All right, good morning, everyone. Thanks for joining us. My name is Derek Archila. I'm one of the Wells Fargo biotech analysts. For our next fireside discussion, we have Exelixis from the company. We have Andrew Peters, who's the SVP of Strategy. Andrew, thanks so much for joining us today.
Yeah, thanks for having us. Excited to be here.
Yeah. All right. Well, maybe just as an intro, maybe just give us kind of the state of the business, what's going on with Exelixis, and then we can kinda, you know, dig into some of the questions.
Yeah, happy to kind of run through that, and you know, glad to be here in Boston this week. You know, weather in the East Coast this time of year is always great, so really enjoying it. Before I begin, as a reminder, I'm gonna be making forward-looking statements today, so please see relevant disclosures in our SEC filings around risks to the business. So Exelixis, I think, is in a really interesting and almost unique position in the industry in that, you know, we're a commercial oncology company really focused on driving standards of care for patients with cancer.
Our lead compound CABOMETYX, cabozantinib, really is a standard of care across multiple solid tumors, HCC, DTC, and then obviously RCC, where it's the number one IO-TKI and the number one TKI monotherapy as well. You know, we've given guidance for product revenue in the kind of $1.6-$1.75 billion range for the year, and so obviously, we've been kind of successful from that end. But the reason I say that we're in a unique position is that as a company, you know, as the CABO franchise continues to hum along, and I'm sure we'll get into kind of the growth drivers there, we're really focusing and investing in kind of the next-gen IO-TKI franchise as well.
That really takes a lot of the lessons and learnings from CABO, where CABO was kind of that second-gen, improved TKI, that improved profile from the first-gen agents. And then similarly, zanzarlitinib takes kind of the, the key liabilities or kind of, you know, key issues with CABO and then improves upon that, notably around its long half-life and some of the challenges from a patient management and HE management perspective. And so as we're investing in the Zanza franchise, we now have four pivotal studies, either announced or ongoing, with the first of them likely to read out in late-line colorectal cancer next year.
So we're kind of at that. I don't want to say transition point as a company, but we're certainly vectoring towards being a multi-product oncology company, then layering in a lot of what we're doing in our early-stage portfolio, whether it's our XL309 or USP1 inhibitor or some of the interesting ADCs that we're developing as well. So really, exciting time to be at Exelixis and exciting time to have a conversation with you.
Great. Awesome. Well, thanks for that. And, you know, maybe starting with CABO and some of the... commentary that you just said, just, you know, how do you think about the growth trajectory, you know, of this product? And, you know, maybe we can go through some of the growth drivers just in RCC and kind of where you think you can maybe get more penetration.
Yeah. So I think if you look back, maybe to kind of around the JP Morgan being in a year timeframe, where we gave product revenue guidance for the year, really kind of the core of that message was unsurprisingly, the RCC market starting to hit a bit of a maturation. We've done a lot of kind of work on the commercial oncology space, and in general, oncology products tend to hit steady state, around five to seven quarters post-launch.
CABO's now in RCC, kind of post 9ER, you know, 12, 13, 14 quarters in, and so as we looked ahead to 2024, we really thought it was gonna be about a maturation of the RCC market, and then looking ahead in 2025 and beyond, to two potential new launches in NETs and CRPC, following two positive phase III readouts last year. What we've seen since is not only kind of enthusiasm and excitement around the NET indication, certainly something that we're getting a lot of interest in, patients, physicians, KOLs, as they see the data and understand the data, are certainly interested in. But PJ and his team on the commercial side have kind of continued to really invest and kind of continue to, you know, increase our share in the RCC space.
So if you look at, you know, Q2 earnings, we gained another market share point, which for a product that is now, you know, many years post that first, you know, 9 ER launch, is really impressive and is I think a testament to not only PJ and his team on the commercial side, but really I think kind of the data that we've been able to generate that really resonates with patients and physicians alike, and kind of has established us as really, you know, a market leader in kidney cancer.
Got it. Yeah, so maybe just a follow-up to that in terms of just in renal cell, you know, what has made CABO so successful there, and you kind of keeping this toe hold, you know, in that specific market, but also, how do you guys think about kind of the evolving competition there? Like, you know, will you be competitive in that market, you know, for years to come and even, you know, going maybe with the future Zanza, again, TKIs, are they gonna be continued to be a mainstay in renal cell?
