Arcus Biosciences, Inc.

Hello everyone and welcome to ARCA's Biosciences first quarter 2025 earnings and financial results call. My name's Lydia and I'll be your operator today. After the prepared remarks, there'll be an opportunity to ask questions. If you'd like to participate in the Q&A, you can do so by pressing star followed by one on your telephone keypad. I'll now hand you over to Pia Eates, Vice President of Investor Relations to begin. Please go ahead.

Good afternoon, and thank you for joining us on today's conference call to discuss ARGUS's first quarter 2025 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, our projected 2025 revenue, and our expected clinical development milestones and timelines. All statements, other than historical facts, reflect the current beliefs and expectations of management and involve risks and uncertainties that may cause our actual results to differ from those expressed. Those risks and uncertainties are described in our most recent quarterly report on Form 10-Q that is filed with the SEC. Today you'll hear from our CEO, Terry Rosen, CMO, Richard Marcus, COO, Jennifer Jarrett, and CFO, Bob Gels. We'll also be joined by our President, Juan Jaen, for questions after the prepared remarks. With that, I'll turn it over to Terry.

Thanks very much, Pia, and thanks to all of you for listening in today. While the world around us has been somewhat or maybe definitely tumultuous. At Arcus, we've really remained focused on execution, and that execution goes with speed, efficiency, and most importantly, rigor. And so before we get into the details, I want to emphasize three points that will be apparent in our discussion today. So first off, our late-stage portfolio is rich, but our number one priority is unequivocally cast data fans. So far, the more data that we generate, the better it looks. So our goal is simple. We bring CAS to market and to patients as quickly as possible and create maximal value for this program. Second, we are well capitalized, and our long-term strategy has positioned us well to advance DOM, QEMLI, and CAS through their respective initial phase three readouts. Nonetheless, we're always cognizant of the macro environment We're committed to ensuring our resource deployment reflects our ongoing assessment of priorities so that our CASH runway extends as long as possible. Third, we expect to have a steady flow of data for CASH StataFan over the next couple of years that will reinforce the advantages relative to both Belzodifan and TKI monotherapy. In that vein, we're thrilled that our abstract describing initial data from the Cas plus Cabo cohort of ARC-20 was accepted for an oral presentation at ASCO. This is the same combination we're evaluating in our first and quarter. And these data should provide further support for the study. This will also be the third oral presentation of Cas-Statafan data at a major medical conference in just seven months, and there are a lot more to come. Okay, now some important granularity around the Cas-DataFan program. In our Phase 1b ARC-20 study, we now have eight cohorts evaluating different dosing regimens, combinations, and settings for Cas and Clear Cell RCC. This is why ARC-20 will generate meaningful data over the next two years that will serve several important purposes. First, continued elucidation of Cas-DataFan's differentiated efficacy profile relative to that of Belzuzudafan and de-risking of our first Phase III study, Peak 1. Second, continuing to drive the already extraordinary investigator enthusiasm for Peak 1 to support its rapid enrollment. And third, demonstrating the opportunity for Casdatafin in earlier line settings where Cas has the potential to ultimately displace TKIs. Before I turn the call over to Richard, I'd like to touch on a few additional topics starting with our development plan and our long-term vision for CasDataFan. Our Phase III trial, Peak 1, will evaluate Cas plus Cabo versus Cabo in clear cell RCC patients who have received prior immunotherapy. For our first registrational trial, we chose to combine Cas with Cabo because Cabo is the gold standard and most widely used TKI in the setting. In fact, in our ARC-20 monotherapy cohorts, 78% of patients received prior CAVO. That's greater than three times more than any other TKI. Clinicians are extremely comfortable administering and managing the toxicities of CAVO, and because of this, there's an extraordinary amount of interest in PEEK1. Also, because Hiv to Alpha inhibition affords a relatively benign safety profile, with the primary AEs being on-target anemia and hypoxia, we do not believe cats will have meaningful overlapping toxicities with cobble. As such, the key objectives of our upcoming ASCO presentation are to clearly demonstrate that these two molecules can be safely combined and that we can add efficacy to that of cobble monotherapy. We expect the data shared at ASCO will demonstrate exactly this. Longer term, Given the strength of CAS's efficacy and safety profile, a vision is to develop CAS in TKI-free regimens and even to displace TKIs in earlier lines of RCC treatment. TKIs have been very effective in treating RCC. Almost every RCC patient receives a TKI during the course of their treatment, but TKIs come