Exelixis, Inc.

Good day, ladies and gentlemen, and welcome to the Exelixis Fourth Quarter and Fiscal Year 2024 Financial Results Conference Call. My name is Cherie, and I'll be your operator for today. As a reminder, this call is being recorded for replay purposes. I would now like to turn the call over to your host for today, Ms. Susan Hubbard, Executive Vice President of Public Affairs and Investor Relations. Please proceed.

Thank you, Cherie, and thank you all for joining us for the XLX's fourth quarter and fiscal year 2024 financial results conference call. Joining me on today's call are Mike Morrissey, our president and CEO, and Chris Center, our chief financial officer, who will review our progress for the fourth quarter and fiscal year 2024, ended January 3rd, 2025. DJ Haley, our executive vice president of commercial, Amy Peterson, our chief medical officer, and Dana Aftab, our Chief Scientific Officer, are also on the call today and will participate in the Q&A portion of the call. During the call today, we will refer to financial measures not calculated according to generally accepted accounting principles. Please refer to today's press release, which is posted on our website, for an explanation of our reasons for using such non-GAAP measures, as well as tables deriving these measures from our GAAP results. During the course of this presentation, we will be making forward-looking statements regarding future events and the future performance of the company. This includes statements about possible developments regarding discovery, product development, regulatory, commercial, financial, and strategic matters. Actual events or results could, of course, differ materially. We refer you to the documents we file from time to time with the SEC, which under the heading Risk Factors, identify important factors that could cause our actual results to differ materially from those expressed by the company verbally and in writing today, including without limitation, risks and uncertainties related to product commercial success, market competition, regulatory review and approval processes, conducting clinical trials, compliance with applicable regulatory requirements, our dependence on collaboration partners, and the level of costs associated with discovery, product development, business development, and commercialization activities. And with that, I will turn the call over to Mike.

All right. Thank you, Susan, and thanks to everyone for joining us on the call today. ExoLexus had a breakout year in 2024, and we're already sprinting into 2025 after a busy January where we provided important updates across all components of our business. ExoLexus has built significant momentum to establish a multi-compound, multi-franchise oncology business as we advance our Cabozantinib, Zanzalentinib, and early pipeline priorities. to meet our aspirational revenue goals of $3 billion for Cabo in 2030 and $5 billion for Zanza in 2033. We're thrilled to see continued growth and momentum of the Cabo franchise in the U.S. and globally, both in terms of absolute revenue and relative growth compared to the competition, and we expect to see additional upside with potential new indications. We outlined important news and priorities to jumpstart 2025 at our corporate update in January at the J.P. Morgan Healthcare Conference. I won't reiterate everything here today, but just focus on the top highlights, including first, we saw a strong performance of the Cabo's Antidote business in the fourth quarter and full year 2024 with approximate 11% growth in demand, new starts and revenue. Cabo Medics maintained its status as the leading TKI for RCC in both the frontline IOTKI market and the second-line monotherapy segment. Fourth quarter, 2024, U.S. Cabo franchise net product revenues grew 20% year-over-year to $515 million compared to fourth quarter 2023. Full year 2024, U.S. Cabo franchise net product revenues grew 11% to $1.81 billion compared to full year 2023. continuing its role as the worldwide leading TKI. Global Cabo franchise net product revenues generated by ExoLexus and his partners were approximately $690 million and $2.5 billion in the fourth quarter and full year 2024, respectively. Chris will review our 2025 financial guidance for the base business in his prepared remarks. We will provide updated guidance, including the net opportunity at a later date post-approval. Second, our top priority is to advance the CABO net indication with ongoing regulatory activities for the SNDA based on the cabinet phase three pivotal trial. As you'll recall, we announced that the FDA had accepted our SNDA seeking approval for CABO xanthinib in both P-net or E-P-net indications with a BDUFA date of April 3rd, 2025. Detailed final results from cabinet were presented at ESMO 2024 and were concurrently published in the New England Journal of Medicine, which supported the addition of CAVO to the recently updated NCCN guidelines for NET. We're collaborating closely with the FDA on the review and won't speak to any details of that process today. As we've highlighted at recent investor conferences and webcasts, we are launch ready and eager to engage as soon as approval is secured. Third, we expect ZANSA to take center stage in 2025 as our next oncology franchise opportunity. Important anticipated ZANSA data milestones from pivotal trials include top line results from stellar 303 in colorectal cancer and stellar 304 in non-clear cell kidney cancer, and a decision to advance to the phase three portion of stellar 305 in head and neck cancer, all projected to occur in the second half of the year pending event rates for each trial. In addition, we expect to initiate the Stellar 311 trial of ZANSA in net in the first half of 2025 and anticipate Merck will initiate two RCC studies evaluating ZANSA plus bosudafan this year. I'll remind everybody again that ExoLexis is running ZANSA pivotal trials against a contemporary standard of care for each trial. Regorafenib for Steller 303, Sinitinib for Steller 304, and a Pembrol placebo combination for Steller 305. Recent speculation during ASCO GI comparing ZANZA to CABO is misguided and a distraction from the focus of our ZANZA development activities. As highlighted on our third quarter call, our $5 billion projection for ZANZA in 2033 is based on success in indications which we believe are independent from any overlap with CABO. Fourth, as we highlighted recently, our ExoLexus IND pipeline is full for the next several years with potentially differentiating molecules based on extensive preclinical testing. In 2025, We're looking to accelerate the Phase I development of XL309 as a potential therapy for tumors that have become refractory to PARP inhibitor therapy, as well as in combination with PARP inhibitors to deepen and prolong responses. Also, we're pleased with our progress of Phase I trials for XB010 and XL495 and see the opportunity to file up to three new INDs for XB628, XB064, and XB371. We expect a significant number of data presentations for these molecules at major scientific meetings throughout 2025. Business development activities continue to focus on late-stage assets in the GUGI space. Back-end loaded paper success transactions that tuck nicely into our existing and potential future oncology franchise remain a top priority. In terms of capital allocation, we're confident we have the balance sheet and the expected free cash flows to advance our pipeline priorities, access new high conviction assets, and continue to repurchase shares. So with that, please see our press release issued an hour ago for our fourth quarter and full year 2024 financial results and an extensive list of key corporate milestones achieved in the quarter.

