Good day, ladies and gentlemen, and welcome to Exelixis' First Quarter 2024 Financial Results Conference Call. My name is Towanda, and I will be your operator 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. Varant Shirvanian, Director of Investor Relations. Please proceed.

Thank you, Towanda. Thank you all for joining us for the Exelixis' First Quarter 2024 Financial Results Conference Call. Joining me on today's call are Mike Morrissey, our President and CEO; Chris Senner, our Chief Financial Officer; P. J. Haley, our Executive Vice President of Commercial; Amy Peterson, our Chief Medical Officer; and Dana Aftab, our Chief Scientific Officer, who together will review our progress for the first quarter 2024 ended March 31, 2024. During the call today, we will refer to financial measures not calculated according to generally accepted accounting principles. Please refer to today's press release, which is posted on our website for an explanation of our reasons for using such non-GAAP measures as well as tables deriving these measures from our GAAP results. During the course of this presentation, we will be making forward-looking statements regarding future events and the future performance of the company. This includes statements about possible developments regarding discovery, product development, regulatory, commercial, financial and strategic matters. Actual events or results could, of course, differ materially. We refer you to the documents we file from time to time with the 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 cost associated with discovery, product development, business development and commercialization activities. With that, I'll turn the call over to Mike.

All right. Thanks, Varant, and thanks to everyone for joining us on the call today. Exelixis is off to a strong start in 2024 and had a productive first quarter across all components of our business. We're pleased to see both revenue and demand growth for the cabozantinib franchise in the U.S. and globally. Top priority is to move the needle for patients and shareholders by advancing cabo, zanza and the rest of our exciting pipeline to improve the standard of care for patients with cancer. We will have to cover today, so let's jump right into it with the key highlights for the quarter, including: first, we saw a strong performance of the cabozantinib business in the first quarter of 2024 with continued growth in demand and revenue year-over-year compared to first quarter of 2023. Even with typical seasonal headwinds that were further magnified by the implementation of the IRA, CABOMETYX maintained its status as the leading TKI for RCC in both the first-line IO TKI market, the second-line monotherapy segment. First quarter 2024. Cabozantinib franchise net product revenues grew 4% year-over-year compared to first quarter 2023, highlighting its role as a worldwide leading TKI, global cabozantinib franchise net product revenues generated by Exelixis and its partners grew approximately 9% year-over-year in the first quarter of 2024 compared to first quarter 2023. As discussed previously, we're excited about the potential for additional cabo growth with the new indications on the horizon that P.J. and Amy will discuss shortly. Chris will review our full first quarter 2024 financial results in his prepared remarks. Second, we continue to advance our industry-leading pipeline across all stages of preclinical and clinical development. Our top priorities for 2024 are to advance potential new cabo indications for NET and metastatic CRPC and expedite zanza clinical…

Thanks, Mike. For the first quarter of 2024, the company reported total revenues of approximately $425 million, which included cabozantinib franchise net product revenues of $378.5 million. CABOMETYX net product revenues were $376.4 million and included approximately $6 million in clinical trial sales. Gross to net for the Cabozantinib franchise in the first quarter of 2024 was 32.9%, which is higher than the gross to net we experienced in the fourth quarter of 2023, but overall, in line with our expectations. This increase in gross to net deductions in the first quarter of 2024 is primarily related to higher Medicare Part D and PHS expenses. Historically, we have experienced higher Medicare Part D expenses in the first quarter of the year due to many Part D patients moving through the donut hole at the start of the calendar year. Our CABOMETYX trade inventory decreased by approximately 350 units when compared to the fourth quarter of 2023 of approximately 2.4 weeks on hand. As I mentioned on our fourth quarter earnings conference call, we experienced a trade inventory build in the fourth quarter of 2023 of approximately 1,000 units and that we had observed an inventory drawdown in January. As discussed previously, Exelixis took a 2.2% price increase on January 1, 2024. This price increase is more than offset by the higher gross to net deductions during the first quarter of 2024. Also, while we don't provide quarterly revenue guidance, we do see some seasonality in net product revenue trends, where first quarter net product revenues have historically been lower than the following quarters in a year. If you analyze the last 7 years of first quarter net product revenue and compare them to the reported annual net product revenues of the same year, in many of those years, the first…

