One of the senior biotech analysts at the firm. Sorry, we're starting a little late. Thank you for the bathroom break. We have with us here from Exelixis, Andrew Peters. He heads up their business development group. I've known Andrew for a while. I'd much rather prefer talking to him over a beer in Barcelona, but a stage will do for now. Any opening comments you want to make before we get into Q&A?
Yeah, yeah, happy to. And thanks for the invite. Always like coming out and chatting. Again, I'd agree with the sentiment. Barcelona over a beer is Sangria always preferred. So just as a reminder, I'm going to be making some forward-looking statements today. So please see all relevant disclosures around risks in our business and our regulatory filings. So great time to be here and kind of chat all things Exelixis. Really kind of on the tail of a couple of pretty meaningful events for us as a company. More coincidental than anything, but the same week that we signed the clinical collaboration with Merck, we also heard from Judge Andrews around our ANDA and the kind of patent dispute we had with MSN.
And then kind of capped off in the last several weeks or so was third quarter earnings, where we had an opportunity not only to kind of talk about the success of the business that we're continuing to have, but also provide somewhat of a forward-looking outlook on the company. Because at the time, a lot of investors had basically been pretty candid with us saying they just couldn't get around the uncertainty of the ANDA. And really the big question was, what does the company look like the day after, and the week after, and the month after? And a lot of that's related to Cabo. A lot of it certainly is related to Zanza.
What we wanted to do is provide kind of a really high-level framework about how we see the business, not only in the short term, but as well as the mid and long terms as well, and so the combination of those three things has really provided us a lot of momentum internally, excitement around how do we execute, but also externally, and having the chance to chat with folks like you and investors to really understand, OK, what does Exelixis look like, and what are the kind of path forward that we have as a company and organization?
Yeah, no, it's been a really interesting confluence of events here over the course of the last month, and I think investors seem to be comfortable with the clarity that they have, if your stock price is any kind of indicator of that. I guess I'd be kind of interested, given you're the BD guy here, what does that clarity around Cabo exclusivity now mean for you? , and I guess to what extent, if at all, was the BD function previously rate-limited by these things? , and has the opportunity set now expanded with this clarity in place, both in terms of development stage and the amount of capital that you're maybe looking to deploy?
Yeah, I mean, it's an interesting kind of question and kind of almost a thought exercise more than anything. But really, I don't think it's been about kind of that clarity. It's really been about conviction. So if there's a phrase that gets used most internally, especially when we're meeting with any of our folks on the external innovation side, whether it's kind of BD, or clinical, or discovery, or commercial, trying to understand opportunities, it's always been around kind of that, can we gain a certain level of conviction that this is the deal that we're going to do? It's not lost on us that in my seat kind of heading up strategy at a company, there's no easier path or faster path towards value destruction than doing bad BD or M&A.
And we want to make sure that what we do ends up kind of aligning with that high conviction level across the board, whether it's kind of clinical, discovery, commercial, finance. And so to tie that to the ANDA kind of makes sense. But I can't say that there's been a deal over the last couple of months that we had, or years, that we had at some high level of conviction, but had this uncertainty hanging over us that caused us to walk away. It's always about, is this the best asset for us? Is this something that fits in our portfolio? And the way that we always look at it is, what does it look like now? And what does it look like in Exelixis's hands?
And if we can't see that clear path of value creation and get comfortable with that high conviction transaction, then we're more than comfortable to kind of wait.
So that portfolio is mostly comprised of kind of GU, GI exposure. I know that you've been kind of very specific in terms of that being an arena in which you kind of want to shop for assets. How would you characterize the breadth of those opportunities right now that you're seeing in those specific therapeutic indications?
Yeah, I mean, one of the things Mike likes to say is we've burned the haystack, and we kind of have a small number of needles, so to speak, but we're taking a pretty close look at those needles. One of the things that one of the drivers of why we're looking at kind of this GI, GU space comes back to something that we talked about at the R&D day in December, so we call ourselves like a big small company. There's a lot of kind of pieces within that, but it really comes down to within our kind of sandbox, that GI, GU, solid tumor oncology space, we have the scale and expertise and ability to execute on par with our pharma peers, but what we also have is a kind of leadership mentality and dynamic and organization, frankly, that lets us be much more nimble and focused.
