Exelixis, Inc. (EXEL) Earnings Call Transcript & Summary

Okay. Good morning, everyone. I hope you're enjoying our wonderful London Healthcare Conference. Really do appreciate the attendance, and I hope you're enjoying the meetings. My name is Akash Tewari. I'm a pharma and biotech analyst here at Jefferies. This is the Exelixis management team, Andrew Peters, and then Chris Senner. I'm going to hand it off maybe to you, Andrew, for some introductory remarks, and then we'll get started with the one-on-one questions as people come in.

Sure. Yes. Thanks for the invite. Always nice to be in London. Just as a reminder, we're going to be making some forward-looking statements today. So please see our regulatory filings with the SEC for disclosures around risks to our business. So Exelixis is at a pretty interesting time for the company, kind of coming off the heels of some pretty strong momentum, first with the collaboration agreement that we signed with Merck, followed by actually the next day, a positive outcome in our trial around the ANDA for cabozantinib. And then on the quarter, it gave us a chance to really kind of take a step back and provide a short-term, mid-term and long-term outlook on how we see the business, because we're getting a lot of questions of basically like now that this ANDA is over with, what is Exelixis? And so talking about the success that we're having with cabo in kind of our base business right now, that's kind of the near-term guidance. In the midterm, we outlined, at a reasonably high level, how we think about not only that base business continuing to grow, but then the upcoming launch of cabo in neuroendocrine tumors on the back of the CABINET data that was presented at ESMO and then had the concordant New England Journal paper. And then kind of the longer-term guidance is really to now frame kind of our next big program, which is zanzalintinib, kind of a third-gen VEGF TKI, and we gave kind of a $5 billion opportunity set number, reflecting kind of the 6 either ongoing or planned Phase III studies there. So really an exciting time at Exelixis, kind of a lot going on and glad we can be here.

Yes. And actually, I'll ask -- I mean, first of all, you had a great Q3 and then you had the ANDA resolution. But I think the question that I got most commonly with the long-term guidance is that's not something that you expect on a Q3 call, right? Long-term guidance on zanza and then even for $3 billion on cabo. You alluded to it, but I'd love for you guys to expand it a bit more. Why was there an urgency to put that out now on the Q3 call and not wait, let's say, to JPMorgan next year to kind of reset expectations?

Yes. As I mentioned earlier, I think it really was a chance to kind of take advantage of a lot of that momentum and remind people that Exelixis isn't just cabo, and it's not just 3Q results. I'm sure we'll get to it. But without kind of giving that high-level framework, people can be lost in the trees as to, "Oh, third quarter beat on gross to net" or all of these kind of incremental dynamics. And we're saying, okay, if you take a step back and think about Exelixis in the business, over the next 3, 5, 10 years, this is how we see the outlook, and it's much different than a lot of the minutia that can happen quarter-to-quarter. And so we saw the third quarter really as an opportunity to essentially reframe the company and remind people that all the stuff that we talked about at our R&D Day in December, we're this kind of big, small company, where in our little sandbox of GI/GU solid tumors, we're more pharma-like than anything in terms of the scale of our developmental organization, where we've run 20-plus pivotal studies. Our commercial organization has certainly been successful in having cabo be a multibillion-dollar global product and the #1 TKI when we're competing against it. And so it was a chance to really strategically reset now that this risk "has been discharged past the ANDA" and just remind people of what the company looks like.

Understood. Now I feel like you kind of led with the conclusion with zanza, in the sense, Mike's been very conservative. And I think rightfully so, the data is going to speak for itself. We'll show you when the data comes out. When zanza's initial clinical profile was kind of announced, the allure of that asset was, "Hey, a, I can have better safety, so I can get better target coverage. I can have patients adherent on the drug", and that's certainly important, especially in RCC. But then b, there's also that potential where I can titrate patients to different levels of exposure, and ergo, I'll actually not only have better safety, but I can actually also have better efficacy. Now you haven't presented a lot of public data for zanza, but you're suddenly putting out a $5 billion peak sales number. I mean, talk to me about, a, the data that we're going to see for zanza. It might not be placebo-controlled, but the data we're going to see in the course of 2025. And then number two, when we think about zanza differentiating not only on safety, but efficacy, is that the right way to think about it when you put out such an exciting long-term peak sales number?

