Exelixis Inc (EXEL) 2025 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Exelixis fourth quarter and fiscal year 2025 financial results conference call. My name is Tawanda, 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, Mr. Andrew Peters, Senior Vice President of Strategy and Investor Relations. Please proceed.

Thank you, Tawanda, and thank you all for joining us for the Exelixis fourth quarter and fiscal year 2025 financial results conference call. Joining me on today's call are Mike Morrissey, our President and CEO; Chris Senner, our Chief Financial Officer; Dana Aftab, our Executive Vice President, Research and Development; and PJ Haley, our Executive Vice President, Commercial, who will review our progress for the fourth quarter and fiscal year 2025 ended December 31, 2025.

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, potential growth opportunities in government drug pricing policies and initiatives. Actual events or results could of course differ materially. We refer you to the documents that we file from time to time with the securities and exchange commission, which under the heading risk factors, identify important factors that could cause actual results to differ materially from those expressed by the company verbally and in writing today, including without limitation, risk and uncertainties related to product commercial success, market competition, regulatory review and of approval processes, conducting clinical trials, compliance with applicable regulatory requirements, our dependence on collaboration partners and the level of cost associated with discovery, product development, business development, and commercialization activities.

With that, I'll turn the call over to Mike.

All right. Thank you, Andrew, and thanks to everyone for joining us on the call today. 2025 was a transformational year for Exelixis with strong growth across all components of our business. We expect to build on this momentum in 2026 and have already made significant progress during a very busy January.

Critically, and we'll emphasize this here and throughout the call, Exelixis has a singular focus to build a multi-franchise business in solid tumor oncology based on the foundation of cabozantinib, the potential of zanzalintinib and the depth of our early-stage pipeline. As outlined at our December R&D Day, our strategy to build a pipeline of franchises in solid tumor oncology covers three critical dimensions: products, tumor indications and modalities, and is based on current Exelixis leadership in GU oncology and our aspirational goal to expand our leadership into GI indications, with equal intensity and potential upside.

The Exelixis strategy for product, tumor and modality franchises provides the framework to drive both the growth of any overall market we choose to pursue and the potential to capture a greater share of the commercial opportunity with multiple entry points. Our operational model to establish, expand and entrench any given franchise highlights the potential value for all our stakeholders.

Importantly, the progress we have made over the last 12 months, as well as our expectations for 2026 and beyond, are well aligned with this franchise focused approach. With that context in place, we outlined important news and priorities to kick off 2026 and our corporate update in January at the JPMorgan Healthcare Conference. I won't reiterate everything here today, but just focus on the top highlights, including: first, we saw continued strong performance of the cabozantinib business in the fourth quarter and full-year 2025. CABOMETYX maintained its position as the leading TKI for RCC and the market leader for neuroendocrine tumors in the oral second-line plus segment.

Full-year 2025, US cabo franchise net product revenues grew 17% to approximately $2.12 billion compared to full year 2024. Fourth quarter 2025, US cabo franchise net product revenues grew 6% year over year to $547 million compared to the fourth quarter 2024. Continuing its role as a worldwide leading TKI, global cabo franchise net product revenues generated by Exelixis and its partners were approximately $754 million and $2.89 billion in the fourth quarter and full year 2025, respectively. Importantly, cabo's US net product revenues exceeded $100 million for the neuroendocrine tumor indication in 2025.

Second, we're excited to accelerate zanza as our next potential oncology franchise opportunity in 2026, with the recently announced acceptance of our NDA for the zanza-atezo combination in third-line plus CRC based upon the STELLAR-303 data. The entire organization is rallying around this important 2026 milestone, and we've taken decisive steps to fortify our commercial footprints to maximize the impact of potentially launching two drugs in different indications in successive years.

Notably, we've expedited the buildout of our GI sales team in January with a focus to accelerate the growth of the CABOMETYX neuroendocrine tumor opportunity before zanza could come online for CRC later in the year. We think this enhancement could be an important component of our growth narrative in the near term and speaks to the confidence we have in both cabo and zanza as we move into 2026.

Third, zanzalintinib is rapidly advancing as our next franchise opportunity with seven ongoing and soon-to-start pivot trials, along with a variety of important trial concepts under consideration as a potential next wave of pivotal trials. We continue to prioritize zanza, both as a monotherapy and in combinations, for existing and new indications as an expeditious path to a second Exelixis oncology franchise. Importantly, we're excited by the level of interest in new clinical collaborations for zanza from the JPM meeting that could expand the breadth and depth of our zanza pivotal trial efforts to potentially define new standards of care for patients with cancer.

