Bell's experience. In addition to Bells naive, I think you want. And and I think that all Nails something that we think we know the answer to, but we'll have those, you know, data uh, even this year.

Jonathan Miller: Excellent. Thank you so much.

Terry Rosen: Thanks, John.

Uh, excellent. Thank you so much.

Operator: Our next question comes from the line of Lee Watsik with Dansker. Lee, your line is now open.

Thanks John.

Speaker #2: Thanks, Lee. So we do think what you'll get to see and it'll be probably in the fall are the initial data from that IPPY anti-PD1 CAS regimen.

Lee Watsik: Hey, guys. Congrats on the progress. I guess just one question on the ARC-20 update, especially from the triplet cohort. Sounds like you guys are enrolling the combination with Zen plus ipi. Can you clarify if we're going to see the initial data from this cohort this year? What data points would you want to see to enable a Phase 3 frontline trial?

Li Watsek: Hey, guys. Congrats on the progress. I guess just one question on the ARC-20 update, especially from the triplet cohort. Sounds like you guys are enrolling the combination with Zen plus ipi. Can you clarify if we're going to see the initial data from this cohort this year? What data points would you want to see to enable a Phase 3 frontline trial?

Our next question comes from the line of Lee Watson with dancers. Lee your line is now open.

Hey guys, uh, congrats on the progress.

Speaker #2: And essentially, we'll get a sense of the safety data, and the rate of primary progression. Well, there may be some early ORR data. We don't consider that critical.

Speaker #2: We're most focused on the safety. That's what we'll we'll have an agreement with the FDA as to what safety data package they would want to see to enable us to get that phase three up and going.

Terry Rosen: Thanks, Lee. We do think what you'll get to see, and it'll be, probably in the fall, are the initial data from that ipi, anti-PD-1 casdatifan regimen. Essentially, we'll get a sense of the safety data and the rate of primary progression. While there may be some early ORR data, we don't consider that critical. We're most focused on the safety. That's what we'll have an agreement with the FDA as to what safety data package they would want to see to enable us to get that phase 3 up and going by the end of this year. Obviously, because that's the first point, but it's also an important point for that regimen, is we'll see the rate of primary progression.

Um, I guess just one question on the R20 update. Especially from the triplet cohort. Uh, it sounds like you guys are enrolling the combination with, um, plus 8P. Um, can you clarify if we're going to see the initial data from this cohort this year? And what data points would you want to see to enable a Phase 3 front-line trial?

Speaker #2: By the end of this year. And then obviously, because that's the first point, but it's also an important point for that regimen, is we'll see the rate of primary progression.

Speaker #2: I think one thing to recognize about that regimen when we think about triplets, doublets, etc., is also just I'd like to make the point is you know we've already talked about the rate of primary progression with CAS Datafam plus anti-PD1 alone.

Speaker #2: And those initial data are quite favorable where we only saw 7% rate of primary progression. Now, if you think about what that CAS anti-PD1 IPPY regimen is going to look like, you basically get four cycles of IPPY at the outset.

Terry Rosen: I think one thing to recognize about that regimen, when we think about triplets, doublets, et cetera, is also just I'd like to make the point is you know we've already talked about the rate of primary progression with casdatifan plus anti-PD-1 alone, and those initial data are quite favorable, where we only saw 7% rate of primary progression. If you think about what that CAS anti-PD-1 ipi regimen is going to look like, you basically get 4 cycles of ipi at the outset, of course, with CAS and anti-PD-1, but then the duration and the bulk of your therapy is going to be anti-PD-1 plus CAS. Both the efficacy that you're seeing with that as well as the safety of that will certainly impact the bulk of the therapy.

Thanks Lee. So, we do think what you'll get to see and it'll be, you know, probably in the fall, are the initial data from that IPI, uh, anti-pd1 cast, uh, regimen and essentially, we'll get a, you know, a sense of the safety data and the rate of primary progression. Well, you know, there may be some early Orr data. Um, we don't consider that, uh, critical. Um, we're most focused on, um, the safety. Um, that's what we'll, you know, we'll have an agreement with the FDA as to what safety, um, data package, uh, they would want to see to enable us to get that phase 3 up and going, uh, by the, by the end of this year. And then, um, obviously because that's the first, um, point. But it's also an important point for that regimen is we'll see, uh, the rate of

Speaker #2: Of course, with CAS and anti-PD1. But then the duration and the bulk of your therapy is going to be anti-PD1 plus CAS. So both the efficacy that you're seeing with that as well as the safety of that will certainly impact the bulk of the therapy.

Speaker #2: So we're excited about that regimen. We think we're well on track to be able to start the phase three by the end of this year and have a good safety data package.

Primary progression. I think, 1 thing to recognize about that regimen. Um, when we think about triplets doublets, Etc, it's um, also just I'd like to make the point is, is, you know, we've already um, talked about the rate of primary progression with cast, data fan, plus anti-, pd1 alone and those initial data are quite favorable, where we only saw a 7%, uh, uh, uh, rate of primary progression now, if you think about,

Speaker #2: And we do plan to share that with the external world as well. This year.

Speaker #1: Thank you.

Speaker #2: Thanks, Lee.

Speaker #1: Our next question comes from the line of Richard Law with Goldman Sachs. Richard, your line is now open.

Speaker #5: Well, hey, guys. Yeah, very helpful to see CAS's development all laid out in its life for all the different lines of therapy. A couple of questions from me.

Terry Rosen: We're excited about that regimen. We think we're well on track to be able to start the phase 3 by the end of this year and have a good safety data package. We do plan to share that with the external world as well this year.

