Exelixis (EXEL) Q3 2024 Earnings Call Transcript

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Exelixis (EXEL 0.81%)
Q3 2024 Earnings Call
Oct 29, 2024, 5:00 p.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Good day, ladies and gentlemen, and welcome to Exelixis’ third quarter 2024 financial results conference call. My name is Towanda, and I will 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, Mr.

Varant Shirvanian, director of investor relations. Please proceed.

Varant Shirvanian — Director of Investor Relations

Thank you, Towanda, and thank you all for joining us for the Exelixis third quarter 2024 financial results conference call. Joining me on today’s call are Mike Morrissey, our president and CEO; Chris Senner, our chief financial officer; and P.J. Haley, our executive vice president of commercial, who together will review our progress for the third quarter 2024 ended September 30, 2024. Amy Peterson, our chief medical officer; and Dana Aftab, our chief scientific officer, are also on the call today and will participate in our question-and-answer session.

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 was 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. 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 and estimates and projections from our annual U.S.

net product revenues and potential marketing growth opportunities. These estimates and projections involve a number of assumptions and limitations, and we caution investors not to place undue reliance on this information. Actual events or results could, of course, differ materially. We refer you to the documents we file from time to time with the Securities and Exchange Commission, which are 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.

With that, I’ll turn it over to Mike.

Michael M. Morrissey — President, Chief Executive Officer, and Director

All right. Thanks, Varant, and thanks to everyone for joining us on the call today. We’ll use our prepared remarks today to provide a strategic perspective on the business with a forward-looking view of the opportunities for cabozantinib, zanzalintinib, and the early stage pipeline to maximize success in building a multi-franchise oncology business. The last few weeks have been extremely busy with the positive cabo ANDA ruling and the zanza collaboration announcement with Merck.

As you saw in our press release issued an hour ago, Exelixis had a very successful third quarter across all components of our business. I’ll start today with a strategic overview to frame our near-term and aspirational vision for the company, followed by financial and commercial updates from Chris and P.J. Amy and Dana are here as well and will address any technical R&D related questions that come up in Q&A. Exelixis is obviously at an inflection point with the clarity on the cabo ANDA and significant momentum for zanza.

cabo is having a strong 2024 and across literally all commercial metrics that we track routinely as performance indicators for the business, and we remain very bullish on cabo’s revenue outlook into 2030. The zanza opportunity represents an important component of mid- and long-term revenue growth starting in the back half of this decade and potentially building into a dominant position in the 2030s. We’re pleased to be working with Merck in kidney and head and neck cancers and that cost sharing, compound sharing agreements, provides significant validation and momentum for zanza while we maintain full global commercial rights. This collaborate with the competition model has been a pillar of our cabo development success, and we’re pleased to get the first one moving with zanza.

We’re obviously not done in this regard and aim to expand into other collaborative opportunities in the future. With the zanza development plan, including six ongoing and planned pivotal trials, and more potentially on the horizon, we believe zanza has the opportunity to surpass cabo in scope and scale with one planned launch per year starting as early as 2026. Exelixis’ aspirational goal is to be a market leader in both GU and GI oncology as our main therapeutic focus. Note that we are arguably already in the pole position as a GU oncology leader.

So, building momentum in the GI space is an immediate priority for both cabo and zanza. Additional zanza indications outside of GU and GI will be pursued opportunistically. Building, developing, accelerating, and pruning our early stage pipeline is critically important as we advance toward a multi-franchise business. With three novel compounds in our early stage clinical pipeline, including XL309, XB010, and XL495, and several near-term INDs close behind, we plan to efficiently profile and prioritize potential winners for advancement into full development.

As I said before, we’re in the pivotal trial and p-value business where clear clinical differentiation is the mandatory prerequisite and the only viable path toward future commercial success. That’s the essence of the cabo story and we’re applying that filter to everything we do in R&D. We have a lot of exciting mature data from our early clinical efforts with zanza, and we expect to present a significant amount of clinical data from STELLAR-001 and 002 throughout 2025 at major medical meetings. We’ll provide more granularity on those data sets as abstracts are accepted and titles published.

In addition, we plan to host another R&D Day in 2025 as well. With the ANDA litigation now largely behind us, we expect future business development activities to ramp up. As highlighted previously, we are targeting late-stage clinical assets in the GU/GI oncology space, where we have clear conviction that clinical differentiation could drive ultimate commercial success. As we’ve highlighted previously, most biotech oncology launches since 2016 have been underwhelming, with cabo being one of the few standouts in terms of indication expansion and revenue growth.

So, we’re very selective as we evaluate the clinical and commercial opportunity of late-stage assets. Exelixis could potentially pursue any type of transaction as we advance with a pragmatic, thoughtful, and unambiguous focus on doing the right deal at the right valuation for the right asset. Finally, we’re executing with an ambitious plan for building success as a multi-franchise company. To that end, I want to be very clear that we’re committed to running the business and specifically R&D at recent expense levels for the foreseeable future.

Our intention is to continue to rigorously and often aggressively prioritize spending and investments toward late-stage molecules to maximize our clinical and commercial success, while we advance the pipeline, generate free cash, and return a healthy portion of that free cash to shareholders. As you all know, clinical success never gets cheaper as compounds advance into late space development. So, we’ll continue to prioritize our spending as we did at previous Exelixis inflection points over the course of the last decade. Our share buybacks over the last two years totaling $1 billion and commitment of another $500 million to the end of 2025 underscores our balanced and pragmatic approach to investing in the pipeline while returning cash flow to shareholders.

