Q2 2024 Arcus Biosciences Inc Earnings Call

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Speaker Change: Today, you'll hear from our CEO , Terry Rosen, COO, Jennifer Jarrett, and CFO , Bob Goeltz. We'll also be joined by our CMO, Dimitry Nuyten, and President Juan Jaen for questions after the prepared remarks. With that, I'll turn the call over to Terry.

Terry Rosen: Thanks very much, Pia, and thank you all for joining us this afternoon. 2024 has already been a very exciting year for us, and also very significant.

Terry: Thanks very much, Pia, and thank you all for joining us this afternoon.

Terry Rosen: 2024 has already been a very exciting year for us and also very consequential.

Terry Rosen: We completed enrollment in our first phase three trial, STAR-221, a 1,000-plus patient study in first-line upper GI adenocarcinoma. And we're on the brink of advancing two additional molecules into phase three studies, both of which are supported by strong data and targeting huge unmet needs and market opportunities. Cassdatafan, or CAS, our HIF-2 alpha inhibitor, will be our newest phase 3 entry. We're going to share a lot of information about this program today and, in fact, throughout the rest of the year.

Speaker Change: We completed enrollment of our first phase 3 trial, STAR-221, 1,000-plus patient study in first-line upper GI adenocarcinomas.

and we're on the brink of advancing two additional molecules in the face through studies, both of which are supported by strong data and targeting huge, unmet needs and market opportunities.

Terry: Casdatafan, or CAS, our HIF-2 alpha inhibitor, will be our newest phase 3 entrant. We're going to share a lot of information about this program today and in fact throughout the rest of the year.

Terry Rosen: The HIF-2 alpha inhibition mechanism has been clinically validated by the approval of Merck's Belzodifan, which has been shown to have robust single-agent activity in clear cell renal cell carcinoma, or clear cell RCC, as we'll call it throughout the call. Belzodifan is already generating over $500 million in annualized run rate sales just six months after approval for clear cell RCC. This clearly demonstrates the unmet need in this indication, the excitement around the mechanism, and the significant opportunity which we intend to capitalize upon.

Terry: The HIF-2 alpha inhibition mechanism has been clinically validated by the approval of Merch Bell Zootephan, which has been shown to have robust single-aging activity in clear cell renal cell carcinoma or clear cell RCC, which is what we're called throughout the call.

Speaker Change: Belzudafan is already generating over $500 million in the annualized run rate sales just six months after approval in ClearCell RCC.

Terry: This clearly demonstrates the unmet need in this indication, the excitement around the mechanism, and the significant opportunity which we intend to capitalize upon.

Terry Rosen: In addition to belzodifam monotherapy achieving a response rate of roughly 20% and meaningful tumor reduction in a much higher percentage of the late-line patient study population, probably one of the most exciting aspects of the HIF-2-alpha mechanism is its durability.

Terry: In addition to Belzutifan monotherapy achieving a response rate of roughly 20% and meaningful tumor reduction in a much higher percentage of the late-line patient study population,

Terry: Probably one of the most exciting aspects of the HIF-2-alpha mechanism is its durability.

Terry Rosen: In the Phase I-II study for Belzodepan, over 20% of patients had not progressed and remained on treatment beyond two years. And several of these patients, in fact, are now approaching four years on treatment. In the phase 3 Registration of LightSpark 05 trial, at the time of the first data presentation, Ward Times is many patients; we're still on treatment with those who defend them with the comparatager of relimance.

Terry: In the phase one, two study for those who defend over 20% of patients had not progressed and remained on treatment beyond two years. In several of these patients, in fact, are now approaching four years on treatment.

Terry: And in the Phase 3 Registrational LightSPARC-005 trial, at the time of the first data presentation,

Speaker Change: Ward Times as many patients were still on treatment with those due to fan, then with the imparager, everalignance.

Speaker Change: This is pretty remarkable for the third-line plus setting, and it contrasts with the many TKI therapies, where patients may respond quickly, but then they rapidly progress.

Terry: The tolerability of belzodifan, with on-mechanism anemia and hypoxia being the only meaningful treatment of emergent adverse events, enables patients to remain on treatment for long periods.

Terry: And we've consistently heard from clinicians how well-tolerated Belzutepin has been for patients, particularly relative to the TKIs.

Speaker Change: While balzutafen is a good molecule, with Cas we have a potentially best-in-class molecule due to its excellent pharmacodynamic and dose-proportional pharmacokinetic profile. It's really a great molecule.

Terry Rosen: Cassus's PKPD profile enables us to deliver five or more times the PD equivalent of the Proust Dosa Bell Zootiffin, which may result in more rapid onset and greater clinical efficacy relative to Dosa Bell Zootiffin. And in fact, in our arc 20 study, we've already seen this differentiation play out in the data, which we look forward to sharing later this year. To further leverage CAST's improved profile, we're pursuing differentiated combinations relative to those being investigated with dozutifan.

Terry: Casus PKPD profile enables us to deliver five or more times the PDA equivalent of the proof dose of those benefits.

Terry: which may result in more rapid onset in greater clinical efficacy, relative to those of Bell Zootafat. In fact, in our arc 20 study, we've already seen this differentiation play out in the data which we look forward to sharing later this year.

Terry: The further leveraged kits and improved profile were pursuing differentiated combinations relative to those being investigated with those artifacts.

Terry Rosen: You're gonna hear more about this today from Jen when we disclose for the first time the design of our first phase three study for CAST, Peak 1. We have some other exciting studies in the works that we're gonna talk more about in the near future. Moving on to our FC silent antigen antibody, DOM Vanillamab, and STAR-221, our phase three trial evaluating DOM plus our anti-PD-1 ZIM, plus chemo, and first-line upper GI cancers. In June, we completed enrollment in STAR-221, enrolling over 1,000 patients in just 18 months. And we expect STAR-121 in the near future.

Terry: If you're going to hear more about this today from Jen, when we disclose for the first time the design of our first phase three study for task, P1. We have some other exciting studies in the works that we're going to talk more about in the near future.

Speaker Change: Moving on to our FC silent, and I dig in about a dominole map.

Speaker Change: and start 2-2-1, our Phase 3 trial, evaluating Dom plus our Anti-PD-1-Zim, plus chemo, and first line upper GI cancers. June, we completed enrollment of start-2-2-1, enrolling over 1,000 patients in just 18 months.

Terry Rosen: Complete enrollment later this year, so we're now turning our focus towards data redox. While we recognize, you know, the anti-TIGIT program and DOM is a show-me story for many of you, our confidence is actually stronger than ever. It's data-driven, and we remain convinced that the FC silent configuration has significant advantages over the FC active antibody. This is because FC anti-tigid antibodies substantially deplete peripheral regulatory T-cells and correspondingly increase immune-related AE. While increasing the incidence of AEEs and is obviously intrinsically undesirable, perhaps more detrimental is the need to withhold or discontinue drugs to manage these AEEs, which may negatively impact ethics.

Speaker Change: And we expect to start 1-2-1, complete enrollment, later this year. So we're now turning our focus towards data readouts.

Speaker Change: Well, we recognize...

Dimitry Nuyten: You know, the anti-digit program in Dimitry Nuyten is a show we store for many of you, our confidence is actually stronger than ever.

Speaker Change: State of Driven, and we remain convinced that the FCC's silent configuration has significant advantages over the FC active antibodies.

Speaker Change: This is because the FC anti-tigid antibodies substantially deplete peripheral regulatory T-cells and correspondingly increase immune-related AEs.

Speaker Change: While increasing the incidence of AEs is obviously intrinsically undesirable, perhaps more detrimental is the need to withhold or discontinue drugs to manage these AEs, which may negatively impact efficacy.

Terry Rosen: We've now seen two Merck studies where they explicitly called out greater rates of immune AEs leading to treatment continuation as the primary reason for trial failure. Recall also that Merck is using a co-formulation strategy. Excessive simultaneous discontinuation, but both components of the R&B PD1 anti-digit therapy. Additionally, because TIGIT is expressed on several other types of immune cells, depleting TIGIT-bearing immune cells can be counterproductive for any therapeutic strategy that's designed to stimulate the immune system to eliminate cancer.

Speaker Change: We've now seen two Merch studies where they explicitly called out greater rates of a Munich ease leading to treatment continuation is the primary reason for trial failure.

Speaker Change: Recall also that Merck is using a co-formulation strategy necessitating simultaneous discontinuation of both components of their anti-PD-1, anti-tiget therapy.

Speaker Change: Additionally, because tissue is expressed on several other types of immune cells, the bleeding tissue bearing immune cells can be counterproductive for any therapeutic strategy that designed to stimulate the immune system to eliminate cancer cells.

Terry Rosen: We have two impactful data sets coming that we're gonna talk about a bit later. Both of which we believe will not only restore but enhance confidence in the potential of the TIGIT pathway, so TIGIT pathway in general. But in particular, in DOM, is an Fc-saline anti-TIGIT antibody.

