Arcus Biosciences, Inc. Citigroup’s Biopharma Back to School Summit 2026

Perfect. Yeah. No, happy to do that, and thanks for having us. Maybe just before I jump into casdatifan, really briefly, just to remind folks about the company. Arcus is a company that is based on very high-quality drug discovery, particular emphasis on high-quality small molecule drug discovery. We like to focus on areas where there are targets that have good biologic validation, and we think that there's a real opportunity for a very high-quality molecule. That's clearly the case with casdatifan. I know we're going to focus on casdatifan today, and we'll jump right into it. Just a quick reminder, the rest of the portfolio for us, we also have a drug that's targeting CD73, that's in a pivotal pancreatic cancer study.

In the update for this conference, we also indicated that we expect an interim analysis in the fourth quarter of this year on that pancreatic cancer study. We are looking forward to seeing data from quemliclustat, which is that compound in PDAC pretty shortly. Then we also have a really exciting early-stage immunology portfolio of largely small molecules that is moving along in the first program, an MRGPRX2 inhibitor is now in a healthy volunteer study in the clinic. Shifting to casdatifan, which is definitely the focus for investors right now. Quick reminder, one of the reasons why we are really excited about the program is that the target HIF-2α of casdatifan has been validated by a molecule from Merck, belzutifan.

It has had three successful phase III studies, LITESPARK-005 in late-line monotherapy, LITESPARK-011 in second line in combination with lenvatinib, and then also in adjuvant therapy in combination with pembrolizumab. Good validation for the target, not drug in the late line monotherapies are doing sales of roughly around a run rate of $1 billion a year. However, that molecule does have a liability that is pretty well characterized, which is that it has absorption-limited pharmacokinetics. That aspect means that as you increase doses beyond the dose that is approved and that they have been using for their clinical trials, 120 milligrams, you only get incrementally higher exposures. Back to the core of Arcus of looking at developing very high-quality small molecules. Our goal was to see if more could be taken from the target HIF-2 if you actually did not have that liability.

Casdatifan has dose proportional and linear pharmacokinetics, and we are essentially, in our clinical trials, utilizing a dose that has roughly fivefold the pharmacodynamic effect of belzutifan. In late line monotherapy, what we saw was that that resulted in a very substantial increase in response rate and progression-free survival. Progression-free survival, for example, 12-15 months versus 5.6 months from LITESPARK-005, which was their pivotal study. We also see a substantially lower rate of primary progression, which is progression by the first scan, which is a particular problem in clear cell RCC, where the primary progression rate can be a third or greater for an agent like belzutifan. That is sort of where we are right now, and our first pivotal study for casdatifan will be combining casdatifan plus cabozantinib, which is the standard of care in second line clear cell RCC versus cabozantinib.

That pivotal study is enrolling, and we have indicated we expect to have this study enrolled around the end of this year. The enrollment is going very well. We are excited about that. Then our frontline strategy will be to combine casdatifan with ipilimumab and nivolumab, which is one of the preferred regimens in the frontline. We can talk about the nuances of what regimens are in the frontline and the pros and cons to each as we get into the details. That will be our second pivotal study. The first one is called PEAK-1, that is the second line study. The second one is PEAK-20, which is the frontline study. That brings us to a very meaty update that we will have in October. We are going to have an investor event on October 20th, and we will be updating data and providing new data across multiple lines of therapy.

We will be providing data on the late-line monotherapy. We will be providing data on the second line in combination with cabozantinib, and then also the front line. I will walk through each of those lines of treatment and the data that we will have and how we are thinking about each of those relatively quickly, and we can jump into as much detail on each of those fronts. For those that are following online, we do have some slides that are incorporated in our corporate deck on our website, and they are available in the appendix to slide deck, which show the details of the data that we will be presenting in October. Let me start with the latest line of therapy first, and then I will work my way earlier, because this will be the maturity of the data.

In the late-line monotherapy, I already indicated that we have presented what we believe is really compelling response rate data and progression-free survival data already. That is pretty mature and I think has indicated to many that they believe casdatifan is clearly differentiated from belzutifan. The new piece of data that we will have at our October update is for the first time, we will be sharing overall survival data in a Kaplan-Meier curve there. Why is that important? Belzutifan in their three pivotal studies has not demonstrated an overall survival benefit yet. In the second line in LITESPARK-011, they came quite close. They had a hazard ratio of 0.85 with a P value of 0.06 on overall survival.

Overall survival, while PFS is the registrational endpoint, would obviously be a massive differentiator from a commercialization perspective, both in the U.S. in terms of label, but also ex-U.S. to open up reimbursement. We think demonstrating that the molecule could bring an overall survival benefit in late-line monotherapy has the potential to read through to multiple lines of therapy. In the late line, we will have 28 months of median follow-up. The benchmark here from LITESPARK-005 was 21 months of OS. We will be able to look at the Kaplan-Meier curve for our data and compare it to that benchmark and see whether or not it appears that there is a difference relative to what we have seen from belzutifan. Pretty simple in the late line.

Yeah, we are cautiously optimistic, for sure. Absolutely, we think that there is a good potential here, and we think it is really frankly the potential for the mechanism. It is just we think a lot of the belzutifan data indicates what belzutifan can achieve, not what a great HIF-2α inhibitor can achieve. So across all of the efficacy metrics in the late line, we are hoping to see what a really good HIF-2 inhibitor can achieve, and so we have already seen it for PFS. And to your point, we think that bodes well for potential OS as well. So very excited about that update.