Good morning. My name is Peter Lawson. Welcome to Barclays Global Healthcare Conference in Miami. Really pleased to have with us up on stage with us, Arcus. We've got management team. We've got Terry Rosen, CEO and Co-founder, and Jennifer Jarrett, COO. I guess the first question would be really around, I guess you've answered this multiple times around ARC-7, kind of underperformance, kind of how you think about your PD-1 versus other PD-1s. I know this, you've got some historical perspective as well around that and how those have changed over time.
Sure. I mean, we don't, we don't think of the anti-PD-1 as underperforming in any way. We think zimberelimab looks just like KEYTRUDA, looks like the other anti-PD-1s. Without spending a ton of time on it, there's this historical data all from its approval in China, run by Gloria in classical Hodgkin's lymphoma, where it looks as good or better than KEYTRUDA. There's a cervical data set where it looks as good or better. In this particular trial, you could just spend time looking at all the differences across all the studies, including with KEYTRUDA looking different from itself, in terms of how the patient population has evolved, how patients are selected for trials, the differences across trials, the differences in time between scans, in trials.
That's, you know, actually Andrew Baum, one of your competitors, did a very nice analysis on that. I think the most compelling illustration of the differences in whether you want to call it real-world data or real-world clinical trial data, would be the recent study that Glaxo reported out where they ran KEYTRUDA plus chemo versus the Glaxo Tesaro anti-PD-1 plus chemo, essentially the KEYNOTE-189 study. You, and you see a change there in PFS of, you know, in historically, that was like nine months for KEYTRUDA, now it's like six point something months.
We would just look at the data and point people to the combination in ARC-7 that where you see a 12-month PFS for that doublet, a hazard ratio of 0.55 within the trial, and that 12 months PFS looking better than any PFS that's reported for any anti-PD-1 study, including KEYNOTE-189 anti-PD-1 or KEYTRUDA plus chemo. We feel like complete confidence. I think when we talk to investigators, they express the same confidence in the performance.
Gotcha. Then the updated data at ASCO, what should we be looking for, and what metrics changed, do you think?
Why don't you say a little bit about that, Jen?
Yeah. We're thinking through that now. Obviously, Gilead will be a big part of that in terms of what exactly we're gonna present. It's only about a five-minute presentation, so it's not particularly long. So it's gonna be a little bit short and sweet. One data set that we're certainly gonna look at is just looking at the same data set that we presented at ASCO Plenary. The interim four data set of about 43 patients per arm and rolling that forward to generate a more mature look at the data. Then obviously, we'll be looking at the 150 patients as well. This time, because the data is gonna be more mature, we'll also, you know, maybe be able to share a few new efficacy measures.
As we said last time, you know, every efficacy measure we looked at, we did see an improvement from dom combinations versus zim. Some of those metrics we didn't provide just because they weren't super mature, but they'll be a bit more mature this time around. Things like 12-month PFS. Those are other things that we're considering presenting. You know, we're doing biomarker analysis. I'm not sure we're gonna have enough time to really get into the weeds of the biomarker analysis, but that's something else that we're thinking about. Also just thinking about things like, you know, is there a difference when you look at PD-L1 testing status, you know, central versus local lab? You know, does different levels of PD-L1 result in higher efficacy with a TIGIT antibody?
There's all sorts of things that we could present, and we're sorting through that now.
Gotcha. Would you end up having a, like, amnesty or some other?
We, it's a competitor, unfortunately. We are doing event with another bank. They just started marketing it about a week ago, or another analyst I said in a bank, that evening. The idea is to be able to share more information or more context for everything, given it's not gonna be a particularly long presentation. There's a lot of information that we wanna.
Would there be a press release or something?
Yeah. No, there'll definitely be a press release. You know, you know, a few things. First of all, there's no abstract, so a little bit different than your typical ASCO presentation. We don't have to submit an abstract. There's not gonna be an abstract that's made public prior to the ASCO Plenary or ASCO session. ASCO will be the first time that people see anything. The actual presentation is, I think, Saturday, late morning. Then, there would be a press release, most likely concurrent with that. Then, you know, like I said, we will have the event that evening, where we'd be able to share some more information.
