Next on stage with us, happy to say we have Andrew Peters from Exelixis. Thank you for joining us. Before we really kind of start digging in, could you walk us through the, you know, what has happened, you know, with Exelixis over the last couple of years? How has the company evolved? What you're just from a top-level standpoint, strategy is going forward and how the company is positioned? Yeah, happy to get into that, and thank you again for the invite. You know, been a great day of meetings and kind of excited to talk about Exelixis here. Just as a reminder, kind of before I begin, we'll be making some forward-looking statements today. So please see relevant risks to our business and disclosures in our SEC filings, so Exelixis, actually really interesting and exciting time to be at the company. You know, a lot of momentum recently, kind of, you know, following the announcement of a collaboration with Merck around zanzalintinib, not only in kidney cancer, but in head and neck cancer as well, and then followed by kind of the long-awaited, so to speak, decision from Judge Andrews around a long-standing kind of patent case that we had around cabozantinib. And then really kind of the third quarter earnings call, which not only kind of highlighted the success and continued momentum we've had around kind of our core business, but it also provided a chance to kind of say that, you know, now that we have this patent case behind us, you know, what does the company really look like? And we use that time to really say, you know, this is the short-term, medium-term, and long-term outlook as to how we think about Exelixis, how we think about running the company, how we think about our strategy, and kind of what those core pillars are. So if you think about what those core pillars are, it's really kind of four main things: cabozantinib, you know, continued momentum around our core business in RCC, looking ahead to potential launches in neuroendocrine tumors. And then zanzalintinib, you know, kind of a next-gen TKI behind cabo that is currently in six ongoing or planned pivotal studies, really kind of executing there ahead of our first pivotal readout in third-line plus non-MSI -high colorectal cancer next year. Kind of the next pillar is then our earlier stage pipeline and portfolio, around 10 programs between DC to IND phase I stage. And then lastly, from a business development perspective, how can we strategically use our balance sheet? How can we use our cash flows to bring in additional assets to complement our portfolio? Kind of really focused around that mid-stage, you know, to really complement everything that we're doing. And then just lastly, you know, one of our comments that we tend to say is Exelixis runs the company like a business, not a biotech, and making sure that we're remaining disciplined, not only on an expense perspective, but being mindful of creating value for all of our stakeholders and using a lot of that financial success, financial tailwinds that we've had to do things like buying back stock, which we've done, you know, $1 billion + over the last, you know, 12, 15 months or so, and we'll continue to do so going forward. And so, you know, really exciting time, kind of firing on all cylinders operationally and just kind of looking to the future. Thank you very much for that. Now, one of the comments you're talking about was the short-term, the medium-term view, and the long-term view and strategizing, and obviously, this is hindsight because we know the answer now relative to the patent, you know, the IP litigation, but were there, you know, obviously had that litigation gone a different direction, doesn't the view theoretically would have had to shift in some regards to manage that, and I guess when I'm thinking about that is how much of your plan that you had outlined would have theoretically been at play for being tweaked relative to that litigation? Yeah, so there's a couple of things within that. I guess the one thing that I'd say is what we had with our intellectual property portfolio around cabo was confidence, but we didn't have that clarity. And so when we've looked, when we were, you know, kind of at trial, either MSN I or MSN II, we had had that confidence in our portfolio, IP portfolio, but we were kind of waiting that clarity as to getting that final answer, which we inevitably did from Judge Andrews. You know, regardless, as it relates to, you know, what those scenarios look like, you know, in some of those different outcomes, you know, suffice it to say we're a company of planners, we're a company of scenario planners. When we think strategically about anything in the future, you know, we're always testing and kind of confirming or, you know, double-checking hypotheses around what we should do around any of our lines of business. And so, you know, when we think about investment in cabo and the NET launch, or when we think about investment in zanza and kind of that next study, those are things that we're always making sure, is this the right incremental dollar to spend? Are we likely to see a positive return on that? What's the opportunity set? What's the risk? These are all kind of dynamics that we pay special attention to, frankly, because this is a tough business and we want to make sure that we're making those correct decisions to make this tough job that much easier and that