Exelixis, Inc.

Good day, ladies and gentlemen, and welcome to the Exelixis First Quarter 2026 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, Mr. Andrew Peters, Senior Vice President of Strategy and Investor Relations. Please proceed.

Thank you, Cherie, and thank you all for joining us. for the Exalexis first quarter 2026 financial results conference call. Joining me on today's call are Mike Morrissey, our president and CEO, Chris Center, our chief financial officer, Dana Aftab, our executive vice president of research and development, and PJ Haley, our executive vice president of commercial, who will review our progress for the first quarter 2026 ended March 31st, 2026. 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, and government drug pricing policies and initiatives. Actual events or results could, of course, differ materially. We refer you to the documents 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, 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. 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. ExoLexus is off to a strong start in 2026 with meaningful progress across our discovery, development, and commercial activities. Our strategy has a singular focus to build a multi-franchise business in solid tumor oncology focused on GU and GI histologies based on the depth of the cabozantinib business potential breadth of the Zanzibar Intentive Opportunity and the scope of our early-stage pipeline. Key highlights for the quarter include, first, we saw continued strong performance of the Cabo Zantative business in the first quarter of 2026. Cabo Medics continued to grow in revenue, demand, and market share as the leading TKI for RCC and the market leader for neuroendocrine tumors in the oral second-line plus segment. Importantly, we expedited the build-out of our GI sales team in the first quarter to accelerate the growth of the Cabo Medics net opportunity before Zanza could come online for CRC later in 2026. First quarter of 2026, U.S. Cabo franchise net product revenues grew 8% year-over-year to $555 million compared to the first quarter of 2025. continuing its role as a worldwide leading TKI, global Cabo franchise net product revenues generated by Exalexis and its partners grew 12.5% year-over-year to $764 million in the first quarter of 2026. Chris and PJ will share our financial and commercial highlights in their prepared remarks. Second, ZANSA is in the pole position as our next potential oncology franchise opportunity. The NDA for the ZANSA-ATEZA combination and third-line plus CRC, based on the Stellar 303 data, is currently under review and is the top priority for the entire ExoLexus organization. The ZANSA development program is rapidly advancing with seven ongoing or soon-to-start pivotal trials, along with additional Phase II trials planned in prostate cancer and lung cancer. Dana will review the highlights for ZANSA and our extensive pipeline of early-stage assets in his prepared remarks. Third, the goal of our development effort is to establish ZANSA as the TKI of choice in the 2030s for RCC and other important indications that could surpass the impact of CABO in the 2020s. ZANSA already has a meaningful development footprint in RCC, with three ongoing phase three studies across multiple lines of therapy, underscoring both the breadth of our ambition and the confidence we and others have in this molecule. At the same time, as our experience with COSMIC 313 highlighted and was also recently seen with news from competitive trials, navigating the complexities of first-line RCC to improve upon existing regimens is a challenging endeavor at best, and requires careful selection of combination partners to improve efficacy parameters while managing tolerability and safety considerations. We remain committed to raising the bar in first-line RCC and continue to prioritize orthogonal MOAs to combine with ZANSA. In parallel, we seek to expand the breadth and depth of our ZANSA pivotal trial efforts, positioning ZANSA for durable leadership in RCC and other important tumor types. Fourth and finally, we remain committed to running the business at the highest level of efficiency as we advance our R&D priorities, and at the same time generate substantial free cash to invest in the pipeline, do the right targeted BD at the right price to access external sources of innovation, and to continue our share repurchase program, including an additional $750 million that was just authorized by the Exalexis board. So with that, see our press release issued an hour ago for our first quarter of 2026 financial results and an extensive list of key corporate milestones achieved in the quarter. And I'll now turn the call over to Chris. Thanks, Mike.

