Our second session, we've got Exelixis, and we're really excited to have them here. They're represented by Andrew Peters, who's the SVP of Strategy. Thanks for being here.
Thanks for the invite. Glad to be here.
Yeah. There's a lot going on at the company. I wanted to start maybe on the commercial franchises first. You guys have given guidance. CABO had a pretty solid quarter. You know, maybe at a high level, I mean, how are you thinking about the balance of the year, you know, the future trajectory this year for CABO across its existing indications?
Happy to get into that. I guess, you know, before answering, I want to make sure that everyone understands we're going to be making forward-looking statements today. Please see our relevant disclosures in our regulatory filings. As you said, kind of, our guide reflects, you know, continued growth for the CABO franchise. You know, kind of specifically where that's going to come from, I think it's really about our organization, our company continuing to be laser-focused on CABO, both on the base business as well as the NET launch. It's one of the things that we've done well historically, it's something that we want to continue to do and make sure that we're not taking our eye off the ball.
We've talked about kind of, you know, over the last several years, continuing to see market share gains, not only in RCC, and in particular frontline RCC, but now as we're kind of launching into that NET segment, you know, really driving that NPS, you know, which, you know, from our perspective, is a pretty good forward-looking indicator. As PJ talked about on the earnings call, highest NPS we've ever had during the quarter. It's that laser focus on additional market share, finding those patients as we've now kind of expanded our commercial footprint, you know, to focus not only on the NET launch and say the community side, but really lay the groundwork ahead of potential zanza launch as well.
It's really kind of that singular focus on making sure that we're going out every day and talking about CABO, talking about the data, and that again, driving market share.
Got it. Maybe just to dive in a little deeper on that, there's obviously two major parts that, you know, we investors been focusing on the RCC side and the NET side. Just on RCC, I mean, there's been some, you know, competitive data, particularly in HIF-2. I guess, how are you thinking about maybe the balance between first line and growth you have there versus maybe competitive pressures in the second line and, you know, how you envision the trajectory?
Yeah. I mean, it's certainly obvious that oncology is competitive, has always been competitive, will always be competitive. That's what, you know, we do every day is we kinda go out and fight, you know, to either develop new therapies to establish standard of care or really ensure that, you know, drugs like CABO are able to be used in the largest number of patients possible. As it relates to the HIF space, you know, obviously this is an evolving dynamic with the recent LITESPARK-012 data as well as our own, you know, initiations of the O323 and O324 space. It's certainly a mechanism that we're paying a lot of attention to.
As it relates to kind of this, you know, dynamic around frontline, second-line use, you know, we've seen a lot of speculation that if lenvatinib does get adoption, say from LITESPARK-0 11 in the second line, does that drive incremental use for CABO in the first-line? That certainly would be an outcome that we'd be okay with, given the kind of the relative duration dynamics between those. You know, I think there's still kind of a lot of additional information that needs to come out around just the, you know, between LITESPARK-0 5, 011, 012, 022. It's just a continuously evolving space. One we're obviously paying close attention to, but, you know, right now, CABO is the number one IO/TKI.
It's the number one IO. We wanna do everything we can to make sure that that dynamic continues in the future.
Got it. The other side of it, the equation is the NET growth. You know, we've done a fair amount of work here, as well and, you know, found pretty high levels of prescriber enthusiasm. I think on your recent call, you guys mentioned it's the number one prescribed oral agent in second line plus NETs. I guess, how are you thinking about how much more growth there is in NETs? You guys recently had the Salesforce expansion that included, you know, the team moving in that space as well. I guess, what are you hearing on the ground?
Yeah. Again, I think we'd agree with your characterization around kind of that level of enthusiasm. You know, we certainly saw a lot of adoption kind of right out of the gate in the academic space, just given the strength of the CABINET data. But again, as we've talked about historically with, you know, our success in RCC, it's really about going in and driving market share gains. If you think about, say, NET, you know, along with RCC, it's not only about penetrating that academic kind of KOL sphere, but then going into that community space as well where, you know, the vast majority of patients are actually treated.
What the Salesforce upsizing allows us to do is kind of do both, continue to kind of really hit hard and kind of hammer home the message around CABO's strength, and, you know, really the benefit for patients here, but also educate those kind of community, more community-based docs who may not see, you know, that same kind of volume either of, you know, RCC patients or NET patients. It's kind of expanding that to drive additional share. You know, we're now kind of a year into the launch, but, you know, one of the dynamics with NET is just understanding that it's a relatively indolent disease.
