Exelixis Q4 2024 Earnings Call Transcript

Quartr
Provided by Quartr
February 11, 2025

There are 19 speakers on the call.

Operator

Good day, ladies and gentlemen, and welcome to the Exelixis Fourth Quarter and Fiscal Year twenty twenty four 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.

Operator

Please proceed.

Speaker 1

Thank you, Sherry, and thank you all for joining us for the Exelixis fourth quarter and fiscal year twenty twenty four financial results conference call. Joining me on today's call are Mike Morrissey, our President and CEO and Chris Senter, our Chief Financial Officer, who will review our progress for the fourth quarter and fiscal year twenty twenty four ended 01/03/2025. DJ 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 and 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.

Speaker 1

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.

Speaker 2

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 $3,000,000,000 for cabo in 02/1930 and $5,000,000,000 for ZANZA in 02/1933. We're thrilled to see continued growth and momentum of the cabo franchise in The U.

Speaker 2

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 jumpstart 2025 at our corporate update in January at the JPMorgan Healthcare Conference. 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 IOTKI market and the second line monotherapy segment.

Speaker 2

Fourth quarter twenty twenty four, U. S. Cabo franchise net product revenues grew 20% year over year to $515,000,000 compared to fourth quarter twenty twenty three. Full year 2024, U. S.

Speaker 2

Cabo franchise net product revenues grew 11% to $1,810,000,000 compared to full year 2023. Continuing its role as the worldwide leading TKI, global Cabo franchise net product revenues generated by Exelixis and his partners were approximately $690,000,000 and $2,500,000,000 in the fourth quarter and full year 2024 respectively. 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 CABNIT Phase three pivotal trial.

Speaker 2

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 04/03/2025. Details, final results from cabinet were presented at ESMO twenty twenty four 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. 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 Zansa to take center stage in 2025 as our next oncology franchise opportunity.

Speaker 2

Important anticipated Zansa data milestones from pivotal trials include top line results from STELLAR-three zero three in colorectal cancer and STELLAR-three zero four in non clear cell kidney cancer and a decision to advance to the Phase three portion of STELLAR-three zero five 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 STELLAR-three eleven trial of ZANZA in net in the first half of twenty twenty five and anticipate Merck will initiate two RCC studies evaluating ZANZZA plus belsutifan this year. I'll remind everybody again that Exellexis is running ZANZZA pivotal trials against the contemporary standard of care for each trial, regorafenib for STELLAR-three zero three, sunitinib for STELLAR-three zero four and a pembroel placebo combination for STELLAR-three zero five. Recent speculation during ASCO GI comparing ZANZZA to cabo is misguided and a distraction from the focus of our ZANZA development activities. As highlighted on our third quarter call, our $5,000,000,000 projection for ZANZA in 02/1933 is based on success and indications, which we believe are independent from any overlap with cabo.

Speaker 2

Fourth, as we highlighted recently, our ex Alexis IND pipeline is full for the next several years with potentially differentiating molecules based on extensive preclinical testing. In 2025, we're looking to accelerate the Phase one development of XL-three zero nine 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 one trials for XB010 and XL-four 95 and see the opportunity to file up to three new INDs for XB628, XB64 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 GUGI space.

Speaker 2

Back end loaded Pay for Success transactions that tuck nicely into our existing and potential future oncology franchise remain a top priority. In terms of capital allocation, we're confident we have the balance sheet and the expected free cash flows to 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 twenty twenty four financial results and an extensive list of key corporate milestones achieved in the quarter. I'll now turn the call over to Chris. Thanks, Mike.

Speaker 3

For the fourth quarter twenty twenty four, the company reported total revenues of approximately $567,000,000 which included cabozantinib franchise net product revenues of $515,200,000 CaboMedix net product revenues were $512,800,000 and included approximately $3,000,000 in clinical trial sales, which is lower than our clinical trial sales in Q3 twenty twenty four. 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 twenty twenty four was 26.8%, which is incrementally higher than the gross to net we experienced in the third quarter twenty twenty. This increase in gross to net deductions in the fourth quarter twenty twenty four is primarily related to higher co pay assistance for our commercial patients and Medicare Part D expenses. Additionally, we estimate that our gross to net for the full year 2025 will be between 2930%.

