All right. All right, everybody. Well, thank you for joining us, and, I'm pleased to be introducing, our next company presenter, Exelixis, at the BofA Global Healthcare Conference. My name is Jason Gerberry. I'm one of the biotech analysts. Pleased to be moderating today's discussion with Andrew Peters, SVP of Strategy at Exelixis. So Andrew, thanks for joining us, all the way over here in London.
Yeah. Thanks for having me.
Yeah, great. So, maybe just one question just to get it out of the way, just from a timing, logistics perspective, you're effectively a single-product company in the eyes of investors, and that product has a patent litigation matter that's ongoing. I know you can't speak to the litigation matter specifically, so that's not where I'm going with this, but just, can you just speak to the timing and if there's... Help us understand, I think it was initially spring, that the decision was expected, a few days, it'll be fall. So just wondering, if you can speak at all to the timeline of that legal matter, which is, you know, very important in the eyes of investors.
Yeah, so I guess before I begin, just to get it out of the way, I'll be making some forward-looking statements today, so please see relevant risks or disclosures around risks of the business, so as Mike talked about at the second quarter earnings, no new updates on the ANDA side. As you can imagine, can't really talk about specifics there, but you know, it remains kind of critical to our business and an important milestone for the company to get that resolved, but you know, at the very highest level, we're going to continue to vigorously defend our intellectual property and you know, beyond that, I can't really say around the timing because it's open.
Yeah. And if you could just maybe help frame, I guess there are scenarios predicated by the IP that you have. So, if you could get sort of at the earliest, right, you have a composition of matter patent and then presumably some pediatric extension off of that, that gets you to, what, early 2027? As for investors thinking through kind of the different patents and different kind of range of scenarios that's in play.
Yeah, I mean, I think it's suffice it to say that there are a pretty extensive and wide range of scenarios, and I think you've kind of sufficiently bookended kind of the earliest and latest and, you know, within that, you know, as a point of practice, we typically haven't gone through each of those, other than, you know, what the ANDA decision is going to ultimately do is giving us certainty and clarity. And so, you know, within that, you know, range that you set out. We have settled with Teva and Cipla for 1/1/31, and that is around kind of the true generic, the key date.
Okay, great. So with Cabo, on the commercial side, you've got a $2 billion business, give or take, right, in terms of product revenues and royalties. And so as we think about where the product is in its life cycle right now, how would you frame where you're at? You know, what are some of the growth drivers, you know, henceforth?
Yeah, that's actually a perfect lead-in for this week, actually. We're coming off the ESMO meeting, where we had a couple of, you know, interesting data sets, final phase III data for a couple of studies. But maybe just to kind of set the table, so to speak, for those who are less familiar with the story, when we gave guidance in the beginning of this year, it was, you know, for a slowing growth year in kind of the core RCC franchise. But then we highlighted, you know, 2025 and beyond is really kind of that potential for reacceleration of growth around new indications.
And so if you think about most oncology products, and we've done a lot of this kind of analytics, any new indication tends to hit steady state around five to seven quarters post-launch. And so now, as we're entering twelfth, thirteenth, 14th quarter post-2L and frontline RCC, unsurprisingly, we're starting to see a bit of slowing. So that was kind of reflected in the guidance. Now, coming back to the ESMO meeting, we had data presented, two oral presentations, first from the CABINET study, that's cabozantinib in kind of a you know broad later line heterogeneous neuroendocrine tumor population, and then CONTACT-02, cabozantinib versus a second NHT in a post-NHT castration-resistant prostate cancer population as well.
As we look towards kind of that longevity, that growth profile of Cabo, it's really about layering in those new indications. The one thing that, you know, I want to say we continue to be surprised by is really the success that P.J. Haley, our Head of Commercial, has had in that core RCC market. We talked about on the last earnings call, we actually saw a point of market share growth in that RCC market, kind of despite the competitive landscape and despite the maturation. It's been something that, you know, we're continuing to be pleased and excited about the success of that franchise.
So thinking long term, it's really going to be about continued execution on the RCC and for approved in-line business, and then expanding into, you know, mets, prostate potential, you know, all of that. Our focus going forward is really about that. If we announce our submission, our filing has been accepted by FDA, and that's with a PDUFA in April next year, and then plan to file in prostate.