Speaker #5: So looking at the LifeSpark 12 failure in both triplets and both CAS discontinuation by AZ, and then all the front-line therapies of doublets or monotherapies so far, what is your confidence that a CAS triplet of any kind, either with IOI or IOTKI, could be safe enough to succeed in 1L?

What that cash anti-pd1 ipy regimen is going to look like you basically get 4, um, cycles of, uh, iffy at the outset, um, of course, with Cass and anti-pd1. But then the, the duration and the bulk of your therapy is going to be um, anti-pd1 uh, plus C. So both the efficacy that you're seeing with that, as well as the um, uh, safety of that, uh, will certainly impact the bulk of the therapy. So, we're excited about that regimen. We think we're well on track to be able to start, uh, the phase 3, uh, by the end of this year and have a good safety, uh, data package and we do plan to share that, um, with the external world as, as well.

Lee Watsik: Thank you.

Li Watsek: Thank you.

Terry Rosen: Thanks, Lee.

Speaker #5: And I mean, what do you think is that safety bar for 1L? Do you think that those triplets have to show comparable safety profile to that IOI or IOTKI doublet for them to work?

This year. Thank you.

Basically.

Operator: Our next question comes from the line of Richard Law with Goldman Sachs. Richard, your line is now open.

Our next question comes from the line of Richard law with Goldman Sachs.

Richard, your line is now open.

Richard Law: Hey, guys. Yeah, very helpful to see CAS's development all laid out in its life for all the different lines of therapy. A couple of questions from me. Looking at the LITESPARK-012 failure in both triplets and Vuru CAS continuation by AstraZeneca, and then all the frontline therapies of doublets or monotherapy so far, what is your confidence that a CAS triplet of any kind, either with IOI or IO TKI, could be safe enough to succeed in 1L? I mean, what do you think is a safety bar for 1L? Do you think that those triplets have to show like comparable safety profile to like that IOI or IO TKI doublet for them to work?

Speaker #2: So I think we feel very confident. And based upon what we already know about our molecules with triplets, whether it's a triplet inclusive of a TKI or a triplet, with the IPPY anti-PD1.

Speaker #2: So keep in mind, while we haven't analyzed in detail and we will later this year, the ZIM, so that anti-PD1 CAS, we know that doublet and we certainly haven't seen anything untoward with that.

Oh hey guys. Um yeah very helpful to see cath's, uh, development, all laid out in his life for all the different lives of therapy, a couple of questions from me. Uh so looking at the Life Part 12 failures in both triplets and Vogue Taps that's continuation by as uh and then all the Frontline therapies of UPS or moral therapy. So far. What is your confidence that a half triplet of any kind either? What ioi or I

Tki could be safe enough to succeed in 1 now. And I mean, what, what do you think is that safety bar for 1l? Uh do you think that that those triplets have a show like comical safety profile to like that IO iot? Tki duplet for them to work.

Terry Rosen: I think we feel very confident and, you know, based upon what we already know about our molecules with triplets, whether it's a triplet inclusive of a TKI or a triplet with the ipi anti-PD-1. Keep in mind, while we haven't analyzed in detail, and we will later this year, the Zim, so that anti-PD-1 casdatifan, we know that doublet, and we certainly haven't seen anything untoward with that. We know, you know, we can combine with cabo well. What we believe is that the ipi nivolumab regimen has been extraordinarily well worked out in terms of dosing of that particular regimen.

Speaker #2: We know we can combine with Cabo well. So what we believe is that the IPPY nivo regimen has been extraordinarily well worked out in terms of dosing of that particular regimen.

Speaker #2: And as I was mentioning, in my response to Lee, you're basically going to treat with four cycles of IPPY that's quite worked out. So we believe that we have orthogonal AEs.

AI or triplet, um, uh, with the, uh, IPI, uh, anti-PD1. So keep in mind.

Speaker #2: We haven't seen anything in terms of a clear combination issues. When you think about CAS Datafan, you're basically bringing those on-target anemia and, of course, rarely or certainly more rarely hypoxia.

Speaker #2: Again, we're going to pick a good TKI we know that CAS anti-PD1 is looking good. So we think a reasonable TKI. We'll not bring anything untoward there.

Terry Rosen: As I was mentioning in my response to Lee, you're basically gonna treat with 4 cycles of ipi that's quite worked out. We believe that we have, you know, orthogonal AEs. We haven't seen anything, you know, in terms of a clear combination issues. When you think about casdatifan, you're basically bringing those on target anemia and of course, rarely or certainly more rarely, hypoxia. Again, we're gonna pick a good TKI. We know that CAS anti-PD-1, you know, is looking good, so we think a reasonable TKI will not, you know, bring anything untoward there.

Speaker #2: Keep in mind, we haven't actually seen the Merck data. And I think the thing that you should take away until otherwise is there hazard ratio must have been not good.

While we haven't, uh, analyzed in detail, and we will later this year, the, um, uh Zim. Uh, so that anti-pd1 Cass. We know that Delta and we certainly haven't seen anything unto uh, with that. Um, we know, you know, we can combine with, uh, Cabo. Well, uh, so uh, what we believe is that the IPI, uh, Neo regimen has been extraordinarily. Well, worked out in terms of dosing of that uh, particular regimen and is a is that was mentioning in my uh response to lie. You're basically going to treat with 4 cycles of hippie that's that's uh, quite worked out. So we believe that we have um, you know, orthogonal uh AES we haven't seen anything, you know. Uh,

Speaker #2: So that doesn't get to an intrinsic inability to have a triplet. It just says when you're bringing that TKI, when you're bringing those Xudafen on top of a pretty rough doublet, and you're treating for a long period of time, and you are undoubtedly introducing some new AEs, but you're not having a robust long-term efficacy effect, you're probably not creating a hazard ratio.