Speaker Change: We have two impactful data sets coming that we're going to talk about a bit later.

Speaker Change: Both of which we believe will not only restore but enhance confidence in the potential of the TIGIT pathway, so TIGIT pathway in general. But in particular, in DOM, is an Fc-saline anti-TIGIT antibody.

Terry Rosen: I want to briefly comment on our CD73 and Adenosine Receptor Programs, QMLE and eTRUMA, respectively. For Etruma at ASCO, we presented data from our randomized ART9 study, which showed unprecedented median overall survival of over 20 months for an Etruma-based combination. These results surpass any survival results reported for clinical trials in third-line colorectal cancer. In the second half of the year, we also plan to present biomarker data from this study that describes the ability of a vaccine to block the effects of a denocene in tumors, as well as the relationship between CDC-73 expression and patient survival.

Speaker Change: I want to briefly comment on our CD73 and Adenosine Receptor Programs, QMLE and eTRUMA, respectively.

Speaker Change: For Etruma at AFCO, we presented data from our randomized ART9 study, which showed unprecedented median overall survival of over 20 months for an intrusive-based combination through a color rectal cancer.

Speaker Change: These results surpass any survival results reported for clinical trials in third line colorectal cancer.

Speaker Change: In the second half of the year, we also plan to present biomarker data from this study that describes the ability of a term in a block the effects of a denocene in tumors, as well as a relationship between CDC-73 expression and patient survival. So we're going to link mechanism to clinical outcomes.

Speaker Change: Both we and our clinical advisors are eager to advance the treatment of colorectal cancer. We're going to update you once we finalize next steps for this program.

Terry Rosen: For Quimley, we expect to start our phase three study in pancreatic cancer, which we're now calling PRISM-1, by early next year. We're extremely excited that TIHO decided last month to exercise its option to the Kremlin program. TIHO will make a payment for the option exercise, and they're also obliged to pay us development milestones, which are expected to be triggered next year. In return, Taiho received development and commercialization rights to Kremlin in Japan, as well as other countries in Asia, but excluding mainland China.

Terry Rosen: DellNata operationalized and was responsible for the class of prison one in Japan. Their exercise of this option further illustrates the potential for QMLE in pancreatic cancer. We expect TIO to play a valuable role in the successful execution of the PRISM-1 study. Finally, Well is enabled to continue to advance our large portfolio with a billion dollars in cash and investments on hand plus the $100 million continuation payment due from Gilliet, as well as the multiple partnerships that provide significant funding for progress.

Speaker Change: For Quimley, we expect to start our Phase III study in pancreatic cancer, which we are now calling PRISM-1, by early next year.

Speaker Change: We're extremely excited that Tyho decided last month to exercise its option to the Kremlin program.

Speaker Change: Ty Ho will make a payment for the option exercise, and they're also obliged to pay us development milestones which are expected to be triggered next year.

Speaker Change: In return, Taiho received development commercialization rights to Kremlin, Japan, as well as other countries in Asia, but excluding mainland China. They'll not operationalize and be responsible for the cost of prison one in Japan.

Speaker Change: Their exercise of this option further illustrates the potential for Quimley and pancreatic cancer. We expect TAIO to play a valuable role in the successful execution of the PRISM-1 study. Finally,

Speaker Change: We're well enabled to continue to advance our large portfolio with a billion dollars in cash and investments on hand, plus the $100 million continuation payment due from Gilead, as well as the multiple partnerships that provide significant funding for programs.

Terry Rosen: So let me summarize where we are today. We are extremely well positioned due to the investment that we've made in Dom, including our three phase three studies, one of which is complete enrollment, and a second that is expected to complete enrollment this year.

Speaker Change: So let me summarize where we are today.

Speaker Change: We are extremely well positioned due to the investment that we've made in Dom, including our three phase studies. One of which is completing enrollment, and the second that is expected to complete enrollment this year.

Terry Rosen: As such, we anticipate 2024 will represent the peak of our R&D investment in DOM. With enrollment in Star 221 behind us, we're now preparing for data and potential registration. The timing of this is perfect. We're now able to shift resources and investment to our next strategic priority, test data. Cass represents a very rare opportunity.

Speaker Change: As such, we anticipate 2024 will represent the peak of our R&D investment in DOM. With enrollment of Star 221 behind us, we're now preparing for data and potential registration.

Speaker Change: The timing of this is perfect. We're now able to shift resources and investment to our next strategic priority, test data fit.

Terry Rosen: We have a validated target in HIF-2-alpha. Belzodepan has been embraced by physicians and patients as an important new standard of care, despite what are very clear limitations.

Speaker Change: CAHPS represents a very rare opportunity. We have a validated target in HIF-2-alpha. Velzutifan has been embraced by physicians and patients as an important new standard of care despite what are very clear limitations.

Terry Rosen: Cass has an improved profile, and this program is now central to our development focus. Our emphasis is on creating a comprehensive development program that fully leverages everything that we have been able to learn from Belzudafan in our growing CAST data set. We expect to share a continuous flow of data and plans over the next year. Our initial phase three trial, peak one, is the start of this transition and commitment. I'd like to now turn things over to Jen to speak a bit about CAST in greater detail.

Speaker Change: Cass has an improved profile and this program is now central to our development focus.

Jen: Six Terry, slide 26, shows the design of arc 20, our phase one study for tasks and late-mind, clear cell RCC. It includes three modern therapy expansion cohorts, each initially enrolling approximately 30 patients that are evaluating 50 migs, 100 migs, and 150 migs of tasks. As well as a combination cohort that is evaluating tasks, let's count them in.

Speaker Change: Our emphasis is on creating a comprehensive development program that fully leverages everything that we have been able to learn from Belzudafan and our growing CAST dataset. We expect to share a continuous flow of data and plans over the next year.

Speaker Change: Our initial phase 3 trial, Peak 1, is the start of this transition and commitment. I'd like to now turn things over to Jen to speak a bit about CAS in greater detail.

Jen: Thanks, Terry.

Jen: Slide 26 shows the design of arc 20, our phase 1 study for cast and late-mind, clear-sell RCC. It includes three modern therapy expansion cohorts, each initially enrolling approximately 30 patients.

Jen: that are evaluating 50-migs, 100-migs, and 150-migs of cast. As well as a combination cohort that is evaluating cast, let's tell us the end of it. Patients in the monotherapy cohort have to have progressed on both an anti-PD-1 and TTI therapy and the metastatic setting to be eligible.

Jen: Patients in the monotherapy cohort had to progress on both an anti-PD1 and TKI therapy and in the metastatic setting to be eligible. We have submitted data from the Hunterley cohort for presentation at a fall medical conference. The presentation will include safety and efficacy data, including ORRs, as well as waterfall charts and swimmer lanes, so that you will be able to assess the depth and duration of response.

Jen: We have submitted data from the Hydrogony cohort for presentation at a fall medical conference. The presentation will include safety and efficacy data, including ORRs, as well as waterfall charts and swimmer lanes, so that you will be able to assess the depth and duration of responses.

Jen: Patients in this cohort had an average of three prior lines of therapy, and 25% of patients had four or more prior lines. In comparison, the phase 3 trial for melzutifan, LightSpark 005, enrolled only patients who had received 1 to 3 prior lines of therapy. And as a reminder, the ORR for LightSpark 005 was 21.9%, and the primary progressive disease, or primary PD rate, was 33%. We expect our data presentation to support CASA's potential best-in-class profile, specifically better efficacy with comparable safety relative to that of belzodifan, even when evaluated in a more advanced patient population than that for LightSpark 005.

Jen: Patients in this cohort had a medium of three prior lines of therapy, and 25% of patients had four or more prior lines.

Jen: In comparison, the Phase III trial for melzutafan, like SPARCO 05, enrolled only patients who received 1-3 prior lines of therapy.

Jen: and as a reminder that O&RR for Lifework 05 was 21.9% and the primary progressive disease or primary PD rate was 33%.

Jen: We expect our data presentation to support CASA's potential best-in-class profile, specifically better efficacy with comparable safety relative to that of belzodifan, even when evaluated in a more advanced patient population than LightSpark 005.

Jen: Because of the significant interest in ART20, we actually just reopened the 100-MIG cohort and are close to enrolling another 30 patients. This would bring us to 120 patients that have enrolled in total across the three monotherapy cohorts, which is incredible for a Phase I study in a single tumor. Moving on to the 15-day cohort, which completed enrollment in April, these data are maturing very nicely, so we also expect to share some information from this cohort in the fall.

Jen: Because of the significant interest in ART20, we actually just reopened the 100-MIG cohort and are close to enrolling another 30 patients.

Jen: This would bring us to 120 patients that have enrolled in total in approximately a year across the three monotherapy cohorts, which is incredible for a Phase I study in a single tumor type.

Jen: Moving on to the 50 mid-cohort, which completed enrollment in April , these data are maturing very nicely, so we also now expect to share some information from this cohort in the fall.

