Exelixis, Inc.

Good day, ladies and gentlemen, and welcome to the Exelixis second quarter 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, Ms. Susan Hubbard, Executive Vice President of Public Affairs and Investor Relations. Please proceed.

Thank you, Tawanda, and thank you all for joining us for the Exalexis Second Quarter 2025 Financial Results Conference Call. Joining me on today's call are Mike Morrissey, our President and CEO, Chris Senner, our Chief Financial Officer, PJ Haley, our Executive Vice President of Commercial, Amy Peterson, our Chief Medical Officer, and Dana Aftab, our Chief Scientific Officer, who will review our progress for the second quarter 2025 and in June 30th, 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, 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 SEC, which under the heading Risk Factors identify important factors that can cause actual results to differ materially from those expressed by the company verbally and in writing today, including without limitations, risks and uncertainties related to product commercial success, market competition, regulatory review and approval processes, conducting clinical trials, compliance with applicable regulatory requirements, our dependence on collaboration partners, and the level of costs associated with discovery, product development, business development, and commercialization activities. And with that, I will turn the call over to Mike.

All right, thank you, Susan, and thanks to everyone for joining us on the call today. XLS has had a strong second quarter, accelerating our progress and building momentum across all components of our business. Thriving growth of the Cobbler's Antidote franchise, now catalyzed by the early stage of a successful net launch, is our top priority while we execute on our R&D strategy to build a multi-compound, multi-franchise oncology business. All corporate activities are aligned on a single focus to improve the standard of care for patients with cancer. The magnitude of our future success will be determined by increasing the number of cancer patients we seek to serve and ultimately the impact we have on their disease with current and future Exalexis medicines. By driving for success across all components of our business, we hope to solidify our leadership in oncology drug discovery, development, and commercialization through intensity, innovation, and collaboration. Key highlights for the second quarter include, first, the robust performance of the Cabo Zantitib U.S. business, the strong growth in demand and revenue from our commercial activities. Cabo Zantitib continues to build on its leadership position as the leading TKI for RCC. Second quarter 2025, U.S. CAVO franchise net product revenues grew 19% year-over-year to $520 million compared to $438 million in the second quarter of 2024. CAVO's second quarter growth is noteworthy because it relates solely to commercial demand with negligible benefit from clinical trial sales and significant gross-to-net headwinds. Importantly, We saw brisk full quarter sales for the recently approved net indications and already built a leading share in the oral second line plus net segment, which contributed to approximately 4% of our second quarter 2025 net product revenue. PJ will provide more information and commentary about our second quarter franchise performance and encouraging dynamics of the net launch in his prepared remarks. And just last Thursday, our partner Ipsen received approval for NET from the European Commission, and revenues from this important new indication, as it rolls out across Europe, will add to our royalty stream. We will continue to evaluate further updates to our 2025 financial guidance as we build momentum on the NET launch and gain further clarity on additional revenue opportunities for the second half of 2025. Second, as outlined previously, vanzalitinib is rapidly advancing as our next oncology franchise opportunity and the subject of numerous ongoing and soon-to-start pivotal trials. We're pleased with the positive top-line results from Stellar 303 and CRC and look forward to engaging with regulators with the intent of filing for approval in this indication as quickly as possible. Stellar 304 and non-clear cell RCC is fully enrolled and continues to progress with top-line results expected in the first half of 2026, pending event rates. Based on evaluation of the data from CELTA-305 in head and neck cancer and the competition in this indication, we made the decision to not advance this trial into phase three. This decision was further supported by our assessment of the commercial opportunity of new ZANSA indications on the horizon that we believe have a higher probability of success little to no competition, and potentially an approximate threefold greater commercial value than the Stellar 305 opportunity. As we've highlighted previously, we stand ready to make tough, decisive capital allocation decisions based on clinical and competitive data and in-depth financial analysis. We're doing it now for Stellar 305, and you can expect the same level of rigor from us and all in the future across all components of the business. we continue to prioritize existing and new ZANZA indications as the most promising path to a second ExoLexus oncology franchise that we believe can eclipse the size, scope, and impact of our Cabo Zantative franchise. Third, the ExoLexus early stage pipeline is advancing quickly with a range of new and potentially differentiated biologics and small molecules heading into and through early clinical evaluation. As I highlighted last quarter, We're not looking to just build a big pipeline, but carefully and quickly identify the winners for advancement into full development as top investment priorities. Early evaluation of XL309 and XB010 continue to advance quickly, and we're pleased to have the bispecific XB628 and our second-generation tissue factor-targeting ADC, XB371, moving into the clinic. Finally, we remain committed to carefully managing capital allocation while we advance our R&D and commercial priorities. Our balance sheet and expected free cash flow provide us with the opportunity to advance our pipeline priorities, access new high conviction assets, and continue to repurchase shares when we believe they are undervalued. Business development activities continue in earnest, and we're focused on doing the right deals for the right assets at the right valuation. So with that, please see our press release issued an hour ago for our second quarter 2025 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 second quarter 2025, the company reported total revenues of approximately $568 million, which included Cabo's Antidote franchise net product revenues of $520 million. CaboMedic's net product revenues were $518 million and included approximately $600,000 in clinical trial sales, which is significantly lower than the $12 million of clinical trial sales we had in the first quarter of 2025. As a continued reminder, clinical trial sales have historically been choppy between quarters, and we expect this to continue into the future. Gross-to-net for the Cabozantin franchise in the second quarter of 2025 was 30.2%. which is higher than the gross net we experienced in the first quarter of 2025. This increase in gross net deductions in the second quarter of 2025 is primarily related to higher 340B volume in the quarter. Over the past several quarters, we have experienced a continued increase in the percentage of our business that is related to 340B volume, which is now over 24% of our total volume, which when compared to the second quarter of 2024 is four percentage points higher. Trade inventory at the end of the second quarter of 2025 was approximately 2.2 weeks on hand, which was higher when compared to the first quarter of 2025. The increase in trade inventory weeks on hand was partially due to the timing of the July 4th holiday week, which had lower volume than the preceding four weeks. Total revenues also included approximately $48.2 million in collaboration revenues. which includes approximately $43.4 million in royalties earned from our partners, Ipsen and Takeda, on their sales of Cabozantib in their respective territories. Our total operating expenses for the second quarter of 2025 were $355 million, compared to $369 million in the first quarter of 2025. The sequential decline in these operating expenses was primarily driven by lower manufacturing costs for drug development candidates, lower clinical trial costs, and lower general and administrative costs. Provision for income taxes for the second quarter of 2025 was approximately $45.6 million, compared to a provision for income taxes of approximately $46.1 million for the first quarter of 2025. Additionally, the One Big Beautiful Bill Act was signed into law on July 4th, 2025, which, among other provisions, permanently repealed the requirement to capitalize domestic R&D expenses for federal income tax purposes for taxable years beginning after December 31, 2024, and allows for the accelerated deduction of any remaining unamortized domestic R&D expenditures. Foreign R&D expenditures are still required to be capitalized and amortized ratably over 15 years. The federal cash tax benefit for previously unamortized domestic R&D expenditures is estimated at $147 million with no corresponding impact to the federal income tax provision. The company reported gap net income of approximately $184.8 million, or $0.68 per share basic and $0.65 per share diluted for the second quarter of 2025. The company also reported non-gap net income of approximately $212.6 million, or $0.78 per share basic and $0.75 per share diluted. Non-gap net income excludes the impact of approximately $28 million of stock-based compensation expense net of the related income tax effect. Cash and marketable securities for the quarter ended June 30, 2025, were approximately $1.4 billion. During the second quarter, 2025, we repurchased approximately $302 million of the company's shares, resulting in the retirement of approximately $7.5 million of the company's shares at an average price per share of $40.10. As of the end of the second quarter 2025, we had approximately $204 million remaining under the $500 million stock repurchase plan authorized by the company's board in February 2025. And finally, we will continue to evaluate further updates to our 2025 financial guidance as we build momentum on the net launch and gain further clarity on additional revenue opportunities for the second half of 2025. We are reiterating our full year 2025 financial guidance, which is detailed on slide 14 of our earnings presentation. And with that, I'll turn the call over to PJ. Thank you, Chris.