Yes. So there are a bunch of components kind of within that. I'd say just to start off with kind of the genesis of zanza really was to overcome the core limitation reliability with cabo, which is long half-life. Right. And so you mentioned kind of the dose titration and tolerability is certainly important. What I'd say is one of the most important or substantial decisions we've made as a company over the last several years is in our 9ER study going from 60 milligrams to 40 milligrams, probably took a little bit off the top in terms of efficacy, but we actually saw is that patients tolerated cabo much better, and they stayed on drug. And so that latter point, staying on drug is something we think is increasingly important. And I'm sure we'll talk later about the 305 study and kind of the head and neck market. But one of the key dynamics there is the importance of making sure that patients don't discontinue either 1 or 2 of those modalities in the combination. So as we think about kind of what are the improvements of cabo and what are the improvements of zanza, zanza by design was designed to really phenocopy the efficacy profile of cabo and provide a much more user-friendly TKI to kind of help manage a lot of those adverse events, but also manage the combinability. And the combination of all of those things is really what gets us excited. The other part of your question that you were asking about is kind of like what data is that based on? Certainly, we have a lot of data that we're excited to share from the STELLAR-001 and STELLAR-002 programs next year. And as that data mature and abstracts are accepted and titles are announced, we can kind of be a little bit more forthcoming about when that's happening. But there's going to be a lot of data from cohorts such as colorectal cancer, for example, looking at zanza, atezo versus zanza in kind of a similar-ish population to 303. But the other dynamic that we like about zanza is that it really builds upon this foundation of the 15-plus years of cabo development. So cabo really points us in the direction of where we can go with zanza. And so it's not just based on the data we've generated previously or concurrently with zanza, but also everything we've done historically with cabo as well. So that's 303 is the CAMILLA study, 304 builds upon kind of our history in RCC with cabo/nivo, and then 305, pembro/cabo data that was presented.

Understood. You mentioned head and neck. I actually wanted to touch on that. Obviously, I think the darling in the room is Mirus. They've shown exciting early data for sure. I do point out to investors, I mean, cabo/nivo with far more end showing a 53% response rate in that kind of first-line population shouldn't be dismissed. You're probably going to see the error bars also overlap there. I think that's probably fair to say. I think there's an angle here, though, that people don't appreciate, which is as we think about PD-1 use in the adjuvant setting, right? First-line head and neck is going to start to transform. You're going to have a lot more patients who are actually refractory to PD-1 being used in that setting and in your clinical trials. Can you talk to me about the clinical profile that you're generating in kind of that PD-1 refractory population in first-line head and neck and how you think that might be able to stack up with the competitive threats that are coming out in that space right now?

Yes. So 305 is our frontline Phase II/III looking at zanza and pembro versus pembro. So that's really the population we're evaluating. I think it's an interesting kind of thought exercise to try and understand where treatments are going in the future. But I think our job is to run, one, successful pivotal studies; and two, pivotal studies that generate data that shifts standards of care. So our goal is that the addition of a TKI to a checkpoint like pembro in that head and neck population, if it is kind of that right TKI that patients are able to stay on drug, not discontinue, you can really see that translation of the benefit of response rates in PFS that, say, Merck saw in the LEAP-010 study, overall survival. And so we're excited to be working with Merck, as I mentioned before. We announced last month that clinical collaboration that not only covers RCC, but they're giving us pembro for head and neck as well.

Understood. I mean maybe to that point, it is interesting that it was Merck, right? I mean Lenvima has been "dirty" VEGF TKI for quite some time. What data did Merck see that kind of gave them confidence? Because even on the Q3 call, Merck explicitly talked about that Exelixis collaboration is one of the things that investors should be paying attention to. Talk to me about, a, what led to that deal actually occurring? And then number two, could this potentially expand beyond just first-line RCC and head and neck, but into other indications as well?

Yes. So we haven't really gotten into a lot of the details yet. We've agreed with our partners, Merck, to kind of keep a lot of those details under wraps until a later date. But suffice it to say, I mean, we're really excited about the collaboration. It's not lost to us that we're working with our biggest competitor. And that really speaks to kind of the excitement we have about the opportunity, but also the potential differentiation around zanza. But in terms of a lot of the background and who saw what and all of that, kind of it's a question for a later date -- or answer for a later date, I'd say.

Chris, I wanted to hit it -- there's an aspect about cabo's development that I think gets lost in the weeds where you had Ipsen, you had Bristol, you had multiple people that you were collaborating with in order to lead such a broad development program. Talk to me about from a cost savings perspective, simply not having to pay for PD-1. How much flexibility does that give you from an R&D perspective to potentially improve your margin profile and actually save money?

