Exelixis, Inc. ($EXEL)

Hi. My name is Jeffrey Walch. I co-lead the U.S. biotechnology coverage at Bernstein. Very excited today to have a nice fireside chat with Michael Morrissey, PhD, President and Chief Executive Officer of Exelixis. Look forward to the conversation and thank you for attending.

All right. Great to be here. Thanks for the invitation today and looking forward to -- we had a great day. Looking forward to a great conversation. Before I begin, let me just state that I'll be making forward-looking statements today. So people listening should see our SEC filings for a description of the risks that we face in our business.

That's perfect. And Michael, really appreciate you and the team coming out today. We've had you attend multiple of these conferences and really appreciate always hearing your story. And personally, I'm excited to have this conversation today. I worked with your company back when I was at Bristol-Myers Squibb. So I know Exelixis well as a drug collaborator.

That's right, collaborator.

Yes, collaborators on dual LAG program. So look forward to a nice conversation and love to hear about your strategy and what you're sort of thinking.

I mean maybe just as a high level, just to kick us off, maybe just give an overview of Exelixis' multi-franchise strategy approach.

Yes, for sure. And I think it's what drives everything we do tactically in terms of how we look at building the business, how we've built the business so far on the strength of cabozantinib, but how we're looking to really take the business to the next level or 2 in terms of how we approach, really, every aspect of biotech R&D, commercialization, the intersection of all those different aspects together. Look, we're all in the same business to a certain degree. We want to help patients. I think we have an overriding focus on improving the standard of care for patients with cancer. And that is largely informed by the success of cabo that we've had over the years. Getting a p-value can sometimes be really challenging. Other times, it can be relatively straightforward, but a p-value and a successful pivotal trial doesn't necessarily mean you're going to be a commercial success. And the way you drive commercial success is you basically change standard of care. You make it such that your offering therapeutically is moving the needle for patients in a way that prescribers, payers and even patients need to stand up and acknowledge and want to be part of. So we've done that, I think, pretty well with cabo. I mean we've learned a lot. We've done a lot. We don't always knock it out of the park in terms of some of the indications we've chosen and combinations that we've chosen, but we've really, I think, been able to funnel our view of what success looks like for a company like us. And it's really franchises. And we -- as we talked about -- previously, we made it a big focus of our R&D Day back in December. We really think about that in terms of different dimensions, right, in terms of how we view a franchise. Obviously, you can have a franchise within a single molecule like cabo. You can reinforce franchises in indications. We focus in the GU and GI space. We don't focus on all of heme/onc. We don't focus on all of solid tumors, but we're really focused on moving the needle for GU and GI patients with cancer. And then we have, I think, a pretty, not strict, but focused view on modalities, like, be able to put -- we want to be able to put basically drug product into a bottle and then make that bottle available commercially. So it really focuses where we want to play relative to the modalities from a manufacturing point of view. We're a relatively small company. We can only do so much heavy lifting from a manufacturing point of view. We obviously have great depth and expertise in small molecules and now biologics as we've moved in that direction. But we have to stay focused. And that's, I think, one of the things that we've tried to strive as a management team is to really focus and prioritize. And strategy often comes down to not really so much what you're doing, but what you choose not to do and to have that discipline to be able to really narrow the focus to, again, bring benefit to patients and shareholders, but at the same time, have the right level of focus, so you can move the needle virtually every day. So that's how we're operating, and we do that from the standpoint of how we look at targets for discovery, how we look at molecules that we can combine with relative to indications that we want to pursue within the GU and GI space. And we obviously have some flexibility. I think you've seen that with the zanza program where we're looking at peripheral indications outside of GU and GI, say, like lung maintenance or meningioma that don't really fit into that kind of strict category, but we have such interesting potential and activity that we can flex a little bit, again, look for data and kind of a surveying effect and go. So -- but I think the team is really well organized and very focused along these kind of lanes of thought and lanes of research. And our job is to execute every day with cabo and zanza in the pipeline and assets that we can find from external sources.