Speaker 3

As previously disclosed, Exelixis has been designated a 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 have mentioned in the past, gross to net tends to be higher in the first quarter of the year and we project that the first quarter twenty twenty five gross to net will be similar, primarily due to higher co pay assistance expenses for our commercial patients. Our CABOMETYX trade inventory was flat at two point one weeks on hand at the end of the year when compared to the third quarter twenty twenty four. Total revenues also included approximately $51,500,000 in collaboration revenues, which includes approximately $44,000,000 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 twenty twenty four were approximately $4.00 $3,000,000 compared to $352,000,000 in the third quarter twenty twenty four.

Speaker 3

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 twenty twenty four. Provision for income taxes for the fourth quarter twenty twenty four was approximately $44,900,000 compared to a provision for income taxes of approximately $37,000,000 for the third quarter twenty twenty four. The company reported GAAP net income of approximately $139,900,000 or $0.49 per share basic and $0.48 per share diluted for the fourth quarter twenty twenty four. The company also reported non GAAP net income of approximately $160,300,000 or $0.56 per share basic and $0.55 per share diluted. Non GAAP net income excludes the impact of approximately $20,000,000 of stock based compensation expense net of the related income tax effect.

Speaker 3

Cash and marketable securities for the year ended 12/31/2024 was approximately $1,750,000,000 During fiscal year twenty twenty four, we repurchased approximately $656,000,000 of the company's shares, resulting in the retirement of approximately $26,400,000 of the company's shares at an average price per share of $24.82 As of the end of fiscal year twenty twenty four, we had approximately two ninety four million dollars remaining under the $500,000,000 stock repurchase plan authorized by the company's Board in August 2024. And finally, turning to our financial guidance for the full year 2025. We announced our 2025 financial guidance during the JPMorgan 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.

Speaker 2

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 continue 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.

Speaker 2

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

Operator

Thank

Speaker 4

And our first question will come from

Operator

the line of Asthika Goonewarden with Chua. Your line is open.

Speaker 5

Hi guys. Thanks for taking my question. And congrats on all the progress made here.

Speaker 2

Mike, just for everyone

Speaker 5

who is worried about Zansa 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 to cabo and where you anticipate XANZZA 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.

Speaker 2

Yes. Thanks, Astika. Look, I don't want to speculate on that level of details. I think the main focus is we are comparing ZAMZA combinations to individual standards of care for STELVR three zero three, STELVR three zero five. We certainly plan to do that with STELLAR-three zero four as well as what we have planned for three eleven in the net area.

Speaker 2

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. So and that's the only comparison that comes to us. All the hand waving between small datasets at single arm or very small randomized Phase two datasets is very, very challenging. Everybody knows that. We certainly know that and we're focused on running, executing and reading out these pivotal trials, because ultimately that's what will enabling efforts that we need to get Stansa 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.

Speaker 3

This is

Speaker 6

Paul on for Michael. 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?

Speaker 6

And then for Prizansa, 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 ZANZZA, especially when combining with checkpoint inhibitors? Thank you.

Speaker 2

D. J, I want to take the first part.

Speaker 7

Yes. Thanks for the question, Paul. So with regards to NET, you know, 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.

Speaker 7

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 contemporary pricing dollars is about $1,000,000,000 So, substantial opportunity. And 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 per NET, all the different grades of the tumor, different SSTR status, etcetera. 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 eighty percent.

Speaker 7

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 really excited and just can't wait to get out there and bring this to patients.

Speaker 7

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 Lemann with Morgan Stanley. Your line is open.

Speaker 8

Hi, Mike, Chris and Susan. I hope you're all well. Hey Sean. My question relates to the balance sheet. There's really good liquidity there despite that I think on the cash flow statement you bought back $650,000,000 worth of stock.

Speaker 8

I think the commentary has been that you winding down investment in Cabo, winding it up in Zansa, 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 three zero nine, potential three new INDs, I think you said, Mike. But it kind of still suggests that you're going to still end up with highly liquid and lazy balance sheet. So how would how do you think about that in terms of further buybacks versus potentially bolstering the pipeline with M and A?

Speaker 2

Yes. 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, yes, look, I think we've articulated a plan where we have built a business and run a business with a great degree of discipline.

Speaker 2

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 buy back 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. So, we have the opportunity and I would argue the responsibility to manage that very carefully, those three different tax in terms of pipeline, in terms of I'm turning 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 we'll spend about $1,000,000,000 in R and 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.

Speaker 2

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.