There's always that NRx/TRx dynamic that's gonna start to happen as well, where you're stacking patients not only with new patients, but refills and kind of that's something that we're gonna continue to look for as well. I think our guidance, which reflects growth not only in the RCC space, but NET as well, kind of takes all of that into consideration.
Got it. I wanna move on to zanza and some of the pipeline updates there. Since we're on the topic of NETs, I just wanted to first touch on three-eleven.
Yep.
I guess how you're thinking about that study, you know, the differentiation that zanza might provide, both in, you know, the paradigm in which it's gonna fall in NETs as well as, you know, how that handoff might work between CABO and zanza in the future.
I think it's a dynamic that's really gonna go into kind of two key areas. One is just the uniqueness or kind of differences between CABO and zanza and kind of the more user-friendly, shorter half-life, potentially more tolerable, you know, all the things that we've started to see earlier on. Just the differences between 3-11 and CABINET. CABINET, relatively later line population, you know, placebo-controlled reflecting that dynamic, versus 3-11, where it's really kind of defining or hoping to answer the question, what should be that first oral option? You know, what that means from a practical perspective is it's an earlier population, and it's also head-to-head against kind of the current standard of care in everolimus. Again, it's gonna come down to levels of evidence.
If we're able to show that zanza's statistically better than kind of the current standard against an active comparator, we think that that's a really powerful message that, you know, in the future our reps will be able to go out and market to. Versus, you know, CABINET, which again, you know, it's really rare in this business to see HRs with a 0.2 and 0.3 in front of it. Again, you know, for the most part, that was also relatively later line population for a lot of those, if you look at kind of the breadth of that study.
I guess the nearest term opportunity for zanza is obviously from STELLAR-303 and CRC. Wanna touch on the commercial there as well. First, and there's also going to be a potential data update in the NLM population. I guess, how are you thinking about what you'd like to see there and, you know, maybe what success in NLMs might mean more broadly for the CRC opportunity in zanza?
Again, there's a couple of dynamics there. you know, on the success side, you know, statement of the obvious, P values. you know, that's really kind of the bread and butter of the industry and what allows our sales force to go out and really hammer that message home that zanza/atezolizumab should be the new standard of care for these later line colorectal patients. you know, in terms of does it matter, you know, obviously the ITT population, which read out last year and has the PDUFA date, in December, is inclusive of both patients with liver mets and non-liver mets.
Again, kind of the, you know, best case scenario, so to speak, is really a data set that enables our commercial organization to go out and have conversations with physicians and prescribers to really emphasize and re-emphasize that dynamic around why the combination should be kind of the standard for patients, what the inclusion of an IO potentially means from the patient's perspective, and really just why we think the data are starting to resonate, kind of as we do these kind of market research and KOL checks, a lot of those messages that are starting to come out. The non-liver met readout, certainly looking forward to it and hoping to show as strong a data as possible.
You know, just again, as a reminder, kind of that ITT population is really inclusive of all patients.
Got it. Appreciate there might not be a lot you can say on the next part of this. You know, as you mentioned the PDUFA, as you guys move towards that date, I mean, anything to note on the regulatory interactions?
Yeah. I mean, you know, other than we have a great relationship with the agency, you know, from our perspective, the review and the filing has kind of, you know, gone as well as we could hope. You know, it's one of those things that This isn't our first rodeo, so to speak, on the regulatory side.
Not a stranger to the FDA then.
Yeah. You know, it's glad that we have that experience and kind of those existing relationships and, you know, it's a great collegial collaborative process so far.
Great. As we look towards, I guess, December and potentially starting that launch, you know, the data you've shown suggested benefits, you know, broadly for CRC patients. Your strategy, as you mentioned, has been, you know, fight for every patient. Is the initial push gonna be broad? Is it gonna be focused on both community and academic? I guess, how do you think about, you know, the initial stages of that launch and where you're gonna position the drug?