Fourth, as we highlighted at our R&D Day in December, our Exelixis IND pipeline is full for the next several years, with potential first-in-class and/or best-in-class molecules, demonstrating differentiating activity based on extensive preclinical testing. All our efforts are focused on identifying the next clinical asset that we can move into full development as another potential Exelixis franchise opportunity.

Dana will summarize our status today at a high level, and I refer you back to the replay of our R&D Day to dive into the details for zanza and the rest of our pipeline.

Finally, business development activities continue to focus on late-stage assets in the GU and GI space. We're pursuing back-end loaded, pay-for-success transactions that fit into our oncology franchise framework as a top priority.

In terms of capital allocation, we're confident we have the balance sheet and expected free cash flows to advance our pipeline priorities, access new molecules from external sources when appropriate and continue our share repurchase program when we believe our shares are undervalued.

With that, please see our press release issued an hour ago for our fourth quarter and full year 2025 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 2025, the company reported total revenues of approximately $599 million, which included cabozantinib franchise net product revenues of $546.6 million. CABOMETYX net product revenues were $544.7 million. Gross-to-net for the cabozantinib franchise in the fourth-quarter 2025 was 28.5%, which is lower than the gross-to-net we experienced in the third quarter of 2025. This decrease in gross-to-net deductions in the fourth quarter of 2025 is primarily related to lower PHS and 340B volume when compared to the third quarter 2025.

Additionally, we estimate that our gross-to-net for the full year 2026 will be between 31% and 32%. As previously disclosed, Exelixis has been designated as a specified small manufacturer, which requires Exelixis to pay a 2% discount in 2026 on all Medicare Part D sales and is included in our gross-to-net estimate for the year.

Our CABOMETYX trade inventory was slightly higher at 2.2 weeks on hand at the end of the year when compared to the third quarter of 2025. Total revenues in the fourth quarter of 2025 also includes approximately $52.8 million in royalties earned from our partners, if to indicate on their sales of cabozantinib.

Our total operating expenses, excluding restructuring expenses for the fourth quarter of 2025, were approximately $363 million compared to $341 million in the third quarter of 2025. The sequential increase in these operating expenses was primarily driven by higher manufacturing costs for drug development candidates, NDA filing fees, personnel expenses and higher marketing expenses, offset by lower stock-based compensation in the fourth quarter of 2025.

Provision for income taxes for the fourth quarter of 2025 was approximately $8.2 million compared to a provision for income taxes of approximately $58.8 million for the third quarter of 2025. This decrease in tax provisions was related to items that were recognized in the fourth quarter of 2025.

The company reported GAAP net income of approximately $244.5 million, or $0.92 per share basic and $0.88 per share diluted for the fourth quarter of 2025. The company also reported non-GAAP net income of approximately $259.5 million, or $0.97 per share basic and $0.94 per share diluted. Non-GAAP net income excludes the impact of approximately $15 million of stock-based compensation expense net of the related income tax effect. Cash and marketable securities for the year ended December 31, 2025, was approximately $1.66 billion.

During fiscal year 2025, we repurchased $954 million of the company's outstanding common stock, resulting in the retirement of approximately 24 million shares of the company's outstanding common stock at an average price per share of $39.61. As of the end of fiscal year 2025, we had approximately $590 million remaining under the $750 million stock repurchase plan authorized by the company's Board in October 2025.

And finally, turning to our financial guidance for the full year 2026. We announced our 2026 financial guidance during the JPMorgan Conference in January, which is detailed on slide 19 of our earnings presentation.

And with that, I'll turn the call over to PJ.

Thank you, Chris. CABOMETYX business remained strong in the fourth quarter of 2025. The team continued to execute at an extremely high level, with CABOMETYX continuing to be the number one prescribed TKI in renal cell carcinoma, the number one TKI plus IO combination in first-line RCC and the number one oral agent in second-line plus neuroendocrine tumors. This is an exciting time for the team with zanzalintinib on the horizon as we prepare to launch our next franchise molecule, which would also expand the Exelixis GI franchise.

Prescription data in the oral TKI market basket of cabo, lenvatinib, axitinib, sunitinib, and pazopanib can make the strength of cabo relative to the competition. Looking at the TRx comparison of Q4 2024 to Q4 2025, CABOMETYX grew 3 share points from 43% to 46%. Importantly, CABOMETYX TRx volume grew 15% in Q4 2025 compared to Q4 2024, outpacing the growth rate of the market basket, which was 7% for the same period.

