Exelixis Inc

NASDAQ:EXEL

Earnings Call Transcript 2022-Q4

[Operator]

Good day, ladies and gentlemen, and welcome to the Exelixis 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.

[Susan Hubbard, EVP, Public Affairs and IR]

Thank you, Vaishnavi, and thank you all for joining us for the Exelixis 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 Senner, our Chief Financial Officer, who will review our progress for the fourth quarter and full year 2022 ended December 31, 2022.

P.J. Haley, our Executive Vice President of Commercial; Vicki Goodman, our Chief Medical Officer; 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 cost associated with discovery, product development, business development and commercialization activities.

And with that, I will now turn the call over to Mike.

[Mike Morrissey, President and CEO]

All right. Thank you, Susan, and thanks to everyone for joining us on the call today.

Exelixis had a strong fourth quarter and full year 2022 across all components of our business. We’re pleased to see continued growth of the cabozantinib franchise in the U.S. and globally in the fourth quarter and full year ‘22 while advancing our discovery and development priorities to build the Exelixis product portfolio of the future.

As we had a complete corporate update a few weeks ago at the JPMorgan 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 cabozantinib business with continued growth in demand and revenue in the U.S. CABOMETYX maintained its status as the leading TKI for RCC in both the first-line I-O TKI market and the second-line monotherapy segment. Fourth quarter cabo franchise net product revenues grew 25% year-over- year compared to fourth quarter 2021. Cabo franchise net product revenues grew 30% for the full year of 2022 compared to full year 2021 and have approximately doubled since 2020. Importantly, global cabozantinib franchise net product revenues generated by Exelixis 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 Exelixis development pipeline with new potential cabo indications, expedite zanzalintinib, development with new pivotal trials and pursuing XB002 monotherapy 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 preclinical 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 Exelixis throughout 2023. The two new option deals with Cybrexa and Sairopa 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 supportive.

And finally, on January 19th, the Federal District Court in Delaware issued its ruling in the first Exelixis versus MSN case, what we refer to as MSN I. MSN’s validity challenge to the cabozantinib compound patent was rejected and MSN’s proposed generic product was ruled to not infringe the Exelixis’ N-2 polymorph patent. MSN did not dispute the validity of the N-2 polymorph patent. So, it is also -- so it also remains valid and in force and no intellectual property in the Exelixis cabozantinib patent state has been invalidated. Our attention and resources have now shifted to MSN II, 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.

[Chris Senner, CFO]

Thanks, Mike. For the fourth quarter of 2022, the Company reported total revenues of approximately $424 million, which included cabozantinib franchise net product revenues of $377.4 million. CABOMETYX net product revenues were $372.6 million and included approximately $7 million in clinical trial sales. Gross to net for the cabozantinib franchise in the fourth quarter ‘22 was 27.9%, which is higher than the gross to net we experienced in the third quarter of 2022, but overall in line with our expectations for the year. This increase in gross to net deductions in the fourth quarter of 2022 primarily related to higher PHS, Medicare Part D and co-pay assistance expenses.

Our CABOMETYX trade inventory increased by approximately 750 units when compared to the third quarter of 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 GAAP net loss of approximately $30 million or $0.09 per share basic and diluted for the fourth quarter of 2022. This net loss was impacted by the approximately $130 million in new business development deals we announced in the fourth quarter of 2022.

The Company also reported a non-GAAP net loss of approximately $10 million or $0.03 per share basic and 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 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 Exelixis 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 2023. We announced our 2023 financial guidance at the JPMorgan conference in January and is detailed on slide 19 of our earnings presentation.

And with that, I’ll turn the call back over to Mike.

[Mike Morrissey, President and CEO]

All right. Thanks, Chris. As you heard on the call today, the Exelixis 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 cabozantinib franchise performance and are completely focused on the growth drivers across all components of the business that we hope will enable Exelixis to help many more cancer patients in the future.