In in terms of a clear combination issues. Uh, when you think about uh, cast data fan, you're basically bringing uh those On Target uh anemia in in of course rarely or or certainly more rarely uh hypoxia again. Uh we're going to pick a good tki.

Terry Rosen: Keep in mind, we haven't actually seen the Merck data, I think the thing that you should take away until otherwise is, you know, their hazard ratio must have been not good. That doesn't get to an intrinsic inability to have a triplet. It just says when you're bringing that TKI, when you're bringing belzutifan on top of a pretty rough doublet and you're treating for a long period of time and you are undoubtedly introducing some new AEs, but you're not having a robust long-term efficacy effect, you're probably not creating a hazard ratio. We really don't know exactly how that played out.

Speaker #2: But we really don't know exactly how that played out. But all the data with our own molecule suggests that CAS Datafan is a very well-tolerated and robust HIF2 inhibitor.

Speaker #2: And with an orthogonal AE profile from anything that we plan to combine with. And we'll have those data within the next six months or so.

Speaker #5: Got it. And then follow up on that, have you seen the efficacy and the safety results from that VoluCAS trial before after discontinued it?

Speaker #5: And would that data be shared? Do you guys even if Asthra does not plan to share that? Thanks.

Terry Rosen: All the data with our own molecules suggest that casdatifan is a very well-tolerated and robust HIF-2 inhibitor and, you know, with an orthogonal AE profile from anything that we plan to combine with. We'll have those data, you know, within the next 6 months or so.

Why uh we we know that chaos anti-pd1 uh, you know, was looking good. So we think uh uh a reasonable tki. Uh, will not, you know, bring anything on towards their. Keep in mind, we haven't actually seen the Merc data and I think the thing that you should take away until otherwise, it's, you know, their Hazard ratio must have been not good. So that that doesn't get an an intrinsic inability to have a triplet. It just says, when you're bringing that tki, uh, uh, when, when you're bringing, um, Bill zuda fan on top of a pretty rough doublet, and you're training for a long period of time, and you are undali introducing some new ways, but you're not having a robust long-term uh, efficacy effect. You're, you're probably not creating a hazard ratio but we really don't know exactly how that played out but

Speaker #2: So we haven't seen anything other than what we said at the outset. Since they did disclose, you can now know that there were nine patients what we described was that initial safety signal that was very CTLA4 and more specifically Volu-like when they dosed down Volu but kept CAS Datafan at the same 100-milligram dose.

All the data with our own molecule suggests that cat data fan is a very well tolerated and robust, uh, if 2 inhibitor, and you know, with an orthogonal AE profile from anything that we plan, uh, to combine with and we'll have those data, you know, within the next, uh, 6 months or so.

Richard Law: Got it. Then follow-up on that, have you seen the efficacy and the safety results from that Vuru CAS trial before Astra discontinued it? Will that data be shared to you guys, even if Astra does not plan to share that? Thanks.

Speaker #2: We didn't see any more of it in those patients. Still continue on. And in fact, the interesting thing out of that is we've come in and before we didn't see any progression.

Got it and then follow up on that. Um, have you seen the empathy and the safety results from that voulu task trial before uh, Astra discontinued it? And, uh, with that data be shared. Do do you guys, uh, even if Astra does not plan to share that,

Terry Rosen: We haven't seen anything other than what we said at the outset. Since they did disclose, you can now know that there were nine patients. What we described was that initial safety signal that was very CTLA-4 and more specifically, Vuru-like when they dosed down Vuru but kept casdatifan at the same 100-milligram dose, we didn't see any more of it. Those patients, you know, still continue on. In fact, the interesting thing out of that is, we've commented before we didn't see any progression. That, if anything, we don't even know, quite honestly, that given that it was nine patients, it's not obvious whether, you know, that was even purely Vuru or not.

Speaker #2: So that, if anything, we don't even know quite honestly that given that it was nine patients, it's not obvious whether that was even purely Volu or not.

Speaker #2: And but what is obvious to us, at least as we were thinking about going forward, is that given that IPPY nivo well worked out regimen, well worked out dose, it's time-tested.

Speaker #2: And of course, probably most importantly, that you're only going to be carrying your anti-CTLA4 dosing for four cycles made that a clear regimen for us to want to proceed with all things considered.

Terry Rosen: That, if anything, we don't even know, quite honestly, that given that it was nine patients, it's not obvious whether, you know, that was even purely Vuru or not.

Speaker #2: Not wanting to have both of those activities for the duration of the therapy.

Terry Rosen: But what is obvious to us, at least as we were thinking about going forward is that given that ipi-nivolumab, well-worked-out regimen, well-worked-out dose, it's time-tested, and of course, probably most importantly, that you're only gonna be carrying your anti-CTLA-4 dosing for four cycles, made that a clear regimen for us to wanna proceed with, all things considered. Not wanting to have, you know, both of those activities for the duration of the therapy.

Thanks, so, we, we haven't seen anything other than what we, um, said at the outset since they did disclose, you can now know that there were 9 patients. Um, we what we described was that, um, that, uh, initial, uh, safety signal, that was very, um, ctla4 and more specifically, uh, voru. Like when they dosed down, uh, voru but kept cast data fan at the same 100 milligram dose, uh, we didn't see any more of it in those patients, you know, still, uh, continue, uh, on. And in fact, the interesting thing out of that is, is we've come in and before we didn't see any uh uh progression. So uh, that if anything, we don't even know quite honestly that given that it was 9 patients, it's not obvious. Whether um, you know, that was even purely vulnerable.

Speaker #5: Got it. Thanks, guys.

Speaker #2: Thanks, Rich.

Speaker #5: Thanks again. Congrats.

Speaker #2: Thank you.