Gotcha. We'll get you for a breakfast then or something.
Yeah, there you go.
Just I guess in the context of Roche's data, kind of how do you think that plays out? Do you think they hit OS? What's your sense there?
Yeah, I mean, we take everything they said at face value. We think it's probably best-case scenario from what we've been thinking, that they've seen a numerical difference. They expect that as they go to OS, they've suggested that they think they will have a data set that allows them approval. We sort of look at their data in a vacuum at this point. We think the field is moving along such that SKYSCRAPER-01 is no longer going to be the center of the solar system. Merck has a very large footprint. They, in their last earnings, talked about how anti-TIGIT is going to be a very meaningful part of what they're doing going forward. As you know, they have a co-formulation. They're running multiple phase III trials. Our data set, you know, again, we're running four registrational trials.
We'll see if there's anything interesting to be learned from them, but we just kind of view that they're gonna be one player and the probably the delta in terms of their advantage from a timing standpoint may be different than the. You know, they obviously didn't knock the ball out of the park with their combination, you know, based upon whatever their trial design was. We'll learn more probably by the end of the year, but nothing in that data set is driving any of our planning.
Is there anything from, I guess, Merck's large footprint in TIGIT that's kind of inspired you or something you wanna-?
Not really, because they've, you know, to date, they've shared, you know, they're able to keep their cards pretty close to their vest. The thing that we find encouraging just is that they're obviously seeing a lot of their own data. What's interesting, you know, I think is when we were talking about the field, AstraZeneca, who's seen all of our data, also in their last earnings, talked about being more aggressive with their bispecific. Clearly they've seen all of our data, however much that influenced or not, but their bispecific includes a Fc-silent, anti-TIGIT, component. We're monitoring everybody else.
You know, we're thinking about as time moves along, I think the questions are gonna move away from what do you think Sky One is going to be versus, you know, how do you plan to compete versus Merck? How do you see your differences? Where are your opportunities? You know, we are running STAR-121 PD-L1 all-comer trial that's being executed by Gilead. STAR-221 in GI, where we have an opportunity to be first. We think there are differences between the Fc-silent and Fc-functional antibodies, and we think there are differences, even when it comes to Merck, between our co-administration that we're planning to use versus the co-form that they're using. A lot to talk about in the competitive situation.
I think as the year evolves that the conversation may switch more to that direction than what do you think Sky One is gonna be?
Gotcha. Just as we think about these combinations and fixed dose and bispecifics, how do you think that kind of plays out? How will physicians use the TIGIT?
I think in the end, this is the feedback that we hear. We, you know, as recently a couple weeks ago, we had an investigator meeting with, I would say is we hit the lead of a group as you might have in the non-small cell lung cancer arena and with a very substantial knowledge of anti-TIGIT. Essentially these combinations are by the time they're developed, they'll be thought of as like a single entity, and they'll be judged on their own performance. As an example, of a differentiation, we did a lot of research when we thought about whether we wanted to go for co-administration or co-formulation. All of the feedback we got suggested that the physicians really didn't like co-formulation. It takes away the flexibility of titrating out one of the agents.
For example, if you see an AE, it forces you to put, you know, a dose in that bag that may be determined for not necessarily the most optimal reasons. It may just be that since you know you're gonna have it in that bag, you wanna ensure that you don't into any liability. All of the feedback that we've heard is that combination, how it performs against versus the historical standard of care, that'll determine uptake. In all four of our registrational trials, we are using what's considered to be the global standard of care. We feel real good about the trial design and then what that leads to in terms of the ability for uptake.
Gotcha.
on approval.
How far behind Roche or Merck do you think you are?
Do you wanna comment on how we look at that?
Yes. I mean, Roche is obviously ahead of everybody with the PD-L1 high subset. That said, you know, it went from feeling like, you know, sort of three years ahead of everyone. Obviously, the gap is narrowing as the analysis keeps getting kicked out. But they're still probably gonna be in the lead in the PD-L1 high patient population. I'd say the settings that we probably care the most about, just because of the size of the market opportunity, is the first-line lung all-comer patient population. That's the patient population that we're pursuing with STAR-121. That's the study that Gilead is operationalizing. Roche has a study, which is SKYSCRAPER-06 in that same patient population. The difference is that was a phase II converted to a phase III.
