Exelixis Q4 2024 Earnings Call Transcript

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Provided by Quartr
February 11, 2025

Key Takeaways

  • Cabozantinib franchise net product revenues grew 20% y-o-y to $515 M in Q4 and 11% for full-year 2024, driving global franchise revenues to approximately $2.5 B.
  • The FDA accepted the sNDA for cabozantinib in pancreatic and GI neuroendocrine tumors with a PDUFA date of April 3, 2025, positioning the company for immediate launch upon approval.
  • Multiple pivotal readouts for zanzalintinib are expected in H2 2025—including STELLAR-303 (CRC), STELLAR-304 (non-clear cell RCC), and a Phase III decision in head and neck cancer—supporting a $5 B peak sales goal by 2033.
  • Gross-to-net deductions rose to 26.8% in Q4, with 2025 guidance of 29–30% reflecting higher co-pay assistance expenses and the Medicare Part D discount as a specified small manufacturer.
  • Strong liquidity with $1.75 B in cash and securities, $656 M of share repurchases in 2024, and $294 M remaining under the $500 M buyback program.
AI Generated. May Contain Errors.
Earnings Conference Call
Exelixis Q4 2024
00:00 / 00:00

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Operator

Good day, ladies and gentlemen, and welcome to the Exelixis fourth quarter and fiscal year 2024 financial results conference call. My name is Sherry, and I'll be your operator for today. As a reminder, this call is being recorded for replay purposes. I would now like to turn the call over to your host for today, Ms. Susan Hubbard, Executive Vice President of Public Affairs and Investor Relations. Please proceed.

Susan Hubbard
Susan Hubbard
EVP of Public Affairs and Investor Relations at Exelixis

Thank you, Sherry, and thank you all for joining us for the Exelixis fourth quarter and fiscal year 2024 financial results conference call. Joining me on today's call are Mike Morrissey, our President and CEO, and Chris Senner, our Chief Financial Officer, who will review our progress for the fourth quarter and fiscal year 2024 ended January 3rd, 2025. P.J. Haley, our Executive Vice President of Commercial, Amy Peterson, our Chief Medical Officer, and Dana Aftab, our Chief Scientific Officer, are also on the call today and will participate in the Q&A portion of the call. During the call today, we will refer to financial measures not calculated according to generally accepted accounting principles. Please refer to today's press release, which is posted on our website, for an explanation of our reasons for using such non-GAAP measures, as well as tables deriving these measures from our GAAP results.

Susan Hubbard
Susan Hubbard
EVP of Public Affairs and Investor Relations at Exelixis

During the course of this presentation, we will be making forward-looking statements regarding future events and the future performance of the company. This includes statements about possible developments regarding discovery, product development, regulatory, commercial, financial, and strategic matters. Actual events or results could, of course, differ materially. We refer you to the documents we file from time to time with the SEC, which, under the heading Risk Factors, identify important factors that could cause our actual results to differ materially from those expressed by the company verbally and in writing today, including without limitation, risks and uncertainties related to product commercial success, market competition, regulatory review and approval processes, conducting clinical trials, compliance with applicable regulatory requirements, our dependence on collaboration partners, and the level of costs associated with discovery, product development, business development, and commercialization activities, and with that, I will turn the call over to Mike.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

All right. Thank you, Susan, and thanks to everyone for joining us on the call today. Exelixis had a breakout year in 2024, and we're already sprinting into 2025 after a busy January where we provided important updates across all components of our business. Exelixis has built significant momentum to establish a multi-compound, multi-franchise oncology business as we advance our cabozantinib, zanzalintinib, and early pipeline priorities to meet our aspirational revenue goals of $3 billion for Cabo in 2030 and $5 billion for Zanza in 2033. We're thrilled to see continued growth and momentum of the Cabo franchise in the U.S. and globally, both in terms of absolute revenue and relative growth compared to the competition, and we expect to see additional upside with potential new indications. We outlined important news and priorities to jump-start 2025 at our corporate update in January at the J.P. Morgan Healthcare Conference.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