Speaker #1: Our next question. It comes from the line of Salim Syed with Mizuo. Salim, your line is now open.

Speaker #6: Hi, this is Mike Linden on for Salim. Thanks for taking our question. Just one from us on CAS Datafan and front line again. Maybe just how you guys are thinking about patient selection for an IPPY nivo plus CAS combination.

Speaker #6: For phase three, would these be all-comers versus poor intermediate, favorable risk patients? Things like that. And I guess how is the thinking around patient selection changed post Lightspark 12 failure?

Uh, and uh, but what is obvious to us at least as we were thinking about going forward is, is that given that it be Neo? Um, well worked out regimen, well, worked out dose, its time-tested and, of course, probably most importantly that you're only going to be carrying your, um, anti-ctla for uh, dosing for 4 Cycles. Um, may get a clear uh regimen for us to want to uh proceed with uh, all all things considered. No, not 1 and a half, you know, both of those activities. Um, for the duration of, um, the therapy

Richard Law: Got it. Thanks, guys.

Terry Rosen: Thanks, Rich.

Got it. Thanks guys.

Richard Law: Thanks again. Congrats.

Speaker #6: Thanks.

Terry Rosen: Thank you.

Correct.

Operator: Our next question comes from the line of Selim Syed with Mizuho. Selim, your line is now open.

Speaker #2: Yeah. So our patient selection strategy hasn't changed. And in fact, we're thinking of all-comers. And we would also be thinking of all-comers insofar as a TKI inclusive regimen.

Thank you.

Our next question comes from the line of Saleem saiyad with miso, Sim your line is now open.

Mike Linden: Hi, this is Mike Linden on for Selim. Thanks for taking our question. Just one from us on casdatifan and frontline again. Maybe just how you guys are thinking about patient selection for an ipi-nivo plus CAS combination for a phase 3. Like, would these be all comers versus poor, intermediate, favorable risk patients, things like that. I guess how has the thinking around patient selection changed post LITESPARK-012 failure? Thanks.

Speaker #2: So what we're really trying to address there is there's clearly we've had to add board meetings. There's clearly a strong preference for TKI sparing regimen.

Speaker #2: So that's unequivocal. And that's the way we describe it is the bedrock of the front line. With that said, it's a little bit one of those things where there's almost a tribalism is the way the investigators in the field would describe it, where there's certain investigators that are very prone particularly if there is a bulky fast-growing tumor.

Hi. This is Mike Lindon on for Selene H. Thanks for taking our question. Just 1 from us on, cast out of sun and front line again. Uh, maybe just how you guys are thinking about patient selection for an an IP Neo Plus Cass combination uh for a phase 3 like with these be all comers versus poor intermediate, favorable risk patients. Um things like that and I guess how is the thinking around patient selection changed post? Um light, spark 12 faile. Thanks.

Terry Rosen: Yeah. Our patient selection strategy hasn't changed, and in fact, we're thinking of all comers. We would also be thinking of all comers insofar as a TKI inclusive regimen. What we're really trying to address there is we've had ad board meetings. There's clearly a strong preference for TKI sparing regimen. That's unequivocal, and that's the way we describe it as the bedrock of the front line. With that said, it's a little bit one of those things where there's almost a tribalism is the way the investigators in the field would describe it, where there's certain investigators that are, you know, very prone, particularly if there is a bulky, fast-growing tumor, but even otherwise to wanna reach for TKI.

yeah, so our

Patient selection.

Speaker #2: But even otherwise, to want to reach for TKI. So we feel from that overlap of particular patient with particular investigator, there should be a HIF2 inhibitor-containing regimen.

Speaker #2: And we think we can offer a very good one. So we look at both of those to be in all-comer patient population. I think, again, the Lightspark-012 data for us until we see something otherwise, we simply think it has to do and certainly, this has to be a contributing factor to that durability of effect and let's just call it on HIF2 inhibition with time that we know that's a dramatic difference between our two molecules.

Terry Rosen: With that said, it's a little bit one of those things where there's almost a tribalism is the way the investigators in the field would describe it, where there's certain investigators that are, you know, very prone, particularly if there is a bulky, fast-growing tumor, but even otherwise to wanna reach for TKI.

Strategy, uh, hasn't changed. And in fact, we're thinking of all comers. And we would also be thinking of all comers, uh, in so far as a, a tki, uh, uh, inclusive regimen. So what we're really trying to address there is there's clearly we've had to add more means there. There's clearly a, a strong preference for tki, uh, sparing regimen. So that's unequivocal. And that's the way we describe it is is the Bedrock of the front line. With that said um it's a little bit 1 of those things where um there's almost a tribalism. Uh, as the way, the, the investigators,

On the field would describe it were there, certain investigators.

Terry Rosen: We feel from that overlap of particular patient with particular investigator, there should be a HIF-2 inhibitor-containing regimen, and we think we can, you know, offer a very good one. We look at both of those to be in all-comer patient populations. I think, again, the LITESPARK-012 data for us until we see something otherwise, we simply think it has to do, and certainly this has to be a contributing factor to that durability of effect, and let's just call it on HIF-2 inhibition with time that we know that's a dramatic difference between our two molecules. Of course, when we look at, you know, the choices of what to combine with, keep in mind we have no commercial predisposition there. Essentially, the world is our oyster.

Speaker #2: And of course, when we look at the choices of what to combine with, keep in mind we have no commercial predisposition there. Essentially, the world is our oyster.

Speaker #2: And if you look at the front line there's a number of TKIs used there's not one that's particularly dominant overall. You have probably 60% of the patients are getting a TKI, but they're spread somewhat evenly.

Speaker #2: So we've gone and looked and been very strategic about it and looked at what's the smartest TKI from a safety standpoint. It's well used.