Physicians are responding positively to the broad NET label and the contemporary trial design and perceive the efficacy and tolerability of cabo as favorable relative to other small molecule therapies in the space. Prescribers are using cabo broadly across patient and tumor characteristics, including patients with neuroendocrine tumors arising in the pancreas, GI tract and lung, across all tumor grades, functional and SSTR status and those who have received prior treatment with LUTATHERA.

Turning to new patient market share for second-line plus neuroendocrine tumors in Q4. We're pleased that CABOMETYX remains the market leader in the oral therapy segment. And additionally, our research indicates that there is opportunity to continue to grow market share, particularly in the community.

As Mike highlighted, cabo 2025 revenue in neuroendocrine tumors exceeded $100 million. And the team is fully engaged on driving growth in this indication in 2026 with a strong focus on the community setting. For that reason, we are pleased that we have completed the expansion of our GI sales team, which will yield greater reach into the community in order to continue to grow net market share for CABOMETYX.

Our new representatives join us with significant oncology sales experience particularly in colorectal cancer and GI oncology. We are excited to have them hit the ground running.

Importantly, the expanded team will be able to gain valuable experience selling cabo before we turn our focus to the potential of zanzalintinib in colorectal cancer. We are thinking about building on and expanding our GI franchise. We are thrilled with the results of STELLAR-303 and a PDUFA date set for later this year. Pending the regulatory approval, we believe that these data will provide Exelixis with a compelling commercial opportunity in one of the big four tumors.

Our market research and advisory boards demonstrate positive feedback and excitement for the STELLAR-303 data. Physicians reiterate the significant unmet medical need for patients in the third-line plus CRC setting and are excited for the potential to have an ICI option available for the broader population of CRC patients.

In closing, we are pleased with the growth of the cabo business, both in RCC and NET. In neuroendocrine tumors, prescribers see CABOMETYX as a more favorable choice versus other previously approved generic small molecule therapies. Simultaneously, our internal team is in full launch preparation for zanza and the excitement around these efforts is palpable.

We look forward to the opportunity to launch the next Exelixis franchise later in the year to be able to help appropriate patients with colorectal cancer. Beyond STELLAR-303, we are enthusiastic about the significant development plan for zanza, which could position the zanza franchise to far exceed cabo in terms of the number of patients that could be impacted across tumor types and settings.

And with that, I will turn the call over to Dana.

Thanks, PJ. Our strategy in R&D is on building franchises in key solid tumor indications, and we continue to be focused on maximizing our productivity with disciplined investment in high-value opportunities for our portfolio. Zanza is clearly our next big franchise opportunity with seven ongoing or planned pivotal studies. So my update today will be focused mostly on zanza, but I'll also touch on our earlier-stage pipeline of small molecules and biotherapeutics.

As Mike mentioned earlier, the FDA accepted our new drug application submission for zanza with a PDUFA target action date of December 3 this year. The NDA is based on the results from the STELLAR-303 trial comparing the combination of zanza plus atezolizumab versus regorafenib in patients with non-microsatellite instability high colorectal cancer who had received multiple prior therapies. As a quick reminder, the trial has dual primary endpoints designed to assess survival outcomes, more specifically in the population of patients without liver metastases, which we refer to as the NLM patients or population; and more broadly in the intention to treat or ITT population, which includes patients both with and without liver metastases.

The study met one of its dual primary endpoints, demonstrating a 20% reduction in the risk of death with the combination in the broader ITT population at the final analysis, while data pertaining to the other dual primary endpoint of overall survival in the NLM population showed a trend in overall survival favoring the combination. The NLM data were immature at the data cutoff, and the trial has been proceeding to the planned final analysis for this endpoint, and we expect to have those top-line results around the middle of this year.

Needless to say, we are very excited about engaging with regulators on this first NDA for zanza in combination with atezo, which, if approved, could potentially become a new standard of care for CRC patients who have received multiple prior therapies. We believe that the STELLAR-303 results demonstrate clear clinical differentiation of zanza from other TKIs and IO combination partners investigated in this space and that zanza's differentiated mechanism of action, including inhibition of the TAM kinases and MET, is a key factor in this clinical differentiation and underscores zanza's franchise potential.

As a next step toward realizing that potential, our team is highly focused on investigating zanza in an earlier setting in patients with colorectal cancer. To that end, we're planning to initiate the STELLAR-316 trial this year in patients with colorectal cancer or a positive for molecular residual disease, or MRD, after completing definitive therapy.