So, with that background in place, let’s review the key highlights for the quarter and drill down into additional details for our near and midterm vision for cabo and zanza. First, let’s start with the quarter. Exelixis delivered outstanding financial performance in third quarter 2024 with top- and bottom-line growth year over year, driven by the strength of the cabozantinib franchise, including increased demand, new patient starts, and revenue. CABOMETYX maintained its status as the leading TKI for RCC in the U.S.

with third quarter 2024 cabo franchise net product revenues of $478 million, up 9% quarter over quarter compared to 2Q 2024 and 12% year over year compared to the third quarter 2023. Global cabozantinib franchise net product revenues generated by Exelixis and its partners grew to $653 million in the third quarter of 2024. We have increased 2024 full-year net product revenue and total revenue guidance based on these robust results, and we’re building on our strong commercial momentum as we wind up the year and headed into 2025. Chris and P.J.

will provide details for the quarter in their prepared remarks. Let’s move next to our future. First, focusing on cabo to drive near-term upside with strong projected revenue growth through the end of the decade and the potential for zanza to drive significant revenue opportunities starting as early as 2026 and accelerating into the 2030s and throughout that decade. We’re obviously pleased with the favorable ANDA ruling, which extends our cabo revenue running into early 2030 subject to Exelixis’ potential additional regulatory exclusivity.

The District Court’s judgment is also subject to appeal by either party. I want to remind everyone that to the best of our knowledge, the FDA has not granted tentative approval of MSN’s proposed ANDA products more than five years after their original submission. Building off the strength of cabo’s leadership position in RCC and potential new indications in net in CRPC, our midterm projections highlight the potential for cabo to reach peak sales in the U.S. of nearly $3 billion annually by 2030, with conservative estimates for growth of the base business, capturing a significant market share of the oral net therapy indication and a limited opportunity in prostate cancer, which is heavily discounted until we get clarity on regulatory traction with our projected fourth-quarter filing.

Let’s turn next to zanza. zanza has been largely under the radar from the Street’s perspective with only a little over half of our covering analysts, including it in their revenue models. We anticipate it will gain more attention and prominence moving forward now with the positive cabo and a ruling and the recently announced collaboration with Merck. Specifically, zanza is built to expand on cabo’s foundation and its early development plan provides a framework to surpass cabo’s clinical and commercial success.

Our first six zanza pivotal trials and four lead indications, including colon cancer, kidney cancer, head and neck cancer, and neuroendocrine tumors represents a large population of over 100,000 cancer patients annually, with overwhelming unmet medical need based on current standards of care with the cadre of generic and established drugs. Critically, recent progress across these trials reinforces our plan to secure our first potential approval for zanza as early as 2026 and then in subsequent years, one additional approval per year and in clinical and regulatory success. The zanza revenue opportunity with this first wave of label enabling trials is substantial, with projected greater than $5 billion of top-line sales in the U.S. to 2033, nearly equally split between GU and GI indications.

Obviously, a second wave of new trials in GU, GI, and other appropriate indications could advance this opportunity to the next level in the mid-30s and beyond. zanza commercialization ex-U.S., either by Exelixis or a potential new partner could drive significant commercial and financial upside as well. I’ll wrap up here with a few additional comments on the pipeline, advancing behind cabo and zanza. We’re thrilled but never satisfied with the depth and scope of the early pipeline assets we built and are moving into and through early clinical evaluation.

Our small molecule and biologic approaches represent the opportunity to match the best modality with the most compelling tumor pathobiology as either monotherapies or combination partners, with checkpoint inhibitors or proprietary Exelixis molecules. We’re advancing lead molecules in the synthetic lethality space with XL309 and XL495 and a variety of biologics in EDC, bispecific, and monoclonal antibody formats. The ultimate goal for all these programs is to rapidly generate clinical data to prioritize advancement into full development, all with the goal of exceeding expectations as a multiproduct multi-franchise oncology biopharma. So, with that, please see our press release issued an hour ago for our third quarter 2024 financial results and an extensive list of key corporate milestones achieved in the quarter.

I’ll now turn the call over to Chris.

Christopher J. Senner — Executive Vice President, Chief Financial Officer

Thanks, Mike. For the third quarter of 2024, the company reported total revenues of approximately $539.5 million, which included cabozantinib franchise net product revenues of $478.1 million. CABOMETYX net product revenues were $475.7 million and included approximately $6.6 million in clinical trial sales, which is similar to Q2 2024. Gross-to-net for the cabozantinib franchise in the third quarter 2024 was 26%, which is lower than the gross-to-net we experienced in the second quarter 2024.

This decrease in gross to net deductions in the third quarter 2024 is primarily related to lower Medicare Part D and DoD and TRICARE expenses. We are now projecting that our gross-to-net deductions for fiscal year 2024 will be between 28% and 29%. Our CABOMETYX trade inventory was flat at 2.1 weeks on hand when compared to the second quarter 2024. As a continued reminder, clinical trial sales have historically been choppy between quarters, and we expect this to continue into the future.

Total revenues included — total revenues included $60.2 million of license revenues for the third quarter of 2024. The largest contributor to our license revenues was $42 million from the royalties we earned from Ipsen and Takeda on their sales of cabozantinib in their territories. Additionally, we recognized approximately $11 million in license revenues for a regulatory milestone resulting from Ipsen’s filing of their application for a potential net indication with the European Medicines Agency. Our total operating expenses, including restructuring and impairment charges for the third quarter of 2024 were approximately $352 million compared to $361 million in the second quarter of 2024.

The sequential decrease in these operating expenses was primarily driven by lower general and administrative expenses, offset by higher clinical trial and licensing costs in the third quarter of 2024. After evaluating our near-term needs for both lab and office facilities on our Alameda campus, we put certain of our unoccupied lease facilities on the market for sublease. As a result, we recorded a noncash impairment charge of approximately $52 million related to these lease facilities. Provision for income taxes for the third quarter 2024 was approximately $37 million compared to a provision for income taxes of approximately $67 million for the second quarter 2020.

The company reported GAAP net income of approximately $118 million or $0.40 per share on a fully diluted basis for the third quarter 2024. The company also reported non-GAAP net income of approximately $136 million or $0.47 per share on a fully diluted basis. Non-GAAP net income excludes the impact of approximately $18 million of stock-based compensation expense net of the related income tax effect. Cash and marketable securities as of September 30, 2024, were approximately $1.7 billion.