I’ll close by thanking the entire Exelixis 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 Exelixis. And we’re now happy to open the call for questions.

[Operator]

[Operator Instructions] Our first question comes from Asthika Goonewardene with Truist Securities. Please go ahead.

[Asthika Goonewardene, Truist Securities]

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. Just wanted to get an idea about updates to those -- combination studies that we can expect. Thank you.

[Mike Morrissey, President and CEO]

All right. Thanks, Asthika. No jaywalking please, okay? Hey, Vicki, do you want to take that question?

[Vicki Goodman, Chief Medical Officer]

Sure. Happy to. Thanks, Mike, and thanks for the question. So, in terms of XL092 where zanzalintinib, as it’s now called, of course, we presented the first clinical data at ESMO last year, which, again, confirmed the overall profile in terms of the shorter half-life compared to cabo, and 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 1 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.

[Asthika Goonewardene, Truist Securities]

Awesome. Thank you so much for taking my question. And no jaywalking.

[Operator]

The next question comes from Michael Schmidt with Guggenheim. Please go ahead.

[Michael Schmidt, Guggenheim]

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 CABOMETYX. And then, secondly, on the CONTACT-02 study, which is the CRPC trial, help us understand your key powering assumptions for CABOMETYX as well as the control arm in the post-hormone therapy setting in prostate cancer. Thanks so much.

[Mike Morrissey, President and CEO]

Thanks, Michael. So first question, Chris, why don’t you start; P.J., you can provide some commentary on the -- on that as well; and then we’ll pivot over to Vicki on second question.

[Chris Senner, CFO]

Sure. Michael, it’s Chris. So, as you know, our guidance is $1.75 billion to $1.675 billion. That has growth in the range of 13% to 20%. And all of that growth is coming from new -- from current indications, no new indications. And we haven’t assumed any comparator sales in there. And I guess P.J. can talk about the market dynamics around growth.

[P.J. Haley, EVP, Commercial]

Yes. 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 I-O combo. As we’ve talked about previously, we are 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. 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 how we’re thinking about growth in 2023.

[Mike Morrissey, President and CEO]

That’s great. Thanks, P.J. Vicki, do you want to handle the CONTACT-02 question at high level?

[Vicki Goodman, Chief Medical Officer]

Sure thing. So, in terms of CONTACT-02, 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, 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.

[Operator]

The next question comes from Do Kim with Piper Sandler. Please go ahead.

[Unidentified Analyst]

Hi. This is Skyler [ph] on for Do Kim. Thanks for taking my question. Regarding the CONTACT-03 study, I’m wondering if you can speak to what you believe the incremental opportunity is, given cabo monotherapy is already leading second line RCC, just where you see the upside and the market share revenues?

[P.J. Haley, EVP, Commercial]

Yes. Thanks for the questions, Skyler. This is P.J. Happy to address that. So, CONTACT-03 -- as you mentioned, we have a strong position in the second line setting in RCC with approximately 50% market share with CABOMETYX monotherapy. But certainly, these patients -- they have metastatic disease, and they’re still greatly in need of more and better options. So, should CONTACT-03 be positive and atezolizumab adds to cabo in that setting, we kind of think about that opportunity in a couple of different ways.

One is, we believe with better data, we can expand that market share beyond 50% for sort of the CABOMETYX backbone in that setting. And we do believe that much of the 50% would convert from CABOMETYX 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-03.

[Operator]

The next question comes from Geoffrey Weiner with Credit Suisse. Please go ahead.

[Geoffrey Weiner, Credit Suisse]

Congrats on the progress. I 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 with the deals and partnerships you already have. Thank you.

[Peter Lamb, Chief Scientific Officer]

Yes. 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 is a very nice bispecifics 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 Catalent 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 6 -- certainly 9 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.

[Operator]

The next question comes from Jason Gerberry with Bank of America. Please go ahead.

