All right, everybody. We're gonna get going with our next company presenter. My name is Jason Gerberry. I cover pharma and biotech at BofA, and I'm pleased to be introducing Exelixis and CEO Mike Morrissey. Mike, thanks again for joining us.
Great to be here. Nice to see you.
Hot off 1 Q and another announced share buyback, I figured I'd start with just a couple questions on capital allocation before we go into kind of program-specific questions. Maybe just to start, as we think about capital allocation priorities longer term, beyond this year, how are you guys thinking about kind of returning capital to shareholders versus, like, managing the next four years of CABO exclusivity and then the investments that you're making in zanza? Are there any specific, I guess, pivot points at all that you could see where, hey, maybe we want to invest more in zanza or some early-stage assets that look particularly promising and you step off the gas a little bit from a share buyback perspective?
Just trying to get a sense of the toggles there, beyond the share.
Yeah, that's great. I could probably spend the next 28 minutes talking about that one topic, and maybe we will. Let me just say great to be here. Thanks again for the invite. It's always great to be in Vegas, talking with the BAML team and all the investors that come. Before I begin, I'll just remind you that I'll be making forward-looking statements today, please see our SEC filings for a description of the risks that we face in our business.
Let's talk about capital allocation in the context of how we view the business, how we run the business, how we see it, how we've seen it in the past, and how we're going forward in terms of some of the themes that we've talked about a lot in the last year, certainly highlighted at our R&D day in December, around, you know, how we view building value for patients and shareholders, and that's through building franchise molecules that can improve standard of care for patients and by doing that drive, you know, good value returns for shareholders.
Our view has been to run the business very efficiently and to keyword is to prioritize how we do everything in discovery, in development, in the commercial world, to make the right set of priorities based upon data and based upon how we see the landscape evolving, how we see early data, how we see the competitor data flow, as well as movement, to be able to maximize our chance of success. Again, for patients, improving standard of care and then having that then drive shareholder value appreciation. In terms of capital allocation, it's not one size fits all. There's not one lane that we look at in terms of temporal terms, sequential terms.
We've been profitable on an annual basis since Exelixis is largely defined by our success with [audio distortion] molecule with different [audio distortion], AI for our [audio distortion]. Last quarter, a good example of that, top [audio distortion] , top drug in second line [audio distortion] , highest start [audio distortion] . Years into a launch, [audio distortion] , even frontline, [audio distortion] . Just lots of [audio distortion]. In terms of how we do that success and how [audio distortion] capital allocation, it's really not only generates so much cash. We efficiently utilize that, placing the right bets behind the right molecules, the right science to go forward.
Zanza right now obviously is our, we think our next big drug, probably undervalued by the street, which is fine. We'll rectify that over time. It's certainly one area that we see driving both [audio distortion]. The way we framed it is, you know, CABO is dominated [audio distortion] that could actually surpass [audio distortion] . We're investing a lot with zanza, but we're doing it in a very controlled, [audio distortion], as we did with CABO. Talk about how we did that, you know, back in the day and, you know, maximize the money we spend, collaborate with partners.
Again, within the zanza framework and company framework, you know, certainly investing our internal R&D development efforts for a lot of sense, having the ability to prioritize that on a month to month, quarter to quarter basis. It's really something that we do well and have the flexibility to be able to do that based upon the data, which obviously takes a portion of that. You'd be surprised, you know, how much flexibility we have there with overall R&D budget, and then to be able to right price, right time, the right asset to this plan. Have the ability to buy back shares that are undervalued.
Capitalized, sure. If I could summarize, it sounds like obviously with a biotech company, things are fluid, but as you've shared today, given the CABO-driven cash flows outlook, it sounds like you need to get four seasons to the next few years maintaining the current balance of how you're deploying capital. Is that fair?
Well, again, I would say we will continue to deploy capital behind best opportunities that was part of data, all the competitive advantage, such a way to maximize that clinical outcome for care, which then takes upon our view with the CABO still being a case. It's that, again, we have the opportunity to prioritize. That's the thing. We talk about that a lot in kind of the consensus and we use that word a lot today. We have the ability to prioritize if it's on data, if it's on insight.
We've got a good landscape evolving and we've got a lot of that to focus on. That's exceptional. The focus is always on maximizing success, which then will drive.
Okay. You talked about the [audio distortion] . This is not an attempt to sort of guidance, say, but just directionally, are we stepping into a timeframe where zanza stands as now more pivotal trials? Does that create any upward lift on the R&D? It seems like the consensus-only models make [audio distortion] of R&D lift over the next four or five years off current levels. I'm just kind of curious, are we not effectively moving into an area of higher trial size?
