Arcus Biosciences, Inc. (RCUS) Q2 2026 Earnings Call Transcript

Hello, everyone. Thank you for joining us and welcome to the ARCIS Second Quarter 2026 Earnings Call. After today's prepared remarks, we will host a question and answer session. If you would like to ask a question, please press star one to raise your hand. To withdraw your question, press star one again. I will now hand the conference over to Pia Eves, Vice President of Investor Relations. Pia, please go ahead.

Good afternoon and thank you for joining us on today's conference call to discuss ARCISO's second quarter 2026 financial results and pipeline updates. I'd like to remind you that on this call, management will make forward-looking statements, including statements about our development strategies and our expectations regarding the advantages and opportunities afforded by our investigational products, our clinical development milestones and timelines, our projected cash runway, and our financial outlook. All statements other than historical facts reflect the current beliefs and expectations of management and involve risks and uncertainties that may cause our actual results to differ from those expressed. Those risks and uncertainties are described in our most recent quarterly report on Form 10-Q that has been filed with the SEC. For today's call, please refer to our latest corporate presentation posted in the Investors section of our website. This afternoon, you'll hear from our CEO, Terry Rosen, CMO Richard Marcus, President Juan Haiyan, and CFO Bob Geltz. With that, I'll turn the call over to Terry.

Thanks very much, Pia, and thanks so much, everyone, for joining us this afternoon. We continue to make substantial progress in advancing our portfolio of oncology and immunology programs. Execution throughout the first half of the year has been tremendous, and this tangible productivity will be a focus of today's discussion. Our highest priority, no surprise, continues to be the advancement of Castatafan, which we believe has clear potential to be a five to ten billion dollar drug. The remainder of our pipeline has also been advancing quite well, and we're beginning to share the details and breadth of our other programs. These create a steady and sustainable stream of additional opportunities as well as strategic optionality. So starting with CAS Datafan, our next generation HIF2-alpha inhibitor. The advancement of CAS has driven an inflection in value for ARKIS, and we expect further data this year to accelerate this inflection. Our first phase three trial, peak one, evaluating CAS plus cabozantinib, the gold standard care and second line clear cell RCC has tremendous investigator enthusiasm and we remain on track to complete enrollment by the end of this year last year we presented a wealth of data that demonstrated clearly cast data fans efficacy advantages over Bell Zutofan over the next six months we will share new data that will provide clear line of sight to cast data fans full market potential. Based upon CAS DataFan's superior profile, as well as our development strategy, we expect CAS to become the backbone therapy for all patients in all lines of treatment in clear cell RCC, and we're maximizing that opportunity by rapidly expanding our development program. With the recent failure of Merck's LightSpark 012 study, CAS now has no competition in the frontline space, and our development plan, already ongoing, creates a clear path for CAS to consolidate what's currently fragmented frontline market GIF-2 alpha inhibitor in this We're leveraging our platform study ARC-20 in addition to collaboration studies to support the key combination regimens we'll pursue for first-line treatments. We had our meeting with the FDA to discuss our first frontline Phase III study in the setting, we're calling that PEEP 20, and we remain on track to start this registrational trial by the end of 2026. The program CasDatafan is being evaluated in several different combinations, in both a capital and resource-efficient manner. These all allow us to retain the full rights to the CasDatafan. We believe that we are the partner of choice for collaborations involving a hip-to-alpha inhibitor. This is enabling investigation of the the smartest mechanistic combinations and settings. Keep in mind, Belzutafan is readily available to anyone. We do not believe it's an accident that others want to combine with Castatafan. We initiated multiple new clinical trial collaborations in the last two months with BMS to evaluate Cas in combination with Pumida, their bispecific anti-PD-L1 VEGF antibody in the first-line setting. In July, we announced a collaboration with Summit Therapeutics to evaluate CAS in combination with Ivo, their bispecific anti-PD-1 VEGF antibody. ARCIS will be conducting this study in a first-line cohort. Three collaborations we've executed to evaluate CAS with an anti-PD-X VEGF bispecific in the first line. So just to emphasize, we have three collaborations with anti-PD-X VEGF antibodies. In addition, in July, we also announced the collaboration with Aveo, in which we'll be combining CAS with TiVo in advanced Belzutafen experienced patients. This study will also enable our planned late-line registration. Let me emphasize an important point. We believe that CAS is designed to provide flexibility to physical inhibitor-enhanced regimen, corresponding to their preferred treatment approach, for a front-line set, but fragmented front-line set in self-inhibitor. A cast data fan-based TKL represents the most commonly used front-line regimen with a market share of about 30% for TKI. Our partner TKI in this setting will be TKIs. The combination choices are not selected in a vacuum. As I mentioned earlier, in combination with three different novel anti-PDX VEGF antibodies. We believe anti-PDX VEGF bispecifics are kidney cancer going forward. In the second line, this combination is now in registrational testing. Cabo is the most commonly prescribed and combination partner of all profiles well-documented, which involves Lenva, higher cardiac dysfunctional profile versus Bells. In Cabo's telephone combination in the second line, with the announcement of our collaboration with Aveo, we picture that this will be a large and comprehensive data to 100 patients. Richard will go into more detail in the specific context. And in this context, to the advancement of the highest quality research in the HIF2-Alpha space, particularly on translational studies, I want to emphasize that this world, the molecule, our initial work on castatafan clinical outcomes, the biomarker changes, and the research showed that HIF2-Alpha inhibition with castatafan monotherapy resulted in epolatin or epoproduction is developing a thorough... For example, let me tie this all together. For example, at the same time, however, PKI exposure has a little bit of a transition Our commitment to research has been since our founding, and despite relatively minimal capital investment, we're at need of an ongoing phase three study. We're coming out of ASCO, we're preparing for initial data from the opportunity for QEMLI.