Yeah. So I think one of the kind of through lines across, you know, everything we do as an organization is the, you know, belief that really, at the end of the day, our job is to shift standard of care for patients. And we're not in the business of developing me-too programs, you know, generating data that, you know, looks just as good. Because I think what a lot of times people miss in this industry is they view FDA approval as the finish line, when in fact it's actually the starting line. And what we've found over and over, and over again, is we've looked. You know, I spent a lot of my time looking externally, kind of on the BD and M&A side.
You know, there are a lot of assets that really are developed through the lens of, you know, "This looks good. Let's just develop it quickly, get on the market and, you know, hope it works out." What we've found is, as you're able to generate differentiating data that truly shifts the standard of care for patients, that's ultimately what drives utilization. That's what drives value creation, both for patients, stakeholders, and shareholders. That's kind of the focus. If you think about what we've been able to do in RCC, ultimately it comes down to that data set that continues to resonate with 9ER.
You know, not only kind of that initial data, but as we've had these incremental, you know, three-year, you know, and longer updates, these are data sets that continue to kind of hammer home that the combination of CABOMETYX, in particular, kind of the key insight that we had ahead of 9 ER, was the 40 milligram dose versus the prior 60 milligram dose. Those are the sorts of data sets that kind of truly shift standards. So as you ask about, you know, where do we think RCC is going in the future? Really, the answer is gonna depend on data. You know, do we think that TKIs have a role? Certainly, you know, we do.
If you look at the data sets that not only, you know, CABOMETYX, but other IO-TKIs have generated, we think it actually really sets a high bar for differentiation from there, so as we think about the RCC opportunity with Zanza in the future, it's really gonna be about understanding how we can shift that standard of care. What are the areas of opportunities that are underserved right now? Whether that's earlier, whether it's, you know, other parts of that journey. You know, again, the way we think about CABO or Zanza or anything in RCC is we wanna make sure we're part of the patient journey for anyone who's diagnosed with kidney cancer.
Got it. And maybe just shifting gears to neuroendocrine tumors. So again, you cited that as an interesting growth opportunity for CABO. I mean, maybe you can just kind of frame up the opportunity and, you know, what type of profile are you starting to see from CABO, you know, in those types of patients?
Yeah. So, just to kind of highlight, so we're gonna have the final data from the phase III CABINET study next week at ESMO. And it's really gonna be kind of the data set that's gonna be going into the filing. So just to kind of preview that for folks. But so CABINET was a large study across both EP and PNET, pancreatic and extra-pancreatic neuroendocrine tumors, run by the Alliance Cooperative Group. Data there were very encouraging, kind of enrolled a little bit of a hodgepodge of patients who had experienced kind of, you know, post TKI, post Lutathera, post SSAs, et cetera. So, fairly heterogeneous group, but really saw pretty robust data with PFS HR ranging from 0.2 to 0.4.
So, across kind of both of those, subgroups, or in that. And one of the things that we've found is kind of we've continued to, and really invest in a lot of kind of market research, KOL work, ad boards, is really an excitement and enthusiasm about the data. You know, one of the things that I get particularly encouraged by is, you know, show kind of a blinded TPP, target product profile, of the data, and physicians are, you know, quite interested. Then we say, "Well, this is CABO." Then they're like: "Oh, okay, no-brainer." Because if you look at, kind of the physician group that treats these NET patients, we've found that there's about 75-80% overlap of patients who... Or physicians who have already prescribed CABO.
So it's a drug that they're familiar with. They understand how to use it. They understand how to titrate based on AEs, and so it's not like they're gonna be learning something kind of the first time around. So that translates to, you know, our enthusiasm about kind of the commercial opportunity when we combine that with a lot of our market research around sizing. So neuroendocrine tumors, relatively indolent disease. We think there's about 15,000 kind of newly incident frontline patients, much larger kind of prevalent pool, given the you know, slow-growing nature of the tumor.
But, you know, as it specifically relates to kind of the CABINET-type subset, you know, PJ talked about on the last earnings call, we think there's around, you know, nine thousand plus, kind of second line plus patients. In the US, that's gonna be kind of our target launch market initially. So when we combine, you know, what we think are a particularly compelling data set that seems to resonate quite significantly or quite well with the patient or the physician groups, with CABO being a kind of a well-known agent in that space, in a market that we think is underserved, you know, that's why you're hearing us increasingly enthusiastic about that and why we're, you know...
