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spk02: Good afternoon. Thank you for attending today's Arcus Biosciences Second Quarter 2024 earnings call. My name is Tamia and I will be your moderator for today's call. All lines will be muted during the presentation portion of the call with an opportunity for questions and answers at the end. If you would like to ask a question, please press star 1 on your telephone keypad. I would like to pass the conference over to your host, Pia East, Vice President of Investor Relations and Strategy. You may proceed.
spk09: Hello everyone and thank you for joining us on today's conference call to discuss Arcus' Second Quarter 2024 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 cash runway and our expected clinical development milestones and timelines. All statements, other than historical facts, reflect the current beliefs and expectations of management and involve risks and uncertainties that may cause our actual results to differ from those expressed. Those risks and uncertainties are described in our most recent annual report on Form 10K and quarterly report on Form 10Q that have been filed with the SEC. We strongly encourage you to review our filings. Today you'll hear from our CEO Terry Rosen, COO Jennifer Jarrett and CFO Bob Gales. We'll also be joined by our CMO, Dimitri Nautin and President Juan Haiyan for questions after the prepared remarks. With that, I'll turn the call over to Terry.
spk06: 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 consequential. We completed an enrollment of our first phase three trial, STAR-221, a thousand plus patient study and first line upper GI adenocarcinomas. 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. Cas-Datafan or CAS, our HIF-2 alpha inhibitor, will be our newest phase three entrant. We're going to share a lot of information about this program today and, in fact, throughout the rest of the year. The HIF-2 alpha inhibition mechanism has been clinically validated by the approval of Merck's 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. Belzutafan is already generating over $500 million in the annualized run rate sales just six months after approval in clear cell RCC. This clearly demonstrates the unmet need in this indication, the excitement around the and the significant opportunity which we intend to capitalize upon. In addition to Belzutafan 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
spk01: its
spk06: durability. In the phase one, two study for Belzutafan, over 20% of patients had not progressed and remained on treatment beyond two years. Several of these patients, in fact, are now approaching four years on treatment. In the phase three registrational light spark O05 trial, at the time of the first data presentation, four times as many patients were still on treatment with Belzutafan than with the comparator Everalymus. This is pretty remarkable for the third line plus setting in contrast with the many TKI therapies where patients may respond quickly, but then they rapidly progress. The tolerability of Belzutafan with on mechanism anemia and hypoxia being the only meaningful treatment emergent adverse events enables patients to remain on treatment for long periods. We've consistently heard from clinicians how well tolerated Belzutafan has been for patients, particularly relative to the TKIs. While Belzutafan 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. CAS' PKPD profile enables us to deliver five or more times the PD equivalent of the improved dose of Belzutafan, which may result in more rapid onset and greater clinical efficacy relative to those of Belzutafan. And in fact, in our ARC-20 study, we're already seeing this differentiation play out in the data, which we look forward to sharing later this year. The further leverage CAS' improved profile, we're pursuing differentiated combinations relative to those being investigated with Belzutafan. You're going to hear more about this today from Jen when we disclose for the first time the design of our first Phase III study for CAS, Peak 1. We have some other exciting studies in the works that we're going to talk more about in the near future. Moving on to our FC-silent antitidgen antibody domvanilumab and START-221, our Phase III trial evaluating dom plus our -PD-1 Zym plus chemo and first-line upper GI cancers. In June, we completed enrollment of START-221, enrolling over 1,000 patients in just 18 months. And we expect START-121, complete enrollment later this year. So we're now turning our focus towards data readouts. While we recognize, you know, the anti-tidget 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 antibodies. This is because the FC-antitidgen antibodies substantially deplete peripheral regulatory T cells and correspondingly increase immune-related AEs. 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. 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, necessitating simultaneous discontinuation of both components of their -PD-1 anti-tidget therapy. Additionally, because tidget is expressed on several other types of immune cells, depleting tidget-bearing immune cells can be counterproductive for any therapeutic strategy that's designed to stimulate the immune system to eliminate cancer cells. We have two impactful data sets coming that we're going to talk about a bit later, both of which we believe will not only restore but enhance confidence in the potential of the tidget pathway, so tidget pathway in general, but in particular in DOM is an FC-silent anti-tidget antibody. I want to briefly comment on our CD73 and adenosine receptor programs, QEMLY and Etruma respectively.
