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spk18: Good day, ladies and gentlemen, and welcome to the XLXS fourth quarter and full year 2022 financial results conference call. My name is Vaishnavi, 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.
spk13: Thank you, Vaishnavi, and thank you all for joining us for the Exalexa's fourth quarter and full year 2022 financial results conference call. Joining me on today's call are Mike Morrissey, our president and CEO, and Chris Fenner, our chief financial officer, who will review our progress for the fourth quarter and full year 2022, ended December 31st, 2022. PJ Haley, our executive vice president of commercials, Vicki Goodman, our chief medical officer, and And Peter Lamb, our Chief Scientific Officer, are also on the call today and will participate in our question and answer 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 results for using such non-GAAP measures, as well as tables deriving these measures from our GAAP results. 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 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 now turn the call over to Mike.
spk06: All right, thank you, Susan, and thanks to everyone for joining us on the call today. ExoLexus had a strong fourth quarter and full year 2022 across all components of our business. We're pleased to see continued growth of the Cabo Zantan franchise in the U.S. and globally in the fourth quarter and full year 2022, while advancing our discovery and development priorities to build the ExoLexus product portfolio of the future. As we had a complete corporate update a few weeks ago at the JP Morgan Healthcare Conference, Chris and I will provide a summary of top corporate and financial highlights for the fourth quarter and key 2023 priorities before moving into Q&A with the full team. First, we saw a strong performance of the Cabo's antediluted business with continued growth in demand and revenue in the U.S. Cabo Medics maintained its status as the leading TKI for RCC, in both the first-line IOTKI market and the second-line monotherapy segment. Fourth quarter CABA franchise net product revenues grew 25% year-over-year compared to fourth quarter 2021. CABA franchise net product revenues grew 30% for the full year 2022 compared to full year 2021 and have approximately doubled since 2020. Importantly, global CABA's antigen franchise net product revenues generated by ExoLexus and its partners were approximately $520 million and $1.9 billion in the fourth quarter and full year 2022, respectively. Chris will review our 2023 financial guidance in his prepared remarks. Second, our top priority for 2023 is to advance the ExoLexus development pipeline with new potential CAVO indications, expedite exams of lintinib, development with new pivotal trials, pursuing XB002 myelotherapy and combination expansion cohorts with the goal of moving this agent into full development by year-end. Our discovery organization is advancing XB010, XB014, and XB628 in developmental development towards potential INDs with a range of additional projects vectoring towards development candidates for both biologics and small molecule platforms. Third, business development activities will continue to be a critical focus for XOXs throughout 2023. The two option deals with Cybrexa and Seropa are off to a great start, and we're working closely with those teams to advance their efforts to get to an option decision as quickly as possible. Our strategy to access clinical and or near clinical stage assets that have the potential to provide differentiated benefits to patients with cancer will continue to be our primary focus in 2023. The option deal framework is a capital and resource-efficient way to generate clinical proof-of-concept data and only pay for success if that data is supported. And finally, on January 19th, the Federal District Court in Delaware issued its ruling in the first XOXs versus MSN case, what we refer to as MSN-1. MSN's validity challenge to the cabozantinib compound patent was rejected and and MSN's proposed generic product was ruled to not infringe the ex-flexus N2 polymorph patent. MSN did not dispute the validity of the N2 polymorph patent, so it also remains valid and in force, and no intellectual property in the ex-flexus cobalt antidepressant patent estate has been invalidated. Our attention and resources have now shifted to MSN2, which goes to trial in October, and we will continue to vigorously protect our intellectual property rights. So with that, see our press release issued an hour ago for our fourth quarter and full year 2022 financial results and an extensive list of key corporate milestones achieved in the quarter. I'll now turn the call over to Chris.