Jen: All patients are eligible to have had at least one scan, so we already know the partner APD rate or the Senate patients that progressed at the before their first. Like we observed in a 100-make cohort, the primary PD-rate is substantially less than the 33% observed in. This is another data point demonstrating that calf bone seems to bring tumor growth under our control more quickly than either it is.

Jen: All patients are eligible to have had at least one scan, so we already know the primary PD rate, or the percent of patients that progressed at or before their first scan.

Speaker Change: Life we observed in a hundred make-to-heart, the primary PD rate is substantially less than the 33% observed in lifespan of 0.05. This is another data point demonstrating a cast, saying to bring tumor growth on our control more quickly than else at a fin.

Jen: Also, like the 100MIT cohort, we're seeing a very significant percentage of patients with tumor reduction, and the ORR for this cohort, including one response that is pending confirmation, is already higher than what was reported in LightSpark 005, even with very limited follow-up. Finally, we recently completed enrollment in the 150-meg expansion cohort. So between now and the end of 2025, we expect to present a steady stream of data from Arc20, including at least 120 patients' worth of data for CAF monotherapy, as well as potentially initial data from our CAF plus CABO combination cohort.

Jen: Also, like the 100MIT cohort, we're seeing a very significant percentage of patients with tumor reduction. And the ORR for this cohort, including one response that is pending confirmation, is already higher than what was reported in LightSpark-005, even with very limited follow-up.

Jen: Finally, we recently completed enrollment of the 150-meg expansion cohort.

Jen: So, between now and the end of 2025, we expect to present a steady stream of data for Mk20, including at least 120 patients' worth of data for CAF monotherapy, as well as potentially initial data from our CAF plus CABO combination cohort.

Jen: These data will be used to support rapid initiation and enrollment of our first phase 3 study, which brings me to our development plan for CAF. Following feedback from the FDA later this year, we plan to begin our first phase 3 trial, Week 1, in the first half of next year. The proposed design at Peak 1, which is shown on slide 29 of our corporate deck, is simple.

Jen: These data will be used to support rapid initiation and enrollment of our first phase 3 study, which brings me to our development plan for CAS.

Jen: Following FDA, following feedback from the FDA later this year, we plan to begin our first phase three trial, week one, in the first half of next year.

Jen: The proposed design of P1, which is shown on slide 29 of a corporate deck, is simple. We will evaluate CAS, plus COBO, versus COBO, consider cell RCC.

Jen: We will evaluate CAS plus CABO versus CABO in clear cell RCC. CABO is the leading TKI prescribed for clear cell RCC, and CABO monotherapy is the standard of care in the post-IO setting. Peaclum Golden Roll Patients would have received prior anti-PD1 therapy. This includes patients who received PEMBRO in the adjuvant, or post-nephrotomy setting, as well as patients who received anti-PD-1 in the first-line metastatic setting.

Jen: CABO is the leading TKI prescribed for clear cell RCC, and CABO monotherapy is the standard of care in the post-IO setting.

Jen: [inaudible]

Jen: This includes patients who received Pembro in the adjuvant or post nefraptomy setting, as well as patients who received Antipd1 in the first line metastatic setting. So P1 will target a huge patient population and a deep patient population that we believe will significantly benefit from PIP2 alpha inhibition.

Jen: So PEEQ-1 will target a huge patient population, and the patient population that we believe will significantly benefit from PF2-alpha inhibition. We plan to use the once-daily dose of 100 mg of CAF in this study. All of our PTAPD exposure, response, and safety data from our test escalation and expansion cohorts. Support 100Mg is a go-forward dose from our combination study. And the primary endpoint of this study will be Pia. We expect the peak of design to be extremely attractive for the best clinicians and patients for a number of reasons. For simplicity, we are using Cabo on both the experimental arm and the control arm.

Jen: We plan to use the one scale dose of a hundred-meg of cap in the study.

Jen: All of our PK-PD exposure response and safety data from our dose escalation and expansion cohorts support 100 mg as the go-forward dose from our combination studies.

Jen: and the primary endpoint of the study will be PFS.

Jen: We expect the Pequin design to be extremely attractive for both clinicians and patients for a number of reasons.

Jen: For simplicity, we are using CABO in both the experimental arm and the control arm. In contrast, in Merck's LIGHTSPARK-022, their similar study, they are evaluating delzutifan with lembatinib as the TKI in the experimental arm versus CABO in the control arm.

Jen: Second, our choice of combination partner is Cabo, the most widely used TKI. We have received consistent feedback from physicians, the Cabo is preferred over other TKI's, because of its proven efficacy, their comfort with managing Cabo-related AEs, and the simplicity of DevSing.

Jen: Specifically, there are only two approved doses for CABO compared to five different doses for lumbatinib, so CABO's use is relatively easy to titrate. And importantly, CABO has also been shown to have a more benign safety profile than that of lumbatinib.

Jen: P1 is just the beginning of our investment in a late stage development program for task, and there's much more to come. We are in the early stages of planning for a study with a collaboration partner that will evaluate tasks in a potential first and class combination and would expand our development plan into the first line setting. We are also in the process of evaluating multiple other opportunities for CAS within the RCC space and potentially beyond, and we'll share more on these over the coming months.

Jen: P1 is just the beginning of our investment in a late stage development program for CAS, and there's much more to come. We are in advance stages of planning for a study with a collaboration partner that will evaluate CAS in a potential first and plus combination, and would expand our development plan into the first line study.

Jen: We are also in the process of evaluating multiple other opportunities for tasks within the RCC space and potentially beyond, and we'll share more on these over the coming months.

Jen: The market opportunity for CAF is substantial. The class of TKIs primarily used for RCC now generates well over $5 billion in sales, as shown on slide 31 of our corporate presentation. With an annual incidence of 12,000 patients per year in the U.S. alone, it is a large population, and patients frequently remain on therapy, cycling through different treatments for many years. We believe our CAF combinations have the potential to be best in class, allowing us to capture a significant share of this large and growing market. I'll now turn the call back to Terry to discuss DOM, or FC Silent Antigens Antibody.

Jen: The market opportunity for CAF is substantial. The class of TKIs primarily used for RCC now generate well over $5 billion in sales, as shown on slide 31 of our corporate NIP.

Jen: With an annual incidence of 12,000 patients per year in the U.S. alone, it is a large population, and patients frequently remain on therapy, cycling through different treatments for many years.

Jen: We believe our CAF combinations have the potential to be best in class, allowing us to capture a significant share of this large and growing market.

Jen: I'll now turn the call back to Terry to discuss DOM, or FcSilent Antigenated Antibody.

Terry Rosen: Thanks very much, Jen. So at ASCO in early June, we had two oral presentations, something we think is pretty incredible for a company of our size and stage. That included new data for Edge Gastric, our phase two trial evaluating Dom's M plus chemo in upper GI cancer. As you can see on slide 16 of our corporate deck, in a 40-patient cohort, the Dom-Zim combination demonstrated a pretty impressive median PFS of 12.9 months for the overall population and 13.8 months for the PD-L1 high population.

Terry Rosen: Thanks very much, Jen.

Terry Rosen: So in ASCO in early June we have two world presentations, something we think is pretty incredible for a company of our size and stage that included new data for edge gastric, our Phase 2 trial of the only Dom's simplest chemo in upper GI cancer industry.

Terry Rosen: As you can see on flight 16 of our corporate deck in a 40-patient cohort, the Domzin combination demonstrated a pretty impressive medium PFAS.

Terry Rosen: of 12.9 months for the overall population, and 13.8 months for the PDL-15 population.

Terry Rosen: These far exceed the benchmark PFS data for anti PD1 plus chemol, that's in the 78th month range. And in fact, the median PFS data for edge gastric actually approached the benchmark, meaning the OS of 13 to 14 months for anti PD1 plus chemol, as we've highlighted on slide 17. Based on this outcome, our OS results should substantially exceed those from all of the benchmark studies.

Terry Rosen: These far exceed the benchmark PFS data for anti-PD-1 plus chemo that's in the 7- to 8-month range. And, in fact, the median PFS data for Edugastric actually approached the benchmark median OS for us.

Terry Rosen: of 13 to 14 months for anti-PD-1 plus chemo as we've highlighted on slide 17. Based on this outcome, our OS results should substantially exceed those from all of the benchmark studies.

Terry Rosen: These results meaningfully de-risk our STAAR 221 Phase 3 study, which is evaluating the same combination in the same setting as EDGE-GAS-1. We expect to have overall survival data for EDGE gastric in 2025. Given this is the primary endpoint for STAAR 221, these data should further enhance the likelihood of a successful outcome for our Phase 3 study. We continue to believe not only that anti-TIGIT will be an important advance in anti-cancer therapy but that DOM will have important advantages over its FC-enabled counterparts. There continues to be a steady flow of data-supporting...

Terry Rosen: These results meaningfully de-risk our STAR 221 Phase 3 study, which is evaluating the same combination in the same setting as edge gastric.