You know, I think there's some risk the study, you know, may be underpowered. The other thing that's different about that study versus what we're doing is they're only targeting non-squamous cell patients. They excluded squamous cell patients for some reason. We're looking at all patients. Merck is running a similar study. We're probably a little bit behind them, but you know, we're trying to be right on their coattails, you know, we think it'll be sort of a race between us and Merck in that setting. The other setting that we care a lot about and study that we're very excited about is STAR-221, which is looking at dom plus M plus chemo and first-line gastric and esophageal adenocarcinoma cancer.
We are the only one today with the phase III study in that setting. We should have the lead. There's a ton of interest in that study, just to view that there's unmet needs. Actually, the ARC-7 data, interestingly, even though it's in lung cancer, has generated a lot of interest in the GI community in the combination. That's a study that could potentially enroll pretty quickly. And like I said, we're the only one with the phase III right now. AstraZeneca, interestingly enough, just started a phase II with their PD-1 TIGIT bispecific in that setting, randomized phase II. They're obviously also interested in the setting, but we're obviously gonna have a big lead over them.
Perfect. Thank you. I'd love to move on to CD73 and kind of what we should expect next, from CD73.
Sure. The next read out there's, you'll recall, we were running a trial called ARC-8 that's in pancreatic cancer. We've reported out initially we saw some very exciting data early in the dose escalation, dose expansion phase. What we had designed was a randomized study. That randomized study was designed to tease out whether anti-PD-1 was doing anything. We essentially get anti-PD-1, CD73 inhibitor, quemliclustat, and then gemcitabine versus the triplet, where you're lacking the anti-PD-1. Along the way, we took an early look and we reported that we weren't seeing big differences between the arms, but that we were gonna let everything go to OS. We're very close to having those data now, and later this year we'll share those.
That's part of if you think of our whole adenosine footprint, etrumadenant in ARC-6 and ARC-9, prostate and colorectal, and then, quemliclustat in frontline pancreatic cancer. All of those are relatively large phase II studies, and they're all randomized, and they'll all be reporting out. We're actually excited about all three of them, and that'll be coming, you know, later this year.
Gotcha. Just with the, I guess, lack of or not showing significance difference you mentioned before, kind of low expectations for first line. Is that how we should be thinking about that?
Not necessarily.
The second line you have-
We'll see what the data reveals. The key thing to keep in mind there is the difference between those arms is going to be reflecting how important anti-PD-1 is in that combination. If you saw OS advantages in both arms that were similar, what that would be pointing you toward would be something where you might be thinking about gemcitabine plus CD73 inhibition alone. You know, to remind people, historically, when you look at gemcitabine, there are a lot of data out there, and, you know, across studies in its approval phase III study, gemcitabine, I think the OS was on the order of eight and a half months or so.
There's a lot of studies that you can probably think of it as ranging from somewhere from eight to like 11 months or so. We'll have a very good historical data set. I think the FDA feels as well that gemcitabine is very well understood. We're looking to see in all of these studies, you know, not just a small difference, but something that would be very clinically meaningful. We'll wait and see.
Gotcha. Thank you. It's then how do you think about the kind of first line versus second line opportunity for CD73?
Yeah. At this point, we're just focused on the first line setting.
Okay.
We'll see how that reads out.
You mentioned ARC-6 and adenosine kind of what should we expect? How much data would we get to see? How many patients in?
Yeah. ARC-6 is about 70 patients. That's 35 patients per arm. That is second line CRPC patients that have failed a novel hormonal therapy. It is a randomized study in comparison with a standard care Docetaxel. You know, we have to worry less about like, you know, what would this show, you know, versus the comparator because we'll have the comparator in the study. That's the prostate cancer study. We also have the colorectal cancer study, that's ARC-9. That's actually a pretty big data set. That's over 200 patients. There we have two different cohorts. We have a second-line cohort and a third-line cohort. What's nice is you kinda have two independent data sets that, you know, will hopefully both prove that Etrumadenant is active in that setting.
