Thank you. Welcome back to the Citizens Life Sciences Conference. My name is Silvan Tuerkcan, and it's my pleasure to host Exelixis with Andrew Peters. Thank you so much for joining us. Yeah, thank you for the invite. Glad to be here. Do you have any opening remarks, or should we start forward-looking statements? Yeah, happy to. Things like that? Happy to get into all that fun stuff. Just as a reminder, today I'm gonna be making some forward-looking statements, so please see all relevant disclosures about risks in our business and, our SEC filings. Yeah, thanks. No, I just wanna give a chance to get that out of the way. Maybe can you walk us through some of the recent cabozantinib numbers and where investors should be focused in 2026? Yeah. 2025 was, you know, an exciting year for Exelixis, not only kind of the first pivotal data from our zanza program, but I think kind of in the background, we continue to kind of operate, you know, at the highest level in our commercial organization and the development organization, kind of across the board. At the heart of that is cabo. Cabometyx was approved in, I guess, seven different indications now, but kind of the heart of that growth is coming from, one, the RCC business, and then the recent launch in neuroendocrine tumors. We did $2.123 billion in revenue, and gave guidance for, you know, I guess $2.4 billion roughly in the midpoint, for 2026. We see that kind of continued momentum, you know, operational focus in that business, you know, just going forward. Within kind of our guidance, we expect growth not only in our kind of core RCC franchise, but our newly launched NET indication as well. You know, hitting on all cylinders, so to speak. Maybe talking about the NET opportunity first. Obviously we've heard a couple numbers on how big that could be, but how far are we penetrated into that opportunity and what's your latest thinking of the size there? Yeah. With the approval in kind of the end of March last year, we're still, you know, almost a year from the launch. You know, it's an exciting indication, one that we think is probably underappreciated, not only by the street, but, you know, historically by pharma as well and why we're so excited about it, not only kind of with the cabo launch, but our development program with zanza as well, and then our SSTR2 program behind that. What we've talked about historically is if you take kind of the oral segment, the oral segment in NET, it's about $1 billion if you kind of apply some contemporary pricing and contemporary duration, just given that, you know, prior to cabo is really a generics market. You know, our goal is to, you know, candidly just launch and penetrate as much into that billion-dollar segment as we can. You know, one of the dynamics that we always highlight about neuroendocrine tumors is oftentimes these can be relatively indolent tumors for patients, disease for patients. There's the dynamic not only of, you know, market share capture, but that time course of waiting for patients to kind of roll off their prior therapy, have the conversation with their oncologists as to kind of what's the new option that they should consider, and we hope that's gonna be cabozantinib. Great. No, I think initially when I added the indication, I think I estimated about $300 million, and then I think in this earnings, you already said they contributed $100 million. I greatly underestimated, like many others, this opportunity. Yeah, there's a lot of patients out there, I think looking for an oral option. Yeah, exactly. I mean, I think it's one of those that, you know, when the cabo NET data read out, we started doing kind of our typical, you know, kind of channel checks, market checks, really putting kind of pen to paper, so to speak, understanding the market size. It was one of those that every time we kind of kept coming back to it kept looking better and better. I think, you know, last year or the year before, what you started to see is this evolution of our enthusiasm and excitement around just NET as an indication over time. You know, right now, the way we think about our business is kinda through the lens of franchises. You know, obviously, kind of within single molecules, cabo, zanza, multiple indications, but also the indication verticals. We wanna have a presence of all of our compounds in RCC, CRC, and now NETs. The reason is, you know, the more we've really come to understand that opportunity, the more we realized it's much larger than I think people appreciate, and it's also an opportunity for us as Exelixis to really become the dominant player there. In the same way that we're, you know, the market leaders in RCC, we wanna be the market leaders in NETs. Certainly kind of with the launch of zanza, hopefully later this year, we wanna grow to be the market leaders in CRC as well. Great. Maybe talk about the existing franchise and the dynamics in renal cancer. At ASCO GU had some updates from competitors, and specifically Merck had the LITESPARK-011 data in the second line. Is this a threat to your cabo monotherapy there? What portion of current cabo sales would that be competing with? Yeah. The 011 data kind of, you know, taking a step back from the weekend and just kind of taking it all in, so to speak, before, during, after, the dynamic we've really heard is kind of as expected. We knew it was a positive study based on the top line release or the headline release on PFS, but all of our kind of physician