Speaker 9

Thank you very much for taking my questions. On the recent net data presented at 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?

Speaker 10

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.

Speaker 10

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 we're seeing 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.

Speaker 2

Hi. This is Anastasia on for Akash. I just had a follow-up question on net. 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.

Speaker 2

Thanks.

Speaker 3

Hey, Anastasia, it's Chris. So we haven't as we said at JPMorgan 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 and 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.

Speaker 11

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 two.

Speaker 11

If you could just speak to your confidence in that regulatory process, of course, an absence of OS and your plan on timing and getting the ducks in the road there? Thank you very much.

Speaker 2

Yes. Thanks, Craig. As we talked about early in the year at AM, our only singular focus right now from a regulatory point of view is getting net over the goal line, having that reviewed or approved. Once we get that done, we will circle back to the prostate opportunity with ContactO2 and at the appropriate time give you updates on where that's going.

Operator

Thank you. One moment for our next question.

Speaker 4

And that will come from

Operator

the line of Eva Forteo Verdejo with Wells Fargo. Your line is open.

Speaker 12

Hi. This is Yvonne for Derek. Thanks for taking our question. A quick one from us. So on STELLAR-three zero '3, the patient population included is both RAS wild type and mutant.

Speaker 12

But in the recent STLR-one 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 zanzo plasma?

Speaker 9

Thanks.

Speaker 10

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-one, which was really to establish or evaluate whether or not there was a contribution of components when you added atezolizumab to zanzolitinib in patients with colorectal cancer. The rationale for choosing wild type RAS wild type patients was because we observed higher responses in those patients and of course that's one metric of contribution of components.

Speaker 10

Suffice it to say that in that study, we actually saw the contribution of atezotuzanza 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 three zero three. I think we're anticipating the events as Mike alluded to the second half of twenty twenty five. We are encouraged by the results that we saw in STELLAR-one. And 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.

Speaker 4

And that will come from

Operator

the line of Jason Gerberry with Bank of America Securities. Your line is open.

Speaker 13

Hey guys, thank you for taking my question. Mike, I just wanted to follow-up on the comments earlier about the non overlap in the $5,000,000,000 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 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?

Speaker 2

Yes. Thanks, Jason. Look, I would just I'll just repeat in a more abbreviated fashion what I said to Asthika, right? I think the way to look at this is looking at how we're running the pivotal trials for three zero three, three zero five, three zero four, three zero five, three 11 and the two more trials that obviously we haven't talked about yet. So there's a little bit more information to come there.

Speaker 2

The main focus is the comparison into 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 02/1930 and 02/1931 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 plan pivotal trials that you'll actually be able to then then frame what success looks like. So I understand the easy part of comparing cabo to ZANZZA and we're certainly excited about how ZANZZA looks with all the caveats of having a number of small single arm and 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.

Speaker 2

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 do with CABO in the late teens and early 20s as we'll do ZAZANZA going forward.

Operator

Thank you. One moment for our next question.

Speaker 4

And that will come from the

Operator

line of Andy Hsieh with William Blair. Your line is

Speaker 2

So the ADC modality is a core corporate focus. So I'm just curious about the learnings that you can leverage from the XB-two program to XB-three 71 to ensure it's best in class? And more specifically, do they share the same antibody component?

Speaker 3

Dana? Yes, sure. Thanks for

Speaker 14

the question, Andy. This is Dana. Yes, so XB-two was anti tissue factor targeting ADC with a microtubule targeting payload. XB-three 71 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.

Speaker 14

And we remain excited about that potential differentiation factor. Most importantly, with three seventy one, we're very excited about how it gives us the 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 STELLAR303, LISANZA and colorectal, even with cabo and NETs. So this gives us another

Operator

question. And that will come from the line of Yaron Werber with TD Cowen. Your line is open.

Speaker 15

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 belsutifen triplet combo going to first line? Is that sort of how you're thinking about it maybe with IO?

Speaker 15

And then secondly, just for STELLAR-three zero five, what's the gono go based on the Phase II? What do you want to see then to progress into the Phase III? Thank you.

Speaker 2

Yes. So I guess I would frame your follow-up question around RCC as I

Speaker 5

think the pharmaceutical biopharma

Speaker 2

community is everybody is 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, right? That's the goal across the board. So, certainly there's nothing different about what our strategy is here with Zanza, right? 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 efficacy, improved efficacy and safety.