Yeah. Okay. With NETs, I know you guys are sort of holding off until you see a label, right? Until you kind of talk about maybe what that can be commercially, but it does sound like your, your tone's a little more bullish about, say, NET than maybe it was with some of the prior label expansions, like DTC. And so I'm just kind of curious, am I reading that appropriately, that you see that as maybe a more substantial market opportunity than, say, DTC was?
I certainly think that's fair. I mean, you know, from my perspective, and as we as a company have really kind of dug into the data and really dug into the commercial opportunity in neuroendocrine tumors, it's something that we kind of continue to be pleasantly surprised by. You know, almost every update that we see, when we're looking at forecasts, looking at kind of the market, is it's something that, you know, continues to have a really high unmet need, but given the dynamics of the disease, the indolent population, relatively slow growing, things like duration, things like with the incidence versus prevalent pool, those are the sorts of dynamics that have kind of got me excited about, us excited about that opportunity.
You know, you did mention that obviously, you know, what the label looks like is going to have a huge impact on, that total kind of market potential. But suffice it to say that NETs is an indication that, you know, we're really excited about, not only with Cabo, but on the last earnings call, we also announced a new phase III study with zanzalintinib, and I'm sure we'll get into that later. But it is an indication that I think, you know, we really feel that as we become market leaders in the RCC space, we can really grow to be kind of the market leaders in that space as well.
Okay. So how should investors be thinking about you guys? On the one hand, you generate a lot of gross profit off of your sales and royalties on Cabo, and you've had tighter expense management this year, leading to greater profitability. So, you know, a lot of companies in the space, there's this balance, right, between profitability and investing in pipeline. So, I guess, how do you guys, you know, manage that balance, and, you know, how do you think about that in terms of profitability and profitability growth from here versus, you know, seeding the pipeline?
Yeah. So this is a topic I think kind of Exelixis, as a company, probably thinks about more than most in the space. And we always joke that we run Exelixis like a business, not a biotech. And I think some of our actions over the last, you know, eighteen months have really kind of shown that. So, you know, on the one hand, kind of obviously, you know, what we want to grow into is a multi-product oncology company to have multiple, you know, differentiated therapeutics to help patients live longer, better lives. And that's, you know, our perspective on true kind of value creation in growth in this industry is when you layer on kind of the margin expansion and the top-line growth from multiple products. You have to balance that with kind of appropriate investment.
You know, the reason I say or kind of highlight appropriate investment is it's been our observation that, really, to be successful in this business, you need to generate differentiating data. And kind of me-too data or undifferentiated data, you know, usually doesn't translate to commercial success. A lot of companies, you know, we tend to observe, tend to view the FDA approval as kind of the finish line, but to us, it's actually the starting line. And so we need to make sure that when we bring products to market so that PJ and his team can bring them out to, you know, clinicians and patients, it's actually doing something and shifting kind of that, that standard of care.
And so what that involves with, from an investment perspective, is making sure we're, you know, developing the right products that have that potential to, to be differentiated. A good example of that is, again, on the last earnings call, we announced the discontinuation of XB002, that's our tissue factor targeting ADC. When we looked at the data, you know, ultimately, we came to the conclusion that it wasn't going to be differentiated than Seagen, now Pfizer's Tivdak. And so when we thought about continuing to invest in that program, if it wasn't going to be differentiated, you know, that wasn't really the investment we wanted to make.
On the flip side, as we've done kind of more work in the area of NETs, not only through kind of the Xanza, CaboMETYX, but understanding Xanza's profile going forward as well, we identified the STELLAR-311 study, the head-to-head of Xanza versus everolimus, in kind of that first oral population, as something that we actually think is a smart investment. So what we talked about on the second quarter earnings call was really a reallocation of resource to kind of make sure that we're making smart investments. So ultimately, as we think about capital allocation and how do we invest in the business versus how do we, you know, act as appropriate stewards of shareholder capital, you know, that's the sort of dynamic.
We've returned about $1 billion in share buybacks over the last 13 months, and we announced another $500 million buyback again on the last earnings call. And so it's really kind of balancing the cash flow generation that we have in the business, investing in our pipeline, and then generating data to allow us to.
Yeah. So if you secure a favorable patent ruling and you get yourself six, seven years of product life off of what seemingly is a pretty stable RCC-driven business, right? How does that affect the capital allocation strategy, if at all, right? In terms of this level of R&D spend, this, you know, periodic share buyback versus perhaps being more aggressive, playing offense on the BD side, or maybe having that runway gives you the comfort to just say, "We're going to play the long game with our internal R&D assets that we have.
