With me, I've got Andrew Peters, SVP of Strategy, and also Chris Senner, EVP and CFO. Maybe the first question I've been asking our companies just because of the, at least part of the disruption we've seen recently, the supply chain disruptions, if there's any that kind of you're worried about, thinking about, how you're planning, and if there's any parallels there with COVID. Yeah. Peter, thanks for having us. It's been a great set of meetings today. Before we start, we just want to say that the questions that Andrew and I will be part of today will make forward-looking statements. For a full understanding of the risks associated in our business, refer you to our SEC filings. From your question perspective, we have a redundant supply chain. We source from many companies. We feel comfortable where we are from a supply chain perspective. We source from India. We source from China. We have a very redundant supply chain that allows us to survive things like COVID. We had a lot of inventory on shore and allowed us to operate and make sure patients had product on time. Good. As we think about the FDA and potential disruptions there, has the dialogue dropped off, slowed down, any noticeable changes? Are you anticipating any changes? Yeah. I mean, I guess we're in the process of discussions with the FDA. Obviously, we have a PDUFA that's on April 3 for the net indication. We've always had a positive relationship with the FDA, and it continues. I can't say that anything's really changed from our perspective. It seems to be normal. Any impact you think or worry about from NIH budgetary cuts? I know you've had fantastic ISTs in the past. Just curious if there's any near-to-mid-term impact that you kind of worry about. Yeah. We always worry when there's change. We don't really see anything directly impacting us right now from an NIH perspective. Obviously, there's a lot of great research that happens at that level. We, as a country, benefit from that. It is an important part of some basic research that companies like us utilize. There's no direct impact that I would say. I don't know if Andrew, you have anything else. No. I think that's exactly the point, is that it's certainly an area that we as an industry are trying to kind of wrestle with and understand what those dynamics are. At the core of it, our industry is dedicated to helping patients kind of full stop. How the NIH and kind of our collaborative relationship over the years kind of plays into that dynamic is something that we want to see continue. Ultimately, we're here to help patients. Yeah. Are there other peripheral effects that we should be thinking about with the change in the administration? I kind of, in my head, kind of run through tariffs and supply chains, FDA, NIH. Are there other kind of secondary effects we should be? How do you kind of plan for it? Yeah. We try to think through everything. Obviously, we don't know everything that's going to happen in the future. Otherwise, we'd be doing different jobs. We try to plan for that. We try to risk mitigate. I can't tell you that we've come up with anything that you haven't asked already. We will continue to manage the business and plan for the business in the best way possible based on the available information. We will try to scenario plan. That's what we get paid for, is to run the business and manage the risks that are associated with the business. Yeah. I mean, one of the themes that we always kind of joke about is that Exelixis is really good at scenario planning, just because I think we want to prepare for and have all of these opportunities or optionality kind of at our fingertips. We got asked that question a lot in the last 12 months around the ANDA. Certainly, it's an exercise that we're familiar with. Okay. Fortune benefits the prepared, right? Yeah. On the Cabozantinib franchise, you mentioned kind of the looming PDUFA. And kind of if we think about that net opportunity, kind of what's the overlap of prescribers, patients, or prescribers and your salesforce? Yeah. We talked about some of this on the third quarter call. We see there's a universe of around 3,500 prescribers or so in prescribing for net, of which we cover probably 80% of those right now. We have good overlap. Doctors have good knowledge of CABO. We're really excited about that. The rest of the universe is a good proportion of those that it's been a call point before. They have some familiarity with CABO, either as part of another group organization. We've been planning for net. For the last several months, we added salesforce, a small amount of salesforce in the fourth quarter. We've been planning. We have been scenario planning for net for many months. We're ready to go. We're looking forward to a launch. We are excited for the opportunity to be able to communicate the data. Obviously, we do not promote off-label or anything like that. When it is approved, we will start promotion right away. Yeah, I mean, just to kind of add to that, one of the dynamics that I think comes through when PJ talks about this or when Mike talks about kind of our enthusiasm for the launch, it's that inherent familiarity with CABO that I think is one of the real kind of initial drivers for us. Because as you think about how patients are managed and kind of these AE protocols, physicians