much more likely to succeed. Now, let's, I guess, start drilling into the commercial business. Second quarter in a row that you raised guidance. Can you walk us through what the drivers have been for the continued strength of cabo? Obviously, there's been a steady build of additional incremental indications. It's just been a growth over time from, frankly, a long time ago when it initially got approved for MTC. What is driving it right now? What are the primary drivers? And then we're certainly going to be going into the next leg of growth as well. Yeah, I mean, you know, kind of the short answer, and I think it's true not only for Exelixis, but for any commercially successful company, it really comes down to the data and the team. You know, obviously, you know, Exelixis and the success we've had with cabozantinib has really been a bit of an outlier in our industry. So we're a very data-driven company. We want to run a lot of analytics kind of across our organization. And one of the things that we've kind of come to realize is, you know, you can generalize and say that on average, most oncology launches tend to hit steady state around five to seven quarters post-launch for an indication. We're now, you know, 12, 13, 14 quarters in after 9ER, kind of our frontline RCC approval in combination with nivo. And we're kind of still seeing that momentum. Again, you know, coming back to it, it really comes down to the data, which, as the longer-term follow-up, as we've presented at places like ASCO GU, continues to resonate with patients and physicians and KOLs that really define us as kind of that number one IO TKI combination, as well as the number one TKI monotherapy. So, you know, P.J., who heads our commercial team, talks about this on, you know, our earnings calls, kind of, you know, the market share gains that we've continued to show. And so kind of that data is really something that differentiated data drives utilization, kind of full stop. That's what's successful in our business. And really that's how we think about not only cabo as it relates to potential launches and NETs, but also how we think about zanza and what we need to be successful in the future. Then the second part of that is really the team. And, you know, again, one of the advantages that I think Exelixis has relative to many of our peers is, you know, coming back to this concept that we talked about at the R&D Day in December: we're a big small company. What we mean by that is that we're small in a sense that we can be fast, we can be nimble, we can be strategic, we can kind of make these quick investment decisions around, you know, a lot of things that may seem on the margin, but have reasonably high ROIs, especially as it relates to kind of our commercial ops and commercial analytics decisions. And so we have that small company ability to move quickly, but that big company team and scale and execution history that really lets us and drives the success that we've had financially. So it's a combination of kind of all of those things that really drives not only kind of our continued momentum in the base business, but as we think ahead to, you know, say the medium term, we're on the third quarter call, we gave guidance, or we kind of outlined a path towards $3 billion in cabo revenue in 2030. You know, that's the sort of thing that drives our excitement and that opportunity is the combination of all of those things. On those numbers, if you were to, you know, try to walk us through the assumptions, which of what those components are, I mean, obviously we know frontline RCC, there's new approvals, but what would you consider the near-term, so to speak, leg of growth versus the more medium-term leg of that growth? And what by the time we get to 2030, 2033, what do you think will be the key factors driving the top line? Yeah, so certainly kind of that 2030 $3 billion cabo number that we've talked about is, you know, really driven by kind of two main things. One, kind of continued success in that base business and RCC, kind of those incremental investments that we can make to continue to gain market share, the stacking of patients as patients stay on therapy for longer and, you know, benefit longer. And, you know, our goal, our job is to really help patients live longer, better lives. So from our perspective, the longer they're on therapy, the longer they're living, the better all of our stakeholders are doing. So, you know, kind of point one, the path towards that $3 billion is certainly continued momentum in the base business. And then it's looking ahead to potential launches in things like neuroendocrine tumors on the basis of the phase 3 CABINET data. You know, that's an indication that it's one of those areas where the more kind of analysis and work and kind of thought we've put into what does a launch and net look like, kind of the more excitement we've gotten, not only from an opportunity set perspective where we've described kind of the current market, you know, using contemporary pricing for the oral therapies that are used in net. So we're in $1 billion right now. But also a lot of the dynamics that are important for any drug launch really seem to be kind of stacking up in our favor. You know, as an example, when we've done, say, market research and kind of evaluated the prescriber base for neuroendocrine tumors, what we found is about 75%-80% of