In the third quarter of 2024, we repurchased approximately $12 million of Exelixis shares at an average price of $25.61, as part of the $500 million share repurchase program authorized by the board in August 2024. And finally, turning to our financial guidance for the full year 2024. We are increasing and narrowing our total revenue and net product revenue guidance given CABOMETYX strong net product revenue performance in Q2 and Q3 of this year. We are increasing our total revenue guidance to $2.15 billion to $2.2 billion.

Additionally, we are increasing our net product revenue guidance to $1.775 billion to $1.825 billion, which increases the midpoint of our net product revenue guidance range by $100 million when compared to our previously provided net product revenue guidance. Given where we are in the year, we are tightening our R&D and SG&A expense guidance ranges. Please see Slide 20 of our Q3 earnings presentation for further detail. And with that, I’ll turn the call over to P.J.

PJ Haley — Executive Vice President of Commercial

Thank you, Chris. The third quarter of 2024 was a very strong quarter as the team continued to execute at a high level, which has resulted in CABOMETYX continuing to be the number one prescribed TKI and RCC. Additionally, CABOMETYX remains the number one TKI plus IO combination in first-line renal cell carcinoma. CABOMETYX TRx volume grew 9% year over year in Q3 2024 compared to Q3 2023.

In the same period, the TKI market basket volume declined by 1%. Importantly, the business continues to grow in terms of demand in new patient starts, both of which were at an all-time high for CABOMETYX in the third quarter. CABOMETYX continued to perform well from a marketplace and competitive perspective. CABOMETYX again led the TKI market basket with TRx share increasing to 42%.

As we have discussed previously, the first-line RCC market is extremely competitive and Q3 was the eighth full quarter in which CABOMETYX plus nivolumab remain the number one prescribed TKI plus IO combination in first-line RCC. In particular, we’re continuing to see strong growth in the community oncology setting. Looking forward, the commercial team is excited about the positive results from the CABINET study in neuroendocrine tumors, as Exelixis aims to become a leader in the net space. We believe the RCC market provides a blueprint for how the net market could develop and grow in the coming years.

The global RCC market grew from approximately $3.7 billion in 2016 to approximately $10 billion in 2023, driven by new therapeutic launches, improved outcomes for patients, leading to longer treatment durations and longer survival with patients receiving more lines of therapy. Similarly, early projections for the global net market show it could almost double going from approximately $2.5 billion in 2023 to approximately $4.6 billion in 2030. Based on the CABINET study, CABOMETYX is well-positioned to capture a significant portion of this market pending regulatory approval. Beyond cabo, the STELLAR-311 study positions zanza well in the neuroendocrine tumor space.

However, it is not included in these early projections. The CABINET data were enthusiastically received at this September’s ESMO meeting and simultaneously published in the New England Journal of Medicine. As we talk to KOLs and physicians and market research, the efficacy data from CABINET is viewed favorably by prescribers in terms of progression-free survival, overall response rate, and disease control rate. They view the CABINET data as clinically meaningful and there is excitement for the potential for cabo to become available to net patients.

The vast majority of physicians in our neuroendocrine tumor market research have experience with cabo in RCC, HCC, or DTC, which is consistent with CABOMETYX utilization data. These oncologists cite their experience with CABOMETYX in these tumors as a positive factor, particularly when it comes to comfort with dose modification and toxicity management. The feedback and research clearly demonstrate that a regulatory approval for CABOMETYX based on the CABINET study would have the potential to help a broad range of net patients and address a significant unmet medical need. The CABINET study had a diverse population that included patients regardless of site of disease origin, tumor grade, prior Lutathera, SSTR status, or functional status of the tumors.

In our market research and clinical feedback, physicians cite the study design as a positive and that it covers a wide range of net patients that they see in their practice, as well as the fact that it is a contemporary data set and is inclusive of patients who have received prior Lutathera. The potential broad utility of cabo in NET is a differentiator in this setting relative to other approved agents. cabo may have the opportunity to be the easy choice to use in neuroendocrine tumors given that it was studied in all relevant clinical segments. In our analysis of the neuroendocrine prescriber universe, we see the vast majority of net business potential in approximately 3,500 prescribers.

We are thrilled that about 80% of these prescribers already have experience writing CABOMETYX. Of these 3,500 NET treaters, 2,800 are already current on-label targets for the sales force, indicating that access to them would be efficient. Also, of the 700 net prescribers who are not currently called on. The vast majority, 550, are co-located with current CABOMETYX targets.

Ending FDA approval, we are confident that we will be able to rapidly reach and educate this net prescriber universe efficiently given the overlap with current sales targets and the fact that we expanded our GI sales team. Turning to the NET market. We have conducted market research, which shows that oral therapies account for approximately 25% of the first-line market and 50% of the utilization in the second and third-line-plus settings. Currently available oral options do not have the same breadth of data across all disease characteristics, including site of origin, grade, and functional status.

Also, in market research, physicians do not view the toxicity profile of these agents in a favorable manner. Majority of NET patients will receive multiple lines of therapy, and there is lack of optimal sequencing data in this setting, particularly in patients previously treated with Lutathera. All of this taken together underscores the need for a contemporary data set that is broadly applicable to address the unmet medical need for this heterogeneous patient population. Looking at the small molecule market for NETs in 2025 using contemporary pricing, the small molecule opportunity would be approximately $1 billion in the U.S.

Additionally, upon approval, CABOMETYX would be the only branded small molecule therapy competing in the neuroendocrine tumor market. This is a critical point as cabo would have a clear advantage in promotional share of voice and be the only oral therapy with comprehensive patient support services. With the CABINET data and a focused launch strategy that leverages the positive prescriber experience with cabo, Exelixis is well-positioned to rapidly penetrate this market. Furthermore, as Exelixis aims to become a leader in the neuroendocrine tumor market, we are excited about the planned STELLAR-311 trial of zanza and NETs.