[Jason Gerberry, Bank of America]

Just one, in terms of the future direction of XL092, I know the message here is that we’ll get future updates as STELLAR-002 data mature. I was just wondering sort of what impacts ongoing cabo trials sort of dictate the future course of the program. So i.e., CONTACT-01, I assume that probably takes long off the table. I’m curious if you’d say contact-02 will dictate whether or not you’d explore 092 in the prostate setting.

And then just one follow-up on CONTACT-03. 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 frontline? I just wanted to clarify that. Thanks.

[Mike Morrissey, President and CEO]

Yes. Jason, thanks for the questions. Vicki, you want to take that first question, and then P.J can follow up on a second?

[Vicki Goodman, Chief Medical Officer]

Sure. So in terms of XL092 or zanzalintinib, 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 3 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, again, demonstrating the promise of the combination of atezolizumab and cabo. And with the similar kinase profile, we started this Phase 3 with zanzalintinib.

I think in terms of the comment about lung cancer, 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 zanza in a lung cancer population.

[P.J. Haley, EVP, Commercial]

It’s P.J. Yes, with regards to your question, the assumption of expanding market share in the second line with CONTACT-03, should it be positive? The assumption there is for patients who didn’t receive cabo in some form, either a combo or monotherapy in the first-line setting, and there is still room to expand that market share, should that -- should we have a positive trial.

[Operator]

The next question comes from Andy Hsieh with William Blair.

[Andy Hsieh, William Blair]

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 cabo, 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 unmet 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 cribriform [ph] histology, it’s really difficult to treat. And so, we’re curious about how that would impact the TAM. Thank you very much.

[Mike Morrissey, President and CEO]

Peter, do you want to take the first part of the question on zanza?

[Peter Lamb, Chief Scientific Officer]

Yes. Thanks for the question, Andy. So obviously, with zanza, the focus as we were developing it was on modulating the pharmacokinetic properties to take it from -- what cabozantinib has is a half-life of around 100 hours in patients, we’re looking to reduce that. And as we showed in the data that came out late last year, happily zanza have half-life around 20 hours, so -- which is significantly shorter. We don’t see nearly as much accumulation, but it’s still consistent with once daily dosing. So, that was the overall goal, initial goal, at least, which was achieved.

If you kind of dig into the data and to your question, start looking at actual drug level, Cmax, AUC, obviously, we’ve looked at that sort of 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, changes of VEGF, VEGFR and AXL, which again, looked very similar to what we saw historically with cabozantinib.

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 efficacy. And I think the efficacy we showed in the initial poster was certainly encouraging to us, pretty nice waterfall plus, but with a reduced half-life again, which we think should lead to easier AE management going forward.

[Mike Morrissey, President and CEO]

Fantastic. Vicki, do you want to take the second question?

[Vicki Goodman, Chief Medical Officer]

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.

[Operator]

The next question comes from Etzer Darout with BMO Capital Markets. Please go ahead.

[Etzer Darout, BMO Capital Markets]

Just one for me for CBX-12, we got some data at your meeting or 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 update sort of with respect to future plans for development? Thank you.

[Mike Morrissey, President and CEO]

Yes. Vicki, do you want to take that one?

[Vicki Goodman, Chief Medical Officer]

Yes. So we’re obviously also encouraged by the early data showing some early responses even while we’re still in dose escalation. So following that update late last year, we’ll work with the team at Cybrexa on future clinical updates. I would say that, again, we’re still in dose escalation at this point and looking forward really to working with them to achieving a recommended Phase 2 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.

[Operator]

The next question comes from Akash Tewari with Jefferies. Please go ahead.

[Unidentified Analyst]

This is Eyli, [ph] on for Akash. Thanks for taking our questions. So we have to 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 2023 guidance? And given some of the setbacks we’ve seen in the last couple of 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 $2 billion to $4 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?