For the first quarter of 2026, the company reported total revenues of approximately $611 million, which included Cabo Zantative franchise net product revenues of $555 million. CaboMedics net product revenues were $552.8 million and included approximately $3.6 million in clinical trial sales. As a continued reminder, clinical trial sales have historically been choppy between quarters, and we expect this to continue into the future. Gross net for the Cabozantin franchise in the first quarter of 2026 was 30.2%, which is higher than the gross net we experienced in the fourth quarter of 2025. This increase in gross-to-net deductions in the first quarter of 2026 is primarily related to higher 340 volume, higher Medicare Part D discounts and rebates, and higher copay assistance when compared to the fourth quarter of 2025. Our Cobb Medics trade inventory was slightly lower at 2.1 weeks on hand at the end of the first quarter of 2026 when compared to the fourth quarter of 2025. Total revenues in the first quarter of 2026 also includes approximately $45.9 million in royalties earned from our partners, Ipsen and Takeda, on their sales of Cabozantinib. Our total operating expenses for the first quarter of 2026 were approximately $359 million, compared to $363 million in the fourth quarter of 2025. The sequential decrease in these operating expenses was primarily driven by lower clinical trial costs, offset by higher FTE-related costs and stock-based compensation expense. Provision for income taxes for the first quarter of 2026 was approximately $57.2 million, compared to a provision for income taxes of approximately $8.2 million for the fourth quarter of 2025. This increase in tax provision was related to certain items that were recognized in the fourth quarter of 2025. Company reported GAAP net income of approximately $210.5 million, or 81 cents per share basic and 79 cents per share diluted for the first quarter of 2026. The company also reported a non-GAAP net income of approximately $232.8 million, or 90 cents per share basic and 87 cents per share diluted. Non-GAAP net income excludes the impact of approximately $22.3 million of stock-based compensation expense net of the related income tax effect. Cash and marketable securities for the quarter ended March 31, 2026, was approximately $1.4 billion. During the first quarter of 2026, we repurchased approximately $430.8 million of the company's outstanding common stock, resulting in the retirement of approximately 10 million shares of the company's outstanding common stock at an average price per share of $42.99. As of the end of the first quarter 2026, we had approximately $159.4 million remaining under the $750 million stock repurchase plan authorized by the company's board in October 2025. We expect to complete the October 2025 stock repurchase plan this month. Additionally, in May 2026, the company's board authorized a new $750 million stock repurchase plan that expires on December 31, 2027. And finally, we are reiterating our full year 2026 financial guidance, which is detailed on slide 16 of our earnings presentation. And with that, I'll turn the call over to PJ.

Thank you, Chris. The CaboMedics business continued to grow in the first quarter of 2026. The team is executing at an extremely high level, with CaboMedics 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. Importantly, Q1 had the highest number of new patient starts in a quarter ever for Cabo Medix, representing strong momentum in the business. At the same time, Cabo Medix plus nivolumab had the highest quarterly first-line RCC market share to date, This is an exciting time for the team. With zanzalitinib on the horizon, we prepare to launch our next franchise molecule, which would also expand the ExoLyxis GI franchise. The prescription data in the oral TKI market basket of Cabo, Linvatinib, Exitinib, Sunitinib, and Pazopinib convey the strength of Cabo relative to the competition. Looking at the TRX comparison, of Q1 2025 to Q1 2026, Cabo Medics grew three share points from 44% to 47%. Additionally, Cabo Medics TRX volume grew 14% in Q1 2026 compared to Q1 2025, outpacing the growth rate market basket, which was 7% for the same period. Physicians are responding positively to the broad net label and the contemporary trial design perceive the efficacy and tolerability of CABO as favorable relative to other small molecule therapies in the space. Academic and community 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 the first quarter, we are pleased that Cabo Medics remains the market leader in the oral therapy segment. Additionally, our research indicates that there is opportunity to continue to grow market share, particularly in the community. For that reason, we expedited the expansion of our GI sales team in Q1, and the team was in the field providing greater reach into the community in order to continue to grow net market share for Cabo Medics. Our new representatives joined us with significant oncology sales experience, particularly colorectal cancer and GI oncology. Importantly, the expanded team will be able to gain valuable experience selling Cabo, before we turn our focus to the potential launch of Xansalitinib in colorectal cancer. As we're thinking about building on and expanding our GI franchise, we are thrilled with the results of STELLAR-303 and the PDUCA date set for later this year. Sending regulatory approval, we believe that these data would provide ExoLyxis with a compelling commercial opportunity in one of the big four tumors. Third-line plus CRC setting consists of approximately 23,000 patients in the U.S. and represents an overall market opportunity of approximately $1.5 billion in terms of contemporary pricing. 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 NETS. In neuroendocrine tumors, prescribers see CABO Medix 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 have been impacted across tumor types and settings. And with that, I will turn the call over to Dana.