work, clinician work had basically said the best way to figure out how this combination can fit in the treatment paradigm for patients is really around overall survival and the importance there. The reason for that is one of the challenges with any oncology drug is the question of do you combine mechanisms? Do you combine modalities or do you sequence them? Typically, you know, if you combine them, you're gonna wanna see a survival advantage because you lose whatever kind of advantages you have if you sequence it. If you look at the LITESPARK-011 data and contrast it with what you would reasonably expect with, say, a second-line TKI and then a third-line belzutifan is 10-11 months plus minus with the TKI 5-6 months with belzutifan. That absolute PFS benefit of the sequence approach is actually, you know, similar, if not a little better than what they saw in the combination. You layer on kind of the added tox of. You know, anytime you combine two molecules, you see kind of this additive tox to the extent that, you know, roughly 40% of patients in that study, 20% for len, 20% bel, is actually discontinued in one of the two, and so you functionally have, you know, pretty good number of patients with a monotherapy anyway. From the patient's perspective, from the physician's perspective, again, that question comes up is, well, what should I do, combine or sequence? The other thing to consider is that one of the dynamics we've heard that's been a pretty significant driver of bel's use is what's called the TKI break, is how patients and clinicians describe it. For a lot of these patients, they'll have been on therapy, you know, IO TKI, oftentimes for the past 2+ years. TKIs all have, you know, a certain set of kind of common adverse events, and so what bel's does is it adds a mechanism that's active in RCC but has kind of a different grouping of side effects. The dynamic that we heard was basically without survival telling us that there's a clear-cut reason to use the combination, you know, it's probably net not a big impact. The other dynamic that we've heard is that for those physicians and clinicians who do choose to use kind of the len, bel's in that second-line setting, what that probably means is they'll incrementally use additional cabo/nivo in the front line. The reason for that is, you know, we're out every day in the market competing for market share in the front-line segment with len/pem. If physicians know that they'll probably use len second line as part of the belzutifan combination, that means they won't use it front line, so they'll go to cabo-nivo as kind of the IO TKI of choice. That kind of dynamic, I think net-net, leads us to believe that the update over the weekend was probably a net slight positive for us. Ultimately is probably not practice-changing, landscape-changing, et cetera. Yeah. My one thought is also, I have one eye on LITESPARK-021, which is, I guess, in the early line, pembrolizumab and belzutifan versus pembro alone. Is there read across from the data that we saw? Or what's your takeaway from the data that we saw, I guess, from LITESPARK-011 to LITESPARK-021? Yeah. I mean, I think the thing to keep in mind for any of these earlier studies, especially kind of in the adjuvant space, is again, the need to show kind of a survival advantage. Because everything I said before about combinations versus sequencing is even more important the earlier you go kind of in that treatment journey for patients with kidney cancer. Because again, as you consider line of therapy, you know, what these patients deal with on a day-to-day basis, especially kind of in that adjuvant space, a lot of these patients are, you know, functionally cancer-free, and what is that cost benefit of adding a second drug in that as part of their kind of treatment, what are they actually getting out of it? That's one of the kind of important dynamics to consider any time you move earlier and, you know, candidly, it's how we think about, you know, development across the board around, you know, optimizing dose, optimizing combinations, why we're so excited about zanzalintinib because it offers some kind of, you know, improved, optimized, you know, ability around dose titration, et cetera. It's one of those things that I think is a through line through all oncology development and commercial utilization and all of that, is that kind of clinical benefit risk as you consider, you know, effect and, you know, adverse events and all that stuff from the patient's perspective. Great. I was also thinking that, you know, since you mentioned adjuvant, the LITESPARK-022, the pembro Welireg, adjuvant setting, would that also drive maybe in the front line, patients into the cabo combo because, you know, when you use, I guess IO up front, would you then gravitate more to a TKI in the front-line setting? Yeah. I mean, again, it's kind of more of that, you know, same dynamic. Our perspective on the 022 data at ASCO GU was, you know, certainly interesting, but adoption based on, you know, somewhat modest DFS benefit probably unlikely, again, because of everything we talked about before around sequencing versus combinations. You lose the benefit of, you know, say, having that HIF later in disease progression. The evolution of the RCC market over time has really been encouraging and rewarding to see, you know, as the kind of five-year survival rates continue to creep up. That's because, you know, companies like Merck and