their prescribers already give cabo for another indication. So as you think about any drug launch, there's kind of this initial time period where physicians need and patients need to get kind of comfortable with the tolerability profile, you know, adverse event management profile, how to down titrate, how to dose hold. All of these things aren't going to be new for the vast majority of prescribers because they already are familiar with cabo. So it's kind of one of those things that when we go through the TPP, the target product profile on a blinded basis, you know, they respond very favorably to the HRs of 0.2 and 0.3 and the 0.2 and 0.3 range and kind of the pNET and epNET across the CABINET cohorts. But then when you unblind it and say, oh, this is cabo, it's like a light goes off and it's like, okay, great, I know it, I got it. And so as we think about kind of the keys to kind of successful execution on that path towards a $3 billion run rate, those are the sort of things that we need to make sure we're keeping our eye on the ball, we're executing across all of our kind of components of the business. And, you know, how do we get to that number? Now, the zanza 2033 number is $5 billion. The cabo 2030 number was $3 billion. What accounts for the difference, number one? And of course, after when we get to 2031, given that generic entry relative to cabo's on there, what's the plan at that point for those? Yeah, so that's kind of an interesting dynamic. And, you know, I always kind of joke with our team about, you know, we get this question a lot, or we were starting to get this question a lot from investors. It's basically like, okay, now that the IP's resolved, what are you guys going to do about this new IP? Which is basically, you know, we have settlements with Teva and Cipla around a generic entrant of kind of Form N-2 of cabo on 1/1/31. And so that was one of the things that we wanted to kind of proactively get ahead of on the third quarter call because the, you know, we're now envisioning kind of this transition from a strategic focus from cabo to zanza. And so as I mentioned before, we have six ongoing or planned pivotal studies with zanza. When we talked about that $5 billion opportunity, we're actually pretty explicit around the breakdown. So if you think about our current business, we're kind of, you know, and for those not in the audience, you know, we're mostly GU focused and a little bit GI. And over time, as kind of the NET indication comes on for cabo, we're going to, you know, meet closer to the middle. But with zanza, it's actually, if you look across those six indications or six studies, it's 45% GI, 45% GU, and 10% kind of the head and neck as it relates to kind of 305. The other thing that we've laid out is with data, pivotal data expected for STELLAR-303, our first study in colorectal cancer for zanza, reading out next year with the potential for approval and launch in 2026. The cadence of enrollment, the cadence of data readout and potential approval is basically one launch a year starting in 2026 for those six indications. And so, you know, partly by design, partly kind of by serendipity that kind of the timing has worked out. Zanza's going to be launching in some of those earlier indications right as cabo is coming off in 2031. And then we're generating additional data from some of the more recently initiated and announced trials, say the two Merck studies and the NET study, STELLAR-311 versus everolimus. And so there's this really nice cadence and build toward that $5 billion opportunity in the U.S. And so that's kind of how we see longer term, how we're managing through that transition and then supplementing that with everything we're doing internally from a portfolio perspective and being opportunistic from a business development perspective if we see, you know, an asset or assets that we think can be really complementary in value creating for our organization. So, let's drill a little bit more deeply under cabo and zanza themselves. Specifically on cabo, it was recently announced that there's going to be an AdCom for neuroendocrine tumors, I believe it was March. Could you, I mean, the drug's been on the market for quite a while. And so there's a panel for the drug with, I mean, granted new indication. What do you see as the panel's real objective in this process? How do you see what their role is going to be? Is this going to be one of these panels where there's a vote at the end of the day, or might it be more of a kind of an information gathering and how to use type situation? Yeah, so, you know, don't really want to speculate on the panel beyond anything that we talked about in kind of the press release announcing it. So kind of stay tuned as details and kind of information begin to mature. But I think the one thing that I want to kind of emphasize and really, you know, hit home is that we have and will continue to work collaboratively with the agency. Again, coming back to this idea that we're this big small company, you know, given our history of approvals and regulatory, you know, working with regulators around cabo and other indications, you know, kind of this isn't our first rodeo, so to speak. So we have relationships, we'll continue to have relationships with regulators, and we'll continue to work collaboratively with them to kind of ensure we're doing everything we