By definitive therapy, we mean rectal cancer patients who have been treated with total neoadjuvant therapy followed by surgery or colon cancer patients who had surgery followed by adjuvant chemotherapy. About 20% of patients are MRD-positive following definitive therapy. And these patients typically have a poor prognosis with median disease-free survival times in the six- to eight-month timeframe. Critically, these patients have no therapeutic options that have been shown in a Phase III trial to prevent or delay metastatic progression of their disease. Thus, this represents a significant opportunity in the colorectal cancer landscape.

In STELLAR-316, MRD will be determined with the Signatera circulating tumor DNA test, and we are very excited to be working with Natera as our diagnostic partner in this endeavor. Their commercial test is very extensively utilized in this setting, and their database built from testing thousands of patients each year gives us incredible insight and clarity regarding patient demographics and outcomes.

Some of the primary hurdles in Phase III trial execution are around site performance and patient recruitment, but we now have information from our partner that should help us focus on prioritizing activation of clinical trial sites that are already known to have the highest cadence of testing and the highest numbers of eligible patients. Thus, once STELLAR-316 is initiated, around midyear, we expect enrollment to be quite brisk.

Moving on to other trials. STELLAR-201 is a signal arm Phase II trial designed to evaluate zanza in patients with recurrent meningioma, and we expect that trial to initiate around the middle of this year.

STELLAR-311 is our Phase III trial evaluating zanza compared to everolimus as an initial oral therapy in patients with neuroendocrine tumors. That study was initiated last year and is proceeding on schedule.

STELLAR-304 is our pivotal trial evaluating the combination of zanza plus nivolumab versus sunitinib in patients with locally advanced or metastatic non-clear cell renal cell carcinoma. We expect top-line results from STELLAR-304 around midyear, and if positive, those results could lead to our second NDA filing for zanza.

Finally, progress continues with regard to the Phase II umbrella study being conducted by Merck, in which the combination of zanza plus belzutifan is being evaluated in patients with previously treated metastatic RCC and two pivotal studies that Merck is running in clear cell RCC evaluate zanza in combination with belz. One of those pivotal studies is LITESPARK-033, which is comparing zanza plus belz versus cabo as frontline therapy for patients who received anti-PD-1 or anti-PD-L1 therapy in the adjuvant setting, and that study initiated in December last year. We will update you on the details of the other Phase III study as they become available.

Given the demonstrated clinical differentiation we've seen with zanza and its potential to be the TKI of choice for combinations with immunotherapies and other mechanisms of action, we're continuing to assess the landscape of additional opportunities for zanza development. To that end, we've engaged in discussions with potential collaborators on some exciting new combinations and we look forward to sharing more details of these opportunities as we get closer to launching the trials.

Now shifting to our early clinical pipeline. We have four molecules in this space that are currently in clinical development, namely XL309, XB010, XB628 and XB371. The Phase I studies for these early molecules are progressing well. In terms of earlier-stage development candidates, we are continuing to advance exciting new small molecule and ADC programs, and I look forward to sharing more details as these early pipeline programs advance.

Our strategy with the early pipeline is focused on identifying the next potential franchise molecules beyond cabo and zanza, so we will continue our approach of getting to go/no-go decisions quickly and efficiently, leveraging our expertise to pick the winners and ultimately maximize impact for patients.

So with that, I'll turn the call back over to Mike.

All right. Thanks, Dana. I'll wrap up here by thanking the entire Exelixis team for their outstanding efforts in 2025. As we reflect on the substantial progress we've made over the last 12 months, we importantly look forward to 2026 as a potentially transformational year for the company. We will continue to execute on all cylinders with cabozantinib while also preparing for what could be our second potential franchise with zanzalintinib, all while we continue to advance our early-stage pipeline.

As always, I want to commend everyone at Exelixis for their individual and collective efforts, urgency and focus as we strive to 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 Exelixis, and we're happy to now open the call for questions.

(Operator Instructions) Asthika Goonewardene, Truist.

So just a technical question here on -- as you launch zanza, how long will you be able to benefit from the small manufacturer discount? And if I can sneak a quick second one in, it’s nice to see the share repurchases step up in Q4. Just wondering if you can give any comments on the cadence of repurchases so far for the first six weeks of the new year? Thank you.

Yeah. Asthika, it's Mike. I will take the first question, and maybe Chris can take the second one. Again, don't want to get too far ahead of ourselves with zanza. We're early in the review cycle for the process. Obviously, the small manufacturer exemptions that we have are tied to having a single product that has the majority of our revenue, and we would think that would be the case for the foreseeable future.