with debilitating side effects that meaningfully impact quality of life. This cannot be overstated. So we believe there's a huge opportunity to develop CAS in earlier lines, driving a long-sought paradigm shift, enabling patients to avoid TKI therapy for as long as possible. This, in fact, reflects a core element of ARCIS's high-level strategy in oncology, driven by the advances in the understanding of tumor biology in the last decade. Being the leader in the development of innovative cancer therapeutics with improved efficacy that preserve quality of life during treatment. Specifically, we're collaborating with AstraZeneca to combine Cas with their anti-PD-1, anti-CTLA-4 bispecific antibody, furustamate, to create the first TKI-free HIF-2-alpha combination option for first-line RCC. I want to repeat that this will be the first TKI-free HIF-2-alpha combination option looked at in first-line RCC. Anti-PD-1, anti-CTLA-4 is one of the most commonly and widely used first-line regimens, particularly in academic centers, because it is TKI-free and conveniently prolongs survival. AstraZeneca will operationalize the study as part of their evolved portfolio, so this collaboration enables us to develop CAS in the first-line setting in an extremely cost- and resource-efficient manner, and with a world-class drug developer in oncology. The study is designed to demonstrate the safety of the combination to support late-stage development. This provides another opportunity to generate confidence-enhancing data for castatopan-based regimens over the next 18 to 24 months. Beyond EVOLVE, we've added three cohorts to ARC-20 that evaluate Cas and other early-line TKI-free settings. These are Cas plus Zim, our NIPD1 antibody, and first-line all-comer clear cell RCC, Cas monotherapy in first-line favorable risk patients, and Cas monotherapy in patients that have received prior IO but have not yet received a TKI. All three cohorts recently opened for enrollment and have generated significant interest in the investigator community, demonstrating and building on the robust interest in Cas, and in TKI-free regimens. As a result, these cohorts should enroll quickly and generate efficacy data over the next couple of years, informing future development opportunities. While cancer has moved front and center in our portfolio, our two other registrational programs, which are targeting massive patient populations with substantial unmet need, continue to advance towards data. For our Fc-saline anti-tidium antibody domedomelamide, first phase three study to read out will be START221, for which we have guided to 2026. This study is evaluating DOMZEM plus chemo versus NEVO plus chemo, the standard of care, and first-line gastric cancer. Later this year, we'll be sharing overall survival data, OS data, from the corresponding phase two study at gastric. This is evaluating the same regimen in the same setting as START221. We expect these data to reinforce confidence in STAR221, which has an overall survival primary endpoint. The competitive landscape in this field has seen a dramatic shift over the last six months, with the FC silent anti-tigit antibodies, specifically ours and AstraZeneca's anti-tigit, anti-PD1 bispecific antibody, now dominating the phase three landscape. These two molecules, have generated similar positive data in Phase II studies in both lung and GI cancers. AstraZeneca is now enrolling 10 different Phase III studies for its Eftesal and antitigin antibody. In addition, PRISM-1, our Phase III trial of QEMLI, our small molecule CD73 inhibitor, in combination with chemotherapy in first-line pancreatic cancer, is enrolling rapidly. There's been a tremendous enthusiasm for PRISM-1, and as a result, we anticipate the study will now be fully enrolled by the end of 2025, less than 12 months after initiation. This is our second global phase three study that will complete enrollment well ahead of initial expectations, and our goal is to replicate the success with the enrollment of peak one. This brings me to my final key point. Today, we have a strong balance sheet billion in cash and investments. This is not an accident. While there has been a dramatic shift in the macroeconomic environment, we are always scrutinizing our capital allocation, prioritizing our molecules and programs, and leveraging strategic collaborations. For example, those of Gilead, Tyho, and AstraZeneca to maintain a strong balance sheet. This will be particularly true going forward. to ensure that our capital stretches as long as possible and to enable us to continue funding our small molecule research programs. The discovery of castanophan, an exceptionally high-quality molecule against an extremely intractable target, is a reflection of the secret sauce of ARCIS, which is our research organization and small molecule drug discovery capability. Our next IMDs are likely to come from our inflammation and immunology programs which have been quietly but rapidly advancing in our focus on the creation of potential first and best in class small molecule drug candidates against validated targets. We're going to share more about these programs later in this year. With that, I'd like to turn the call over to Richard to speak about Cas-Statafan in greater detail.