Yeah. So I think the best way that I would think about it is what the ANDA decision will give us certainty, whereas right now, we have confidence. But on the capital allocation side, I wouldn't say that historically, kind of that's been, you know, say, the biggest, or kind of the biggest factor to consider. It's actually around conviction. And so what we mean by conviction is this the appropriate investment? Is it the appropriate investment internally, and importantly, is it the appropriate investment externally? You know, this is an area that I spent, you know, a good chunk of time looking externally on the kind of, you know, BD, M&A side.
And historically, we've had an opportunity to, you know, bring in many, many, many different assets across all of the kind of in vogue, hot targets that, that you can imagine. But ultimately, as we dug into the data, more importantly, dug into these commercial opportunities, we recognized that we didn't have that conviction to trigger. And, you know, what I always say is, there's almost no more value disruptive dynamic in this business than doing bad M&A.
Yeah.
And so we need to make sure that we have that kind of conviction in the asset. So I wouldn't necessarily link it to the ANDA. I would say when we find an appropriately... You know, when we find that high, high conviction, either clinical or, you know, commercial, program, that's the thing I think that we're going to be excited about.
Curious, what are you seeing out there in terms of at a high level? It seems like the oncology space, publicly traded names, have maybe had a bit of a setback in the past few years. When we look at deal flow, there's a big, it seems like a big uptick in private health companies are getting bought, and maybe that's a challenge accessing the capital market. So as you kind of see where your position, do you feel like the opportunity set maybe is more on the private side?
I think the opportunity set has always been small, because it really comes down to, at least for us, it's not about, you know, we don't have a set dynamic of, "We're going to do 10, 15, 20 deals a year and hope that one or two of them work." That's just not a game that we want to play. It's, we want to be more specific, more selective, focus on high-quality assets where we can get conviction in the target, we can get conviction in the clinical plan, we can get conviction in the commercial opportunity. And so I don't think that dynamic of the world of oncology, of really high-quality assets, has always been small and continues to be small. I think what we always view things through is, what we call the Cabo lens.
So what we mean by that is we actually got Cabo back twice, and so just because something may be out of favor or, you know, passed over or whatever, that doesn't necessarily mean that we think it's, you know, not a great opportunity.
Mm-hmm.
It's we have to have that differentiated perspective. In the case of Cabo, it was mechanism-related, it was data-related, and it was market-related. And we can apply that same filter, or we do apply that same filter to every kind of asset we look at externally. And so-
Mm-hmm.
Whether it's a public or private company, it's probably less relevant to us than how does it fit in kind of with our core skill set in that GI, GU, oncology space. You know, one of the lenses that I always look through is not what does the asset look like right now, but what does it look like in our team's hands?
Mm-hmm.
Because oftentimes, we can go to our clinical team and, oh, the current study that a company is running, it's probably not the ideal one. Here's how we would amend it. Here's what we would do. We would expand it of this indication. Here's how we could potentially combine Zanza. So those are all of the dynamics that when we look externally, really kind of points us in the direction of, is this an attractive asset?
Yeah. And is investing in Exelixis' stock still something that, like, investors should expect that to continue in the future, or were those more one-offs in terms of the repurchase programs?
Yeah, I mean, now that we're in our third program, it's something that, you know, we're quite familiar with, and even before kind of they were first announced, the topic of buybacks has been something that we've discussed internally for years and years and years. Under the understanding, the dynamic of when, how much to execute, you know, ultimately, that depends on a variety of factors, including, you know, our confidence that the stock is undervalued, but I think one of the things that you can think about, in particular, the last two buybacks that we've announced has really been about understanding the dynamic of the capital.
So the one that we recently completed and the one that we've announced, kind of the core there is really about them being funded by cash flow and not being end of the balance sheet, balance sheet dilutive. And so when we started getting additional, you know, say, milestones from our Ipsen collaboration and our, you know, outlook on Cabo revenue going forward, that confidence in the cash flow is something that we could look at and say, "Okay." This gets us much more comfortable with kind of the buyback dynamic while saving that kind of balance sheet, strategic asset.
Mm-hmm.
Should we find something externally to invest in, as we also continue to invest internally.
Okay. Maybe just in terms of your, ADC ambitions, about four years now or so, you've been kind of piecing together a series of partnerships and transactions, and where do you see the company right now in terms of the, the ADC ambition? Maybe the lead program didn't maybe go as quickly as, as you maybe hoped, and, and how quickly could you maybe have an asset that's ready for prime time?