[Mike Morrissey, President and CEO]

There’s a lot there. So, we’ll try to answer those questions one at a time. We may have to check back with you around specific sub questions. But, Chris, take the first one?

[Chris Senner, CFO]

Sure. From an R&D expense perspective, I mean, what we’re seeing is we’re seeing the costs related to the cabo studies coming down, and we’re seeing the costs related to the zanza and the XB002 study is 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, including what’s driven the big increase this year in 2022 where the BD deals, and we’ll continue to look at those.

[Mike Morrissey, President and CEO]

Yes. And in terms of -- I’m not going to give future guidance for the out years, obviously, leading TKI for RCC across the first line I-O TKI 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, but gets the opportunity to keep growing the business. So stay tuned.

[Susan Hubbard, EVP, Public Affairs and IR]

And I think her point of question was larger deal uptake.

[Mike Morrissey, President and CEO]

Yes. Okay. And that’s -- 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 cabo, 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.

[Operator]

The next question comes from Yaron Werber with Cowen.

[Yaron Werber, Cowen]

Great. I have a couple of questions on the pipeline. The first one on STELLAR-002, the LAG-3 PD-1 combos is really interesting. Has LAG-1 -- just give us a little bit of a sense, it’s obviously approved in melanoma. What has LAG-3 with PD-1 showed in, let’s say, RCC? And which other solid 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 Opdivo have any share, or is it really sunitinib that’s dominating that segment?

[Mike Morrissey, President and CEO]

All right. Great. So thanks, Yaron. Vicki, you want to take the first question, and then P.J. can address the second?

[Vicki Goodman, Chief Medical Officer]

Yes. So as you noted, LAG-3 in combination with nivolumab is approved in melanoma. 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 several major tumor types now to really evaluate that combination, not only in the GU tumors, such as RCC, but in other major solid tumors, including hepatocellular carcinoma and others. So, really an interesting combination that we’re looking forward to what it will show up in terms of activity.

[P.J. Haley, EVP, Commercial]

Hi Yaron, this is P.J. 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. Certainly, cabo has good utilization. There’s guidelines in that market. Combos get utilization as well. But I guess how I think about it is with a Phase 3 -- there’s no randomized Phase 3 study in that setting. So, should there be a positive Phase 3 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.

[Yaron Werber, Cowen]

And maybe if I can, just throwing a quick question, on the 27.9% gross to net, 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.

[Chris Senner, CFO]

Yes. Yaron, thanks for the question. Yes. 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 to 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 through the year -- throughout the year in Q2, Q3 and Q4. But thanks for the question.

[Operator]

The next question comes from Jay Olson with Oppenheimer. Please go ahead.

[Unidentified Analyst]

Hello. This is Cheng [ph] on the line for Jay. Thanks for taking the question. So maybe for cabo, 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 will -- that trend will continue in 2023? And separately, on zanza, I think in the press release, you mentioned you expect to initiate the next wave of Phase 3 studies. So maybe some color on the next wave of Phase 3 study in terms of the indication and also the combination approach we should expect? Thank you.

[Mike Morrissey, President and CEO]

Yes. Thanks for the question. P.J. can take the first question and then over to Vicki for the second one.

[P.J. Haley, EVP, Commercial]

Yes. Thanks. This is P.J. So with regards to the new patient starts, I think not necessarily new patients from an epidemiological setting increasing that 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 the team is executing at a high level. We have a great balance of data in terms of superior overall survival, safety, and tolerability and quality of life, and that’s 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 to increase new patient starts and gave us momentum in the second half of the year.

[Vicki Goodman, Chief Medical Officer]

And with zanzalintinib, 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.

[Operator]

The next question comes from Peter Lawson with Barclays. Please go ahead.

[Peter Lawson, Barclays]

Great. Just on zanza, kind of when we should see the next data sets or the next data for STELLAR-304 and 303 and then if there’s any interim PFS reads that we should be thinking about?