I won't reiterate everything here today, but just focus on the top highlights, including first, we saw a strong performance of the cabozantinib business in the fourth quarter and full year 2024 with approximate 11% growth in demand, new starts, and revenue. CABOMETYX maintained its status as the leading TKI for RCC in both the frontline IO TKI market and the second-line monotherapy segment. Fourth quarter 2024, U.S. Cabo franchise net product revenues grew 20% year-over-year to $515 million compared to fourth quarter 2023. Full year 2024, U.S. Cabo franchise net product revenues grew 11% to $1.81 billion compared to full year 2023. Continuing its role as the worldwide leading TKI, global Cabo franchise net product revenues generated by Exelixis and its partners were approximately $690 million and $2.5 billion in the fourth quarter and full year 2024, respectively.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

Chris will review our 2025 financial guidance for the base business in his prepared remarks. We will provide updated guidance, including the net opportunity, at a later date post-approval. Second, our top priority is to advance the Cabo NET indication with ongoing regulatory activities for the sNDA based on the CABINET phase III pivotal trial. As you'll recall, we announced that the FDA had accepted our sNDA seeking approval for cabozantinib in both pNET or epNET indications with a PDUFA date of April 3rd, 2025. Detailed final results from CABINET were presented at ESMO 2024 and were concurrently published in the New England Journal of Medicine, which supported the addition of Cabo to the recently updated NCCN guidelines for NET. We're collaborating closely with the FDA on the review and won't speak to any details of that process today.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

As we've highlighted at recent investor conferences and webcasts, we are launch-ready and eager to engage as soon as approval is secured. Third, we expect Zanza to take center stage in 2025 as our next oncology franchise opportunity. Important anticipated Zanza data milestones from pivotal trials include top-line results from STELLAR-303 in colorectal cancer and STELLAR-304 in non-clear cell kidney cancer, and a decision to advance to the phase III portion of STELLAR-305 in head and neck cancer, all projected to occur in the second half of the year pending event rates for each trial. In addition, we expect to initiate the STELLAR-311 trial of Zanza in NET in the first half of 2025 and anticipate Merck to initiate two RCC studies evaluating Zanza plus belzutifan this year.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

I'll remind everybody again that Exelixis is running Zanza pivotal trials against a contemporary standard of care for each trial: regorafenib for STELLAR-303, sunitinib for STELLAR-304, and a pembrolizumab combination for STELLAR-305. Recent speculation during ASCO GI comparing Zanza to Cabo is misguided and a distraction from the focus of our Zanza development activities. As highlighted on our third quarter call, our $5 billion projection for Zanza in 2033 is based on success and indications, which we believe are independent from any overlap with Cabo. Fourth, as we highlighted recently, our Exelixis IND pipeline is full for the next several years with potentially differentiating molecules based on extensive preclinical testing.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

In 2025, we're looking to accelerate the phase I development of XL309 as a potential therapy for tumors that have become refractory to PARP inhibitor therapy, as well as in combination with PARP inhibitors to deepen and prolong responses. Also, we're pleased with our progress of phase I trials for XB010 and XL495 and see the opportunity to file up to three new INDs for XB628, XB064, and XB371. We expect a significant number of data presentations for these molecules at major scientific meetings throughout 2025. Business development activities continue to focus on late-stage assets in the GU/GI space. Back-end-loaded pay-per-success transactions that tuck nicely into our existing and potential future oncology franchise remain a top priority.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

In terms of capital allocation, we're confident we have the balance sheet and the expected free cash flows to advance our pipeline priorities, access new high-conviction assets, and continue to repurchase shares. So with that, please see our press release issued an hour ago for our fourth quarter and full year 2024 financial results and an extensive list of key corporate milestones achieved in the quarter. I'll now turn the call over to Chris.

Chris Senner
Chris Senner
CFO at Exelixis

Thanks, Mike. For the fourth quarter of 2024, the company reported total revenues of approximately $567 million, which included cabozantinib franchise net product revenues of $515.2 million. CABOMETYX net product revenues were $512.8 million and included approximately $3 million in clinical trial sales, which is lower than our clinical trial sales in Q3 2024. As a continued reminder, clinical trial sales have historically been choppy between quarters, and we expect this to continue into the future. Gross-to-net for the cabozantinib franchise in the fourth quarter 2024 was 26.8%, which is incrementally higher than the gross-to-net we experienced in the third quarter 2024. This increase in gross-to-net deductions in the fourth quarter 2024 is primarily related to higher copay assistance for our commercial patients and Medicare Part D expenses.