spk08: Thanks, Mike. For the fourth quarter 2022, the company reported total revenues of approximately $424 million, which included Cabo's anti-franchise net product revenues of $377.4 million. CaboMedic's net product revenues were $372.6 million and included approximately $7 million in clinical trial sales. Growth to net for the Cabo's anticipated franchise in the fourth quarter of 2022 was 27.9%, which is higher than the growth to net we experienced in the third quarter of 2022, but overall in line with our expectations for the year. This increase in growth to net deductions in the fourth quarter of 2022 primarily related to higher PHS, Medicare Part D, and co-pay assistance expenses. Our Cabo Medics trade inventory increased by approximately 750 units when compared to the third quarter 2022 to approximately 2.7 weeks on hand. This increase in inventory was partially related to the timing of the Christmas and New Year's holiday at the end of 2022 and the beginning of 2023. Based on what we can see in the trade, most of this inventory has been utilized in the first few weeks of January 2023. Total revenues also included approximately $46 million in collaboration revenues, which includes approximately $34 million of royalties earned from Ipsen and Takeda on their sales of Cabozantinib. And finally, clinical trial sales have historically been choppy between quarters, and we expect this to continue in future quarters. Our total operating expenses for the fourth quarter of 2022 were approximately $472 million, compared to $329 million in the third quarter of 2022. R&D expense was the primary driver of the increase in total operating expenses, which was primarily related to higher licensing expenses for the three business development deals we announced during the fourth quarter, which added approximately $130 million to our R&D expenses. Benefit from income taxes for the fourth quarter of 2022 was approximately $1.3 million, compared to a provision for income taxes of approximately $19 million for the third quarter of 2022. The company reported gap net loss of approximately $30 million, or 9 cents per share, basic and diluted for the fourth quarter of 2022. This net loss was impacted by the approximate $130 million of new business development deals we announced in the fourth quarter of 2022. The company also reported a non-gap net loss of approximately $10 million, or 3 cents per share, basic and diluted. Non-gap net income excludes the impact of approximately $20 million of stock-based compensation expense net of the related income tax effect. Cash and investments for the year ended December 31, 2022, was approximately $2.1 billion. This level of cash and investments supported by our ongoing cash flow from operations provides us with the flexibility to invest in internal discovery activities and also allows us to pursue external business development opportunities to expand our pipeline. And finally, turning to our financial guidance for the full year of 2023. We announced our 2023 financial guidance at the J.P. Morgan Conference in January, and it is detailed on slide 19 of our earnings presentation. And with that, I'll turn the call back over to Mike.
spk06: All right. Thanks, Chris. As you heard on the call today, the XOXS team had a great year in 2022, and we have even greater expectations for 2023 and beyond. As we hit our stride this year, we're thrilled to have the momentum from our Cabo's Antidote Franchise performance and are completely focused on the growth drivers across all components of the business, that we hope will enable ExoLexus to help many more cancer patients in the future. I close by thanking the entire ExoLexus team for their individual and collective efforts to support our range of discovery, development, and commercial activities. The team is highly motivated every day to fulfill our mission to help cancer patients recover stronger and live longer. We set our expectations high and drive for results. While we grew considerably in 2022, we remain committed to being nimble and creative and to foster a culture of collaboration and engagement. We look forward to updating you on our progress in the future. Thank you for your continued support and interest in Exalexis. And we're now happy to open the call for questions.
spk18: Thank you. We will now begin the question and answer session. To ask a question, you may press star, then one on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star, then two. At this time, we will pause momentarily to assemble our roster. Our first question comes from Astika Gunwarden with True is security. Please go ahead.
spk05: Hey, guys. Thanks for taking my question. And apologies for the background noise. I'm crossing streets in New York City right now. Just on XL092, I just want to get a read from you as to what kind of data we can expect this year. I know previously we've seen data at ESMO last year. I just wanted to get an idea about updates to those explanation and combination studies that we can expect. Thank you.
spk06: All right, thanks, Asika. No jaywalking, please, okay? Hey, Vicki, you want to take that question?
spk15: Sure, happy to. Thanks, Mike, and thanks for the question. So, in terms of XL092, or zanzilinthanib, as it's now called, of course, we presented the first clinical data at ESMO last year, which, again, is you know, confirm the overall profile in terms of the shorter half-life compared to CABO. And, you know, we're pleased to see early evidence of activity and a tolerable safety profile. We're heavily focused on execution this year in terms of the Phase 3s that we've recently initiated and additional Phase 3s that we plan to initiate this year, as well as the expansion cohorts on our ongoing Phase 3s. one studies. And so we'll be presenting additional data as we have a meaningful data set to present, but I don't have any specific updates in terms of timing on that for you today.
spk05: Awesome. Thank you so much for taking my question. And no jaywalking.
spk02: The next question comes from Michael Schmidt with Guggenheim.
spk18: Please go ahead.