spk01: For Etruma
spk06: and ASCO, we presented data from our randomized ARC9 study, which showed unprecedented median overall survival of over 20 months for an Etruma-based combination of third-line colorectal cancer. 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 described the ability of Etruma to block the effects of adenosine in tumors, as well as the relationship between CD73 expression and patient survival. So we're going to link mechanism to clinical outcomes. Both we and our clinical advisors are eager to advance Etruma and colorectal cancer. We're going to update you once we finalize next steps for this program. For QEMLY, 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 Taiho decided last month to exercise its option to the QEMLY program. Taiho 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 QEMLY in Japan, as well as other countries in Asia, but excluding mainland China. They'll now operationalize and be responsible for the costs of PRISM-1 in Japan. Their exercise of this option further illustrates the potential for QEMLY in pancreatic cancer, and we expect Taiho to play a valuable role in the successful execution of the PRISM-1 study. Finally, 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. 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 was completed enrollment and the second that is expected to complete enrollment this year. 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. The timing of this is perfect. We're now able to shift resources and investment to our next strategic priority, CAS DataFan. CAS represents a very rare opportunity. We have a validated target in HIP2-alpha. Belzutafan has been embraced by physicians and patients as an important new standard of care, despite what are very clear limitations. CAS has an approved 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 Belzutafan and our growing CAS 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 CAS in greater detail.
spk08: Thanks, Terry. Slide 26 shows the design of ARC-20, our phase one study for CAS in late-line clear cell RCC. It includes three monotherapy expansion cohorts, each initially enrolling approximately 30 patients that are evaluating 50 Migs, 100 Migs, and 150 Migs of CAS, as well as a combination cohort that is evaluating CAS plus calzatinib. Patients in the monotherapy cohorts had to have progressed on both an -PD-1 and TKI therapy in the metastatic setting to be eligible. We have submitted data from the 100-Mig 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. Patients in this cohort had a medium of three prior lines of therapy and 25 percent of patients had four or more prior lines. In comparison, the phase three trial for Belzutafan, like SPARC-005, enrolled only patients who received one to three prior lines of therapy. As a reminder, the ORR for SPARC-005 was 21.9 percent and the primary progressive disease or primary PD rate was 33 percent. We expect our data presentation to support CAS's potential -in-class profile, specifically better efficacy with comparable safety relative to that of Belzutafan, even when evaluated in a more advanced patient population than SPARC-005. Because of the significant interest in R20, 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 in approximately a year across the three monotherapy cohorts, which is incredible for a phase one study and a single tumor type. Moving on to the 50-Mig cohort, which completed enrollment in April, these data are maturing very nicely. We also now expect to share some information from this cohort in the fall. 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 before their first scan. Like we observed in the 100-Mig cohort, the primary PD rate is substantially less than the 33 percent observed in like SPARC-005. This is another data point demonstrating that CAS seems to bring tumor growth under control more quickly than Belzutafan. Also, like the 100-Mig 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 like SPARC-005, even with very limited follow-up. Finally, we recently completed enrollment at the 150-Mig expansion cohort. So between now and the end of 2025, we expect to present a steady stream of data for Mark 20, including at least 120 patients worth of data for CAS monotherapy, as well as potentially initial data from our CAS plus CABO combination cohort. 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. Following FDA – following feedback from the FDA later this year, we plan to begin our first phase 3 trial, peak one, in the first half of next year. The proposed design of peak one, which is shown on slide 29 of our corporate deck, is simple. 