Chris Senner
Chris Senner
CFO at Exelixis

Additionally, we estimate that our gross-to-net for the full year 2025 will be between 29% and 30%. As previously disclosed, Exelixis has been designated as specified small manufacturer, which requires Exelixis to pay a 1% discount in 2025 on all Medicare Part D sales and is included in our gross-to-net estimate for the year. As we've mentioned in the past, gross-to-net tends to be higher in the first quarter of a year, and we project that the first quarter 2025 gross-to-net will be similar, primarily due to higher copay assistance expenses for our commercial patients. Our CABOMETYX trade inventory was flat at 2.1 weeks on hand at the end of the year when compared to the third quarter 2024.

Chris Senner
Chris Senner
CFO at Exelixis

Total revenues also included approximately $51.5 million in collaboration revenues, which includes approximately $44 million in royalties earned from our partners, Ipsen and Takeda, on their sales of cabozantinib. Our total operating expenses, excluding restructuring and impairment charges for the fourth quarter 2024, were approximately $403 million, compared to $352 million in the third quarter 2024. The sequential increase in these operating expenses was primarily driven by higher manufacturing costs for drug development candidates, higher clinical trial and licensing costs, and by higher general and administrative costs in the fourth quarter 2024. Provision for income taxes for the fourth quarter 2024 was approximately $44.9 million, compared to a provision for income taxes of approximately $37 million for the third quarter 2024. The company reported GAAP net income of approximately $139.9 million, or $0.49 per share basic, and $0.48 per share diluted for the fourth quarter 2024.

Chris Senner
Chris Senner
CFO at Exelixis

The company also reported non-GAAP net income of approximately $160.3 million, or $0.56 per share basic and $0.55 per share diluted. Non-GAAP net income excludes the impact of approximately $20 million of stock-based compensation expense net of the related income tax effect. Cash and marketable securities for the year ended December 31, 2024, was approximately $1.75 billion. During fiscal year 2024, we repurchased approximately $656 million of the company's shares, resulting in the retirement of approximately 26.4 million of the company's shares at an average price per share of $24.82. As of the end of fiscal year 2024, we had approximately $294 million remaining under the $500 million stock repurchase plan authorized by the company's board in August 2024.

Chris Senner
Chris Senner
CFO at Exelixis

And finally, turning to our financial guidance for the full year 2025, we announced our 2025 financial guidance during the J.P. Morgan Conference in January, which is detailed on slide 19 of our earnings presentation. As Mike mentioned, we will provide updated net product revenue guidance, including the net opportunity, at a later date post-approval. And with that, I'll turn the call back over to Mike.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

All right. Thanks, Chris. I'll wrap up here by thanking the entire Exelixis team for their outstanding efforts in 2024. As I've said previously, success never comes in a straight line in this business, and I want to commend everyone at Exelixis for their individual and collective urgency and resilience as we navigated our past challenges and continued to advance our discovery, development, and commercial priorities. 2025 is already shaping up to be another inflection year for the business and the patients we hope to serve now and in the future. I am so proud to be part of the team that makes every hour count as we excel on our mission to help cancer patients recover stronger and live longer. We look forward to updating you on our progress in the future.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

Thank you for your continued support and interest in Exelixis, and we're happy to now open the call for questions.

Operator

Thank you. If you would like to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, press star one one again. Due to time restraints, we ask that you please limit yourself to one question. You may then return to the queue. Please stand by while we compile the Q&A roster. Our first question will come from the line of Asthika Goonewardene with Truist. Your line is open.

Asthika Goonewardene
Asthika Goonewardene
Managing Director at Truist Securities

Hi, guys. Thanks for taking my question and congrats on all the progress made here. Mike, just for everyone who's worried about Zanza looking like Cabo, the misguided notion that you talked about earlier today, can you just, just to dismiss that a little bit more, could you just talk to us a little bit about, one, the lack of overlap in the approved indications for Cabo and where you anticipate Zanza will be? And I think the important one here is, if you've ever seen the payers, I guess, force a substitution with a generic of something that is not the actual generic product. I don't think I've ever seen that happen, but would like to get your thoughts on that.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

Yeah, thanks, Asthika. Look, I don't want to speculate on that level of details. I think the main focus is we are comparing Zanza combinations to individual standards of care for STELLAR-303, STELLAR-305. We certainly plan to do that with STELLAR-304 as well, as well as what we have planned for 311 in the NET area. So the goal here is to obviously run large global randomized pivotal trials that will allow us to generate positive data, if it's there, to be able to push those indications forward. And that's the only comparison that counts to us. All the hand-waving between small data sets of single-arm or very small randomized phase II data sets is very, very challenging. Everybody knows that.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

We certainly know that, and we're focused on running, executing, and reading out these pivotal trials because ultimately that's what will drive the label-enabling efforts that we need to get Zanza moving forward into more patients in the commercial setting and really helping those patients who need better therapies.