The commercial team is excited and motivated by the launch planning and preparation for the opportunity in NETs. The cabo franchise is closing out 2024 with significant momentum in our currently approved indications and a potential regulatory approval of CABOMETYX in NET, would provide the opportunity to continue the growth and momentum in the coming years. Looking through the cabo lens, it is clear that great data with a great team behind it, can significantly help patients and expand markets. We have seen this in RCC as the oral therapy market has expanded by nearly 40% since the beginning of 2021.

We are extremely excited about the portfolio announced Phase 3 zanza trials. We are motivated to expand the cabo franchise to a kinase inhibitor franchise with zanza having the potential to help patients in tumors where cabo has demonstrated activity such as NETs and RCC as well as new tumors such as colorectal and head and neck cancers. So, we can continue to help more patients with cancer as we strengthen our GU and GI franchises. And with that, I will turn the call back over to Mike.

Michael M. Morrissey — President, Chief Executive Officer, and Director

All right. Thanks, P.J. I’d like to close our call today by thanking all of our very talented and dedicated employees, who are unwavering and fulfilling our mission to help cancer patients recover stronger and live longer, successfully litigating the ANDA with the results of extremely hard work and perseveres over literally years led by our excellent legal team in partnership with outside counsel a little more hailed. I’m grateful to the numerous internal employees who were interviewed deposed and otherwise engaged in supporting this litigation, including scientists and discovery and manufacturing leaders, and members of the commercial and medical affairs teams as well as finance and public affairs.

It was a true team effort across the entire company, and I appreciate the commitment of everyone who is involved in seeing you through to fruition. I’d also like to recognize the team involved in successfully negotiating the Merck clinical development collaboration, which was another cross-functional effort led by our business development colleagues. With this collaboration, we’re on our way to helping many more cancer patients with zanza. I’d also like to thank our commercial organization, which has driven cabo’s outperformance and contributed to our strong financial results over the first nine months of this year.

And finally, I’d like to recognize our entire R&D organization, who have propelled our pipeline efforts forward at a rapid pace. The collective Exelixis team has accomplished a great deal thus far in 2024 and with much more to come on the horizon as we strive to deliver results for cancer patients and our shareholders. We look forward to updating you on our progress. Thank you for your continued support and interest in Exelixis, and we’re happy to now open the call for questions.

Questions & Answers:

Operator

Thank you. [Operator instructions] Please stand by while we compile the Q&A roster. Our first question comes from the line of Asthika Goonewardene with Truist. Your line is open.

Asthika Goonewardene — Analyst

Hi, guys. Thanks for taking my questions and congrats on the beating the race here. It’s very encouraging to see that. Since I’m restricted to just one question, I’ll just focus on the Merck collaboration that was recently announced.

Can you maybe give us some color on the diligence process that way into that deal? How extensive was it? I know it’s hard to comment on that, but that will be useful. And the reason I’m asking is because Merck already has lenvatinib, a drug that where tolerability and half-life has been debilitating to its development. I’m just trying to get a sense of how the — what they did when they did analysis with zanza. Thanks.

Michael M. Morrissey — President, Chief Executive Officer, and Director

Yeah, Asthika. It’s Mike. Thanks for the question. Yeah.

It’s a hard question to answer. We don’t want to speak for Merck. We certainly want to respect the process that took place over many, many, many months. We’re thrilled to be working with arguably our main competitor in the RCC space with cabo moving forward together with them with zanza.

So, we’re excited about moving forward. Obviously, there’s nobody better in the industry to actually executing trials than Merck. So, the fact that they’re running two large pivotal trials is just awesome from our point of view, and we’re certainly excited to work with them going forward with these first set of trials with zanza.

Operator

Thank you. Please stand by for our next question. Our next comes from the line of Jason Gerberry with Bank of America Securities. Your line is open.

Unknown speaker — Bank of America Securities — Analyst

Hi. This is Chi on for Jason. Thanks for taking our questions. Congrats On securing a favorable ruling on cabo IP.

One on business development. I understand you look to do the right view of the right valuation for the right asset within the GU/GI space. I’m curious if you have a preference for modality, whether it’s small molecule, monoclonal bispecific, or ADC, and whether you have a feeling on the size of the deal, you will consider for BD. Thanks so much.

Michael M. Morrissey — President, Chief Executive Officer, and Director

Yeah. Thanks for the question on BD. Look, we’re agnostic to, I think, almost all those factors, we are focused on active molecules, as I mentioned in our prepared remarks, that we have conviction on in terms of having the ability or the opportunity to generate differentiating clinical data that we can then convert into commercial success. I mean, again, that’s the learning from cabo.

That’s the cabo lens that we base everything on. So, we obviously want to be able to work in the GU/GI space because we’re really set up to execute very well there, both clinically and commercially. But in terms of modalities, we’re open. We’re looking for active molecules that we think we can build into a franchise number one, and then get over the goal line numerous times from a regulatory point of view with the obvious upside in helping more patients and then having that translate into commercial success.

Operator

Thank you. Please stand by for our next question. Our next question comes from the line of Silvan Tuerkcan with Citizens JMP. Your line is open.

Silvan Tuerkcan — Analyst

Yeah. Thanks, team. Thanks for taking my question and congrats on the beat. I would like to know about maybe that there’s a gap between — obviously, between your near-term growth with cabo and zanza.

And then you want to do with BD and then your earlier pipeline, but maybe talking about the earlier pipeline, your synthetic lethality assets. When can we expect some data there? And how have you — what’s your view on the space with all the competitive data that has come out recently here? Thank you so much.

Michael M. Morrissey — President, Chief Executive Officer, and Director

Dana, I want to take that one first from a competitive point of view. And then I think both Amy and I can provide some color commentary as well.

Dana Aftab — Chief Scientific Officer

Sure. So, thanks for the question. Just regarding — so let’s just be clear, we’ve got two compounds in the clinic now that are in the synthetic lethality space XL309, which targets you as design. And as we announced in the press release, XL495 has now been filed, and the Phase 1 trial is running.