spk04: Hey, guys. Thanks for taking my questions. Just two quick ones for me. I mean, first, on your 2023 product sales guidance, just help us understand some of the key assumptions for where the additional growth is coming from this year for Cap-O-Matics. And then secondly, on the CONTACT-02 study, which is the CRPC trial, Help us understand your key powering assumptions for calvomatics as well as the control arm in the post-hormone therapy setting and prostate cancer. Thanks so much.
spk06: Thanks, Michael. So first question, Chris, why don't you start? PJ, you can provide some commentary on that as well, and then we'll pivot over to Vicki on the second question.
spk08: Sure. Michael, it's Chris. So, you know, as you know, our guidance is $1.75 billion to $1.675 billion. You know, that's has growth in the range of 13% to 20%. And all of that growth is coming from current indications, no new indications. And we haven't assumed any comparator sales in there. I guess PJ can talk about the market dynamics around growth.
spk10: Yeah, thanks, Chris. And thanks for the question. With regards to the business, we had a strong 2022 and finished the year not only as the number one monotherapy, TKI and RCC, but also the number one TKI-IO combo. As we've talked about previously, you know, we're seeing continued growth in demand driven by market share increases from increasing duration. And particularly in the last four months or so of the year, we saw an increase in new patient starts. So both of those together should fuel growth, we believe, in 2023. You know, on top of that, we're certainly excited to have 44-month follow-up data from the 9ER study presented at ASCO GU and believe that will further support our positioning in the marketplace. So that's, you know, how we're thinking about growth in 2023. That's great.
spk06: Thanks, PJ. Vicki, you want to handle the contact O2 question at a high level?
spk15: Sure thing. So in terms of contact O2, as you mentioned, this is our study of cabozantinib and atezolizumab in metastatic castrate-resistant prostate cancer. As we've announced, we expect to have data for the progression-free survival endpoint in the second half of this year. And in terms of the power, you know, what I can say is it's powered for both progression-free survival as well as overall survival to demonstrate a meaningful effect in those two endpoints.
spk03: Okay, thank you.
spk02: Michael, thank you.
spk18: The next question comes from Do Kim with Piper Sandler. Please go ahead.
spk14: Hi, this is Skylar on for Do Kim. Thanks for taking my question. Regarding the contact O3 study, I'm wondering if you can speak to what you believe the incremental opportunity is, given CABA monotherapy is already leading second-line RCCs, just where you see the upside in market share revenues. Thanks.
spk10: Yeah, thanks for the question, Skylar. This is PJ. I'm happy to address that. So, you know, contact three, as you mentioned, we have a strong position, you know, in the second line setting in RCC with approximately 50% market share with CaboMedic's monotherapy program. But certainly these patients, you know, they have metastatic disease and they're still, you know, greatly in need of more and better options. So should contact three be positive? And atezolizumab, you know, adds to Cabo in that setting. We kind of think about that opportunity in a couple different ways. One is, you know, we believe With better data, we could expand that market share beyond 50% for sort of the CaboMedx backbone in that setting. And we do believe that much of the 50% would convert from CaboMedx monotherapy to combination therapy. So we see market share expansion. And then as you see a potential double in that setting, we would expect a longer duration of therapy there. So both expanding the Cabo market and a longer duration of therapy is how we think about framing the growth from contact three.
spk02: Got it. Thanks so much. Welcome, Tyler.
spk18: The next question comes from Jeffrey Reno with Credit Suisse. Please go ahead.
spk12: Hi. Thanks for taking my question, and congrats on the progress. Just have one here, which is I think that Ajinomoto announced a deal in January. And I think that was the most recent addition to your ever-evolving ADC tech stack. So just wondering if you can talk a little bit more about the specific technology you got access to there and how those capabilities fit with the deals and partnerships you already have. Thank you.
spk09: Yeah, this is Peter. Thanks a lot for the question. You're absolutely right. That's the kind of most recent addition to our kind of suite of collaborations on the antibody drug conjugate side. I think as most people know, We're really kind of advancing our ADC pipeline, both through some internal efforts, but also through a network of collaborators. We have Invenra, who makes most of our antibodies, and also has a very nice Biospecifics platform. And then we have a couple of collaborations that give us access to some site-specific conjugation technology, as well as a range of payloads. Those are Catalan and NBE. And Ajinomoto is... really another access to a different site-specific conjugation technology. So we've been using it on the research side for six, seven, eight, nine months now. I've been very happy with the way it's performed. So we went ahead with the deal. So we're using it to make a variety of different ADCs with different payloads, but with a very controlled drug antibody ratio.
