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On Wednesday, 10 September 2025, Exelixis Inc. (NASDAQ:EXEL) presented at the H.C. Wainwright 27th Annual Global Investment Conference. The company outlined its strategic initiatives, focusing on the commercial success of CABOMETYX and the development of Zanzalintinib (Zanza). While highlighting growth opportunities, Exelixis also addressed challenges such as potential patent cliffs. The discussion underscored a commitment to innovation and strategic R&D investments.
Key Takeaways
- Exelixis aims for $3 billion in CABOMETYX revenue by 2030-2031.
- Zanza is projected to reach $5 billion in revenue by 2033.
- The company maintains a $1 billion cap on R&D expenses.
- Strategic trials for Zanza are underway, focusing on unmet medical needs.
- Exelixis is committed to discontinuing less promising programs to prioritize high-potential investments.
Financial Results
- CABOMETYX Performance:
- Revenue guidance for CABOMETYX is set at $3 billion by 2030-2031, with current 2023 revenue guidance at $2.1 billion.
- The recent launch in neuroendocrine tumors (NET) achieved a 35% market share for new patient starts, contributing approximately $20 million in Q2 revenue.
- R&D Spending:
- Exelixis is committed to keeping R&D expenses at or below $1 billion, ensuring strategic focus and efficient allocation of resources.
Operational Updates
- Zanzalintinib Development:
- Positioned as a next-generation TKI, Zanza is undergoing multiple pivotal trials, including STELLAR-303 in colorectal cancer and STELLAR-311 in NET.
- The molecule is designed to maintain CABOMETYX’s efficacy while improving patient management with a shorter half-life.
- Pipeline Expansion:
- Exelixis is advancing its earlier-stage pipeline with the USP-1 inhibitor and a tissue factor targeted ADC, emphasizing differentiation through unique designs and optimized molecules.
Future Outlook
- Revenue Projections:
- Zanza is expected to achieve $5 billion in revenue by 2033, with strategic trials supporting its growth trajectory.
- Strategic Prioritization:
- The company prioritizes investments in programs with the highest potential, discontinuing less promising projects like the head and neck cancer program.
Q&A Highlights
- Colorectal Cancer Strategy:
- Plans are in place to advance Zanza into earlier therapy lines, particularly in the post-adjuvant setting.
- Combination Strategies:
- Exelixis is exploring potential combinations with novel bispecifics, aiming to optimize Zanza’s development and commercial success.
For a complete understanding of Exelixis’s strategic initiatives and financial guidance, readers are encouraged to refer to the full transcript.
Full transcript - H.C. Wainwright 27th Annual Global Investment Conference:
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Welcome to our first fireside chat of the morning. I’m Robert Burns, Managing Director and Senior Biotech Analyst at HC Wainwright, and I’m joined today by Chris Senner, the Chief Financial Officer of Exelixis, as well as Andrew Peters, Senior Vice President of Strategy at Exelixis. Gentlemen, thank you for joining us today.
Unidentified speaker: Yeah, Robert, thank you very much for having us.
Chris Senner, Chief Financial Officer, Exelixis: Yeah, thanks for the invite.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Awesome. I guess let’s start from a high-level perspective. Obviously, I would assume that a lot of people are familiar with Exelixis and its pipeline, but for those who aren’t, can you provide a broad, high-level overview of the company as well as what your lead assets are?
Chris Senner, Chief Financial Officer, Exelixis: Sure. I’ll start, and Andrew can fill in where things I’ve missed. Before we get started, in the process of this discussion today, we’ll be making forward-looking statements and as such involve risk, and we refer you to our SEC filings for a full description of the risks associated with our business. Exelixis has been around for 25 plus years. Our primary product is CABOMETYX. We launched CABOMETYX for second-line RCC back in the spring of 2016, and we’ve added seven, eight different indications since, primarily in RCC, but most recently in NET or neuroendocrine tumors, which we launched in the second quarter of this year. We have about 1,000, 1,100 employees. We’re based in Alameda, California, and we have a pipeline of products coming along, including Zanzalintinib, which is another TKI, which we’re developing in many different indications. Generally, we’re a commercial oncology company.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah.