Thanks, Terry. I'll first recap the highlights of our recent ASCO-GU presentation for Cas monotherapy and late-line clear cell renal cell carcinoma. After that, I'll speak about our upcoming data presentations and near-term development plans for CAS. I'll start with a reminder of the study design of ARC-20 on slide 9. ARC-20 now includes eight cohorts evaluating CAS monotherapy or CAS combinations in clear cell RCC. As a reminder, our ASCO-GU presentation included data from three of the monotherapy cohorts in late-line clear cell RCC. I also want to highlight here the cohort evaluating 100 milligrams of Cas plus 60 milligrams of cabozapinib, and this is the same combination and dosing regimen we will evaluate in peak one, and the cohort that is subject of the data presentation at this year's ASCO. Patients in this cohort are all previously treated and have received one or two prior lines of therapy, with their most recent prior line being an anti-PD-1. and patients did not need to have received prior TKI therapy, so this is a very similar population to that of TQAN. On slide 14, we compare the efficacy assessments for the monotherapy cohorts relative to data from LightSpark 5, the Phase 3 study of Biltudafen. Importantly, we enrolled a more advanced patient population than that of LightSpark 5. In fact, approximately one-third of our patients would not have been eligible for LightSpark 5. Though we recognize the limitations of cross-trial comparisons, CAST performed better on every efficacy measure in every cohort, despite this more advanced patient population. Rates of primary progressive disease were close to half that of biltudafan. Confirmed ORR was consistently higher than that of biltudafan, and two cohorts achieved confirmed ORRs greater than 30%. The ORRs for valzudafan monotherapy studies have ranged from 18 to 21.9%. So the castatafan ORR is trending about 50% higher. For disease control rate or DCR, over 80% of patients should benefit from castatafan versus just 61% for valzudafan. Lastly, the median PFS of 9.7 months for the 50mg BID cohort was meaningfully longer than the 5.6 months for Belzudafen, and the median PFS had not even been reached for the 50 mg QD and 100 mg QD cohorts. However, when we pooled data from the 50 mg BID and 50 mg QD cohorts, the median PFS was 13 months, so significantly longer than that of Belzudafen. Slide 11 shows the waterfall and spider plots for the 100 mg QD dose, and these data give us confidence in the selection of 100 mg QD as a dose for our Phase III studies of Cas. On slide 12, we show the spider plots for the 50 mg BID and 50 mg QD cohorts, which highlight the durability of Castatopam's efficacy. Across all three cohorts, remarkably, only two of the 26 confirmed responders have progressed, and many of the stable disease patients clearly derived benefit and will therefore contribute meaningfully to the median PFS. We have a number of upcoming data presentations for Arc20, and these are summarized here on slide five. First up will be initial data from our Cas plus Cabo cohort at ASCO. A key objective of this dataset will be to demonstrate that these molecules can be safely combined. In addition, given that we had approximately 25 patients enrolled by the end of the year, We plan to present overall response rates for data for those patients who are eligible for two or more scans at the data cutoff. So to be clear, the ORR denominator will include all patients who are enrolled at least 12 weeks prior to the data cutoff, regardless of the number of scans actually recorded. I also want to point out that the data included in the ASCO abstract are from a prior data cut, and the ASCO oral presentation will feature data from a more recent data cut. Later in the year, we expect to present more mature data from all four monotherapy cohorts of ARC20 in late-line Clear Cell RCC. In 2026, we plan to share more mature data from the Cas plus Cabo combination cohort, as well as an initial data from the newly added cohorts evaluating the TKI-free regimens in early-line settings. Now onto the development plan, slide 16, which shows the design of Peak 1. where we are evaluating Cas plus Cabo versus Cabo in IO experience patients who had one prior line of immunotherapy. Target enrollment is 700 patients, and we expect that the study will enroll quickly for several reasons. First, as Terry mentioned earlier, we are using Cabo, the most widely used and preferred TKI, in both arms of the study. Second, patients will be randomized two-to-one between the experimental arm and the control arm, And third, there's already very substantial awareness of CAS in the clinician community, and we expect to include multiple ARC-20 sites in the PEAK-1 study. Merck is running a somewhat similar study called LightSpark 11, which is evaluating Belzunafan plus a TKI, and is now expected to read out in 2027. However, there are some important differences I'd like to highlight. First, while PEAK-1 has CABO in both study arms, LightSpark 11 has lumbatinib in the experimental arm, but CABO in the control arm. And using different TKIs in the same experiment could add risk to the trial outcome for LightSpark 11. In addition, we are using a single primary endpoint of PFS in PEEK1 rather than a dual endpoint of OS and PFS, which is being used in LightSpark 11. And given how quickly we expect PEEK1 to enroll and the anticipated timing of the PFS primary endpoint, we have significantly narrowed the gap between our readout and that of LightSpark 11. Meanwhile, in the IO-Naive setting, our strategy is very different. In this setting, Merck is evaluating Beldudafan in combination with Pembro and Levatinib. In contrast, we are collaborating with AstraZeneca to evaluate Cas plus Lorucevig, AstraZeneca's anti-PD-1 CTLA-4 bispecific. And as Teri mentioned, this is a highly attractive TKI-free combination that may enable patients to remain on therapy for several years while avoiding TKI-related toxicities. We have not yet disclosed the design of the study, but we expect to share more information very soon, and we think you'll be excited about our strategy in this setting. I'd now like to turn the call over to Jen to speak about the market opportunity for CasDataCon.