spk18: The next question comes from Jason Gerbery with Bank of America. Please go ahead.
spk19: Good evening, guys. Thanks for taking my questions. In terms of the future direction of X0092, I know the message here is that we'll get future updates of Stellar-002 data mature. I was just wondering what impact ongoing CABO trials dictate the future course of the program, Contact 01, I assume that probably takes long off the table, and curious if you'd say contact 02 will dictate, you know, whether or not you'd explore 092 in the prostate setting. And then just one follow-up on contact 03, you know, the ability to expand share beyond 50% in the second-line setting, is that just primarily patients who got a non-CABO regimen in the front line, just given the protocol restrictions in that trial around having gotten CABO front line? Just wanted to clarify that. Thanks.
spk06: Yeah, Jason, thanks for the question. Vicki, you want to take that first question, and PJ can follow up on the second?
spk15: Sure, thanks. So in terms of XL092 or Zanzalitinib, you know, so as we've said before, we are looking at data that we have from the CABO program and using it to inform ZANZA development. And I think a prime example of that is the first Phase III that we started last year, Stellar 303, which is a non-MSI high colorectal cancer. And that was based on data that was presented early last year, you know, again, demonstrating the promise of the combination of atezolizumab and CABO. And with the similar kinase profile, we started this phase three with stanzalitinib. I think, you know, in terms of the comment about lung cancer and We're evaluating the data from CONTACT-01. I wouldn't necessarily say that lung is off the table based on that one trial. Obviously, that's a difficult patient population in which to develop drugs, and I think careful evaluation of data may lead us to consider how best to develop ZANSA in a lung cancer population.
spk10: Thanks. Go ahead, PJ and Jason. It's PJ. Yeah, with regards to your question, The assumption of expanding market share in the second line, you know, with contact three, should it be positive? The assumption there is for patients who didn't receive CABO in some form, either in combo or monotherapy in the first line setting, and there is still room to expand that market share should we have a positive trial.
spk19: Okay, thanks.
spk18: Thank you, Jason. The next question comes from Andy Cia with William Blair. Please go ahead.
spk07: Great. Thanks for taking my question. So for ZANZA, I'm just curious if you could characterize the CMAX or AUC over, let's say, like a 24-hour period and maybe comment on the tissue distribution compared to CAVO just to help us gauge the potential for maybe like a superior efficacy profile. So that's my first question. Number two, really glad to see the start of that non-clear cell stellar 304 study, a very high medical need. So from a modeling standpoint, could you give us a sense of what percentage of non-clear cell patients are eligible for the trial? Specifically, I understand excluding the chromophore histology is really difficult to treat, and so we're curious about how that would impact the TAM. Thank you very much.
spk06: Peter, I'm going to take the first part of the question. Yeah, thanks for the question, Andy.
spk09: So, obviously, with ZANVA, you know, the focus as we were developing it was on modulating the pharmacokinetic properties, you know, to take it from a, you know, What Cabozantinib has is a half-life of around 100 hours in patients. We were looking to reduce that, and as we showed in the data that came out late last year, happily Zanzibar has a half-life of around 20 hours, which is significantly shorter. We don't see nearly as much accumulation, but it's still consistent with one's daily dosing. So that was the overall goal, initial goal at least, which was achieved. If you kind of dig into the data and see your questions, start looking at Yeah, the actual drug level, CMAX AUC, obviously we've looked at that and started calculating three fractions of drug as well. We're very confident that we're at doses that are pretty similar to the approved doses of cabozantinib. I think that calculation is also backed up by some of the changes that we put on the poster as well with respect to various biomarkers. For example, you know, changes in VEGF, VEGFR, and AXEL. which, again, look very similar to what we saw historically with Kawasaki. So at the end of the day, I think we're in a nice spot with respect to CMAX and AUC with what we expect to see from advocacy. And I think the advocacy we showed in the initial poster was certainly encouraging to us, pretty nice waterfall plot, but with a reduced half-life again, which we think should lead to easier AE management going forward. Fantastic. Fantastic.
spk06: Vicki, want to take the second question?