The Cabo Medics business was very strong in the second quarter of 2025, and importantly, the launch in neuroendocrine tumors is off to a great start. Cabo continued to show growth in terms of revenue, demand, and new patient starts, and notably, perform well relative to the competition. The team continued to execute at an extremely high level, with CaboMedix continuing to be the number one prescribed TKI in renal cell carcinoma, as well as the number one TKI plus IO combination in first-line RCC. The commercial team is delivering on the launch in nets with great urgency, with the goal to rapidly establish CaboMedix as a small molecule market leader in the net space. We are pleased that prescribers are responding positively to the data and are excited to have a new therapy available to unmet need in neuroendocrine tumors as we look to build on the strong momentum of the CaboMedx business. The prescription data in the oral TKI market basket of Cabo, Livatinib, Exitinib, Sunitinib, and Pazopinib convey the strength of Cabo relative to the competition. Looking at the TRX comparison of Q2 2024 to Q2 2025, Cabo Medics grew four share points from 41% to 45%. Cabo Medics TRX volume grew 18% in this time period, outpacing the growth rate of the market by 10 percentage points. Importantly, the Cabo Medics RCC business remains strong and continues to grow. The new indications for previously treated NETs are providing our experienced sales team great access to customers. We're able to discuss both the cabinet data as well as the RCC Checkmate 9ER five-year follow-up data with relevant physicians. These 9ER data presented at GU-ASCO in February resonate with prescribers in the RCC space and help our team continue to drive differentiation from the competition in the first line RCC market. Turning to neuroendocrine tumors, we are thrilled that the launch is off to such a strong start. The team has been working tirelessly to execute tactics across channels and customer segments since approval, including personal promotion, targeted non-personal digital and social media tactics, peer-to-peer education, a comprehensive patient support program, as well as patient and allied healthcare professional education. The team is working to rapidly establish CaboMedix as a new standard of care in second-line plus net patients. Our market research and feedback from customers demonstrate that prescribers are excited for a new treatment option for their neuroendocrine tumor patients, the first broadly applicable new oral small molecule therapy in nine years. Physicians are responding favorably to the broad net label and the contemporary trial design and perceive the efficacy and tolerability of the CAVO data as favorable relative to other small molecule therapies in the space. Prescribers envision using CAVO 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. As we look at early utilization in our market research, we are pleased to see the positive perception data from prescribers. We're seeing rapid uptake of CaboMedix in both second and third line nets across all the relevant patient and tumor characteristics. Encouragingly, this uptake is similar in both academic and community settings. The launch in NETS is both expanding our prescriber base and increasing prescriptions for legacy CABO prescribers. Turning to the new patient market share for Second Line Plus neuroendocrine tumors in Q2, we are pleased that CABO Medix has rapidly become the market leader in the segment. approximately 35% new patient share for oral therapies. This share is very encouraging so early in the launch as Cabo Medix was approved on March 26th. Hence, we believe that new patient share should continue to increase and importantly, patients will have the opportunity to benefit from being prescribed this therapy. Over time, as more patients start therapy with Cabo and receive refills, We believe demand will continue to increase. Neuroendocrine demand contributed just over 4% of total demand for CABO and Q2, and we expect that contribution to increase going forward. Finally, the second quarter market research indicated that CABO Medix was viewed as the best in class oral therapy in neuroendocrine tumors. We are pleased that this perception was achieved so rapidly after the approval. This perception is typically A leading indicator of prescribing behavior gives us confidence that CaboMedic's new patient market share will continue to increase in coming quarters. This research finding aligns well with the anecdotal feedback our experienced sales team is receiving from their customers, many of whom are saying they will prescribe Cabo for their net patients once they progress and need a different systemic therapy. Taken together, The data and customer feedback give us a high degree of confidence in the growth of CABO medics in neuroendocrine tumors. As this can be a more indolent tumor type, new patient starts for CABO are governed by patients progressing on their current therapy. In closing, we are excited by this opportunity to serve net patients, and our enthusiasm is matched by physicians' excitement to have a new and effective option for their patients. In general, prescribers see CaboMedix as a more favorable choice versus other previously approved small molecule therapies. Additionally, the competition in the oral segment of the net market are generic therapies, which puts CaboMedix at a significant advantage with a full commercial organization energized to support the launch. All of this taken together drives our conviction that the net market will be a substantial opportunity for the CaboMedix business. And with that, I will turn the call over to Amy.