Full speed ahead, investing ahead of the launch, and then even looking ahead to something like Xanza and the 311 study, which we announced recently, which is potentially going to help us establish, you know, Exelixis not only as an RCC company, but potentially in the future, as kind of a NET company as well.
Got it. Interesting. Can you maybe just help us understand what the standard of care is in NET right now? And, I mean, presumably, you know, most of these patients will progress, so, you know, I guess, what's your kind of expectation in terms of utilization of CABO, you know, if it's once it's approved?
Yeah. So the standard of care is a little bit kind of, I want to say, totally across the board, but, you know, NETs are a, you know, somewhat heterogeneous group of different types of sub-tumors. As I said, EP-NET and PNET, SSTR positive, negative, SSTR positive, kind of the somatostatin receptor. It's about 80% of patients. There's another 20%, who are negative, who don't get kind of the SSA analogs, the octreotide, lanreotide, for example. Those are used, but on the kind of oral space, the oral TKI space, standard of care is really Sutent and everolimus.
You know, we think about or kind of the closest analog that helps me visualize at least, NETs is it's kinda more similar, if anything, to where RCC was in, like, that 2013, 2014 timeframe before a lot of the newer next-gen agents like CABO came out. Coincidentally, you know, you have the Sutent and the everolimus there, but it's really a market that is ripe for kind of new agents. You know, there hasn't been a new oral agent approved there since, I believe, 2016. So it just shows kind of the opportunity set that we have, not only with CABO and the cabinet data, but as we look to STELLAR-311 and running head-to-head Xanza versus everolimus.
That's the sort of opportunity that we think we can, you know, again, really begin to capture and kind of establish that beachhead into an indication we think is underserved, and we think we can, you know, really become a leader there.
What do you think the ramp looks like in terms of, you know, sales and utilization, you know, in this type of, you know, tumor?
Yeah, so, you know-
Is it different than, I guess, RCC? Like, what, what do you... What's, you know?
So, that'd be an area kind of I don't wanna get ahead of. Usually, what I'd say is it depends on the label.
Mm-hmm.
And it depends on the label, and it depends on a lot of factors. What I can say is that we're making those investments now.
Okay.
A lot of those pre-launch activities to make sure that we really optimize that. You know, I think, you know, we'll see ultimately how the label shakes out. The cabinet dataset, you know, we're compelling across a relatively broad patient population, but anything as it relates to market size or ramp, just too early.
I mean, what are some of the variables in the label? Is it, you know, specifics about the data that you wanna get included or you're pushing for? Like, what's the bull case label in your opinion?
Yeah, it's probably an area I want to stay away from, just kind of-
Okay
... as we're entering, you know, discussions and continues back and forth with the FDA after the submission. But I think a lot of the key, you know, unknowns with any label is-
You know, what is the indication statement? What is the, you know, patient population? Those sorts of things.
Okay.
Just very generically.
Yep. Okay. Gotcha. Is there anything else that, like, for NET, that, you know, at least from a CABO perspective, from, you know, the way that physicians will use it? Like, again, some of them already have experience. Anything change there? Like, is there any, like... I'm trying to understand, like, is there anything that would be a hurdle for them to use it in NET patients?
You know, again, we'll see how the label shakes out, but I think one of the things that I'm particularly encouraged about is kind of that familiarity.
Mm-hmm
... you know, on the physician side with CABO. You know, understanding the differences between 60 and 40 and how to down titrate.
Mm-hmm
Once you see adverse events. You know, any VEGF targeting TKI, you ultimately see AEs and need to down titrate, and so understanding that algorithm, having the familiarity in that experience, certainly we're starting from a favorable position, I'd say. So, you know, that's probably kind of the core of it.
Got it. And then maybe, you know, shifting to, you know, one of the other growth areas for CABO in prostate cancer, maybe just, you know, frame up that opportunity based on the data that we've seen from CONTACT-02 and kind of the confidence level of, you know, potential approval there.