can, you know, to get this product to patients. Because as I mentioned before, you know, we think the CABINET data are certainly resonate with the patient community, the advocacy community, the physician community. We want to do everything we can to kind of help this get this option available to patients. As you said, this hasn't been your first rodeo. How would you compare and contrast the nature of this FDA application with different, you know, what differences are there with applications that have been submitted previously? Yeah, again, I think it's, you know, kind of everything's the same, but everything's different kind of thing. You know, so probably too many things to get into a lot of the nuance and minutiae. But, you know, at the end of the day, you know, the CABINET data represent a, you know, a data set that's been especially well received, you know, as I think back over the last six, 12 months, kind of the presentation at ESMO, the concordant publication in New England Journal of Medicine of the data and really the response from kind of all stakeholders in that neuroendocrine tumor community. That's really been something that's been heartening to me. You know, as kind of the thing that I think, you know, folks on the investors can often miss is kind of that, you know, patient dynamic that we see a lot more kind of in and have a first row seat with, and so hearing from that patient community about what the data could potentially mean to them, that's the sort of thing that, you know, really excites me and, you know, is why we want to continue to work collaboratively with regulators because that's how we can kind of work towards a potential approval. In terms of sizing up the net market opportunity, how should we look at that population? Yeah, so as I mentioned before, kind of the two, you know, current oral options for patients in NET. So everolimus and Sutent, if you look at their current utilization, given that both are generic, if you were to kind of assume more contemporary type drug pricing, branded drug pricing represents kind of like a $1 billion opportunity collectively between the two. But one of the things that we've talked about and P.J. highlighted again on our third quarter earnings call was, you know, some of the similarities between, say, where RCC was in that 2014, 2015, 2016 timeframe before cabo had launched and where NET is today. So what I mean by that is, you know, back in, say, 2015, RCC wasn't really seen as kind of this robust large market. But, you know, lo and behold, when you have effective agents that generate, you know, compelling data to shift that, you know, Kaplan-Meier curve, shift that standard of care to the right, patients benefit, companies benefit, you know, the total addressable market, you know, has grown substantially now. RCC is something like a $10 billion opportunity. Similarly, you know, I think in general, neuroendocrine tumors have probably been underinvested across the industry. You know, there aren't as many kind of new novel therapies being developed there outside of, say, you know, radioligand therapies. And so one of the things that we're excited about not only is to kind of launch into this real high unmet need, but kind of have the opportunity to grow and become really the market leader in this space. And so we've talked about how we think that the, you know, kind of the total market, as we think about some of the new therapies and new modalities coming into that space can grow in, you know, to a $3 billion-$4 billion opportunity. And so when you've heard us talk about why we're excited about NETs and kind of why the launch of the CABINET data is priority number one for Exelixis, it's really because we see that bigger strategic picture of how do we grow from becoming kind of the market leader in kidney cancer, but the market leader in kidney cancer and something like NETs, which we think we can play a central role in growing that total opportunity. So if we take a step forward to prostate cancer, success on PFS, OS, strong trends, how should we think about the path forward at the NDA approaching and whatnot? And would you be able to comment on any of the debates that some investors have had when trying to assess the design of the trial versus other trials? Yeah, so kind of taking a step back kind of before I dig into a lot of those questions. You know, I think one of the intents and kind of unique aspects about CONTACT-02, that's a pivotal study we ran in that population, was that we really wanted to ask a fundamental question of can the combination of cabo plus a checkpoint, atezolizumab, have an effect on the tumor themselves? And so in this prostate population, we thought the best way and the cleanest way to answer that question was to look at a population who had visceral metastases at baseline. Because one of the challenges, you know, that we certainly have historic experience with in prostate cancer is, you know, there's a good chunk of patients have essentially bone-only metastatic disease. And monitoring responses or lack thereof can often be challenging in kind of patients with bone-only disease. And so we wanted to ask kind of more of a simple, straightforward question. And so CONTACT-02 was unique in that sense in that we specifically targeted it. But kind of the heart of your question is really around how do we think about the potential