I think the cutoff is around 20% for a second product to come into play, soI think we're okay there for a while. Obviously, it's all about the kinetics of any subsequent launch, so stay tuned on that, still very early days. I don't want to speculate on the timing for when that could be an issue, okay? Chris?

Thanks, Mike. So Asthika, from a share repurchase perspective, as Mike mentioned in his prepared remarks, we're going to continue to do share repurchases as long as we feel like we're undervalued and that continues today. We have $590 million left over on the most recent $750 million authorization from the Board, and our commitment is to complete that this year.

Paul Choi, Goldman Sachs.

Can you comment on recent 340B purchasing behavior and whether you expect that channel to increase. And as along with the Part D redesign, just sort of your views on how that could potentially also impact zanza as you commercialize that in '27?

Yeah, Chris?

So thanks, Paul. It's Chris. Yeah, from a 340B perspective, we've seen variability throughout 2025, and we're expecting variability throughout 2026, and that could have an impact on the gross-to-net just based on the fact that it's a heavily discounted segment of the business.

Yeah. On the Part D redesign, PJ, you want to address that?

In terms of zanza, obviously we'll be designing our channel to optimize results going forward there. Having all the experience we have from cabo and being in the market for a decade, we'll obviously look to customize that for sort of the current state of the business in the markets.

Silvan Tuerkcan, Citizens.

Thank you for the detail from STELLAR-316. I just have a big picture question here. How big do you think this population is since it's so early in colorectal cancer? And what's the rough timeline for readout here?

And additionally, are there any reference trials? I know that this design is very popular with immunotherapy, but for targeted therapies, I've not seen that yet. Thank you.

Sure. Thanks, Silvan, this is Dana. I'll take the question. With STELLAR-316, the population we're calculating is based on approximately 20% of the patients who have completed definitive therapy and are positive based on the ctDNA tests from Natera. The data that they have and that we've gleaned from public sources and presentations indicates an opportunity of 20,000 to 25,000 or so in that range.

Yaron Werber, TD Cowen.

Maybe a quick question on NET. It sounds like revenues were over $100 million for the year. In the past, we thought the opportunity can reach even $500 million to $600 million, and it was sort of more than 50% of the quarter-over-quarter growth in Q2. Can you maybe just help frame what is it going to take? Do you need to move it up to get a higher share? What’s the dynamic on the market?

And then secondly, just any update on when Merck will start the next study in combination with zanza. Thank you.

Yeah. PJ, can you take the NET question?

Yeah. Thanks for the question, Yaron. With regards to NET, we're really pleased with the start to the launch here, which I'll remind you of approval is just kind of the very end of March there at the end of Q1. As you mentioned, we're very happy to achieve the $100 million in NET revenue in 2025. It's still very early days in terms of the launch.

We're very pleased that we've become the number one oral therapy in the second-line plus neuroendocrine tumor segment. But our market research, as I mentioned, indicates that there's still plenty of room to grow there, and really, as we look at it, that's primarily in the community setting. Our uptake has been broad across all sort of clinical features of NET, which is great.

What’s exciting about having opportunity in the community setting is the fact that we've expedited and really now completed our expansion of our GI sales team to really put it on par with the size of our GU team. Gives us the ability to reach much further into the community and really do what we need to do to change behavior more broadly because what we see is physicians responding very favorably to the data and having positive experiences with the drug, so we just need to be in front of them so that they have the opportunity to use cabo for appropriate patients, so we're looking forward to that.

Akash Tewari, Jefferies.

Can you talk about why you and Merck chose to kind of run a trial like LITESPARK-033 in this post-adjuvant first-line RCC study versus what your team did with CHECKMATE-9ER when you went after PD-1 naive patients? And kind of what I'm trying to understand is really what percent of first-line RCC patients now are actually getting a PD-1 in an adjuvant setting? And how do you think that figure will really evolve as we approach the end of the decade?

And maybe just lastly, what profile do you think zanza plus belzutifan will need to show in a second-line plus setting to support running a trial in the same population as LITESPARK-001? Thank you.

Yeah. Akash, let me start, and I can pass it on to PJ and/or Dana to provide color commentary. So again, I think the way we look at the problem, and I would advise that you look at the problem is not so much on what's happening today, but what's going to be happening in the future. I think early to mid-30s, 2030s, we're really targeting having zanza a standard of care for RCC, right?

If you look at the cabo story, we have a dominant standard-of-care TKI for RCC in the 20s based upon all the data we've generated, and we aspire to do the same thing for zanza but fast forwarding years ahead to be able to understand how standard of care will evolve between now and then so that zanza can be a great player there.