I'll now turn the call over to Chris. Thanks, Mike. For the fourth quarter of 2024, the company reported total revenues of approximately $567 million, which included Cabo Zantanen franchise net product revenues of $515.2 million. Cabo Medics net product revenues were $512.8 million and included approximately $3 million in clinical trial sales, which is lower than our clinical trial sales in Q3 2024. As a continued reminder, clinical trial sales have historically been choppy between quarters, and we expect this to continue into the future. Growth to net for the Cabozantinib franchise in the fourth quarter 2024 was 26.8%, which is incrementally higher than the growth to net we experienced in the third quarter 2020 patient. This increase in growth to net deductions in the fourth quarter 2024 is primarily related to higher copay assistance for our commercial patients and Medicare Part D expenses. Additionally, we estimate that our growth to net for the full year 2025 will be between 29% and 30%, as previously disclosed Exelixis has been designated a specified small manufacturer, which requires Exelixis to pay a 1% discount in 2025 on all Medicare Part D sales and is included in our gross net estimate for the year. As we've mentioned in the past, gross net tends to be higher in the first quarter of a year. We project that the first quarter 2025 gross net will be similar, primarily due to higher copay assistance expenses for our commercial patients. Our Cabo Medics trade inventory was flat at 2.1 weeks on hand at the end of the year when compared to the third quarter of 2024. Total revenues also included approximately $51.5 million in collaboration revenues, which includes approximately $44 million in royalties earned from our partners, Ipsen and Takeda, on their sales of Cabo Xanthidus. Our total operating expenses, excluding restructuring and impairment charges for the fourth quarter of 2024, were approximately $403 million, compared to $352 million in the third quarter of 2024. The sequential increase in these operating expenses was primarily driven by higher manufacturing costs for drug development candidates, higher clinical trial and licensing costs, and by higher general and administrative costs in the fourth quarter of 2024. Provision for income taxes for the fourth quarter of 2024 was approximately $44.9 million, compared to a provision for income taxes of approximately $37 million for the third quarter of 2024. The company reported GAAP net income of approximately $139.9 million, or 49 cents per share basic, and 48 cents per share diluted for the fourth quarter of 2024. The company also reported non-GAAP Net income of approximately $160.3 million, or $0.56 per share basic and $0.55 per share diluted. Non-GAAP net income excludes the impact of approximately $20 million of stock-based compensation expense net of the related income tax effect. Cash and marketable securities for the year ended December 31, 2024, was approximately $1.75 billion. During fiscal year 2024, we repurchased approximately $656 million of the company's shares, resulting in the retirement of approximately $26.4 million of the company's shares at an average price per share of $24.82. As of the end of fiscal year 2024, we had approximately $294 million remaining under the $500 million stock repurchase plan authorized by the company's board in August 2024. And finally, turning to our financial guidance for the full year 2025. We announced our 2025 financial guidance during the J.P. Morgan Conference in January, which is detailed on slide 19 of our earnings presentation. As Mike mentioned, we will provide updated net product revenue guidance, including the net opportunity at a later date post-approval. And with that, I'll turn the call back over to Mike.