Thanks, TJ. Starting first with STELLAR-303, on June 22nd, we announced positive top-line results in which the combination of zanzalitinib plus atezolizumab demonstrated a statistically significant improvement in overall survival versus rigorapinib in the intent-to-treat or ITT population. As a reminder, STELLAR-303 is our phase three study comparing zanzalitinib plus atezolizumab to redurapidib in patients who have received multiple prior therapies for their advanced colorectal cancer. The trial has dual primary endpoints designed to assess survival outcomes more broadly in the ITT population and more specifically in the population of patients without liver metastases referred to as MLM. Secondary endpoints of STELR-303 include progression-free survival in the ITT and NLM subgroup of patients, as well as overall survival and progression-free survival in the subgroup of patients with liver metastases. These top-line results represent the final OS analysis in the ITT, and the trial will proceed to the planned final analysis of the other dual primary endpoint of OS in the NLM patient population the timing of which is event driven. It's worth highlighting that this is the first IOTKI combination to show a statistically significant survival benefit in a broad population and against an active standard of care control arm. We plan to discuss these positive data with regulators with the intention to file a new drug application. We also look forward to sharing these results at an upcoming medical conference and will be more specific when abstract titles become available. Stellar 304 is our pivotal study evaluating the combination of zanzalitinib plus nivalumab versus sunitinib in patients who have not yet received systemic therapy for their locally advanced or metastatic non-clear cell RCC. Based on the current event rate, we are now anticipating top-line results in the first half of 2026. So let's go next to Stellar 305, our Phase 2-3 study comparing zanzalitinib plus pembrolizumab to placebo plus pembrolizumab in patients who have not yet received systemic treatment for their advanced PD-L1-expressing squamous cell carcinoma of the head and neck. As Mike said in his opening remarks, we have made the decision not to proceed into the phase three portion of the trial and are in the process of study closeout. We will share data at a future time and are shifting our focus into new development opportunities for zanzalitinib. Speaking of which, I'd like to now turn to our first pivotal trial evaluating zanzalitinib as monotherapy. I'm pleased to announce the initiation of Stellar 311. which will compare zanzalitinib to everolimus as a first oral therapy in patients with neuroendocrine tumors. We're also excited about the recent initiation of the zanzalitinib plus belzutifan cohorts in the Phase II umbrella study being conducted by Merck. In this study, the combination of belzutifan plus zanzalitinib is being tested in patients with previously treated metastatic kidney cell carcinoma. Progress also continues with regard to the two pivotal studies that Merck is running in clear cell carcinoma, evaluating zanzalitinib in combination with belzutifan, and we anticipate these studies could start towards the end of 2025. As we think about the aforementioned studies representing wave one in the zanzalitinib development program, I want to convey that we are moving full steam ahead into wave two pivotal trial planning to continue building on the franchise. In light of the positive data from Stellar 303 and metastatic colorectal cancer, we are considering how best to move zanzalitinib earlier into the CRC treatment landscape. We're specifically investigating the post-adjuvant setting where patients have received maximal care with surgery and in many cases chemotherapy yet still have a high risk of recurrence. These patients have nothing else available to them. The only option available being frequent scanning and basically entering a watch and wait period until a distant or local recurrence is found, at which point they are mostly rendered incurable. Given the profile of zanzolitinib and its ability to inhibit targets like MET and VEGF, well known for their role in metastatic spread and local establishment of tumor growth, we believe there's reasonable probability that treatment with zanzolitinib could lower these patients' risks of recurrence, improving disease-free survival and unmet need in this setting. There's also interesting data coming out of an IST Investigating cabozantinib in patients with high-grade and or recurrent meningiomas, where the only treatment options are surgery and radiation. Given their central location, neither of these modalities are considered optimal salvage modalities. Offering patients an oral agent like zanzolitinib that could impair further growth and potentially reduce tumor size could represent a breakthrough in the treatment paradigm. We will continue to assess the landscape to consider other areas where zanzalitinib could be developed, leveraging data from our cabozantinib experience, as well as emerging data from our ongoing clinical trials. I look forward to sharing more details of these important opportunities that we believe could enhance the reach of zanzalitinib when we are closer to launching those studies. I'll now turn the call over to Dana.

