Arcus Biosciences at Citi’s Biopharma: Strategic Clinical Moves

On Wednesday, 03 September 2025, Arcus Biosciences (NYSE:RCUS) took the stage at Citi’s Biopharma Back to School Conference. The company, led by CEO Terry Rosen and COO Jennifer Jarrett, provided a strategic overview of its clinical development programs, highlighting both promising advancements and competitive challenges. The focus was on their HIF-2α inhibitor, Casdatafan, and its potential superiority over Merck’s belzutafen, alongside updates on their differentiated development strategies.

Key Takeaways

• Arcus is advancing two Phase 3 trials, Peak One and Evolve, targeting renal cell carcinoma (RCC) with innovative combinations.
• The company emphasizes Casdatafan’s superior pharmacokinetic profile and potential as a best-in-class molecule.
• Arcus plans a significant data release on October 6th, including progression-free survival data for Casdatafan.
• Enrollment for their Quemly Phase 3 trial was completed ahead of schedule, driven by strong investigator interest.
• Arcus is positioned for transformation with four molecules in Phase 3 studies across major markets.

Operational Updates

• Peak One Phase 3 Trial: Initial sites activated, with the first patient expected soon. The goal is to complete enrollment in 18 months or less.
• Evolve Phase 3 Trial: Conducted with AstraZeneca, focusing on a safety run-in phase, with full Phase 3 trials beginning next year.
• Quemly Phase 3 Trial: Enrollment completed nine months ahead of schedule, with results anticipated in the near term.
• Upcoming Investor Event: Scheduled for October 6th, featuring substantial data releases including Casdatafan monotherapy results.
• Star121 Trial: Expected full enrollment by year-end, targeting non-small cell lung cancer.

Future Outlook

• Casdatafan: Ongoing data updates from ARC-20 aim to confirm its best-in-class efficacy. Additional data expected mid-next year.
• Edgastric: Overall survival data from the EDGE gastric study will be presented at ESMO, potentially derisking the Start 221 trial.
• Start 221: Results anticipated in 2024, with positive outcomes likely benefiting the Star 121 trial.
• Quemly: Results expected within the next 12 to 18 months.
• Long-term Data Flow: Continuous updates are expected through 2027.

Q&A Highlights

• Casdatafan vs. Belzutafen: Arcus highlighted the superior pharmacokinetic and pharmacodynamic properties of Casdatafan.
• Peak One Trial Design: Cabozantinib was chosen for its widespread use and clinician familiarity.
• Evolve Trial Design: Focused on a TKI-sparing regimen, an approach not pursued by Merck.
• TIGIT Inhibitors: Discussion on the advantages of Fc-enabled antibodies over Fc-silent ones.
• Quemly: Aiming to improve upon existing survival rates in pancreatic cancer treatment, with enrollment completed 14 months ahead of expectations.

In conclusion, Arcus Biosciences is strategically advancing its clinical programs with a focus on differentiation and potential market leadership. For more details, refer to the full transcript below.

Full transcript - Citi’s Biopharma Back to School Conference:

Yigal Nachomovitz, Biotech Analyst, Citi: So welcome, everyone. I’m Yigal Nachomovitz, biotech analyst at at Citi. This is the Citi Biopharma Back to School Summit. So we’re all got our notebooks out and back to school. So the next session is with Arcus Biosciences.

So I have with me Terry Rosen, CEO Jennifer Jarrett, chief operating officer and and Pia Eves, head of the investor relations. So welcome all of you. And for those in the room, if you wanna ask questions, are microphones. And also welcome to those listening online. So, Terry, you wanna you wanna kick it off and kinda just, you know, give us the highlights of the last couple quarters of, you obviously had a very, good ASCO, and you have, some cat more catalyst coming up for for CAS, you know, in the fall.

So a lot of lot to talk about CAS related, but other topics too.

Terry Rosen, CEO, Arcus Biosciences: So thank you, Yigal, and I I will do that. I’ll lay out, what’ll probably be, high level for the topics and questions that you’ll have for us today. But we have presented a lot of data. We presented, you know, three medical conferences in relatively short period on Casdatafan. And then we have, not only a flow of data, but, you know, readouts coming from major phase three program.

Four molecules, I’ll just start off by mentioning the molecules. You’ve got Domzim, our anti TIGIT, anti PD one. You’ve got Quemly, our c d seventy three inhibitor, and you’ve got Casdatafan, all of these in late stage programs. Clearly, Casdatafan is of greatest interest right now in the investor community. We’ve shared data, and I’ll just say at a high level without getting into any of the numbers.