Thank you, Chris. In the first quarter of 2024, team continued to execute at a high level, which has resulted in CABOMETYX continuing to be the #1 prescribed TKI in RCC and second-line HCC. Additionally, CABOMETYX in combination with nivolumab remains the #1 TKI plus IO combination in first-line renal cell carcinoma. With regards to prescriptions, CABOMETYX TRx volume grew 4% year-over-year in Q1 2024 relative to Q1 2023. In the same period, the TKI market basket was flat. Furthermore, the business remains strong, both in terms of demand and new patient starts. CABOMETYX continued to perform well in the first quarter from both a marketplace and competitive perspective. CABOMETYX again led the TKI market basket in TRx share at 40%. As we have discussed previously, the first-line RCC market is extremely competitive. And Q1 was the sixth full quarter in which CABOMETYX plus nivolumab, remain the #1 prescribed TKI plus IO combination in first-line RCC. Furthermore, long-term data from the CheckMate 9ER study now with a minimum of 4 years follow-up, was presented at ASCO GU this year and continues to reinforce the leadership position that CABOMETYX has in the RCC marketplace. Looking forward, the commercial team is excited about the positive results from the CABINET trial in neuroendocrine tumors as well as the CONTACT 2 trial in metastatic castration-resistant prostate cancer, which Amy will discuss in some detail. Neuroendocrine tumors comprise a large and heterogeneous patient population. The patients become metastatic and progress treatment options become limited. The only oral therapy options are sunitinib and everolimus and there has not been an approval in the U.S. for an oral agent in NET since 2016. There is a strong unmet need for new options for patients who have progressed on systemic therapy. There are approximately 8,000 incident second-line plus…

Thanks, P.J. Today, I'll provide a high-level update on our clinical stage pipeline. The team is continuing the momentum across all of the programs we highlighted during our R&D Day last December, with laser focus on execution for the cabozantinib franchise as well as for our clinical pipeline. Our pipeline is broad, both in terms of modalities and targets, representing a variety of development opportunities, which combined with our robust translational and clinical development capabilities provide an exciting and high potential platform for growth. Today, I'll share the progress we are making towards executing on our clinical trials across the development pipeline and on our potential regulatory submissions for cabozantinib. So let's start with cabozantinib and CABINET, which is a Phase III study that evaluated cabo versus matched placebo in patients with previously treated advanced or metastatic pancreatic or extra pancreatic neuroendocrine tumors, which I'll refer to as PNET or EPNET, respectively. The study was conducted by the Alliance for clinical trials in oncology and data was presented by Dr. Jennifer Chan at ESMO 2023. The study had 2 independently powered cohorts, one for PNET and the other for EPNET. Notably, the PFS hazard ratio for each cohort strongly favored cabo with hazard rates of 0.27 and 0.45 in the PNET and EPNET populations, respectively. The safety profile of monotherapy cabo was consistent with its known profile and no new safety signals were identified. This initial analysis was based on local assessments with limited data available from the Blinded Independent Radiology Committee or BIRC. The compelling results triggered an IDMC recommendation and Alliance decision to stop enrollment, unblind the study and allow patients to cross over from placebo to cabozatinib. The final analysis by BIRC will be shared at a conference later this year and support our intention to file…

Thanks, Amy, and good afternoon, everyone. Today, I'm giving a brief update on our progress in the first quarter of 2024 toward our goals for preparing for IND filings and for advancing new compounds to development candidate status. And then I'll wrap up with some preclinical updates on our USP1 inhibitor, XL309, and our next-generation VEGF receptor tyrosine kinase inhibitors, zanzalintinib. On the IND front, we are making good progress on all of our pre-IND programs and are on track to file up to 3 this year. The first one we expect to file this year is for XB010, our 5T4 targeted antibody-drug conjugate that carries the cytotoxic antitubulant payload MMAE. IND preparation is wrapping up soon, so we expect that one to file around midyear. The second IND we expect to file this year is for XL495, which is a small molecule inhibitor of PKMYT1 that shows synthetic lethality in the context of increased cyclin E levels, which occurs across a wide range of tumors. IND preparation is progressing, and we are on track to also file this one around mid-2024. The third IND we expect to file this year will be for XB628, our bispecific antibody that targets PD-L1 along with NKG2A and displays NK cell engager activity in preclinical models. The GLP tox study for XP628 is now complete, and manufacturing and other activities have us on track for IND filing in the fourth quarter of 2024. Each one of these programs has a solid rationale for generating differentiating data in the clinic. So we're excited to get these INDs filed and to get the trials up and enrolling quickly. In terms of new development candidates this year, we are currently on track to achieve our goals of at least 2 this year with some exciting new…