Operator

Thank you. One moment for our next question. And that will come from the line of Michael Schmidt with Guggenheim Securities. Your line is open.

Operator

Hi, this is Paul from Guggenheim. Thanks for taking our question. One is on Cabo for NETs. Sort of pending the label discussions and formalization, how are you currently thinking about the launch trajectory and expectations for uptake? Do you see any potential for an initial bolus here given that this is a sort of indolent disease? And then for Zanza, can you just comment on the emerging safety profile now that we have more data and indications beyond RCC? On balance, what are your current thoughts on the ability to maintain dose intensity with Zanza, especially when combining with checkpoint inhibitors? Thank you.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

P.J, you want to take the first part?

P.J. Haley
P.J. Haley
EVP of Commercial at Exelixis

Yeah, thanks for the question, Paul. So with regards to NET, as Mike mentioned, we are completely launch ready, and the team is, I would say, very excited and just ready to go so we can have the opportunity to help appropriate patients with neuroendocrine tumors pending an FDA approval. That said, as we've said previously, we believe that the opportunity is significant. We've talked about the fact that in 2025, we look at the NET market and the oral shares within that market. We believe the oral market in 2025 in constant pricing dollars is about $1 billion, so substantial opportunity. When we think about the CABINET study and the data set, it's a broad data set, really the only of its kind that addresses all sites of origin for NET, all the different grades of the tumor, different SSTR status, etc.

P.J. Haley
P.J. Haley
EVP of Commercial at Exelixis

So it can really be a choice for any type of NET patient pending approval. We've talked about before, too, the overlap of customers that we see in terms of customers, both that we are calling on currently for our approved on-label indications, as well as prescribers who have already written CABOMETYX is about 80%, so that's significant. So that speaks to really the ability for us to really come out of the gates fast and accelerate the launch trajectory of this. And we hear from market research that physicians are excited about the data. They like the efficacy they see. They understand the safety. And when they find out this is Cabo that they're familiar with, it really makes them comfortable in terms of dose reduction and managing that toxicity profile. So we're really excited and just can't wait to get out there and bring this to patients.

P.J. Haley
P.J. Haley
EVP of Commercial at Exelixis

The final thing I'd mention here, too, is that the oral therapies we're competing with, effectively sunitinib, everolimus, and CAPTEM, are all generic. So this will also give us, we believe, a substantial advantage in terms of share of voice and other aspects of things. So we're excited for the launch.

Operator

Thank you. One moment for our next question. And that will come from the line of Sean Laaman with Morgan Stanley. Your line is open.

Sean Laaman
Sean Laaman
Analyst at Morgan Stanley

Hi, Mike, Chris, and Susan. I hope you're all well.

Sean Laaman
Sean Laaman
Analyst at Morgan Stanley

My question relates to the balance sheet. There's really good liquidity there, despite that I think on the cash flow statement, you've bought back $650 million worth of stock. I think the commentary has been that you're winding down investment in Cabo, winding it up in Zanza, but you're probably looking at a net neutral outcome, if I got our past discussions correct in terms of OpEx. Then you've talked about accelerated development of 309, potential three new INDs, I think you said, Mike. But it kind of still suggests that you're going to still end up with a highly liquid and lazy balance sheet. So how do you think about that in terms of further buybacks versus potentially bolstering the pipeline with M&A?

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

Yeah, thanks for the question. So I'm not sure I'd characterize that much free cash flow as lazy. If so, then most other companies would want to aspire to that. So yeah, look, I think we've articulated a plan where we have built a business and run a business with a great degree of discipline so we can move our pipeline priorities forward with Cabo, with Zanza, with the rest of the pipeline. We can do the appropriate capital allocation to buyback shares when we think the price is appropriate, and then to invest in new assets when we have the conviction that they will help move the needle for patients and for our revenue goals going forward.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

So we have the opportunity, and I would argue the responsibility to manage that very carefully, those three different hacks in terms of pipeline, in terms of returning cash to shareholders, and then BD in a way that moves the business forward in the short term and the long term. So I like that optionality, and I like that flexibility. We're spending about $1 billion in R&D this year, and we think we have the opportunity to prioritize and focus based upon how the data comes in and what that tells us in terms of where to put money behind the winners and when to stop the losers. So I think we've got that well handled, and we're looking forward to continue to move the ball downfield in a way that helps patients and builds value for our shareholders.