I think it’s a this is a two horse race, belzutafan from Merck and castadafan, our molecule. And I think we’ve presented very compelling data from a 120 patients that show that cast out of an is clearly best in class molecule that’s been in monotherapy. We’ve also at ASCO presented data combining it with cabo, which is standard of care in second line clear cell RCC. Again, substantially better data at least on ORR compared to belzudafant combined with cabo. This is all in what’s a very substantial market.

This total addressable market here we’re talking, you know, probably on the order of $10,000,000,000. We’ve just initiated our phase three program with Casdatafan. Two programs, first our phase three study peak one, nice design, really great from investigator, great from patient, great from execution. That’s CAS plus cabo, versus cabo. We expect that to enroll really rapidly, not only investigator enthusiasm, but we’ve had with all of these cohorts in arc 20, the phase two corollary, we’ve got a lot of investigators who are jumping right into phase three.

The other of phase one, phase three program that just started our collaboration with AstraZeneca, that’s, in the frontline, setting, and that’s all looking at Casdatafan plus their anti PD one, anti CTLA for bispecific, Volru. So we’ll have a lot more data coming from the monotherapy cohorts we just announced today that we’ll be holding an investor event. It’ll be very substantial, a lot of data in October, October 6. Not only will we share the data there, updated data from those cohorts, but also get into depth on how we look at the market. The data there will just be that will have durability.

So we’ll have updated, ORRs, and and other, data that we’ve already presented, but it should be our first look at, progression free survival data. In addition to cast data fan, which again, I think is central to what we’ve been talking about, we actually have a lot of other exciting and major data readouts coming. So we’ll be sharing data at ESMO from Edge Gastric, which is looking at DomZim, our anti TIGIT, anti PD one combination chemotherapy. We’ll have the first OS data for what’s the phase two correlate of what we call start two two one, our phase three study. That’s edgastric.

That’s in patients with upper GI cancers. I’ll remind you that we shared PFS data, which were essentially equivalent to the, OS data from the standard of care. And, I think the dots will connect in, the data that we shared ESMO should reinforce confidence in our phase three study. That phase three study will be reading out in 2026, and I’m I’m sure you’ll have some questions on that. Finally, the one other phase three study that we’ve had ongoing is Quemly, our c d seventy three inhibitor in pancreatic cancer.

And that study has enrolled incredibly rapidly. And as a matter of fact, we’ve stopped screening. It’ll be fully enrolled this month. The study will have enrolled in roughly nine months over a year ahead of schedule. And that’s clearly been driven by investigator, enthusiasm.

Unfortunately, pancreatic cancer, as you know, has a fairly dismal prognosis. So, that study is looking at Quemle gemmobraxane versus gemma braxine and that gemma braxine OS is, you know, generally gonna fall in the range of something like nine or ten months. So you could imagine that reading out in the in the relatively near time too. So between now and the 2027, it’s gonna be a continuous flow of data as well as phase three readout. So we’re in a real transformational period for the company.

People would use that term, I think it gets overused, but for an early stage company, they have four molecules in phase three studies. They’re all major markets. They’re all major, phase three studies ranging from 500 to thousand plus patients, and they’re in very competitive fields with huge markets. So I’ll stop there, and we can go to your questions.

Yigal Nachomovitz, Biotech Analyst, Citi: Well, so you mentioned a lot of things. The Merck drug, belzutafen, you obviously, it’s the same it’s the same MOA, but there’s you’ve you made the argument that you’re that what you’re doing with with Cas is different in terms of the way that it’s it’s hitting the target and the way that you’re, you know, having ramifications on the the the target genes for HIF two alpha. So maybe you can kinda just walk us through that aspect of the biology just in a in a simple way. And then, you know, how that you believe that’s translated at least in the early innings to better better numbers.

Terry Rosen, CEO, Arcus Biosciences: Sure. So the primary advantage of Casdadafin relative to belzudafin is its pharmacokinetic and pharmacodynamic profile. And the most measurable tangible data that are out there on that is looking at the the gold standard biomarker for HIF two inhibition in a human, which is the blockade of the production of erythropoietin. So that’s under the control of HIF two. And not only have we shown a deeper effect on that, but what what’s actually turned out to be the case, Merck published data for belzutafan.

We’ve also put data out for casdatafan and the Merck pharmacodynamic effect, you know, wears off roughly somewhere between nine and thirteen weeks where we’ve shown we maintain a robust effect, you know, all past thirty six weeks. We’ve recently presented data and we’ll be reinforcing this at that investor event that actually shows a correlation in patient outcome. So whether you have progressive disease, whether you have a response, whether you have stable disease that can be linked to that individual patient the ability to suppress erythropoietin. But how does that translate to clinical benefit? Basically, we see a dramatically different rate of primary progression.