get to, when a new drug is launched, physicians have to understand how the drug is used, how to work through adverse events, how to down-titrate patients, how to do all of those things. Given the overlap in prescriber base with existing CABO prescribers for other indications, there's just not really as much of that that we need to do. I think the other thing, candidly, is when you have a data set like ours in Cabozantinib that was published in the New England Journal, it's one that I think has been embraced enthusiastically by the community. We have done market research. We show the profile of the drug without name and with physicians. They are like, yeah, we will prescribe it. When we tell them it is CABO, they are like, oh, it is CABO. We know CABO. We think it is going to be very well received as another option for patients and doctors. Okay. Perfect. Thank you. The commercial launch, how far into that commercial launch will it take before you kind of include that into the guidance? Or how do you think through that process? Yeah. We haven't given a specific time or date. We're going to look at it. We're going to see where we are, where we projected to be on the launch timeline, and see where that is. When we feel comfortable we can project the future better, then we'll provide guidance at that point in time. We're not giving guidance on guidance yet. When we get to that point in time, we'll let you guys know. It's something that we understand very well that the street generally wants us to provide guidance. We'll do that like we have in the past, when we're comfortable being able to predict the future with some, obviously, error bars around it. Yeah. It's kind of a matter of taking your internal projections, see how they play out over the course of the year. Yeah. Just seeing the dynamics in the market. How is it being utilized? Where is it being utilized? Where do we see opportunity? Then trying to translate those data into a projection that we feel comfortable we can meet. The comment you made about adding to the salesforce ahead of that launch, is that the classic pattern? Do you kind of add, is it 50% before, 50% after? How do you kind of think? It was a small number. It was literally like a handful of sales reps. It was not that many. We felt confident, one, in the data in our filing, but two, in our ability to utilize those sales reps and other indications in the meantime. We have added them. We are ready to go, literally, today. Good. Okay. Perfect. How do you kind of square away the market opportunity for pNETs? I think the way we talk about it, and we talked about it on the third quarter call, contemporary pricing, we think it's like a $1 billion opportunity from a market perspective. We haven't given any guidance on what we think our proportion of that is. Obviously, we think CABO is a very good alternative for physicians. We're going to do everything appropriately to get it in patients' hands so that they benefit from that. Yeah. And then just as we think about prostate, where are you for the NDA submission? Yeah. Kind of as Mike has talked about, when we were getting ready to file or going through the regulatory conversations with net, obviously, we heard about the Adcom. That became an all-hands-on-deck opportunity, given the prioritization and the opportunity that we see for NETs. We essentially put the prostate filing on the back burner and said, let's devote all of our time, focus, energy, et cetera, in getting kind of NETs across the finish line. Now the Adcom has been canceled. We're waiting on the PDUFA. Once that is over the finish line, we're going to refocus again on prostates. We'll give an update there later this year. No adding of salesforce for prostate yet. As we think about your next generation molecules, Zanza, I guess, STELLA- 101 is forefront of my mind, at least at the moment. In CRC, what are we going to learn from the additional data that we see in the first half of 2025? Yeah. That was the data set that was presented at the ASCO GI conference earlier this year. That was really a study that we embarked on to really flush out kind of the contribution of components from a regulatory perspective. Given this is the first pivotal study with Zanza, we really wanted to understand contribution of components. That trial, that randomized study that we presented there, was looking at the combination Zanza/Atezo versus Zanza alone to really understand what those dynamics there. The data showed really across all of the core efficacy endpoints, response rate, PFS, and overall survival that the doublet performs better than Zanza monotherapy. We looked at that data and kind of were enthusiastic about kind of that contribution of components angle. One of the obvious questions that we got in response to it was really to understand, well, how does this make you feel about 303? I'm sure we'll get to that later. Understanding how that Zanza/Atezo compares to what would be expected with Rego and with OS in the 18-20 month range at ASCO GI in that non-liver met segment, we think that compares, all the caveats with cross-route comparisons, et cetera, compares favorably with that kind of 12, 12-and-a-half month expectation for Rego that we would expect to see based on some of the ARCAD data. Okay. Did we get an update of