Terry Rosen: We expect to have overall survival data for EDGE gastric in 2025. Given this is the primary endpoint for STAR 221, these data should further enhance the likelihood of a successful outcome for our Phase 3 study.

Terry Rosen: We continue to believe not only that anti-TIGIT will be an important advance in anti-cancer therapy, but that DOM will have important advantages over its FC-enabled counterparts. There continues to be a steady flow of data supporting this.

Terry Rosen: While the failure of Skyscraper 6, Roche's Phase 2, 3 study, which evaluated Turago plus Atizo plus chemo versus Pembroke plus chemo, is disappointing for patients, we've articulated to you the many important differences between our studies and Sky 6, and we really think that most of you have agreed with us on these points. We've generated a tremendous amount of data that support DOM's potential to add meaningful clinical benefit in both non-small cell lung cancer and upper GI cancers.

Terry Rosen: Well, the failure of Skyscraper 6.

Terry Rosen: Roche's Phase II-III study, which evaluated Turago plus Atizo plus chemo versus Pembroke plus chemo, is disappointing for patients.

Terry Rosen: We've articulated to you the many important differences between our studies and SCI-6, and we really think that most of you have agreed with us on these points.

Terry Rosen: We've generated a tremendous amount of data that support DOM's potential to add meaningful clinical benefit to both non-small cell lung cancer and upper GI cancers.

Terry Rosen: And we expect to present two new data sets that will further support DOM's significant potential in lung and upper GI cancers. So first off, by year end, we in Gilead plan to report data from ARC-10 Part 1, a randomized phase three study in PD-L1 high non-small cell lung. So let me just give you a reminder.

Terry Rosen: And we expect to present two new data sets that will further support DOM's significant potential in lung and upper GI cancers.

Terry Rosen: So, first off, by year end, we in Gilead plan to report data from ARC-10 Part 1, a randomized phase 3 study in PD-L1 high non-small cell lung cancer.

Terry Rosen: We stopped enrollment for strategic reasons early this year to focus on the much larger opportunity with STAR-121. The initial design of ARC-10 evaluated DOM plus ZIM versus ZIM versus chemotherapy. Approximately 40 patients were enrolled in each of the DOM plus ZIM and ZIM monotherapy arms, and approximately 20 patients were enrolled in the chemotherapy arms. As we promised at the time, we shifted our focus to star one, two, one. We will present both PFAS and OS, including hazard ratios, and we believe that these data will re-affirm what we observed in arc seven.

Terry Rosen: So let me just give you a reminder, we stopped enrollment.

Terry Rosen: For strategic reasons, early this year, the focus on the much larger opportunity would start [inaudible]

Terry Rosen: The initial design of ARC-10 evaluated DOMPLA-ZIM versus ZIM for chemotherapy.

Terry Rosen: Approximately 40 patients were enrolled in each of the DOM plus ZIM and ZIM monotherapy arms and approximately 20 patients were enrolled in the chemotherapy arm.

Terry Rosen: As we promised at the time we shifted our focus to STAR 121, we will present both PFS and OS.

Terry Rosen: Including Hazard Ratios.

Terry Rosen: And we believe that these data will reaffirm what we observed in ARC-7, that DOM plus ZIM demonstrates clinically meaningful improvements over anti-PD-1 monotherapy in the setting with limited additional toxicity.

Gilead: Second, we in Gilead expect to present OS data from EdgeGastric in 2025.

Terry Rosen: As I mentioned, given that our median PFS is already in line with the O.S. results observed for anti-PD-1 plus chemotherapy alone.

Terry Rosen: We expect to report very compelling overall survival data, and I can say, today, well over 50% of patients remain on study 18 months after enrollment completed in this cohort.

Terry Rosen: We continuously evaluate the entirety of our data to confirm our confidence in our study designs, and we remain as confident as ever about our three phase three studies, and we have the potential best-in-class anti-TGIT, anti-PD-1 combination. He screens into the potential timing of our phase three read-out. We've consistently said that our first readout will most likely be Stark 221. So let me spend the minute on the study design, which we show on slide 18.

Terry Rosen: We continuously evaluate the entirety of our data to confirm our confidence in our study designs, and we remain as confident as ever about our three Phase III studies when we have the potential best-in-class anti-TIGIT, anti-PD-1 combination.

Terry Rosen: This brings me to the potential timing of our phase three readouts.

Terry Rosen: We have consistently said that our first readout will most likely be Star 221, so let me spend a minute on the study design, which we show on slide 18.

Terry Rosen: Importantly, this trial has dual primary endpoints of OS, the PDL-1 High Population, and then the ITT population. So send we put the study we'll be passing there. The Dom-Zim arm shows a statistical improvement in the PD-L1 high patients or in the ITT population. The study is well-powered with over a thousand patients, and we've closely monitored our recruitment to ensure the ratio of PDL-1I to PDL-1Mot patients is consistent with the assumptions used in the first statistical analysis plan. Given that O.S.

Terry Rosen: Reportedly, this trial has dual primary endpoints of OS.

Terry Rosen: In the PD-L1 high population and in the ITT population.

Terry Rosen: So, simply put, the study will be positive, the Dimitry Nuyten arm shows a statistical improvement in the PDL-1 high patients or in the ITT population.

Terry Rosen: The study is well-powered with over 1,000 patients and we've closely monitored recruitment to ensure the ratio of PD-L1 high to PD-L1 low patients is consistent with the assumptions used for our statistical analysis plan.

Terry Rosen: has been in the 13-month range for anti-PD1 Potskimo studies, and we completed enrollment in June. We think all of you can do the math and figure out when we might get to read out. The addressable market here is enormous, with 24,000 patients in the U.S. alone, approximately 50% of whom are PD-L1 greater than 5, and 80% of whom are PD-L1 greater than 1. This translates into a market opportunity of well over $3 billion in the U.S. alone. Before I close, I'm going to turn the call over to Bob to review our financial results for this quarter.

Terry Rosen: Given that OS has been in the 13-month range for anti-PD-1 plus chemo studies and we completed enrollment in June , I think all of you can do the math on when we might get to a readout.

Terry Rosen: The addressable market here is enormous, with 24,000 patients in the U.S. alone, approximately 50% of whom are PD-L1 greater than 5 and 80% of whom are PD-L1 greater than 1.

Terry Rosen: This translates into a market opportunity of well over $3 billion in the U.S. alone.

Terry Rosen: Before I close, I'm going to turn the call over to Bob to review our financial results for this quarter. Thanks, Terry. Arcus continues to be in a strong financial position. Our cash as of June 30th, 2024, was $1 billion, as compared to $1.1 billion as of March 31st, 2024.

Robert Goeltz: Thanks, Terry. Arcus continues to be in a strong financial position. Our cash as of June 30, 2024 was $1 billion, as compared to $1.1 billion as of March 31, 2024. Turning to our P&L, we recognize GAAP revenue for the second quarter of $39 million, which compares to $145 million for the first quarter of this year. Our revenue is primarily driven by our collaborations with Gilead and TIHO, and in the first quarter, we included a cumulative catch-up of $107 million, resulting from the Gilead amendment we executed in January.

Robert Goeltz: Turning to our P&L, we recognize gap revenue for the second quarter of $39 million, which compares to $145 million for the first quarter of this year.

Robert Goeltz: Our revenue is primarily driven by our collaborations with Gilead and TIHO, and in the first quarter included a cumulative catch-up of $107 million resulting from the Gilead amendment we executed in January .

Robert Goeltz: We continue to expect to recognize GAAP revenue of approximately $30 million per quarter for the remainder of 2024. Our R&D expenses for the second quarter are stated net of reimbursements from Gilead, and we're $115 million as compared to $109 million in the first quarter of this year. In the second quarter, known cash and stock compensation represented $10 million of R&DX. The increase in second quarter expenses was related to higher clinical trial costs offset partially by lower clinical manufacturing costs associated with our late stage program.

Robert Goeltz: We continue to expect to recognize gap revenue of approximately $30 million per quarter for the remainder of 2024.

Robert Goeltz: Our R&D expenses for the second quarter are stated net of reimbursements from Gilead, and were $115 million as compared to $109 million in the first quarter of this year.

Robert Goeltz: In the second quarter, non-cash.compensation represented $10 million of R&D expenses.

Robert Goeltz: The increase in the second quarter expenses was related to higher clinical trial costs offset partially by lower clinical manufacturing costs associated with our late-stage programs.

Robert Goeltz: We continue to expect modest increases in R&D expenses through 2024 and per-share expenditure to level off heading into 2025 as our late-stage investments shift from DOM towards CAAS and Quimley over time. As Terry noted, we expect our R&D investment in DOM to peak this year. G&A expenses were $30 million for the second quarter compared to $32 million in the first quarter of this year.

Robert Goeltz: We continue to expect modest increases in R&D expenses through 2024 and suspend a level off heading into 2025 as our late-stage investments shift from Dom towards cats and quimly over time.

Robert Goeltz: As Terry noted, we expect our R&D investment in Dom to peak this year.