[Mike Morrissey, President and CEO]

Okay. Thanks, Peter. Hey Vicki, do you want to answer that question again?

[Vicki Goodman, Chief Medical Officer]

Yes. So, in terms of -- for 303 and 304 specifically, of course, these are Phase 3 trials that we’ve just initiated in the last few months or six months or so. So, we’re really focused right now on getting countries up and running, enrolling patients. In terms of timing, this will all be event-driven. And so, it’s too early at this stage to say when we expect those analyses, but we’ll have more details forthcoming as those are available. The Phase 1 data, I would say, as I said earlier, when we have a meaningful data set, we will be sharing those at medical conferences.

[Peter Lawson, Barclays]

And then a question for Chris, I missed it. But the revenue contribution for clinical trial sales for ‘22 or Q4 would be great.

[Chris Senner, CFO]

Yes. So Peter, it was about $7 million in the fourth quarter.

[Peter Lawson, Barclays]

And you don’t expect that to continue or just not included in that in your guidance?

[Chris Senner, CFO]

All I’ve said is we’re not including that in our guidance numbers.

[Operator]

The next question comes from Silvan Tuerkcan with JMP Securities. Please go ahead.

[Silvan Tuerkcan, JMP Securities]

Just a quick question. Could you please remind me where we are with COSMIC-313, so with the triplet in 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?

[Mike Morrissey, President and CEO]

Thanks for the question. Vicki, do you want to take that?

[Vicki Goodman, Chief Medical Officer]

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. 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 an IDMC risk category and really, again, just looking at the study enrolled poor and intermediate risk patients whether we see differences in the benefit and safety profile across those risk groups.

[Operator]

The next question comes from Mike King with EF Hutton. Please go ahead.

[Mike King, EF Hutton]

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 right now. So I appreciate your interest. Just real quick on zanza as well. I’m just wondering how you guys are thinking about the -- do you have sort of like a menu of Phase 3 trials that you have conceptualized and just waiting for data to confirm those, or do you -- is it purely going to be data-driven based on some of the Phase 1 and Phase 2 trials that you’re having going right now?

[Mike Morrissey, President and CEO]

Yes, Mike, great question. Vicki, do you want to take that one?

[Vicki Goodman, Chief Medical Officer]

Yes. So first, I’m glad you’re safely seated in your office. In terms of zanza development, 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 zanzalintinib cohorts, in particular, from STELLAR-001, but will increasingly be looking also from STELLAR-002, all of which may inform future development.

That said, we’re also looking at the competitive landscape, areas of unmet need, 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 and as we consider next indications for zanza.

[Mike King, EF Hutton]

Yes, because I would think that there’s indications that, let’s say, bevacizumab has or pazopanib or sunitinib where those are not indications for cabo and perhaps those are some areas where you could take the market share. Is that a good way to think about it?

[Vicki Goodman, Chief Medical Officer]

Looking at lots of different possibilities. Certainly, we could think about where other TKIs have shown activity as well. I would say 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 nivo-rela combination is a great example of that, where we see good evidence of activity, then there may be unexplored areas where we can -- where it might be -- makes sense to develop those combinations.

[Mike King, EF Hutton]

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, the MSN litigation? But just from the ongoing portfolio, what’s the most important data point to Exelixis holders this year?

[Mike Morrissey, President and CEO]

Yes. 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 zanza and XB002. Obviously, we’ve been very successful with cabo, to our business and a few companies that even have one franchise molecule like cabo want more. And there’s certainly, the large unmet medical need for patients across the board, and we think both zanza and 002 are first step in that direction, and then we have a strong discovery and collaborative pipeline of molecules coming up as well. So, our focus is building a pipeline of 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.

[Susan Hubbard, EVP, Public Affairs and IR]

Operator, do we have any more questions? I assume we don’t. So, I would say thank you very much for joining us today. And certainly, you’re welcome to give myself a call or shoot us an email if you have any follow-up questions. Thanks again.