Chris Senner, Chief Financial Officer, Exelixis: I don’t know if Andrew Peters got me.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah, I mean, I think, yeah, thanks again for the invite. You know, it’s a good time to kind of tell the Exelixis story. You know, as Chris highlighted, kind of CABOMETYX is our core product. Zanza is moving fast behind it, and then we have kind of a whole pipeline beyond that of earlier stage molecules. The focus and breadth is simply about treating more patients with cancer and building value that way.
Chris Senner, Chief Financial Officer, Exelixis: Yeah.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Let’s start with the commercial success of CABOMETYX. Obviously, you know, there’s going to be PANEX versions coming relatively soon. I wanted to get your, to get a sense as to, you know, the financial guidance long term, you know, what role does CABOMETYX play within the next five years? Can you give us some insight into the launch of CABOMETYX in the GEP-NET situation?
Chris Senner, Chief Financial Officer, Exelixis: Okay. Yeah, so from a broad perspective, you know, we put out, you know, aspirational guidance, looking at Cabo in 2030, which is around the time 2030, 2031 when we have loss of exclusivity, around $3 billion. Right. That’s made up of primarily current, you know, the indications prior to NET, which is RCC, and then NET, which we launched in the second quarter. You know, we’ve launched really well. We had, you know, based on market research, we had about 35% market share for new patient starts. You know, we thought of it as about 4% of our revenue in the second quarter, and so, you know, that’s about $20 million or so. So it’s been, it’s been successful. Our guidance for this year, the midpoint of the guidance from a product revenue perspective, around $2.1 billion.
You know, we’ve gone from, you know, in the last eight, nine years, from, you know, a very small amount of sales to around $2.1 billion from the midpoint perspective. Yeah, and then kind of, you know, similarly on the aspirational guidance side, we also laid out what we think is the opportunity for Zanza kind of long term. We talked about by 2033, the clinical trials that we had running at the time represented about $5 billion in revenue. If you think kind of longer term as kind of that Cabo revenue is ramping up, rolls off in that 2030, 2031 timeframe, that’s right around the time that Zanza is really kind of hitting what we think could be kind of escape velocity, so to speak, from a revenue perspective, if you look kind of across those indications.
You know, it’s a story where, you know, we think the investments that we’re making today in Zanza as kind of a next-gen TKI set us up well to kind of, you know, normally you see these patent cliffs. If anything, we’ve been very deliberate and strategic about the indications we’ve selected, you know, the market opportunities that we’re pursuing to, you know, think of it more as a pothole, if anything, than anything different.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: All right, let’s talk about the son of Cabo, aka Zanza. Obviously, you’ve got a very broad clinical development strategy here. Why don’t you walk us through the clinical trials that you have ongoing and the ones you have planned as well that you’re going to disclose later this year?
Chris Senner, Chief Financial Officer, Exelixis: Yeah, so, you know, before I kind of get into the breadth of the studies and really kind of why we think of Zanza as a franchise molecule, I think it’s helpful to kind of provide a little bit of context as to kind of what Zanza is or how it was envisioned. You know, as we look back at the development of Cabo as kind of the next-gen TKI, VEGF targeting TKI, really the core insight there was to not only, you know, hit VEGF hard, given the angiogenic drivers, a lot of different tumors, but also understand what are the potential resistance mechanisms that can often develop in these patients who are on anti-angiogenic drugs, such as kind of the first-gen TKIs. That was kind of the core concept behind Cabo.