That's great. I mean -- and you said before that sort of you have this product strategy, the modality strategy, the tumor franchise strategy. What would you say sort of distinguishes your approach between the three? How are they similar? How are they different? How you approach each of these three?

Yes. So I would say they're all -- I think they're all interrelated, right? You really have to be able to -- in the most simplistic term is kind of the Venn diagram view of the world. The more overlap, the better, right? And that -- I think from our point of view, then is just kind of dimensionalized on multiple levels in terms of what we're doing by ourselves, what we can do in collaboration, right? We've talked about this in BMS. I mean that interaction, that collaboration, which goes back for literally decades is a good example where sometimes we collaborate, sometimes we compete, sometimes we're collaborating with the competition in terms of, say, some of the early cabo/nivo work. It's all part and parcel with the focus and the priority for us is what's the right science, what's the right biology to kind of embrace and then what are the right clinical work that we need to do to be able to, again, move the needle for patients. And I think with that focus on -- again, we're not looking at nano niche indications because I think history has shown that -- I mean that can certainly help a small number of patients, but the upside can be limited to a certain degree. So again, we're focused on big indications in both the GU and GI space, renal cancer, colon cancer, prostate cancer, et cetera, where we really think we have the opportunity to do well by patients and also drive value for the company and shareholders.

Yes. And I've seen the collaboration firsthand and I think this is a great part of Exelixis. Anything -- in terms of collaboration, anything that you look for, anything in terms of the benefits that the company has from that? Or when you think to collaborate with other companies, what are some of the things that you're looking to achieve?

Yes. It's always the common language of our -- do we have aligned goals and philosophies around what success looks like, number one? Do we have the right scientific, I would say, both overlap and complementarity that we need to, really, in some ways, synergize what each side can bring to the table and then provide even super additive, if not synergistic value to patients? So it's that kind of special place where you're kind of working above the fray of the noise that normally happens kind of in the background and able to operate in a way that, again, allows you to move. And I think that a lot of the collaborations that we had in the early days on the discovery side were just fantastic in terms of being able to have a situation where 1 plus 1 was 5, equals 5 as opposed to 2 or 1.5, which is often the case. And on the clinical side, too, I mean the 9ER study that we did, as I've said previously, it's kind of in the ROI hall of fame in terms of we had cabo and nivo, 2 leading single agents that were actually had initial single-agent top line data literally on the same day. And then from that day on in terms of second-line studies, people ask the question, well, if they work so well by themselves, both have a survival advantage, both with the nivo for patients, what happens when you combine them? And it was certainly a very rewarding process then to collaborate between the 2 companies, the top KOLs in a way that was really allowed us to move quickly and dramatically and to win on response rate, PFS, overall survival and quality of life together, set us up really well to move -- continue to move cabo up in terms of being a market leader for RCC. So we're super excited about that. And that -- I think that success, and that comes after the typical kinds of failures that happen in this game. But it certainly builds a level of focus, of resilience of conviction that we've done this, we can do this again and then get out there and make the whole process work from asking the right questions on the discovery side or on the combination side and then doing the right level of clinical work to be able to -- again, to really get over the goal line time and time again. So done that with cabo. It's a molecule that has, I think, 8 different indications or 8 successful pivotal trials that led to a very broad label. Obviously, it's a commercial success across different indications. We think zanza is probably a better next-gen molecule based upon some of the early data. First trial in third-line plus CRC was successful in overall -- enhancing overall survival. That comes on the back of 4 failed checkpoint-based trials. So different kind of clinical phenotype, if you will, getting a lot of positive feedback in terms of the market potential, and we're under review right now. So it's one that we're really excited about. And again, that we think really kicks off the opportunity for zanza, which I'm sure we'll talk more about today. But it's indicative of how we think about building a franchise, right? The right combinations, the right indications, the right lines of therapy, really, pushing the needle in terms of where you're in a hypercompetitive space indication-wise versus maybe what's kind of wide open right now and pushing that envelope. So it's how you expand in a measured fashion and doing that in a way that I think reflects how we view running the business because we run the business like a business. We've been profitable, I think, since 2017 or so. We're very convinced that buying back shares right now makes a lot of sense, and we have for the last several years because we just think we're undervalued based upon how The Street views zanza currently. But we think over time, that will change. We have 7 ongoing or soon-to-start pivotal trials of the first wave. And I think the next wave kind of forming as we speak. So there's lots of moving pieces with zanza following on the success of cabo. And then the question is what's potentially the third franchise molecule? What's the fourth franchise molecule? Because that's -- in our view, that's how you build really important growth in the story and how you kind of change the vector each time in terms of what growth in terms of impact on patients in terms of revenue, in terms of market cap can be. So that's the focus. Team is -- it's lean and mean, and I'm really excited about where we're at and what our future looks like, and we're just committed to executing every single day.