Thank you, Richard. RCC is a unique oncology market in that metastatic patients can remain on therapy for many years. In fact, five years' survival is becoming the norm in this disease, and patients will cycle through multiple treatments, often staying on treatment for well over a year, even in the second-line setting. As a result, we believe the revenue opportunity for a good RCC drug is very substantial. On slide 17, we highlight the total market opportunity for the first two settings we are pursuing for CAFs. First, we show the IO-90 patient population, which we are addressing with CAFs plus folders. The addressable population here is about 13,000 patients in the U.S. and 20,000 in other major markets. Given that most of these patients progress and go on to subsequent therapies, the addressable patient population for the IO experience setting is very similar. With a two-plus-year duration of therapy in IO-90 patients and a 12-month-plus duration of therapy in IO-exclusive patients, we believe the total market opportunity for these two settings combined is $5 billion. With a better molecule than valbutafan and differentiated combinations and development plans, we should capture a significant share of this market. On slide 18, we show U.S. market share by regimen. TKI-based regimens dominate the ClearShell RCC market with approximately 65% share in first line and 75% in the second line setting. This explains why our first phase three study will focus on a cast TKI combination, and you can see here why we chose CAVO as our combination partner. We believe there is a strong clinician preference for CAVO. However, as Terry described earlier, our vision is that over time, Estatifans will move up in lines of therapy and take shares from TKI-based regimens, either as monotherapy or in combination with IO treatments, particularly given CAPS's low rate of primary progressive disease relative to the one competitor, selzudifan. We believe selzudifan's high rate of primary progressive disease is a key reason why it's used today primarily in the third-line setting. I will now turn the call over to Bob to review our financials.

Thanks, Jen. Our cash as of the end of the first quarter was $1 billion, as compared to $992 million as of the end of 2024. Our cash position was bolstered by a $150 million equity financing, which we completed in February 2025. We expect our cash and existing facilities will enable us to fund operations through our initial pivotal readouts for DOM, QEMLI, and CAS, which include the Peak One readout. Given the faster-than-anticipated enrollment of our PRISM-1 trial in pancreatic cancer and the completion of enrollment of STAR-T21 last year, we expect 2025 to be a peak year for development expenses. We expect both our DOM-related and aggregate development expenses to decline meaningfully in 2026 and 2027, inclusive of our investment in CasDataFans. As Terry mentioned, we've also carefully scrutinized our capital allocation and have made pipeline prioritization decisions to ensure we maintain our strong financial position. Turning to our P&L, we recognize gap revenue for the first quarter of $28 million, which compares to $36 million for the fourth quarter of last year. Our revenue is primarily driven by our collaboration with Gilead. We expect to recognize gap revenue of $75 to $90 million for the full year 2025. Our R&D expenses for the first quarter are stated net of reimbursements from Gilead and were $122 million as compared to $111 million in the fourth quarter of last year. G&A expenses were flat at $28 million for the first quarter compared to the fourth quarter of last year. Total non-cash stock-based compensation with $16 million for the first quarter compared to $17 million for the fourth quarter of last year. For more details regarding our financial results, please refer to our earnings press release from earlier today and our 10Q. I will now turn it back to Terry.

Thanks, everyone, for joining us. We appreciate your interest and your continued support of ARCIS, and we'll now open the call for questions.

Thank you. Please press star followed by the number one if you'd like to ask a question, and ensure your device is unmuted locally when it's your turn to speak. Our first question comes from Peter Lawson with Barclays. Your line's open. Please go ahead.

Great. Thank you so much. I guess the first question was just off the back of your comments about pipeline re-prioritization. I wonder if you could talk through that a little bit more, and then whether you're exploring the adenosine inhibitor further if that's the program ended.

Thanks, Peter, and I'll answer that all together. So, as I mentioned, we're always doing this, and in the context of your question about the adenosine modulator, and I think you're probably speaking to the A2 receptor, and that's a perfect example. So, we did have a meeting, and quite good meeting, actually, with the FDA about On that, there's a path forward, but our plans right now are not to move forward at this time, at least. The way I think you should look at our portfolio and how we prioritize things is we have those three late-stage programs. Our number one priority, of course, is Cast Data Fan. Dom Zim, as Bob articulated, is on its natural trajectory. We're excited about data coming, but spend is winding down. PRISM-1, our other adenosine-related molecules, so the CD73 inhibitor, will be fully enrolled this year. So that'll be heading towards data shortly. Keep in mind, the standard of care there has an OS on the order of 10 months. So we're going to get to a readout pretty quick on that. And then on the other side of things, our early-stage portfolio, we've been evolving that too. We still have a number of oncology targets, but we've been quietly, as I described, pushing along some really great inflammation and immunology targets. And so later this year, I think we'll disclose those and you'll find those exciting as well. So the way you can kind of look at it is strong investment, biggest investment in later stage programs, Nothing overly heavy on the middle, and then keeping the sustainable pipeline with what's a relatively minimal investment, but with really that secret source of ARC is to generate the next IND candidates beyond those we talked about now.

Gotcha. And then on the oral presentation, Aska, what should we expect to see in the abstract versus the oral presentation, and what do you kind of press release beyond the abstract?