Obviously, we’ve been successful, and it’s now grown to be kind of the number one TKI, both as a monotherapy and as well as in combination in RCC. The one, you know, liability or issue that kind of comes up with Cabo is its relatively long half-life. It’s about a half-life of four days. From a patient management perspective, that can present certain challenges because all patients who are on these kind of chronic anti-cancer drugs develop adverse events and need down-titration, dose holds, et cetera. With that long half-life, it can add some, you know, challenges from a pure patient management perspective. Zanza was conceived to really understand, can we maintain those core kind of kinase drivers, that core efficacy profile of Cabo, but engineer it in a way to include some metabolic liabilities under that scaffold to shorten its half-life.
All the data we’ve presented so far has certainly suggested that we’ve been successful in that way. Zanza is really kind of a next-gen TKI that kind of takes the best, kind of the efficacy drivers of Cabo in a more kind of user-friendly format. The hypothesis is to, you know, does it allow for increased combinability? Is there the ability to potentially, you know, earlier lines of therapies, say, maintenance, kind of dose for longer periods, things like that. We have five pivotal studies up and running, or soon to be running right now. As we talked about on the second quarter call, a couple more that we’re excited to begin, as well as we, again, think of it as a franchise. The first, obviously, is STELLAR-303. That’s the combination of Zanza and atezolizumab against Rego in a third-line+ CRC setting.
We toplined that data earlier this year and are excited to share it as soon as we can, pending acceptances of abstracts and all of that. The next is STELLAR-304. That’s Zanza nivo against Sutent in a non-clear cell RCC population. That’s one where we think we really have a chance to establish a standard of care. It’s always surprising to me, reflecting on that indication where there’s never been a real randomized pivotal study in that patient population. We can get into a little bit more there. To us, it’s really an opportunity to define a standard of care in that patient population and help with that next leg of the Zanza story. Behind that, we have a clinical collaboration with Merck, evaluating Zanza and balsudafen. Details TBD, we’ve agreed with our partners to hold off on those details until they’re up and running.
We hope that those will be available and up and running by the end of the year. Lastly, STELLAR-311, that’s Zanza versus everolimus as a first oral option in the neuroendocrine tumor space. That really builds upon our experience and success that we’ve had with Cabo in that space. We really see the combination of all of those studies as the driver behind this concept that Zanza is a franchise, in the same way that Cabo is a franchise. We want to go deep into multiple different indications. As I’m sure we’ll get to later on, we think about franchises multidimensionally, not only with Zanza and investing broadly, but within each of those indications, we want to make sure that we can be the market leader in NET, in colorectal, with other programs as well.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah, you know, I’m glad that you mentioned the STELLAR-303 results. Obviously, we saw the significant overall survival improvement, but it’s a co-primary endpoint study, and particularly in the non-liver met, we’re still waiting for that readout. Give us a little background as to why you have that as a co-primary endpoint specifically, and whether the prognostic value of non-liver mets versus liver mets, is there a difference there?
Chris Senner, Chief Financial Officer, Exelixis: Yeah, so the liver met, non-liver met dynamic is something that’s emerged over the last four or five plus years in kind of the colorectal cancer landscape. It’s really kind of an empiric observation that these patients really had different prognoses. Unsurprisingly, if a patient unfortunately has a metastasis to the liver, they’re less likely to kind of live as long, unfortunately. The other dynamic there is patients who do not have metastases in the liver, there’s again kind of this observation that maybe they were potentially more sensitive to something like a checkpoint inhibitor, at least that was the hypothesis. Given kind of the expected differences or observed differences in past studies between these two groups, STELLAR-303 was really conceived to understand, can the combination of Zanzalintinib and atezolizumab be effective in either of those populations, or ideally both?
As we announced earlier this year, we hit on the ITT, which is reflective of both of those groups. At that time, the number of events that we had seen in the non-liver met cohort or non-liver met group was just immature. Waiting for those events to mature and accumulate so we can see an analysis there.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Can we expect that event accumulation to occur this year by end of year? Do you think that we might see top line?
Chris Senner, Chief Financial Officer, Exelixis: It’s event-based, so kind of stay tuned on that.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Okay. No, that’s completely fair. Given the late line nature of that data set, what are your plans to advance Zanza into earlier lines of therapy within the colorectal space? I know you were thinking about the post-adjuvant setting.