So belzutafen reports out of over thirty percent, roughly thirty five percent. We’re somewhere in the fifteen percent range and essentially that drives all of the other endpoints because those when we’re talking about primary progressive disease, those are patients that progress at or before a first scan. And with this mechanism because of its safety, even if a patient has stable disease, they’re going to contribute very meaningfully to PFS. So we’ve also seen, this is translated into a better ORR than they had a belzanofan roughly, you know, fifty percent better. We’re seeing over thirty percent.

They’ve reported just over twenty percent at best. And then, we’ve shown improved PFS and I think, we’ll show even more, improvement on that, when we when we share updated, datas. So really in multiple cohorts, there’s not an endpoint that we’ve looked at that hasn’t been better than that of belzutafan and usually by at least 50% or so.

Yigal Nachomovitz, Biotech Analyst, Citi: Okay. So you have that that data. I’ll get it. It’s not obviously, it’s not head to head, but it’s, it’s still, you know, a good comparison. But then in addition to that, since, I mean, you are the same mechanism, one of the other things which I wanna talk about is the strategy for the phase threes because, you know, having a unique strategy for the phase threes is super important given it is a competitive space.

And, obviously, Merck is doing more than just the studies they’ve already done. They’re doing new studies with the new LightSpark study. So maybe Jen can also comment on this. You know, what talk about the strategy and how you design Peak One and and Evolve to be different and answer different questions and address the market in a in a way that Mark isn’t doing.

Jennifer Jarrett, COO, Arcus Biosciences: Yeah. So we believe we have a very different and a better development strategy. And, you know, two years ago, before we saw the efficacy data from CasMano, we used to say that even if we didn’t show better efficacy, we believe we have a better development strategy now. We know we have a better molecule than Bell’s with Cas based on the efficacy data of which we’ll show more of in about a month. But on top of that, as I said, we definitely have, we think, a better development strategy.

So starting with our study in the IO experience patient population of RCC. So these are patients that have had prior anti p d one, either in the adjuvant setting or in the first line metastatic setting. So this is a very large patient population. We are combining with cabo, which is the most widely used by a very significant margin TKI in that setting, and then we’re comparing to that TKI to cabo. So it’s CAS plus cabo versus cabo.

In contrast, Merck is combining Bell’s with lenvatinib because that’s the TKI that they own, which is less widely utilized in that setting. And, therefore, we believe there’s less clinician comfort in managing toxicities, and other attributes of lenvatinib. Lenvatinib is also more complicated to dose. So the dosages that are used are anywhere from four mgs to twenty four mgs. Like, every clinician you talk to probably doses Lembas slightly differently.

The dosing of cabo is very, very simple. Usually, start at sixty, and then you’ll dose reduce either forty or twenty if you see toxicity. So we love the idea of combining with cabo for all those reasons. Just much easier dose, more widely used, and clinicians are more comfortable managing managing the toxicities of that TKI. Mhmm.

On top of that, Merck and their control arm is using cabo.

Yigal Nachomovitz, Biotech Analyst, Citi: I was about to ask.

Jennifer Jarrett, COO, Arcus Biosciences: So they’re combining Bell’s plus Lemba versus cabo. Mhmm. So, obviously, if Lemba underperforms cabo, that’s gonna put them at a disadvantage of that experimental arm. So we think it’s a much cleaner study to be able to combine with cabo and then to compare the combination.

Yigal Nachomovitz, Biotech Analyst, Citi: Had to do it. They had to do it that way. Right?

Jennifer Jarrett, COO, Arcus Biosciences: They had to because compared with. They could. They could’ve. Yeah. So it’s kind of interesting why they have it.

But keep in mind, also, LEMBA the way LEMBA is used in that setting is it’s used in combination with everolimus, which a lot of people forget about. So if you look at some of the data that’s out there, like PFS data for LENVA, most of that data is LENVA plus everolimus while they’re combining with lenvatinib alone, not LENVA plus everolimus. So that’s also probably why if they had had a control on, they would have had to use Lemba plus everolimus. Yeah. But it made things Okay.

More difficult. So, the other difference is, on the, statistical analysis plan. So they used dual primary endpoints of PFS and OS. You know, we believe that they have some interim analysis as well. So because of that, you’re having to chop up your alphabet.

We have no interim analysis, one primary endpoint of PFS. We will obviously look at OS, and so the key secondary endpoint is OS. So we’ll continue to track for that, but it’s one endpoint. All of the alpha is on that one endpoint. So we think we also have a better and just much cleaner, simpler statistical analysis plan.

Yigal Nachomovitz, Biotech Analyst, Citi: Okay.