Yeah, I mean, kind of as we've shown in RCC, going out and competing commercially is something that we do especially well, and it's really gonna be about kind of targeting all of those populations. Fighting for, you know, every patient, fighting for every, you know, market share point, is something that we wanna do. You know, as I mentioned, kind of those dynamics around the messaging that's really resonating with patients, it's, you know, the potentially the first IO that's gonna be available to these patients is something that, you know, we continuously hear, but also kind of that chemo-free dynamic as well. As you think about the patient's journey from, you know, diagnosis towards that treatment decision and kind of the third line space, you know, functionally they'll have been on chemo that entire time.
Understanding, you know, a IO-containing chemo-free regimen that has a clear survival advantage over a prior standard of care really does resonate. You also understand, you know, say, relative differences between our data and as you mentioned, kind of this robust benefit across all prior subtypes. Whereas if you look at, say, some competitor data, you know, that same dynamic around something like prior Avastin use or prior bevacizumab use, and the differences kind of in efficacy there, that's something that I think given how patients are treated in the U.S. could be especially relevant.
Got it. Just to remind everyone, Salesforce there is largely in place, so you can hit the.
Yeah. I think again, kind of what we've talked about is a key part of the Salesforce expansion that we completed last quarter, was not only kind of to continue to accelerate that NET launch, but also lay the foundation for zanza potential approval later this year.
Got it. You guys have talked about how this could be potentially a $1.5 billion market opportunity. You know, as investors start doing more work on the launch, I mean, are there any other metrics that you'd point to, any other launches that we should think about to, you know, better understand how the shape of, you know, zanza and CRC could look?
Yeah, I mean, you know, I think the best way to think about CRC is kind of that $1.5 billion opportunity when you apply kind of contemporaneous pricing and duration and all of that. It's really a reasonably fragmented market, and that's in part driven by, you know, this academic versus KOL dynamic, which is probably more prevalent in CRC than some other tumor types. But it's, you know, kind of a third, a third, a third. You know, a third roughly that SUNLIGHT regimen, a third kind of TKIs, a third, you know, hodgepodge of, you know, chemo type options. Our goal, our mission, our singular focus, again, is to make sure that we're taking as much share from each of those three buckets as we can.
Can't and, you know, won't be able to give guidance on what that trajectory looks like other than, you know, it's gonna be our job every day to kinda come in and drive that adoption.
Got it. I wanted to pivot towards zanza in RCC and non-clear cell as well with the STELLAR-304 trial. You know, we're looking for data from that this year. I guess, can you talk about, you know, given that there's no approved, formally no approved treatment options in this setting, specifically for this, you know, what you're gonna tell me P values, but, you know, what looks like what would be a win for you guys that can help you know, get competitive, move into this underserved patient population? I guess, how are you thinking about that?
I mean, don't want to say it again, but I think that's the honest answer is, you know, great data. You know, P values, one of the things that's driven success in for CABO and RCC and why it's the number 1 IO/TKI is that kind of, you know, PFS, response rate, survival, all of those improvements really resonate with patients and physicians. It really comes down to kind of what the existing dynamic is in that kind of non-clear cell space and what we're hoping to achieve there. You know, it's this relatively unique aspect of the non-clear cell segment where there's really no data kind of across the board.
You know, we were having a conversation with an investor earlier, and adoption is really driven somewhat by inference from the clear cell space, and then as well as guideline-driven recommendations based on some really sparse data sets. You know, single arm, unrandomized data and, you know, potentially selected patient populations. It can be really hard to kind of understand, well, how is my patient gonna respond to individual therapy or combination X? What this study does is it provides kind of robust data really to answer that question. That exact dynamic is actually something that I think we've heard continuously from physicians that they're really looking forward to because we're really You know, the leaders here in defining how patients should get treated.
Is how much of non-clear cell is more of a foothold for zanza in the space initially versus a large opportunity in and of itself, given it's 20% and, you know, CABO's a great drug as well as you get?
Yeah. I mean, I think 20% of a large market's still relatively, you know, sizable. I don't want to underplay that dynamic. You know, we'd certainly agree that as we think about, you know, zanza going forward, one of the things that we often talk about in the way, you know, we think about development is CABO has been the TKI in RCC of the 2020s. Zanza's gonna be the TKI in RCC of the 2030s. It's not only about the non-clear cell segment, but how are we approaching kind of that clear cell space as well, you know, with O33 now O34 and then, you know, kind of the next steps, the next wave of investment, so to speak, to continue to build that out.