So again, we've got three ongoing or planned pivotal trials so far with RCC. We're having a lot of very important discussions with other potential combination partners that I'll frame as having orthogonal MOAs that could, again, give us a lot more bang for the buck also in RCC that we're really excited about. I certainly look at it, and I recommend you to look at it, as this non-clear cell trial, the two Merck trials are really just the beginnings of building a franchise for RCC, where we can have a dominant position with zanza in the 2030s.

Andy Hsieh, William Blair.

So kind of going back to the previous question, maybe for PJ, do you see an increased utility of cabo monotherapy in the first-line setting just driven by the evolving dynamics in the IO usage, mostly in the adjuvant setting?

Yeah. Thanks for the question, Andy. What I'd say is we've always had a very reasonable utilization of cabo monotherapy in the first-line setting. If you kind of think back to the CABOSUN study, which we did was a cooperative group study that we got an indication based on in sort of single agent first-line utilization. So there's always been a role in a place for cabo in the first-line setting, and that really continues to be the case, particularly in terms of the monotherapy segment of that population.

Sean Laaman, Morgan Stanley.

Ahead of the non-liver met OS final analysis in mid-26, Mike, how do you anticipate positive data impacting your commercial strategy or communication with physicians?

Thanks for the question, Sean. That's a great one for PJ to answer. Over to you, PJ.

Yeah. Thanks for the question, Sean. I'd say first and foremost, obviously, the non-liver mets is a subset of the overall ITT population where we've been positive. So as we think about that, that's a big deal, and the liver mets patients in a sense were kind of the harder-to-treat segment.

We’re really excited about the data we have in hand in the sense that that's really going to help us move the needle pending approval for those patients, as I mentioned, that we see from our research, our advisory boards, where there's a significant unmet medical need and where the STELLAR-303 data is really being received positively. Obviously, we'll see what the non-liver mets data show when that comes.

And I think the way we think about it, that's just more opportunity to help us elucidate the benefit across the board in advanced third-line plus CRC. We just heard a lot of positives in terms of the data particularly when we think about the mechanism of action of the combination as well as the potential to have an immune checkpoint inhibitor available to a broader population outside of the MSI high population. That's really something we're hearing across the board from oncologists is important. And in fact, what we hear from them is literally almost all their patients are asking for an immune checkpoint inhibitor. So we think this will be really important for the treating physicians and their patients.

Michael Schmidt, Guggenheim.

This is Rosy on for Michael. I guess just, first of all, as we look ahead to the December PDUFA date for STELLAR-303, can you just comment on intereactions with the FDA to date and whether you currently anticipate an advisory come as part of the review process?

And then secondly, regarding your earlier-stage pipeline, how are you thinking about the cadence of initial data disclosures? Can you provide some color on how you're evaluating those early signals or making the go/no-go decision on advancing programs? Thank you.

Thanks for the question, Rosy. This is Dana. Regarding the STELLAR-303 NDA and interactions with the agency, I'll just reiterate, we're super excited about the acceptance of the NDA, and we're very actively engaging with the agency on the filing as is the norm in these types of activities. Regarding the non-liver mets data, those data are due in the middle of the year. Those data as well as any other data, including like the 120-day safety update, additional analyses or data cuts that the agency asked for, will be shared with the agency as part of the normal process.

All of that is going according to plan, and we're quite excited about our interactions. We're very positive on how things are proceeding, and we're working with the agency very actively, so we're happy.

Sudan Loganathan, Stephens.

First I wanted to ask, can you comment on any trials ongoing and potentially reading out this year that could challenge cabo in the second-line plus RCC setting?

And then secondly, how do trials such as that LITESPARK-033 and even the combo trial ARCUS is running with cabo in the post-IO setting help retain the lead share in RCC as we look into the remainder of 2026?

Okay. Sudan, thanks for the question. PJ, why don't you take that one on?

Yeah. Thanks for the question. With regards to ongoing trials, obviously, we're aware that there's data reading out at the upcoming GU ASCO meeting. We're following that very closely.

I guess the press release says it's positive for PFS. I would just remind you, and we heard this sort of very clearly from our KOL in our R&D Day event and sort of broadly across the board from KOLs and research that to really raise the bar in the standard of care in RCC at this point, overall survival is really critical to do that. So we'll see what the data are.

Any time you add more drugs into the mix, there's incremental toxicity, and you have to kind of see what the overall profile of the product is, but we're confident in cabo and our position in the marketplace and our team and the data. The data has ripened well as we've seen data such as CONTACT-03 from cabo, so we're confident in our position in RCC.