As I highlighted at our R&D Day presentation in December, both of those molecules are substantially differentiated from the other molecules that are in the clinic. Regarding XL309, we now believe we are the front runner in the clinic with Roche pulling back on their molecule to rework and work through some PK issues. They really hit a ceiling in terms of exposure. So, we’re quite happy with our position now in the clinic with that compound.

And then with 495, the PK-1 inhibitor, the main competition there is from repair with lunresertib. And as we presented at R&D Day in December, our compound, we believe, has a PK advantage as well as selectivity advantage. With our PK modeling, we believe we can hit well into the efficacious range of exposure with once-daily dosing. And we also have — we also hit about 33% or 35% fewer kinases in a broad selectivity panel compared to that competitor compound.

So, we think there might be a safety advantage as well.

Michael M. Morrissey — President, Chief Executive Officer, and Director

Amy?

Amy Peterson — Chief Medical Officer

Yeah. So, I know we spent a lot of time talking about cabo and zanza because those are sort of the nearer-term things. But trust me, Dana is keeping the development team very busy with some of these assets in the pipeline as they advance. And they are – here we really are focusing on best-in-class.

And with the modality that we have around USP1 and single-stranded break repair, there’s really an opportunity to not only extend the reach of PARP inhibition and BRCA mutations but potentially also take it beyond BRCA mutated patients into HRD and potentially other indications. And we have XB010 ADC with MMA payload that targets 5T4 advancing. And now as Dana just pointed out, FPI to 495. So, we are busy with the pipeline.

There’s a lot coming. There’s more to come. And we are really focusing on that just as much as intensely as we are focusing on zanza and maturing it.

Operator

Thank you. Please stand by for our next question. Our next question comes from the line of Michael Schmidt with Guggenheim Securities. Your line is open.

Michael Schmidt — Analyst

Hey. Thanks for taking my question. Great to see reacceleration of cabo sales growth to double-digits here in the second half of this year. Could you just comment on what’s been the primary driver for that? And then on zanza, congrats on the Merck collaboration.

I’m just curious if you could comment on the two planned Phase 3 studies of zanza and [Inaudible] in RCC and how you think about positioning that versus cabo and the ARCUS HIF-2a inhibitor longer term. Thanks so much.

Michael M. Morrissey — President, Chief Executive Officer, and Director

OK. P.J., take the first one, and I’ll comment on the second one. OK.

PJ Haley — Executive Vice President of Commercial

Yeah. Thanks for the question, Michael. We’re certainly very pleased. As I mentioned, with the quarter and the significant momentum we have with cabo now and the franchise, as I’ve mentioned previously, we were sort of continuing to see new highs in both demand and new patient starts and really primarily driven by first-line RCC.

We’ve maintained our market leadership position there. And as we see increasing new patient starts there, we continue to see patient stacking and sort of demand moving forward. So, very pleased with that. And really, it comes down to we’ve got great data across the board there and then a great team really focused on executing at a high level and just continue to see that moving forward.

Michael M. Morrissey — President, Chief Executive Officer, and Director

In terms of zanza with Merck, again, we’ve agreed with Merck to keep the details to ourselves for now. As I’m sure time goes on and trials are moving forward. Merck again, who’s running those trials will communicate the design and those kinds of issues. So, stay tuned on that.

I don’t have much to say in terms of other competitive programs. We’re very, very happy to be partnered with Merck, which has the only FDA-approved HIF inhibitor on the market right now. And with the momentum we’ve got with zanza, and certainly with their firepower, we’re very excited to be moving forward here with them going forward.

Operator

Thank you. Please stand by for our next question. Our next question comes from the line of Greg Renza with RBC Capital Markets. Your line is open.

Gregory Renza — Analyst

Great. Good evening. Good afternoon, Mike and team. Congrats on the quarter and also on the string of recent great update.

Mike, maybe sticking with zanzalintinib and we appreciate the layout of some of the peak opportunity longer term, that’s great to see. Just wanted to ask if you could maybe elaborate a little bit further on some of the assumptions there, you certainly mentioned of the patient stacks, which is helpful that the differentiating data that you would expect to get to those numbers and even the unadjusted nature. But as we think about sort of those breakdowns with respect to GU and GI and head and neck, would be great. And certainly, related, Mike, what is the optimal pipeline constructed — portfolio construct for you having gone back, having lived through the cabo days establishing and defending the competitive positioning is zanza at sort of that single asset to get that full white space and diversity of opportunity, the right way of thinking for Exelixis moving forward.

Thanks so much, and congrats again, guys.

Michael M. Morrissey — President, Chief Executive Officer, and Director

Yeah. Thanks, Greg. I appreciate the comments and the question. Look, as we talked about previously, cabo provides the foundation for which we’re building future opportunities with zanza going forward that we’ve learned a lot with cabo.

We’ve spent 15-plus years developing that molecule. We’ve had a string of successes. We’ve done, I think, a lot of really great science at the lab bench in the clinic, been able to learn a lot as an organization to be able to maneuver. So, think we’re applying all those learnings from all those different lanes into how we view the zanza opportunity.

In terms of details on assumptions, we have a very sophisticated commercial organization that does modeling professionally, I mean, this is what they do. So, we’ll share that — those assumptions and that data in time. I think it’s important for the sell-side now to be quite frank to roll up their sleeves, start with their pencils and look at these opportunities, start doing your own modeling, and we can talk about that together when some of that data, some of your modeling is more mature in the future. But we’re thrilled about having zanza where’s it’s at to have a molecule at this stage in six ongoing their planned pivotal trials.

We think there’s more opportunity on the way collaboration with Merck top-line data in 303 in 2025, potentially first launch in ’26. The momentum is palpable right now, coming off the strength of cabo. So, we’re excited to be – to again, to be past the ANDA, so everybody can focus on the business moving forward, positive direction forward without having the – some of the overhang that we’ve had with the ANDA and other stuff in the past. So, happy to engage with you going forward and looking forward to making this happen.