All right. Thanks, Chris. I'll wrap up here by thanking the entire XOXS team for their outstanding efforts in 2024. As I said previously, success never comes in a straight line in this business, and I want to commend everyone at Exalexis for their individual and collective urgency and resilience as we navigated our past challenges and continue to advance our discovery, development, and commercial priorities. 2025 is already shaping up to be another inflection year for the business and the patients we hope to serve now and in the future. I am so proud to be part of the team that makes every hour count, as we excel on our mission to help cancer patients recover stronger and live longer. We look forward to updating you on our progress in the future. Thank you for your continued support and interest in Exalexis, and we're happy to now open the call for questions.

Thank you. If you would like to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, press star one one again. Due to time restraints, we ask that you please limit yourself to one question. You may then return to the queue. Please stand by while we compile the Q&A roster. And our first question will come from the line of Astika Gunawaran with Truist. Your line is open.

Hi, guys. Thanks for taking my question. And congrats on all the progress made here. Mike, just to everyone who's worried about Zanja looking like CAVO, the misguided notion that you talked about earlier today. Can you just, just to dismiss that a little bit more, could you just talk to us a little bit about, one, the lack of overlap in the approved indications for CAVO and where your anticipated ends will be? And I think the important one here is, if you've ever seen the pairs I guess, force a substitution with a generic of something that is not the actual generic product. I don't think I've ever seen that happen, but would like to get your thoughts on that.

Yeah, thanks, Astika. Look, I don't want to speculate on that level of details. I think the main focus is we are comparing ZANZA combinations to individual standards of care for Stelver 303, Stelver 305. We certainly plan to do that with Stelver 304 as well, as well as what we have planned for 311 in the NET area. So the goal here is to obviously run large global randomized pivotal trials that will allow us to generate Positive data if it's there to be able to push those indications forward so and that's the only comparison that comes to us all the hand waving between small data sets a single arm or a Very small randomized phase two data sets is very, very challenging. Everybody knows that. We certainly know that, and we're focused on running, executing, and reading out these pivotal trials because ultimately that's what will drive, you know, the label enabling efforts that we need to get SANS and moving forward into more patients in the commercial setting and really helping those patients who need better therapies.

Thank you. One moment for our next questions. And that will come from the line of Michael Schmidt with Guggenheim Securities. Your line is open.

This is Paula for Michael. Thanks for taking our question. One is on CAVO for NETS. Sort of pending the label discussions and formalization, how are you currently thinking about the launch trajectory and expectations for uptake? Do you see any potential for an initial bolus here, given that this is a sort of indolent disease? And then for ZANZA, can you just comment on the emerging safety profile now that we have more data and indications beyond RCC? You know, on balance, what are your current thoughts on the ability to maintain dose intensity with ZANZA, especially when combining with checkpoint inhibitors? Thank you.

DJ, I'm going to take the first part. Yeah, thanks for the question, Paul. So, with regards to NET, you know, as Mike mentioned, we are completely launch ready. And the team is, I would say, very excited and just ready to go so we can have the opportunity to help appropriate patients with neuroendocrine tumors pending an FDA approval. That said, as we've said previously, we believe that the opportunity is significant. We've talked about the fact that in 2025, we look at the net market. And the oral shares within that market, we believe the oral market in 2025 in contemporary pricing dollars is about a billion dollars. So substantial opportunity. And, you know, when we think about the cabinet study and the data set, it's a broad data set, really the only of its kind that addresses all sites of origin for NET, you know, all the different grades of the tumor, you know, different SSTR status, et cetera. So it can really be a choice for any type of NET patient, you know, pending approval. We've talked about before, too, the overlap. of customers that we see in terms of customers, both that we are calling on currently for our approved on-label indications, as well as prescribers who have already written. Cabo Medics is about 80%, so that's significant. So that speaks to really the ability for us to really come out of the gates fast and accelerate the launch trajectory of this. And we hear from market research. that physicians are excited about the data. They like the efficacy AC. They understand the safety. And when they find out this is Cabo that they're familiar with, it really makes them comfortable in terms of dose reduction and managing that toxicity profile. So we're really excited and just can't wait to get out there and bring this to patients. The final thing I'd mention here too is that The oral therapies we're competing with effectively, sunitinib, everolimus, and CAPTEM are all generic. So this will also give us, we believe, a substantial advantage in terms of share of voice and other aspects of things. So we're excited for the launch.