Jennifer Jarrett, COO, Arcus Biosciences: So that’s for, peak one. For and then one other, slight difference is we’re also using two to one randomization. So we think that’ll make our study even easier and more interesting to people to enroll because patients are two times more likely to get an experimental arm than the control arm, which is something that patients and clinicians that always like.

Yigal Nachomovitz, Biotech Analyst, Citi: Before we get to evolve, just what’s so this peak one is, has started or is about to

Jennifer Jarrett, COO, Arcus Biosciences: started. So we’ve activated our first sites, and we should have first patient in any day now.

Yigal Nachomovitz, Biotech Analyst, Citi: Okay. And then, roughly, is there a timeline for when

Jennifer Jarrett, COO, Arcus Biosciences: you So we haven’t provided specifics, but if you look at the typical either first line or second line RCC study, they tend to enroll in eighteen months or less. There’s actually one study that’s fairly recent called CANTATA that enrolled in ten months. So, you know, we think this study should enroll less than eighteen months. It’s really set up to succeed for a number of different reasons. As we talked about, it’s going right on top of the standard of care when we’re comparing the combination to the standard of care.

So that obviously makes the study very, very attractive. In Europe, belzutafan is not paid for yet, same with South America and some other regions. So the only way to get access to a HIF two alpha inhibitor, if you’re a clinician or a patient, is to be in a clinical study. And then as of today, there’s no other directly competing phase three studies. So for all these reasons, we think we’re in a very good position to get peak one enrolled quickly and and get us to date as quickly as possible.

Yigal Nachomovitz, Biotech Analyst, Citi: Okay. Alright.

Terry Rosen, CEO, Arcus Biosciences: You’re gonna say anything about voting?

Jennifer Jarrett, COO, Arcus Biosciences: Yeah. And then I’ll send a call. Yeah.

Yigal Nachomovitz, Biotech Analyst, Citi: I was waiting for letting you all get all way. Okay. Yeah. So

Jennifer Jarrett, COO, Arcus Biosciences: So and then our strategy in the first line setting is even more different than what Mark is doing. So our strategy in the first line setting is to combine with anti p d one c t l a four. That is the most widely used regimen in the frontline setting. So today, it has about thirty five percent share. Clinicians like that combination for two reasons.

First of all, it’s TKI free. So in the first slide, it enables you to avoid all the TKI related toxicities, like hypertension, diarrhea, rash, etcetera. The other advantage that it has is it gives patients the best chance at long term survival. So if you look at CheckMate two one four, about thirty percent of patients were still on treatment and doing very, very well, you know, five years plus after start of therapy, which is very remarkable, in metastatic cancer. So we’re going on top of that combination that instead of using ipinivo, we are working with AstraZeneca and combining with their anti p d one CTLA four bispecific.

So they are actually operationalizing the study. We are splitting the cost of this study. So this is also very different than, like, your typical supply agreement where we’re just getting drug supply, but we’re having to pay for this study and actually operationalize this study. It’s very nice that they’re operationalizing it because that allows us to avoid the resources we would need to have to operationalize this study. And, obviously, having the cost sharing is very helpful from an economic standpoint.

And we get to keep all of the economic and commercial rights for a molecule. So that study is being designed as a phase one b three study, so it’s one seamless design. The phase one b portion is really a safety run-in. So we’re looking at two different doses of VULRU on top of a hundred mgs of CAS. So we’ll look at the safety data from those two cohorts, make a decision on dose for VULRU, and then open up the phase three portion as fast as we can assuming that it all looks well.

And so that would be sometime next year.

Yigal Nachomovitz, Biotech Analyst, Citi: So the reason you decided to do the this way versus just epo ipinivo is is what? Is there

Jennifer Jarrett, COO, Arcus Biosciences: So we think this this could actually be a better molecule. You know, it’s a bispecific. And so some people think that there could be efficacy advantages by combining those two mechanisms in one molecule. There’s other p d one CTLA for bispecifics out there. They are the only one that has generated a robust dataset to date in RCC.

They are super excited about the combination as well. They’re obviously a world class oncology partner. We love the idea of working with them, combining with their bispecific, which we think could have some efficacy advantages, and then, obviously, you know, allowing them to operationalize the study.

Yigal Nachomovitz, Biotech Analyst, Citi: So the third you mentioned the 35% share. Is that for Volar, or is that just for

Jennifer Jarrett, COO, Arcus Biosciences: That’s for info. It’s about 35% share.

Yigal Nachomovitz, Biotech Analyst, Citi: Yep. Okay.