Robert Goeltz: GNA expenses were $30 million for the second quarter compared to $32 million in the first quarter of this year. NungCash stock compensation represented $10 million of our GNA expenses for the second quarter, and we expect GNA expenses to remain stable for 2024.

Robert Goeltz: Non-cash stock compensation represented $10 million of our G&A expenses for the second quarter, and we expect G&A expenses to remain stable for 2024. Finally, we now expect our cash and investments balance at the end of 2024 to be between $885 and $925 million, as compared to our prior guidance of $870 to $920 million. We continue to expect these resources to fund operations into 2027. As a reminder, this guidance includes a $100 million partnership continuation payment from Gilead and the Kremlin opt-in payment from Tyho of $15 million.

Robert Goeltz: Finally, we now expect our cash and investments balance at the end of 2024 to be between $885 and $925 million, as compared to our prior guidance of $870 to $920 million.

Robert Goeltz: We continue to expect these resources to fund operations into 2027. As a reminder, this guidance includes a $100 million partnership continuation payment from Gilead and the Quimley opt-in payment from Taiho of $15 million.

Robert Goeltz: Both payments are due in the third quarter. Our guidance excludes, however, additional potential opt-in payments and milestones from our partners.

Robert Goeltz: For more details regarding our financial results, please refer to our earnings press release from earlier today in our tank queue. I'll now turn it back to Terry for concluding remarks.

Terry Rosen: Thank you very much, Bob. So, please let me end by reviewing our near-term data events. You know, they're both meaningful and very substantial.

Terry Rosen: Thank you very much, Bob. So, please let me end by reviewing our near-term data events. You know, they're both meaningful and very substantial.

Terry Rosen: First, in the fall, we expect to present ORR and other data from the 100-milligram dose expansion cohort of CAF. Those data will be followed closely by results from the 50-mg and 150-mg dose expansion cohorts and then data from our Cas-Cabo combination cohort in 2025. We also expect to initiate our first Phase III trial for Cas in the first half of 2025. With respect to DOM, we expect to present a few important data sets ahead of our first phase 3 readout.

Terry Rosen: First, in the fall, we expect to present ORR and other data from the 100 mg dose expansion cohort of CAF.

Terry Rosen: Those data will be followed closely by results from the 50mg and 150mg dose expansion cohorts and then data from our Cas-Cabo combination cohort in 2025.

Terry Rosen: We also expect to initiate our first Phase III trial for CAS in the first half of 2025.

Terry Rosen: With respect to DOM, we expect to present a few important datasets ahead of our first phase 3 readouts.

Terry Rosen: These include PFS and, very importantly, OS data from our original ARC-10 trial, which evaluated Domplazim versus Zim versus chemo in PD-L1 high lung cancer by year end, followed by OS data from our EDGE gastric phase 2 study in 2025. Meanwhile, we're continuing to advance our other programs, including the initiation of a phase 3 trial for QMLE in pancreatic cancer and the evaluation of All of these studies are enabled by the strength of our balance sheet and the great relationships with our partners.

Terry Rosen: These include PFS and, very importantly, OS data from our original ARC-10 trial.

Terry Rosen: which evaluated DOM plus ZIM versus ZIM versus CHEMO.

Terry Rosen: and PD-L1 High Lung Cancer by year-end.

Terry Rosen: followed by OS data from our Edge Gastric Phase II study in 2025.

Terry Rosen: Meanwhile, we're continuing to advance our other programs, including the initiation of a face-view trial for quimly in pancreatic cancer and the valuation next step for each human colorectal cancer.

Terry Rosen: All of these studies are enabled by the strength of our balance sheet and the great relationships with our partners.

Terry Rosen: Lastly, we continue to have a robust discovery engine at Arcus that enables a sustainable pipeline of future programs. The next program we expect to advance into mid-stage studies is AB801, our highly selective axon inhibitor. I want to conclude by thanking all of you. Thank you very much for your continued support of Arcus and our mission to bring innovative therapies to patients in need. And so we'll now open up the call for questions. Thank you.

Terry Rosen: Lastly, we continue to have a robust discovery engine at Arcus that enables a sustainable pipeline of future programs. The next program we expect to advance into mid-stage studies is AB801, our highly selective axial inhibitor.

Terry Rosen: I want to conclude by thanking all of you, thank you very much for your continued support of Arcus and our mission to bring innovative therapies to patients in need. So we'll now open up the call for questions. Thank you.

Operator: We will now begin the question and answer session. If you would like to ask a question, please press star followed by 1 on your telephone keypad. If for any reason at all you would like to remove that question, please press star followed by 2. Again, to ask a question, please press star 1. As a reminder, if you're using a speakerphone, please remember to pick up your handset before asking your question. You may proceed.

Operator: We will now begin the question and answer session. If you would like to ask a question, please press star followed by 1 on your telephone keypad.

Operator: If for any reason at all you would like to remove that question, please press star followed by 2.

Operator: Again, to ask a question, please press star 1. As a reminder, if you're using a speakerphone, please remember to pick up your handset before asking your question. The first comes from Yigal Nochomovitz with Citi. You may proceed.

Yigal Nochomovitz: Hi, great, Terry and the JAN team. Thank you. There are a lot of updates there. So on the expansion cohort that you're embarking on with CAS and CABO, can you just explain, is that something that you need to check the box on before initiating the PEAK-1 Phase 3 trial? Are there some expected overlapping talks that you may or may not see with CAB and CABO? And is the goal there mainly just to clear safety before moving into Phase 3 with that combo? Thanks.

Yigal Nochomovitz: Hi, great. Terry and the Jan team, thank you. A lot of updates there.

Speaker Change: So, on the expansion cohort that you're embarking on with CAS and CABO,

Yigal Nochomovitz: Can you just explain, is that something that you need to check the box on before initiating the peak, the peak one, phase three trial?

Yigal Nochomovitz: is there some expected overlapping talks that you may or may not see with Captain Cabo and is the goal they're mainly just to clear on safety before moving into the face to you with that Combo.

Terry Rosen: Thanks, Yigal. Dimitry, why don't you give a clear and concise answer to that question?

Terry Rosen: Thanks, Yigal. Dimitry, why don't you give a clear and concise answer to that question?

Dimitry Nuyten: Thank you, Terry, for your question. Yes, I wouldn't call it a checkbox, but it's important to establish safety information for a specific combination before you start a larger trial. So that's what the cohort is designed for. I do have to say, to your point about overlapping toxicities based on the individual safety profiles, CAS has now been studied in quite a few patients as monotherapy. CABA, of course, is

Dimitry Nuyten: please

Terry Rosen: Thank you, Terry.

Dimitry Nuyten: question. Yes, it's I wouldn't call it a checkbox, but it's important to establish safety information for a specific combination before you start a larger trial.

Dimitry Nuyten: So, that's what the cohort is designed for. I do have to say, to your point of overlapping toxicities, based on the individual safety profiles, CAS has now been studied in quite a few patients as monotherapy. CABO, of course, is very well established.

Dimitry Nuyten: We don't expect any relevant overlapping toxicity with the exception of fatigue, something that's impactful for patients but typically can be managed with those interruptions. Also, I'd like to note for CAS, in our experience so far, it is really rare for people to have even been dose-reduced, let alone discontinued treatment for toxicity. It's a very well-tolerated agent where short interruptions are pretty much what we need to do in the case of drug-related toxicities. And then lastly, we can refer to the experience with galsutafen and cabosanthineptase published in the Lancet, a series of about 55 patients showing, indeed, that the combination does not show any unexpected toxicities.

Dimitry Nuyten: We don't expect any relevant overlap in toxicity with the exception of fatigue.

Dimitry Nuyten: Something that's impactful for patients, but typically can be managed with those interruptions.

Dimitry Nuyten: Also, I'd like to note for CAS, in our experience so far, it is really rare for people to have even to be dose-reduced, let alone discontinued treatment for toxicity. It's a very well-tolerated agent where short interruptions is pretty much what we need to do in the case of drug-related toxicities. And then lastly, we can refer to the experience with galsutafen and carboxanthin, which was published in The Lancet.

Dimitry Nuyten: A series of about 55 patients showing, indeed, that the combination does not show any unexpected toxicities.

Jen: Okay, great. Thanks. And I just wanted to confirm what you said. I'm going to turn it over to you, Jen. Thank you. Jen, what you mentioned in terms of the data for the 50 mg, the primary progression of disease was less than the rate seen in LightSpark V, and we're going to get the 50 and 100 mg data separately from the 100 mg data later this year, is that correct?

Jen: Okay, great, thanks. And I just wanted to confirm what you said.

Jen: Jen, what you mentioned in terms of the data for the 50 mg, the primary progression of disease was less than the rate seen in LightSpark V, and we're going to get the 50 and 100 mg data separately from the 100 mg data later this year, is that correct?