Absolutely. And on that -- on the point where you ended, so what do you think of how the pipeline is situated for future pan-tumor leadership? Anything in particular you want to highlight, anything you'd like to talk about?

Yes. So we have 4 molecules in the clinic now. We've got a few more on the way. Obviously, zanza is leading the charge. We stopped really investing in cabo per se, and we've talked about that for the last few years now why we're doing that. But we think zanza is the right molecule to put a lot of energy behind right now. And from a pure resource allocation point of view, that gets fed first relative to how we're doing it. We're -- and we have consistently embraced the idea that if you want to be a leader, if you want to move the needle for patients, you've got to belly up to the table and invest in and run and execute on pivotal trials. That's the only way the p-values that you hope to get are the only way to move the needle and get the attention of regulators and payers and HCPs down the table. So a lot of companies, certainly in our -- where we were 10 years ago, we were hesitant to do that because it's a big gulp moment in terms of do I really want to spend $100 million, $200 million doing this? We do that readily. Once we've done the analysis of the situation, both clinically and commercially, if it makes sense to us within that analysis and we have the data supporting it, we're -- we understand you've got to be able to put that risk capital to work to be able to generate value for patients. So we do that readily, and we do that in a way that, again, gives us the conviction that we can do that again and again and again. So -- and it's picking your fights to a certain degree, right? So obviously, we're a leader in renal cancer with cabo. And we certainly plan to try to maintain that with zanza. We've got 3 pivotal trials going right now. And probably, we'll have more on the way in the future. We think colon cancer is another good example of an indication that is ripe for innovation. And certainly, the STELLAR-303 success really underscores that. We have a trial for called STELLAR-316 looking at really post-adjuvant kind of therapy for high-risk patients based upon the Natera Signatera technology, where you can preselect high-risk patients based upon their MRD status. Again, there's no standard of care for those patients. They're just kind of -- they get surgery. They get chemo, in either order, depending upon if it's colon or rectal and then they just kind of watch and wait, right? And that's -- if there's a way you can identify, preselect these high-risk patients as has been done recently in, say, bladder with a very well, I think, just elegant technology. It really brings potentially a lot of value to patients. And 303 and 316 kind of travel together. We're constantly getting talk about one with a cabo and the other one comes up and vice versa. So it really reinforces the idea that that's how you build leadership in a given area in a given franchise, whether it be a molecule or an indication or a modality is you just -- you keep investing in a very thoughtful, pragmatic way. You use data, you use your insights, you certainly -- whatever conviction you have to be able to kind of push that ball, if you will, move that ball downfield in the football analogy. And that's something that we do, I think, really well and have the conviction that more often than not, if we make the right choices and we execute well, we'll be successful. So -- but the pipeline is full. Early stage, we have 4 compounds in Phase I, Phase Ib, a couple of ADCs, USP1 inhibitor and bispecific XL628 that we're just starting to look at zanza combinations with. So that's super exciting. And looking to do more. We've got a couple of INDs kind of on the way with DLL3 and an oral SSTR2 antagonist. So those should be at the IND stage this year. And we're looking, I think, pretty aggressively for potentially later-stage assets in the GU, GI space. We've got a very great balance sheet, Again, we're profitable. Lots of cash flow. So we have room to maneuver there as well. So again -- but we're looking at doing the right investments based on the right data, based upon the right view of the commercial opportunities in these indications. And I think more often than not, we're going to be successful.