Terry Rosen, CEO, Arcus Biosciences: You know, one other thing that I think is important because differentiation is a very common topic, and I think sometimes people miss different for the sake of different doesn’t always mean it’s better. The reason that we’re able to do this particular study and the reason I think AstraZeneca wanted to collaborate with us on this is because of that lower rate of primary progression of castadefan when you compare to belzutafan. So one of the limitations despite the fact that anti p d one anti c t l a four is the most commonly used frontline regimen. There’s still about twenty five percent primary progression. So there’s a sense that we can bring that down with casdatafen.

So this is actually the first TKI sparing frontline regimen that’s being investigated. It’s not something that Merck is doing. Merck is forced to always go with a a TKI upfront. And interestingly, it’s not only, you know, fits, like, a a difference that might be of interest in general from the efficacy standpoint, but also when you talk to investigators and patients, it it sort of speaks to a paradigm shift where the idea is to try to drive

Yigal Nachomovitz, Biotech Analyst, Citi: the

Terry Rosen, CEO, Arcus Biosciences: TKI to the later line of therapy and bring HIF two on earlier because it’s such it from a patient standpoint, it’s so much better tolerated. So, essentially, that’s one of the reasons there’s extraordinary, not only company enthusiasm, but investigator enthusiasm for the this TKI sparing regimen. Think of people should tend to think about when you think about TKIs, you should think a lot similarly, like, with chemo. And the idea being that if you could push that to later Yeah. As opposed to earlier, you’re doing a lot for the quality of life on the patient.

Yigal Nachomovitz, Biotech Analyst, Citi: So for both these studies, you’re ready I mean, you’ve already obviously, identified in the dose. It’s a hundred hundred milligram. So but you will have some additional, as you pointed out, some additional, data updates for the ARC 20, the earlier. So what will what additionally are we gonna learn from these updates, you know, that would help understand probability of success for these phase two trials, or is it more other things that are necessary for drug developers

Jennifer Jarrett, COO, Arcus Biosciences: like a project optimist? Yes. So project optimist has been done. So that was why we did the fifty mg QD and a hundred and fifty mg QD cohorts in our 20. But what’s nice about that was each of those cohorts had 30 patients.

So we now, across this four monotherapy cohorts, have about a 120 patients worth of data. So that’s the data that we’ll be presenting at this upcoming investor event. So, you know, it’s a very significant cohort in terms of patient population. 120, you know, that’s almost the same size as a lot of phase three arms. Mhmm.

And then the idea behind this dataset and this presentation is really to confirm that CAS has a best in class efficacy profile relative to pelsutafen and also to start to establish a benchmark for PFS that we’ll be building upon by combining CAS with the TKI in that first phase three study. So that’s the next update that’s coming as we go into next year. You know, we’re still, like, early in the year at ASCO GU to be able to present something from that 120 patient dataset given it is a significant dataset. We’ll probably start to look at patient subsets and that sort of thing. And then later in the year, next year, so probably around midyear, we’ll have more mature data from that CAST plus cabo cohort, which we presented initial data on at ASCO this year.

And as a reminder, we showed a forty six percent confirmed response rate at that point in time.

Terry Rosen, CEO, Arcus Biosciences: I think that the, you know, as Jen laid out, the, role of this presentation with those 120 patients, all the data that we presented thus far, which look better than Merck, we’re comparing very early test data fan datasets to final Merck datasets. So five months to twenty months, etcetera, those type of things. And this is a mechanism where the data get better with time, and our data have continued to get better with time. So I think from a confidence standpoint, whether it’s an investigator or an investor, the investigators frankly have extraordinary enthusiasm for castadefan and the combination of castadefan plus cabo and exploring other regimens. But I think this will leave no doubt that there’s a black and white difference when you look at the monotherapy, same patient population for castadepam compared to belazutafan that will bode quite well for now when you combine it with cabo.

Yigal Nachomovitz, Biotech Analyst, Citi: So does that mean we’re gonna be getting an even more updated set of of numbers on primary progression and no responses even more than what we’ve seen before? Or

Jennifer Jarrett, COO, Arcus Biosciences: Yeah. So the PD rate obviously won’t change just because you know that at the first scan. But everything else, you know, will be updated ORR, obviously updated safety data. And then as a reminder, at ASCO GU, we only presented PFS data for the fifty mg BID cohort. That was the only cohort that we had a mature and stable median PFS.

You know? Not surprised that the PFS has not changed for that reason, but we’ll now have PFS from these other cohorts. So either, you know, median PFS has been reached or it hasn’t been reached, but we will show a Kaplan Meier curve for that cohort.

Yigal Nachomovitz, Biotech Analyst, Citi: Okay. And as far as the interplay of CAS and CABO, that there’s anything to mention there regarding, overlapping talks or lack of overlapping talks?