All right. Thanks, Dana. I will close by highlighting the 2 long-standing Exelixis executives are retiring after serving our company for nearly 2 decades. First, Peter Lamb, EVP of Scientific strategy was with Exelixis for nearly 25 years, and as you all know, made an outsized impact on our drug discovery efforts during his tenure at the organization. Additionally, Laura Dillard, our EVP of Human Resources, spent nearly 20 years leading our HR efforts to ensure we are keeping pace with the evolution and growth of the company. On behalf of the entire Exelixis team, I'd like to thank both Peter and Laura for their friendship, dedication to Exelixis and most importantly, commitment to cancer patients on a global level. We wish them all the best as they start their retirement. So with that, I want to thank the entire Exelixis team for their efforts to support our discovery development and commercial activities. We're off to a great start in 2024 and expect this year to be critical for our science and the patients we hope to serve in the future. We built and are constantly fortifying Exelixis as a big, small company with all that we do every hour of every day. The Exelixis team is highly motivated to exceed expectations and our mission to help cancer patients recover stronger and live longer. We look forward to updating you on our progress in the future, and thank you for your continued support and interest in Exelixis, and we're happy to now open the call for questions.

[Operator Instructions] Our first question comes from the line of Joe Catanzaro with Piper Sandler.

I appreciate you taking the time here. So I'm wondering if you could elaborate a bit on your earlier comments in the events of a positive outcome with regards to MSN patent litigation and sort of interested in looking for later-stage assets in GU, GI, oncology. I guess, how would you define later stage? Is this sort of modality agnostic? And what size deal do you think you could execute with the balance sheet and clarity around the cabo revenue tail?

Yes, Joe, it's Mike. Thanks for the question. Yes, this isn't really a new approach. We talked about this earlier in the year as we were implementing the restructuring focusing our BD efforts on later-stage assets in terms of new modalities that are either in or entering pivotal trials as well as their focus on helping us find collaborations with zanza and other molecules in our pipeline to collaborate on in terms of cost and/or compound sharing arrangements. So, look, we're very interested in building a pipeline. We've got a great discovery, development and commercial organization, and late-stage assets fit well into that overall approach, whether they be already in pivotal trials or about to enter, we think we can add a lot of value as we go forward. So wouldn't want to comment on size, wouldn't want to comment and certainly on individual targets. We're modality agnostic in terms of small molecules and biologics. We have, I think, a very good eye for good data and good compounds. Again, the cabo lens, if you will, really informs that. We talked about that at R&D Day back in December. So we're all in, in terms of finding potential assets to be able to bring into our pipeline and that will continue as we go forward.

Our next question comes from the line of Jason Gerberry with Bank of America.

So my -- I just wanted to follow up on the any key commercial opportunity slide. I'm just curious how you guys think an indication like that could ramp. The second line incidence is a decent-sized number. I just wonder about the availability of an established oral TKI, which wasn't studied head-to-head, again, if that creates a barrier at all or might slow the launch versus the launches we're accustomed to seeing like CheckMate 9ER just given the need to potentially retrain physicians or educate them about your data.

Yes. Jason, this is P.J. Thanks for the question. I'd say we're really excited about the data that Amy went into a little more detail on. As I mentioned, we've kind of conducted some preliminary market research. We've certainly had some advisory boards. I guess what I'd say at a high level is there's a lot of enthusiasm for the data. I don't think there'll be anything significantly different than prior launches. You mentioned 9ER in terms of kind of trajectory or uptake or sort of retraining physicians per se. I think they're very comfortable, obviously, with TKIs and even in this setting. So we think this is a really nice opportunity potentially should we receive approval. For cabo, as I spoke to, I think the broad population that was studied with regards to pancreatic, extra pancreatic, site of origin, tumors, including lung, which is a little bit different from some of the other agents, which weren't studied as broadly as well as the fact that were studied in SSTR positive and negative as well as kind of having a modern data set, which included a lot of patients treated with Lutathera before the study really gives us the potential to be broad and I think, in a sense, very user-friendly for oncologists who are really looking for something new in this setting.