Thanks, Terry. As Terry described, our strategy is currently pursuing multiple different combination studies In order to conduct this work in a capital and resource-efficient manner, we have been leveraging our ARC-20 platform study and generating data. Our ongoing and planned will have multiple important data readouts from ARC-20 later this year, and there will be a lot of data. Starting with the first-line CCRCC, we are pursuing a TKI-free approach as the foundation of our strategy, while also developing a TKI-inclusive option. The current TKI-free standard of care is the IO doublet IPI-NEVO, and let me remind you exactly what this regimen is. It's a maximum of four cycles or 12 weeks of IPI plus NEVO, followed by NEVO for the duration of the treatment. This therapy is highly valued for the overall survival benefit it provides, but it would be used more if the rate of primary progression, which is roughly 20%, were lower. We believe a combination with castatafen can improve upon that rate of primary progression in addition to improving progression-free survival and ultimately overall survival. To support the TKI-free approach, there are two key cohorts in ARC-20. First, castatafen plus zemberlimab, power anti-PD-1, plus IPI, and anti-CTLA-4. This cohort has enrolled well, and we expect enrollment to complete very soon. We're also evaluating a CAS plus ZIM first line cohort in our 20, which completed enrollment at the beginning of this year, for which we've already described a very low rate of primary progression of 7%. That's just 2 of 30 patients. Keep in mind that anti PD-1 monotherapy was previously reported to show a 30% rate of primary progression in this frontline setting. Now, for the TKI-inclusive approach, we'll be developing Castatafan in combination with Zaxipnib, a well-established TKI in the front line that will sequence well with Cas plus Cabo as the subsequent regimen. We expect a new cohort in ARC-20 evaluating this combination to initiate in the fourth cohort of this year. In collaborations with BMS and Summit, we are also evaluating novel TKI-free VEGF targeting combinations with anti-PDX-VEGF bispecific antibodies in the first-line setting. BMS will be evaluating two CAFs plus Pumidic-based combinations in its platform study, Rosetta RCC208. In collaboration with Summit, we'll be adding a new Colartark20 to evaluate CAFs plus Ivo in first-line CCRCC. Both of these studies are expected to begin by the end of this year. Now, in the second line, the current standard of care is cabozantinib monotherapy, representing roughly 40% of the second line market. Peak 1, which is evaluating CAF plus CAVO versus CAVO, is our first registrational study for castatafan. Site activation and enrollment have been going quite well, and we expect to complete enrollment by the end of this year. We also have an ongoing cohort in ARC-20 evaluating CAS plus CABO in a second line IO experience setting. We shared initial efficacy data for this cohort last year at ASCO. And finally, in late-line clear cell RCC, where the current standard of care is belzutafan or TKI monotherapy, we're adding a new randomized cohort in ARC-20 to evaluate cascatafan plus Tivo versus Tivo alone in patients that have received prior bilzutafam. This cohort will generate data to support a registrational strategy combining CAS with Tivo by clarifying casdatafam's benefit specifically in IV-2-alpha inhibitor experience patients. We expect enrollment to begin later this year. Now, let me briefly summarize the readouts coming from ARC-20 this here. In the first line, initial safety data from the ARC-20 cohort, evaluating CAS plus ZIM plus IPI. We've already met with the FDA and EMA to discuss how these data will support the start of our registrational trial, evaluating CAS plus NEVO plus IPI as the bedrock of our frontline strategy. We'll also be able to share preliminary data on primary progression. Also, in the first line, we'll have ORR data with approximately 11 months of follow-up from the cohort evaluating CAFs plus ZIM. We will share waterfall and spider plots for that cohort. And given that the median progression-free survival for Ipenevo from Checkmate 214 in this first line is just 12.4 months, we expect the spider plots for this cohort to be informative since they may impart an early look at how PFS will unfold for this cohort. In the second line, we'll have more mature ORR and PFS data for CAF plus CAVO in approximately 45 patients with at least 18 months of follow-up, and we may have an early read on OS. And in our late-line monotherapy cohorts, we'll be able to share an early look at overall survival with approximately 28-month median follow-up from the approximately 120 late-line monotherapy patients. While OS is not required for approval in registrational trials for CCRCC, it could impact access in ex-US regions and is recognized as another potential major differentiator relative to bluzudafone, which has now failed to show statistically significant benefit in OS in three out of three registrational trials. So, this first look at OS for Castataphan will provide important comparative data. Taken together, these data readouts will create a holistic picture of Castataphan's efficacy across all lines of therapy and should generate strong conviction in its potential as the new backbone of kidney cancer treatment. As Terry mentioned, we expect to share the totality of these data together in an investor form in October prior to ESMO. And with that, I'll turn the call over to Juan to discuss our immunology portfolio.