Thanks, Amy, and good afternoon, everyone. Today, I'm giving a brief update on our recent progress regarding the early clinical compounds in our pipeline, new IND filings, and advancing new compounds to development candidate status. Regarding the early clinical pipeline, our most advanced molecules in this space are XL309, our selective inhibitor of USP1, and XB010, our 5T4 targeting antibody drug conjugate, both of which have first-in-class potential. The Phase I studies for both compounds have been progressing well, and importantly, in patients, both compounds have achieved exposures that are associated with efficacy in preclinical human tumor xenograft models in mice. We've also made good progress in the Phase I study for XB628, our bispecific antibody targeting PD-L1 and NKG2A. Despite filing the IND for XB628 so recently, we have already seen brisk enrollment in this phase one trial, reflecting a high degree of enthusiasm at the clinical sites for this novel molecule. On the new IND front, in the second quarter, we filed our second IND this year, which is for XB371, our tissue factor targeting ADC that carries a topoisomerase inhibitor payload. XB371 has a nominal drug-to-antibody ratio, or DAR, of eight, and utilizes Smart Tag technology that employs site-specific conjugation of the linker payload to the antibody, which, among other benefits, increases control over the DAR species during manufacturing. The technology also takes a belt and suspenders approach to prevent inappropriate payload release outside of the tumor, by utilizing a dual tandem cleavage mechanism that occurs inside the tumor cells, first by glucuronidase enzyme, which then exposes a protease site for the ultimate release of the free payload from the antibody. Our presentation at AACR this year showed deep and durable regressions of human colorectal, lung, and pancreatic xenograft tumors in mice after a single dose of XB371. underscoring the significant potential for this molecule to address unmet need. So the team is excited to now be focused on enrolling the Phase I clinical trial for this molecule. In terms of new development candidates, we are continuing to advance exciting new programs, including some innovative small molecules and antibody drug conjugates, and I look forward to sharing more details about those programs at the R&D Day event for later this year. So with that, I'll turn the call back over to Mike.

All right, thanks, Dana. We'll wrap up here with a big thank you to the XOXS team for helping make our second quarter so successful. As you've heard me say previously, we work in a tough business, and I'm pleased to see our resilience and drive as we progress important projects across our discovery, development, and commercial activities in the first half of 2025. As we said last quarter, we're never satisfied or content with the status quo and look to improve our efficiency and performance on a daily basis. as we make every hour count 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 Exalexis, and we're happy to now open the call for questions.

Thank you. Ladies and gentlemen, to ask a question, please press star 11 on your telephone, then wait for your name to be announced. To withdraw your question, please press star 11 again. We're asked that you limit yourself to one question only. Please stand by while we compile the Q&A roster. Our first question comes from the line of David Liberwitz with Citi. Your line is open.

Thank you very much for taking my question. I know it's early and we haven't really seen the data yet, but any particular takeaways that we have from head and neck that can be extrapolated or not extrapolated to future studies.

Amy? Yeah, thanks for the question. So, let me just back up a second and remind everybody. Zanzolitinib is a franchise molecule, and there's much more to be done than what we have contemplated in the initial six pivotal trials that we've been discussing. Rigorous drug development requires continuous assessments of internally and externally emerging data. And we have multiple areas to continue developing in. We're not going to share any of the data at this point in time, but we will share it with you at a future point.

Thank you. Please stand by for our next question. Our next question comes from the line of Sean Lawman with Morgan Stanley. Your line is open.

Thank you. Hi, Mike and team. Hope everyone's well. Just thinking a little bit longer term at the three billion peak revenue guidance for Carbo it looks like I think looking at guidance for this year probably do around about 2.1x NET and other revenue opportunities. Just looking at the market share gains you had I'm just wondering sort of how long how enduring do you think such share gains can be and And the second part would be, do you think you can achieve the same market share in net as what you've seen in RCC?