Operator

Thank you. One moment for our next question. And that will come from the line of David Lebowitz with Citi. Your line is open.

David Lebowitz
David Lebowitz
Analyst at Citi

Thank you very much for taking my question. On the recent NET data presented to the ASCO GI, could you tell us about how we should view the various subgroups relative to actually how the drug might be used in clinical practice and what the label might ultimately look like?

Amy Peterson
Amy Peterson
Chief Medical Officer at Exelixis

Hi, David. This is Amy. Thanks for the question. So we can't really speak to what the label might look like. We're in negotiations and discussions with the agency. But given the population that was evaluated in CABINET, it really reflects a very broad patient population. We have pancreatic neuroendocrine tumor, GI neuroendocrine tumor, lung neuroendocrine tumor, functional/non-functional neuroendocrine tumors, and neuroendocrine tumors enrolled regardless of their somatostatin receptor expression levels. And benefits were seen across all subgroups. And what was shown at ASCO GI was that the benefit within those patients whose tumor originates from a GI origin, their benefits were consistent with the benefits seen in the overall population. So again, broad population, we think broadly applicable.

Operator

Thank you. One moment for our next question. And that will come from the line of Akash Tewari with Jefferies. Your line is open.

Operator

Hi, this is Anastasia on for Akash. I just had a follow-up question on NETs. Specifically for your 2025 guidance, just wondering how much of that comes from NETs versus other indications. If you could give us a sense of what near-term versus long-term growth might look like, that would be great. Thanks.

Chris Senner
Chris Senner
CFO at Exelixis

Hey, Anastasia. It's Chris. So as we said at J.P. Morgan and we've said today, we haven't put net in our guidance. We'll do that at some point in the future when we understand what our final label is, but also understand what the launch trajectory is post-approval.

Operator

Thank you. One moment for our next question, and that will come from the line of Gregory Renza with RBC Capital Markets. Your line is open.

Gregory Renza
Gregory Renza
Analyst at RBC Capital Markets

Great. Good afternoon, Mike and team. Congrats on the progress. Thanks for taking my question. Mike, just in relation to that pursuit of expansion, getting more out of Cabo, just beyond NET, I just wanted to ask that you comment a bit on the pushes and pulls for a submission in, of course, prostate cancer and CONTACT-02. If you could just speak to your confidence in that regulatory process, of course, in absence of OS and your plan on timing and getting the ducks in a row there. Thank you very much.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

Yeah, thanks, Greg. As we talked about early in the year at PM, our only singular focus right now from a regulatory point of view is getting NET over the goal line, having that reviewed and approved. Once we get that done, we will circle back to the prostate opportunity with CONTACT-02 and, at the appropriate time, give you updates on where that's going.

Operator

Thank you. One moment for our next question. And that will come from the line of Eva Fortea-Verdejo with Wells Fargo. Your line is open.

Eva Fortea-Verdejo
Eva Fortea-Verdejo
Analyst at Wells Fargo

Hi, this is Eva on for Derek. Thanks for taking our question. A quick one from us. So on STELLAR-303, the patient population included is both RAS wild-type and mutant. But in the recent STELLAR-001 readout, the patient population was just RAS wild-type. So how should we be thinking about how the differences in patient population could impact the overall survival for Zanza plus atezo? Thanks.

Amy Peterson
Amy Peterson
Chief Medical Officer at Exelixis

Hi, Eva. This is Amy. Thanks for the question. So I'm just going to step back a second to remind everybody what was the purpose of STELLAR-001, which was really to establish or evaluate whether or not there was a contribution of components when you added atezolizumab to Zanzalintinib in patients with colorectal cancer. The rationale for choosing RAS wild-type patients was because we observed higher responses in those patients. And of course, that's one metric of contribution of components. Suffice it to say that in that study, we actually saw the contribution of atezo to Zanza across all three efficacy components, namely ORR, PFS, and OS. And so we're encouraged by those results. As far as the read-through to STELLAR-303, I think we're anticipating the events, as Mike alluded to, the second half of 2025. We are encouraged by the results that we saw in STELLAR-001.