Chris Senner, Chief Financial Officer, Exelixis: Yeah, as I mentioned before, I think we really think about Exelixis and how we kind of build and create value is on that kind of franchise approach. One is to really take that initial signal from 303 and go deep, go broad in colorectal cancer. As we looked across the CRC landscape, one of the things that certainly jumped out is the opportunity in that post-adjuvant space. I think there’s a lot of really emerging, compelling data to suggest that there’s kind of this patient population that after they’ve had surgery and adjuvant chemotherapy, they’re still at very high risk of recurrence. 15% plus minus of patients basically understand that they’re at high rate or high risk of recurrence, but currently the standard of care is watch and wait.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah.
Chris Senner, Chief Financial Officer, Exelixis: What we’re thinking about, Zanza studies to really understand, can kind of a therapeutic intervention like Zanza, which we know colorectal cancer is sensitive to, in a kind of maintenance type setting, is that enough to essentially delay recurrence in these patients. It’s one we’re excited about, doing a lot of work on right now to get that study up and running. It really goes along with this idea that once we see a signal, we want to invest in.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah.
Chris Senner, Chief Financial Officer, Exelixis: That’s true for Zanza, it’s true for the pipeline, and it was certainly true with Cabo.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah. Why don’t we shift gears a little bit now to the clear cell RCC data that you presented at ASCO, which I thought was highly encouraging relative to CheckMate 9ER. One of the things that I noticed is that you’re still combining with nivolumab. Obviously, there’s the burgeoning class of the PD-1, PD-L1 VEGF inhibitors. Any thoughts here on potentially combining with one of those agents instead of just the regular individual monospecific checkpoint inhibitor?
Chris Senner, Chief Financial Officer, Exelixis: Yeah, I mean, I guess the short answer is, you know, we’re constantly evaluating how to best optimize development of Zanza.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah.
Chris Senner, Chief Financial Officer, Exelixis: I think kind of one of the core principles that we talk a lot about internally is everything we do at Exelixis is really through the Cabo lens.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah.
Chris Senner, Chief Financial Officer, Exelixis: What we mean by that is Cabo is successful really because of its profile and the data that we’ve been able to generate. That data we believe are differentiating and really have helped kind of shift to the right standards of care for patients. When we think about Zanza development, it’s through the lens of can this combination truly shift, right shift, you know, PFS, OS for patients with cancer.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah.
Chris Senner, Chief Financial Officer, Exelixis: As we evaluate opportunities to combine Zanza with something like a novel bispecific, it’s really asking the question, is it truly differentiated kind of versus today’s standard? What are the opportunity sets that we can develop? Certainly, these novel classes of bispecifics are interesting. I think kind of the industry at large is waiting to see how that overall survival data.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah.
Chris Senner, Chief Financial Officer, Exelixis: If it translates, one of the things that I always bring up is we certainly are kind of developing our own portfolio of potential combinations as well.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah.
Chris Senner, Chief Financial Officer, Exelixis: As we look at both internal and external combinations, it’s through that lens of can we generate differentiating data because that’s the only way we can be successful commercially and treat more patients and all of that. Stay tuned there. It’s really a matter of can we get that conviction ourselves that this combination, whether it’s a doublet or a triplet, really has the ability to kind of right shift that curve.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: You know, when we think about Zanza, obviously, you put out some projections where you thought that it could generate up to $5 billion, right? Obviously, I saw that you called the potential for head and neck cancer not too long ago. Factoring in that change as well as the additional phase 3 trials that you plan to initiate later this year, is that $5 billion benchmark that you sort of have put out there into the ether? Is that liable to change higher or lower at this point?