Yeah. I mean, ultimately, kind of the short answer to the question is as soon as we can generate data. You know, XB010, our 5T4 ADC, recently entered the clinic, and, you know, we're hoping to bring XB371 into patients next year as well. That's the kind of the next gen topo-based tissue factor that we're developing. To kind of take a step back for those in the audience who are maybe less familiar with the dynamic, go back to, say, 2018 or so when Exelixis functionally restarted our discovery effort, what we kind of had the opportunity to do is almost not say blank page, but say, "Okay, where do we want to focus on from a research perspective, and what are the modalities? What are the indications, all of that.
One of the things that we chose to focus on was ADCs, because it was really a great marriage of kind of our cancer biology background, small molecule chemistry, and emerging expertise as we were building up in the biotherapeutic space. So if you think about ADCs, it's a combination of the binder, the antibody, the linker, you know, the conjugation part, and then the warhead. And so we looked at the landscape of ADC companies, and kind of the conclusion that we came to is there wasn't really one company or one platform that we felt had really solved that dynamic. ADCs are a tremendously interesting modality, but they're unsurprisingly complicated.
Cancer's complicated, drug development's complicated, and just because you have a, you know, high-affinity antibody with a relatively stable linker and a medium-sized DAR, doesn't mean that that same combination will fit across every tumor type, every target. And so what we've realized is a better approach was to actually develop this kind of Network of collaborations where we could mix and match and kind of iterate and optimize on the binder side, on the linker side, and on the warhead side. Tissue factor is a great example of that, where we have what we think is a differentiated antibody versus, you know, any of the other tissue factor ADCs, where, unlike Tivdak, the antibody we use for XB371 is uncompetitive with factor seven, which, given its role in the coagulation cascade, leads to bleeding risk, and so differentiated there.
And then on the linker warhead side, XB371 actually takes a very stable linker that requires two different steps to release the warhead, and then it has a topoisomerase payload. And so if you think about why is that relevant? Well, tissue factor, widely expressed across a wide range of tumor types, but somewhere tissue factor is highly expressed, may be less sensitive to more kind of auristatin-based warheads, where they're especially sensitive to topoisomerase-based warheads. So we kind of looked at that heat map, that landscape, and developed 371 with that same dynamic. Similarly, with 010 , the 5T4 that I mentioned before, we kind of looked at a number of differentiation iterations of that combination and ultimately came down to what 010 is.
And so 5T4, again, a promising target that maybe was interrogated in the past with earlier gen ADC technologies that may not have really fully explored the opportunity there. So when we think about ADCs, it's certainly part of our core strategy going forward, but we have to make sure that we're developing what we think are differentiating drugs, and if we generate data that suggests, you know, our hypothesis of differentiation isn't there, we're going to kill them. And I think we've seen, you know, recent examples of that.
Okay. Maybe shifting gears to neuroendocrine tumors, and, you know, this is an opportunity both for Cabo and for Xanza. It's, you know, our understanding as you kind of framed it, it's a very indolent disease. People tend to have a pretty long lifespan, and cycle through a lot of different therapies. So maybe how you think about the size of this, how the prevalence plays into the market sizing, if at all, and then just the sort of segmentation that, you know, you think about that's relevant to thinking about the opportunity for first, Cabo, and then eventually for Xanza.
Yeah. So, you know, I guess at the very highest level, and I think PJ talked about this last call, in that kind of second-line plus population, there's about nine thousand drug-treated patients annually in the U.S. And as you mentioned, kind of they tend to cycle through multiple different therapies. I mean, if you look at the CABINET population, which is really kind of the most contemporaneous trial, you know, about half the patients had seen Lutathera, a good number had seen everolimus, a similar number, or a good number, had also seen Sutent... and a lot of them have also seen CAPTEM, kind of the chemo combination in these patients as well. So they cycle through a lot of different options.
One of the things that always has jumped out to us is, you know, this is a population that certainly has parallels to kind of RCC in the 2013, 2014 range, where coincidentally, Sutent and everolimus were the two standards of care, so we understand how data can kind of shift that market opportunity. You know, the ESMO meeting was a really positive one for me, just to kind of hear from the podium kind of the data being presented and the discussion that happened afterward, and the Q&A and all of the KOL work that we've done, ad boards, et cetera, that really kind of talked about the excitement for bringing a new therapy like Cabo. You know, we've done this blinded market research of TPPs, Target Product Profiles.