Amy Peterson
Amy Peterson
Chief Medical Officer at Exelixis

That's really about all I can say with regard to how to pull that through.

Operator

Thank you. One moment for our next question. That will come from the line of Jason Gerberry with Bank of America Securities. Your line is open.

Jason Gerberry
Analyst at Bank of America Securities

Hey, guys. Thank you for taking my question. Mike, I just wanted to follow up on the comments earlier about the non-overlap and the $5 billion peak. I think the thing that I think investors struggle with is RCC is still a big percentage of the addressable patients in the kind of patient build. And then the comment about the non-overlap, I guess it suggests either that the novel agents added to an RCC combination are really what drives the incremental benefit or that you won't compare against Cabo, which is one of the RCC standards of care. And I imagine the answer is we can't tell you much until the second half when you and Merck disclose your trial designs. But anything you can offer just to help maybe investors get around that, I guess, that issue or that lack of understanding?

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

Yeah. Thanks, Jason. Look, I would just repeat in a more abbreviated fashion what I said to Asthika. I think the way to look at this is looking at how we're running the pivotal trials for 303, 305, 304, 305, 311, and the two Merck trials that obviously we haven't talked about yet. So there's a little bit more information to come there. The main focus is the comparison to the standard of care that's being run in those pivotal trials. We think, and just to look forward in the RCC space, that RCC will look differently in 2030 and 2031 than it does in 2024 and 2025. You have to look at what's happening and the competitive nature of that indication. And true for all of oncology, to look forward to planned pivotal trials that you'll actually be able to then frame what success looks like.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

So I understand the easy part of comparing Cabo to Zanza, and we're certainly excited about how Zanza looks with all the caveats of having a number of small single-arm, in some cases, small randomized studies. The bottom line is you generate good comparative data by running the right pivotal trials where you compare against standard of care and you compare efficacy and safety. And we're doing that. We have three going with Zanza right now. We'll have three more going this year. And we expect a second wave coming after that. And that's how you define really the next wave of standard of care, as you did with Cabo in the late teens and early 20s, as we'll do with Zanza going forward.

Operator

Thank you. One moment for our next question. And that will come from the line of Andy Hsieh with William Blair. Your line is open.

Andy Hsieh
Andy Hsieh
Analyst at William Blair

Thanks for taking my question. The ADC modality is a core corporate focus. I'm just curious about the learnings that you can leverage from the XB002 program to XB371 to ensure it's best in class. More specifically, do they share the same antibody component?

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

Dana?

Dana Aftab
Dana Aftab
Chief Scientific Officer at Exelixis

Yeah, sure. Thanks for the question, Andy. This is Dana. Yeah, so XB002 was an anti-tissue factor targeting ADC with a microtubule targeting payload. XB371 uses the same antibody with a drug-antibody ratio of eight and a topoisomerase inhibitor drug payload. We're excited about how that antibody differentiates from other tissue factor antibodies because of the epitope that it binds to, not causing problems with blood clotting. And we remain excited about that potential differentiation factor. Most importantly, with 371, we're very excited about how it gives us a potential opportunity to move with a biologic with an ADC into colorectal cancer. As you know, Mike's talked many times in the past about how we're really focused on building a franchise in GI with Stellar 303 with Zanza and colorectal, even with Cabo and NETs.

Dana Aftab
Dana Aftab
Chief Scientific Officer at Exelixis

So this gives us another opportunity to move into this indication and create a bit of a franchise with that ADC.

Operator

Thank you. One moment for our next question. And that will come from the line of Yaron Werber with TD Cowen. Your line is open.

Yaron Werber
Yaron Werber
Analyst at TD Cowen

Great. I have an interrelated question, Mike, or whoever wants to take it. For RCC, I mean, it sounds like the future is going to look different than now. So should we, and I know you don't want to say too much ahead of announcing the trial design, but should we assume there's going to be a Zanza-belzutifan triplet combo going to first line? Is that sort of how you're thinking about it, maybe with IO? And then secondly, just for Stellar 305, what's the go-no-go based on the phase II? What do you want to see then to progress into the phase III? Thank you.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