companies like Exelixis continue to invest in the space. But a lot of that's also driven by new drugs, new modalities that can be used kind of both early and late. The decision to kind of use them at a particular time point, you gotta make sure that over the course of the journey for patients that they have, it really is worthwhile for them. Is there anything we could read across from any of the ASCO GU data with Welireg to your zanzalintinib combo there? For example, LITESPARK-033, anything that makes maybe you incrementally more positive on that combination? Yeah. I mean, you know, from my perspective, I'd say, you know, certainly the data show that bel is a very active and interesting drug in RCC. The question then becomes how do you optimize it, where do you optimize it, and what do you combine it with? Certainly our perspective that if you contrast, say, len versus cabo versus zanza, we certainly think that zanza is an, you know, optimized best-in-class TKI. You know, it. We're asking the question with oh-three-three, if you have, you know, a HIF inhibitor like belzutifan with an optimized TKI like zanza, can some of the challenges that patients faced around discontinuations, toxicity, and all of those dynamics that may have limited the oh-one-one data, with a better TKI, can you overcome some of those limitations? You know, the way that we think about development in RCC isn't how are patients treated today, it's how are patients treated in the future. What we talk about internally is Cabo is the TKI for the 2020s. We want Zanza to be the TKI for the 2030s. When we kind of sat down with our partners, Merck, to really pencil out how do we wanna work together on this combination, the reason we kind of settled on that 033 setting, that post-adjuvant setting, is now that pembrolizumab has an overall survival advantage in the adjuvant space, more, we think, more and more patients will kind of be treated much earlier there. The question becomes, well, what do they get if they ultimately do relapse? That's kind of the dynamic that we wanted to focus on. It's more of a question of what's that patient journey in 2030, 2031, as opposed to what does it look like today? Overall, I think we're really encouraged, and excited about the combination. Yeah. Maybe talking about Zanza a little bit more at a high level, and, you know, obviously, that's the focus of many investor questions we get today. A year and a half ago, you put roughly, you know, a potential for $5 billion on this drug. I don't know if that's still accurate. How are you at a high level thinking about the different indications? Which ones are really the key ones to get to a really, you know, good number for that program? Which are maybe the smaller ones and which ones are the high-risk ones? Yeah. You know, when we put that $5 billion number out, I think it's. We wanted to kind of highlight, one, the breadth of the opportunity that we're pursuing, but also, you know, just candidly say we're excited about zanza. We think it can be bigger than cabo, kind of full stop. You know, subsequent to that, we've actually continued to expand our clinical program. We now have seven pivotal studies ongoing. You know, if anything, that number is probably a little bit low. One of the important dynamics that I'd highlight around kind of that market build, so to speak, is that it's not driven by any single indication. You know, the other kind of part of that messaging that we wanted to put out there is that as we're evolving as a company, kind of from the cabo RCC story to cabo NETs and now zanza, it's also about the expansion of not only owning as a GU oncology, but GI oncology as well. As part of that $5 billion or so is a roughly kind of 50/50 split between the two. You know, we've since added additional indications like STELLAR-316 in an earlier CRC setting, and that's one we're particularly excited about. I think, you know, the best way to think about zanza and my goal for 2026 is for investors and stakeholders to really understand that while we're really excited about Stellar 303 and the commercial launch, potentially later this year, I think a kind of a hyper-focus on you know, we get questions all the time around market share and all of that stuff. That's really important, but it also risks kind of missing the forest for the trees, so to speak, that we think zanza collectively has a really big opportunity, and we've been particularly thoughtful and deliberate about which indications we're selecting, why we think we're likely to be successful. Because at the end of the day. Our business is to run successful studies to help patients live longer, not to kind of just run studies for the sake of running studies. We wanna be successful kind of across the board. Okay, maybe talk about your first successful study there, the STELLAR-303 zanzalintinib/atezolizumab, in late-line colorectal. Obviously a very fragmented market. You know, you are still awaiting some OS data here on a subset of patients. Can you just kinda walk us at a high level about how you think about that market and maybe give investors an idea of how big that can be? Yeah. I guess kinda to the latter question, you know, our best guess, our market research suggests that collectively in the U.S., that third line plus segment's about $1.5 billion kinda total. Market share, as you highlighted, you know, is reasonably fragmented. About 1/3 of the market's kind of the SUNLIGHT regimen, 1/3 of it's