Operator

Thank you. Please stand by for our next question. Our next question comes from the line of Yaron Werber with TD Cowen. Your line is open.

Yaron Werber — Analyst

Great. Thanks for taking my question. Congrats on the quarter and on the litigation. So, Mike, just the one thing that really caught my mind is your comment about potentially looking at late-stage deals.

I think you’ve kind of commented that, but I think this is kind of something you’re highlighting a bit more now, at least in our view. Am I thinking about this correctly and are you open for acquisitions, or is this like really in-licensing only? Thank you.

Michael M. Morrissey — President, Chief Executive Officer, and Director

Yeah, Yaron. So, thanks for the question and the commentary. Look, we’ve been talking about late-stage opportunities for a while now. As you heard from Dana and Amy, we have a very full early stage pipeline.

We like these molecules. We think they’re best-in-class. We have a lot of work to do to interrogate and then prioritize what moves into full development. So, to be quite frank, we don’t need more development candidates, more INDs, more Phase 1 molecules because we’ve got our plate full, right, in terms of what we’re doing internally, right? We’re interested in building Exelixis into a multiproduct multi-franchise oncology business, that’s the goal.

And to do that, and obviously, we have cabo going full steam. Zanza have got great traction. But if we can find again, the right asset that has the right level of — gives us the right level of conviction on being able to generate differentiating clinical data that can then drive commercial performance we’re very interested in finding a way to bring that molecule or those molecules into the organization. As I said in my prepared remarks, we have any number of different potential business development opportunities going forward.

We can do virtually anything we think makes sense, but it’s got to be the right deal, the right valuation with the right asset.

Operator

Thank you. Please stand by for our next question. Our next question comes from the line of Jay Olson with Oppenheimer. Your line is open.

Jay Olson — Analyst

Wow, congrats on all the progress across so many fronts, really appreciate the optimism around zanza, an impressive $5 billion peak U.S. sales potential. Can you comment on what gives you the conviction at this point in time to share your thoughts on the commercial potential? Is it related to the Merck collaboration or something else? And since you have global rights to zanza, why did you focus your outlook on U.S. revenues and how are you thinking about the ex-U.S.

opportunity? Thank you.

Michael M. Morrissey — President, Chief Executive Officer, and Director

Yeah, Jay. Thanks for the question. It’s really the right time, as I said in my kind of my early comments this afternoon, right, we’re at this inflection point organizationally, where we’re past — we’re past the ANDA, we have that overhang finally removed. We want everybody, all of our various stakeholders to look at us today, as we’re going forward with a successful product in cabo, an asset in zanza that has multiple, I would say, high PTRS shots on goal in terms of new indications that we think could really build on cabo’s success and expand it from the scale and scope that we’re seeing currently with cabo.

So, it’s really the right time to get everybody focused on the future. Again, as I mentioned with Greg, there’s — we’ve been — we’ve had a challenging time getting people to pay attention to us from the standpoint of where we’re at and where we’re going. So, to get you guys, everybody off the sidelines and looking at us in maybe a new light with the momentum we’ve got right now, I think, is super important. We are focused on building a multiproduct multi-franchise business because that’s where the value is for patients and for shareholders.

And with the momentum we have with cabo and with zanza and the pipeline, lots of optionality, BD-wise we’re super excited about our path going forward.

Operator

Thank you. Please stand by for our next question. Our next question comes from the line of Andy Hsieh with William Blair. Your line is open.

Andy Hsieh — Analyst

Thanks for taking our questions. Really encouraged to see the durability of cabo’s leadership there. Two questions, if I may. One for P.J.

So, there’s a pet imaging agent for CA-9 for RCC that could get approval potentially next year. I’m just wondering how you view that potentially pulling some patients who otherwise would have gone undiagnosed, and would that be a potential upside to your $10 billion TAM that you laid out for RCC? Second question has to do with the — also the $1 billion TAM that you mentioned for the small molecule NET. Just kind of back of the level of calculation I think you’re probably projecting anywhere from a five- to six-month duration. I’m curious, if you look at the landscape, especially with like Afinitor label some of the durations for earlier lines are basically nine, 10 months.

So, is it unreasonable to assume that if zanza entrenches earlier in the treatment landscape for NET, that duration will be significantly higher, given that it’s a more indolent cancer? Thank you.

PJ Haley — Executive Vice President of Commercial

Yeah, Andy. Thanks for the questions. Briefly, with regards to RCC, I think a lot of patients are in the funnel, and we’re certainly — as I mentioned, pleased with our performance there and our leading TRx market share, which continues to grow, now up to 42% in that market basket. And I think that market — most of the patients are being treated.

And I think the bar for success, particularly in the first line, and really, even with cabo in the second line is quite high. So, I view that market as relatively stable in the near term vis-a-vis other mechanisms of action. And thinking about NET, as you mentioned, yeah, as I mentioned, about a quarter of the patients in first-line NET are getting oral therapies approximately 50% in the second, third-line settings getting orals. And we basically use, I won’t go into the details of all of our assumptions, but we’ve done a lot of market research there.

I understand it very well. And using durations that we see from that. I certainly think you’re correct. Obviously, the earlier — you do go the longer the duration of therapy, particularly in neuroendocrine tumors, which is a bit more indolent than some other solid tumors.

And I think there is the potential for zanza in the long term, pending trial results, regulatory approval, etc., of having earlier utilization and therefore, a longer duration. I think that’s certainly right. But what I’d say in the near term, we’re really excited about cabo and the potential approval that we’re looking at with a PDUFA date of April 3. And as we think about that market and that $1 billion market in 2025 that I mentioned, we think we’re incredibly well positioned to not only penetrate it and achieve a lot of that market but do it rapidly.