I'm wondering if someone planted that question. It's one we think is important. So I think you should recognize, everyone should recognize the abstract is more of a placeholder abstract. And so the data cut that we'll be sharing at ASCO will be much more recent. And what it will include is you can think about as two populations. First, the safety population will be about 40 patients, and then we'll also wanna give you a read on efficacy. So even though probably the median time of follow-up is barely over four months, what we've done is we've assembled all the patients who've had at least two scans, so that gives them the opportunity to potentially have had a confirmed response and will be sharing efficacy data for that 25 or so patients. You'll see a waterfall plot. Obviously, the data are far too mature to talk about maturity. And I think the data, you know, I think you'll find them compelling, but you should recognize, given that they are early, they will likely continue to improve beyond on what we share at this conference. Great. Thank you so much. Thank you, Peter.

Our next question comes from Dana Graybosh with Learing Partners. Your line's open.

Hi. Thank you. I have two really different questions. First, on TIGIT, as you pointed out, the TIGIT phase 3s are dominated by the EPC silence. You're then asked to specify specific. And let's say we assume, as I think you believe, that FC Sila is really the key to maximizing digit benefit. Are you under-investing and ceding leadership to Astra? Can you just remind us what you're learning in phase two? And is there a gate of success that you might actually ramp investment back up? And then I have one on CAS after that.

Yeah, I think... So, first of all, I think we feel very good about the bets that we've made because they're targeting some of the largest IO markets out there. So, our study in lung, STRAT121 is targeting all-comer non-sulfate lung cancer patients, obviously the biggest market there is for anti-PD-1. And then, you know, our other phagocytic, STRAT221, is targeting all-comer gastric cancer patients, which is another really, really good market. So we feel like those are two great bets to make. You know, we do have active discussions going on all the time about other things that we would want to do if those studies read out positively. So I said there's other things that are teed up and ready to go if our first phase three readouts are positive. But we agree with what you're saying. And then the other study to point out, Trace, just reminding me, is the stage three lung cancer study that we're doing with AstraZeneca, which AstraZeneca is operationalizing PacAids. And so, you know, they've obviously seen a lot of our data because we have that partnership on PAC-AID. And so, we do think that that's something else that's given them even more conviction in their own PD-1 digit program.

Awesome. And then on CAS and the potential for CAS mono to replace TKI in second line, you have that ARC-20 cohort. Is there any particular bar for efficacy you're looking for that would give you conviction to go head-to-head versus a TKI?

So I think at this point we would look at those as a little bit more exploratory. They're different. In the monotherapy, keep in mind in those favorable risk patients, basically you're the standard these days would be more just watch and wait. So if you see reduction, meaningful reductions in tumor, given the safety profile, we think that could encourage people to want to invest in this. And keep in mind, those patients could be a couple years. So the idea there is to get a sense how it looks in those favorable risk patients I know that's not a patient population that's getting TKI, but that's sort of where we're, you know, one of those areas where we don't necessarily have something numerically in mind, but we're looking to see if there's a signal, and we think there's a really good opportunity there.

Yeah, I think, you know, like our settings that are out there for TKI mono, you know, range anywhere from sort of high teens, 20%. It's a very high end of the range, 40%. You know, so if we could be in line with that, with a better safety profile, we think that would be really exciting for clinicians. We were actually just talking to a clinician yesterday that's been one of the high enrollers in our CAST-CABO cohort. She just put her first patient on the cohort that you were asking about, the CAST mono and second-line patients, and she was very excited about how that patient was doing. And so we look forward to hearing more anecdotes like that.

I think the thing is, is even if you look at our late-line studies, is already pointing to something that would tell you you've got a good chance to be better than TKI. And the enthusiasm there really does ramp up because of two things. The fact that it is TKI-free in the safety profile, but also because of the low rate of primary progression. That's probably why you haven't seen bells be able to go there. And, you know, that's really important as you go to the earlier lines. But we feel like we're already seeing numbers, even in the later line, that would encourage us for the opportunity going earlier as a model.

Great. Thank you.

Thanks, Dana.

The next question comes from Yigal Neshomovitz with Citigroup. Your line's open. Please go ahead.

Hi, thanks. Can you just talk about the timing for peak one PFS primary? And then you said LightSpark is going to be dual. So do we know which of these is coming first? And if LightSpark hits on OS and PFS, then what's the plan to answer the OS question for peak one? And under what timeframe would that happen relative to the mark? Thanks.

Yeah. Yeah. So, there's a lot of questions in there. So, first of all, you know, it's too early for us to give. No, it's all very good questions. All very good questions. So, on peak one, yeah, I think it's too early given we're just about to start the study to get guidance on when we might see PFS data. You know, we talked to some of you. You can probably do some back-of-the-envelope math just based on, you know, how likely you think it would take to complete enrollment based on other RCC studies, you know, and then what the PFS is that you would expect to see in the control arm. And you can kind of get to when you might expect to see a readout. So it's not in the too-far distance because we do think this is a study that's going to roll quickly, and because it is a PFS readout, On your question on OS and what we're doing, OS is a key secondary endpoint. To your point, we do think it's important to collect that information, and it is a key secondary endpoint in our studies. That data will be collected. As far as LifeSpark 011, they had it as a dual primary endpoint of OS and PFS. So if they hit on one of those, then the study would be successful. You do have to split alpha in that case because there's two different endpoints versus what we're doing, which is a sole primary. So that can work against you. But if they are waiting for that OSM point, that is what's giving us the opportunity to really catch up to them and narrow that gap between when our readout might occur versus theirs.