Terry Rosen: Of course, when we look at, you know, the choices of what to combine with, keep in mind we have no commercial predisposition there. Essentially, the world is our oyster.

Um, that are, you know, very prone. Uh, particularly if there is a, a bulky fast growing thinner but even otherwise to want to reach uh, for tki. So we feel from that overlap of particular, patient with particular investigator, uh, there should be a hip to, uh, inhibitor containing regimen. And we think we can, you know, offer a very good 1. So we look at both of those uh to be in full Comer. Uh, patient populations. I think again, the light spark 012 data for us on until we see something. Otherwise we we simply think it it it has to do um, or and certainly this has to be contributing factor to that um durability of effect. And let's just call it on Tiff 2 inhibitor with time that we know that's a dramatic difference between our 2 molecules

Speaker #2: It's well tested. Approved. Understood. That we should combine with in the front line. We know that we're going to have Cabo in a second line.

Terry Rosen: If you look at the front line, you know, there's a number of TKIs used. There's not one that's particularly dominant. Overall, you have probably 60% of the patients are getting a TKI, but they're, you know, spread somewhat evenly. We've gone and looked and been very strategic about it and looked at what's the smartest TKI from a safety standpoint, that's well-used, that's well-tested, approved, understood, that we should combine within the front line. We know that we're gonna have cabo in the second line, and then we've done the same in thinking about that late line patient population with what then becomes another TKI that you would use in the late line.

Speaker #2: And then we've done the same in thinking about that late line patient population. With what then becomes a another TKI that you would use in the late line.

Molecules. And of course, um, when we look at, you know, the choices of what to combine with, keep in mind, we have no commercial predisposition there. I essentially, the world is our oyster, and if you look at the front line, you know, there's a number of tkis uh, used. Um, there's not 1, that's particularly dominant. Overall you have probably 60%, um,

Speaker #2: And like I said, the other important thing there is that we are going to look at that combination of CAS with that TKI in Belzutafan experience patients and establish that unequivocally you get the activity that you want to see in that HIF2 experience patient.

Speaker #5: Thank you.

Speaker #2: Thanks.

Speaker #1: Our next question comes from the line of Jason Zemansky with Bank of America. Jason, your line is now open.

Speaker #7: Hi. This is Jackie on for Jason Zemansky. Congrats on the progress. And thanks for taking our question. Just a quick one for you. So what do you think is necessary to drive broad uptake of a TKI-free regimen in the first line?

Terry Rosen: Like I said, the other important thing there is that we are gonna look at that combination of CAS with that TKI in belzutifan-experienced patients and establish that unequivocally, you get the activity that you wanna see in that HIF-2 experienced patient.

Speaker #7: RCC, given how popular TKIs are overall, especially given their ability to rapidly debulk tumors. Or is the goal to compete directly with dual IO therapies?

Of the patients are getting a tki but they're, you know, spread somewhat, uh, evenly. So we've gone and looked and been very strategic about it and looked at, what's the smartest tki from a safety standpoint? It's well used, it's well tested approved. Uh, understood, uh, that we should combine with, in the front line. We know that we're going to have Cabo in a second line and then we've done the same and thinking about that late line, uh, patient population with what then becomes uh, a another tki that uh you would use in the late line. And and like I said, the other important thing there is that we are going to look at that combination of Cass with that tki in uh belza Fan Experience, patients and established that unequivocally. Uh you you get the activity that you want to see in that if 2 uh uh

Experienced patient.

Mike Linden: Thank you.

Speaker #7: Thanks.

Terry Rosen: Thanks.

Speaker #2: I think that so what's interesting is we think there's a strong receptivity toward this. Now, one of the most important things that we've seen today is that CAS monotherapy, even in the late line, performs as good or better than TKI in any line of setting.

Thanks.

Operator: Our next question comes from the line of Jason Zemansky with Bank of America. Jason, your line is now open.

Jackie: Hi, this is Jackie on for Jason Zemansky. Congrats on the progress, and thanks for taking our question. Just a quick one for you. What do you think is necessary to drive broad uptake of a TKI-free regimen in the first line RCC given how popular TKIs are overall, especially given their ability to rapidly debulk tumors? Is the goal to compete directly with dual IO therapies? Thanks.

[Analyst] (Bank of America): Hi, this is Jackie on for Jason Zemansky. Congrats on the progress, and thanks for taking our question. Just a quick one for you. What do you think is necessary to drive broad uptake of a TKI-free regimen in the first line RCC given how popular TKIs are overall, especially given their ability to rapidly debulk tumors? Is the goal to compete directly with dual IO therapies? Thanks.

Our next question comes from the line of Jason Zamansky with Bank of America. Jason, your line is now open.

Speaker #2: So if you go we have in our deck somewhere you can actually look that even in the late line, CAS Datafan monotherapy, whether you're looking at ORR or PFS, looks quite good.

Terry Rosen: I think that, what's interesting is we think there's a strong receptivity towards this. Now, one of the most important things that we've seen to date is that casdatifan as a monotherapy, even in the late line, performs, you know, as good or better than TKI in any line of setting. If you go, we have in our deck somewhere, you can actually look that even in the late line, casdatifan monotherapy, whether you're looking at ORR or PFS, looks quite good. The thing that's standing out, and I think this is the, you know, the issue that was identified with belzutifan at the outset was that rate of primary progression.

Hi. This is Jackie on for Jason's me. Congrats on the progress and thanks for taking our question. Uh just a quick 1 for you. So what do you think is necessary to drive broad uptake, um, of a tki free regimen in the first line? Our RCC given how popular tkis are overall especially given their ability to rapidly debulk tumors or is the goal to compete directly with dual um iio therapies. Thanks.