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. Peak one will enroll patients who have received prior -PD-1 therapy. This includes patients who received PEMBRO in the ADGE event or post-nephraxomy setting, as well as patients who received -PD-1 in the first-line metastatic setting. So peak one will target a huge patient population and deep patient population that we believe will significantly benefit from HIF-2 alpha inhibition. We plan to use the once daily dose of 100 mg of CAS in this study. All of our PKPD exposure response and safety data from our dose escalation and expansion cohorts support 100 mg as a go-forward dose from our combination studies, and the primary endpoint of this study will be PFS. We expect the peak one design to be extremely attractive for both clinicians and patients for a number of reasons. First, simplicity. We are using CABO in both the experimental arm and the control arm. In contrast, in Mark's Lightspark 022, their similar study, they are evaluating Belzudafan with Limvatnib as the TKI in experimental arm versus CABO in the control arm. Second, our choice of combination partner is CABO. The most widely used TKI. We have received consistent feedback from physicians that CABO is preferred over other TKIs because of its proven efficacy, their comfort with managing CABO-related AEs, and the simplicity of dosing. Specifically, there are only two approved doses for CABO compared to five different doses for Limvatnib, so CABO is viewed as relatively easy to titrate. And importantly, CABO has also been shown to have a more benign safety profile than Limvatnib. Peak one 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 the advanced stages of planning for a study with a collaboration partner that will evaluate CAS in a potential -in-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. The market opportunity for CAS 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 dip. 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 CAS 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, our FC silent and titrated antibody.
spk06: Thanks very much, Jen. So in ASCO in early June, we had two oral presentations, something we think is pretty incredible for a company of our size and stage, and that included new data for EDGE gastric, our phase two trial evaluating DOMZim plus chemo in upper GI cancers. As you can see on slide 16 of our corporate deck, in a 40-patient cohort, the DOMZim combination demonstrated a pretty impressive medium PFS of 12.9 months for the overall population and 13.8 months for the PD-L1 high population. These far exceed the benchmark PFS data for -PD-1 plus chemo that's in the 7 to 8 month range. And in fact, the median PFS data for EDGE gastric actually approached the benchmark median OS of 13 to 14 months for -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. These results meaningfully de-risk our start 221 phase three study, which is evaluating the same combination in the same setting as EDGE gastric. We expect to have overall survival data for EDGE gastric in 2025. Given this is the primary endpoint for start 221, these data should further enhance the likelihood of a successful outcome for our phase three study. We continue to believe not only that anti-TIDGET 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. While the failure of skyscraper six, Rocha's phase two three study, which evaluated Turago plus Atiso plus chemo versus Pembroke plus chemo, is disappointing for patients, we've articulated to you the many important differences between our studies and skysix. And we really think that most of you have agreed with us on these points. We've generated tremendous amount of data that support DOM's potential to add meaningful clinical benefit both non-small cell lung cancer and upper GI cancers. And we expect to present
spk01: two new
spk06: data sets that will further support DOM's significant potential in lung and upper GI cancers. So first off, by year end, we and Gilead plan to report data from ARC-10 part one, a randomized phase three study in PD-L1 high non-small cell lung cancer. So let me just give you a reminder. We stopped enrollment for strategic reasons earlier 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 chemotherapy arms and approximately 20 patients were enrolled in the chemotherapy arm. As we promised at the time, we shifted our focus to STAR-121. We will present both PFS and OS, including hazard ratios. And we believe that these data will reaffirm what we observed in ARC-7, that DOM plus ZIM demonstrates clinically meaningful improvements over -PD-1 monotherapy in this setting with limited additional toxicities. Second, we and 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 -PD-1 plus chemotherapy alone, 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. 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 -PD-1 combination. This brings me to the potential timing of our phase three readouts. We've 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. Importantly, this trial has dual primary endpoints of OS, in the PD-L1 high population and in the ITT population. So simply put, the study will be positive if the DOMS MR 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 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. Given that OS has been in the 13 month range for -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. The addressable market here is enormous with 24,000 patients in the US alone, approximately 50% of whom are PD-L1 greater than 5 and 80% of whom are PD-L1 greater than 1. This train translates into a market opportunity of well over three billion dollars in the US alone. Before I close, I'm going to turn the call over to Bob to review our financial results for this quarter.
