Investor Update Transcript - RCUS 2026-10-20

Terry Rosen, CEO

ended up just logistics, timing, everything, and intent used primarily in the intermediate poor because of the poor.

Jason Barker

Maybe I'll quickly add, you know, that I know the immediate approval originally was just intermediate poor and not favorable, but the broad use today is across the spectrum, and that's probably why, as we enroll this cohort and enroll it fast, we have the distribution because the patients and physicians do like to use Epinevo regardless of the IMDC risk, And that's a global, you know, Europe, the same. There's a lot of use across all risk groups, despite the initial interpretation, which has evolved over time to appreciate its use across every group.

Terry Rosen, CEO

It was interesting. It was subtle. But you remember when the question came up to Raina about her use of TKI, and she emphasized she's almost like 100% yippee-nevo, and a lot of the academic centers more and more go in that direction where they basically want to get that OS. So obviously bringing CAS in and lowering that rate of primary progression would be a big help.

Juan Carlos Jaen

There's a disconnect between what they're doing, but she's doing water.

Terry Rosen, CEO

That's right. We need data to turn it around.

Priyanka, Analyst — J.P. Morgan

Hi, I'm Priyanka from J.P. Morgan. So it was mentioned that in Frontline there was no overlapping talks with the Zim-IPI combo. So as we're thinking about the registrational data set and given that these patients will be in the combination for a longer time, how does the anemia and hypoxia-related side effects, how do you think those could drive physician-prescribing choices for castatophant in front line versus second line?

Jason Barker

Yeah. I think the, I'll call it beauty of this combination as a triplet is it's barely a triplet, if you will, right, meaning the first four cycles or up to the first four cycles is all three, and then after that, it's really CAS plus PD-1, or in this case, NEVO, and we're very comfortable with that profile. Like I said, in our CAS-ZIM group, we now have nearly a year of median follow-up, so we have a lot of experience there. The anemia and hypoxia, we see that occurring regardless of line of therapy. It's clearly HIF2-driven. I'll say that I'll expect all patients to have anemia to some degree when they're on castatophant, especially in a prolonged use, so we tell all the investigators, physicians, just expect it, look for it, treat it fast, use an ESA if your institution allows an ESA, rethropotent stimulating agent. Otherwise, if they get anemia, depends on the degree, and if they're symptomatic, if they're symptomatic, they'll get a transfusion, but they stay on Cas. That's the key, is we haven't seen discontinuations of Casdatafan due to the anemia. Hypoxia occurs at similar rates as Belzutafan, again, that's considered on target, but again, that's kind of regardless of the combination partner, meaning Zim, a PD-1 versus Cabo from that standpoint. And hypoxia is obviously not a desirable event, but the higher grade hypoxia is still quite low in occurrence, and that'll drive patients to take a holiday or lower the dose of Cas, but they generally are staying on Cas even with the events of hypoxia. That's the AE that they'll end up lowering down to 50 milligrams maybe, but the key as you saw in the PDE data, even at 50 milligrams of Cas, that's a more potent HIF-2 inhibitor than the commercial dose 120 milligrams of belzutafan, so I'd say even though they dropped it down, they're still on conceptually full strength inhibition of HIF-2.

Operator

Last couple questions.

Supor, Analyst — Truist

Hi, I'm Supor from Truist. Thanks for the rationale for why Cas plus capital could extend OS despite some more similar PFS. I'm just curious if you have post-progression data of sequence therapy, post-progression data in Act 20 to support the hypothesis. And related to that question, now Bells and Lens have been approved. I'm just curious if it's use, potential use, you know, in progressive, in the peak one study might alter or influence the OS outcome in peak one. Thank you.

Jason Barker

Sorry, can you restate that last part?

Supor, Analyst — Truist

So presumably that Bells and Lens now approved And I was wondering if it could be used, for example, in the CABO control arm in peak one and may change how the OS hazard ratio might look.

Jason Barker

Yeah, so the CABO arm in peak one is exclusively CABO, right? So there'll be no Len Bell patient coming in.

Jason Barker

There's no prior HIF to alpha exposure allowed.

Jason Barker

Right, so there's no, yeah, so that's exclusion. So you're saying what will happen after peak one progression? Can a patient – so, sure, after progression on peak one, a patient could go on Bells, for example, if they were on the Cabo arm. If they didn't have the treatment arm, that will be up to the physicians as to what to give. Now, it's a global study, and Bells isn't really available outside the U.S. for these patients from an access and reimbursement perspective. So I would expect the majority in either arm, really, to go on to an alternative TKI, probably, you know, or they can go on LEN-EVE if they haven't had LEN before. So I don't expect much LEN-BELL anywhere in Pequon, and it'll be LEN-EVE, TiVo, or in the U.S. they could get Bells if they were on the Cabo arm.

Dana Graybosh, Analyst — Learring Partners

Last question. Excuse me. Dana Graybosh from Learning Partners. I'm wondering if BMS is contributing to funding Peak 20 and whether you allow patients to receive subcutaneous nivolumab, particularly when you go down to the doublet with CAS.

Bob Goeltz, CFO

I can comment on the financial arrangements first. So we haven't disclosed the financial arrangements, but I would just comment, and we said this previously, that if you look at the totality of our collaborations with BMS, with Pfizer, and with Summit, the aggregate of those is very financially attractive to ARCUS. And in the aggregate, we're spending less than we would have spent on one arm for ourselves. I was asking about peak 20. Oh, sorry, for peak 20. Okay, yeah, no, and we haven't disclosed anything there yet.

Terry Rosen, CEO

But the trial, just to be clear, if anything there, that would just relate to some sort of supply. So there's no collaborative aspect of peak 20 with EMS. It would just, if we did something, it would involve the just supply.

Jason Barker

And we're planning on IV use, not sub-Q use, open-minded, but just for consistency in a global trial, which is very important that everyone knows how to use it. And we're picking centers that obviously have a lot of experience with the PNIVO, but predominantly that experience is IV, and so we're sticking with what they know.

Operator

Thank you, everybody, for joining us. We'll end the webcast now, and we're happy to take questions one-on-one afterwards.

Terry Rosen, CEO

I'll thank everybody, too. We really appreciate the engagement, and not just today, but on an ongoing basis. So thank you very much.