Jennifer Jarrett, COO, Arcus Biosciences: Yeah. I mean, that was, like, one of the headlines, I think, from the data that we presented at ASCO that there was really no overlapping toxicity. The only overlapping toxicity that we expected to see us a little bit of was fatigue. But even that, I I would say, was actually pretty minimal. And think it just makes a point of one the things that we love about CAS and its safety profiles.

We really think it could become a backbone agent in CCRCC, and it could be combined with anything. Because you think about even anti p d one plus TKI, which are combined today in a frontline setting, have overlapping toxicity, particularly GI toxicity, fatigue, rash, hepatotoxicity versus CAS where we expect to have probably no overlapping tox with anti p d one. We’re looking at that combination actually now in r twenty, so combining CAS with anti p d one in the frontline setting. And then as we talked about, also very little overlapping toxicity with TKIs. And if you think about, like, one of the reasons why combining two anticancer drugs doesn’t always result in improved PFS is because of that out of toxicity.

And so patients just can’t tolerate the optimal doses of both drugs. And so one of the data that one piece of data we thought was very exciting at ASCO was the dose intensity data, the fact that we’re able to keep patients on optimal doses of both drugs throughout their treatment.

Yigal Nachomovitz, Biotech Analyst, Citi: And is it and so it’s you and Mark. Is there anyone else that’s got a a late stage shift to alpha that you need to worry about, or this is it? This

Jennifer Jarrett, COO, Arcus Biosciences: is it. Two horse race. Okay.

Terry Rosen, CEO, Arcus Biosciences: I mean, this is, you know again, we remind people of this and this this we started this from scratch and it’s what Arcus does well. A small molecule that inhibits transcription factor. It’s very unusual and that’s why you can’t just have a garage in China that’s gonna, you know, in three months, they can make an antibody, but you’re not you you can probably spend three years or ten years, and not only do you have to do good work, probably need a little luck. So that’s what yes. You know, there were a couple other molecules, and they had they ended up with pretty terrible clinical properties.

One that Novartis had and one that Nanking had. That’s still in development. None of them are in late stage at this point.

Yigal Nachomovitz, Biotech Analyst, Citi: Oh, we better move on to some other topics too. Okay. So you mentioned so edge gastric, you said the you know, your your your data was very comparable to the prior standard of care’s OS. The to s data was already comparable to the standard care OS data. So how does that intersect with the, you know, thinking about the probabilities of success for the start 02/22/2021.

Right? Yeah.

Jennifer Jarrett, COO, Arcus Biosciences: Yeah. So, I mean, the next disclosure will be OS from EDGE gastric, and so, you know, that should be derisking what could happen with star two two one, which also has an OS endpoint.

Yigal Nachomovitz, Biotech Analyst, Citi: So how like, any perspective on what what the numbers could look like there?

Jennifer Jarrett, COO, Arcus Biosciences: Yeah. Haven’t said anything. It’ll you know, when, the abstract is out, the abstract actually has the most up to date information, so it’s not one of those. The abstract has an early dataset. And then when you see the actual presentation, you’ll get a more updated number.

So that number will be in the abstract. As a reminder, the benchmark data is about twelve to fourteen months for OS for anti p d one plus chemo. So And is it it’ll be better than that? Right.

Yigal Nachomovitz, Biotech Analyst, Citi: The people that were enrolled in as gastric phase two is how comparable are they to the phase three population?

Jennifer Jarrett, COO, Arcus Biosciences: Very simple. I mean, basically, the exact same patient population, like, from an inclusion exclusion criteria. The only difference is we’re obviously in a lot more countries for start two two one. It’s much bigger studies since it was a phase three versus a phase two. But the phase two included Europe, Asia, US, just fewer countries.

So also geographically diverse, but obviously, we’re just in more countries for start two two. What is the difference?

Terry Rosen, CEO, Arcus Biosciences: So Jen said, our our PFS was on the order of thirteen months similar to what you see for OS or whether it’s pisley chemo, nivo chemo, or Keytruda chemo. And if you connect the dots, there will be no one that’s disappointed with the dataset when we show OS. I think what’s important, I think the thing that probably is the bigger question to the rest of the world that just be when it gets through is that the FC enabled versus the FC silent is that differentiator. So if you look, what’s interesting is that AstraZeneca with their FC silent anti TIGIT, anti PD one bispecific also showed a PFS on the order of twelve months, a little less than what we showed, but very similar. So between us and AstraZeneca, there’ve been five anti TIGIT studies run that have all been positive all with the Fc silent backbone.

So I think these data will be as reinforcing as they could possibly be. If you didn’t have the Merck and Genentech huge numbers of datasets with, you know, the effector enabled, f c enabled anti TIGITS, I think there’d be like these would these data would be as positive and reinforcing for a phase three study as you could have. So it’s a matter of of those who understand the difference between those two antibodies, essentially makes them two different mechanism. So This is they have the word TIGIT in them, but they’re not.