spk05: Thanks, Jerry. ARCUS continues to be in a strong financial position. Our cash as of June 30th, 2024 was one billion dollars as compared to 1.1 billion as of March 31st, 2024. Turning to our P&L, we recognize gap revenue for the second quarter of 39 million dollars, which compares to 145 million for the first quarter of this year. Our revenues primarily driven by our collaborations with Gilead and Taiho and in the first quarter included a cumulative catch-up of 107 million dollars resulting from the Gilead amendment we executed in January. We continue to expect to recognize gap revenue of approximately 30 million dollars per quarter for the remainder of 2024. Our R&D expenses for the second quarter are stated net of reimbursements from Gilead and were 115 million dollars as compared to 109 million in the first quarter of this year. In the second quarter, non-cash stock compensation represented 10 million dollars of our R&D expenses. 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. We continue to expect modest increases in R&D expenses through 2024 and spend a level off heading into 2025 as our late-stage investments shift from DOM towards CAS and QEMLY over time. As Terry noted, we expect our R&D investment in DOM to peak this year. G&A expenses were 30 million dollars for the second quarter compared to 32 million in the first quarter of this year. Non-cash stock compensation represented 10 million dollars 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 dollars as compared to our prior guidance of 870 to 920 million dollars. We continue to expect these resources to fund operations into 2027. As a reminder, this guidance includes a hundred million dollar partnership continuation payment from Gilead and the QEMLY opt-in payment from Taiho of 15 million dollars. Both payments are due in the third quarter. 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 10Q. I'll now turn it back to Terry for concluding remarks.
spk06: 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. First, in the fall, we expect to have a 50-milligram dose expansion cohort of CAS. Those data will be followed closely by results from the 50-milligram and 150-milligram dose expansion cohorts and then data from our CAS-CABO combination cohort in 2025. We also expect to initiate our first phase three 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 three readouts. These include PFS and, very importantly, OS data from our original ARC-10 trial, which evaluated DOM plus ZIM versus ZIM versus chemo and PDL-1 high lung cancer by year end, followed by OS data from our EDGE gastric phase two study in 2025. Meanwhile, we're continuing to advance our other programs, including the initiation of a phase three trial for QEMLY in pancreatic cancer and the evaluation of next steps for atruma and colorectal cancer. All of these studies are enabled by the strength of our balance sheet and the great relationships with our partners. Lastly, we continue to have a robust discovery engine at ARCIS that enables a sustainable pipeline of future programs. The next program we expect to advance into mid-stage studies is AB801, our highly selective axle inhibitor. I want to conclude by thanking all of you. Thank you very much for your continued support of ARCIS and our mission to bring innovative therapies to patients in need. So we'll now open up the call for questions. Thank you.
spk02: We will now begin the question and answer session. If you would like to ask a question, please press star followed by one on your telephone keypad. If for any reason at all you would like to remove that question, please press star followed by two. Again, to ask a question, please press star one. As a reminder, if you're using a speakerphone, please remember to pick up your handset before asking your question. The first comes from Egal, Nochama Seats with Citi. You may proceed.
spk12: Hi, great. Terry and Jen team, thank you. 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 one phase three trial? Is there some expected overlapping talks that you may or may not see with CAS and CABO? And is the goal there mainly just to clear on safety before moving into the phase three trial? Thanks.
spk01: Thanks, Egal. Dimitri, why don't you give a clear and concise answer to that question?
spk11: Thank you, Terry. 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 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. 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 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 Pelsudafen and Cabosanthin, it was published in the Lancet, a series of about 55 patients showing indeed that the combination does not show any unexpected toxicities.