Thanks, PJ. Our strategy in R&D continues to focus on developing ZANSA as a multidimensional solid tumor oncology franchise molecule. And as you'll hear in my upcoming remarks, we continue to be focused on maximizing our productivity with disciplined investment and high-value opportunities for ZANSA, as well as the rest of our portfolio. Today's update provides a little more clarity on the seven ongoing or soon-to-start pivotal studies for ZANZA, so my update today will be focused mostly on those trials, but I'll also spend some time on additional exploratory studies that we've designed to investigate ZANZA's potential in certain patients with prostate or lung tumors. Starting with our NDA for ZANZA plus Atezo and colorectal cancer, which is based on the results from the STELLAR-303 trial, our team has been highly engaged during the review process, And from our standpoint, the review has been proceeding on schedule toward the PDUFA date in early December. As a quick reminder, the trial has dual primary endpoints designed to assess overall survival, both in the broad intention to treat or ITT population, which includes patients both with and without liver metastases, as well as more specifically in the population of patients without liver metastases, which we refer to as the NLM patients or populations. The study met one of its dual primary endpoints, demonstrating a 20% reduction in the risk of death with the combination in the broad 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 continue to expect to have those top line results around the middle of this year, depending on event rates. The level of excitement here is really high right now about what a potential approval would mean for this large and underserved patient population. And as you heard from PJ, our preparations for launch are in full swing. So we'll be ready to go the moment we receive a positive decision. But as we've discussed since late last year, we believe there is significant additional franchise potential for ZANSA and colorectal cancer in an earlier stage of the disease. To realize that potential, our team has been highly focused on launching the STELLAR 316 trial, which will investigate ZANZA with and without an immune checkpoint inhibitor in patients with resected stage 2 or 3 colorectal cancer who, following definitive therapy, have tested positive for molecular residual disease, or MRD, and have no radiographic evidence of disease. 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 time frame. 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. So this represents a significant opportunity in the colorectal cancer landscape. As we've communicated in the past, MRD and Stellar 316 will be determined with the Signatera circulating tumor DNA test, with Natera as our diagnostic partner. Their database, built from testing thousands of patients each year, has been incredibly helpful to us in terms of prioritizing activation of clinical trial sites that are already known to have the highest cadence of testing and the highest numbers of eligible patients. We're quite pleased with the level of enthusiastic feedback on Stellar 316 that we've gotten from key opinion leaders and other stakeholders, and we are on track for initiating the trial around mid-year. Moving on to kidney cancer, ZANSA's target profile, including the TAM kinases, MET, and VEGF receptors, positions ZANSA for success given the known roles played by these kinases in kidney tumors. Stellar 304 is our first pivotal trial for ZANSA in kidney cancer. evaluating the combination of zanza plus nivolumab versus sunitinib in patients with locally advanced or metastatic non-clear cell renal cell carcinoma. The non-clear cell RCC space is underserved, with no positive readouts from a Phase III study specifically focused on these patients, despite them representing approximately a quarter of all RCC cases. If positive, Deller 304 could potentially establish the first standard of care based on a randomized control phase three trial for these patients. We completed enrollment last year and given current event rates, we now expect top line results from the study in the second half of 2026. And in positive, those results could lead to our second NDA filing for ZANZA. In terms of opportunities in the Clear Cell RCC space, Walgreens continues with regard to the two pivotal studies that Merck is running in Clear Cell RCC, evaluating ZANZA in combination with Belzudipine. LightSpark 033, which compares ZANZA plus BELZ versus CAVO as first-line therapy in patients who received anti-PD-1 or anti-PD-L1 therapy in the adjuvant setting, was initiated last year. In addition, Merck recently initiated LightSpark034, a global phase three pivotal trial evaluating ZANZA plus BELS versus BELS plus placebo in second or third line patients with advanced RCC who have progressed on or after both anti-PD-1 or L1 and VEGFR-TK therapies in sequence or in combination. We are certainly excited to see these phase three studies in clear cell RCC moving forward. And based on our franchise experience in the syndication, we believe there are other important opportunities to explore. As we've mentioned previously, we continue to have discussions with potential collaborators to investigate novel combinations pairing ZANSA with other modalities and orthogonal mechanisms when there is strong scientific rationale for the combination. 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 looking to advance novel combinations in the future that have significant potential to move the needle for clear cell RCC patients. We hope to give further updates on these activities in the future as we get closer to launching the trials. Moving on now to neuroendocrine tumors, Stellar 311 is our phase three trial evaluating ZANZA compared to Everolimus as an initial oral therapy in patients with pancreatic or extrapancreatic neuroendocrine tumors. That study was initiated last year and we have been quite pleased by the speed of enrollment in the trial. In fact, we are now far ahead of our initial enrollment projections. The sites and investigators are very enthusiastic about the trial given their growing experience with CABO and later Lyme disease and the opportunity presented by Stellar 311 to improve on the current treatment landscape in earlier lines, which hasn't seen anything new for over a decade. That enthusiasm appears to be driving the very strong momentum we're seeing in the trials. Another opportunity for ZANZA that we've been discussing since late last year is in meningioma, which is the most common primary central nervous system tumor, accounting for approximately 40% of cases. Most meningiomas are benign, slow-growing neoplasms. However, up to 22% will recur after primary therapy, which consists of surgery and radiation. Importantly, there are no approved systemic therapies for meningioma that's refractory to local therapies. So this represents a very high unmet need in neuro-oncology. Today, we announced that we have now initiated Stellar 201, our Phase II trial evaluating ZANZA in patients with recurrent meningioma or no longer responsive to or eligible for local therapies. The primary endpoint of the trial is objective response rate, with secondary efficacy endpoints including duration of response, progression-free survival, and overall survival. The trial will enroll up to 100 patients, and given the extremely high level of interest and enthusiasm for the trial among neuro-oncologists, we anticipate enrollment to be brisk. Pending favorable results, and given the absence of any approved systemic therapies in this setting, The STELLAR-201 trial represents an important opportunity for ZANSA to become the first systemic therapy that could improve outcomes for these patients. Today, we also announced two additional studies exploring ZANSA combinations in indications where significant unmet need exists. STELLAR-202 is a planned Phase II trial in squamous non-small cell lung cancer that will explore the addition of ZANSA to PEMBRO in the maintenance phase after induction with PEMBRO plus chemotherapy. Part of the rationale for this trial comes from data we obtained from CAVO plus ATESO in the CONTACT-01 trial, where the subgroup of non-small cell lung cancer patients with squamous histology appeared to derive substantial benefit from the combination compared to chemotherapy. This is an important opportunity given the relatively short PFS in the maintenance setting and the lack of any new approvals in the frontline squamous non-small cell lung cancer since Keynote 407 established the current standard of care with PEMBRO plus chemo. We're also planning an additional expansion cohort in the ongoing STELLAR-002 study to evaluate ZANSA in combination with docetaxel in patients with metastatic castration-resistant prostate cancer who have measurable disease. This is also based on initial observations with CAVO, where a small Phase II study showed favorable outcomes when combined with docetaxel in metastatic CRPC patients. This cohort in STLR002 is particularly meaningful because if ZANSA in combination with chemotherapy is shown to be safe and active, that could open up a number of opportunities across a range of solid tumors where chemo or potentially even ADCs carrying chemo payloads are standard of care. Our teams are super focused on launching these new studies soon, and we expect both to be initiated in the second half of this year. 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. And the phase one studies for these early molecules are progressing well. In terms of earlier stage development candidates, we are continuing to advance exciting new small molecule NADC 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 will wrap up here by thanking the entire ExoLexus team for their outstanding efforts in the first months of 2026. We think 2026 could be a potentially transformational year for the company, and everyone at Exalexis is working together to move the needle for cancer patients and continue building value for all our stakeholders. We are focused on growing the Cabo business, at the same time advancing Zanza as our second potential franchise opportunity, all while continuing to investigate our early stage pipeline. As always, I want to thank everyone at Exalexis for their individual and collective efforts. great teamwork, and positive energy as we work every day to exceed expectations 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 ExoLexus, and we're happy to now open the call for questions.