The physician KOLs are actually, you know, excited about the data. And when we unblind it and say, "This is actually Cabo," they go, "Oh, okay, I get it." That's because if you look at the prescriber base of NET, we find that about 75%-80% of those NET prescribers actually already give Cabo in other indications. So there's this high amount of familiarity. There's this understanding of how to give Cabo, how to really deal with the AEs that will inevitably pop up, down titrate, how to dose them, all of those things. And so kind of that dynamic is something that, you know, you, you mentioned it before, and our excitement, our focus, our enthusiasm about NET, certainly that gets layered into as well.
Yeah. So one thing I wonder about, like, so you mentioned that 75% are Cabo writers. You know, is this concentrated in GI, GU type of specialists? The reason where, where I'm going with this is, you know, we've seen in certain, like, maybe more rare cancers, you have this community oncs see one or two patients sporadically over the year, and these become, like, more challenging markets to launch into versus, maybe markets that are maybe better understood and patients are concentrated within certain specialist offices.
Yeah, I wouldn't necessarily group it in kind of the more challenging niche oncology space.
Yeah.
Coming back to how I was framing it before, the more we've dug into the market opportunity, the patients, prescriber base, I think the more comfortable we've been, that, you know, our existing commercial footprint, plus some additional investment, but frankly, not a lot, should be sufficient to kind of help us launch into the space. You know, if you think about our business overall, kind of the GU side is certainly kind of our largest component. But as we look ahead to first with CABINET and then potentially with STELLAR-303, our Xanza and colorectal study, you know, ultimately, we hope to see our kind of both sides of the GI, GU, businesses be more kind of online.
Yeah.
And so, you know, our commercial organization is really primed and ready to be kind of, you know, again, label-dependent, you know, launchable.
So with the CABINET data, I imagine in the base cases, second line plus with, you know, treatment, irrespective of, I guess, the site of the tumor location, and you've generated a lot of data broadly, right? That the activity in patients, irrespective of the site of the tumor location. So is that a fair kind of base case framing?
Yeah. Again, I don't really want to get ahead of, put words in FDA's mouth, but if you look at the CABINET population, it really was a reasonably broad, fairly heterogeneous group, not only across pancreatic and extra-pancreatic NETs, were actually two different parts of that study, but also included patients, as I mentioned before, who had seen prior Lutathera, prior everolimus, prior CAPTEM, prior Sutent. And so it really was kind of a mix of a lot of different patient types. And so this question came up during, you know, during the oral discussion afterwards, and it's certainly going to be, you know, one of those things of where does Cabo fit in there? Obviously, it's label dependent, but the CABINET data certainly provide, you know, a broad range of patients-
Yeah
-to help physicians and patients get healthy.
Is the right way to think about the primary competition, then, effectively everolimus or chemo in that sort of post Lutathera setting, or alternatively, could even play a second line for people who don't want exposure to the radiation, with Lutathera?
Again, it's going to be dependent on the label, so probably a little too soon to think about that.
I realize the answer to this question leads to the obvious, well, it depends on the data, right? But I think about Xanza versus Cabo, right, and what the study that you're running could afford you competitively in that space versus what Cabo you know gives you. Having an active comparator, you know is like the main difference, right?
311 .
Yeah.
Yeah. So 311 's a head-to-head study of Xanza versus everolimus. We haven't kind of published the details specifically of that study, so stay tuned a little bit here.
Yeah.
But really, you know, as Amy and PJ kind of talked about it last fall, it's really about generating data on being that first, or, and so that's the kind of, you know, value of that study, is to establish a standard of care there.
Yeah. Okay. You know, as we think about this idea of functional status of the tumor, when we've talked to physicians, at least as it pertains to something like everolimus, what we tend to hear is that, irrespective of functional status, they'll use the therapy and that it's very difficult, I think, to distinguish functional, non-functional. So not asking you to speak to the label, right, but as it pertains to sort of a practical marker reality and how these clinicians are, you know, wrestling with that distinction, in treating these types of patients.
Yeah, I mean, I think, again, I point to one of the benefits of the CABINET data is really kind of the breadth and the heterogeneity of the patient population and the consistency of data there. I think, you know, one of the things you can point to is just one spot.
Yeah.