Our next question comes from the line of Michael Schmidt of Guggenheim.

I had one for Amy on STELLAR-305. And so -- just wondering how the enrollment criteria in the study compared to that from KEYNOTE-048 or LEAP-010. And to what degree you feel like you may need to adjust the trial based on the LEAP-010 data that was presented recently? And what your confidence level is in demonstrating a positive overall survival trend, which was obviously not the case in LEAP-010?

Yes. Thanks for the question, Michael. It was very interesting to actually get a chance to see the final -- the results from the presentation earlier this year in terms of LEAP-010. Notably an ORR and a PFS that favored len/pem but an OS that didn't. And an interesting duration of response with monotherapy pem favored over the doublet. So this is a different population, frontline head and neck, a little bit more frail than other patient populations. And we're interested in trying to uncover as much as we can. Around the dose of len, the dose reductions and how much that may have aggregated a patient's ability to receive full pembro dose. So we are deeply trying to understand that and if need be, make a change to the 305 study with regard to dose in the context of very -- a frailer patient population, if you will. I think that there's a differentiation between zanza and len and that zanza does inhibit the TAM kinase family, which is implicated, if you will, in favoring an immune permissive environment. So the mechanism of action of zanza is different from len, and because of that could very likely have a differential outcome and we believe it will. So we'll see how -- what ultimately needs to be changed and we'll keep you posted on those changes as they're made. Right now, the eligibility criteria for the most part are posted on clinicaltrials.gov. And where we need to make an update, we will.

Our next question comes from the line of Gregory Renza with RBC Capital Markets.

Mike, maybe just to ask a little bit building on the neuroendocrine tumor opportunity, certainly nicely in context with respect to Cabo but as you do think about zanza and the combo optionality there and the white space that you have, I'm wondering if you could just comment a bit about zanza in this indication. I mean is there opportunity? And what are the potential development to have pass as you think about combos would potentially zanza and Luta therapy be something to explore?

Yes, Greg, thanks for the question. It's a great one. I can punt over to Amy and P.J. to opine upon, Amy?

Yes, sure. As I mentioned during the call, we're always assessing what is the next best thing to think about for zanzalintinib. We look at all things that are strategic in our assessment. So I talked about the probability of technical success. That's a big one for us to consider as well as the time it takes to conduct the study and the competitive and evolving landscape and the value proposition. And I would say that neuroendocrine tumor is high on the list for zanza and we are very interested in it. I'll let P.J. comment a little bit on the commercial.

Yes. I mean I think just at a high level, if I go back to kind of the opportunity here, certainly, a large unmet medical need, as I mentioned, with not many new therapies, really any oral therapy is being approved since 2016. So I think there's a lot of room to maneuver in this tumor type, in particular. The orals, as I mentioned, in my remarks and on the slide account for approximately 50% of the second line plus population. So if you think about Lutathera, for example, which is doing over $400 million in revenue annually. Basically a second line-plus population, they have the NETR-2 data. at ASCO GI this year but those revenue kind of predate that. So that's a pretty significant opportunity in less than 50% of that market. So I think this is a big space that's really there's a high appetite for new therapies, for new trials and really an opportunity for this market to grow over time. So I see it as very exciting.

Yes, that's great, P.J. I would just add. I think the way we talked about NET here, and we're really excited about certainly the CABINET data and the opportunities to go forward with zanza, we think NET is similar to what we saw with RCC back in the 2014, 2015, 2016 time. And there's lots of similarities between the 2, even though they're obviously different -- very different indications. So we're excited about this. We hope to invest more as we go forward. Lots of opportunities with zanza and other potential combinations. So stay tuned. As that evolves, we'll keep you in the loop.

Our next question comes from the line of Yaron Werber with TD Cowen.

This is Joyce on for Yaron. Maybe just another follow-up on the NET market opportunity. I think you guys have previously said that the prevalent population is about 5x the size of the second-line plus incident population or about 40,000 patients. Just wondering how much of that market you think you can capture or pull into this opportunity with cabo and/or zanza?