Yes. So I mean, I guess from an overall perspective, we haven't given specific guidance about how much cost savings there would be with the Merck trial and the collaboration. But from an overall perspective, we're looking at trying to keep -- and Mike talked about this on the third quarter call about keeping R&D expenses relatively flat as we see in the near future here. This year, we guided originally to $925 million to $975 million. We think it's in that range, like sub-$1 billion range. And so we'll continue to act towards that and allocate capital in that regard. So talking about the Ipsen and Takeda relationship we had on cabo, that allowed us to really have a lot of efficiency in our P&L. We had -- you mentioned 9ER. We shared costs with BMS, and then we took that shared cost and shared it further with Ipsen and Takeda. So it created a lot of efficiency in a P&L perspective. And you know, Merck collaboration can do similarly, but not the same necessarily fully from a full perspective, but will help us. And that's what we want to continue to do is have an efficient P&L and allow us to continue to provide free cash flow, which then we can allocate to share repurchases, we could allocate to further BD, but also to R&D, continuing R&D.

Understood. And maybe to that point, I mean, just to clarify, is the Merck collaboration exclusive, right? Like does it mean that I can't do a deal with -- a collaboration deal with Bristol? Is that the case or not necessarily? And then number two, could we expect Exelixis to look at partnerships in ex U.S. territories to help, again, spread the cost burden a bit more just like you did with cabo?

Right. So we haven't talked in a lot of detail around the Merck collaboration, but we still have some freedom to operate here from a zanza perspective. We haven't fully built out a U.S. organization from a cabo perspective, because we have Ipsen and Takeda. We'll look at all the opportunities from a zanza perspective. Do we launch it ourselves or do we bring in a partner? And we'll start to do that as the data starts to mature and we start looking at what the value proposition is for us versus having a partner.

Understood.

Yes. I mean the best way to think about it simplistically is it's a much different conversation to have with a p-value. And so with data from 303 coming next year, Chris' team and we have a really good sense of kind of what that European opportunity looks like from a build-out perspective, from an ROI perspective, but also kind of who those potential partners could be. But we think that kind of once those data are available from 303, really the opportunity set around zanza becomes a lot clearer. So expect those conversations to ramp up.

Understood. Now the rage all the day in oncology is these PD-1 VEGFs or PD-L1 VEGF bispecifics. And I can't help but think there's a lot of similarities between what you're talking about with zanza about patients staying on drug having that sustained benefit. You talked about LEAP-001, and that actually will then translate to OS. I mean, I know those bispecific companies talk about the cooperative binding, and that's really what's leading to the potential differentiation on efficacy versus just 2 separate targets. But is that the right way to think about it? I mean, could zanza also provide that same kind of higher therapeutic index sustained exposure that you've seen with the bispecifics? Yes, any thoughts would be interesting to see.

Yes. I mean, I guess that's the $1 billion, $10 billion, or $100 billion question that everyone seems to be grappling with. I mean from our perspective, again, kind of pointing back or bringing things back to our little slice of the world. At least in RCC, any of the early data that started to come out certainly doesn't really suggest to me that there's a big difference between, say, cabo alone versus a PD-1 VEGF, limited data cross-trial comparisons, all the caveats. And then understanding how kind of a lot of the response rate and PFS benefit translates to overall survival in some of the bigger tumor types, again, kind of TBD. So we certainly can point to the 15-plus years of cabo and the history of VEGF targeting TKIs and being active and say, well, could a better tolerated TKI provide a lot of that lift that we're looking for. That's why we're enthusiastic about zanza. That's why we have these 6 ongoing or planned pivotal studies. But I think we all live in this environment where we want to know the answer now. And it's just going to take a while for that data to play out. But again, in our little kind of slice of the world, I think zanza plus is pretty well positioned for the GI/GU tumor types that we're really focused on.

And just finally to close that out, why not lung, right? I mean, obviously, the LEAP studies were run in first-line lung. You had a PFS benefit, didn't translate to an OS benefit. I mean it's the same dynamic that you're talking about with Lenvima, where you have a PFS benefit doesn't translate to an OS benefit, maybe you're not getting sustained exposure. Is there appetite to maybe explore some of these larger indications outside of GU/GI cancers. You look at lung, you look at bladder cancer, other areas where VEGF inhibition and PD-1 inhibition could show a signal. Should we be thinking about that scope of the opportunity? Or it's like really no, our focus is really GU/GI?

Yes. I mean if you go back to JPMorgan from a couple of years ago, we had laid out essentially a framework of how to think about zanza in terms of waves. And those waves of development kind of get incorporated into our prioritization, get incorporated into how we think about clinical collaborations and partnerships. But I think the most important thing when, say, why not focus on lung or something like that is the through line for the company is that we view things what we call through the cabo lens, which is how do we generate differentiating data, because cabo is successful not because it's an approved VEGF TKI, but it's successful commercially because we've been able to generate differentiating data. And so the question when we would go to, say, our clinical team and say, think about a zanza study in lung. The real answer is how do you prove and shift that standard of care to the right, so that patients are living longer. And that's why whether it's RCC or NET or -- we've been very specific and deliberate and thoughtful about those kind of green space areas around utilization where we have the potential to shift standard of care and really define a new treatment, so that zanza is going to be used in the same way that cabo is used in the same way that successful drugs are used.