spk12: Okay, great, thanks. And I just wanted to confirm what you said, Jen, what you mentioned in terms of the data for the 50 milligrams, the primary progressive disease was less than the rate seen in LightSpark-5. And we're going to get the 50 and 100 milligram data separately from the 100 milligram data later this year, is that correct?
spk08: Yeah, so first of all, you heard correctly on primary progressive disease. So for LightSpark-05, the primary progressive disease was 33%. And I said that for the 50-mig cohort, some of what we saw for the 100-mig cohort were significantly or substantially lower 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 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, that it wouldn't likely be pooled, they'd be shown separately.
spk12: Okay, and then for the first line trial, which you... 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?
spk06: 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 weeks off. And I think it'll fit within something that would meet your expectations. 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, 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 with a combination that Merck is not doing and we feel we're going to be ahead of Merck.
spk08: Yeah, and then 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-sufficient manner.
spk12: Okay, gotcha. Thank you. Thanks, you go.
spk02: Thank you. The following comes from Terrence Flannan with Morgan Stanley. You may proceed.
spk03: Hello, this is Alex calling in for Terrence and thank you guys for taking our question. Can you give us any insights on potential presentation venue for this -50-ALF inhibitor for our 20 data that you presented in the fall and can you remind us on the number of patient and duration of the follow-up we should expect with this update?
spk08: Thanks. 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. You may be able to guess it since we're running out of conferences that it could be presented at it. It won't be at ESMO just to be clear on that. And then for the second part of your question, and I'm actually, the second part of your question was... The number of patients. The 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 meeting follow-up at that point in time.
spk03: Okay, thanks. And maybe just on the peak one trial. Right, right. Thank you. And on your new trial design, can we do any read through from your expansion cohort that you currently enroll in? Is it going to be the same patient population? Anything you can comment on that?
spk08: Yeah, 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. So obviously the fact that the drug is looking very good in arc 20 obviously we think bodes positively for peak one. 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 that is using patients post nephroctomy that are at high risk of recurrence. We'll go on PEMBRO. And then we'll also include patients that receive PD-1 in the first line metastatic setting. 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 -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've decided upon.
spk03: Great. Thank you very much.
spk02: Thank you. The next question comes from Jonathan Miller with Evercore. You may proceed.
spk10: 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. And I just wanted to get some confirmation that that was what you said. And also, is the ORR better in the 100-mig arm as well? I know you've stopped short of saying that in the past. 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-hundred, 150 at this point?
spk08: Yeah. So good question, Jon. So yeah, so for 50-mig, I did say that we're seeing a higher ORR today than the .9% that we've seen with Lightsparco O5. I did also clarify that that's with one response of pending confirmation. We would be above the 21.9%. And so pointed out that 50-migs, given that started enrollment after the 100-mig, that's a much less mature cohort from a follow-up perspective relative to the 100-migs. And then the 100-migs, yes, we're now north of where Lightsparco O5 is. And I'll let Terry speak about
spk06: that. I'll take to the dose response question. So the first thing to sort of caveat is that the patient populations also are slightly different. So the 100-mig cohort is slightly more advanced patient population. As we've noted, it's a more advanced population when compared to Lightsparco O5. But with that said, I would say at this point, particularly given that the 50-mig 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 any distinguishing that we'll be able to do between them will probably potentially be reflected in durability. So I don't think you're going to... The 50 is looking good enough that 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 to contextualize that you're actually... Even the 50-mig cohort is at two and a half the PDE equivalent of Belzutafan. And as you know, Belzutafan 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. They're 30-patient cohorts. While 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 and treat these cohorts not like one was at homeopathic, one was at medium, one was at heart. You're going to have doses that let you look at these patients in total and make an assessment of how you feel our molecule looks compared to anything you've seen with Belzutafan.
spk10: All right. Great. Makes sense. And maybe one more question on CASP strategy. Obviously, you talked about a combo going to phase three, this other mystery combo in first line setting. How broad should we expect to see the late stage development program for CASGAD in terms of number of different combos, number of different settings, maybe beyond RCC as well?