Speaker #2: And the thing that's standing out and I think this is the issue that was identified with Belzutafan at the outset was that rate of primary progression.

Speaker #2: So I think that's raised the question for HIF2 inhibition. Can you compete with TKI? It bringing that tumor under control quick enough that you don't have that high rate of primary progression.

Um, that we've seen today, is that cast data? Fan is a monotherapy even in the late line performs, you know, as good or better than tki.

Speaker #2: So we believe that Belzutafan was forced in the front line to combine with the TKI to address a potential high rate of primary progression.

Speaker #2: But we actually think that despite the fact that HIF2 inhibition is well tolerated, it can get the tumor under control quite fast. And the place where we've already seen our evidence of that is in combining with anti-PD1, where in 30 patients, we only saw two progressors, two primary progressors.

Terry Rosen: I think that's raised the question for HIF-2 inhibition, can you compete with TKI at bringing that tumor under control quick enough that you don't have that high rate of primary progression? We believe that belzutifan was forced in the front line to combine with the TKI to address a potential high rate of primary progression. We actually think that despite the fact that HIF-2 inhibition is well-tolerated, it can get the tumor under control quite fast. The place where we've already seen our evidence of that is in combining with anti-PD-1, where in 30 patients we only saw 2 primary progressors. 7%, very much in line with the TKI.

Speaker #2: So 7% very much in line with the TKI. So we think there's a receptivity to the TKI sparing regimen. And we think that the key thing to driving that uptake will be to show that our rate of primary progression and then everything that flows from that looks like a TKI.

Um in in any line of setting. So if you go, we we have in our deck somewhere, you can actually look that even in the late Line, cast data fan monotherapy, whether you're looking at or our or PFS uh looks um quite good. And the thing that's standing out and I think this is the the um, you know the issue that was identified with belan at the outset was that rate of primary progression so I think that's raised the question for if 2 inhibition um can you compete with tki? It bringing that uh, tumor under control quick enough, that you don't have that high rate of primary aggression. So we believe that those ludifu,

Speaker #2: The last point I would make is it's almost like they're the mentality would be like because TKIs are a rougher treatment, it's sort of like when you think about chemotherapy, that there's a linkage that sort of in people's minds, they associate rougher but bringing the tumor more under control.

Speaker #2: Keep in mind that 85 to 90-plus percent of clear-cell RCC has HIF2 as a key driver. So you're hitting the tumor with something that really matters.

Terry Rosen: We think there's a receptivity to the TKI-sparing regimen, and we think that the key thing to driving that uptake will be to show that our, you know, rate of primary progression and then everything that flows from that, you know, looks like a TKI. The last point I would make is it's almost like the mentality would be like because TKIs are a rougher treatment, you know, it's sort of like when you think about chemotherapy, that there's a linkage that sort of in people's minds they associate, you know, rougher but bringing the tumor more under control. Keep in mind that 85% to 90% plus of clear cell RCC has HIF-2 as a key driver.

Speaker #2: And we think that's why with a robust HIF2 inhibitor, like CAS Datafan, you actually can compete with the efficacy effects of a TKI.

Speaker #3: Just add one other point. I think Dr. McKay, in our event in the fall, indicated this, that the reason she really prefers using EpiNevo for the most part is it gives the patients the best chance for long-term survival.

But we actually think that, despite the fact that hif 2 inhibition is well, tolerated. It can get the tumor under control quite fast and the place where we've already seen our evidence of that is in combining with, um, anti-pd1. We're in 30 patients. We only saw 2 Progressive 2 primary progressor, so 7%, very much in line with the tki. So we think there's a receptivity to the tki spurring regimen and we think that the key thing to driving that uptake will be to show that our, you know, rate of primary progression and then everything that flows from that, you know, looks like a tki. The, the last point I would make is it's almost like they're the mentality would be like because tki are a rougher treatment, you know, when it's sort of like when you think about chemotherapy that there's a, a linkage that sort of in people's minds, they associate

Speaker #3: And the problem is the Achilles' heel is Terry described of the primary progression. So if you could blunt that and still give patients the best chance at long-term survival and we just saw 10-year follow-up data with 40% of patients alive, 10 years later, that's a very compelling regimen, we think.

Terry Rosen: You're hitting the tumor with something that really matters, and we think that's why with a robust HIF-2 inhibitor, like casdatifan, you actually can compete with the efficacy effects of a TKI.

Speaker #1: Sure. Thank you so much for the caller.

Speaker #2: Thank you.

Speaker #4: Thanks.

Speaker #1: Our next question comes from the line of Emily Bodman with HC Wright. Emily, your line is now open.

Bob Gelb: Just to add one other point is, I think Rana McKay in our event in the fall indicated this, that the reason she really prefers using ipi-nivo for the most part is it gives the patients the best chance for long-term survival. The problem is the Achilles heel, as Terry described, of the primary progression. If you could blunt that and still give patients the best chance at long-term survival, and we just saw 10-year follow-up data with 40% of patients alive 10 years later, that's a very compelling regimen, we think.

Bob Goeltz: Just to add one other point is, I think Rana McKay in our event in the fall indicated this, that the reason she really prefers using ipi-nivo for the most part is it gives the patients the best chance for long-term survival. The problem is the Achilles heel, as Terry described, of the primary progression. If you could blunt that and still give patients the best chance at long-term survival, and we just saw 10-year follow-up data with 40% of patients alive 10 years later, that's a very compelling regimen, we think.

You know, rougher, but bringing the tumor more under control. Keep in mind that 85 to 90 plus percent of clear cell RCC has hit 2 is a key driver. So, you're, you're hitting the tumor with something that really matters. And we think that's why with a robust to inhibitor. Um, like cast the other fan, you actually can compete with the um, uh, efficacy effects of a tki 1.