Leonid Timashev, RBC.

I just want to follow up on some of the RCC questions from Sudan and Yaron. I guess, with gross-to-net looking better than expected, and the NET launch being stronger than expected, how much growth are we expecting from RCC in 2026? Is that coming from new patient starts? Are there still segments of the population that are underutilizing cabo in RCC? Or is it more a more playing defense and maintaining share in 2026? Can you just maybe talk about that? Thanks.

Yeah, sure. PJ, you want to take that, and I'll provide some color commentary, too?

Yeah. Thanks for the question, Leonid. As I mentioned, we're very pleased with our position and the year we had in 2025 with a significant growth in both RCC and obviously, from the NET launch. So as we look forward, you obviously see from our guidance that we have significant growth we're expecting in 2026, and we really do see that coming from really both aspects of the franchise.

In terms of neuroendocrine tumors as well as RCC as we continue to compete in that space, we're doing so very well. And the first-line market is very much our focus, and we believe we can continue to get growth coming from those patients in the first-line setting.

Jason Gerberry, Bank of America.

My question is more of just a conceptual one because I know you can't really comment on potential zanza pricing, but as you kind of observe what we're seeing is maybe a trend in higher launch pricing in the last 12 months for cancer therapies, I'm just wondering maybe if you can speak to that as a trend. It seems like perhaps maybe sponsors are factoring in things like IRA and compensating for that and investors have taken notice as well of these higher launch prices. So I wonder if you can just comment at all in terms of what you're seeing from a trend perspective? Thanks.

Yeah. Thanks, Jason. I think you actually covered it pretty well in terms of the data and the facts out there. I wouldn't want to speculate why people are behaving in a certain way, but you certainly can and you did, which is fine. We'll certainly keep potential pricing opportunities for Exelixis drugs, certainly zanzalintinib, under our hat until the appropriate time. But I'm really glad that you highlighted some of the trends as they're going forward, which I think the way you frame it is probably a reasonable way to kind of put things in perspective, so thanks for doing that.

Etzer Darout, Barclays.

This is Luke on Etzer. For non-clear cell, can you give us some color around like what you expect the market size to be and what your expectations around outcomes relative to standard of care?

I mean, in your R&D slide, you list sunitinib or cabo/nivo or pembro as standard of care. Do you have any visibility as to what proportion of patients get those three regimens? And with that, do you have any idea as to how much cabo revenue is currently attributable to non-clear cell?

PJ?

Yes. Thanks for the question, Lucas. I guess to start with, as we've said before, non-clear cell RCC is approximately 20% of renal cell carcinoma. And I guess a little perspective on the non-clear cell portion of RCC today, just like sort of the entire market of renal cell carcinoma, it's very competitive. You mentioned a number of regimens therapies that can be used there and are used there.

And just like there's hotly contested sort of the broader RCC, non-clear cell is the same. We believe that that sets us up really well in terms of 304 should we have a positive outcome there, because this is very much an underserved and understudied part of the population in terms of the non-clear cell patients. And 304 is really the first pivotal registrational Phase III study looking at this population.

So as you think about that, that becomes very significant in terms of the ability to really identify those patients in a specific benefit in that population.

So what we hear from KOLs is that will be very important in terms of the potential benefit for those patients and elucidating it. Furthermore, it's really exciting to us to have a potential entry point, obviously, for zanza into RCC. This is obviously our major franchise in terms of cabo and something we look forward to expanding on. And as Mike kind of alluded to earlier, we view this as just the beginning for zanza and RCC. We've got the Merck studies.

And as has been mentioned here today, many other potential opportunities we're looking at in combination partners. So kind of like we did in cabo in cutting the landscape with multiple clinical trial data readouts to really become the standard there. That's our view and approach for zanza and RCC as well.

Stephen Willey, Stifel.

I think you have previously intimated that you're conducting some additional work on zanza dose optimization. Curious if this data is going to be used to inform a starting zanza dose for STELLAR-316 and whether you would potentially expect to submit any of this additional dose optimization data as part of the ongoing NDA review? Thanks.

Sure. This is Dana, Stephen. Thanks for the question. Our approach is always to use the optimal dose in any pivotal study that's appropriate to each individual setting, which might be influenced by a number of factors, including stage of disease, potential combination partner, expected duration of treatment, et cetera. We take that approach with every study, and we'll continue to do so for the foreseeable future, certainly for STELLAR-316.

With STELLAR-303, as we mentioned during an event at ESMO, we do have data that we feel are quite strong supporting contribution of components and shared those data with the agency as part of the review.