And so the reason kind of we have this focus on the GI, GU space in particular, especially as it relates to late-stage assets, is that we can take an external opportunity, an external molecule, whether it's small molecule, biologic, ADC, whatever, and plug that into our organization and see immediate value creation. Because we can go to Amy and say, what do you think of this? Oh, it's an interesting program, but I would probably make X, Y, Z tweaks to the clinical development plan. Or go to our NET team. NET's obviously an area we're particularly focused on and saying, how do you think this fits in within the commercial opportunity? So we have a particular lens that lets us evaluate opportunities.
Again, something I mentioned before, it's not what does this asset look like, but what does it look like in the hands of Exelixis, where execution risk is much lower, or the clinical development opportunity could be potentially broader. Those are the levers that we can pull to add value on these sorts of things. And so as I think about why we're focused in that space, it's that sort of thing. But the flip side is, I'm sure as you can appreciate from the investor world, there aren't that many high-quality assets either. And so the last thing that we want to do is try and bring in something that maybe we don't have that conviction level on, just to kind of plug a hole in the portfolio.
So I always say having a couple more bars on a pipeline chart doesn't really help anyone if we ultimately think that that risk isn't worth it.
OK, so a lot of the BD that we're kind of seeing play out now is being paid to a lot of non-oncology indications, right? Whether it's like obesity, INI, CNS. Is that a tailwind for you in terms of your freedom to operate? Or has the competitive density in terms of BD that you're seeing in oncology right now, has that not changed?
I mean, the difference between my seat and my peers at some of the larger companies is I get to focus on just one thing. They have to focus on everything. And because of that dynamic, they can't really let up in any one area. And so oncology is competitive. Oncology has always been competitive. Oncology, I think, will always be competitive just because the opportunity set in terms of the ability to meaningfully address patients' lives and patients with cancers' lives. Historically, there's been that kind of translation to market opportunities. And so when I look at the oncology world, I can say there's certain total addressable markets today. But what are those markets like RCC was in 2014, where improved standards of care can really shift total markets?
As patients live longer, companies like Exelixis are able to generate more revenue and drive value for all of our stakeholders. On our last earnings call, we talked about NETs in a similar way, where you can draw parallels, certainly, to RCC. But oncology, one of the benefits is you have this ability to grow the market as we help patients live longer, better lives. So that's something that's fulfilling as someone who works in the industry. And kind of I see that tangible benefit to patients. But we can see really the value of that oncology landscape is as we shift standard of care, which is ultimately what our job is, that has historically translated to opportunities and value creation and all that.
OK, maybe just a couple more BD questions, and then we'll kind of get into the rest of the pipeline and the commercial space. But most of the deals you've done thus far have been in licensing transactions. And I guess, is there an argument to be made versus kind of a structured asset transaction like that versus something like M&A? Is the latter just too inherently complex and something that you guys want to stay away from, or?
I wouldn't necessarily say it's more complex. To a certain extent, it's much easier. I'm sure our transactions and contracting folks would probably quibble a little bit. But oftentimes, there's a lot more kind of effort in terms of making sure the contracts are written in certain ways to kind of give cover to both sides in these option deals or any of that. I don't think they're mutually exclusive. If you look at the deals that we've done over the last three, four, five years, what our team was able to do was really restart and rebuild a portfolio from a standing start.
If you think back to Exelixis shutting down our discovery engine following the failure of the comet studies and restarting it in 2018, in order to kind of catch up and accelerate that, not only did we have to invest internally, but what we wanted to do is complement those efforts with kind of an external innovation engine as well. A good example of that is kind of what we're doing with ADCs, where we could have bought some ADC platform X. But what we actually realized was that the technology and the concept of the antibody-drug conjugate is so complicated that there's really no one-size-fits-all approach.
So what we wanted to do instead is basically say, can we, through a series of kind of platform collaborations, collectively engineer a platform that lets us essentially optimize the antibody side, the linker side, and the warhead side according to the tumor biology? And so those option deals kind of allow us to have a greater breadth of opportunity sets. But when we see and had we seen kind of that high conviction idea, we certainly have the ability financially and the kind of desire to become a multi-product oncology company. So I don't necessarily see the two as one or the other.