Yeah, why don't I start with that, and I'll pass it off to PJ for some color commentary. So we have built a very strong franchise with CAVA over the years, seeing consistent growth in market share and revenue. First, in the RCC realm, we've been focused primarily with 90R and then having that data propel us forward over the last four or five years of market share growth. I think as PJ mentioned, year over year, Q2 24 to Q2 25, we saw four points of market share growth well into the launch, which underscores our ability to commercialize and generate, at least talk about new data from existing trials that help us frame the opportunity for patients. And we think we can do exactly the same thing in the NET space. So again, we have one quarter behind us now with NET. 35% market share is a great place to start. Best in class in the oral therapy is a great place to start, both within literally months of launching the drug post-approval. So early days, we're very excited. As you I'm sure you're aware, Sean, first quarter is usually the NPS quarter where new patients come on and you start to stack with refills later as you're growing NPS. So we're very excited and I think very confident that we can continue to drive the business forward by growing the base business driven by RCC and then this net opportunity, which we think is large and substantial going forward. PJ, any comments?

Yeah, I mean, thanks, Mike. Slight color maybe on the net launch beyond that. You know, as I said, we're certainly pleased with RCC. That continues to grow. But in terms of net, very early innings, you know, we really are excited by the 35% share growth in the second line plus oral market. That's just really strong for the first few months of launch. And I think importantly, As we look beyond that, the fact that we're already seen as the best-in-class oral therapy in neuroendocrine tumors, that's really great that, A, we've done it so quickly, and our research actually indicates it's not even close. We're sort of well out in front of the pack there. And that's important because that's a metric that is typically a leading indicator of physician behavior. So kind of as I mentioned in my prepared remarks, we really do think that we'll continue to you know, to increase in new patient market share there. And as Mike kind of mentioned, you know, first quarter, quarters of launch, you're getting a lot of new patients on therapy, and it takes time to really get the benefit of refills for those patients. So we anticipate that as patients continue to come on therapy, we have more and more patients on therapy, we'll start to sort of stack those refills driving demand. And finally, you know, I mentioned that this is a more indolent disease, so a lot of what we're seeing and hearing from our sales force, advisory boards, et cetera, is physicians really like the data. They have patients on other therapies and neuroendocrine tumors who are stable. And when those patients need progress and need another therapy, they're planning on using CABO for that choice. But obviously, you know, it's great if patients are stable with metastatic cancer. And so there is an element of time that, you know, we need kind of the growth governed by patients coming off therapy. But we anticipate all these dynamics giving us really strong growth in NETs going forward.

Thank you. Our next question comes from the line of Michael Schmidt with Guggenheim. Your line is open.

Yeah, hey, guys. Thanks for taking my questions. Yeah, a question on Stellar 303. Obviously, great positive announcement here earlier on hitting OS in the ITT analysis. And, yeah, I think some of us are just curious how you think – Zanza may be positioned in a broader colorectal cancer landscape, perhaps relative to other new treatment options, including long-term best, which we hear is making some inroads in the market. And yeah, question number one. And then question number two, obviously the trial hit the ITT analysis. So at this point, how important is succeeding on the NLM subset later on? in terms of regulatory approvals or commercial marketing ability down the road. Thanks so much.

Great.

Thanks, Michael. Amy, please have at it. Sure, I'll try and answer both of those. So just stepping back, I appreciate the recognition of the importance of an OS benefit in colorectal cancer, which is the fourth leading cause of cancer-related deaths in the U.S. And OS is unequivocal in that it is the gold standard in oncology drug development. Also noting that this is the only IOTKI positive phase three study. Four have failed before us, not exclusive to Emblaze, Leap, Relativity, and I think T-form is the other one. So we're also excited about the data, and we're excited about the fact that this did hit. In the ITT patient population, it's really important to be able to continue to bring novel therapies to patients. So it would be the only other potential doublet available to patients if it gets approved, including LONSERV-FEV. How we think about the NLM subgroup, it's a different prognostic subgroup. We know that their survival is longer. It's a dual primary endpoint, so we did hit on OSS and the ITT, so we have a positive study. We will continue to follow, though, as per the statistical design for the NLM patient population. And I think it's important to show that there's benefit equally across all subgroups. So we're looking forward to waiting for that data, which we will know more about later as we get closer when we have it. But we're really looking forward to discussing with the regulators the top line data in the ITT as well as sharing the data to the broader community in a medical conference.

Thank you. Please stand by for our next question. Our next question comes from the line of Astica Gombordini with Truist Securities. Your line is open.

Hi, guys. Thanks for taking my questions. I want to layer on to Michael's previous question. Sounds like we're having similar thoughts about this, too, in our investor discussions. Maybe if you can tell us, you know, we're still in 303. The language in the press release was a little bit maybe on the conservative side. So could you maybe tell us if you have a view whether the data in the ITT population is is clinically meaningful. I think that's been a debate point here in our discussions with investors. And secondly, do you have plans to advance Zanza in combinations in earlier lines in CRC? And could you maybe tell us what looks most attractive to you? Thanks, guys. Amy, please.