Thank you. One moment for our next question. And that will come from the line of Sean LeMann with Morgan Stanley. Your line is open.

Hi, Mike, Chris, and Susan. I hope you're all well. My question relates to the balance sheets. There's really good liquidity there, despite that I think on the cash flow statement, you've bought back $650 million worth of stock. I think the commentary has been that you're winding down investment in Carbo, winding it up in Zanza, but you're probably looking at a net neutral outcome. If I'd got our past discussions correct in terms of OPEX. Then you've talked about accelerated development of 309, potential three new INDs, I think you said, Mike. But it kind of still suggests that you're gonna still end up with a highly liquid and lazy balance sheet. So how do you think about that in terms of further buybacks versus potentially bolstering the pipeline with M&A?

Yeah, thanks for the question. So I'm not sure I'd characterize that much free cash flow as lazy. If so, then most other companies would want to aspire to that. So, yeah, look, I think we've articulated a plan where we have built a business. run a business with a great degree of discipline so we can move our pipeline priorities forward with cabo with zanza with the rest of the pipeline we can do the appropriate uh capital allocation to buy back uh shares when we think the price is appropriate and then to invest in new assets when we have the conviction that they will help move the needle for patients and for our revenue goals going forward. So we have the opportunity, and I would argue the responsibility to manage that very carefully, those three different tacks in terms of pipeline, in terms of returning cash to shareholders, and then BD in a way that moves the business forward in the short term. in the long term. So I like that, you know, I like that optionality, and I like that flexibility. We're spending about, we'll spend about a billion dollars in R&D this year, and we think we have the opportunity to prioritize and focus based upon how the data comes in and what that tells us in terms of where to put money behind the winners and when to stop the losers. So I think we've got that well handled, and we're looking forward to continue to, you know, move the ball downfield in a way that helps patients and builds value for our shareholders.

Thank you. One moment for our next question. And that will come from the line of David Leibowitz with Citi. Your line is open.

Thank you very much for taking my question. On the recent net data presented in the ASCO GI, could you tell us about how we should view the various subgroups relative to actually how the drug might be used in clinical practice and what the label might ultimately look like?

Hi, David. This is Amy. Thanks for the question. So, we can't really speak to what the label might look like. We're in negotiations and discussions with the agency. But, you know, given the population that was evaluated in cabinet, it really reflects a very broad patient population. We have pancreatic neuroendocrine tumor, GI neuroendocrine tumor, lung neuroendocrine tumor, functional, non-functional neuroendocrine tumors, and neuroendocrine tumors enrolled regardless of their somatostatin receptor expression levels. And benefits were seen across all subgroups. And what was shown at ASCO GI was that the benefit within those patients whose tumor originates from a GI origin, their benefits were consistent with the benefits seen in the overall population. So again, broad population, we think broadly applicable.

Thank you. One moment for our next question. And that will come from the line of Akash Tiwari with Jefferies. Your line is open.

Hi, this is Anastasia on for Akash. I just had a follow-up question on NETs. Specifically, for your 2025 guidance, just wondering how much of that comes from NETs versus NETs. other indications, if you could give us a sense of what, you know, near-term versus long-term growth might look like, that would be great. Thanks.

Hey, Anastasia. It's Chris. So, we haven't, as we said at J.P. Morgan and we've said today, we haven't put NET in our guidance. We'll do that at some point in the future when we understand what our final label is and also understand what the launch trajectory is, you know, post-approval.

Thank you. One moment for our next question. And that will come from the line of Gregory Renza with RBC Capital Markets. Your line is open.