Thank you. To ask a question, you will need to press star 11 on your telephone. To withdraw your question, press star 11 again. Due to time restraints, we ask that you please limit yourself to one question.

Please stand by while we compile the Q&A roster.

And our first question will come from the line of Paul Choi with Goldman Sachs. Your line is open.

Oh, thank you. Good afternoon, and thanks for taking the question. My question is for Dana. In light of the recent miss from the LightSpark 012 study, can you maybe just comment on your thoughts on updated thoughts or learnings from that trial result for your Belzutivan plus Zanza combination development program, specifically LightSpark 033 and 034, and just any learnings or potential trial considerations that you've had in the wake of that data? Thank you very much for taking the question.

Sure. Thanks for the question, Paul. Yeah, so first of all, you know, our strategy with ZANZA is to really focus on creating the next franchise molecule in RCC and the top TKI combination therapy in clear cell RCC in the 2030s. So, you know, the results from LightSpark 011 are, you know, that was with a, sorry, with 012, that was a triplet of PEM-LEN plus BELS versus PEM-LEN. As Mike mentioned earlier, triplet therapy in clear cell renal cell carcinoma is not an easy game, and, you know, our strategy is really focused on trying to establish a standard of care that covers multiple possible outcomes based on trials that are going on now. So we have multiple shots on goal with LightSpark 033, 034. We have the Stellar 304 data coming out hopefully soon, and non-clear cell and renal cell carcinoma. And as I mentioned earlier, we're evaluating a number of other potential novel and innovative combinations to further explore the Clear Cell RCC space. So that includes molecules from our own early pipeline. If XB628, which is our novel and innovative bispecific with multiple IO arms on it pans out, that could be a very interesting combination to explore in these patients. It would be very innovative and nothing in that space has been explored so far. So as Mike said earlier, we have multiple shots on goal to really establish and drive the Zanza franchise into Clear Cell RCC in the future, especially focused on the 2030s, not on today, but on the 2030s.