Yes. Joyce, this is P.J. Thanks for the question. I think as I mentioned, the 8,000 patients, those are kind of new incident patients in a given year. And as you mentioned, the prevalent population is much larger. I think I wouldn't want to speculate before we get to a label on the potential upside or where it might play out in the marketplace but I think when we think about the 8-K patients, et cetera, that's kind of the baseline, and there certainly could be many more patients given that this is an indolent disease where patients receive many lines of therapy that might be kind of out there. But again, I think we need to wait until we get in the market to really get a good sense of that. But we're very confident and comfortable in the 8,000 patients as it is being a really significant potential opportunity for cabo.

Our next question comes from the line of Andy Hsieh with William Blair.

Two quick one, if you don't mind. One financial one, [ I got a ] scientific. In terms of Medicare D exposure, Chris, do you mind reminding us your exposure there for the cabo franchise? Several companies like Gilead kind of called out the potential impact next year stemming from the Medicare Part D redesign, so that's part one. Part two, very provocative differential partitioning data, cabo versus zanza. I am curious, one, how was that determines? Would it be based on kind of radio labeling experiments? And then perhaps from a hypothesis perspective, do you have any sort of initial working in terms of why that is? Is that kind of a difference in passive diffusion or maybe transporters are involved? So those are the 2 questions.

Yes. Thanks, Andy. It's Mike. Dana, why don't you take that second question first, and then we'll punt it over to P.J. for the Medicare Part D question.

Sure. Okay. Thanks for the question, Andy. Yes, so in terms of the partitioning, we generated data in rats, and this is really data for preparing for the mass balance studies in humans. That was the first sort of view into differential partitioning into normal tissues that we got. So that was using radio-label drug. So of course, that measures everything metabolites and anything else that's attached to the radioactive tracer. In terms of the tumors and actually the data that I showed on the slide came from sort of a side-by-side experiment in mice where we were determining the compound concentrations by mass spectrometry. And at doses that generated similar free drug concentrations in the plasma, which again were determined by doing protein binding experiments, et cetera, we saw those free drug concentrations in normal tissues and tumors, and that was just one of several representative normal tissues. So we're still generating a lot of data. There's obviously a lot of different components that go into how drugs distribute within a living animal or person, including things like protein binding, tissue binding, which involves other components other than protein, membranes, lipids and whatnot, transporter effects, pH-dependent effects. There are so many different pieces of the puzzle that go into understanding how this happens. So we're still gathering data to try to understand the full model that is driving these differences. And what I would just say is stay tuned as we generate more data and publish those data that will hopefully lay out the full mechanism of how this happens. But I must say that it was a surprise to us to see this happen. We had not anticipated or predicted that this would happen with these drugs a priority.

Great. Thanks, Dana. P.J.?

Yes. So Andy, our Part D -- Medicare Part D accounts are approximately 40% of the business. And as you know, with regards to the IRA, that will continue to evolve in 2025. So the out-of-pocket cap for patients will be even lower next year, around $2,000 and also it will be spread out over a monthly basis. So the thinking is that could potentially reduce the burden on patients even further.

Our next question comes from the line of Jay Olson with Oppenheimer.

Thank you for providing this comprehensive update. For zanza, can you talk about when we should expect to see some combination data. And Bristol recently mentioned initial clinical proof-of-concept for Opdualag in non-small cell lung cancer. What's your thinking and interest level in the combination of zanza with Opdualag and STELLAR-002?

Sure. Thanks for the question. I'll take that. This is Amy. So you saw in the slides, we do have a variety of cohorts that we are expanding in both STELLAR-001 and STELLAR-002 and in combination with PD-1 in addition to other IO agents, including CTLA-4 and LAG-3. We will present the data when it is mature. Some of these are early line cohorts. It just takes a while because you want to get ORR, you want to get DOR, you want to get PFS. Some of them actually also have OS, they're event-driven. And we just have to wait for those events before we can report on that. When it comes to interest with combination partners, I also presented the various combinations that we're doing, not only IO, IO, IO but also we have the collaboration with HIF-2 alpha, and we're looking another combinations. So I would say that we're data-driven. And we'll go where the combinations tell us we should go but we are and we remain open. I think that what we're continuing to identify and uncover is that the ability for zanza to combine with all of these other agents is actually rather straightforward that's reasonably well tolerated at full doses. And so we don't think that there's an issue in terms of zanza's ability to combine with any of these agents. It just has to be -- the decision to move forward into additional studies just has to be made upon the data that we see as it matures in the 001 and 002 cohorts.