Yeah, thanks for the question. So the language, Jessica, in the press release is purposely conservative. We are in a new and highly dynamic regulatory environment such that a conservative tone is warranted. And qualitative interpretation is by definition subjective. But let me please be very clear. OS is unequivocal as an endpoint and is the gold standard for approvals. The combination of ZANZA-ITISO demonstrated an improvement in overall survival against an active comparator, and it was statistically significant. And we look forward to sharing the data with the broader community. With regard to additional studies with zanzalitinib and moving into earlier lines of therapy, I did talk a little bit about an area that we are keenly interested in, which would evaluate monotherapy zanzalitinib in the adjuvant setting in patients who have really exhausted all available care to them, which is typically surgery and sometimes includes chemotherapy. And these patients have a high risk of disease of recurrence. And sometimes recurrence can come as soon as a year, and these patients have nothing available to them but to sit and wait for their next CT scan to determine whether or not their disease has recurred. So if we could offer something there to delay disease-free recurrence, potentially prevent the recurrence of disease, we think that that would be a really meaningful impact to patients.

Thank you. Our next question comes from the line of Sylvan Turkin with Citizens. Your line is open.

Thank you. Thanks so much for taking my question, and congrats on the execution this quarter. I just want to see if you could comment, please, on the pricing dynamics with Capesat NIP, especially with respect to the 340B volume and the reimbursement there in the near future and post the big, beautiful bill. Thank you.

Yeah, thanks, Sylvan. Chris, want to take that?

Yeah, Sylvan, thanks for the question. Yeah, you know, I mentioned that we saw a four percentage point increase in our volume shifts, you know, towards the 340B segment of the population or segment of our customers. And, you know, that payer segment is highly discounted segment. So it's having an impact on our gross to net. You know, from an overall, and that's also from an overall industry perspective, you know, there are a lot of companies that are seeing higher utilization in this payer segment. But, you know, from a CABO perspective, what we're seeing is our continued success becoming the standard of care. We're also seeing the sites of care expanding. And so, you know, we have more or a greater number of 340B facilities utilizing CABO. So, you know, based on what we know today, we're projecting gross net will probably come in closer to the 30% range versus what I had previously provided in the 29 to 30% range.

Thank you. Our next question comes from the line of Yaron Webber with TD Cohen. Your line is open.

Great. Thanks for taking that. I have a couple of interrelated questions. Maybe the first one on 304, the primary endpoint is PFS and ORR. Do you have to hit them both, or is it one that it's a dual, one of them can oversway over the other? Because I imagine ORR might be earlier than PFS. And then maybe secondly, just on 303 against Trivago in the past, did like six months, you know, 10 years ago, and then nine months more recently. How would you expect that control to sort of, you know, perform given that Avast and Lancet does about 10.8 months? So how it does historically is a bit relevant. Thank you.

Yeah, thanks, Jeroen. Amy, want to take this?

Yeah, thanks for the question. To clarify for Stellar 304, it is a dual primary endpoint, PFS and ORR. So hitting on either one of them would constitute a positive study. The endpoints are also assessed by Blinded Independent Radiology Committee. So these are not investigator-assessed endpoints. When it comes to the control arm and 303, I'm not going to really talk about the data. I'm looking forward to sharing it with you at a future time. And as I mentioned, we will be discussing it as well with regulators with an intention to file a new drug application.

Thank you. Please stand by for our next question. Our next question comes from the line of Akash Tewari with Jefferies. Your line is open.

Hey, thanks so much. So, Mike, I think when we had caught up at ASCO, you had described the head and neck go or no-go decision to be a relatively low bar to proceed, and your team was confident you could have a competitive profile despite some of the emerging single arm data from bispecifics. I think Cabo Nivo has shown historically a response rate over 50% in that setting. Can we infer that the ZANDA data looks similar or worse to Cabo, and that's what drove your decision to not move that forward? And what were you expecting from a clinical profile there? relative to what was shown from an event rates perspective. Thank you.

Yeah, Amy, you want to take that? Yeah, sure. So I wasn't at the conversation, but I can tell you that, you know, it's a dynamic landscape. We're in the business of developing drugs and really are, hopefully you can hear from the sense of urgency in my voice, unwavering in our mission to develop areas of high unmet need and generate results that really will have meaningful impact to patients. Rigorous drug development requires continuous assessments. We had the study designed as a phase two, three with a gate. We looked at the data and decided not to proceed to phase three based on the competitive landscape, the regulatory environment, and the other areas that we would really like to focus the development in when we talk about wave two of the franchise.

Thank you. Please stand by for our next question. Our next question comes from the line of Jason Gerberry with Bank of America Securities. Your line is open.

Hey, guys. Thanks for taking my questions. So, I just want another follow-up on Stellar 303 and to the extent that you could comment on the enrollment demographics and, you know, maybe if there are any variables that help lead to a different outcome than LEPO1.7. I believe that you could have enrolled up to 40% of patients with non-liverment, so pretty much highly similar to LIPO17, but potentially that could have gone a little bit higher. So I don't know if you're able to comment on directionally the enrollment skew with patients with non-LiverMed. And the opportunity with 303 in the adjuvant CRC setting, do you have a rough sense of what the U.S. patient number is for that market? I imagine there's some proprietary market segmentation data that maybe goes into sizing that, but any idea if you can give us a sense on sizing there?