Yigal Nachomovitz, Biotech Analyst, Citi: So it’s like the it’s like the baby being thrown out with the bathwater to to a large extent here. I mean, people are written off TIGIT, but but this Exactly. This f c, non f c thing. Like, I remember at the ASCO event a few years ago, you had the fellow from where is he now? From your end.

Yeah. Yeah. Yeah. He was great, and he made the point about the Fc silence. So can you go through that again and and the fact that how does it, you know, not destroy the the So

Terry Rosen, CEO, Arcus Biosciences: the difference between the two antibodies is it doesn’t always happen, but when you have an Fc enabled antibody, it has the potential to kill cells that bear that protein. The problem is is that the the cells that are loaded with TIGIT that are in the periphery very accessible to the antibody are t regulatory cells. So those Fc enabled anti TIGITs, this has been demonstrated. It’s not some sort of esoteric science. If you go look in those patients, what you see is they’re getting roughly eighty percent of their t regulatory cells depleted.

T regulatory cells are a huge critical component of your immune system that basically is what protects you from, you know, autoimmune diseases. So when what happens is, those Fc enabled anti TIGITs are depleting t regs, They’re creating immune AEs. Those immune AEs not only result in a safety signal, but they cause in the study arm, patients to have to go off the therapy. So they also have less efficacy. If you look at taking an f c silent anti TIGIT, where really the mechanism that you’re looking for there is pure blockade, you see almost if you look at anti TIGIT plus anti PD one, particularly in the context of chemo, adding the anti TIGIT

Yigal Nachomovitz, Biotech Analyst, Citi: But they

Terry Rosen, CEO, Arcus Biosciences: and when it’s Fc silent brings essentially no additional agents.

Yigal Nachomovitz, Biotech Analyst, Citi: So what was the mean, obviously, you know, the people at pharma are you know, they they are smart. Right? So they they they do have reasons to do the Fc activated. They must have known about this. Or Or what was it something they didn’t anticipate?

I was No.

Terry Rosen, CEO, Arcus Biosciences: I think so an Fc enabled antibody generally may or may not have effector function. There was old there there was multiple reasons that people might have thought about why they wanted, an effector enabled. So in in mouse, and that’s been, you know, probably a decade ago, people showed Treg depletion in mouse models will lead to efficacy. There was a then a post you know, a lot of the basic science was done at Genentech. Post having the FC enabled anti TIGITS, I think that Ira Melman, in particular his group, reported a number of features that weren’t relying on the Treg depletion, but other things that in effect are enabled the anti antibody might do.

Mhmm. But interestingly enough, I think the it was unanticipated that you would get such profound Treg depletion. So I don’t think that in general, by the time these companies were going into their development, they they were thinking they were gonna get peripheral Tregs that were gonna lead to such profound immune

Yigal Nachomovitz, Biotech Analyst, Citi: the kinda headline, you know, that escape with all all the studies, the the the big ones that we know that didn’t work, they were universally all Fc activated. Yes. So that’s just there’s just like a bifurcation there.

Terry Rosen, CEO, Arcus Biosciences: There was and there was basically you had you had both Merck and Genentech and then Beijing similarly. Interestingly, AstraZeneca, who has an Fc silent molecule, now not only has 10, phase three studies going, but they started a phase three study in the SKYY one population after the SKYY one failure. So you could see, again, this notion of smart people. Yeah. Companies have smart people, and I think AstraZeneca has smart people too, and they, started that after the failure

Jennifer Jarrett, COO, Arcus Biosciences: that abstract at, WorldLag where they looked at their bispecific, their p d one anti TIGIT bispecific or anti p d one TIGIT bispecific, and they looked at two different forms of the bispecific. One was Fc enabled. The other was Fc silent. And they showed that with the Fc enabled TIGIT antibody, they were actually depleting T cells, which, again, is exactly what you don’t wanna have happen when you’re trying to stimulate the immune system. And they showed that with the Fc silent TIGIT bispecific, they did not see that phenomenon.

So it it just makes the point in a data oriented way, which Harry was just saying. But that data is being presented presented at at WorldLung. WorldLag.

Yigal Nachomovitz, Biotech Analyst, Citi: Okay. But so you’ve been I mean, you spend more time so that’s a good argument around around, you know, optimism for the edge gas for the two two one. But you don’t spend a lot of time talking about the other one, which is still running. Right? The other lung the lung study.