That's one of the kind of overarching themes for us is that 2020s to 2030s dynamic for zanza in making sure that we're covering all the bases, so to speak, not only in non-clear cell, but, you know, post-adjuvant, frontline, de novo frontline, and then kind of that second line plus segment. We can make sure that as, you know, patients are treated differently now than they will be in the future, we wanna make sure that zanza is a central part of that.
Yeah. You guys clearly have a leadership position in RCC, and you know, maybe going back to this HIF discussion, there's a number of trials that zanza's participating in with these HIF targeting agents. You know, are we viewing it too much through a competitive lens where really uptake, you know, growth of these agents is gonna be a positive for zanza given the potential combination approach here?
Yeah, I mean, you know, it's again, it's an interesting and relatively unique dynamic where we're now collaborating with functionally our biggest competitor. You know, we love working with Merck. We announced another clinical collaboration with them this morning for the 316 study.
Touch on that in a second.
You know, it's a, it's a relationship that I think reflects, you know, not only our confidence in the uniqueness of zanza, but that dynamic around understanding if we fast-forward the clock, you know, five years or so, how are patients going to be treated? Our job as drug developers is really to define new standards of care for patients and really ask the question, you know, the way we drive value for patients, for all stakeholders, for shareholders, is really if we can define a new standard of care, if we can help patients live longer, that translates to, you know, higher revenue, kind of more value, all of that dynamic.
We think that the combination of, you know, a HIF inhibitor like belz and zanza plays well together, and importantly has the potential to answer really important questions from a clinical perspective, such as if more and more patients will get pembro on the adjuvant side, what should they get if their cancer returns? Again, we're gonna be the first to define that answer. Similarly, kind of as adoption of all these different agents kind of changes in the future, what should be that kind of second line plus segment as well? Again, that zanza belz combination is something that we're really excited about. O33, O34, kind of I'd say the last piece is stay tuned for that next wave. You know, you talked about we're the leaders in RCC.
We wanna continue to be the leaders in RCC. We're gonna invest there, but importantly, we're gonna invest there smartly. I think the lessons not only from our own 313 study, but the recent LITESPARK-012 study kind of can certainly help inform what is it gonna take to be successful there. You know, orthogonal combinations of orthogonal mechanisms, and smart trial design is gonna be kinda central to that.
You alluded to 316 earlier.
Yep.
I wanted to touch on that. It's an adjuvant study in MRD positive patients. I guess the focus there right now is on execution as you guys work to ramp that up. I guess, can you talk about that? You know, how quickly you can get that running. Obviously, there's some unique approaches to that study, looking at, you know, minimum residual disease, the Natera collaboration, Umbra and Merck. Just, you know, how should we think about timelines there and how quickly it can start, you know, layering onto the zanza opportunity?
Yeah, I mean, I think this is, this is a study that, you know, we're particularly proud of because again, you know, we're involved in defining a new way for patients to get treated. As the recent IMvigor approval will show, you know, this is an approach that's, you know, really cutting edge and offers an opportunity for patients to really, you know, define kind of a new journey for them. Right now in CRC, unfortunately, you know, the Signatera test can help you define, you know, based on ctDNA positivity or negativity, you know, how your treatment journey will likely go. If you look at the data, the separation of those curves between ctDNA positive and negative is really striking.
It shows that unfortunately for that kind of, you know, 15%, 20% or so of patients, you know, there is a really high degree of relapse. Unfortunately right now, kind of the current standard is watch and wait. From the patient's perspective, that can be particularly challenging. You know, it's coming in and waking up every day and understanding, you know, is the tumor gonna come back? What we're now offering is kind of that question of either zanza alone or zanza in combination with KEYTRUDA, can that push out that DFS interval that unfortunately for these ctDNA positive patients is relatively short, you know, there is six months or so.
That dynamic along with working with Natera to help operationalize the study is something that I think we can build on because these are patients with a high unmet need. They're being identified, you know, literally every day. That operational advantage from a kind of clinical trial execution perspective, you know, is something that we think we can accelerate.
Got it. Unfortunately, we're out of time. There's so much at the company to talk about. We didn't touch on, you know, prostate, lung, the early-stage pipeline, business development.
Yeah.
Just given how much is going on. Thanks for being here again.