Jen: Yeah, so, first of all, you heard correctly on primary progressive disease. So, for LIGHTSPARK-05, the primary progressive disease rate was 33%, and I said that for the 50-MIG cohort, some of what we saw for the 100-MIG cohort, we're seeing a significantly or substantially lower rate of primary progressive disease. As far as data presentation is concerned, we would present the cohort separately, but the point I was trying to make is that when we present the 100-MIG cohort of data in the fall, we will likely at least say something about the 50-MIG cohort and probably show some data from that as well, but it wouldn't likely be pooled.

Jen: So, first of all, you heard correctly on primary progressive disease, so for light spark 05, the primary progressive disease was 33%.

Jen: And I said that for the 50-MIG cohort, some of what we saw for the 100-MIG cohort were significantly or substantially lower.

Jen: primary progressive disease rate. As far as data presentation, we would present the cohort separately, but the point I was trying to make is that when we present the 100-MIG

Jen: Cohort of data in the fall, we will likely, at least, say something about the 50-meg cohort, and probably show some data from that as well that it wouldn't likely be pooled, they'd be showed separately.

Speaker Change: Okay, and then for the first line trial, which you...

Jen: Okay, and then for the first line trial, which. Yes, thank you. And then for the first line metastatic study, what sort of combo partners would you be considering there? TKI and PD-1 or anything else?

Jen: And then for the first line metastatic study, what sort of combo partners would you be considering there? TKI and PD-1 or anything else?

Terry Rosen: Yigal, we're going to be disclosing that very shortly. We would have loved to be able to disclose it today, but it's probably a couple of weeks off. And I think it'll fit within something that would meet your expectations.

Terry Rosen: You go we're gonna be disclosing that very shortly we would have loved to be able to disclose it today, but it's

Terry Rosen: It's probably a couple weeks often, I think it'll fit within something that would.

Terry Rosen: But the key thing about it and the reason we wanted to get it in today is because we wanted to show, sort of comprehensively, both what data we're going to have and what we're going to be starting in the next year. And we want to make it really clear that we're going to be going into the front line setting, and we're going to be doing it with a combination that Merck is not doing. And we feel we're going to be ahead of Merck. Yeah, and one last thing.

Terry Rosen: New York's expectations, but the key thing about it and the reason we want it.

Terry Rosen: to get it in today is because we wanted to show sort of comprehensively both what data we're going to have and what we're going to be starting in the next year and we want to make it really clear that we're going to be going into the frontline setting and we're going to be doing it.

Terry Rosen: with a combination that Mark is not doing, and we feel we're going to be ahead of Mark. Yeah, and the one last thing to mention, we called out that we would be doing this with a collaboration partner just to make it clear that we would be doing this in a very capital and resource efficient manner.

Terry Rosen: And one last thing to mention; we called out that we would be doing this with a collaboration partner just to make it clear that we would be doing this in a very capital and resource efficient manner.

Yigal Nochomovitz: Okay, I gotcha. Thank you.

Dr.: Okay, I'm Dr. Thank you.

Terence Flynn: Thank you. The following comes from Terence Flynn with Morgan Stanley. You may proceed.

Terence Flynn: Thank you all.

Terence Flynn: Thank you. The following come from Terence Flynn with Morgan Stanley . You may proceed.

Alex Kornin: Hello, this is Alex Kornin for Terence, and thank you guys for taking our question. Can you give us any insights on potential presentation than you for this cast, if it's all fun to see better data for our 20 data? The presentation will be in the fall, and can you remind us on the number of stations and duration of the follow-up we should expect with this update?

Speaker Change: Hello, this is Alex and Colin infotainants and thank you guys for taking our question.

Proud: Proud, can you give us any insights on potential presentation menu for this task, if to also consider for our 20 data, the presented info, and can you remind us on the number of patient and duration of the follow-up we should expect with this update?

Jen: Yeah, sure. But we're not going to, unfortunately, disclose the medical meeting that we've submitted the data for presentation at. It's in the fall. You may be able to guess it since we're running out of conferences that it could be presented at. It won't be at ESMO, just to be clear on that. And then, for the second part of your question. Um, and I'm actually going to figure out when the second part of your question was... We have our patients, they'll be about 30, they'll be just a little bit above 30, and we'll have about 10 months of medium follow-up at that point in time.

Jen: Yeah, sure. So we're not going to unfortunately disclose the medical meeting that we've submitted the data for presentation at. It's in the fall.

Jen: You may be able to guess it since we're running out of conferences and it could be presented at it. It won't be as mode just to be clear on that. And then for the second part of your question.

Jen: and I'm actually going to read one of the second part of your question was

Jen: A number of patients. A number of patients. It'll be about 30. It'll be just a little bit above 30, and we'll have about 10 months of medium follow-up at that point in time.

Jen: Okay, thanks, and maybe just on one trial. Right. Right. Thank you. And on your new trial design, like, can we do any read through from your expansion cohort that you're currently enrolling, is it going to be the same patient population? Anything you can comment on that?

Jen: Thanks.

Jen: Okay, thanks. And maybe just on trial. Right, right. Thank you. And on your new trial design, like, can we do any read through from your expansion call-hort that you currently in rolling, is like, is it going to be the same patient population? Anything you can comment on that?

Jen: It's what we said, so P1 will enroll a healthier, less advanced patient population than what we're looking at in our 20. So, obviously, the fact that the drug is looking very good in ARC-20, obviously, we think bodes positively for peak one.

Jen: So what we said, so peak one will enroll a somewhat healthier, less advanced patient population than what we're looking at in ARC-20.

Jen: I'm sorry for the fact that the driver's looking very good in our 20, obviously we think though it's possibly for peak 1.

Jen: But the patient population that we would be looking at is a bit of a mix of first and second line. So, it would include patients that receive PD-1 therapy in the adjuvant setting. So, as a reminder, PEMBRO is approved in the adjuvant setting. So, patients post-nephrectomy that are at high risk of recurrence will go on PEMBRO. And then we'll also include patients that receive PD-1 in the first line metastatic setting.

Jen: But the patient population that we would be looking at is a bit of a mix of first and second lines. So it would include patients that receive PD-1 therapy in the adjuvant setting. So as a reminder, PEMBRO is approved in the adjuvant setting. So that is used in patients post-nephrotomy that are at high risk of recurrence will go on PEMBRO.

Jen: And then we'll also include patients that received PD-1 in the first-line metastatic setting, so they would then be part of our study.

Jen: So, they would then be part of our study as a second-line metastatic patient. But as we've spent a lot of time analyzing all the data that's out there for the different light spark studies, we feel like this is a patient population that will benefit particularly well from HIF-2-alpha inhibition. So we spent a lot of time working with our advisors to identify what we think is the best patient population for this drug, and this is what we decided on.

Jen: as a second line metastatic patient.

Jen: but as we've spent a lot of time analyzing all the data that's out there for the different life-sport studies, we feel like this is a patient population that...

Jen: will benefit particularly well from his 12th inhibition, so he said a lot of time working with our advisors to identify what we think is the best patient population for this drug.

Jen: And this is what we've decided upon.

Jen: Great, thank you very much.

Jen: Great, thank you very much.

Jonathan Miller: Thank you. The next question comes from Jonathan Miller with Evercore. You may proceed.

Speaker Change: Thank you. The next question comes from Jonathan Miller with Evercore. You may proceed.

Jen: Hi guys, thanks for taking my question. Thanks for all the detail this afternoon. Jen, I just – I feel like I missed it, and I wanted to get clarification. You suggested that ORR was better than Merck in the 50 milligram CAS cohort, and I just wanted to get some confirmation that that was what you said. And also, is ORR better in the 100 mg arm as well? I know you've sort of stopped short of saying that in the past.

Jen: Hi, guys. Thanks for taking my question. Thanks for all the detail this afternoon. Jen, I just – I feel like I missed it, and I wanted to get clarification. You suggested that the ORR was better than Merck in the 50-milligram CAS cohort.

Jen: And I just wanted to get some confirmation that that was what you said, and also, is the aura better in the 100-MIG arm as well? I know you've sort of stopped short of saying that in the past.

Jen: And then, I guess, given what you've seen so far with primary progression rates and ORR data that you've got in hand, do you see a dose response in those higher dose cohorts, 50, 100, 150, at this point?

Jen: And then, I guess, given what you've seen so far with primary progression rates and ORR data that you've got in hand, do you see a dose response in those higher dose cohorts, 50, 100, 150, at this point?

Jen: Yeah, so good question, John. So, yeah, so for 50 MIG, I did say that we're seeing a higher ORR today than the 21.9% that was seen with LightSpark 005. I did also clarify that with one response pending confirmation, we would be above the 21.9%. And I also pointed out that 50 MIGs, given that they started enrollment after the 100 MIGs, that's a much less mature cohort from a follow-up perspective relative to the 100 MIGs. And then the 100 MIGs, yes, you know, we're now north of where LightSpark 005 is. And I'll let Terry speak about that.

Terry Rosen: Good question John. So yeah, so for 50-mig, I did say that we're seeing a higher ORR today than a 21.9% that we've seen with like Sparkle 5.