spk15: Sure, happy to. So in terms of non-clear cell overall, about 25% of renal cell carcinoma is non-clear cell. Papillary actually makes up most of that, so it's about 15% of the overall RCC population, whereas chromophobe is only about 5%. So between papillary, unclassified, you're already almost at 20%. So again, the majority of patients with non-clear cell RCC would be eligible for this trial and ultimately for treatment.
spk07: Got it. That's very helpful. Thank you so much.
spk18: All right. Thank you, Andy. The next question comes from Edzer Durout with BMO Capital Markets. Please go ahead.
spk20: Great. Thanks, Seth, for taking the question. Just one for me. For CBX12, we got some data at Tribal Meeting, the initial data there. We saw some interesting signals in ovarian and breast cancers. Just wondered if we could expect a clinical update this year on that program or any updates sort of with respect to future plans for development. Thank you.
spk06: Yeah, Vicky, you want to take that one?
spk15: Yeah, so, you know, we're obviously also encouraged by the early data, you know, showing some early responses even while we're still in dose escalation. So, following that update late last year, you know, we'll work with the team at Cybrexa on future clinical updates. You know, I would say that, again, we're still in dose escalation at this point, but And, you know, looking forward really to working with them to achieving a recommended phase two dose and moving into the next stage of development, which would be expansion in a range of tumor types, obviously, which will be informed by some of the early data that we're seeing in dose escalation.
spk03: Thank you.
spk18: The next question comes from Akash Tiwari with Jefferies. Please go ahead.
spk16: Hi, this is Ivy on Forkash. Thanks for taking our questions. So we have two if we may. The first is about the R&D spend. So what's roughly the breakdown of your R&D spend per program in your 2003 guidance? And given some of the setbacks we've seen in the last couple years, I guess what programs do you feel most confident that will show a positive return on your invested capital And also like what's your appetite to do a larger two to four billion M&A transaction? I guess my second question is on Cabo. So just curious, do you think Cabo will still be a growing product over the next three years on just RCC alone? Thank you so much.
spk06: Okay, there's a lot there. So we'll try to answer those questions one at a time. We may have to check back in with you around specific sub-questions. But Chris, you take the first one.
spk08: Sure. From an R&D expense perspective, I mean, what we're seeing is we're seeing the cost related to the CABA studies coming down and we're seeing the cost related to the ZANDA and the XBO2 studies increasing as we look at 2023. And those will continue to grow into the future as the studies continue to enroll. And then from a discovery perspective, we're continuing to do our discovery investments to look at those.
spk06: Yeah. And in terms of, you know, not going to give future guidance for the out years, obviously, you know, leading TKI for RCC across the first line, IOTKI market as well as second line. So trials we have going between 313 and contact 03, those look good. And again, we're in the data business, so good data begets the opportunity to keep growing the business. So stay tuned.
spk13: And I think our final question was larger deal uptake.
spk06: Yeah, okay, and that's, look, we've been talking about that for a while, looking for the opportunity to pursue larger, later stage assets and potentially larger deals that won't qualify the size, obviously. It's all about conviction in the asset and the probability of success, our view on that, and then the ability of those assets to generate differentiating data that we can then move forward into the commercial setting. I think we've I think it's fair to say we've proven that when we can generate differentiating clinical data, we can use that to drive the top-line growth with COW. And we're certainly proud of that and understand that we have to do it again and again and again. And doing it through both internal and external sources is the plan. So stay tuned.
spk16: Thank you so much.
spk03: Thank you.
spk18: The next question comes from Yaron Berber with Cowan. Please go ahead.
spk01: Great. I have a couple of questions on the pipeline. The first one, on stellar O2, the LAG3-PD1 combo is really interesting. Has LAG1, just give us a little bit of a sense, it's obviously approved in melanoma. What is LAG3 with PD1 showed in, let's say, RCC, and which other cell tumors are you interested in? And then for non-clear RCC, any sense, is Cabo, what's the leading drug in that segment right now in first line? Does Cabo or Optivo have any share, or is it really sunitinib that's dominating that segment? Thank you.
spk06: All right, great. So thanks, Jeroen. Vicky, you want to take the first question, and then PJ can address the second?
spk15: Yeah, so as you noted, LAG3 in combination with nivolumab is approved in melanoma. You know, other data I would say across other tumor types right now that are in the public domain are relatively sparse. But we're interested in the combination across a range of different solid tumors. So we've expanded that trial across, you know, several major tumor types now. you know, to really evaluate that combination, not only in the GU tumors, such as RCC, but in other major solid tumors, including, you know, hepatocellular carcinoma and others. So, really an interesting combination that we're looking forward to what it will show us in terms of activity.