I wouldn't say that from an expense point of view because we have a pretty good sense of product cost. We're not starting all the trials at the same time. [audio distortion] , we do it ourselves or we do it with clinical collaborators. It's a collective. Our job and something that Michelle and Chris and others talk about on a regular basis, where's the best place to put our capital? That's what has the most successful place. We have a very rigorous approach, one of the benefits of having this. How we work with partners is that we do kind of modeling, I would imagine you guys do maybe at a different level to be able to figure out what success looks like in terms of year-over-year. Really play by that playbook.
Sounds good.
Flexibility is always built into what we do. As you know, we've always been very here to take the hard decisions. Our priority. I'm not worried about scaling here or there because you're still getting credit. You get credit for that. That's the CABO story.
A couple of commercial questions before we get into the zanza program. You're going to have multiple products with the zanza approval coming end of the year. I'm just wondering, as you get to the later stages of the CABO lifecycle, how you go about strategy at all, if you get towards the tail end and focus towards the zanza, are there any things you kind of modify as it pertains to pricing or resourcing of CABO relative to zanza as you get to the last couple of years of the product CABO lifecycle?
You know, the CABO runway goes to 36 months. Four and a half, five years from today, whatever that is. I'll say the following. I don't want to give too much specifically from our point of view, but we don't take our foot off the gas on CABO. Right? We're not going to glide on one while the other. Our view is, and we put a lot of thought into how to really navigate the clinical program narrative so that we don't really cannibalize CABO's maximum value. It's not a, again, they're not mutually exclusive. It's not a either or. It's how do you run fast both ways in a way that, again, expands the opportunity set across the entire portfolio, which is why we're focused on it. There's so much you can do in that space. There's so many patients that need better therapies.
[audio distortion] . Again, it's not a matter of trying to displace CABO. It's continuing to build CABO. The metric we talked about last week, gaining three share points with CABO. That's fine. At this stage of the launch, that's probably fine. Right? For one, KI monster growth from one segment. That's because we're focused on building. We're never content. We're never satisfied. CABO can keep growing. Certainly trials with zanza and, you know, the first two pivotal trials going. We thought to start the second one soon. Paul's back with, you know, prostate cancer treatment, non-small cell lung cancer going there in terms of other combination approaches. Yeah, look, it's a high value opportunity.
We have to execute at the highest level and we have to have the right mindset to always have data driving the process at each facility.
Okay. What you're seeing with CABO and [audio distortion] so far, it seems like the early launch was successful in 2025. Where are the incremental [audio distortion] in the market?
Yeah. We talked about that last week too. Yeah. Really pleased with the launch. Certainly had the academics locked in from the dose signal. We have an opportunity to expand that even further in the reps because they can handle that extra. The adoption of the KOLs is super encouraging almost immediately. Having them in now is fun because everybody's using them. We can start the PRT when we launch the clinical data later in the year, hopefully. We're beginning.
We're building up to this important CABO, sole CABO marketing, hopefully using the CABO data successfully. It's all part of the grand plan and it's going really well so far.
Yep. All right. The last CABO question and we'll go to zanza. Competitive impact [audio distortion] from the LITESPARK-011 readout for, well, it hasn't gotten formal approval yet, but some at least anecdotal feedback suggests some doctors are moving to that as like a second line, but that could also be an opportunity for greater CABO frontline utilization. What you're seeing now and just your view on how that will evolve.
Yeah. That's been the narrative that we've heard too from KOLs. Certainly LITESPARK-005, [audio distortion], LITESPARK-012, [audio distortion] continuum.
As that data gets stronger, it's curious to see LITESPARK-012 data that was announced that did not hit the first interim, not pass the first interim. Certainly [audio distortion] , et cetera. It's really important. Yeah. You know, we'll see. I don't want to speculate super. You know, I think the narrative that, you know, if we lose a little bit of share second line, we can probably gain some back first line. If that situation plays out, that's one that for us is really important to keep the share longer on the second line and certainly putting a lot of effort there. We have been for a couple of years now. Last couple quarters we've seen encouraging that that's paying off.
But again, we are in the most competitive space in oncology. We collaborate with everyone in that space. I would say of our CABO program, certainly it's an important part of the zanza program. We're all, everybody's working either with each other or competing with each other to improve outcomes. We're all aligned on that issue and we'll figure it out. Certainly from the standpoint of dose and price, that seems we're the most people that come knock us off and we accept that and, you know, maintain our position on the hill and keep climbing.