Understood. Now Summit had data -- I mean, you're starting to see these combination targets, like your Merck partnership includes potentially HIF-2 alphas in combination with cabo and VEGF. Summit had data with the CD47 in first-line head and neck. You actually have -- no one talks about anything in Exelixis' pipeline ex zanza right now. But you also have some synergistic targets that you could potentially layer on top of zanza and a PD-1. Can you talk about maybe some of the hidden gems that could be synergistic with your development strategy in GU and GI cancers that maybe aren't getting enough attention by investors right now?

Yes. I mean kind of not surprising, I guess, but just a lot -- between the ANDA and then the focus on zanza now, a lot of that gets overlooked because it's not necessarily immediate term next catalyst, next catalyst, next catalyst. But we're kind of -- we've been slowly in the background developing this interesting and what we think is differentiated portfolio of about 10 different assets if you count kind of DC, IND and Phase Is. And then I think you're referring to our Sairopa option deal that's a SIRP-alpha and that's the other side of the CD47 axis that we think actually is a pretty differentiated compound that we're waiting to see some data about whether or not we opt in there. But certainly, when we think about portfolio construction, a lot of the questions that we ask internally are exactly that. How does it combine with zanza? How does this play with this? How does this play with this? And one of my favorite parts about sitting in my seat is kind of getting to be a little bit of fly on the wall on those sorts of discovery and clinical combinations and discussions and arguments about how do these things fit together, because ultimately the science that we're trying to do is really establish standards of care, as I mentioned. And so we're thinking big. We're thinking longer term, what does the standard of care look like today versus 5 years from now? How does an ADC plus combination strategy look? All of those sorts of things we're focused on. So I don't want to name my favorite kids, so to speak. But if you look at our early portfolio and kind of everything we highlighted at the R&D Day in December, there's a lot of hidden gems there potentially. But our job is to generate data and kill things quickly if they don't work.

Okay. Understood. On IRA, I just wanted to hit on an outpatient drug like this, can you remind us, a, Medicare Part D exposure? How much is that for cabo? And then number two, isn't this one of the drugs where you feel like it's an expensive drug, it's out of pocket, you're going to be eating into catastrophic coverage. This might be a drug that actually has a negative impact with Medicare Part D reform. Is that the right way to think about it?

Yes. I mean, so from an IRA perspective, we do have that small company exemption. So we pay the 1%. I mean, Medicare from an overall business perspective is in that 40% to 50% range, which we've talked about before, of our overall business or overall volume, but the out-of-pocket in 2024 versus the out-of-pocket in 2025 is different for the patient, right? It's going from 3,500 to around 2,000. And so we don't feel like it's going to be this big change. We're not giving guidance yet, but we don't think it's going to be a big change from a gross to net perspective, at least for 2025. But as time goes on, that small company exception, our piece of what we need to pay continues to increase, whereas big pharma goes straight to the 20%, we pay 1% this year, and it goes up to around 20% in 2030 time frame. So for a 2025 perspective, it's not a big impact to us.

I don't think a lot of people appreciate that. It's really interesting. Now obviously, you had a really, really strong Q3. But on Wall Street, we always get ahead of ourselves. When I look at the fundamentals of your business, you've been pretty clear. On first-line RCC, we've kind of tapped out how much growth we can have. And then maybe the majority of the growth is going to be NETs expansion and really that's the opportunity. I just want to make sure we're level set as we go into 2025. Like, a, are we going to start to see market uptake in NETs given some of the clinical data that you've generated with cabo already? Or is that really going to take 2 or 3 years before we start seeing that? And then number two, how much more room is there really for upside in first-line RCC expansion?

Yes. So there's a couple, obviously, questions within that. So right, from an overall base business perspective, we still have room in frontline RCC, right? And that from how long a patient stays on drug from a first-line perspective versus a second-line perspective is considerably longer from a front line. And so we still have that ability to continue to garner first-line market share. And so there's a growth opportunity there that will -- that base business will continue to grow as we look into 2025 and beyond. And then we have a PDUFA date of April 3 for the NET indication. And with that, we're hoping for growth there, too. Obviously, part of that is the fact that we already cover about 80% of the docs that will prescribe NET. They've already used cabo previously. And so we think there'll be -- our ability to get uptake and quick uptake should be pretty good just because we have that -- we have familiarity with those docs. The docs have familiarity with cabo. And so there should be that ability to get some good exposure from a detailing perspective.

Understood. Thank you so much. I know we're out of time. I really do appreciate everyone. Thank you so much to the team.