Jen: I did also clarify that that's with one response as pending confirmation. We would be above the 21.9%, and I also pointed out that 50 MIGs, given that started enrollment after the 100 MIGs, that's a much less mature number.

Terry Rosen: cohort from a follow-up perspective relative to 100 MiGs and then the 100 MiGs, yes, you know, we're now north of where LightSpark 005 is.

Terry Rosen: I'll take the dose response question. So the first thing to sort of caveat is that the patient populations are also slightly different. So the 100-milligram cohort is a slightly more advanced patient population, and as we've noted, it's a more advanced population when compared to LightSpark-005. But with that said, I would say at this point, particularly given that the 50-milligram cohort is somewhat or substantially less mature, it would be hard to distinguish. So I actually think, given that they're each in the 30-ish range, as you might anticipate, John, more likely than not, none.

Terry Rosen: And I'll let Terry speak about that. I'll take the Goeltz response question. So the first thing...

Terry Rosen: The sort of caveat is that

Terry Rosen: The patient populations also are slightly different, so the 100 milligrams cohort is slightly more advanced patient population, as we've noted it's more advanced population, when compared to light spark 0.5.

Terry Rosen: But with that said, I would say it's this point, particularly given that the 50 milligram cohort is somewhat or substantially less mature.

Terry Rosen: It would be hard to distinguish, so I actually think, given that they're each in the 30-ish range, as you might anticipate, John, more likely than not any.

Terry Rosen: The last point I want to remind you about that, though, is that to contextualize that you're actually, even the 50 milligram cohort is two and a half times the PDE equivalent of Belzodepan. And as you know, Belzodepan was enough to really shift the change in the standard of care. So the nice thing about that, as all these data start to unfold as well, they're 30 patients, and while we're not gonna combine the data from just an understanding of the program and the potential of the molecule, you're gonna start to be able to look at these and treat these cohorts, not like one was it homeopathic, one was it medium, one was sitting at heart. You're gonna have doses that let you sort of look at these patients in total and make an assessment of how you feel our molecule looks compared to anything you've seen with Belzuda.

Terry Rosen: Distinguishing that we'll be able to do between them will probably potentially be reflected in durability. So I don't think you're gonna, the 50 is looking good enough that

Terry Rosen: You won't be able to probably tell a difference between the 50 and 100. The last point I want to remind you on that, though, is that

Terry Rosen: To contextualize that.

Terry Rosen: You're actually, even the 50 mg cohort, is at 2.5, the PD equivalent.

Terry Rosen: And...

Terry Rosen: and Bill Zutophan. And as you know, Bill Zutophan, you know, was enough to really shift the change in the standard of care. So the nice thing about that is all these data start to unfold as well. There are 30 patient cohorts.

Terry Rosen: Well, we're not going to combine the data from just an understanding of the program and the potential of the molecule. You're going to start to be able to look at these in

Terry Rosen: You know, treat these cohorts, not like one was it homeyopathic, one was it medium, and one was sitting at heart. You're going to have doses that let you sort of look at these patient populations in total and make an assessment of how you feel our molecule looks compared to anything you've seen with those due to fan.

Jen: All right, great. Makes sense. And then maybe one more question on the CAS strategy. Obviously, you talked about a CABO combo going to phase three, this other mystery combo in the first line setting. Should we expect to see, how broad should we expect to see the late stage development program for CAS get in terms of the number of different combos, number of different settings, maybe beyond RCC?

Jen: All right, great. Makes sense. And maybe one more question on CAS.

Jen: Strategy. Obviously, you talked about a Cabo combo going to phase three, this other mystery combo in first line setting.

Jen: Should we expect to see, how broad should we expect to see the late stage development program for CAS, GED in terms of number of different combos, number of different settings, maybe beyond RCC as well?

Jen: Yeah, so, you know, I say over the next six to nine months. The two phase three studies that we called out today will probably be it for us for now. It's our phase three studies. That's a lot of our opportunity of massive, so we will be focused on getting the studies off the ground. You should expect to see some of the additional work in our 20 where we're looking at some other interesting patient populations that we want to explore within that study that could then lead to later stage studies in the future.

Jen: Yeah, so, you know, so I'd say over, you know, sort of the next six to nine months.

Jen: The two phase three studies that we called out today will probably be it for us for now, as far as phase three studies. That's a lot. Market opportunity is massive, so we will be focused on getting

Jen: This study is off the ground.

Jen: Where you should expect to see some of the additional work in our 20 where we're looking at some other interesting patient populations that we want to explore within that study that could then lead to later stage studies in the future. But we asked them really.

Jen: And, I think, we're going to have a lot of interesting populations in mind where we think HIF-12 inhibition, even as monotherapy, can have a really interesting effect. And so, we'll talk more about those over the coming months.

Jen: And then I would say, you know, your question on other tumor types, you know, we do think there's some interesting opportunities there as well, but I think.

Jen: You know, over the near term, you should expect to see more out of us from RCC, which is kind of keeping our hands full. Although, you know, interestingly, we're getting a lot of IST requests for studies at HCC. So there's definitely a lot of interest out there in the clinical community in evaluating CAF.

Jen: Over the near term, you should expect to see more out of us from RCC, which is kind of keeping our hands full, although, interestingly, we're getting a lot of IST requests for studies at HCC, so there's definitely a lot of interest out there in the clinical community in evaluating CAF and HCC in particular.

Jonathan Miller: All right, that makes sense. Thanks so much.

Jonathan Miller: All right, that makes sense. Thanks so much.

Salveen Richter: As a quick reminder, if you would like to ask a question, please press star one on your telephone keypad. The next question comes from Salveen Richter with Goldman Sachs. You may proceed. Hi, this is Lydia on behalf of Salveen. Thanks so much for taking our question. We just have one on etruma and colorectal cancer. Just given the phase one, two data that you shared at ASCO, what do you see as the likely registration path here? And when do you expect to share the next steps for this program? Thank you so much. Okay, so obviously, you can tell

Speaker Change: Thank you. Thank you.

Salveen Richter: As a quick reminder, if you would like to ask a question, please press star 1 on your telephone keypad. The next question comes from Salveen Richter with Goldman Sachs. You may proceed.

Salveen Richter: Hi, this is Lydia Onford, so I'll be in thanks for taking our question. We just have one on each room, I encoded our talk answer. Just give them a phase one to the data that you've started to ask. What do you see as the likely next Wednesday's additional path here? And when you expect to share an access to this program, thank you so much.

Daina Graybosch: Thanks so much. Thank you. Thank you. The next question comes from Daina Graybosch with Learing Partners. You may proceed.

Terry Rosen: And so obviously, from what we've been talking about today, we've been doing a lot of planning and execution, and that's certainly a program that we're very excited about, Gilead's very excited about, and we're working through. I'll just throw out there, since you asked a question, we'd like to give answers. We have had a lot of push from our advisory board that it might be smart to move this towards the frontline setting, move a little earlier than where we were, but we haven't sorted through all that, and we're literally in the midst of those discussions to decide exactly where we might go, but you shouldn't be surprised if we end up going in that direction.

Terry Rosen: So, obviously, you can tell from what we've been talking about today, we've been doing a lot of planning and execution and that's certainly...

Terry Rosen: a program that we're very excited about, Gillia is very excited about, we're working through.

Terry Rosen: I'll just toss out there, since you asked question we'd like to give answers. We have had a lot of push from our ad board that it might...

Terry Rosen: Be smart to move this towards the frontline setting move a little earlier than where we were, but we haven't sorted through all that. And we're literally in the midst of those.

Terry Rosen: Discussions to society exactly where we might go, but you shouldn't be surprised if we end up going in that direction.

Speaker Change: Thanks so much.

Speaker Change: Thank you.

Terry Rosen: Thank you. The next question comes from Daina Graybosch with Learing Partners. You may proceed.

Speaker Change: Hi, I have a question on TIGIT on ARC-10. I wonder if you can help set expectations, given this is from, you know, early in the ARC-10 design, about the type of patients you enrolled in terms of prognosis and region, so that we can think about comparing the data to the other.

Daina Graybosch: Great. So I'll set a little bit of expectations for the data, and then I'm going to let Dimitry get to the specifics of your question on patient demographics. But I'll just say that, you know, we believe that these data will be, you know, positive for the field, positive for DomZim, and positive for Zim in terms of it being a really nice data set. And in fact, if you think about all of the randomized data sets out there, you know, I would put this against any of them in terms of the information that it'll convey with a good anti-PD-1 and the So, you know, we definitely want to lean into this being an important, a good data set. And I'll let Dimitry say a little bit about the patient population.

Dimitry Nuyten: Trials in the setting, including ARC-VII.

Daina Graybosch: Great. So I'll set a little bit of expectations on the data and then I'm going to let Dimitry

Dimitry Nuyten: get to the specifics of your question on patient

Dimitry Nuyten: Demographics, but I'll just say that, you know, we believe that these data will be, you know, positive for the field, positive for Dom's M and positive for them in terms of it being a really nice.