Speaker #8: Hi. Thanks for sending the questions. Based on the Lightspark 11 data, how are you kind of looking at your upcoming CAS plus Cabo updated data?

Speaker #8: And what are you kind of hoping to see to feel confident that you might have a superior profile versus what we saw in the Lightspark 11 trial?

Speaker #8: Thank you.

Speaker #2: Yeah. So we already feel that confidence. And we're obviously running the phase three trial. I think you kind of have to think of things holistically.

Jackie: Okay. Thank you so much for the color.

[Analyst] (Bank of America): Okay. Thank you so much for the color.

1 other point is like, I, I think Dr, McKay in our event in the fall indicated. This, that the reason she really prefers using ify Neo, um, for the most part is it gives the patients the best chance for long-term survival. And the problem is, is the Achilles heel is Terry described of the of the primary progression. So, if you could blunt that and still give patients the best chance at long-term survival and we just saw 10-year, follow-up data, with 40% of patients alive, 10 years later, you know, that's a very compelling regimen. We think

Terry Rosen: Thank you.

Sure, thank you so much for the color.

Bob Gelb: Thanks.

Bob Goeltz: Thanks.

Operator: Our next question comes from the line of Emily Bodnar with H.C. Wainwright. Emily, your line is now open.

Thank you, thanks.

Speaker #2: What in the end, what you're going to have is a hazard ratio. And what's nice is that since we're both running versus Cabo, those will be directly comparable.

Our next question comes from the line of Emily Bowman with HC, right? Emily, your line is now open.

Emily Bodnar: Hi, thanks for taking the questions. Based on the LITESPARK-011 data, how are you kind of looking at your upcoming cas plus cabo updated data, and what are you kind of hoping to see to feel confident that you might have the superior profile versus what we saw in the LITESPARK-011 trial? Thank you.

Speaker #2: While our data when we share later this year, we'll still be early. We're going to give Kaplan-Meier curve. We'll have landmark PFS. We'll have ORR.

Terry Rosen: Yeah. We already feel that confidence and we're obviously running the phase 3 trial. I think, you kind of have to think of things holistically. You know, in the end, what you're gonna have is a hazard ratio. You know, what's nice is that since we're both running versus cabo, you know, those will be directly comparable. While our data, you know, when we share later this year will still be early, we're gonna give, you know, a Kaplan-Meier curve. We'll have landmark PFS. We'll have ORR. You know, the people will be able to extrapolate to whatever extent how they wanna look at those data, but we'll give a very holistic view.

Hi, thanks for being the questions. Um, based on the life, spark 11 data, how are you kind of looking at your upcoming tasks plus Cabo updated data? What are you kind of hoping to see to feel confident that you might have a superior profile versus what we saw on the lights, spark, 11 trials.

Speaker #2: And people will be able to extrapolate to whatever extent how they want to look at those data. But we'll give a very holistic view.

Speaker #2: I think the other thing that's we don't want lost on people because we think it's an interesting other aspect of the data that really will only be emerging.

Yeah, so, um, we already feel that confidence and we're obviously running, uh, the Phase 3 trial. I think, um, you kind of have to think of things holistically. Um, you know, in the end what you're going to have is a hazard ratio. And, um, you know, uh, what's nice is that since we're both...

Speaker #2: And we'll see how things play out by the time we have some mature data later this year. So while from a regulatory standpoint, the PFS is what matters, we're going to have data now from our monotherapy cohorts that are getting mature enough that we'll start to get a sense of whether we do bring NOS advantage there, albeit in the late line.

Terry Rosen: You know, the people will be able to extrapolate to whatever extent how they wanna look at those data, but we'll give a very holistic view.

Terry Rosen: I think the other thing that we don't want lost on people because we think it's an interesting other aspect of the data that really it will only be emerging. We'll see how things play out by the time we have some mature data later this year. While from a regulatory standpoint, the PFS is what matters, we're gonna have, you know, data now from our monotherapy cohorts that are getting mature enough that we'll start to get a sense of whether we do bring NOS advantage there, albeit in the late line. The reason we feel that's important is it just depending on how that looks for casdatifan, it will potentially give a good sense that this mechanism can not only drive enhancements in PFS, but bring enhancements to OS.

Speaker #2: And the reason we feel that's important is it just depending on how that looks, for CAS Datafan, it will potentially give a good sense that this mechanism can not only drive enhancements in PFS but bring enhancements to OS.

Speaker #2: And while that may not be a requirement from a regulatory standpoint, we certainly could see it as an important differentiation that would drive more uptake by clinician if, in fact, we start to show that there can be OS enhancement from HIF2 inhibition, which we believe there's no reason there shouldn't be.

Terry Rosen: The reason we feel that's important is it just depending on how that looks for casdatifan, it will potentially give a good sense that this mechanism can not only drive enhancements in PFS, but bring enhancements to OS.

Speaker #8: Thank you.

Speaker #2: Thank you.

Speaker #1: Our last question comes from the line of Yigal Nakomovitz with Citigroup. Yigal, your line is now open.

Terry Rosen: While that may not be a requirement, from a regulatory standpoint, we certainly could see it as an important differentiation, that, you know, would drive more uptake by a clinician if in fact, we start to show that there can be a OS enhancement from HIF-2 inhibition, which we believe there's no reason there shouldn't be.