OK, and then you've been in this role now, I think, for a few different market cycles. What's your perspective on asset valuations right now in the oncology space? And given, obviously, all of the uncertainty that's afoot right now, whether it's interest rate-related, RFK-related, do you think there's going to be some meaningful impact on the pace of BD that we as an industry are going to see now until we start to get clarity on some of these things?
Yeah, it's an interesting question. Because again, when I talk to Mike and the board about deals, valuation really isn't the first thing that comes up. It's, do we like this? How does it fit? Why do we like it? That sort of thing. One of the analogies we often tell is if you go to a used car lot and there's some lemon on the lot, and you drive it, and there's some funky sound in the engine, if you say, hey, not for me, thanks, if the dealer says, how about it's 50% off, does that mean that you're going to all of a sudden realize that this is a great car? Oftentimes, a lemon is a lemon, and risk is still risk. And so that conviction level is really kind of the hurdle that we're always moving towards.
The flip side is that, yes, the capital market environment is something we really pay attention to understand the perspective on the other side of the table when we're kind of negotiating. But the reality is, for savvy companies, for savvy boards, everyone kind of has been running these dual-track strategic capital market processes for years anyway. And especially the kind of higher quality assets, the ones that we all kind of know and could get comfortable with, again, it's really about the quality of the asset. And these boards and management teams understand those relative dynamics. Obviously, if it's much harder to access capital via the public or private markets, strategics become a really important partner. But at the same time, I don't want to be seen as my job is to take someone else's risk. We want to find partners. We want to find collaborators.
We want to find assets that we can really build value. And so it's a lot of that dynamic that we certainly pay a lot of attention to. But just because the XBI is down doesn't mean that I'm going to go shopping. We want to make sure that we're being prudent about how we spend our capital.
OK, maybe we can talk about Cabo. So I think, as you referenced, kind of a really strong quarter. I know you guys talking about the continued growth that you're seeing in frontline renal. What are some of the levers that have been driving that growth? I know you're obviously kind of stacking patients here in the model as a function of these long treatment durations. But are you taking share from competitor IO TKI regimens? Are you taking share from IpiNivo within that poor and intermediate risk bucket? Are you still making inroads into the single-agent TKIs and the favorable risk population? What are you seeing out there in terms of where you're generating growth?
Yeah, so I think it's heartening and encouraging to us that we're still kind of seeing this growth in RCC for Cabo. I mean, if you look at industry data, on average, most oncology launches kind of tend to hit the plateau five to seven quarters post-indication, and we're now 13, 14 quarters post-90R, and we're still seeing that consistent growth, and I think it's a testament to not only our team and everything that PJ and his team do, but also kind of the data. We have an expression at Exelixis that everything we do is kind of viewed through the Cabo lens, good and bad, and the Cabo lens on the commercial side is that differentiating data drives utilization.
And as we continue to have longer-term follow-up of the 90R data set in particular, we tend to see increased appreciation and differentiation relative to Cabo versus some of the other IO TKI data sets. As it relates to kind of how we're still gaining that market share, that could take the rest of our time on its own, but I think it's a little bit of everything, and it's a little bit of the benefit that us as an organization has in that kind of we know the sandboxes we play in. Our competitors, so to speak, don't have the luxury of living and breathing and focusing on this kind of narrowed landscape all the time.
And so our analytics capabilities have the ability to identify kind of pockets of opportunity that we can quickly identify and really devote resource to with a reasonably high ROI. And so from that perspective, we're able to kind of continue to generate share because we live and breathe and pay attention and focus on this stuff every day and our foot's on the gas at all times. And so that's what's kind of driving the continued momentum, raise guidance this year, all of that. And it's why we kind of continue to be an outlier from a launch perspective.
OK, so the Cabometyx data was just presented at ESMO. I know you guys have filed, have an April 3 PDUFA. I know you talked about how you've seen the neuroendocrine tumor opportunity as maybe kind of looking like what renal cell did maybe 10 years ago. What are your thoughts around maybe just what that initial label looks like in terms of the line of therapy that it specifies? And I guess, how does that broadness of the label impact your perspective of kind of this accessible market opportunity?