Terry Rosen, CEO, Arcus Biosciences: That will be fully enrolled at the end of this year. So the thousand patient study, EDL one, all comer, non small cell lung. We don’t over talk about it, but we’re extremely excited about it. And that’s essentially the biggest part of Keytruda’s market. And we’ll have a I think if you see positive star 221 data, you’ll immediately see a FOMO around star 121.

Because we’ve as you know, we’ve shown randomized data in the PD L one high non small cell lung population relatively small was, you know, that phase three study that we ended early in favor of the PD L one all comer, but we had a hazard ratio point six four. So we believe strongly in lung. But we also believe strongly that the place where the Fc enabled anti TIGITs had their most profound AEs is in the context of chemotherapy and the PD L1 all comers in in in that context. And so ours our thousand patient study will be fully enrolled at the end of this year. We’re very

Yigal Nachomovitz, Biotech Analyst, Citi: excited about that. Start two two one, that’s coming next year?

Terry Rosen, CEO, Arcus Biosciences: Start two two one readout So start two two one, that’s the upper GI cancer. That was fully enrolled in June 2024.

Yigal Nachomovitz, Biotech Analyst, Citi: And that’s an o an OS? OS. Right. So next year. And then when is the other one?

The one

Terry Rosen, CEO, Arcus Biosciences: We haven’t we yeah. Obviously, that’s gonna be a a longer time out because

Yigal Nachomovitz, Biotech Analyst, Citi: Start 02/21 got kinda caught up or something. Did that is that correct or no? It seems like it’s moving faster than it used to.

Terry Rosen, CEO, Arcus Biosciences: No. So Start 221 was fully enrolled June.

Yigal Nachomovitz, Biotech Analyst, Citi: Okay.

Terry Rosen, CEO, Arcus Biosciences: Star121 is enrolled well, and it’ll be fully enrolled at the end of this year. The reason it’ll take longer to read out is simply that the standard of care there is, you know, getting over twenty months in general. So you’ve got a longer wait. But a star two two one positive will bode very well for star 121.

Yigal Nachomovitz, Biotech Analyst, Citi: But that and how big is that study? Thousand patients. It’s also they’re both that big.

Terry Rosen, CEO, Arcus Biosciences: So Star221 was a 47. Star121 will be similar.

Yigal Nachomovitz, Biotech Analyst, Citi: And those would allow for a global of filings, I assume? Oh, yeah. Yeah.

Terry Rosen, CEO, Arcus Biosciences: Right. Oh, yeah.

Yigal Nachomovitz, Biotech Analyst, Citi: Right. Oh, okay. Quickly on family then. So well, what’s the the tell us about what you need to to see there for that for that what’s the bar for success?

Jennifer Jarrett, COO, Arcus Biosciences: So, you know, it’s a randomized study. So, you know, we’re going on top of gemmobraxane comparing to gemmobraxane alone. So, you know, you don’t have to worry about, like, what do we need to show. Typically, with gemmobraxane in the first line pancreatic cancer setting, you expect nine to eleven months OS. Obviously, we wanna build on that, just given the very, very high unmet need, in that disease.

You don’t need to show a lot as far as improvement over that nine to eleven months to have a very big drug and, you know, really exciting opportunity for patients. The, studies sort of completing enrollment as we speak, enrolled about fourteen months ahead of our expectations, enrolled in nine months total, which is pretty remarkable and, I think, just highlights the need for new therapy new therapeutic options for those patients as well as just the enthusiasm that existed for the combination. One of things that we’re hearing is once patients or once clinicians have patients on drug, just especially seeing, like, how safe and well tolerated Prumly seem to be on top of chemo, that was really encouraging these clinicians to put more patients on drug at their sites. So it did enroll quickly, and, you know, a readout will happen in the next twelve to eighteen months or so.

Terry Rosen, CEO, Arcus Biosciences: And I’ll remind you that the phase two correlate that showed a NOS on the order of sixteen months, and it also held up in, you know, different between a lot of other pancreatic studies. The data look quite compelling in liver met patients as well.

Yigal Nachomovitz, Biotech Analyst, Citi: Okay. Well, I guess we’re sort of out of time.

Terry Rosen, CEO, Arcus Biosciences: It’s a blinking red light.

Yigal Nachomovitz, Biotech Analyst, Citi: Yeah. So I guess we’re mean, stop. But thank you so much. A lot to look forward to.

Terry Rosen, CEO, Arcus Biosciences: Thanks, Ben. Lot of data coming. We’re looking forward to continuously sharing them.

Yigal Nachomovitz, Biotech Analyst, Citi: Okay. Thank you.

Jennifer Jarrett, COO, Arcus Biosciences: Thank you.

Terry Rosen, CEO, Arcus Biosciences: Thanks, Igor.

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