STELLA 101 in the first half, or that's. Yeah. Beyond kind of what was published at ASCO GI, do not want to say when that data is going to be presented next. I think kind of really in that CRC segment, the next big step is going to be pivotal data later this year from 303. Gotcha. Okay. You kind of talked through the Rego, kind of what you want to see for OS. Kind of what's the feedback you're getting from physicians, just like physicians, what they want to see for an improvement? Yeah. I mean, kind of somewhat of a statement of the obvious. One of the things that we talk about a lot internally at Exelixis is we're in the business of changing the standard of care. What we want to see, what we think physicians want to see, is a data set that is compelling enough that has an opportunity to show that patients hopefully live longer on the combination of Zanza/Atezo versus regorafenib alone. Obviously, a large study. We haven't talked about the specifics around the SAP. We think the study is both designed to show statistically significant and clinically meaningful advantage, again, to hopefully establish a new standard of care so we can go out and help patients. Just as a reminder, the amendment that we made to the study a couple of years ago now really looks at first that delineation between the liver met and the non-liver met population, which is kind of this emerging, continuing to emerge dynamic in colorectal cancer, where you really see this big distinction in terms of how those two patient groups perform, not only on kind of sensitivity around checkpoint inhibitors, for example, but even kind of the ARCAD data for Rego show kind of clear differences there. That is something that we are keeping in mind. It was a kind of key feature of the data that we presented at GI. Okay. What's the path to success, you think, in that non-liver met, kind of just that for OS? Yeah. Again, coming back to the ARCAD data. ARCAD is a French group that has a robust database of virtually every clinical trial that's been run for Rego and Lonsurf and those active agents that are used in colorectal cancer. Their data would show that in that kind of non-liver met population, it's probably around 12, 12 and half months. In ITT, probably closer to 9-10 months, maybe 9, 10, 11. In that liver met segment, it's a little bit lower, kind of at 6-8 months or so. Okay. How should we think about dividing that group into the non-liver mets versus the broader intent to treat? What's the cut? Like the market opportunity? Yeah. I think that's kind of one of the interesting dynamics is from a TAM perspective, market opportunity perspective, we really think that they're about the same. Even though the non-liver met patient group is about 30% of patients overall, given that those patients tend to live a little bit longer, have longer duration, as you think about kind of the smaller number of patients, but potentially longer duration, they're about equal in size, actually. Obviously, we're hoping to show a strong signal in the ITT group. Non-liver mets, we think, is a sizable opportunity on its own. Gotcha. Thank you and then STELLA 02 and kind of what we should expect from it. Because I believe there's additional data there rolling out in the first half. Kind of what should we expect to see? Yeah. We have not kind of given the what, when, where of it all, kind of per our practice, where we wait for abstract titles to be presented to make sure that everything is all locked in place. We have guided, we have commented that there are going to be updates from STELLA 02 this year. Kind of stay tuned on the specifics. It is going to give another more mature look at how the emerging Zanza profile is looking. All the caveats with a small end, early studies aside, what we always joke about internally is the cosmic truth of all of this is ultimately going to come out in these large randomized pivotal studies. The good news there is what we said is we are expecting data from both 303 and 304 to potentially happen this year. The go, no go on the Phase 2, 3 for 305 also this year. It is going to be a very kind of data-rich year for Zanza, not only kind of with these more early updates on kind of the Phase 1, 2 programs, but seeing real pivotal data is a good thing. Yeah. Is there, under different indications in a sense, but in RCC, is there a nice read-through from 02 over to 304? I think understanding kind of the similarities and differences between clear cell and non-clear cell RCC can be challenging sometimes. Obviously, it's a sensitive tumor type. CABO is used there. All RCC-approved drugs are used in that non-clear cell space. I do not want to get ahead of, again, of specifics and kind of when we'll see what. Certainly, we're excited to share not only that data, but importantly, the pivotal 304 readout as well. Gotcha. As we kind of do those cross-draw comparisons, what's the basis for success as we think about the 304 readout? What's the best way of thinking about the patient types, et cetera? Yeah. I mean, ultimately, as I was saying before, we're in the business of P-values. And we're in the business of shifting standards of care. The one kind of interesting thing or important thing to consider about 304 is that while all of the existing RCC drugs have kind of on-label approval for the