Other aspect of the data that really will only be emerging and we'll see how things play out. By the time, we have some mature data later this year. So while from a a a regulatory standpoint, the PFS is what matters. Um, we're going to have, you know, data now, our from our mono therapy, uh, cohorts that are getting mature enough that will start to get a sense of whether we do bring in OS, is is Advantage there albeit in in the late line. And the reason we feel that's important is it just um, depending on how that looks for data and it will, um, potentially give a good sense that this mechanism can not only uh Drive enhancements in PFS uh but uh bring enhancements to OS. And while that may not be a requirement

Speaker #5: Hi. This is John Kim on for Yigal. Congrats on the progress. And thanks for taking our question. Maybe just to mix in a non-CAS question, regarding AB102, while it's still early, is there any color you can provide on the intended proof of concept study design, whether you're planning on going into CSU versus AD first?

Speaker #5: Any color on primary endpoints or level of clinical signal you would need to see to give confidence to advance into a future registration program?

Um from a regulatory standpoint we certainly could see it is an important differentiation um that you know would drive uh more uptake by uh clinician. If in fact we we start to show that there can be uh uh OS enhancement uh from if to inhibition, which we believe there's no reason. There shouldn't be

Emily Bodnar: Thank you.

Terry Rosen: Thank you.

Thank you.

Speaker #5: Thanks so much.

Operator: Our last question comes from the line of Yigal Nochomovitz with Citigroup. Yigal, your line is now open.

Thank you.

Speaker #2: So what I want you to describe how we see ourselves going from A to B to C in the near time.

Speaker #5: Yeah. So at a very high level, we recognize that while we think we may have a better molecular profile, we have a little bit of ground that we need to make up relative to the couple of existing clinical players.

Our last question comes from the line of yugal. Nits with Citi group. Yigal your line is now open.

John Kim: Hi, this is John Kim on for your call. Congrats on the progress. Thanks for taking our question. Maybe just to mix in a non-cash question, regarding AB102, while it's still early, is there any color you can provide on the intended proof of concept study design, whether you're planning on going into CSU versus AD first? Any color on primary endpoints or level of clinical signal you would need to see to give confidence to advance into a future registrational program? Thanks so much.

Speaker #5: So what we've devised is a fairly accelerated plan for establishing PK tolerability in healthy volunteers followed by a fairly quick, rapid mechanistic confirmation of biological activity and very quickly progressing into a phase two study in CSU.

Terry Rosen: Juan, why don't you describe how we see ourselves going from A to B to C in a minute?

Hi, this is Joan Kim on for your golf. Congrats on the progress and thanks for taking our question. Maybe just to mix in a non-cap question. Uh, regarding a102 uh, while it's still. Early is there any color you can provide on the intended, uh, proof of concept study design, whether you're planning on going into CSU versus add first. Uh, any color on primary end points or level of clinical signal? You would need to see to give confidence to advance into a future registration program.

Juan Heyen: At a very high level, we recognize that while we think we may have a better molecular profile, we have a little bit of ground that we need to make up relative to the couple of existing clinical players. What we've devised is a fairly accelerated plan for establishing PK tolerability in healthy volunteers, followed by a fairly quick, rapid mechanistic confirmation of biological activity and very quickly progressing into a phase 2 study in CSU. We think we will at reasonable speed catch up and hopefully begin to illustrate the better profile of our drug. In parallel with that, we're thinking about where it might make sense concurrently with that CSU type of phase 2 study to demonstrate the value of an MRGPRX2 inhibitor.

Juan Jaen: At a very high level, we recognize that while we think we may have a better molecular profile, we have a little bit of ground that we need to make up relative to the couple of existing clinical players. What we've devised is a fairly accelerated plan for establishing PK tolerability in healthy volunteers, followed by a fairly quick, rapid mechanistic confirmation of biological activity and very quickly progressing into a phase 2 study in CSU. We think we will at reasonable speed catch up and hopefully begin to illustrate the better profile of our drug. In parallel with that, we're thinking about where it might make sense concurrently with that CSU type of phase 2 study to demonstrate the value of an MRGPRX2 inhibitor.

Speaker #5: So we think we will in reasonable speed catch up and hopefully begin to illustrate the better profile of our drug. In parallel el with that, we're thinking about where it might make sense concurrently with that CSU type of phase two study to demonstrate the value of an X2 inhibitor.

So, what I'm want, you to describe, how we see ourselves going from A to B to C.

So it, it is very high level. We recognize the well, we think we have may have a better

Molecular profile. We have a little bit of ground that we need to make up relative to the couple of existing.

uh,

Clinical players. So what we've devised is a fairly accelerated plan for establishing

Speaker #5: Right now, our lead candidate for that additional indication seems to be allergic asthma. But that's still at a very early stage of conceptual framing.

PK tolerability in healthy volunteers, followed by a fairly quick rapid. Mechanistic confirmation of

Biological activity, and very quickly progressing into a Phase 2 study in CSU. So we think we will

Speaker #5: Great. Thanks.

Juan Heyen: Right now our lead candidate for that additional indication seems to be allergic asthma, but that's still at a very early stage of conceptual framing.

Juan Jaen: Right now our lead candidate for that additional indication seems to be allergic asthma, but that's still at a very early stage of conceptual framing.

Reasonable uh speed, uh, catch up, and hopefully begin to illustrate that, the better uh, profile of our drug in Peril with that, we're thinking about um, where it might make sense concurrently with that CSU type of, uh, face to study to demonstrate the value of an of the next 2 inhibitor. Um, right now, our our

Lead candidate for that additional indication seems to be allergic to Cosmo, but that's still a very early stage of—

Conceptual, uh, framing.

John Kim: Great. Thanks.

Great, thanks.

Operator: There are no further questions at this time. This concludes today's call. Thank you for attending. You may now disconnect.

Terry Rosen: Thanks, everybody.

There are no further questions at this time. This concludes today's call. Thank you for attending. You may now disconnect.

Operator: Goodbye.

Thanks everybody. Goodbye.