Juan Gupta- Thanks, Richard. Over the past few years, the same discovery team that created Gestataphan has been working on creating a broad portfolio of programs that span the whole spectrum of autoimmune and allergic diseases. While we haven't said much about this effort until now, we are very proud of its quality and scope. The overarching strategy has been to design molecules that might provide safe treatments for important patient segments across the immunology landscape. We have also prioritized approaches that leverage our demonstrated expertise in designing potent and selective molecules that work in the real world under physiological stress rather than just in a culture dish. Further, we have looked for ways to minimize the inherent biological risk associated with novel mechanisms of action. You may notice a couple of recurring themes in the mechanisms of action that we have chosen to pursue in implementing our portfolio strategy, including the development of oral small molecule alternatives to establish biologics and an emphasis on targeting immune cell populations that have generally been understudied. We expect a steady cadence of molecules advancing into the clinic, beginning with our MRG-TRX2 antagonist, and followed by our TNF receptor 1, CCR6, STAT6, CD89, and CD40 ligand programs, all of which are positioned to deliver IND-ready candidates between now and the end of 2027. Our first program, AB-102, an oral MRGPRX2 antagonist being developed for chronic spontaneous urticaria, or CSU, and atopic dermatitis, is wholly owned by ARKIS. Available biologics have meaningfully advanced the treatment of allergic conditions, but substantial clinical need remains. X2 is a key regulator of mast cell activation in these diseases, releasing inflammatory signals that drive swelling and itch, making this a promising target for conditions like CSU and atopic dermatitis. At the Society for Investigative Thermatology annual meeting earlier this year, we presented preclinical data on an oral X2 approach showing full blockade of X2-dependent mast cell degranulation and inhibition of all common human X2 variants. These data support the potential for a potent selective once daily oral X2 antagonist to impact key disease outcomes in conditions driven by aberrant mast cell activity. AB-102 is entering the clinic imminently with PK profile data expected in the fourth quarter from the first cohorts of our first in Human Healthy Volunteer Study. We expect to follow with a proof-of-concept study in CSU in mid-2027. Unlike other recent clinical failures in the X2 space, we believe that the excellent potency of AB102, optimized to be efficacious under physiological conditions, provides the best opportunity to run the definitive proof-of-concept study with an X2 antagonist in CSU. We also are developing an oral small molecule TNF inhibitor as a potential treatment for conditions such as an inflammatory bowel disease. Our TNF inhibitor is designed to selectively block TNF receptor 1, which we believe could translate into better safety and efficacy relative to approved anti-TNF biologics, which block both TNF receptors 1 and 2. As you may know, blocking TNF receptor 2 can paradoxically lead to an inflammatory response in some patients. We expect this program to enter the clinic in early 2027. Behind AB102 and our TNF programs, we have a portfolio of earlier-stage immunology programs for which we will share more details as they approach entry into the clinic. I'll now hand it over to Bob to discuss the market opportunity for CasDataphan as well as our financial results.