Yep.
Okay.
Yep. Yep. [audio distortion] zanza, I know you've been asked this question before, but I'll ask it again just because things are fluid and changing in oncology at all times. The rationale for the STELLAR-304 trial in non-clear cells, that's the next big clinical readout that we have, right?
My understanding is a lot of patients are already on high-dose TKI. Maybe just talk about what you're trying to solve for in that space. Is it mainly about getting a stronger NCCN recommendation and that can really drive commercial success for zanza? As we think ahead to clinical success and how to define that, right?
I guess if you look at the overall program, looking [audio distortion] . Overall biochemical profile, [audio distortion] biochemistry. Target drive tumor growth that drives [audio distortion] . It's the right framework of going. To go back to where we're at with, say, [audio distortion] . Level one evidence.
They flew based on predominance. We're so dominant. A [audio distortion] . There is no level one evidence. Go back [audio distortion] . Develop some of these small opportunities. [audio distortion] , but it was viewed as a good place. Very early days. Certainly one that CABO has nobody even dominates. They eat each other. We all know, you know, small 50-patient single-arm unrandomized phase I studies somewhat overestimating the budget. We're doing that with 304. We're going to have top-line data second half of the year.
It sounds like lower clinical risk, good way to get your foot in the door with the first or second expansion.
Imagine just by the fact that you're running this trial, you don't think that a lot of these modalities, lower level recommendations in the frontline setting, that in frontline space, that you have an opportunity.
There's no clear market need. We can achieve that goal and capture [audio distortion] of the population. That's beautiful. As you saw on the slides that we had, [audio distortion], I mean, the whole picture of our company is really fairly well frontline, classic, close. Signal static, second line. Our view is cover the landscape with trials and commercial opportunities. Have the right combination partner and the right overall approach. Best trials possible, best partners possible. That's last foot on just non-clear-cell is
Is PFS delta separation enough? Do you need meaningful OS separation to drive these recommendations, to drive the clinical success in non-clear cell?
Statement of the obvious. It's always good to have an overall survival signal in your label, right, in terms of marketing. I mean, that was the special sauce, if you will, with the first approval we got with METEOR, right, was we had survival when no one else didn't. It would really help just differentiate. Survival, I'm not sure you need it for approval, but in terms of building a winning commercial position, survival really helps, obviously.
Yep. Okay, fair enough. Your clear cell strategy, I guess just your outlook, right, in lieu of the LITESPARK-011, maybe it's hard to answer this question without seeing detailed data, just how you see the read across to the ongoing frontline studies. You've got LITESPARK-033, LITESPARK-034, I guess that's the second line study. Just with respect to the ability to generate practice-changing data with like a zanza-WELIREG combination, given overlap in the combination mechanisms.
Well, I think that's one approach that we're taking. I think that's juxtaposed with what we're looking at relative to the first line, where we've talked about, I think, pretty clearly that we're looking for combination opportunities with orthogonal MOAs. Before the fact, you've got hypotheses and you have to test those hypotheses, right? We're doing that, say, with zanza in a couple of different trials. We're talking to a lot of people and are in pretty advanced discussions now around looking at the first line de novo metastatic population opportunity with zanza ± a checkpoint plus a potentially orthogonal mechanism that doesn't have the same overlap with either one of those. That gives you more room to play on the upside for efficacy and potentially minimize the downside on safety tolerability. I think that's a really important component here.
Obviously working in the same pathway. There's examples of that working well sometimes, other times not within oncology, but it's a fine balance. You really have to thread the needle in terms of efficacy and safety, right? I think our view, and we certainly have some experience here with COSMIC-313, is that you've got to pick your combination partners with care. We've done a very careful survey and know the space really well, looking at a variety of potentially bispecifics or add-ons to a zanza checkpoint combination that we think could give us some really interesting opportunities in that frontline de novo metastatic space. Again, we look at this as part of our, again, aspirational vision to take the success of CABO had in the 20s and translate that to a much larger scale for Zanza in the 30s.
We've got some time to navigate all that and be able to figure that out and get that going and get that done. I'm excited about that for sure.
One thing that your commercial org has done really well, like when you roll out NET, is you have physicians that are highly familiar with CABOMETYX . They're maybe more inclined to be prescribers in the neuroendocrine tumor setting. As we think ahead to the CRC launch, you've expanded the sales force in the GI setting. Can you talk about the ability to kind of leverage that competency in perhaps a newer subset of oncology?
Yeah, well, certainly part of the.