Yeah, so, CONTACT-02, that was our phase III study, looking at CABO/Atezo in against a second NHT in later line castration-resistant prostate cancer. Again, that data, the final data, is gonna be presented next week at ESMO as well. And we think it's another area of high unmet need for patients. You know, obviously, if you think about kind of the treatment algorithm for men who have castration-resistant prostate cancer, you know, there's been a lot of progress in that kind of NHT, first gen, second gen, side, but unfortunately, when men ultimately do progress, they have relatively limited options.
Right now, one of the standards of care is docetaxel, and really, CONTACT-02 was designed to really understand, is there a chemo-free option for these men who tend to be older, who tend not to want to use something like docetaxel, where, you know, the AE profile is just exceptionally challenging. And if you look at kind of the real-world utilization data, certainly suggests that, that, you know, no one wants to use chemo. And so, CONTACT-02 was really designed to set out and ask that question, is, you know, in the kind of current use of second NHT is one of the more common agents used in that space, can we provide a more effective option?
The other kind of important dynamic on CONTACT-02 is we evaluated it in a relatively unique patient population, where all of the patients at baseline in CONTACT-02 had visceral disease or extranodal adenopathies. The reason we wanted to look at it is really kind of the cleanest experiment to ask the question of does the combination have an effect on shrinking tumors? One of the challenges, you know, that we certainly have experience with it at Exelixis, is kind of the dynamics of the bone-only patients, where they have bone disease, but understanding progression in bone only disease can be somewhat complicated. And so patients with baseline visceral mets, we were able to really ask a pretty clean and straightforward question. And so the data ultimately showed the answer is yes.
So if you look at the PFS HR from 0.64, 0.65 in doubling or so or significant improvement in progression-free survival, you know, that's quite an improvement as well. And so it really asked the question of c an we show a benefit in these patients? And, you know, we think the data are particularly compelling. You know, what we'll see next week is the final look at overall survival, where we showed a trend in improvement numerically, but not statistically. And so it just becomes a question of discussion with regulators about kind of what that benefit to patients is, and ultimately, you know, how do we make the case that this would be an effective therapy?
I mean, are there analogs, at least in prostate cancer, where you've seen approval on PFS and not OS, or not, like, when you don't see an OS benefit? I guess, you know, what are your arguments gonna be to compel based on PFS and missing on OS?
Yeah. So I think Amy Peterson, our CMO, has done a particularly great job of kind of articulating a lot of those dynamics. I don't want to take up all the time. I think if you go back a couple of the last couple of earnings calls, she has very robust and great evidence around each of those topics. I think it's certainly safe to say that there are analogs certainly in GU oncology, where kind of that PFS improvement, but no detriment in survival, is certainly translated to approval in patients. But we'll see. So we're planning to submit the SNDA later this year and really make that case to the agency that this is an opportunity for patients.
I guess if you look at both NET and, you know, prostate cancer, I mean, do you... You know, how are you viewing, just kind of like, commercially, those opportunities from a revenue perspective, and which one do you think is the most attractive?
Yeah. So again, I'd say, the answer around revenue opportunity ultimately depends on the label, so kind of stay tuned there. I think, you know, as we have talked about, both those indications are really the opportunities for re-acceleration of growth, in the CABO franchise. But again, you know, as we saw this quarter, kind of that RCC market continues to chug along and do well, also. So don't wanna kind of pick our favorite children, so to speak, between the two indications. But certainly we're excited about NET, and then look forward to submitting the filing with the FDA and prostate later this year.
I guess, how does your commercial strategy change with CABO, with the inline business, but also these growth opportunities, depending on the outcome of the MSN trial litigation? Obviously, you don't need to comment on the trial itself, but just trying to understand like, you know, what happens, you know, in either scenario.
Yeah, I mean, I think it's safe to say, you know, we've been a we're about the world's best scenario planners at this point. But at the end of the day, you know, really kind of the CABO business in particular really is about continuing to kind of drive growth. And so full speed ahead in that, full speed ahead with the filing and prostate. And so that's kind of where our focus is. And so I don't necessarily think the two are necessarily, you know, interlinked, so to speak.
Gotcha. And then I wanted to just chat on STELLAR-303. Maybe just give us, you know, a quick, you know, review of that study and I guess kind of the opportunity that you see for, you know, Xanza and CRC.