Thanks, Juan. Before I get into the quarter's financials, I want to spend a few minutes on the multibillion dollar market opportunity for CasDataphan. Sales for RCC drugs in just the major markets are expected to grow to roughly $13 billion by 2030. Historically, this market has been fragmented, primarily split across the IO and TKI classes. With only two HIF2-alpha inhibitors on the horizon and clear advantages for casdatafan, we believe ARCIS has a path to become a common denominator across lines of kidney cancer treatment. Casdatafan is targeting lines of therapy with large patient populations and long treatment durations. peak one addresses approximately 20 000 io experienced patients in the major markets representing an opportunity of more than two billion dollars and the first line opportunity is even larger exceeding four billion dollars all told we see a total peak sales opportunity for casdata fan of five to ten billion dollars driven in part by duration of therapy from a long-term tail effect. This is something we've seen consistently in our late-line monotherapy data, where approximately 25% of patients remain on treatment beyond two years. As a reminder, ARKIS owns all commercial rights to cast out of hand outside of Japan and certain other Asian territories where rights are held by our partner, Tayo. Turning to QEMLI, we continue preparations for the readout from PRISM-1. While there's been exciting progress made in the treatment of later-line pancreatic cancer, QEMLI has the opportunity to be the first meaningful advancement in the front line in decades. We believe this is a multi-billion dollar commercial opportunity. Further, we believe QEMLI's well-tolerated profile, as well as its promise to substantially enhance the benefit of immunogenic chemotherapy, would make it attractive as a combination partner if PRISM-1 is successful. I also want to touch on capital efficiency. Full ownership of Casdatafan gives us significant and strategic optionality and supports a capital-efficient collaboration strategy. Our new agreements with BMS, Summit, and Aveo are structured to advance casatafan combinations without placing outside demands on our own resources. The same is true of our wholly-owned immunology portfolio, where the TNF program is turning to our financial results for the quarter. Our cash and investments as of June 30, of 2026 were 775 million dollars as compared to 876 million at the end of the first quarter we continue to expect to end 2026 with approximately 600 million dollars in cash and investments and expect these resources to provide runway into at least we recognize gap revenue for the second quarter of 41 million dollars 2026 gap revenue of 65 to 70 revenue continues to be driven primarily by our collaboration agreements. Future operating results are expected to reflect lower collaboration revenue due to reduced activity under the Gilead collaboration. Driven by the wind down, our R&D expenses for the second quarter were $113 million net of reimbursements and we continue to expect meaningful decrease in overall R&D spend in 2026 and 2027 relative to 2025 as a result of the wind down of the DOM phase three trials and reduce spend on QEMLI. Together with broader by 2027, we expect more than 80% of our portfolio spend to be directed toward CASDAT. G&A expenses were $24 million for the second quarter and total non-cash stock-based compensation. For more details regarding our financial results, please refer to our earnings press thank you filing.