That there's not really kind of a patient group that jumps out, that's driving all of the benefit, which frankly, you've seen a lot of other data sets. There was just at ESMO in Barcelona. I can't tell you how many, you know, presentations I sat through, where kind of that's one of the core dynamics. And so, one of the benefits and value really jumps out in these kind of KOL ad board-type things, is just that it, it seems to work in a fairly heterogeneous group, and there's not one population-
Mm-hmm.
-that does or doesn't do well.
Yeah. Okay. And I know you mentioned that the phase III Xanza design isn't been fully made available yet, but I mean, going head-to-head against something like everolimus, what gives you the confidence that you can win on a PFS endpoint? So I guess we would look at CABINET, we'd look at the RADIANT trial for everolimus. And is that the right way to think about it, or is the internal assumption that, you know, Xanza can generate a more profound PFS in this setting, and that's what underpins confidence that you can ultimately win on a PFS endpoint?
Yeah. So I don't want to jump kind of into the specifics there, but speaking broadly, you know, a couple of things to talk about. The first, you know, obviously, it's a different tumor type, different indication, but we look to kind of Cabo's experience with METEOR, beating everolimus head-to-head in an RCC population. There's certainly some things that we can point to and kind of get us incrementally more comfortable. You know, this is a drug, this is a mechanism, a target that we beat head-to-head in another tumor type. And the data we've generated with CABINET and the data that we've generated with Xanza kind of, you know, showing maybe the emerging differentiation profile of Xanza versus Cabo, that's something that gives us confidence as well.
So, you know, combination of, you know, the fact that everolimus is a standard of care, but I don't think physicians would necessarily describe it as, you know, the first drug.
Yeah.
And I think the fact that, you know, we're getting increasingly comfortable with the profile of Xanza. We're certainly comfortable with how kind of Cabo's done, either head-to-head or, you know, in NETs as something that plays in as well.
Mm-hmm.
You know, it's a combination of all of these factors, I think, at least at a very high level, kind of, that gets you.
How do you think about... You know, you're effectively competing against non-promoted treatment options, and just simplistically, having a promoted treatment option where physicians are sort of forced to make some cross-trial inferences, right, around Cabo versus, say, everolimus or, or chemotherapy. And so, have you looked at just the basic premise of how a promoted treatment option may compare against non-promoted options? And sometimes physicians just want the newest, more innovative thing.
I certainly think that's something that P.J. and his team think about a lot. Probably gonna, you know, come back to. We'll see what the label looks like.
Mm-hmm.
We'll see everything, but you know, suffice it to say, you know, the thing that always kind of gives me comfort is that the thing that I mentioned before is when, you know, we unblind that TPP, and it's Cabo, physicians know Cabo.
Yeah.
They know how to use it, and, you know, that's a dynamic that, you know, has always jumped out.
Yeah. Okay. Maybe shifting gears to Xanza and the frontline non-clear cell RCC opportunity, and realizing that a lot of TKIs are currently used there. So what does the current landscape look like in terms of non-clear cell? Is that a space where Cabo derives a lot of utilization? Because we think ahead to the world that Xanza could potentially be launching into if it secures a label in non-clear cell.
Yeah. So there are a couple of dynamics at play there. You know, at a very high level, even if you look at kind of guidelines, you know, factually speaking, all drugs that have a label for clear cell RCC also have a label for non-clear cell. And so you tend to see somewhat fragmented utilization across each of those therapies, Cabo. What the STELLAR study is designed to do is really generate that first pivotal randomized data in a population that what we think or we hope kind of define a standard of care there. Whereas you look at the data sets that have been generated, that are label-enabling, that are guideline-enabling for other drugs, again, Cabo included, they tend to be kind of single-arm, phase II, IST-type studies that frankly just have different levels of evidence.
304 was really designed to just establish a standard of care there. You know, how that plays out competitively will ultimately depend on the data, and but really kind of the intention with that study is, you know, as we thought about Xanza development early on, 303 , 304 , 305 , were kind of those obvious low-hanging fruit studies to run. Because, you know, either Cabo data that we've generated or something like, you know, non-clear cell RCC, where we believe it's especially sensitive tumor type. 304 is really that chance to kind of plant a flag in the ground in that kidney cancer population, establish a standard of care, and then layer on additional studies over time. Yep.
Okay. You've guided, I think, to completing enrollment of the study middle of next year. How quickly could we expect top line, with, with this study?
Yeah. So generally, kind of as a point of corporate practice, we talk about timelines once we've completed enrollment.
Yeah.