Yeah. So, 303, that's gonna be the first of the pivotal studies that we'll read out with zanzarlitinib. It's a phase III study looking at the combination of Xanza and atezolizumab versus regorafenib in a third-line plus non-MSI-high colorectal cancer. Another area we think that we have a chance to really you know potentially shift the standard of care. You know, unfortunately for patients, regorafenib you know one of the standards of care in that space really isn't a particularly effective option. And so, we based that study off of a prior kind of CABO data set, like we have with a lot of our Xanza studies showing pretty compelling clinical profile for CABO plus a checkpoint inhibitor there.
And so that was kind of the underlying basis for the 303 study. You know, colorectal cancer across both either the liver mets or non-liver mets population, we think is fairly substantial and really allows us to continue to potentially grow our kind of GI footprint. So if you think about Exelixis right now, strategically, we're really focused in kind of two areas: GU oncology with CABO and then GI oncology with CABO as well. But now, with the NET opportunity starting to really look compelling to us across both CABO and Xanza, and then 303 , you know, the mid to long-term goal for us is to, you know, have those two kind of verticals be fairly similar, so to speak.
And so if we think about colorectal plus HCC, plus NET, that's the sort of profile on that GI space, that we're particularly excited about. And so 303 is gonna be the first readout there. As I said, we're expecting top-line data sometime next year. Event-based studies, so you know, can't really, don't really know when exactly that's gonna happen, but study's fully enrolled, so we're expecting it.
What do you think you need to show in that trial?
So coming back to one of the earlier points that I was making is, you know, it's our belief, it's our view, that when the way you're successful commercially and drive real value is to drive standard of care. And we don't think that incremental improvements in, you know, how patients are managed necessarily translate to utilization, and lack of utilization tends not to translate to significant revenue. So as we think about value creation, it's really about generating those data sets that truly shift the standard of care.
And so, without kind of getting into, powering assumptions and a lot of that, suffice it to say that when we think about kind of 303 or 304 or 305 , the trials we've designed with Xanza are really, set out to ask the question: Can we shift the standard of care for patients? Can we take that Kaplan-Meier curve and, you know, move it to the right so that patients live longer? You know, ultimately, that's what we're trying to do. Live longer without their disease in the case of PFS, and for something like three oh three, where the endpoint's overall survival, are they gonna live longer taking Xanza versus not? So...
I mean, is there a bar, again, in terms of, like, where standard of care is in terms of, you know, survival?
I wanna say, you know, don't quote me here, I guess, but I think it's about ten months, plus or minus for Rego.
Okay.
But again, one of the dynamics that we've identified, I think that the industry has identified in colorectal cancer is kind of the differences between liver mets and non-liver mets, especially for patients and their sensitivity to IO. And so we've actually designed three oh three with the non-liver met population being the primary and kind of the liver met being more inclusive on the overall ITT basis. So that's kind of one of the dynamics to kinda keep-
Okay.
In mind ahead of that data.
Understood. Okay. And then for STELLAR-304, you know, for Xanza and renal cell, I mean, obviously, the opportunity to, I guess, you know, look at the market in a different way with Xanza there and CABO. So I guess, how do you think about that dynamic and, you know, ultimately, what's... If you're going to try to shift standard of care, is it... Or just is it, it will, again, using your words of shifting standard of care, are you trying to, you know, do better than CABO, or are you just trying to get CABO-like efficacy with maybe potentially a little bit better safety? Like, what, what's kind of the profile that you wanna get, you know, from that trial?
Yeah. So three oh four, for those in the audience who aren't familiar, it's again a phase III study looking at Xanza plus nivo, in this case, against sutent non-clear cell RCC. So non-clear cell RCC is about 20% or so, plus minus of kidney cancer, and it's a space that's a little bit unique, kind of in oncology, in a sense that there are many standards of care, but there's no real one standard of care. What I mean by that is there hasn't been any real pivotal data to establish what the true standard of care in that indication is. The labels for all of the RCC agents, whether it's CABO, whether it's any of the other.
TKIs are all inclusive of the non-clear cell population as well. And so what three oh four is really designed to do is really establish that for the first time with a pivotal study. So it enables physicians to have a much better level of evidence, so to speak, of a large pivotal study to establish, you know, Xanza as, you know, an appropriate standard of care versus understanding what relative guidelines say and, you know, trying to parse out limited data sets from the other, you know, other agents, CABO inclusive of that, whether it's as a monotherapy or whether it's in combination with nivo itself. And so three oh four is really designed to set out to kind of answer that question reasonably definitively and provide that first pivotal data set in that space.