So let me close by summarizing our priorities for the CASDATFAN remains our number one priority. We're working aggressively with the goal of positioning CAS to be the C-H-E, all caps, backbone of kidney cancer treatment across all lines of therapy. Data for CAS DataFan is monotherapy and in combination in first, second, and later. We expect these to further reinforce CAS DataFan's best and drive conviction in its potential. and a broad registrational strategy, bringing both the qualitative and the nation partner for cancer remains on track for a readout next year. And Juan walked you through the exciting progress inhibitors shortly thereafter and other immunology programs with $775 million in cash and investments and runway.

We will now begin the question and answer session. If you would like to ask a question, please press star 1 to raise your hand. To withdraw your question, press star 1 again. We ask that you pick up your handset when asking a question to allow for optimum sound quality. If you are muted locally, please remember to unmute your device. Please stand by while we compile the Q&A roster. Your first question comes from the line of Salim Syed with Mitsuo. Your line is open. Please go ahead.

Great. Congrats on the progress, guys, and thanks for the question. Just one kind of going into all the October data, obviously a lot of data that we'll be getting. Is there a bogey or measure of success that you're looking at in each of these lines that you would care to elucidate here for folks? And also while we're there, are there any particular parts of the data set that you would place a little bit more prominence on where you want people to anchor to? Thanks so much.

Thanks, Salim. Great question. And I'll address all that. I'll start at a very high level, and then I'll get, you know, increasingly granular. So I think you can walk away with some, you know, very clear expectations as to how we're looking at things. So at the highest level, I think we want people to walk away and believe they will walk away, knowing that castatophan is going to become the backbone standard in RCC across all lines of therapy. So I think one of the ways to frame this is put it in the context of value and value creation and looking at it through an investor standpoint. So I think it's very clear that, you know, last year we received an inflection in value that was due to recognition in the investor community that there was really a very substantial differentiation between Cast Data Fan and Belzuda Fan. And what we've heard from a lot of investors is that led sort of to a recognition of value that was reflected in our second line strategy, that we were given value for an expectation that cash plus Cabo is going to be Cabo and that's going to look good. I think the other piece, though, was that with that differentiation, there still remain questions as to whether that differentiation, which is clearly there, how will that translate more broadly, and particularly in the front line. And I think a couple things have happened. First, you had the failure of LightSpark 012, but then we've also had another year's worth of follow-up clinical data. So I think what's going to happen as we come into this readout is that we'll be able to give very strong conviction across all lines of therapy, including the frontline. And the front line is huge because that's the $5 billion plus part of the market opportunity. So keep in mind, we have no competition in the front line without Bell Zudeph and there the competition is the standard of care. So in that context, let me go down another layer and talk about the front line and build out on a couple of things that Richard pointed out. So our foundational registrational study there will be CAS plus IPI plus NEVO versus IPI-NEVO. And what we're going to have, we'll have at least 20 patients' worth of data from that CAS anti-PD-1 IPI cohort that we're running as part of ARC-20. Keep in mind, this is exactly what we've agreed upon with the FDA in terms of safety. So we'll have a safety profile with that 12 or more weeks, and we'll also have a look at the rate of primary progression. And I think the thing that might surprise people as they're thinking about this now, and we get more granular, is that the CAS-ZIM data set is actually going to be relatively mature despite being an early data set. Because if you contextualize a PFS for ipinevo that's just over 12 months, as well as a well-done study with Pembro alone where you have a PFS on the seven to eight months, you'll be able to get a feel from our curve as to how our PFS is looking compared to those regimens. Also, with over 18 months of median follow-up, I think we'll have a good look potentially at how OS, as we move into the second line, is playing out, and some of these things will start to go across studies. So let me now talk about the second line and build on what I just said there. So in the second line, our CAS-CABO data will really support that we will have what will look like a better PFS than what was seen with Bell's Lemba. And I think given the safety, and we talked a little bit earlier about what's been associated with LEMBA and LEMBA bells, that we think we'll have advantages that read on both the safety and efficacy. The other thing to look at is that given that maturity, as I was saying, of over 18 months, I think the shape of our curve will give you a sense that we could have a very dramatically different hazard ratio when we compare it to Cabo versus the hazard ratio of 0.7 that was seen for Bell's Lemba. I think the more important piece, though, is that given that what's known for the OS of Cabo, which is just over 21 months, given that we'll have that 18 months of follow-up, we may see, in fact, what appears to be an OS advantage for the CAS Data Fan regimen. Keep in mind, our OS is only going to be based upon how we look relative to direct comparison to Cabo, and that will be defined by its hazard ratio. As Richard mentioned, thus far, Belzutifan has been 0.43. So we're pretty excited about, you know, having those first data that read on OS. And that brings me to the late line. So the late line, we've clearly shown a single agent, a very dramatic difference compared to the data that have been generated with Belzutifan. But we'll have 28 months of follow-up. And again, given that the OS for Belzutafan is just over 20 months, I think it gives us an opportunity. You'll see the Kaplan-Meier curves. We don't know how it's going to play out, but I think with a very robust, durable IF2 inhibitor, This will start to perhaps show us how important HIF2 really is as a target in ClearCell RCC, and you'll clearly have some sense, we all will, of how OS will look in that setting. And I think the nice thing there, since it's a single agent, that will give read-through. And you were asking about what things are important. I think that will read through to the mechanism across lines of therapy. So just to summarize, I think overall success will be that you come away knowing that not only do we have a plan for CAS data fans to win, I think we've laid that out pretty We clearly were executing on it, but those data will have enough data now that you'll see we actually will win, and that cast data fan, you know, really will look like it's going to become the common denominator for all clear cell RCC treatment.