Charm of CABO is that, you know, we've had such broad success, in the GU space, that, again, in the community setting where, you know, the HCPs are much more generalists in terms of what they see in terms of patient, tumor types. You know, they have the ability to mix and match there pretty readily. Using that to then build off of with zanza certainly in colon is a really important part of that, right? We're building that awareness, and we're building that, I would say, that information.
You know, the good news about building out the GI team and to a certain degree the GU team as well over years now is that, by location and by, you know, therapeutic area overlap, most of our reps have some experience, say at Genentech, you know, within the oncology setting.
Avastin, with colon, with other tumor types. We have a very deep knowledge of that commercial space from a sales and marketing point of view, and I think that depth will play off dramatically in terms of a CRC launch both for STELLAR-303 if that happens in the near term, and then, you know, the STELLAR-303 and STELLAR-316 play together really well. I like that idea of doubling down, you know, in these indications. Again, building franchises along that dimension of tumor types.
Multiple lines, multiple shots on goal, potentially combination partners, so it just gives you much more reach there as well.
Okay. It sounds like you've mentioned community a couple times with respect to CRC.
I would think third line would've been maybe more academic focused 'cause it's like a later line patient, but maybe I'm wrong. Do you see this more as a community-
It's truly a community setting. Yeah.
Okay.
Yeah.
Yeah.
Yeah. Yeah.
Um-
Which is why it's so important for us to really make sure that we've got that covered on the GI side going into that. Yeah, for sure.
I would say your sales force probably plays pretty significantly in the community setting already.
We do well, both areas extremely well. Right. For sure.
Okay. stellar STELLAR-316, maybe if you can just talk a little bit about, like, the rationale for that study and what data points you saw, what really inspired the decision to go after that market opportunity that can really, like, expand?
Yeah. It's a really exciting approach and one that, as I said before, you know, STELLAR-303 and STELLAR-316, they just play together really well. We're talking to KOLs about one, and they bring up the other one, and vice versa, right? It just reinforces our commitment to GI oncology to all lines, all opportunities within CRC. You know, the high risk post-adjuvant population is truly high risk. Those patients can progress within, you know, five, six months of their last round of adjuvant chemotherapy. They're in a tough spot because there's nothing really approved for them besides basically, nothing.
They can go back on more chemo or go onto a clinical trial, but all that's, you know, kind of tenuous, right? We saw that as a very important first step. The Natera technology we think works extremely well. You know, the application to bladder with IMvigor just highlights the opportunity there, where, you know, atezolizumab was shown to be successful at improving both DFS and overall survival, with a selection process that was driven by the MRD positivity.
It's a very good way to find patients who are at risk, you know, select them, if you will, again, study them as a, as their own little group, or in this case big group, and then go forward and run the trial. We're very excited about that. The good news in terms of operationalizing a trial like that is that they have such a deep level of experience and data around both institutions and investigators that use that technology for late lines, for post-adjuvant CRC, that it makes site selection and, you know, investigator kind of recruitment, very straightforward. We think this is a trial that we could get up quickly, run fast.
We're gonna enroll it only in the U.S. because that's where the technology is used. It'll be a 3-arm study. Excuse me. It'll be zanza monotherapy, zanza plus a checkpoint inhibitor that we'll talk about later, versus best supportive care. It'll be a very straightforward trial using, again, MRD positivity as the selection criteria for getting into the trial.
How many cycles of zanza plus PD-1 are you testing?
It's not limited.
Not limited, okay.
Yeah. Yeah.
The motivating force here, was this more the ALTAIR study which looked at LONSURF and ctDNA, DNA positive in CRC setting or zanza, PD-1 data in metastatic setting and seeing that synergistic benefit?
Yeah, it was more the latter. Certainly some of the earlier data, from the competition was enlightening. It wasn't that helpful 'cause it was just such a complicated kind of convoluted study. I think the best way to frame the logic, and I'm we're almost done here, but I'll just wrap it up like this, is, you know, if zanza plus a checkpoint was effective at, improving survival for patients with radiographic-
you know, tumor, you know, a large enough tumor mass where you could see it on a MRI or a CT scan, then going after, micrometastases, with the same approach, was a pretty good bet, right? From the standpoint of being able to, you know, go after the same mechanisms, that are driving established tumors, in this case trying to block, you know, micrometastases from forming, right? so the logic is kind of, it's kind of a no-brainer. It begs the question, we've got survival from STELLAR-303 which supports that, and, you know, we're super excited about being able to get that going very, very soon.
All right. Great. Well, we're out of time.
Okay.
Thank you, Mike, for joining us.
You bet. Thank you.
Yeah.