You know, just to put something out there that is out there, you know, Merck recently pushed out that study on clinicaltrials.gov for a second time out to 2027. whenever you do your back of the envelope calculations, while we haven't given guidance, that even that potential delta is dramatically closed from when we first started contemplating this. And we actually do feel we're going to have agenda in common on this, but we've got real tailwinds as we launch this study. The investigator enthusiasm not only is very strong, but from a practical standpoint, because we've invested pretty heavily in these monotherapy cohorts, not only have we engendered a lot of enthusiasm, all kind of anecdotal studies, every one of these investigators has their own interesting story of what they've seen, so they want to jump on this, but the other practical matter is that we've got 30 or 40 sites that are going to transition potentially into peak one. I think we're really going to be hitting the ground running in an unusual way versus going from a standing start.

So having an ASCO presentation of the Cabo cohort is obviously perfect timing. You know, I think the investigators are particularly interested in seeing – efficacy is obviously important, but I think everyone believes we're going to add efficacy. But they really want to see safety and just make sure there's no additional toxicities or overlapping toxicities or – and so that will be a very important part of the data presentation.

Okay, okay, gotcha. And then, you know, post the Gilead decision on TAS, is the plan now to just fund this to completion yourselves, or would you entertain, you know, help from another partner potentially?

Yeah, so the first thing I want to mention, because I think it's an important point because of a lot of the questions that were out there right at that time. These new data, you know, are new. So this will give you yet another look. The cascabo data are, you know, we think quite exciting, and obviously they were not mature data when Gilead made their decision. Getting to the specific question, You know, we feel really confident in our abilities for some of the reasons we were just talking about. You know, we've been working with the molecule. We've been working with the sites. We've got a steering committee that's, you know, couldn't be better. They're excited. We feel we're in a great position to execute this, not only from a capital position, as we talked about. We have the resources, but from the people standpoint, Our team has been working with this all along. So our plans are to execute Peak One on our own. With that said, could there be some other collaborations? As we mentioned, we'd like to use collaborations in an efficient manner. As an example, the AstraZeneca collaboration, we might do other things like that. And of course, on an opportunistic basis, there could be other things we would do. But the base case you should be thinking about is that we feel very good about our ability to execute this trial in a very efficient and, you know, strong manner.

All right. Thank you, Terry. Thanks, John.

The next question comes from Uma Rafa with Evercore. Please go ahead.

Hi, guys. Thanks for taking my question. I have a few here, if I may. Perhaps first, the choice of dose being 100 milligrams for your first phase three, which admittedly is a cabo combo. Is there anything to read into the choice of that 100 milligram dose relative to any early data you're seeing on the 150 and 200 milligrams? And I have a couple of follow-ups.

Okay. And you can have as many questions as you like, Umar. So 100, not being... Based upon any new data that we've seen, we had a really good discussion with the FDA in the context of Project Optimist. The 100 milligram dose, we talked about that. We talked about potentially 150. We talked about potentially 50. Safety profile of the 100 looked great. We feel, based upon all the data we've seen, that 100 is essentially on the asymptote for efficacy. What we're seeing with 150, I think we'll share that at the end of the year, but I would just foreshadow that you're going to see something that looks pretty similar, and we'll see just how things play out. One thing that's important to note, for our 50 and 100 milligram doses, we still do not have medium PFS. Maybe as we get towards the end of the year and we're sharing data, we'll be there, but obviously we'll have some sort of landmark PFS. And it may be that there's a bit of more AE creeping in on the 150. I couldn't even say that with certainty now. So I think the way to look at the 100 milligram dose is everything we've seen suggests that you're essentially maxing out efficacy there, and it's a very safe profile. So there's not a whole lot of rationale to even be thinking about the 150. And what about 200?

Yeah, same. I mean, we only looked at 200 in the dose escalation. Didn't see any DLTs, which was good. But we haven't looked at it beyond the dose escalation. And I think, you know, Sherry was saying, you know, based on everything we've seen so far, so we now have, you know, 30 patients worth of 50-meg, 100-meg, 150-meg data. And I think that all gives us a lot of confidence that 100 megs is the right dose.

I think the other thing that we're actually thrilled about, it's not a surprise, but, and will draw your attention when you look at the CAS-CABO data, is, you know, an important aspect of that is being able to keep patients on therapy. And the data look, you know, we think pretty compelling, even though they're early, and obviously with time, you might see otherwise, but I think you'll come away feeling like, efficacy, on those patients that have, you know, had two scans looking good. Waterfall looks good. And the AEs look like combo by itself plus cast by itself and, you know, very well-tolerated combination.