... Got it. So not necessarily like competing with CABO, but trying to be more niche, I guess, or like, is that the best way to look at it?
Yeah, I think it's a way to establish a foothold in kidney cancer for Xanza. Given that there's no real pivotal data for CABO or any of the other agents-
It's right now, there's a lot of, like, you know, squinting and cross-trial comparisons-
... of these, you know, somewhat limited phase II studies, and then just understanding what's used in the clear cell RCC population. So instead, three hundred and four is really designed to kind of give a definitive pivotal data set to really help physicians understand that profile. So it's kinda a little bit of everything, but really, it is to give a level of evidence to the space to establish it there.
Got it. And then just kind of on the broader, earlier stage pipeline, I mean, obviously, you guys have held an R&D day, kind of let us under the hood to kinda show us, you know, what you're working on and different things. Maybe, if you can just walk us through, like, some of the or highlight some of the key programs that you think, you know, that are coming from the emerging pipeline, that we should be focusing on.
Yeah. So, you know, certainly, I'm glad you mentioned the R&D day. You know, that was one, we hadn't had one in, I want to say, you know, five, 10 years or something. But it really was a chance to kind of, you know, reestablish Exelixis as a kind of R&D powerhouse, so to speak. You know, post kind of the launch of CABO in RCC, that 2016 to 2018 timeframe, was really when we had the chance to restart and reestablish discovery, having had to shut it down prior to that, due to kind of, you know, capital constraints.
And so since then, we've been, you know, as prolific as any company can be of our size in terms of, you know, not only reestablishing discovery, but complementing that, with, you know, a whole host of licensing transactions that have enabled us to be particularly effective in kind of IND generation and, you know, really refill that pipeline. And so it's spanned areas from, you know, synthetic lethality with something like XL309, which we think is kind of a, you know, best-in-class, potentially best-in-class, USP1 inhibitor to, you know, XB010, 5T4 ADC, XB371, similarly, a tissue factor targeted ADC. So, you know, we're really in kind of the small molecule and biotherapeutic space.
You know, what Mike always likes to say is, our focus is GIGU oncology with mechanisms that ultimately we can put in a bottle and sell. And so, you know, we have a hint, kind of a wide range of mechanisms, but really in a fairly narrowed focus in that, in that kind of space. You know, would certainly highlight our ADC effort. We had a chance, you know, again, coming back to twenty eighteen, to really look around and understand what everyone's doing and where do we wanna focus, and ADCs seem like a natural fit for Exelixis with our historic capability, expertise, leadership in small molecule chemistry, and then our emerging kind of growing effort in biotherapeutics. ADCs are a natural marriage of that.
Again, we looked around and kind of at everyone's platforms, and we're trying to understand, you know, how do you really make the best ADC? And what we found was, what we ultimately came to is, platforms ultimately can have the square peg, round hole issue, where if you have a certain platform that does X, every drug you make needs to do X, even if the biology doesn't necessarily call for it. So what we've done is we've put together kind of a network of technology collaborations that allows us to optimize and iterate each of these molecules, where we take the binder, we take the linker, and we take the warhead, and really understand, for this target, for this tumor type, what is the best combination of those three components? And really, that's kind of the through line across our ADC effort.
XB010 and 5T4, great example of that, similarly with XB371, and kinda the differentiation on the antibody, then on the warhead linker side as well, so.
Got it. Maybe last question, just in terms of the ADCs that you mentioned, like, when will we get kinda like a first look at some of the data and kinda start to validate, you know, your approach there?
Yeah. So i know in the clinic right now, recently in the clinic, and then we've guided for 371, file the IND next year. So-
All right
... you know, ultimately, this business is about data, so we'll generate some data and understand, does this have the potential to shift standard of care or not? You know, we're in the position that we don't wanna develop bad drugs, and so if it doesn't look like that, we'll kill it quickly and move on to the next thing.
All right, well, let's leave it there.
Yeah.
Andrew, thanks so much.
Thank you.
Appreciate it. Good to see you.