Speaker 2

So it's a standard process, but looking ahead, if you assume these are going to be the same five years ahead, then to be frank, we're all dropping the ball, right? Come on, that's the goal. The goal is to improve outcomes for patients. That's why we're here. So again, I don't want to get into the weeds or into the roots about what's going to happen with RCC.

Speaker 2

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 three zero three in CRC, three zero four in non clear cell RCC, three zero five in 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.

Speaker 15

Great. Thanks so much. Thanks for all the detail for taking that question. I guess maybe just around contacting two, just if you give us an update where that stands? I didn't hear you mentioned today.

Speaker 15

I know you talked about it at the beginning of the year.

Speaker 2

Yes. Thanks, Peter. I think as I mentioned to Greg a few minutes ago, our main focus, 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 two 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.

Speaker 16

Yes. Thanks for taking the question. Maybe just a follow-up on the question of RAS mutational status in 03/2003. 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.

Speaker 16

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.

Speaker 10

All right. Thanks for the question, Steven. So you are right. We did modify the primary endpoint to focus more on patients with out liver metastases, also 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 VPD patient or wild type.

Speaker 10

And as well, the data that we understand from others and that we have been following that I O therapy seems to do well for especially in patients without Libermets, which doesn't mean that it doesn't work in patients with Libermets, it's just most of the patients have been studied without them. So we modified the study to really focus on the non Libermet versus the ITT patient population. 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. Yes.

Speaker 2

And Steve, I would refer you back to the Merck, LEAP 17, 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, okay. Has a ratio and 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 1b or from a 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 Liberumet kind of story started to evolve and then LEAP-seventeen came out where liver mets went the right way.

Speaker 2

In fact, the RAS mutants went the other way. That was very important for us to take into account. Again, that's a large randomized global 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-three zero three.

Operator

Thank you. One moment for our next question.

Speaker 4

And that will come from

Operator

the line of Ash Verma with UBS. Your line is open.

Speaker 9

Hi, great. Thanks for taking my question here. So for XANZAN CRC, with this ASCO GI data in hand, I'm not trying to compare it to cabo. But if if you look at the Xantepress Ateezo efficacy versus what we've seen with the rigoraptorinib, would this level of efficacy still allow you to get to your peak sales guidance, more broadly speaking? Thanks.

Speaker 10

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 eleven point seven months for XANZATIZO, that actually bodes well against what one might expect or what has been published in the literature with rigorafenib where the median overall survival is anywhere from 6.5 to seven point five months. How that pulls through to three zero three remains to be seen as Micah said.

Speaker 10

And as we have said, it requires a very large randomized Phase three study that can generate a P value that gives you some sense of truth. And the other thing I'll point out as well in the non liver met patient population, the median survivals ranging from eighteen to twenty one months also I think bodes well given that the, RCAD Foundation published data from their data set that includes CORRECT and ReCore and a couple of Phase II studies with TAS and RIGO as the control arm. And in the non liver met patient population, the median overall survival ranges from twelve point one to twelve point nine months. And we know the median overall survival from BOTVAL and IO combination in non liver mets was about twenty months. So we're benchmarking well.

Operator

Thank you. One moment for our next question.

Speaker 4

And that will come from

Operator

the line of Sudan Loganathan with Stephens. Your line is open.

Speaker 17

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

Speaker 17

Thanks.

Speaker 2

Yes. Thanks for the question. Yes, the only gauge 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.

Speaker 2

So we've done that numerous times with cabo and certainly plan on doing that again here if successful. So we're just we're in the execution phase, but there's no gates, clearly no gates besides us having studies work.

Operator

Thank

Speaker 4

you. And that will come from

Operator

the line of Chris Shibutani with Goldman Sachs. Your line is open.

Speaker 18

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.

Speaker 18

Just wanted to ask on the amount of data that we might see in 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.

Speaker 14

Dana? 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 is published. So I would just say stay tuned on those programs.

Speaker 14

So 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. The assets pass all of the bars for that are required to convince us as well as investigators that the that there is a good hypothesis to be tested, we then file the INDs and start the Phase one trials. 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.

Speaker 4

And so, I will turn the

Operator

call over to today's host, Susan Hubbard. Ms. Hubbard?

Speaker 1

Thank you, Sherry. 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.

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Earnings Conference Call
Exelixis Q4 2024
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