Really, the more we think about it is we’re the only branded oral therapy in the space, it really gives us a big advantage in terms of the promotional share of voice and really just the ability to help patients comprehensive patient support services, we think it will be really important. So, we’re really excited about that opportunity in the near term.

Operator

Thank you. Please stand by for our next question. Our next question comes from the line of David Lebowitz with Citi. Your line is open.

Unknown speaker — Bank of America Securities — Analyst

Hi, guys. Jon for David. Thanks for taking our question. For cabo and neuroendocrine tumors, I know you just — you’re touching on some of the commercial considerations for this market, but what sort of work still needs to be done before a potential launch? And assuming approval, how should we be thinking about initial launch cadence? Are there any existing indications that might serve as sort of a proxy for how we should be thinking about early uptake? Thanks.

PJ Haley — Executive Vice President of Commercial

Yeah. Thanks for the question, Jonathan. Our team, as I mentioned, are incredibly excited and motivated across the board getting ready for this launch. We will be ready to go on day one as we always are for launching a new indication.

And frankly, the more we do it, I think the better we get at it. So, what I would anticipate here, as I mentioned, not having really the amount of competition that you have in RCC, which is, for example, very competitive we would anticipate a very strong uptake right from the beginning. And we believe our data is very strong. I went into some detail on the prescriber universe.

The sales force has been expanded and we’re frankly really ready to go. And we believe we can really move into the market rapidly and efficiently. And really, we’re very excited about the opportunity to help potentially a lot of patients with neuroendocrine tumors.

Operator

Thank you. Please stand by for our next question. The next question comes from the line of Akash Tewari with Jefferies. Your line is open.

Unknown speaker — Bank of America Securities — Analyst

Hi. This is Anastasia on for Akash. Congrats on the quarter and on the recent IP decision. Just a couple on my end.

The first is about the potential to expand Merck partnership beyond RCC and head and neck. Do you think that’s possible as we get more data from the PD-L1 VEGF bispecifics? And then the second question is, do you think that your head and neck data would compare well versus mirrors in the PD-L1 refractory population, or do you see this kind better or worse on our front?

Michael M. Morrissey — President, Chief Executive Officer, and Director

Anastasia, thanks for the questions. Amy, why don’t you start with the head and neck question, and then I’ll address the Merck?

Amy Peterson — Chief Medical Officer

Yeah. So, when it comes to zanza, we’re obviously interested in developing it broadly as its best-in-class, and we have multiple collaborations to that and with other IOs, including Arezo, including nivolumab and now recently with pembrolizumab in head and neck. So, whether or not there’s expansion beyond head and neck, I would say, we’re always looking. And of course, we’re interested in getting zanza into as many indications as possible.

What we combine with remains to be seen. And I guess, when it comes to the data with the bispecifics in the PD-1 refractory space, I’m not quite sure we’re competing with them. We have about a year lead time with Bicara against Bicara in the frontline space and Merus. And we are leveraging that lead time very aggressively to ensure sites that we can enroll and read that study out.

How it plays out in the P1 refractory, so maybe I didn’t understand the question, but I’m not sure I’m able to answer that for Bicara.

Michael M. Morrissey — President, Chief Executive Officer, and Director

OK. Thank you.

Operator

Thank you. Please stand by for our next question. The next question comes from the line of Stephen Willey with Stifel. Your line is open.

Stephen Willey — Analyst

Yeah. Good afternoon. Thanks for taking the questions and congrats on the quarter. So, I know you previously characterized STELLAR-305 as a Phase 2/3.

I think you’re now kind of explicitly referring it to, to it as a Phase 3. So, just wondering if you’ve completed that formal assessment of Phase 2 data to officially transition into Phase 3. And I guess if so, can you speak to those metrics that you’re evaluating to make that decision and just whether you might be disclosing that data at some point? Thanks.

Michael M. Morrissey — President, Chief Executive Officer, and Director

Amy, please go ahead.

Amy Peterson — Chief Medical Officer

Yeah, quickly. Thanks for the question. It is a Phase 2/3. We are still in ruling, and we’ll disclose data when it is mature.

Operator

Thank you. Please stand by for our next question. Our next question comes from the line of Ash Verma with UBS. Your line is open.

Ash Verma — Analyst

Hi. Thanks for taking our questions. So, I just wanted to understand the capital allocation priorities from here. You have a pretty sizable buyback program outstanding.

Do you think this was the right focus when you were dealing with the IP uncertainty, but now that the IP decision is behind you, why not focus most of your capital deployment on the pipeline build-out? Thanks.

Michael M. Morrissey — President, Chief Executive Officer, and Director

Yeah. Thanks for the question. It’s Mike. Yeah.

I think with our cash flows, we can do all of the above. So, as I mentioned in my prepared remarks, we’re committed to being very disciplined as we go forward in terms of expense levels, kind of keeping expense levels kind of where they are currently for the foreseeable future with the cash flows that we have and project, we think we can continue investing in the pipeline doing BD and then returning cash to shareholders.

Operator

Thank you. Please stand by for our next question. Our next question comes from the line of Peter Lawson with Barclays. Your line is open.

Peter Lawson — Analyst

Great. Thanks for taking the question. Just I have a question around Slide 9 that the guidance around zanza. So, should we read that as kind of zanza $5 billion in 2033, and then what cabo kind of essentially declined to zero?

Michael M. Morrissey — President, Chief Executive Officer, and Director

Peter, it’s Mike. I think the cabo LOE is in the 2030 time frame. So, as outlined on Slide 9, that is a 2024 number, and we see zanza growing dramatically over the next several years as these pivotal trials read out, and if successful, could drive a lot of upside growth for zanza.

Operator

Thank you. Please stand by for our next question. Our next question comes from the line of Etzer Darout, BMO Capital Markets. Your line is open.

Lukas Shumway — Analyst

Hey. It’s Luke Shumway on for Etzer. Thanks for taking my question. For the zanza colorectal cancer update next year, the primary endpoint is OS in patients without liver events.