Daina Graybosch: Data Set, and in fact, if you think about all of the randomized data sets out there, you know, I would put this against any of them in terms of the information that I'll convey with, you know,

Speaker Change: Good anti-PD1 in the FC Silent Anti-Tedget. So...

Daina Graybosch: You should, you know, I we definitely want to lean in to this being an important and a good data set now let the meet you say a little bit about the patient population.

Dimitry Nuyten: Yeah, so the face population, just to break it down, and also for others, so it was a three-arm trial, ARC-10 Part 1. It was a 2-to-2-to-1 randomization, so there were about 40 patients, 4-0, on DOM and ZIM, another 40 on ZIM alone, and then about 20 on chemotherapy. That does mean that the study was run outside the US and did not include some of the core European countries because of the availability of checkpoint inhibitors as standard of care and monotherapy there.

Dimitry Nuyten: Yeah, so the face population, just to break it down, and also for others, so it has, it was a three-arm.

Dimitry Nuyten: trial, ARC-10 Part 1. It was a 2-to-2-to-1 randomization, so it's about 40 patients, 4-0 on DOM and ZIM, another 40 on ZIM alone, and then about 20 on chemotherapy.

Dimitry Nuyten: That does mean that the study was from ex-U.S. and did not include some of the core European countries.

Dimitry Nuyten: because of the availability of checkpoint inhibitors as standard of care and monotherapy there. However, it is still a, let's say, by inclusion criteria, very comparable to other trials run in this space. And it has the chemotherapy control arm that, of course, can be compared to other chemotherapy trials that were run slightly earlier. And I think that's gonna be very helpful to benchmark the population. But in principle, it's a very straightforward first line population.

Dimitry Nuyten: However, it is still, let's say, by inclusion criteria, very comparable to other trials run in this space, and it has the chemotherapy control arm that, of course, can be compared to other chemotherapy trials that were run slightly earlier, and I think that's going to be very helpful to benchmark the population. But in principle, it's a fairly straightforward first-line population. And there's quite another thing to point out.

Dimitry Nuyten: And one other thing to point out with that data set that's, I think, interesting is there are really two different readouts within the data set. One is Dom plus Zim versus Zim, and the other is Zim versus Chemo, which is how the study was set up. So, you'll also see that comparison of stem versus chemo.

Dimitry Nuyten: [inaudible]

Dimitry Nuyten: And one other thing to point out with that data set that's, I think, interesting is there's really two different readouts within the data set. One is Dom plus Zim versus Zim, and the other is Zim versus Chemo, which is how the study was set up. So you'll also see that comparison of Zim versus Chemo.

Dimitry Nuyten: and that right out.

Dimitry Nuyten: [inaudible]

Dimitry Nuyten: The next question comes from Astika Kwanin with Truist Securities. You may proceed. Hey, guys. Thanks for taking my question.

Astika Kwanin: Thank you.

Speaker Change: The next question comes from Astika Kunwani with Truist Securities. You may proceed.

Astika Kwanin: Hey, guys. Thanks for taking my questions. Apologies if I asked something that has already been asked. I just briefly jumped on the call here. But just very quickly, can you tell us when Cohort A of the TRUMA NCRC study is going to be reading out? He just made a comment about how the carelels are pointing, and that's a suitable tumor type to go into.

Astika Kwanin: Hey, guys. Thanks for taking my questions. Apologies if I asked something that already has been asked. I just recently jumped on the call here. But just very quickly, can you tell us when Cohort A of the TRUMA NCRC study is going to be reading out?

Speaker Change: You just made a comment about how the KOLs are pointing that that's a suitable term to go into. So just wondering about that. And then when you think about the HIF combination, obviously, Ricardo, that makes a lot of sense.

Speaker Change: And given the function on TREG, you know, we can rush both PD-1 and CPLA-4 as good combination partners. I just want to get your thoughts on that. Thank you.

Astika Kwanin: And...

Terry Rosen: Okay, so I'll take, let me take the question on the second cohort. It'll be, like, sometime next year. It's simply, again, the OS in the upsetting is substantially longer and data simply, I'm sure at this, at this point. Remind me of the second question.

Terry Rosen: Okay, so let me take the question on the

Speaker Change: Second cohort, it'll be.

Terry Rosen: Likely sometime next year. It's simply, again, the OS...

Terry Rosen: and they are setting is substantially longer and data simply are sure at this point. So, will you remind me the second question?

Operator: The second question was on TEF. Can you run to the second question?

Operator: Yeah, when you think about HIT in combination with PD-1, it obviously makes sense to think about a combination of PD-1, but yeah. Unknown Speaker Yeah, so actually, we're

Speaker Change: The second question was on TEF. Can you run to the second question?

Unknown Speaker: Yeah, when you think about HIF and in combination with PD-1, it obviously makes sense to think about a combination of PD-1, but yeah, how do you like...

Terry Rosen: Yeah, so actually, we're going to be disclosing very shortly a second registrational trial that takes us into the frontline setting. But your point about anti-PD-1, anti-CTLA-4, and combinations thereof, obviously those are all reasonable combinations to be thinking about that would make a whole lot of sense to go with HIF-2 inhibition.

Terry Rosen: Yeah, so actually, we're going to be disclosing...

Terry Rosen: very shortly a second registrational trial that takes us into a front-line setting. But your point about...

Terry Rosen: You know, in that PD1, anti-CTLA for combination, there are obviously those are all reasonable combinations to be thinking about that would make a whole lot of sense to go with if-to-inhibition.

Terry Rosen: Thanks for watching!

Terry Rosen: Thank you.

Operator: There are currently no other questions queued at this time. I will pass this back over to the management team for closing remarks. Thank you all for joining us. Thanks, everybody. This concludes the conference call. Thank you for your participation. You may now disconnect your line.

Speaker Change: Thank you. They are currently no other questions cute at this time, and we'll pass it back over to the management team for closing remarks.

Speaker Change: Thank you all for joining us.

Operator: [inaudible]

Operator: This concludes the conference call. Thank you for your participation. You may now disconnect your line.

Operator: Pia Eaves, Pia Eaves, Pia Eaves, Pia Eaves, Pia Eaves, Pia Eaves, Pia Eaves, Pia Eaves, Pia Eaves, Pia Eaves, [inaudible]

Terry Rosen: It's pretty remarkable for the third line plus setting, in contrast to the many TKI therapies, where patients may respond quickly, but they rapidly progress. The tolerability of Belzodifant, with on-mechanism anemia and hypoxia being the only meaningful treatment of emergent adverse events, enables patients to remain on treatment for long periods. We've consistently heard from clinicians how well tolerated belzutifen has been for patients, particularly relative to the TKI. While valzutifan is a good molecule, with Cas, we have a potentially best-in-class molecule due to its excellent pharmacodynamic and dose-proportional pharmacokinetic profile. It's really a great molecule.

Jen: The Cabo is preferred over other TKIs because of its proven efficacy, their comfort with managing Cabo-related AEs, and the simplicity of Diff. Specifically, there are only two apprentices for Cabo, compared to five different distances for LaVatnaus. The Cabo is used as relatively easy to titrate. And importantly, it has also been shown to have more of a 9-staffy profile than that of LaVatnaus.

Jen: In contrast, in Mark's light spark 022, similar studies, they're evaluating Dell due to Flynn, with whom that nibs as the TKI and experimental arm versus Cabo in the control. Second, our twice-of-combination partner is Cabo, the most widely used TKI. We have received consistent feedback from physicians.

Astika Kwanin: He's just wondering about that. And then we think about the case combination, obviously recovered, you know, that makes a lot of sense. And given the function of the key rig, you know, we can get rush as both Peter 1 and Peter 4 as good combination partners. I just want to get your thoughts on that. Thank you.

Robert Goeltz: Both payments are due in the third quarter. However, our guidance excludes, however, additional potential opt-in payments and milestones from our partners. For more details regarding our financial results, please refer to our earnings press release from earlier today in our tank queue. I'll now turn it back to Terry for concluding remarks. Thank you.

Terry Rosen: So we're going to link the mechanism to clinical out. Both we and our clinical advisors are eager to advance the treatment for colorectal cancer. We're going to update you once we finalize the next steps.

Terry Rosen: The DOM plus them demonstrates clinically meaningful improvements over anti-PD-1 model therapy in the setting, with limited additional toxins. Second, we in Gilead expect to present OS data from Edge Gastric in 2025. As I mentioned, given that our median PFS is already in line with the OS results observed for anti-PD1 plus chemotherapy alone, we expect to report very compelling overall survival data. And I can say today that well over 50% of patients remain on study 18 months after enrollment is completed in this cohort.

Jen: But we have some really interesting populations in mind where we think it's also an addition, even as a monitor, if you can have a really interesting effect. And so we'll talk more about those over the coming months. And then I would say, you know, your question about other tumor types, we do think there are some interesting opportunities there as well.