Our next question comes from the line of Akash Tewari with Jefferies.

This is Kathy on for Akash. I just wanted to follow up on the Medicare Part D question that was asked earlier. And specifically on how will the restructure of the catastrophic coverage component impact cabo in the coming years? And also how does Exelixis specifically plan to mitigate these pricing impacts?

Thanks for the question. This is Mike. Yes, I certainly wouldn't want to comment on what's going to happen in the years ahead. We have a pretty good idea about what to expect relative to '25 and beyond. So again, I wouldn't want to opine beyond what's happening in 2024. And we have a high degree of confidence that we've got that really good sense of where that's going and how to navigate those different changes. So moving full steam ahead and when we get to '25 and beyond, we'll talk about those changes then, okay? Thank you.

Our next question comes from the line of Chris Shibutani with Goldman Sachs.

Great. Perhaps if you could help us understand your prioritization of capital allocation between the share repurchases and the business development activity, I think Joe had tried to ask earlier and recognizing that you aren't necessarily thinking of sharing specifics. But it sounded as if it was contingent upon the outcome of the MSN IP decision for you to perhaps lean in more intentionally on the BD front. I just wanted to make sure I understood because you also included in your release that you plan on completing the share repurchase allocation that the Board approved for the full year 2024.

Yes. Thanks for the question, Chris. Yes, I would not certainly assume those 2 activities are mutually exclusive. We have plenty of cash. We're generating free cash every quarter. We've been profitable for years. I think we have the appetite to do both. As Chris and others -- we've all talked about previously, the share buyback between last year and this year will be $1 billion. The idea that we want to add additional late-stage assets to our portfolio, certainly makes sense in the context of growing the business in terms of both top line and bottom line growth by having a diversified offering of products that we can use in the context of our development and commercialization platform to move the needle for patients and shareholders. So we are certainly very excited about the options we have ahead of us. Getting beyond -- getting certainty with the ANDA is the first priority. Once we have that in place, then I think the next steps are relatively straightforward with how we want to maneuver the business. So thanks for the question and happy to follow up at a later time if you want.

Our next question comes from the line of Derek Archila with Wells Fargo.

So just, I guess one from us, how do you envision the cabo approvals in both prostate and neuroendocrine tumors, how does that change the volume growth profile of cabo relative today? How much acceleration could we potentially see in the future?

Yes. Derek, this is P.J. So certainly, we don't want to give guidance beyond this year, specifically on revenue or volume. I guess, I'd kind of reiterate some of my earlier comments with regards to NET obviously and CRPC, for that matter, both significant areas of unmet medical need. As I mentioned, NET is 8,000 patients in the second line plus setting and more broadly, we have the potential to be really have a broad opportunity in that marketplace. CRPC is obviously a really large market, again, ultimately with limited treatment options with regards to primary treatment options being chemo, NHT, radioligand therapy, but you're talking about tens of thousands of patients. So we're very excited about the opportunities. And should we have the opportunity to bring them to market and help patients, we think there'll be really significant opportunity for growth.

Our next question comes from the line of Silvan Tuerkcan with Citizens JMP.

Congrats on the quarter. I just want to ask about the overlap in sales force and call points between RCC and a potential sales force for prostate cancer. And basically, what I'm trying to get to, is, can you tell us what's kind of the incremental cost for potentially launching NET in prostate cancer?

Yes. Silvan, thanks for the question, P.J., why don't you address both in terms of prostate RCC and then on the GI side, NET and HCC.

Yes, happy to, Mike. Thanks for the question, Silvan. So I'll start with RCC. We see really significant overlap in terms of GU oncologists, right? So whether it's in the community setting or even an academia in particular, GU-onc focus are really treating the majority of these GU indications. So again, significant overlap there, which is potentially great for a number of reasons. One, we really, as I mentioned in my prepared remarks, we can leverage our existing RCC infrastructure. So without having to invest significantly to build that for a potential prostate cancer launch. And two, these are physicians who are very familiar with cabozantinib in RCC managing side effects, et cetera. So that could be certainly something that would be in our favor as well. With regards to NET, a lot of these is 50% plus -- really 60% plus are GI related. We have another sort of sleeve of our team, if you will, is GI-focused, and there's a heavy overlap there as well with our call points, both in the community as well as, again, in academia, who are -- physicians who are treating NET as well as those GI tumors. So again, it's a really nice potential for us to leverage our existing infrastructure as well as launch into a market where a lot of the prescribers have existing comfort and familiarity and frankly, positive experiences according to all our market research. [Audio Gap] Tumors whether it's HCC, thyroid cancer, DTC or in many different settings in renal cell carcinoma. So that's certainly something we look forward to.