Great. Good afternoon, Mike and team. Congrats on the progress. Thanks for taking my question. Mike, just in relation to that pursuit of expansion, getting more out of Cabo, just beyond NET, I just wanted to ask that you comment a bit on the pushes and pulls for a submission in, of course, prostate cancer and Contact Zero 2. I think it could just be to your confidence in that regulatory process, of course, that absence of OS and your plan on timing and getting the ducks in the row there. Thank you very much.

Yeah, thanks, Greg. As we talked about early in the year at AM, our only singular focus right now from a regulatory point of view is getting net coverage. Over the goal line, having that reviewed and approved, once we get that done, we will circle back to the prostate opportunity with contact 02, and at the appropriate time, give you updates on where that's going.

Thank you. One moment for our next question. And that will come from the line of Eva Fortia Verdejo with Wells Fargo. Your line is open.

Hi, this is Eva on for Derek. Thanks for taking our question. A quick one from us. So on Stellar 303, the patient population included is both RAS, wild-type, and mutant. But in the recent Stellar 001 readout, the patient population was just RAS, wild-type. So, you know, how should we be thinking about how the differences in patient population could impact the overall survival for Zanzibar plus epizole? Thanks.

Hi, this is Amy. Thanks for the question. So, I'm just going to step back a second to remind everybody what was the purpose of STELLAR-001, which was really to establish or evaluate whether or not there was a contribution of components when you added atezolizumab to zanzalitinib in patients with colorectal cancer. The rationale for choosing wild-type, RAS wild-type patients was because we observed higher responses in those patients, and of course, that's one metric of contribution of components. Suffice it to say that in that study, we actually saw the contribution of atezotuzanza across all three efficacy components, namely ORR, PFS, and OS. And so we're encouraged by those results as far as the read through to 303. You know, I think we're anticipating the events as Mike alluded to, the second half of 2025. We are encouraged by the results that we saw in Stellar 001. And that's really about all I can say with regard to how to pull that through.

Thank you. One moment for our next question. And that will come from the line of Jason Gerberry with Bank of America Securities. Your line is open.

Hey, guys. Thank you for taking my question. Mike, I just wanted to follow up on the comments earlier about the non-overlap and the $5 billion peak. I think the thing that I think investors struggle with is RCC is still a big percentage of the addressable patients in the kind of patient build. And then the comment about the non-overlap, I guess it suggests either that the novel agents added to an RCC combination are really what drives the incremental benefit or that you won't compare against CABO, which is one of the RCC standards of care? And I imagine the answer is we can't tell you much until second half when you and Merck disclose your trial designs, but anything you can offer just to help maybe investors get around that, I guess, that issue or that lack of understanding?

Yeah, thanks, Jason. Look, I would just... I'll just repeat in a more abbreviated fashion what I said to ASTICA. I think the way to look at this is looking at how we're running the pivotal trials for 303, 305, 304, 305, 311, and the two more trials that obviously we haven't talked about yet, so there's a little bit more information to come there. The main focus is the comparison into the standard of care that's being run in those pivotal trials. We think, and just to look forward in the RCC space, that RCC will look differently in 2030 and 2031 than it does in 2024 and 2025. You have to look at what's happening and the competitive nature of that indication, and true for all of oncology, to look forward to planned pivotal trials that you'll actually be able to then you know, frame what success looks like. So, I understand the easy part of comparing CABA to ZANSA, and we're certainly excited about how ZANSA looks with all the caveats of having a number of small single-arm and, in some cases, small randomized studies. The bottom line is you generate good comparative data by running the right pivotal trials where you compare against standard of care, And you compare efficacy and safety. And we're doing that. We have three going with Zanza right now. We'll have three more going this year. And we expect a second wave coming after that. And that's how you define, really, the next wave of standard of care, as you did with Cabo in the late teens and early 20s, as we'll do with Zanza going forward.

Thank you. One moment for our next question. And that will come from the line of Andy Shea with William Blair. Your line is open.

Well, thanks for taking my question. So the ADC modality is a core corporate focus. So I'm just curious about the learnings that you can leverage from the XB002 program to XB371 to ensure it's best in class. And more specifically, do they share the same antibody components?