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

Hi, team. Congrats on the quarter, and thanks so much for the question. Just two quick questions from us. One, if you could please provide some color on the contribution in renal cell carcinoma versus NET for CABO. And then second, I recall that CABO failed as a monotherapy in advanced unselected non-small cell lung cancer and also on OS in phase 3 for pancreatic, even though it showed a response in PFS. So you touched on some of the combo regimens that have shown early data, but could you maybe expand on the rationale for testing combo therapies in stellar 202 and 002. Thank you.

Dana, why don't you take that second question first? And I think she was talking about prostate cancer. So what's the rationale for going into phase two in non-small cell and then prostate cancer?

Sure. So, you know, as I mentioned, the data that support our hypothesis for testing xantholinib in patients with non-small cell lung cancer comes from the CONTACT-01 study, which I think you're referring to. So this is the phase three study evaluating cabozantinib plus atezolizumab versus docetaxel in a broad population of non-small cell lung cancer patients. So in that study, the subpopulation of patients with squamous histology actually did quite well, appeared to have a favorable benefit compared to the control arm in the study. For that reason, the STELLAR-202 trial is focused 100% on the squamous patient population with non-small cell lung cancer. In this population, the current standard of care is platinum-based chemotherapy plus pembrolizumab during induction, which is up to four cycles of chemotherapy or 12 weeks. And then they go on pembrolizumab maintenance. So we are looking to add zanzalitinib onto the maintenance arm of pembrolizumab. We've already shown that ZANZA can sensitize patients to benefit with IO in the STELLAR-303 trial, a population of colorectal cancer patients that have historically been refractory to treatment with IO. So we think this is a very rational exploration to pursue for these patients with squamous histology, non-small cell lung cancer, and high unmet need. In prostate cancer, similarly, there was a small Phase I study combining cobizantinib with docetaxel. So the phase three trials that failed were not combining cobizantinib with chemotherapy. In the small phase one, however, we saw very, I'd say, favorable outcomes in the patients that were treated in this small study. So based on the results from that, we believe there is rationale to pursue that combination in the phase one stellar OO2 trial. Once we get data showing safety and potentially activity of that combination, that opens up a lot of different avenues of exploration, either in castration-resistant prostate cancer, potentially in lung cancer, and potentially in other indications where either chemo or chemo-based therapies, including ADCs, might be standard of care.

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

Hi, thank you for taking my question. So my first one, I wanted to get your comments on the quantifiable metrics regarding Cabo sales in net and how the maybe sales team has grown over this time and how it will continue to. And then secondly, on Zanza, ahead of the CRC launch, what are some quantifiable metrics there as well that we can keep in mind ahead of the potential launch towards the end of this year. Thanks.

Great. Thanks.

PJ, want to take that one? Yeah, thanks for the question. You know, with regards to NET, we are really pleased with how the business is going. As I mentioned, you know, overall in the first quarter, we had our highest new patient starts ever for Cabo Medics in a quarter, so that's certainly a You know, a really strong sign of the health of the business now, and as those new patients start, you know, ultimately translate to refills going forward, puts us in a really good position. Our business and net is broad, as I mentioned in the prepared remarks, really across all segments and is viewed very favorably by physicians. Importantly, you know, we are the market leader in the Second Line Plus oral segment. And our research and feedback really indicate that we have opportunity to continue to grow, particularly in the community setting, which is why we expedited the build out of our GI sales force so we could really have that deeper reach into the community and drive further business there. I'm really pleased to say that, you know, as I mentioned, we brought in a very strong team with GI and CRC experience. in sales and we're really already seeing impact from that team. So we're very, very pleased with that. You know, importantly, you know, that team gets here and gets a chance to know the customers in the GI segment, gets experience selling Cabo and a TKI, which is fantastic. As we think about looking forward, you know, to the potential approval of ZANSA and CRC, which, as I mentioned, we're all really excited about. Our launch preparation is really in full swing, and the team is really focused on driving that forward. We're really excited to be able to optimize that launch and help patients with CRC. This is a really big and exciting opportunity for us in terms of the potential to be in one of the big four tumors of colorectal cancer, the third line plus setting, as I mentioned, is 23,000 patients. And as we look at that market in terms of contemporary pricing, that's a $1.5 billion opportunity. But really, the way we're thinking about Zanza is, you know, obviously that initial launch will be really important, but we're thinking about it in terms of franchises and, you know, how do we expand ultimately then the CRC franchise with an earlier study such as Stellar 316. And ultimately, how do we build it out in RCC, as Dana discussed, potentially, you know, in lung, meningioma, et cetera, with just so many exciting opportunities. So really looking forward to getting going on ZAMS.