Our next question comes from the line of David Lebowitz with Citi.

When you discussed the strategy zanza versus Cabo going forward, it seems it's clearly an effort to focus on different overall indications. Does that strategy evolve in the event of an unfavorable MSN 2 [indiscernible]?

Yes, David, thanks for the question. Yes, I wouldn't want to -- we wouldn't want to speculate on that right now. So I think we've made the commitment to evolve the overall approach in terms of how we're developing TKIs, VEGFR are targeting TKIs over to zanza, and that's still the plan going forward. We think we have what looks like to be an emerging improvement in overall activity and safety, the totality of data. It's still early. We would suggest that. So we're all in on zanza and there's a lot of excitement there in the community. And we're having, I think, a lot of very interesting productive discussions about how we might combine with zanza. So lots of opportunity, a lot to do there. So stay tuned.

Our next question comes from the line of Jeff Hung with Morgan Stanley.

Following up on the neuroendocrine tumor prevalent population. Given heterogeneity of tumors, are you planning to stratify the prevalent population to focus on specific subgroups initially? I appreciate any details you can provide.

Yes, Jeff, this is P.J. Thanks for the question. Generally, what I would say is as we focus coming out of the gate, given that, as I mentioned, we kind of really have broad inclusion criteria in our study of whether that's site of origin, SSTR receptor status, what patients have been previously treated with, we really believe we have the opportunity to go right out of the gate. Should we be approved and launched this very broadly. And I think that will be in what we're hearing in ad boards, et cetera, very much appreciated and adopted well from a physician community perspective because they need new options, for really all of these patients. And in some cases, like right now for patients who have been on a variety of therapies. So I think it would be a broad opportunity and we would certainly position it to as such.

Our next question comes from the line of Etzer Darout with BMO Capital Markets.

This is Lukas Shumway on for Etzer. For the prostate and NET filings, what are the key factors that are going to influence the timing of those filings, what are you waiting on for those? And are those only going to be U.S. filings? Are we also looking for ex U.S.? And are there any other gating factors for filing those?

Thanks, Lukas. This is Amy. I'll take that question. So I can't comment on what our partners are going to be doing with regard to ex U.S. filing. Cabo is in collaboration under a -- collaboration agreement with Ipsen for non-U.S., non-Japan and with Takeda for Japan. What we're focused on and what I mentioned in the call is that we needed the data by BIRC in order to complete the dossier for a filing. And the data, and we're in discussions, and we really are hoping to be able to submit in the coming months for the CABINET study. For CONTACT, I also mentioned we have final OS, which we're anticipating in the coming months. The study was a positive study. Statistically significant OS is not required in order for the study to be positive. We showed a really nice trend favoring cabo/atezo, which I will point out, given the -- what else is going on in prostate cancer in terms of radioligand to PSME4 assets where initially hazard ratios for OS were above 1. Novartis just announced there's a less than 1, probably very close to 1, the fact that we had a nice trend, I think, is also supportive of a risk-benefit profile that is -- that favors the patients. And so stay tuned. We'll let you know how conversations and filings progress with the agency.

Our next question comes from the line of Peter Lawson with Barclays.

Chris, just a question on the share buyback and thoughts on expanding that, especially if there's a negative outcome around IP, would that be something you'd expand or accelerate?

Peter, thanks for the questions. It's Chris. Yes, I'm not going to speculate on what we're going to do depending on the different variables around outcomes on the MSN trial. We're -- as I mentioned in our prepared remarks, we're committed to executing on the $450 million, we did $191 million in the first quarter, and we're committed to getting the rest done this year.

Thank you. At this time, there are no further questions. And I would now like to turn the call back over to your host Varant for closing remarks.

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

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