spk08: So as 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 as far as phase three studies. That's a lot. Market opportunity is massive, so we will be focused on getting the studies off the ground. Where you should expect to see some of the additional work is in R20 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 have some really interesting populations in mind where we think H2O2 inhibition even as monotherapy could have a really interesting effect. So we'll talk more about those over the coming months. And then I would say your question on other tumor types, we do think there's some interesting opportunities there as well, but I think 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 in HCC, so there's definitely a lot of interest out there in the clinical community in evaluating CAF and HCC in particular.
spk10: All right, that makes sense. Thanks so much.
spk02: Thank you. Thank you. 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.
spk13: Hi, this is Lydia on for Salveen. Thanks so much for taking our question. We just have one on e-trumor in colorectal cancer. Just give them a phase one, two data that you shared at ASCO. What do you see as the likely like registration path here? And when do you expect to share next steps for this program? Thank you so much.
spk06: Thanks. 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 a really certainly a program that we're very excited about. Gilead's very excited about. We're working through. I'll just toss out there, since you asked a question, we like to give answers. We have had a lot of push from our ad board that it might be smart to
spk01: move
spk06: 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.
spk13: Thanks so much.
spk06: Thank you.
spk02: Thank you. The next question comes from Dana Grayboss with Learing Partners.
spk07: You may do it on ARC-10. I wonder if you can help set expectations given this is from 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 trials in the setting, including ARC-7.
spk06: Great. So I'll set a little bit of expectations on the data, and then I'm going to let Dimitri get to the specifics of your question on patient demographics, but I'll just say that we believe that these data will be positive for the field, positive for DOM-Zem, and positive for Zem 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, I would put this against any of them in terms of the information that it will convey with a good -PD-1 and the FC-silent anti-TIGIT. So you should, we definitely want to lean into this being an important and good data set, and I'll let Dimitri say a little bit about the patient population.
spk11: Yeah, so the patient population, just to break it down and also for others, so it was a three-arm trial, ARC-10 part one. It was a two to one randomization, so it's about 40 patients, four zero on DOM and Zem, another 40 on Zem alone, and then about 20 on chemotherapy. That does mean that the study was run ex-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. 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 very straightforward first-line population.
spk08: And it's 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 Zem versus Zem, and the other is Zem versus chemo, which is how the study was set up. So you'll also see that comparison of Zem versus chemo in that readout.
spk02: Thank you.
spk00: The
spk02: next question comes from Aspika Gwarni with Truis Securities. You may proceed.
spk04: Hey, guys. Thanks for taking my questions. Apologies if I asked something that already has been asked. We just recently jumped on the call here. But just very quickly, can you tell us when cohort A of the TRUMA in CRC study is going to be reading out? You just made a comment about how the KOLs are pointing that that's a suitable TRUMA type to go into. So just wondering about that. And then we think about the HIF combination. Obviously, with carbon, that makes a lot of sense. And given the function on Preg, we can get Russia's PD-1 and C-PLA4 as good combination partners. I just want to get your thoughts on that. Thank you.
spk01: Okay. So let me take the
spk06: question on the second cohort. It'll be likely sometime next year. The simply, again, the OS in that setting is substantially longer and data simply is at this point. So remind me of the second question.
spk08: The second question was on TEF. Can you answer the second question?
spk04: Yeah. When we think about HIF and in combination with PD-1, obviously it makes sense.
spk06: So actually, we're going to be disclosing very shortly a second registrational trial that takes us into the front line setting. But your point about -PD-1, anti-CTLA4 combination 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.
spk04: Thanks,
spk01: guys. Thank you.
spk02: Thank you. There are currently no other questions queued at this time. I will pass it back over to the management team for closing remarks.
spk09: Thank you all for joining us. We look forward to speaking with you.
spk01: Thanks, everybody.
spk02: This concludes the conference call. Thank you for your participation. You may now disconnect your line.
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