Yeah, Jason, thanks for the questions. Amy, take the first part and then I'll opine on the second part. Sure, sure.

So, you know, this was a global registrational study. We enrolled 900 patients. Whenever we're designing these, we need to make sure that the study is relevant to the various areas of the world so that we can maintain equipoise in the enrollment and as well ensure that there's consistency of benefit across all subpopulations. I'm not going to go into any details, but I'm looking forward to sharing those with you in the future.

Yeah, and in terms of future studies and earlier lines of CRC, as Amy's spoken to about a potential adjuvant-type study or post-adjuvant-type study with ZANZA monotherapy, we'll get into the details later as we're closer to launching that trial. We're really excited about it. We think it's a large opportunity, both from a patient point of view and a potential revenue point of view. Again, low to no competition, and one that we think Zanza, based upon his profile, could do really well in. So stay tuned. We'll talk about it more as we go forward, but this is the beginning of wave two, and we're certainly excited to be able to prioritize our investments as we go forward. I think that's the key thing. Look at the 305 decision as really simply prioritizing how we're going to invest in terms of high PTS, high commercial potential opportunities as we go forward.

Thank you. Will you stand by for our next question? Our next question comes from the line of Leonid Tomashev with RBC Capital Markets. Your line is open.

Hey, guys. It's Anish on for Leonid. Thanks for the updates this quarter and for taking our questions. Just with Zanza not moving forward in head and neck, how are you thinking about balancing Zanza's potential as a lifecycle play to Cabo in indications like RCC or net versus in broader indications as we think about leveraging an existing prescriber and patient base and work required to broaden that beyond what CAVO touches. How are you framing your priorities there? Thanks so much.

Yeah, I guess the status quo in terms of wave one and wave two is still moving forward. We're thinking, again, we're looking to maximize success with ZANSA by impacting more patients as possible and making that, having the impact on their disease, the maximal impact we could have on their disease. So, when you think about the overlap with CAVO, we're looking at newer indications in terms of ZANSA combinations with Belsudafan with the studies that Merck are doing. Amy talked about 311 today, launching that study in NET, ZAN's monotherapy against everolimus head-to-head. So a win there would really define a superior product in terms of a head-to-head study. And then the second wave, in terms of reinforcing the success we've seen so far clinically in 303 and CRC by moving up in therapy, is certainly very important. And then new indications that we talked about as well, further getting beyond the CAVO reach. So again, the whole story here, the whole focus here is to reinforce the expertise that we have, the strength that we have in the TKI franchise to go beyond combo to build a larger franchise in terms of scope, impact for patients, and revenue. And that plan is only being reinforced today with the overall schemes that we're pushing forward.

Thank you. Our next question comes from the line of Andy Shea with William Blair. Your line is open.

Hey, thanks for taking our questions. So, maybe one epidemiology question. So, what percentage would you characterize as high-risk post-adjuvant in the CRC setting? And maybe one that's a potential read across Forum 303 is the duration. I guess in RCC, most of the adjuvant therapy trials were one year in duration. I'm just thinking about if that's something that you're thinking about as well, and whether the 303 tolerability profile and safety profile could also inform that treatment duration, too. Thank you.

So, Amy, take the second question first, and then I'll follow up on the adjuvant.

Yeah, so appreciate the question with regard to duration, which, you know, defines how long, obviously, how long patients are on therapy. I think we have to take that in the context of colorectal is still the fourth leading cause of cancer-related deaths in the U.S. So duration plus population of patients, I think, brings a potential to make a difference in a lot of people's lives. when we think about moving it earlier in lines of therapy and an adjuvant, you know, the duration there would be obviously defined by probably a longer period of time. And the patients that we're talking about who have higher risk of disease, you're looking at stage two, three patients who have, whose risk of recurrence is measured more in months, early months, not years. As for the number,

Yeah, let me take that. So, again, Andy, we'll give you more details about the ZANs, the post-adjuvant study as we get closer to launching. What I'll say is the following, is that we look at the commercial opportunity. We have a great team within commercial that does that analysis for us. We think the combined opportunities that is represented by the post-adjuvant study as well as the menogenoma study is probably around 3x higher than what the head and neck study was. So, again, from the standpoint of how we're prioritizing investments and allocating resources, both in terms of capital as well as resources, human resources, we think it makes a lot of sense to move forward in these new indications as quickly as possible because, again, the need is there, the competition is very low to none, and the commercial opportunity is very, very high.

Thank you. Our next question comes from the line of Andrew Behrens with Leroy Partners. Your line is open.

Hi. Thanks. A couple more questions on the CRC program and Stellar 303. The FDA has made demonstrating contribution of parts a priority. Just wondering if you think that Stellar 303 has met that bar. And then some concerns I've heard from investors are that the intent to treat OS benefit may have been driven by an improvement in the non-liver med patients that are part of the cohort and the impact on checkpoint inhibitor efficacy. I know the NLM OS analysis is not read out yet, which is probably contributing to this concern, but is there anything you can say to address this? How important is it that you demonstrate a definitive benefit in the patients that have liver meds? Thanks.