for cabo and prostate? And I think it's really kind of twofold. The first is, you know, we've continued to say we plan to submit the sNDA by the end of this year. But kind of the caveat to that or the other dynamic to that is when we highlighted that $3 billion cabo opportunity in 2030, we made sure to also highlight that it included a pretty significant risk adjustment that we apply to the prostate opportunity. Kind of, you know, suggests that going in eyes wide open about, you know, some of the dynamics, say, in that market and that data set that we're very well aware of. And so, you know, probably kind of the best answer around how do we view prostate is ultimately we view it as a heavily risk-adjusted opportunity as we think about kind of that longer medium-term cabo number. Very, very helpful. If we move forward to zanza, I guess, could you start by running us through the recent partnership with Merck? Yeah, so that, you know, I'm particularly excited about because it's, you know, not very common in this industry, say, to kind of collaborate with your biggest competitor, so obviously kind of in RCC, kind of the two leaders in the IO-TKI space are us and Merck, and, you know, this collaboration is really a chance for us to work together to evaluate their HIF inhibitor, belzutifan, with zanza and really kind of ask the question, you know, how does this combination look and how can it help patients. We've agreed with our collaborators, our partners, Merck, to kind of hold off on a lot of these specific details around the, you know, specifics around indication, trial design, et cetera, till those are a little more mature and kind of up and running because, you know, obviously it's a little bit of a competitive space. But, you know, it's a deal that not only are we excited about, you know, Merck running those studies, Merck funding those studies or partially funding those studies, which is a model that, you know, we liked, we executed on with cabo and we're going to continue to do with zanza, but we also were able to then secure kind of a supply agreement on pembro, so as we think about STELLAR-305, our phase III study in frontline head and neck cancer of zanza, pembro versus pembro, you know, that's a reasonably sized win for us just from a pure kind of clinical trial operations and cost perspective, and so, you know, kudos to our team and, you know, the countless number of people that are involved in a large collaboration like this, you know, it really shows our ability to kind of execute and get things done. And not only our excitement, but kind of the oncology world's excitement around what a next-gen TKI, kind of that third-gen VEGF TKI like zanza could do. Now, while you can't tell us the specifics of indications and trial designs, is there some timeline when you think you might be able to tell us? Stay tuned. This is kind of all I can say. Got it. Got it. So clearly when zanza was designed, obviously the basis for the design was on an already successful drug with some nuanced differences that might allow it to expand the opportunities of where your programs could go. Could you talk a little bit about the molecule itself and how that informed you and what tumors to pursue? Yeah, so I think kind of zanza, again, is a little bit of a unique molecule and program in biopharma in a sense that it kind of builds upon this continuum of tyrosine kinase inhibitors and really is kind of the real third-gen VEGFR targeting TKI. So taking a step back, if you think about kind of the core insights around cabo being a second-gen TKI, it's really understanding, you know, what were some of the emerging and known resistance profiles to those first VEGF TKIs. And this hypothesis and this insight is, can we also target additional kinases beyond VEGF and kind of the angiogenesis pathway to kind of get in front of that resistance development and help patients stay on drug longer and, you know, ultimately drive standard of care to the right? And really we were successful in doing that kind of across, you know, first METEOR and then CABOSUN and 9ER and kind of all of the success that we've had clinically. But similar to kind of the cabo hypothesis where we wanted to improve upon the really known and emerging liabilities of the first-gen agents, what zanza was envisioned was, is there a way to improve upon kind of the known liabilities of the second-gen TKIs? And we think kind of that optimal, you know, kinase inhibition profile, VEGF, MET, AXL, MER, kind of TAM kinases has really been optimized in cabo, but it's one real liability we think is probably around its longer half-life, around 100 hours. And if you think about the practical implications of that, the implications in clinical practice and as it relates to patient management, one of the challenges with a long half-life is all patients with any VEGF targeting TKI inevitably see some sort of adverse event. When you do, you need to dose hold, down titrate until resolution. But the challenge of the long half-life is given the accumulation in plasma, that period of washout can be 10 days, two weeks, or potentially even longer. And so that time period where, you know, you're potentially giving sub-therapeutic levels of kinase inhibition, you know, are you giving the tumor a chance to kind of, you know, develop resistance? Are you finding that the inertia needed to get a patient