spk10: Hi, Jeroen. This is PJ. With regards to the non-clear cell RCC market currently, I guess I'd characterize it as relatively similar to what you see, what we see in the overall market, including Clear Cell. You know, certainly Cabo has good utilization. There's guidelines in that market. Combos get utilization as well. But, you know, I guess how I think about it is with a phase three, there's no randomized phase three study in that setting. So, you know, Should there be a positive phase three study there, I think it's a significant area of unmet medical need without a high level of data available. So I think that would really provide an opportunity to drive a new standard of care in the setting for a lot of those patients.
spk01: Right. And maybe if I can just throw in a quick question on the 27.9 gross to net incidence. Can you give us any sense at all how much of that is 340B, just given how fast that program has grown over time? Thank you.
spk08: Yeah, Jeroen, thanks for the question. Yeah, I mean, it's continued to grow throughout 2022. I'm not going to give you a specific number, but as we look at 2023, we think gross net is going to be in the range of 31% or so. And as we've seen in prior years, we saw that be higher in Q1 and then and go down as we went throughout the year in Q2, Q3, and Q4. But thanks for the question.
spk03: Thank you.
spk02: The next question comes from Jay Olson with Oppenheimer.
spk18: Please go ahead.
spk17: Hello, this is Cheng on the line for Jay. Thanks for taking the question. So maybe for CAVO, I think you mentioned there's higher new patient start in second half 22. And just curious whether that is due to maybe more patients in the first-line setting and whether that trend will continue in 2023. And separately on DENTA, I think in the press release you mentioned you expect to initiate a next wave of phase three study. So maybe some colors on the next wave of phase three study in terms of the indication and also the combination approach we should expect. Thank you.
spk06: Yeah, thanks for the question. PJ can take the first question and then over to Vicki for the second one.
spk10: Yeah, thanks. This is PJ. So with regards to the new patient starts, you know, I think not necessarily new patients from an epidemiological setting, increasing that, you know, in first-line RCC. I think what we're seeing there is we've taken share from competitors, particularly in the second half of the year. I think... team is executing at a high level. You know, we have a great balance of data in terms of superior overall survival, safety, and tolerability and quality of life. And that's, you know, well-received and perception of that data is strong in the marketplace. So, additionally, as things kind of opened up after the pandemic, I think the opportunity to really interact more with healthcare professionals and educate them on the data helped drive the increased new patient starts and give us momentum in the second half of the year.
spk15: And with zanzalitinib, so just as a reminder, of course, we initiated our pivotal program last year with stellar 303 and 304 in microsatellite non-MSI high colorectal cancer and non-clear cell renal cell carcinoma, respectively. And as we've mentioned, we intend to initiate multiple additional pivotal trials in 2023. I'd say stay tuned there for additional details, and we'll certainly be happy to provide more color once we announce those trials. Okay, thank you.
spk03: Thanks, Vicky.
spk18: The next question comes from Peter Lawson with Barclays. Please go ahead.
spk21: Great. Thanks so much. Just on ZANs, kind of when we should see the next data sets for the next data for STLA 304 and 303, and then if there's any interim PFS reads that we should be thinking about.
spk03: Okay. Thanks, Peter. Hey, Vicki, you want to answer that question again?
spk15: Yes. So in terms of for 303 and 304 specifically, of course, you know, these are phase three trials that we've just initiated, you know, in the last few months or six months or so. You know, so we're really focused right now on, you know, getting countries up and running, enrolling patients. In terms of timing, you know, this will all be event driven. And so it's too early at this stage, you know, to say when we expect those analyses, but we'll have More details forthcoming as those are available. You know, the phase one data, I would say, as I said earlier, you know, when we have a meaningful data set, we will be sharing those at medical conferences.
spk21: Thank you. And then a question for Chris. I missed it, but the revenue contribution for clinical trial sales for 22 or Q4 would be great.
spk08: Yes, so Peter, it was about $7 million in the fourth quarter.
spk21: And you don't expect that to continue or just not including that in your guidance?
spk08: All I've said is we're not including that in our guidance numbers.
spk21: Perfect. Thank you so much.