Amy, go ahead, please. Yeah. Yeah. Thanks for the question. So contribution of components is something that we have long recognized as an important factor for this study. And I will remind you of ASCO GI earlier this year, where we showed stellar 001 colorectal cancer cohorts, ZANZA versus ZANZA plus ATISO, and across all efficacy parameters, ORR, PFS, OF, DOR, the addition of Atizo to Zanza was there. So we have contribution of components coming from a separate study. And in terms of the NLM and subgroups, I'll share it with you. Again, I'm not going to get into any of the data. We have a positive OS readout in the intent to treat patient population. As you yourself pointed out, we continue to follow for OS and NLM. And we look forward to sharing all the data as soon as we can.

Thank you. Our next question comes from the line of Derek Archela with Wells Fargo. Your line is open.

Hey, thanks for taking the questions. Just one on net in terms of, you know, how should we be thinking about the revenue trajectory post-second quarter? And, you know, are the next couple of quarters of launch more bolus-like before steadying off, you know, as you need to roll over these indolent patients that become candidates for therapy? And then just follow up, you know, just can you discuss the breadth of prescribing that you're seeing among the target physicians so far? Thanks.

Yeah, thanks for the question. Look, we're not going to give quarter-to-quarter guidance. Obviously, we don't do that. So, we're very excited about where we stand in the second quarter, which, again, is our first full quarter of launch. All the, you know, all the narratives that we've been talking about in terms of what that means, I think, are pretty clear. I won't repeat those here. PJ, you want to add some color commentary on the second part of that question?

Yeah, you know, as far as the prescriber base, I'd say we're pleased generally. We're seeing... you know, prescriptions broadly, as I mentioned, in terms of academic, in terms of community. We're seeing prescriptions from Cabo Naive prescribers as well as legacy Cabo prescribers. So, basically, we're seeing, you know, activation and or sort of, you know, more prescriptions from prior prescribers. So, we're pleased with those kinetics across the board.

Great. Thank you. Our next question comes from the line of student Logan Nathan with Stevens. Your line is open.

Hi, excellent team. Thank you for taking my question. My first one, you know, in regards to the positive pipeline release that you had for the OS benefit in Stella 303, does the dual endpoint give the opportunity to at least get approval for one of the patient populations if if there are any nuances with either the NLM or the liver mass population that makes it not as favorable when filing with the FDA. And then secondly, we want to squeeze in if you can opine if the current reiterated guidance ranges includes contributions from NET.

Thanks. Go ahead, Amy.

Yeah, thanks for the question. I'm not going to really speculate on what would suffice for approval. The dual primary endpoint is designed such that you can be positive on one.

Chris, take the second one. Yeah, so thanks for the question. As Mike mentioned last quarter, we increased guidance by about $100 million to the midpoint. Some of that was related to NET, but a lot of that was related to the base business.

Thank you. Our next question comes from the line of Peter Lawson with Barclays. Your line is open.

Chris, just following up around the details around the guidance, is there any way how we should think about clinical trial revenues in the second half? Thank you.

Yeah, Peter, thanks for the question. I mean, as we've said probably a couple of years now, the clinical trial sales are choppy. You know, we have some visibility occasionally, but we don't have a very good line of sight to when the clinical trial cells are coming through. So it's hard to say. So that's about it.

Thank you. Our next question comes from the line of Stephen Woolley with Stiefel. Your line is open.

Yeah, thanks for taking the questions, and congrats. on the stellar 303 readout. Just, I guess, a quick clarification question on the 305 decision. So, I think I remember you guys were blinded to the data and that a DMC would be, I guess, evaluating some threshold level of efficacy metrics and then allowing you to proceed on a blinded basis and potentially upsize the study. Can you just kind of talk through the cadence of the decision in terms of assessing the competitive landscape and then seeing the data? Were those two things done in lockstep, or did the former precede the latter? Thanks.

Go ahead, Amy, please. Yeah, thanks. So I'm not going to go into a whole lot of detail here. The trial was designed with a gate. We reviewed the unblinded data. We may have a path forward in head and neck, and we'll determine if additional studies are warranted. But for now, we're prioritizing other indications and allocating resources accordingly. Head and neck is a unique population, and we'll share the data at a future time.

Thank you. Please stand by for our next question. Our next question comes from the line of Ash Verma with UBS. Your line is open.

Oh, yeah, thanks for taking my question. So, for STERIL-303, I'm trying to understand if this ITT data can come at a medical conference this year, or do we wait until next year? Just another way to ask the same thing, can you still present the ITT portion of the study without reaching the final analysis on NNM? Thanks. Go ahead.

Yeah, thanks for the question. We're not discussing the venue for the data presentation, but we'll provide the data once the abstract titles are made publicly available. We presented the dual primary endpoints before where we've hit on one and still waited for the other.

Thank you. At this time, I'm showing no further questions, so I will now turn the call over to today's host, Susan Hubbard, Ms. Hubbard.

Yeah, thank you, Tawanda, 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.

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