One moment for our next question. And that will come from the line of Shawn Lamann with Morgan Stanley. Your line is open.

Hi, good afternoon. This is Catherine on for Shawn. Thank you for taking our question. We just had one on the updated Cellar-3 or 4 data readout timing. Could you provide a bit more color on whether the slower Vanik rule reflects better than expected disease control? Was it a mix of the enrolled histologies or other trial dynamics? And then as a quick follow-up, just given that the population is highly heterogeneous, how are you defining success against or across histologies? And are there specific subtypes where you believe the rationale is strongest here? Thanks so much.

Sure, thanks for the question, Catherine. So, regarding 304, again, this is our Phase III study comparing zanzolitinib combined with nivolumab versus sunitinib. And as such, it really is the first Phase III trial to address this high unmet need patient population. Currently, there is no level one evidence supporting a standard of care in these patients. So we see a huge opportunity here for the combination of Zanza plus Nevo. Regarding the slight change in timing for events, I really don't want to speculate on what's driving that. We're just in the late stages of collecting events. So as we mentioned, we expect to get those soon, sometime in the second half of the year.

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

Oh, great. Thanks for taking our question. So talking about 316 for a little bit, there's an adcom recently that kind of talks about a progression, definition of progression or change of therapy that's based on non-radiographic progression. And so for the adjuvant CRC study, I'm just curious about the back and forth with the FDA agreeing on an MRD positivity as a way to change therapy, just to educate us on what the dialogue was and then how you come to the conclusion that this is actually a regulatory approvable approach. Thank you.

Thanks, Andy. Dana, want to take that one?

Sure. Thanks for the question, Andy. So, you know, we've discussed the STELLAR 316 trial, I think, since December last year. We're super excited about this study because it really addresses a high unmet need population. This is the population of patients who are resected, stage 2 or 3 colorectal cancer, have completed definitive therapy, and now are in a watch and wait game. to wait and see if they develop late-stage disease. The Signatera test has shown in a number of different studies to very, with a high degree of accuracy, predict rapid progression of patients. So the patients who are positive for the test typically have a median disease-free survival of around six months. So it's a very high unmet need population. The trial has been well-designed with, I'd say, a large degree of input from key opinion leaders, other stakeholders, as well as the agency. And we're very, very confident in our design, and we're really excited to release more details as we get closer to launch. And when we do, you'll see a lot more design characteristics of the study, especially when it gets posted at clinicaltrials.gov. So just stay tuned for more information.

One moment for our next question. That will come from the line of Michael Schmidt with Guggenheim. Your line is open.

Hey, guys. Thanks for taking my question. I have a question on RCC and just wanted to understand the size of the opportunity for the LightSpark 033 study. What percentage of patients would be qualified for this? And then beyond 033 and 034, Are there any other studies you're considering for RCC specifically with ZANSA? Thanks so much.

Thanks, Michael. PJ? Yeah, thanks for the question. You know, with regards to, you know, LightSpark 033, and as we've talked about here, we're really thinking about RCC broadly as establishing ZANSA as a franchise in RCC and certainly beyond. You know, that opportunity, as you look at the first-line setting, can be, you know, approximately a quarter of patients, you know, coming off of adjuvant therapy, and obviously that can evolve as more and more patients are getting adjuvant therapy, but approximately a quarter of the first-line setting. But, you know, I think the important thing, too, is really doing multiple studies, as we've laid out in terms of LightSpark 33, 34, Stellar 304, kind of drawing off our experience from CAVO, how we did multiple studies in RCC to really establish ourselves as, you know, the leader, the leading TKI in the 20s here, and we're building towards our vision of establishing ZANZA as the leading TKI of the 30s. As Mike and Dana mentioned, we're looking at, you know, combinations with orthogonal MOAs and different approaches to continue to really raise the bar in the standard of care in the first line setting in RCC generally.