Yeah, so there's kind of a lot within that question. I guess maybe just first off, certainly don't want to get ahead of any kind of this is what I think the label will look like because Amy Peterson or Sienna will kill me. But I think the Cabometyx data set at the end of the day was a data set that enrolled a reasonably broad population, not only in number of prior therapies, but also across kind of both PNET and EPNET, so a relatively broad cohort of the underlying disease. And what we're fortunate to have, and you mentioned the ESMO presentation and the New England Journal paper, is robust activity kind of across all of those different segments.
And so it provides us kind of a starting point that we have the ability to look relatively broadly in terms of how a drug like Cabo can benefit these patients. So we talked about the parallels to RCC. Coincidentally, on the oral side, Everolimus and Sutent are kind of the current standards. And we can all remember going back to that 2014, 2015, 2016 time frame where Everolimus and Sutent were standards in RCC as well. So we certainly have a history of kind of competing there. But I think one of the things that's most encouraging about NET is, as we've sat through a lot of these ad boards and kind of KOL work, the response and reception of the data has been particularly encouraging. But then when you unblind the profile, the TPP, and say this is Cabo, it's kind of like the light goes off.
We've talked about there's a 75%, 80% overlap of NET prescribers who already give Cabo for another indication. Then if you look at the segment of physicians who don't currently prescribe, again, there's a relatively sizable overlap of treatment centers. Our reps are actually already going to those sites. They know a lot of the back office personnel. They know a lot of the people there. That incremental lift to get kind of that new NET prescriber familiar with Cabo, it's a little bit of a different story than kind of most standard drug launches. As we look to kind of the NET opportunity, it's that epidemiology of kind of a relatively indolent disease that standards of care haven't really changed in a long time.
Potentially launching a drug where there's a high degree of familiarity, there's an understanding on how to work through a lot of the down titration, tolerability issues that present challenges to any oncology launch, and so it's something that not only we're excited about, but it's priority one, two, three as an organization as well.
OK, and then you mentioned the New England Journal of Medicine manuscript that was published in conjunction with the ESMO presentation. Should we assume that you're going to be leveraging that publication as a means to petition for a compendia listing pre-approval?
Yeah, again, don't want to kind of get ahead of a lot of those activities. But I think as a broad brush statement, one of the benefits we have as an organization, even going back to something like Cabometyx was not our study. It was an investigator trial. And we have an experience through CABOSUN of understanding what some of those, say, regulatory challenges can be when you have cooperative group trials. And we incorporated a lot of those learnings and lessons from CABOSUN into Cabometyx. And so we kind of have that institutional memory and institutional knowledge across the board. So suffice it to say that we're not taking our eye off the ball on any of these things. Obviously, don't want to get ahead of things. But things like compendia listing are something we're always aware of. But certainly don't want to promote to that.
Yeah, so maybe we can shift gears to Zanza. You guys made a pretty big splash on the recent earnings call by guiding the $5 billion in peak U.S. Zanza sales by 2033. I know you have a number of planned and ongoing phase three trials from which you derived that number. I think we're going to have a diminished amount of time to probably talk about those. But we still haven't really seen a lot of data for this drug yet. I think just that single second line RCC cohort, maybe 30 patients worth. So I guess, why push that guidance out there now? And when might we begin to see some additional data to kind of help us think about the longer-term opportunity for this asset in the context of the guidance that you gave?
Yeah, so there are a couple of things there. So I guess on the question of why. So I mentioned before, almost every meeting we've had over the last years, literally, it's been questions on the ANDA. And once kind of we got reasonable resolution on the ANDA, the next question we started getting was essentially, well, how are you going to replace Cabo? And is Zanza big enough? And the time course on all of that. And so we wanted to kind of level set and make sure people weren't missing kind of the forest for the trees. Big picture, we think that we have an opportunity with Cabo to be a $3 billion product by 2030 and Zanza to be a $5 billion product by 2033.