Yeah, I think one of the really exciting opportunities about the combination, too, is that if you're just getting TKI mono and you get hand-foot-mouth syndrome or greater hypertension, whatever it is, it would typically have to come off your TKI for a bit. In this case, even though you're coming off the TKI, you're still getting a HIP-12 inhibitor, so you're still getting an active drug, and that's one of the things that I think positions the combination to perform very well relative to carbamonotherapy because throughout, you know, in most cases, patients are going to be getting at least one of those two drugs. So if you do get TKI-related toxicities, they will stay uncapped.

Got it. So I guess that brings me to my sort of main question here, which is what exactly is the makeup of this post-IO cohort in ARC-20 that we're going to see at ASCO or the cohort in general? And I ask because you could have double IO experienced or you could have IO plus SEG FTKI experienced. And my understanding is ORR is a little lower when it's IO plus SEG FTKI versus dual IO. So what exactly is that? And is there any data to read into from your which is also second-line plus and may presumably have some of these post-IO patients as well.

Yeah, so you're right. It's going to be a mix, and we'll disclose that mix. And it's in line, actually, with the LightSpark OO3 study that looked at cas plus combo. You know, one thing that I would mention, when you look at patients that got IO-IO versus patients that got IO plus VEGF, so far the ORRs actually look very similar. So there's not seem to be a difference. if patients had gotten prior TTI versus just prior IO. Does that make sense?

Okay. And, Jen, do you acknowledge about 30? Right. And would you acknowledge from CABA point trial about low 30s in ORR is the comp for CABA monotherapy following IO therapy?

Go ahead. Go ahead, Richard.

Yeah, I think the CABO alone, right, has a range of ORRs, depending on what study you look at and what data source you have. So, kind of in the 20 to 40. So, if you pick 30, you know, that's one of the choices, I'd say. But, you know, it's quite a range across the different data sets there for CABO alone.

The one other relevant data set is there was a Bell's CABO arm. And that, again, on the ORR front, came in just over 30%. And it's PFS in that study. Obviously, we won't have PFS to compare it to yet, but the PFS there was on the order of 13 months.

And again, just so I'm clear, we talked about 20 to 40 being the range, maybe 30-ish being the midpoint, which is also consistent with the Cabo Point trial. But the critical thing is, you guys are emphasizing safety, not an efficacy advantage. Is that reasonable? Or do you want to have higher ORR as well?

No, I think the goal is absolutely to have both. We're just saying both is important, and we're just trying to make the point that safety is going to feed into efficacy because you want to keep patients on drugs. You want to avoid dose reductions. So the more we think we can safely combine these two drugs, that should further enhance efficacy. So the goal is absolutely to show an improvement on both those metrics. Nuts. and efficacy and safety that you aren't getting additive toxicity or even worse toxicity than what you'd expect with eukaryotic alone.

Thank you so much. Thanks, Omer.

Next, we have Astika Gunawadin with Truist. Your line's open.

Hi, this is Karina for ASTICA. Thanks for taking my question. I had a question on prostatafan. So, beyond the AstraZeneca study with the bullish stomach, are there any plans to initiate registrational studies, potentially in combinations with PD-1s or Zambia in frontline?

Yeah, so nothing registrational that we've disclosed so far. So, as Trey talked about on the call, we did just open a cohort in ARC-20 where we're combining CAS with our anti-PD1 sembrilimab and first-line patients. So that's something, you know, we could ultimately initiate a registrational study for some sort of, you know, more end-to-end guideline-enabling study. But that's the combination we're super excited about, investigators are super excited about. We think that cohort's going to enroll incredibly quickly because, again, I think there's a lot of interest in just avoiding TTIs in the front-line setting when patients are still feeling really good and are relatively healthy. Yeah, so we'll see how that goes and some of these other cohorts that we started, and those can be future registrational studies for sure.

I think the way you should think about our approach is that basically we're not just going to be throwing a bunch of spaghetti up on the wall where we jump. You know, we think we have a great molecule, but we're not just going to start peppering the world with Phase III studies. So we're going to do, you know, early work to ensure that any Phase III study we do really makes sense.

Okay, that's helpful. Thank you.

Thank you.

The next question comes from Lee Watzek with . Please go ahead.

Hey, this is Dan on for Lee. I was wondering if you could kind of set expectations for your combination with Volro and what you're looking for in the setting and for a potential pivotal frontline trial what would you be comparing your doublets to?