spk18: The next question comes from Sylvan Dukjan with JMP Securities. Please go ahead.
spk11: Thank you for taking my questions, and congrats on the quarter. Just a quick question. Could you please remind me where we are with COSMIC 3013, so with the triplet and frontline RCC in terms of the next readout? And I saw that there may be some data at ASCO GU next week by risk score. What could we learn from that, and how could that inform your thinking about eventually getting this maybe into registration? Thank you so much. Thanks for the question.
spk06: Vicky, you want to take that?
spk15: Sure, happy to. So in terms of COSMIC 313, just as a reminder, we had the readout for the primary endpoint of progression-free survival last year. At that point, the overall survival data were immature. We did discuss the data with FDA, and they asked to see more mature survival data before considering a filing. So we are expecting that we will have the second interim analysis of overall survival sometime later this year based on current projections. You know, as appropriate, depending on the data, we would have a conversation again with FDA about whether or not a filing would be appropriate. In terms of the ASCO-GU data, they're still embargoed at this point, so I can't share any details. But, yes, we do have a presentation by IDMC risk category and really, again, just looking at this study enrolled poor and intermediate risk patients, whether we see differences in the benefit and safety profile across those risk groups.
spk03: Great. Thank you so much.
spk02: The next question comes from Mike King with EF Hutton.
spk18: Please go ahead.
spk22: Hey guys, thanks for taking the question. I just want you to know that I'm sitting comfortably in my chair in my office and there's no vehicular traffic around. I'm actually quite safe. I'm actually quite safe right now. So, so I appreciate your interest. Just real quick on Zanza as well. I'm just wondering how you guys are thinking about the, you know, do you have sort of like a menu of, of phase three trials that you have conceptualized and just waiting for, uh, data to confirm those? Or do you, is it purely going to be a data driven based on, you know, some of the phase one and phase two trials that you have on going right now?
spk06: Yeah, my great question. Vicki, you want to take that one?
spk15: Yeah. So first I'm glad you're safely seated in your office. Um, in terms of, uh, You know, ZANSA development, you know, we're looking again at data from a number of different sources. Of course, the CABO data, again, coming back and referencing 303, our study in colorectal cancer. Also looking at emerging data from ongoing Zanzalitinib cohorts, in particular from Stellar 001, but we'll increasingly be looking also from Stellar 002, all of which may inform, you know, future developments. You know, that said, we're also looking at the competitive landscape, areas of unmet need, you know, really to evaluate what are the best opportunities here and really places where we can make a difference for patients. And so we're factoring all of that information in as we consider next indications for Vanta.
spk22: Yeah, because I would think that there's, you know, there's indications that, let's say, Bevacizumab has or Pazopanib or... where, you know, those are not indications for CABO and perhaps those are some areas where you could take the market share.
spk15: Is that a good way to think about it? Looking at lots of different possibilities, you know, certainly we could think about where other TKIs have shown activity as well. I would say, you know, CABO is a particularly good place to look because, of course, we have a similar kinase profile. But then also looking at novel combinations, right? And so I think the Nevo-Rella combination is a great example of that, where if, you know, we see good evidence of activity, then there may be unexplored areas where we can, you know, where it might make sense to develop those combinations.
spk22: Right. Okay. And then just at a really high level, what would you say to investors is the most important milestone outside of, let's say, you know, the MSN litigation. But just from the ongoing portfolio, what's the most important data point to Exelixis holders this year?
spk06: Yeah, so, Mike, it's Mike. We talked about it in the prepared remarks. The main priority for us is to advance the non-CABO pipeline in development, both ZANSA and XB002. Obviously, we've been very successful with Cabo. You know, tough business, and a few companies that even have one franchise molecule like Cabo want more, and there's certainly a large medical need for patients across the board, and we think both Zanza and OO2 are, you know, first step in that direction, and then we have a strong discovery and collaborative pipeline of molecules coming up as well. So, yeah, our focus is building a pipeline molecules that we can get over the goal line from a clinical and regulatory point of view and then get into HCPs and patients' hands as quickly as possible.
spk22: Okay. All right. Thanks, Mike.
spk03: You bet. Operator, do we have any more questions?
spk13: I'm going to assume we don't, so I'm going to say thank you very much for joining us today, and certainly you're welcome to give Ron or myself a call or shoot us an email if you have any follow-up questions. Thanks again.
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