Implicit within that is kind of a launch curve, hopefully starting in 2026, with kind of a new approved indication every year afterwards. And so it provides that kind of big picture perspective that, say, in my role, I was getting questions, well, don't you need to plug a hole with Kaba Loe? Don't you need to plug a hole with BD? And kind of the framework was our conviction, our confidence in Zanza with now six ongoing or planned pivotal studies is that Zanza provides kind of that framework and that that's the framework that we're going to build upon and become a multi-product oncology company. So as it relates to kind of the data, there's a couple of layers within that as well.
So one of the reasons that we've been so enthusiastic about Zanza is that we really think it has a different risk profile that most other late-stage programs in oncology have and that it builds upon this 10, 15-year history of Cabo development. So it's not necessarily looking at Zanza data in isolation, but also looking at the thousands and thousands of patient data that we've generated with Cabo to kind of understand, one, is the hypothesis that we generated around how Cabo and Zanza are different, not only on the efficacy side where the kinase inhibition profiles are kind of phenocopied. So we're ideally looking for a similar efficacy profile. But from a PK and tolerability perspective, is the data that you mentioned that IKCS, does that show a difference in frequency and severity of adverse events?
We presented some data earlier this year looking at tissue distribution differences between Cabo and Zanza that may help interrogate why we're seeing things like different rates of PPE, so things like that. And then we can layer on all of the data that we've generated in STELLAR-01 and STELLAR-02. The first kind of that tip of that spear of that data set, the most mature, was that IKCS data last year. But as we talked about on the last earnings call, 2025 is going to really be a data-rich year for Zanza, not only pivotal data from 303, but there's going to be a lot of other readouts from STELLAR-01 and STELLAR-02 as that data mature that are going to give stakeholders a better sense of what the molecule looks like. So stay tuned on kind of where, what.
A lot of that's driven by abstract acceptances, titles being out, blah, blah, blah. But next year, we're certainly planning a reasonably robust effort to kind of get data out there. We've talked about something like Zanza, Tezza versus Zanza in a colorectal cancer population. That's from a STELLAR cohort that should give incremental information as stakeholders, again, think about 303, for example.
OK, and so yeah, I think if you kind of compare and contrast Zanza, Cabo, the trials you have ongoing for the former, the sales you generate with the latter, I mean, obviously, 303 gives you kind of this new opportunity in colorectal. 305 gives you this new opportunity you didn't have with Cabo and head and neck. But how are you thinking about Zanza as kind of a life cycle extender of the $3 billion in Cabo sales that you're now guiding to by 2030? I mean, you have STELLAR-311 in neuroendocrine. But I think RCC will obviously be very important to that. I know you just did the collaboration with Merck. How does the Cabo or the Zanza/Belzutifan combination? And again, I'm not sure this is something you can speak to. But two planned phase three trials.
Merck obviously has three ongoing phase three trials with Belzutifan right now, adjuvant, front line, a second line trial, head to head versus Cabo. How does your plan with Merck kind of overlap with what Merck's already doing with that asset in renal cell?
Yeah, so we've agreed with Merck not to kind of share details of our collaboration until a later date. But at a very high level, what I can say is we consider ourselves either a market leader or the market leader in kidney cancer. And now with the collaboration with Merck, we certainly can point to and want to continue to kind of maintain that leadership position. At a very high level, it's true for any of our programs. We're not in the business of running studies. We're in the business of running successful studies. We're not in the business of developing drugs. We're in the business of shifting standards of care.
And so, as you think about our intention, our aspirations, whether it's 311, a head-to-head study against everolimus, or it's the two RCC studies with Merck, the intention there is to drive and shift standard of care to ultimately help patients live longer and live better lives. And so, as it relates to everything that Merck has ongoing, I can certainly say that we consider Zanza a differentiated TKI. And understanding how that part of multi-modality combinations fit going forward is ultimately viewed through this lens of our goal is to shift standard of care because utilization, commercial success, only really happens kind of when that differentiating data is generated. So that's kind of how we think about it.
OK, we are over time, Andrew. I appreciate it very much.
Thank you.
Good seeing you.
Yeah.
Enjoy the rest of your day.
You too.
Hopefully, we can catch up at another.