non-clear cell indication, there's actually been no pivotal studies run in that space. They tend to be based on single-arm, un-randomized data. What 304 does is it provides that opportunity to really plant a flag in the ground with level 1 evidence and say, this is the only treatment option out there, the only combination out there that has been proven, hopefully, in a large randomized study against a standard of care to show activity. That's kind of the initial goal around 304 was to actually provide some real level 1 evidence around activity and let that kind of inform utilization decisions and all of the kind of the downstream effects from there. Gotcha. Because all these are in collaboration with Merck, is there any kind of restriction about how much data you can release? Or you've kind of got a clear strategy around? Yeah. 304 is actually our study. The two Merck studies we'll announce details on later this year. Just as a reminder for the audience, we announced in October a collaboration with Merck, who, one of the things I like about it is Merck's our biggest competitor in RCC. Anytime you can work with your biggest competitor, it tends to be a good thing. We're running, or Merck is running, two studies in RCC evaluating Zanza and Belzutifan, their HIF-2 inhibitor. The important thing in one of the dynamics that we've certainly done in the past with the 9ER study that we're continuing is this clinical collaboration model where Merck's running the studies, Merck's paying for one of the studies, and we're paying for half of the other study. That gives us kind of a pretty nice attractive bang for the buck, so to speak, on the expense side, as Chris can talk about, where coming back to the 9ER study, Bristol paid for half. Our partners, Ipsen and Takeda, paid for half of our half. We took a $0.25 on the dollar investment to really more than double top-line revenue. That is a model that we liked and learned a lot from 9ER. We are hoping to continue that with Merck. That was kind of opening the gates, so to speak, for other clinical collaborations with potential partners to come up as well. Yeah. Yeah. I mean, it's a great way to leverage both of our P&Ls and de-risk it to some degree. They're also providing free pembrol for 305. That's another benefit to the P&L that allows us to continue to think about how we manage R&D expense. Mike has said we'll keep R&D expense in that billion-dollar range. We're below that this year. We'll continue to strive towards that around a billion-dollar number over the next several years. Gotcha. I guess 305 head and neck, how should we think about that for just like the data disclosure within the second half? Is that? Yeah. That one's pretty straightforward. It's a Phase 2, 3 trial design. That includes a go, no go decision at the Phase 2, 3 gate, so to speak. Given the design of the study, it's really going to be a yes or no, will the study continue? Because we actually won't see that data. If we did and we were unblinded to it, we wouldn't be able to use that for the Phase 3 portion. The decision we'll get later this year, the data we'll get later this year is really, will the study continue to the Phase 3 portion or not? We haven't talked about what exactly the parameters are that are behind that gate. From a disclosure perspective, it's will it continue or not? Gotcha. Okay. Perfect. Thank you, and then the USP1 inhibitor, kind of where are you for the monotherapy in combinations that is data? Yeah. That's a program that I kind of think of as like next on deck, so to speak, after Zanza. It's a target. It's a mechanism that we're particularly excited about, just given the complementary nature of the USP1 pathway and kind of DNA damage repair and to the PARP space. Really, the opportunity there is, can adding a USP1 either as a monotherapy or in combination with the PARP, deepen responses? Can it broaden responses? Can we grow upon that $3.5 billion or so PARP inhibitor market right now? We're continuing to escalate not only in the monotherapy, but in combination. We want to generate data as quickly as possible to make a decision on that program. We're in the business of making smart, prudent investment, as Chris talked about, kind of P&L management. We want to be able to decide as soon as we can, is this something we're going to invest in and really run? Or is it not going to hit the bar for differentiation? Are we going to shut it down? Those cohorts are continuing to enroll. Yeah. Because there's at least been one company that's pulled out of the USP1 space. And what do you want to solve for? What's the differentiation? Yeah. I mean, from a pure structure perspective, and Dana, our CSO, talked about that a little bit at our R&D day in 2023. It's an instance where we went from kind of third in class, but with what we thought was a best-in-class asset, to not only first in class, but likely best in class, as well as some of the other molecules either fell off from tox or due to kind of drug-like properties, solubility issues, dosing issues. It is one where we kind of found ourselves all of a sudden in the lead with what we think of as a differentiated molecule. We are excited to generate that data. Perfect. At the bottom of the hour. Thank you so much. Thank you. Thank you. Thanks again for having us here.