And one moment for our next question. And that will come from the line of Sylvan Turkin with Citizens. Your line is open.

Good afternoon and thanks for taking my question. I just want to ask a little bit broader around your strategy around resource allocation. You're running one of the broadest development strategies for an unapproved drug at this moment, and you even expanded it now. And obviously, you're sitting on a lot of data that we don't see, but that clearly makes you very excited on Zanza. How do you balance that broad strategy with buybacks and potential M&A, which hasn't happened yet? Thank you.

Yeah, Sylvan, thanks for the question. Chris, want to take that one?

Yeah, Sylvan, thanks for the question. So from a capital allocation perspective, and that's how we look at it, is how do we allocate capital against R&D? How do we allocate capital against BD opportunities? And how do we allocate capital against share repurchases? And we're a financially strong company. We have significant cash flows. We're prioritizing our R&D spend on a constant basis so that we're understanding what projects are kind of sticking their heads up and saying, fund us. And so we'll continue to do that. Andrew and Stefan and the team are continuing to look at BD opportunities. And we do have access to capital also. So we have a lot of things going on here that allows us to execute on all those three elements of R&D investments, BD investments, and share buyback. And, you know, from a share buyback perspective, we believe that ZANZ is a great opportunity and that, you know, that if that opportunity is not really being appreciated generally and we think we're undervalued, so we're going to continue to buy back shares.

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

Hey, guys. This is Chiang for Jason. Thanks for taking our question. And so my question is on Lysbac034. Can you contextualize the choice of using Balsutifan monotherapy as the control arm as opposed to, say, an alternative TKM monotherapy or perhaps even Balsutifan plus Venvima given the pending S&DA review there. And I also noticed that OS is listed as a dual primary endpoint. So would PFS alone be sufficient to support approval, or would you need an OS win there? So just, again, thinking about both likelihood of success and regulatory bar based on the recent LISPAC 011 data. Thanks so much.

Yeah, Dana, go ahead. Sure. So, you know, LightSpark 034 is Merck's study. And as you mentioned, it's evaluating ZANSA plus BELS versus BELS plus placebo in the second line plus setting in patients who have progressed both on an IO-based regimen and a VEGFR TKI regimen, either in sequence or in combination. So the dual primary endpoints are two different efficacy endpoints. In Clear Cell RCC, OS has really become a gold standard. So having two different efficacy endpoints in the trial typically requires both to hit, but it really depends on the data, right? It's always data dependent and the timing of when those results come in. Regarding the population, you know, this study as well as many other studies that are ongoing now or planned for the future really anticipate multiple potential treatment landscapes for patients. So this is really in the landscape of patients who are really going to be candidates for Belzodipan alone or Belzodipan in combination with a TKI. So these are, you know, typically, again, patients who have already progressed on a TKI-containing regimen and an IO-containing regimen. So that really should be an important opportunity, important unmet need when this trial reads out.

One moment for our next question. And that will come from the line of Leonid Timishev with RBC. Your line is open.

Hey, guys. Thanks for taking my question. I want to stick with the franchise approach by 2030 that you've been talking about. I wanted to focus on NETS and how you're thinking about the franchise there in the future. I mean, you're running 311, but are there any other combinations that you're looking at, especially as that treatment landscape evolves with radiopharmaceuticals, ADCs? I mean, how are you envisioning building out ZANs into the 2030s in NETS? Thanks.

Yeah, thanks for the question. Why don't we tag team this? PJ, why don't you go first, and then Dana can add some commentary. Okay.

Yeah, thanks for the question, Leonid. You know, with regards to kind of the way we're thinking about 311, I guess, in the marketplace, you know, as I mentioned, Cabo's off to a really strong start in terms of kind of the second line plus setting. And that study is designed specifically to go head-to-head with Everolimus as an active comparator, which is kind of a first in the setting. So really positioning... that patient population in the first or second line setting, so earlier lines of therapy, and obviously, you know, then a larger patient population and really, you know, potential to be an active comparator head-to-head. A lot of excitement around the study design, as Dana mentioned in his prepared remarks, and so we're excited about that ZANS opportunity.