You know, 303, where we recently completed enrollment and have gotten towards the data next year.
Yeah.
Obviously, with any of these studies, they're event-based, so it can be a little tricky to guide specifically, when that top-line readout will occur, just because it's event-based, predictable-ish.
Yeah. Yeah. Okay. Within the non-clear cell, I know Merck with Lenvima has gotten a label update. They've run a, I should say, like, more of a single-arm study. And so I guess, how do you see that as a competitive interplay? You know, Merck planting its flag, maybe in the non-clear cell space with Lenvima. And I imagine you might come back to, "Hey, look, we've done pretty well against Lenvima in the broader RCC market, and we feel pretty good about how our profile will stack up.
Yeah, I mean, I think it's, again, it's about the data and all of the above. Pretty simple. Wait and see what the data look like, but you know, certainly, Cabo has been able to, you know... We're the number one TKI, both as monotherapy and combinations, despite that kind of competitive pressure.
Yep.
And so a lot of those things.
Yeah. Okay. So you've got, what, four pivotal programs right now, I think, for Xanza, that have been announced. You've got a phase I basket trial evaluating Xanza, I believe, in multiple combinations, different tumor types. Maybe if you just talk about the progress that's made in this basket study and, you know, when we could expect perhaps new data to emerge out of this?
Yeah. So, you know, 2025 is going to be a big year for us for Xanza, not only kind of with the 303 readout, but we've also talked about data from the early STELLAR studies, you know, RCC, colorectal cancer, kind of combinations in RCC. That's the sort of data set that you'll expect next year, and frankly, kind of if you can see this increased excitement from, you know, from Exelixis, it's, you know, we're very happy with how that data continues to progress and to mature, and so we're, you know, excited to share it, but stay tuned next year. It's going to be a really great.
Yeah. Okay. And your just current thinking on sort of the, in RCC, the HIF-2 kind of PD-1 combination approach. I know competitors are looking at this approach, and you guys have been a leader in RCC, and so, you know, is that something that you guys, I imagine, look at and think about as something?
Yeah, certainly. I mean, you know, RCC is kind of. We're a leader in RCC, and we certainly want to continue to be that. You know, one of the dynamics that we want to make sure we're getting right is, again, coming back to this concept that we talked about before, we're not in the business of running trials just to run trials. We want to shift standard of care. So what those combinations are and how that differentiates is really important and critical, and we got to think about, you know, the best combination partners, the best indications within RCC are really all central to that dynamic. So kind of stay tuned there in what we're doing in RCC, but, you know, needless to say, it's an area we're watching.
Yeah. Okay. So more to come, I guess, on the frontline RCC kind of strategy from the company.
Yeah.
All right. And then maybe just you know, at ESMO, you had updates in Net and in prostate, you know, maybe what do you feel like are some of the key highlights that you'd emphasize to investors? I feel like from a Net perspective, I think you've disclosed a lot of the data maybe previously, but what do you feel like maybe was incremental coming out of ESMO for either of those two opportunities?
Yeah, so CABINET, pretty straightforward. Kind of the best way to think about it is that's going to be the data that will eventually be in the label. You know, especially, you know, the central versus investigator review, PFS data, and then a lot of the AEs, were kind of cleaned up as well. And so the, the CABINET data from ESMO is really, you know, what I would think of as kind of label data. And then CONTACT-02, was the final survival analysis, and it kind of gave, you know, the first look at that survival data, not only overall, where we again showed no decrement in survival, but also kind of the key subgroups that were, pulled out, especially going to be discussing afterwards.
You know, the populations like patients with liver mets, patients with bone mets, and how Cabo-Lenvima does, and, you know, really those are the patient groups of highest unmet need.
Yeah.
And so CONTACT-02 data, ESMO just reiterated the point of, you know, positive co-primary endpoint and PFS, and then that survival data and kind of looking at the different subgroups.
So with prostate, then, I guess, you know, still on track to submit the sNDA later this year.
Yeah
... for Cabo, and then I guess the bet here is, you know, based on some precedents that are out there, the PFS with no OS detriment underpins sort of the confidence that you can get this as a label add-on.
Yeah. So, you know, again, it's ultimately going to depend on the totality of the data, now that the CONTACT-02 is available, it's really that dynamic. But, yeah, we've guided for submission of the sNDA later this year.
Yeah. All right, well, we're out of time, but thank you so much for joining us at the conference.
Yeah, thank you. Yeah.