Okay, super helpful. Thanks so much, Terry.

Thanks, Salim.

Your next question comes from the line of Dana Graybosh with Leerink Partners. Your line is open. Please go ahead.

Thanks for the question. Looking forward to another fall event. I wonder if you can talk about LightSpark 12, which we'll see at ESMO after that event, and your expectations for PFS and OS from that study. And is there a specific signal that would give you confidence or increase your confidence that CAS can exceed there with AXE and a PD-1 where Bells, Lemva, and Pembro failed? Thank you.

Thanks, Dana. So this is going to be a theme we come back to. People, you know, ask a lot of times about read-through from trials and talk about there's read-through from things where we have the data. LightSpark 012, we don't have the data. But I think the most important thing is go to slide five. You know, you can say like elections have consequences, biomarker data have consequences, and when you look at the comparative durability of the ability to suppress erythropoietin, so the ability to inhibit HIF2, I think that's the thing that tells 90 plus percent of the story. So people speculated about safety issues of the triplet, et cetera. I think everything comes down to a dramatic differentiation of the molecules. And I think what you're starting to see now is data where that'll play out. So I think the biggest problem that, you know, Belzutifin probably had is the durability and the, you know, decrease with time and ability to inhibit HIF2, where their own papers talk about effect on the biomarker, you know, looking very nominal at just 12 weeks. keep in mind the PFS for the control arm there is 24 months. So the fact that you're not inhibiting strongly for that durability, I think that's the issue. And then the thing that gives us confidence is we know that Casdatafan is inhibiting not only robustly on day one, but out past the year. And in fact, as long as you're on treatment. So you do not run in those issues. Keep in mind one last piece that, again, however that affects things. As we've talked about, treatment with TKI does induce the increased activity of HIF-alpha. So you get more HIF-2-alpha activity. So essentially what you have in that study is the treatment with the TKI. This is not a discontinuous event. That happens in a continuous way. So you've got increasing levels of HIF-2 activity and you've got a HIF-2 inhibitor that is measured by that, you know, biomarker work is clearly not inhibiting HIF2 is strongly with time. So, less activity of the molecule, more activity coming from the TKI-induced HIF2 activity. So, I think that's a recipe for difficulty. Whereas the ARCUS molecule, you're talking about a paradigm of a tumor where, you know, 85 to 90-plus percent of the patients have HIF2 as a driver, and you're going to put a HIF2 inhibitor, which only brings anemia on top of a good regimen of a TKI and an anti-PD-1, and we feel super excited about it. And we can't even imagine something that would come out of LightSpark 012 that would cause us to think differently. And I'll remind you, our number one focus there is on top of Ipinivo, and you'll see a really strong data set, I think, as we go into fall. So we'll feel really great about the front line.

Your next question comes from the line of Jonathan Miller with Evercore ISI. Your line is open. Please go ahead.