How readily identifiable are patients without liver events in the real world? And would that require a companion diagnostic?

Amy Peterson — Chief Medical Officer

Hi. This is Amy. Thanks for the question. So, this is an imaging assessment.

All patients, when they’re diagnosed with advanced disease tend to get scanned from head to toe. And that absolutely includes a liver scan, especially for patients with colorectal because of its predilection to metastasizes to the liver. So, all patients with colorectal will have a scan of their liver. And it’s pretty straightforward to identify whether or not there is a disease present in the liver or not.

So, it’s an imaging. It’s a clinical assessment. It’s actually not a companion diagnostic, and it’s readily utilized by physicians every day.

Operator

Thank you. Please stand by for our next question. Our next question comes from the line of Sudan Loganathan with Stephens. Your line is open.

Sudan Loganathan — Analyst

Hi. Thank you for taking the time to share your quarterly results. Good evening. Congratulations on all the great — the great quarter and the recent progress on many fronts.

With the breadth of clinical program opportunities for cabo and zanza, the GU, and GI space, what indications or therapeutic technologies are left out there of interest when you’re looking for assets during the BD endeavors? Are you specifically looking for assets primarily for novel combinations with cabo and zanza or monotherapy options out there to cover the GU/GI indications?

Michael M. Morrissey — President, Chief Executive Officer, and Director

Yeah, Sudan. Thank you for the question. It’s Mike. Yeah.

I would say simplest answer is all of the above. Our conviction is around clinical differentiation that can drive commercial success if those are — those assets combined with zanza, other XL molecules in the pipeline, great. If they’re stand-alone agents or combined with checkpoints, that’s fine, too. So, again, we’re agnostic when it comes to modality MOA type of transaction.

We’re focused on really high level of conviction on clinical differentiation that then drives commercial success.

Operator

Thank you. Please stand by for our next question. Our next question comes from the line of Chris Shibutani with Goldman Sachs. Your line is open.

Chris Shibutani — Analyst

Thank you. Mike, as you think about how you’re staffing your teams and obviously monitoring how you’re spending, noting that SG&A, the R&D has come down. What are the areas that you feel are going to be important to expand further?

Michael M. Morrissey — President, Chief Executive Officer, and Director

Thanks, Chris. Yeah. I think we’re in a pretty good spot right now. Obviously, if we have in the out years continued clinical success and we need to augment what we’ve got commercially.

That’s a relatively easy and incremental growth as we’ve seen so far in our planning for the net space. But in terms of the company, we have 100-plus employees. We are – I think we’re leading mean in terms of what we are aspiring to do organizationally in terms of building this multi-franchise oncology business. But we’ve got a lot of momentum in the organization from an R&D point of view, from a commercial point of view with the right size G&A to make it all work.

So, we’re excited about where we are, and we think we’ve got the right team and certainly the right horsepower both talent-wise as well as energy-wise to make that happen as we go forward.

Operator

Thank you. Please stand by for our next question. Our final question comes from the line of Joe Catanzaro with Piper Sandler. Your line is open.

Joe Catanzaro — Analyst

Hey, great. Thanks for taking my question. Congrats on the quarter. I had one on the PK MIT program since it’s now in Phase 1.

So, you mentioned on restorative and that program seems to have honed in a biomarker-selected population in endometrial and ovarian cancer. So, maybe can you speak to your strategy around tumor type selection and biomarkers that you may be using. And then you also mentioned potential cytotoxic combinations for that program. Wondering if maybe you could elaborate a bit more on that.

Thanks.

Dana Aftab — Chief Scientific Officer

Yeah. Thanks for the question, Joe. This is Dana. I’ll take that one.

So, yes, so XL495 as you’re quite aware as a PK-1 inhibitor, which has shown synthetic lethality in tumors that have increased cyclin E levels that can be driven by a number of different actual genetic biomarkers, including CCNE amplification and a few others. So, we’ve certainly identified those biomarkers in our preclinical models, but we’ve also identified some other interesting biomarkers that we have not yet disclosed, which we’re also quite excited about. So, we are looking at all of these biomarkers in the Phase 1 study. We have also conducted quite a few combination studies preclinically looking at, as you mentioned, cytotoxics, but also a very expanded range of drugs that have direct or indirect impacts on generating sort of a replication stress type phenotype in the cells and we have a lot of opportunities there.

So, we haven’t been – we haven’t really disclosed details of our Phase 1 program yet. We will do that at some point in the future. But until then, we’re looking at quite a few different hypotheses in the clinic for both biomarkers and combinations.

Operator

Thank you. Ladies and gentlemen, I’m showing no further questions in the queue. I would now like to turn the call back over to your host, Varant, for closing remarks.

Varant Shirvanian — Director of Investor Relations

Thank you, Towanda, and thank you all for joining us today. We welcome your follow-up calls with any additional questions you may have that we were unable to address during today’s call.

Operator

[Operator instructions]

Duration: 0 minutes

Call participants:

Varant Shirvanian — Director of Investor Relations

Michael M. Morrissey — President, Chief Executive Officer, and Director

Christopher J. Senner — Executive Vice President, Chief Financial Officer

PJ Haley — Executive Vice President of Commercial

Mike Morrissey — President, Chief Executive Officer, and Director

Asthika Goonewardene — Analyst

Unknown speaker — Bank of America Securities — Analyst

Silvan Tuerkcan — Analyst

Dana Aftab — Chief Scientific Officer

Amy Peterson — Chief Medical Officer

Michael Schmidt — Analyst

P.J. Haley — Executive Vice President of Commercial

Gregory Renza — Analyst

Yaron Werber — Analyst

Jay Olson — Analyst

Andy Hsieh — Analyst

Stephen Willey — Analyst

Ash Verma — Analyst

Peter Lawson — Analyst

Lukas Shumway — Analyst

Sudan Loganathan — Analyst

Chris Shibutani — Analyst

Joe Catanzaro — Analyst

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