back onto cabo as opposed to trying something else is reasonably high? As you think about multi-drug, multi-modality combinations, do you just dose hold cabo or do you dose hold the other drug? How does that work, especially if they're similar but kind of overlapping toxicities? Just from a practical combination and combinability perspective, there's real challenges kind of with that half-life. Again, with the idea that we wanted to kind of move towards this third-generation VEGF TKI, what we did with zanza was phenocopy the kinase inhibition profile of cabo, but our team was able to engineer in kind of a metabolic liability to that core scaffold, which changed the half-life from 100 hours to a little under a day. What that means, and kind of we've since proved that hypothesis, is that we've been able to have kind of a more user-friendly, potentially differentiated TKI. You know, we've presented data kind of in the most apples-to-apples comparison population and kind of kidney cancer, and we've shown not only do we have, you know, as good, if not potentially better efficacy, you know, all the caveats around, you know, small single-arm unrandomized trials, but similarly potentially differentiated safety. Again, looking at that IKCS data that we presented last year, you know, not only is kind of there's a lower frequency, but severity of some of kind of the core VEGF-associated AEs. And then kind of that more user-friendliness, combinability of that shorter half-life, especially as we think about a lot of the studies that we're running in pivotal trials where zanza's in combination with checkpoint inhibitors, for example. And so how does that play out, especially in areas where keeping patients on drug is especially critical to driving that efficacy? So that's really kind of the key points of differentiation and why we're excited about it. And just lastly, you know, I think one of the advantages we have as an organization is we can kind of use this 10, 15-year history of cabo development to help inform where we're going to go with zanza. Because if, you know, cabo points us in the direction of where a cabo-like efficacy profile could be effective and then improved upon with all the things that I just talked about. So if you look at, you know, especially the first three studies that we've run, 303, 304, 305, in colorectal cancer, non-clear cell RCC, and head and neck cancer, those really all started based on data sets that we generated with cabo. And so, we think we kind of have this advantage because not only are we continuously generating data with zanza kind of in an earlier stage setting in the STELLAR-001 and STELLAR-002 studies, but we have kind of this wealth of information that we can also rely upon to kind of help inform and shape things about how we think about risk, how we think about probability of success, how we think about patient populations, kind of all of those things that are really important. So what should we think of in terms of cadence for when more data starts to come and we are able to start, you know, in our minds looking at de-risking events for zanza across these indicators? Yeah, so, you know, one of our kind of key points or jokes we always joke around internally is at the end of the day, we're in the business of P-values. The big de-risking event, so to speak, is really going to be that first pivotal data from STELLAR-303 next year. Ahead of that, one of the things that we outlined on the third quarter call is that 2025 is going to be a really busy year from a zanza data perspective. Beyond the pivotal readout, you know, kind of we're working to continue to execute in the background to enroll these studies, but we're also going to start to share data from some of the earlier STELLAR studies. You know, one of the things that we've highlighted, kind of time, location, TBD, pending acceptance of abstracts and titles being published, et cetera, is, you know, a smaller randomized study, say, of zanza, atezo, versus zanza in colorectal cancer to, again, kind of understand the activity of that doublet as well as a monotherapy zanza in that population and kind of a contribution of components type dynamic. Similarly, we're going to have kind of more mature data from some of our combination arms or combination cohorts in RCC, so in the STELLAR-002 study, we looked not only, you know, across a wide range of checkpoints, you know, PD-1, et cetera, and so we're going to start to share that data as well. Just from kind of a corporate data disclosure philosophy, you know, given that we're profitable, given that, you know, we're at a more mature stage, we generally don't do kind of the small cap biotech thing of, here's eight patients' worth of data for unconfirmed responses and claim that's a 50% response rate just so that we can kind of juice the stock and raise money. That's philosophically kind of not how we approach data disclosure. And so when we talk about kind of 2025 being a big year, that's really a presentation or kind of a series of presentations of what we think are reasonably mature data sets to really help all stakeholders get an idea, get a sense of kind of what is the profile of zanza kind of emerging into. Excellent. Now we've come up on the end here. Thank you so much for your time. Appreciate it. And look forward to seeing more in the future. Yeah, thank you. Thank you again.