Dana? Yeah, sure. Thanks for the question, Andy. This is Dana. Yeah, so XB002 was an anti-tissue factor targeting ADC with a microtubule targeting payload. XB371 uses the same antibody with a drug antibody ratio of 8 and a topoisomerase inhibitor drug payload. We're excited about how that antibody differentiates from other tissue factor antibodies because of the epitope that it binds to, not causing problems with blood clotting. And we remain excited about that potential differentiation factor. Most importantly, with 371, we're very excited about how it gives us the potential opportunity and move with a biologic, with an ADC, into colorectal cancer. As you know, Mike's talked many times in the past about how we're really focused on building a franchise in GI with Stellar 303, with Zanza, and colorectal, even with CAVO and NETS. So this gives us another opportunity to move into this indication and create a bit of a franchise with that ADC.

Thank you. One moment for our next question. And that will come from the line of Yaron Werber with TD Cowan. Your line is open.

Great. I have an interrelated question, Mike, or whoever wants to take it. For RCC, I mean, it sounds like the future is going to look different than now. So should we, and I know you don't want to say too much ahead of announcing the trial design, but should we assume there's going to be a ZANZA, Belsutifen, triplet combo going to first line? Is that sort of how you're thinking about it, maybe with IO? And then secondly, just for Stella 305, what's the go-no-go based on the phase two? What do you want to see then to progress into the phase three? Thank you.

Yeah, so I guess I would frame your follow-up question around RCC as I think the pharmaceutical biopharma community is, everybody's working to improve standard of care. going forward. I think that's how we help patients, and that's obviously how we, you know, move new molecules into the system, right? That's the goal across the board. So certainly there's nothing different about what our strategy is here with Zanza, right? We're using, you know, what we think is a best-in-class TKI with the appropriate combination partners to be able to compare against contemporaneous standards of care molecules, to be able to prove efficacy, improved efficacy and safety. So it's a standard process. But looking ahead, if you assume things are going to be the same five years ahead, then to be frank, we're all dropping the ball, right? Come on. That's the goal. The goal is to improve outcomes for patients. That's why we're here. So again, I don't want to get into the weeds or into the roots about what's going to happen with RCC. We will announce those trials at the appropriate time with Merck. But again, we're focused on improving standard of care for patients with cancer. We're doing it right now. The plan is with 303 in CRC, 304 in non-clear cell RCC, 305 in head and neck cancer, and many more to come after that. So stay tuned.

Thank you. One moment for our next question. And that will come from the line of Peter Lawson with Barclays. Your line is open.

Great. Thank you so much. Thanks for all the detail in taking that question. I guess maybe just around contacting to just if you'd give us an update on where that stands. I didn't hear it mentioned today. I know you talked about it at the beginning of the year.

Yeah, thanks, Peter. I think as I mentioned to Greg a few minutes ago, our main focus, our singular focus right now from a regulatory point of view is on cabinet and the net indication, getting that approved and moving that forward. Once that's secured, then we'll focus back on contact two and CRPC. Nothing more to add on that today.

Thank you. One moment for our next question. And that will come from the line of Steven Willie with Stifel. Your line is open.

Yeah, thanks for taking the question. Maybe just to follow up on the question of RAS mutational status in 303, can you just help us understand kind of what the expected distribution of wild type versus mutant is now expected to be in the upsized version of this trial? I know the first version, I believe, specified a primary efficacy endpoint that was in RAS wild type only. I think there was an enrollment cap that you had put in place for RAS mutants. So just wondering if you can comment on whether the upsizing now changes the expected distribution here of RAS status. Thank you.

All right. Thanks for the question, Stephen. You are right. We did modify the primary endpoint to focus more on patients without liver metastases, also we refer to as the non-liver met patient population. The rationale for that was because of publications demonstrating that the prognostic situation with those patients is much stronger than, say, for example, RAS or communication or wild type, and as well the data that we understand from others and that we have been following that IO therapy seems to do well, especially in patients without liver mets, which doesn't mean that it doesn't work in patients with liver mets. It's just most of the patients have been studied without them. So, we modified the study to really focus on the non-liver met versus the ITT patient population. You know, and right now, I can't give you what the breakdown is of the RAS mutational status to wild type in the study, but it will be, you know, when the data comes, you'll have that answer.