Yeah. So I guess I would frame your follow-up question around RCC as I think the pharmaceutical biopharma community is. Everybody's working to improve standard of care going forward. I think that's how we help patients, and that's obviously how we move new molecules into the system. That's the goal across the board. So certainly, there's nothing different about what our strategy is here with Zanza. We're using what we think is a best-in-class TKI with the appropriate combination partners to be able to compare against contemporaneous standards of care molecules to be able to prove improved efficacy and safety. So it's a standard process. But looking ahead, if you assume things are going to be the same five years ahead, then to be frank, we're all dropping the ball. Come on. That's the goal. The goal is to improve outcomes for patients. That's why we're here.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

So again, I don't want to get into the weeds or into the roots about what's going to happen with RCC. We will announce those trials at the appropriate time with Merck. But again, we're focused on improving standard of care for patients with cancer. We're doing it right now. The plan is with 303 and CRC, 304 and non-clear cell RCC, 305 and head and neck cancer, and many more to come after that. So stay tuned.

Operator

Thank you. One moment for our next question, and that will come from the line of Peter Lawson with Barclays. Your line is open.

Peter Lawson
Peter Lawson
Analyst at Barclays

Great. Thanks so much. Thanks for all the details. Thank you for that question. I guess maybe just around CONTACT-02, just if you'd give us an update on where that stands. I didn't hear it mentioned today. I know you talked about it at the beginning of the year.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

Yeah. Thanks, Peter. I think as I mentioned to Greg a few minutes ago, our singular focus right now from a regulatory point of view is on CABINET and the NET indication getting that approved and moving that forward. Once that's secured, then we'll focus back on CONTACT-02 and CRPC. Nothing more to add on that today.

Operator

Thank you. One moment for our next question. And that will come from the line of Stephen Willey with Stifel. Your line is open.

Stephen Willey
Stephen Willey
Managing Director at Stifel

Yeah. Thanks for taking the question. Maybe just to follow up on the question of RAS mutational status in 303, can you just help us understand kind of what the expected distribution of wild-type versus mutant is now expected to be in the upsized version of this trial? I know the first version, I believe, specified a primary efficacy endpoint that was in RAS wild-type only. I think there was an enrollment cap that you had put in place for RAS mutants. So just wondering if you can comment on whether the upsizing now changes the expected distribution here of RAS status. Thank you.

Amy Peterson
Amy Peterson
Chief Medical Officer at Exelixis

All right. Thanks for the question, Stephen. So, you were right. We did modify the primary endpoint to focus more on patients without liver metastasis, also what we refer to as the non-liver met patient population. The rationale for that was because of publications demonstrating that the prognostic situation with those patients is much stronger than, say, for example, RAS or mutation or wild-type, and as well, the data that we understand from others and that we have been following that IO therapy seems to do well, especially in patients without liver mets, which doesn't mean that it doesn't work in patients with liver mets. It's just most of the patients have been studied without them, so we modified the study to really focus on the non-liver met versus the ITT patient population.

Amy Peterson
Amy Peterson
Chief Medical Officer at Exelixis

And right now, I can't give you what the breakdown is of the RAS mutational status to wild-type in the study, but it will be when the data comes, you'll have that answer.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

Yeah. And Steve, I would refer you back to the Merck LEAP-017, both presentation and paper. When they broke out the RAS mutational status by at least by hazard ratio in their forest plot, the mutant RAS population actually did better than the wild-type population. Hazard ratio from that study was 0.76 for the mutants and 0.9 for the wild-type. So again, I think if people are focused on 30 patients from a Cabo phase Ib or 30 patients from a Cabo IST, I mean, that was interesting to us. It certainly was hypothesis-generating. But I think when the, as the non-liver met kind of story started to evolve and then LEAP-017 came out where liver mets went the right way, in fact, the RAS mutants went the other way, that was very important for us to take into account.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

Again, that's a large randomized globally run pivotal trial. So it's really the gold standard from our point of view about guiding us on how to then evolve STELLAR-303.

Operator

Thank you. One moment for our next question. And that will come from the line of Ash Verma with UBS. Your line is open.

Ash Verma
Ash Verma
Analyst at UBS

Hi. Great. Thanks for taking my question here. So for Zanza and CRC, with this ASCO GI data in hand, I'm not trying to compare it to Cabo, but if you look at the Zanza plus atezo efficacy versus what we've seen with the regorafenib, would this level of efficacy still allow you to get to your peak sales guidance, more broadly speaking? Thanks.