Yeah, and then beyond that, I'd say that we are... I think we've mentioned this before. We're very committed to this patient population. We've seen how much benefit CABO is bringing to the table for these patients. We've seen the excitement around Stellar 311, so we're really focused on how else we can really address this patient population. So I think as we discussed at R&D Day, we're also looking at a number of other potential opportunities earlier in the discovery pipeline to either address specifically the neuroendocrine tumor patients who require treatment also with an SSTR2 agonist. These are mainly patients with functional tumors, but any other patients who express the receptor and are known to be potentially sensitive to that type of treatment. We're developing a small molecule that we hope to file an IND on later this year. That could be a novel approach. to offer in combination with Zanzibar. If the STELR 311 trial is successful, we might do that type of combination in the future. And then broadening out to other types of neuroendocrine carcinomas, this is namely tumors that express DLL3, so primarily small cell lung cancer, but a range of other neuroendocrine carcinomas that occur throughout the body and the GI tract. And in the prostate and that molecule, we presented some data at AACR this year, XB773, the DLL3-targeted ADC, that with a very novel format, it's a very small format, with a topoisomerase inhibitor payload that we think is differentiated versus the other competitive molecules that are in the space right now. And that molecule can be quite exciting once we generate some data. And if it does stand up and show some interesting activity, there we can also explore combinations with ZANZA. So we have multiple irons in the fire exploring this space across histologies in different patient populations.

One moment for our next question. Our next question will come from the line of Kalpit Patel with Wolf Research. Your line is open.

Yeah, hey, good afternoon and thanks for taking the questions. Maybe one on the LightSpark 012 trial. There was no benefit of the triplet there compared to the doublets in that first line setting. So I guess for your and Merck's strategy, would you ever entertain a triplet in that exact same first line setting? or what would that future study look like in CCRCC?

Go ahead. Yeah, I'll take the question. Thanks for the question. Yeah, so, you know, as you know, we are collaborating with Merck on LightSpark 033, which is evaluating Zanza plus bells in the frontline setting, and that's versus apazantinib. So, you know, slightly different hypothesis that's being addressed here. There's no IO in this combination because it's assuming that the patient is coming in after adjuvant, or it's requiring patients to come in after having been treated in the adjuvant setting with IO. So, you know, looking at other potential combinations beyond this, especially triplets, that requires a lot of very specific and focused scientific rationale. So, you know, we're not opposed to doing it. It just has to be the right molecule in the right setting. As I mentioned in my prepared remarks, We have been looking at a lot of orthogonal MOAs to pair with zanzalitinib in this space, as well as, you know, we're actually going to be investigating the combination of ZANZA plus our own novel bispecific IO in its phase one study. So, you know, we're pending more discussions and more data that we can generate in phase one, and we'll reveal or disclose more details about any of those trials as they come to fruition and get closer to launch.

One moment for our next question. And that will come from the line of Edser Darut with Barclays. Your line is open.

Hi, Luke. I'm Fred Sahura. Thanks for taking my question. First, how are you thinking about how you're planning to leverage the non-Livermet data from Stellar 303 given the December previous date? Are you going to update your NDA to include that data? And then it'd be interesting to hear your thoughts around the investigator-sponsored trial coming up at ASCO of Cabo Nevo in non-clear cell renal cell carcinoma and how to think about that data set relative to ZANZA and 304.

Dana, go ahead. Thanks for the question. Yes, regarding the stellar 303 trial, as I mentioned, we are on track to see those results of the non-liver metastasis subgroup, the primary endpoint that's focused on that subgroup, around mid-year this year. We're still on track for that. You know, regarding the data and sharing with the FDA, you know, we certainly plan to share those data as well as any other data that the agency might ask for as part of the ongoing review. And again, as I mentioned, from our standpoint, that review is progressing on schedule toward the PDUFA date in early December.

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

Oh, hi. Yeah, I wanted to just get the latest thoughts on TABO comparativeness in RCC. So just given there, we saw earlier the LIGHTSPAR 022 study that had a PFS positive. Do you think it's unlikely to show OS separation because there isn't enough alpha attributes to that analysis? Thanks.

PJ? Yeah, thanks for the question. You know, I think we're really pleased with where we are competitively in RCC. Generally, I wouldn't want to speculate on, you know, how other trials continue to read out their data. But what I'll say is, you know, kind of as we talked about earlier, building a franchise, we've done so many studies in RCC that we have strength of the business really in every segment. We saw this quarter the highest frontline market share for cabomedics plus nivolumab in the first-line setting, which we're very pleased with. And we continue to see strong momentum there in the first-line setting, given just sort of the breadth and depth of the data and also the experience that prescribers have using this combination now for so many years. So we see potential to continue growing in RCC, and particularly in the first-line settings.

At this time, there are no further questions, and so I will turn the call over to today's host, Andrew Peters. Mr. Peters?

Yeah, thank you, Cherie, 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. Thank you all again, and have a great rest of your week.

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