TKIs, and 1/3 of it's kind of a chemo and a bunch of other stuff. The other dynamic there is, you know, there's the community versus kind of academic center and, you know, like all oncology drugs, the vast majority of patients ultimately are treated kind of in that community space. When we think about kind of the zanza/atezo opportunity ahead of the PDUFA date in December, you know, our market research really suggests that quite a bit of enthusiasm for the combination. Part of that is driven by the fact that there have been, you know, many prior attempts to get checkpoint inhibitor in these patients. Our study was actually the first to be successful there. One, we think that highlights kind of the differences between zanza and some of the other TKIs. You know, it comes on the heels of LEAP-017, it was a study that Merck ran that evaluated Len and Pem, and that study actually was unsuccessful. We did atezo/zanza, kind of in a very similar population and obviously showed a survival benefit. One of the things that keeps coming up is, one, offering patients a checkpoint-containing regimen. It's really driving a lot of enthusiasm. You know, kind of simply put, everyone is watching the Super Bowl, they see ads for pembro, they see ads or nivo, they see ads for these, you know, drugs that seem to have quite an effect in cancer patients and ask their oncologist, "Hey, you know, is this an option for me?" Until now, the answer has been no. Having the ability to offer patients a chemo-free regimen, a checkpoint-containing regimen that has shown a survival advantage over a standard of care, that we think is a compelling message. Plus when you layer on the fact that in kind of the U.S. contemporary market, the way patients are treated, the number of prior cycles or prior lines of Bevacizumab use, it can kind of complicate the picture for how SUNLIGHT is used because if you look at their data, there's a pretty stark difference between how that combination behaves, whether or not patients had seen prior bev use. We're really excited about it. You know, we're kind of doing a lot behind the scenes to kinda get up and running and be ready for that potential approval later this year. We're still missing a little piece of the data, the OS in the non-liver mets patient. What's the importance of that or, I mean, it's not gating for the- Yeah. I mean. At all. You know, overall the data that we presented at ESMO and was published reflect kind of the ITT population. You know, I think one of the most important parts of that data set was really showing we had benefit across all of those different cohort subtypes, liver met, non-liver met, prior bev use, et cetera. Really kind of that consistency of response is something that jumped out to me, jumped out to KOLs, et cetera. The liver met, non-liver met dynamic kind of goes back to, say, our clinical hypothesis prior to the start of the study. You know, thankfully, you know, it just shows its efficacy is not driven by any particular subgroup. It's kind of broad across the board, but it's also somewhat of the statement of the obvious that if we're able to show robust benefit across each of those populations statistically, that's better from a commercial perspective. You know, my ideal scenario is being able to show a Kaplan-Meier curve of the ITT liver met population and non-liver met population, because that's a powerful message to clinicians and the patients that's basically saying, you know, the robustness of this combination really has the opportunity to affect patients' lives and, you know, help them live longer, better, et cetera. That's really the goal at the end of the day, is to shift that standard of care. Yeah. Well, I'd love to talk more in detail about that, but I wanted to touch on another study, STELLAR-304, that we are getting a few questions on as we're awaiting the readout in the non-clear cell RCC setting. Can you just tell us about maybe what the bar here is and to date, what data, you know, or what investors can find confidence in for that readout? Yeah. I mean, the 304 study is, you know, an interesting one in that, it's actually the first pivotal study that's ever been run in non-clear cell RCC. Just functionally speaking, all drugs that are approved in kidney cancer have a label for both clear cell and non-clear cell, despite, you know, no data, kind of no randomized data I should say, suggesting kind of how they perform. What we wanted to do is really kind of plant our flag in the ground and say, "This is the standard of care," and the segment of patients is about 15%-20% of kidney cancer. Because right now use is based on relatively limited single arm unrandomized studies that, as you know, can be kind of challenging to interpret. You know, if Sutent or Cabo or any of the agents that are used show pretty wide confidence intervals around each of these studies that are single center or select patients a certain way, it's actually kind of hard to define what performance is expected. You know, unsurprisingly, as a result, use is a little bit of a hodgepodge across the board. There's no real dominant player in the non-clear cell space. This gives us a chance to come out with level one evidence and say, you know, hopefully zanza/nivo is the standard of care in this patient space. We'll see. We've guided for data in the middle of the year. Great. Well, thank you so much. Thanks for joining us today. Thank you for having me. It's a pleasure hosting you.