Amy Peterson
Amy Peterson
Chief Medical Officer at Exelixis

Thanks, Ash, for the question. So we're actually encouraged by the data that we saw. Again, the study design was really to demonstrate whether or not there was a contribution of components, which we clearly did demonstrate across all three efficacy endpoints. When you actually look at the outcomes of OS, say, for example, in the ITT of 11.7 months for Zanza atezo, that actually bodes well against what one might expect or what has been published in the literature with regorafenib, where the median overall survival is anywhere from 6.5-7.5 months. How that pulls through to 303 remains to be seen, as Mike has said. And as we have said, it requires a very large randomized phase III study that can generate a p-value that gives you some sense of truth.

Amy Peterson
Amy Peterson
Chief Medical Officer at Exelixis

The other thing I'll point out as well, in the non-liver met patient population, the median survivals ranging from 18-21 months also, I think, bodes well, given that the ARCAD Foundation published data from their dataset that includes CORRECT and RECOURSE and a couple of phase II studies with TAS and regorafenib as the control arm. In the non-liver met patient population, the median overall survival ranges from 12.1-12.9 months. We know the median overall survival from BOT/BAL and IO combination in non-liver mets was about 20 months. We're benchmarking well.

Operator

Thank you. One moment for our next question. And that will come from the line of Sudan Loganathan with Stephens. Your line is open.

Sudan Loganathan
Sudan Loganathan
Managing Director at Stephens

Hi. Good afternoon. Thanks for taking my question. I specifically want to ask about the STELLAR programs, 303, 304, and 305. What will be the driving force to prioritize one program over the others to bring to market first? Or does the balance sheet and the R&D guidance kind of include the potential of taking all three indications simultaneously, submitting for regulatory approval if the data looks good? And it's undeniable that you have that strategy to submit for approval. Thanks.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

Yeah. Thanks for the question. Yeah. The only gain here is a p-value. If the trials work, obviously, we would take those forward with great speed and focus. We're in the game of running pivotal trials and then moving them forward from a regulatory point of view. And that's our business. So we've done that numerous times with Cabo and certainly plan on doing that again here if successful. So we're in the execution phase, but there's no gauge. Clearly, no gauge besides us having studies work.

Operator

Thank you. As a reminder, if you would like to ask a question, please press star one one. One moment for our next question. And that will come from the line of Chris Shibutani with Goldman Sachs. Your line is open.

Operator

Hi. This is Kevin on for Chris. Thanks for taking our questions. I just wanted to touch on the earlier stage pipeline. You mentioned that there should be a number of presentations this year. Just wanted to ask on the amount of data that we might see and the cadence of these updates. And then as you think about three new INDs coming in, how are you making go/no-go decisions as it relates to these programs? Thank you.

Mike Morrissey
Mike Morrissey
President and CEO at Exelixis

Dana?

Dana Aftab
Dana Aftab
Chief Scientific Officer at Exelixis

Okay. So as Mike said in his prepared remarks, we're planning for presentations at scientific meetings. We don't typically give more information than that until the abstract's published. So I would just say stay tuned on those programs. But we're excited about the data that we're planning to present to the community on those programs. And then regarding the early stage pipeline, we follow what I would consider to be best practices in the industry, which is we follow a certain cadence of IND-enabling activities, including GLP toxicology. If the assets pass all of the bars that are required to convince us, as well as investigators, that there is a good hypothesis to be tested, we then file the INDs and start the phase I trials.

Dana Aftab
Dana Aftab
Chief Scientific Officer at Exelixis

So we are progressing on that track with all three of those assets, and we'll continue to make announcements as those INDs are accepted by the FDA and we start executing those trials.

Operator

Thank you. At this time, there are no further questions. And so I will turn the call over to today's host, Susan Hubbard. Ms. Hubbard?

Susan Hubbard
Susan Hubbard
EVP of Public Affairs and Investor Relations at Exelixis

And thank you all for joining us today. We certainly welcome your follow-up calls with any additional questions you may have. Thank you.

Operator

This concludes today's program. Thank you all for participating. You may now disconnect.

Executives
    • Dana Aftab
      Dana Aftab
      Chief Scientific Officer
    • Susan Hubbard
      Susan Hubbard
      EVP of Public Affairs and Investor Relations
    • Mike Morrissey
      Mike Morrissey
      President and CEO
    • P.J. Haley
      P.J. Haley
      EVP of Commercial
    • Amy Peterson
      Amy Peterson
      Chief Medical Officer
    • Chris Senner
      Chris Senner
      CFO
Analysts
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