Chris Senner, Chief Financial Officer, Exelixis: Yeah, I mean, you know, again, as Chris mentioned earlier, kind of that aspirational guidance about what those five studies with Zanza could do. What we talked about on the second quarter call is, you know, one of the things that I think is unique about Exelixis is, you know, we always say we run it like a business and not a biotech. What that means is that we make prioritization a key focus across everything we do. What that 305 decision ultimately was is, you know, did we think it was competitive, you know, with kind of the emerging profiles in that space, as well as was this the best kind of use of our investment dollar relative to the opportunity set?
What we’ve talked about is kind of the two studies, whether it’s post-adjuvant colorectal cancer or the opportunity in meningioma, you know, those two to three times kind of the market size relative to what we saw or what we thought in head and neck. It really was a prioritization decision at the end of the day where we wanted to make sure we were making the right investments in a space that we could truly own.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah.
Chris Senner, Chief Financial Officer, Exelixis: You know, unfortunately for patients, the current standard in post-adjuvant colorectal cancer is watch and wait, and meningioma kind of similarly, once they’ve exhausted options, either surgery or radiation, there aren’t many opportunities for patients. It’s really layering on kind of that CABOMETYX experience where we’re able to look at where we can best make that investment decision and prioritize. That was a key part of it.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: To the prioritization point, we’ve committed to keeping R&D expense at $1 billion or less. That really makes Mike and I and the team prioritize where we’re investing from an R&D perspective. If we don’t see the value and we see better value somewhere else, we will make that decision to cut a program and pursue others that have better return.
Chris Senner, Chief Financial Officer, Exelixis: Okay.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Why don’t we shift gears a little bit to your earlier stage pipeline? Let’s start with your USP-1 inhibitor. Obviously, we’ve seen other players try to develop a USP-1 inhibitor, but they have been since discontinued due to toxicity issues. What do you think the differentiating factor is with regard to yours? I want to get a sense as to why you believe that 309 won’t suffer the same fate that those other USP-1 inhibitors suffered.
Chris Senner, Chief Financial Officer, Exelixis: Yeah, so there’s a couple of dynamics there. I think, first, it hasn’t necessarily been surprising to us that we found ourselves kind of alone in the USP-1 space, just given what we had thought were some kind of core liabilities with those other molecules. As it relates to 309, we think we have a particularly optimized molecule itself to really ask the question, can USP-1 inhibition again differentiate and shift that patient outcome curve to the right, either as a monotherapy or in combination with PARPs? We think we kind of have the optimized molecule to ask that hypothesis. Really what we’re doing right now is just running those studies to answer it yes or no. Our philosophy across the board, to Chris’s point on prioritization, is we want to get that answer as soon as we can.
We want to invest in the winners and discard ones that don’t really rise to the top of differentiation. Stay tuned there. We’re in the midst of generating all that data. We’ll see.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah. You know, you’ve got a few other, earlier stage assets. One I’m highly intrigued by is your tissue factor targeted ADC. Obviously, TIBC has been very successful. When we think about the competitive landscape there, obviously there are several other tissue factor targeted ADCs in development as well. Where do you see differentiation for SP-371 relative to those other ADCs?
Chris Senner, Chief Financial Officer, Exelixis: Yeah, I think our excitement around SP-371 is not only around the biology of tissue factor and why it’s an interesting target from an antibody-drug conjugate (ADC) perspective, but really incorporates three differentiating dynamics around the ADC. We think the antibody itself, given how it’s designed to be non-competitive with factor VII, is an important point of differentiation, especially relative to something like TIBC. The linker technology is particularly stable, and then, importantly, it has a TCAN-based warhead. The reason that TCAN-based warhead is particularly important comes back to this franchise idea that I mentioned before, where we know that colorectal cancer in particular is sensitive to TCAN-based chemotherapies. Given the expression profile of tissue factor and the sensitivity of colorectal cancer to TCANs, this is an opportunity for us to really go deep in colorectal cancer.
We’re excited to get that one up and running and generating data as soon as we can.
Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: It seems like we’re running up on time. I’m going to open up the floor to any questions if anyone has anything. All right. Thank you, gentlemen.
Chris Senner, Chief Financial Officer, Exelixis: Thanks, everybody.
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