And Steve, I would refer you back to the Merck LEAPs. 2017 both presentation and paper when they broke out the RAS mutational status by at least by hazard ratio in their forest plot the mutant RAS population actually did better than the wild type population okay hazard ratio and And from that study was 0.76 for the mutants and 0.9 for the wild type. So, again, I think if people are focused on, you know, 30 patients from a CABO phase 1B or from 30 patients from a CABO IST, I mean, that was interesting to us. It certainly was interesting. hypothesis generating, but I think when the, you know, as the non-Liberman kind of story started to evolve and then LEAP 17 came out where Liberman's went the right way. In fact, the RAS mutants went the other way. That was very, very important for us to take into account. Again, that's a large, randomized, globally run pivotal trial. So it's really the gold standard from our point of view about guiding us on how to then evolve stellar 303.

Thank you. One moment for our next question. And that will come from the line of Ash Verma with UBS. Your line is open.

Great. Thanks for taking my question here. So for Zanzibar and CRC, with this ASCO-GI data in hand, I'm not trying to compare it to CABO, but if you look at the Zanzibar plus Atezo efficacy versus what we've seen with the Rigorafenib, Would this level of efficacy still allow you to get to your peak sales guidance, more broadly speaking? Thanks.

Thanks, Ash, for the question. So we're actually encouraged by the data that we saw. Again, the study design was really to demonstrate whether or not there was a contribution of components. which we clearly did demonstrate across all three efficacy endpoints. When you actually look at the outcomes of OS, say, for example, in the ITT of 11.7 months for Zanzitizo, that actually bodes well against what one might expect or what has been published in the literature with regorafenib, where the median overall survival is anywhere from 6.5 to 7.5 months. how that pulls through to 303 remains to be seen, as Mike has said, and as we have said, it requires a very large randomized phase three study that can generate a p-value that gives you some sense of truth. And the other thing I'll point out as well in the non-Livermet patient population, the median survivals ranging from 18 to 21 months also, I think, bodes well given that the Our CAD foundation published data from their data set that includes correct and recourse and a couple of phase two studies with TAS and RIGO as the control arm. And in the non-Livermet patient population, the median overall survival ranges from 12.1 to 12.9 months. And we know the median overall survival from Botval and IO combination in non-Livermets was about 20 months. So we're benchmarking well.

Thank you. One moment for our next question. And that will come from the line of Sudan Loganathan with Stevens. Your line is open.

Hi, good afternoon. Thanks for taking my question. I specifically want to ask about the seller programs, 303, 304, and 305. You know, what will be the driving force to prioritize one program over the others, you know, to bring to market first? Or does the balance sheet and the R&D guidance kind of include the potential of taking all three indications simultaneously, you know, submitting for regulatory approval if the data looks good and it's undeniable that you have that strategy to submit for approval. Thanks.

Yeah, thanks for the question. Yeah, the only gauge here is a p-value. If the trials work, obviously we would take those forward with, you know, great speed and focus. You know, we're in the game of running pivotal trials and then moving them forward from a regulatory point of view, and that's our business. So we've done that numerous times with CAVO and certainly plan on doing that again here if successful. So we're in the execution phase, but there's no gates, clearly no gates besides us having studies work.

Thank you. As a reminder, if you would like to ask a question, please press star 1-1. One moment for our next question. And that will come from the line of Chris Shibutani with Goldman Sachs. Your line is open.

Hi, this is Kevin on for Chris. Thanks for taking our questions. I just wanted to touch on the earlier stage pipeline. You mentioned that there should be a number of presentations this year. Just wanted to ask on the amount of data that we might see and the cadence of these updates. And then as you think about three new INDs coming in, how are you making go, no-go decisions as it relates to these programs? Thank you.

Dana?

Okay, so as Mike said in his prepared remarks, we're planning for presentations at scientific meetings. We don't typically give more information than that until the abstract is published, so I would just say stay tuned on those programs. We're excited about the data that we're planning to present to the community on those programs. And then regarding the early stage pipeline, You know, we follow what I would consider to be best practices in the industry, which is we follow a certain cadence of IND-enabling activities, including GLP toxicology. The assets pass all of the bars that are required to convince us, as well as investigators, that there is a good hypothesis to be tested. We then file the INDs and start the Phase I trials. So we are progressing on that track with all three of those assets, and we'll continue to make announcements as those INDs are accepted by the FDA, and we start executing those trials.

Thank you. At this time, there are no further questions, and so I will turn the call over to today's host, Susan Hubbard. Ms. Hubbard?

Thank you, Cherie, and thank you all for joining us today. We certainly welcome your follow-up calls with any additional questions you may have. Thank you.

This concludes today's program. Thank you all for participating. You may now disconnect.