Hi, guys. Thanks for taking my question. A couple more about what we're expecting in October. In the second line cohort, can you remind us how much prior Lenvima those patients have gotten? Terry, to your point, not all TKIs are created equal, and we know that sequencing has effects. I think we've seen prior TKI treatment numbers, but how many patients got Lenvima prior? And then secondly, in first line, I'm a little surprised that you're so hesitant about giving ORR or broader efficacy readouts for the triplet in first line. You'll have two scans or more for most patients. You know, what do you expect to see for time to response in first line versus second line?

Why are you so hesitant to give ORR and why do you think that there won't be enough to at least start directionally talking about that okay so um uh remind me the first question um and then i'll get to the uh that or um which by the way we're not we're not hesitant so yeah oh prior prior lemba yeah so um we'll give you specific numbers at the time let me let me remind everyone else as well it's probably when And people talk about differences between the ARC-20 CASCABO as well as our registrational study versus the LightSpark 011 study because in that study, Merck had CABO in the control arm and Alemba in the study arm. Really, the only TKIs of probably substantial number that they saw were patients on Axie, so it was probably a mix of Axie and Ipenevo. We'll give specific numbers at that time, but what I'd say is our Lenva patients are, you know, very representative of what you would normally see in the first line. So we'll have a substantial number of LEMVA patients out of that 40-some-odd patients. It looks relatively like the distribution. In terms of your other question, we will share those information. There's no hesitancy. I think just on expectations, given that, keep in mind that studies enrolled very quickly, that triplet, we think the most important part of those data will be first the safety and second the rate of primary progression because that's really what you're addressing. And we think even what you'll see from just our anti-PD-1 plus CAS, that'll give you warm feelings about efficacy, given, you know, we'll have that 11 months of median follow-up, and that still may improve. But with the, we'll share what the early responses look like. I think So the thing to think about is that the timing of an IO plus a CasDatafan regimen may look, you know, a little bit more like IO alone or HIF-2 inhibitor alone where, you know, responses, you know, that did you cross 30% or not when that happens, um, may be, um, more prolonged. The thing is when you combine with the TKI, you know, as you know, you're, you're really affecting the vascular system and, you know, it's a very, um, uh, or a very sort of response, fast type of phenomena, but then obviously it doesn't give you the durability. So we'll share those data, but I think the more important things that you'll get out of it are the safety of the triplet, the rate of primary progression, the rate of primary progression from any of the studies we've done that don't include a TKI, particularly those in the earlier lines, as well as a few other monotherapy data sets, and then the CAS plus VIM, simply because you will have a longer period of treatment. And so not only will you see ORR there, but I think the shape of the curve, particularly knowing that if you look at actually Ipenevo, out at 12 months, you're getting in that 50-ish percent, you know, plus or minus place. It'll just be a very, you know, clear comparison. But you shouldn't think we have any hesitancy sharing those data. It's just that time will probably, you know, affect more of the response rate. I think one other thing that, you know, is worth, I'll just use this as an opportunity to highlight this. I think it's probably not fully appreciated because of the totality of the Belzutifan data, how profound the ability to inhibit GIF-2 is on durability, but I'll just use actually Belzutafen data. You know, people ask for read-through. We get asked about read-through from LightSpark 012 where we haven't seen the data, but the places where we've seen a lot of data, for example, LightSpark 005, and we've seen a monotherapy data. Now, interestingly enough, if you go back and look at those data, median PFS for belzutafan in that late-line setting was about 5.6 months, which is about the same as the median PFS for Everolimus. Similarly, the rate of primary progressions for the two were very much the same. We think those sort of relate to the ability to hit the target heart. However, they still won. They got approval, and that's because so much of the manifestation of hitting HIF2 is coming from what that does to the tumor and how it plays out, you know, on the other side of the median. So we think HIF2 is going to turn out, and I think our data will certainly, you know, give the opportunity to assess that, that HIF2 is going to turn out to be something that affects everything on those durability measures. And I think that the Belzutofan data have foreshadowed that because despite what's probably a marginal ability to really hit too hard and hit it long, they still had, you know, very good effects. I think the first place where you saw the manifestation of that less than optimal durability of hitting too hard for a long period of time came in their frontline study, and that's probably not surprising because it's comparing versus the longest PFS in the control arm, so the percentage of time that it's bringing value is, you know, smaller compared to whether it's the LightSpark 05 or LightSpark 011, where it's fighting a shorter battle compared to the standard of care.