That's a lot of good questions. And it's a lot of information we just haven't disclosed yet for competitive reasons. And as Richard alluded to on the call, you know, probably around mid-year, which I'm getting close to, we should be able to talk a lot more about that study. And so right now, really, all we can disclose is that the plan is to go by cast with Bull Roo in the first-line setting. The big issue with ipinevo and PCLA-4s is that you do have a very high rate of primary progressive disease. So about 25% to 30% of patients don't respond to ipinevo and just flow right through therapy. And so that's why today, actually, ipinevo is typically used in patients that don't have really aggressive disease, so, you know, more slower-growth tumors. And so one of the reasons why I think Astra was very excited about combining ball-road tests is that opportunity to bring down the rate of primary progressive disease, given we're seeing a very low rate of primary progressive disease so far with cats. And so what we will be looking for initially is obviously that you can safely combine these two mechanisms, which today we have no reason to believe you couldn't. And then we will be looking, you know, at some of these early signs of efficacy, particularly the rate of PD. And then eventually, you know, we'll be looking at ORRs, et cetera. But, you know, we do think that PD rates could be particularly interesting to look at because you do have that high rate of primary progressive disease with ipunivo. There's a huge amount of interest in that combination. We talked about it on the call. We just actually did some market research, and I think we were actually even surprised about how much interest there is in the investigator community to combine these two mechanisms and to try to avoid TKIs in the front lines.

Okay, great. Thank you.

Our next question is from Salveen Richter with Goldman Sachs. Your line's open.

Great. Thanks. This is Matt on for Salveen. Maybe first just on CAS to follow up on a prior question. Is it fair to say you guys would consider a commercialization partnership post-peak one or when you're close to reading out peak one, or is that no longer of interest to you? And then on the broader portfolio, any thoughts on the newly announced CBER director from just kind of a portfolio risk perspective? Thank you.

Yeah, so on the first question, our intent is to commercialize. We want to fully leverage the opportunity. We think this is really huge for Arcus. I think we probably consider a partner in Europe. but we feel really good about taking this forward, commercializing it. The whole piece for us seems very manageable. I don't have any comments on the latter. I don't think anyone here does. In macro, I would even elevate that our whole sense about everything happening at the FDA when it comes to what we're doing, what we're executing, you know, things have just been business as usual as far as we can tell. So, you know, what's happening in the news, I have no comment, but from a practical standpoint, we're pretty comfortable with everything we're doing right now, that it's proceeding just as it would have, you know, six months or one year ago.

Thank you.

Sure, thanks.

Our next question is from Eva Forteo with Wells Fargo. Please go ahead.

Hi, thanks for taking our questions. A couple from us. First, on the fall 2025 update forecast, can you just provide a bit more color on, like, expectations here in terms of, like, the different cohorts, number of patients, and duration of the follow-up? And the second question, as you mentioned, an emerging INI franchise, when should we expect to learn more about this? Would this be more towards the end of the year in an R&D day type of event? Thanks.

Yeah, I could address the first part of the question, Elise, with regards to the follow-up in the fall. And it's really looking, again, at the monotherapy data we had at ASCO-GU. We'll have more mature data. coming, so we'll have another data cut there. We haven't stated or selected if this will be at a medical conference or other ways of sharing that data, but we will be able to provide updates to that data since it will have matured a fair bit since the cut at the beginning of this year.

And on the immunology inflammation front, I think the way to think about that is, you know, conceptually, whether it's an R&D day or part of one of our other releases, you know, we'll find a form to describe, you know, the breadth of what we're doing and where we sit. And I think it's an exciting portfolio. It takes advantage of, you know, what we do well. And I think that'll be highlighted, you know, the small molecules for challenging targets where, you know, the targets are highly validated, but there's not a great So we've been building on that. You know, I'll remind you, because we're like a real company in terms of with people, and, you know, we have a biology group, we have a med chem group, and all of the associated functions that there is, but our biology is actually more immunology because the roots are in, you know, immuno-oncology. And so even though where oncology has been our clinical endpoint, you know, we have a strong immunology group and, in fact, you know, have invested in that. And, you know, now we're getting to the point where we can start to talk about those programs with, you know, we like to talk about things when we've got tangible matter, not glint in the eye. And I think that these will be very tangible. And all done without machine learning. But we have machines.

We'll take one more question before ending. And our final question comes from Emily Bodnar with HC Vainwright. Please go ahead.

Hi, thanks for taking the questions. My first one for Kaz, the monotherapy doses, can you comment on how the 100 meg QD cohort is progressing relative to the 50 mg BID cohort and if you're starting to see similar results in terms of median PFS. If you could just comment on timing for the STAR-121 trial for DOM in lung cancer and if there's any timing updates for the top line results. Thanks.

Yeah. So, there's really no timing update yet on 1-to-1 study. You know, two things, it's still enrolling, and then it has, you know, OS for the standard care is, you know, over 20 months, so it's pretty mature. It's obviously enrolled well and will continue to enroll, but we haven't said anything on timing there. Nothing to say yet, really, on the maturing data, other than to point out that we haven't reached a median PFS. And so I think as we get towards the end of the year, we don't even know for sure that we'll be there. But if we're not, we still will be sharing data, and it would then undoubtedly include some sort of landmark PFS.

All right. Thank you.

Thank you.

Thank you. This concludes our Q&A session today as well as the call. Thank you everyone for joining. You can now disconnect your line.