Jay Olson, Oppenheimer.

As you plan for the commercialization of zanza, since this would be the first approval, how should we think about the launch trajectory in CRC? And since it's also a new indication for atezo, is there any work that Roche is doing that you're aware of to ensure a rapid uptake for this innovative combination regimen? Thank you.

Yeah. Thanks for the question, Jay. What I'd say in terms of what we're expecting in the marketplace, as I mentioned, we see a significant unmet medical need here, and it's very exciting to launch a new product and a new combination in the marketplace. As I mentioned, we've been working very hard on it, and folks are very excited about that.

I don't want to sort of get ahead of any specific forecasts or guidance with regards to that, but what I would say is that the market here is fragmented. We've talked about that before. In the third-line plus CRC market, you see approximately a third TKIs, you see about a third lonsurf/bev in terms of the SUNLIGHT regimen. And the remaining third is either chemo or sort of targeted therapies directed at specific biomarker-driven populations. When you see a fragmented market like that, there's certainly really opportunity to have significant impact, so that's certainly exciting.

As I mentioned previously, significant overall survival benefit over an active standard of care, as well as the opportunity to have immunotherapy for this broader patient population, have been resonating really well with prescribers in our market research. We’re excited to get there. We are devoting every sort of appropriate resource to this, so we're fully ready to go on the first day of a potential launch.

Eva Fortea-Verdejo, Wells Fargo.

On the STELLAR-304 readout, should we be expecting similar to what we saw last year with 303 where we got a press release to limited data and then followed up at a medical meeting with the full-data release? If that's the case, what would be a good target meeting? Is this like a second-half 2026 event?

And then the second question, just within the ASCO-GU topic, should we expect a significant update from zanza? We see a few titles in the program, but perhaps you could comment on these? Thanks.

Thanks for the question, Eva. It's Mike. In terms of 304 top-line results, how we'll communicate that, stay tuned on that. We look at every opportunity as a separate opportunity based upon what's happening, the data, the timing, other meetings, et cetera. As we get closer to having top-line results, we figure that out and then obviously communicate that to you guys in a very compliant fashion.

On ASCO-GU, I'm not sure we have a lot to offer on that right now. The titles are out, so I would look at those carefully and we'll see you there, for sure.

Ash Verma, UBS.

On Q4, looking at the strong net growth that you saw and also some gross-to-net improvement quarter over quarter as well, did RCC grow for cabo? That’s the first question.

And then secondly, for this upcoming LITESPARK-011 data at the end of February, so OS is still maturing we know that, but in terms of median PFS, what type of delta versus the cabo prior 10 months can have a near-term impact on your RCC sales? Thanks.

PJ?

Yeah. Thanks for the question. As I mentioned in my prepared remarks, we're really pleased with the business and the momentum. As we looked at the quarter, we had strong growth in terms of 15% TRx growth year over year, which we're very pleased with. That’s clearly was driven both by RCC and NET.

So again, we're excited about that, as I alluded to earlier, we expect to continue to grow both of the franchises this year as is indicated by our guidance.

Kalpit Patel, Wolfe Research.

For STELLAR-304, I know you have overall survival as a secondary endpoint. But with the recent FDA draft guidance on using OS, when it seems most reasonable, do you anticipate the need to show a benefit in OS to receive a full approval?

And then also for that same trial, you have sunitinib as the control arm, but do you think, at least on a cross-trial basis, you need to look better than what cabo plus nivo delivers historically in the setting?

PJ, can you take a shot at that?

Yeah. So I'll talk about what we need to see in the marketplace. It's competitive in terms of non-clear cell just as it is in the overall RCC market. Again, though, as we dial into the specific patient population of non-clear cell RCC, that's obviously a separate and distinct population from the broader Phase III studies for all the regimens on the market today, including cabo/nivo. We’ll have to be very careful not to mix the data in terms of very different patient populations. So that said, as I mentioned earlier, we are certainly excited about a specific Phase III trial, which is the only one studying this underserved and understudied population in terms of non-clear cell RCC, and having positive results, we believe, will be very impactful for the marketplace.

Thank you. Ladies and gentlemen, at this time, there are no further questions. And so I will turn the call over to today's host, Andrew Peters. Mr. Peters?

Thank you, Towanda, and thank you all for joining us today. We welcome your follow-up calls with any additional questions you may have that we were unable to address during today's call. Have a great rest of the week, everyone.

Ladies and gentlemen, that concludes today's conference call. Thank you for your participation. You may now disconnect.