The second-line cohort is looking at etrumadenant plus SIM plus chemo versus chemo. The third-line setting is looking at etrumadenant plus SIM plus chemo versus regorafenib, which is a standard care in that setting. Again, randomized study. You know, we worry less about, like, what would you expect to see with the comparator.
Gotcha. What are the lessons from ARC-7 adenosine and kind of how that reads through to other indications or other combinations?
Really, there were a couple different hypotheses when we started in the adenosine program. Interestingly, one was looking at, like, settings where you have high CD73, but let's say you have anti-PD-1 activity like frontline lung. The others, and this was probably our principal emphasis, and we started looking at this earlier perhaps than others, were in settings that are really non-anti-PD-1 responsive, but you're using chemo to drive a response. That chemo, when it kills through an immunogenic cell death type of mechanism, produces a ton of adenosine. There are two very different hypotheses. These three trials that we just talked about, ARC-6, ARC-8, ARC-9, really read on that chemo mechanism, so we'll have a good feel from that.
With respect to ARC-7, we're still playing that out. Obviously, we weren't seeing anything differentiating it either interim analysis three or four in terms of that high PD-L1, anti-PD-1 plus, anti-TIGIT. We'll see if we see anything from an overall survival standpoint. I'll remind you that interestingly, in the patients where we looked at those who progressed on anti-PD-1 alone, and they were confirmed progressers, while that was a very, I'll call it exploratory, aspect of that phase II study, we saw a couple of very interesting responses in those patients that had progressed when they went on to the triplet. We'll see how that all plays out.
I think that the readouts from ARC-6, ARC-9, and ARC-8 will have really given, you know, the best opportunity to see how in this chemo type setting where you're generating a lot of adenosine does that adenosine inhibition bring advantage. You know, we'll know a lot about that in the next, you know, six months or so.
Gotcha. I'd love to move on then to HIF-2α, just kind of what we should expect to see, what late this year, early next year.
We're in the dose escalation study right now. We're in the second dose escalation cohort, which is 50 migs. We are pretty close to wrapping up that dosing cohort, and then we'll move on to 100 migs. At 100 migs of AB521, we think we're getting to 4x-5x the drug levels that Merck gets with belzutifan. We actually think that could be our going forward dose. We'll probably explore some higher doses, just to see what we get. But, you know, we think we're pretty close to getting to our going forward dose. As we announced in our Q4 earnings, the plan right now is to start a phase II study in combination with another molecule in the second half of the year.
The plan is to try to start a phase III study as quickly as possible. You know, going back to what could we see, we plan on trying to present some data either end of this year, early next year from the dose escalation portion of the study. It is an all-comer study, we are trying to enrich for clear cell RCC patients to try to give us a little bit of a sign of efficacy. The data that would be presented would be safety, PK/PD, and then hopefully some efficacy data as well. Once we complete the escalation cohort, we will also start enrolling an expansion cohort within that same study.
That'll be just clear cell RCC patients, and that'll be running in parallel to the phase II that we'll be starting in the second half of the year. Next year there should be a lot of data from HIF-2α.
Gotcha. Then the combos you're thinking of, I mean?
Yeah, we haven't disclosed anything yet. I mean, you know, you can see what Mark's doing with those and, you know, I think that'll give you a sense for, like, the types of combos we're thinking about. You know, we're super excited about the program. You know, we think we have a better molecule than belzutifan. You know, we think we can find a better combination partner and have found a better combination partner than lenvatinib, which is what Bel is being combined with. Yeah, more to come.
Okay. Perfect. I guess just, the topical question just around SVB, kind of what's the exposure not only there, but I guess other regional banks or?
Nothing. Yeah. We're all. We had some SVB exposure. We were just on the operational cash side, we were smart on Thursday, kind of got ahead of things and moved almost everything out of SVB to going into.
Took all of ours out.
Yeah. Going into Friday, we had very little exposure. You know, I think as we communicated to you, we had very little exposure. Today, you know, all of our operational cash and investment cash sits with, you know, large global banks. We have no exposure to Signature, First Republic, et cetera. We are in very good position.
Thank you so much. Great.
Thank you.
Bless you tons. Thank you.