Your next question comes from the line of Lee Wastick with Cantor. Your line is open. Please go ahead.

Hey, guys. Thanks for taking our questions, and congrats on the progress. I have two questions. Maybe first to follow up on the length question for the second line, CAS plus CABO cohort, how should we think about the impact of prior lymph exposure on the types of patients you enrolled into the study relative to the LIHSPARC-11 trial, just trying to understand the right PFS benchmark given some differences in the patient population. And then second, Terry, you mentioned prior TKI exposure increases the HIP2 levels. I'm just trying to clarify if you're implying CASAS-PFS has a positive relationship with prior lines of TKI.

Okay. So, thanks on both of those. So, the first thing we would say is we actually feel quite good, and I mentioned what we saw in the late line, that we did not see a degradation in the monotherapy, 120 patients prior TKI, and we'll share very specific data in the fall, but we did not see a fall off in efficacy associated with those patients that had seen more TKIs versus the trend that was seen in LightSpark 005 and LightSpark 13. So going in, you know, we're feeling really confident that despite the fact that we'll have those, you know, TKI experienced patients and LEMBA patients, we feel very optimistic about the benefit that those patients will receive. So sort of across the front line strategies, we feel good that the benefit that GIF2 will bring on top of Cabo will, you know, be advantageous. In terms of comparisons, to your point, one of the things that's given me an opportunity to talk about how we'll present the data. So, you know, I'll even use the word that John used a second ago about hesitancy. We're going to be effusive with the data. And, you know, I think when we share our data, you can assume we've squeezed all the water out of the sponge of what we know at the time, and you'll have complete knowledge of what we have. And one of the things we're going to do is we're going to use every comparative data set that we can to illustrate, you know, what the advantages of Cast Data Fan are. We feel like it's a great opportunity because, you know, Cast Data Fan is going to bring a lot to the table. And one of the tools that we'll have is the study CobblePoint. And Cabo Point, if you go back and read what the intent was, it really was designed where it looked in two separate groups, randomized, where you had patients that were treated with TKIs and patients that were treated with IOIO, and then how did those different groups look when they then received Cabo? So it's a perfect comparison. Yes, we'll compare to Bell's Lenva. Yes, we'll compare it to any other registrational data with Cabo alone. But we also have those nice data sets that were really, if you look at the genesis of that study, the intent was that for future combinations, you'd be able to have a clean data set to see how anything knew what it was bringing to the table. So it's a perfect data set. So we will do subpatient analyses since we'll be forced to go across trial comparison as much as everybody doesn't like it. Actually, everybody loves it. And so we'll look at how we compare to both of the segments of the population from the Cabo Point study to see how the advantages we're bringing to Cabo, whether it's from prior TKI treatment or prior IOIO treatment. And keep in mind, we're going to have curves. So those curves will not only, you know, give you a sense of static differences, but I think they'll give you a sense of how the hazard ratios are going to play out. Because with that 18 months of follow-up and all the landmark data that comes with that, knowing that the tails are a big deal, you'll see how those tails are corresponding both to what you would see with Cabo and what you saw with Bell's Lenva. Nicely, both of our programs are run against the same control, and so you'll get a sense of, you know, both our hazard ratio versus Cabo, as well as how you might think that compared to a hazard ratio of what you saw for Bell's Limba.

This brings us to the end of the Q&A session. I will now turn the call back to Terry Rosen, CEO, for closing remarks.

So I want to thank everybody. You know, we're looking forward to speaking more. A couple of you asked some really great questions, and I think not only will we have a lot of clinical data, but we'll have a lot of science and translational work, much like we had in the Nature paper. So I think we're going to have a lot of great discussions about, you know, the future of castataphan-based therapy. So thanks for joining, and we look forward to speaking to you, you know, over the coming months.

This concludes today's call. Thank you for attending. You may now disconnect.