Yes. Any of those ADCs in particular that you want to highlight or that you heard about?

Yes, I think -- I mean they're both really interesting and there's more on the way. But I think XB371 is a tissue factor targeting ADC with the topo warhead. It's designed kind of de novo to play in the CRC, in the colon cancer space where we want to build. So you can imagine getting to a point where whether we have single agent or we have combinations with zanza, a combination with zanza and a checkpoint, just building off the foundation of 303, and that's how kind of building a franchise in that indication across molecules, in this case, across modalities as well. So it's that kind of multifactorial view of what's the best way to bring value, additional value, change standard of care for patients. And again, part of it is obviously empirical. You've got to generate data. Part of it is very clear looking at -- if you look at that example of 371, zanza and say, a checkpoint, right, you've got 3 orthogonal MOAs, which arguably kind of at least de facto should have minimal kind of AE overlap liabilities. And the question is, do you have the right -- are you picking the right pathways? Are you picking the right, if you will, warheads or the right agents to be able to bring maximal benefit at the right level of therapeutic index, right? So it's theoretical. You look at the situation, you look at the genetics, you look at the evolution of the -- of that -- how that indication is actually -- from a standard of care and how it's treated. And then you've got to look downfield 2 years, 5 years, 10 years and say, "okay, how am I going to move the needle in that time frame?" So it's a bit of kind of putting the Carnac hat on and asking some important kind of forward-looking questions. But we're not doing anything to change standard of care today. It's always what happens 3 years, 5 years down the road because everything is moving so quickly. You've got to almost preselect kind of where you think the bar is going to be and then try to beat that, right? So -- but yes, there's a lot going on, and it's fascinating to watch the technology advancements on the translational side. Certainly, on the discovery side, we have our own cryo-EM that the structural team is just -- I mean the rapidity and the depth of data we can generate on new areas of research, say, in the RAS space or in the SSTR2 space is just -- it's amazing to be able to have an idea, make a molecule, get some data, solve the structure, say, well, I guess I was wrong on that, but it does bind. It just binds this way or that way, and then you'll be able to modify your thinking and then go forward. So it's a full court press and with multiple inputs from multiple, if you will, perspectives. But I think that's what makes Exelixis so strong is that we can pull all that together with the right team and the right approach and move things forward.

And you've talked a lot about CRC so far in RCC and also neuroendocrine is a focus. And just curious what you're thinking for your SSTR2 and your DLL3. They sound very small cell neuroendocrine type focus. Maybe you could just expand just in general, neuroendocrine, about those targets.

Yes, exactly. So that's -- I mean that's a franchise that we talked about this in December, where we're just starting kind of scraping the surface with cabo based upon the CABINET study. We've got the STELLAR-311 study that's ongoing. We're currently recruiting, looking at zanza compared directly to everolimus, which is standard of care, second line plus, first-line plus in that situation as usually before cabo, the first oral therapy that was used. So CABINET looked at cabo against placebo in later-line patients. This is going -- kind of going 1 or 2 steps up in terms of line of therapy but also against an active control. So you would imagine if that wins, it really kind of opens up a lot of additional leeway for us in terms of how that might be used, right? The mainstay of neuroendocrine tumors is really SSAs, somatostatin agonist, right, which are all peptidic and parenterally administered. Having an oral therapy that could displace those being used in the frontline setting is a huge opportunity for patients. These are all subcu injections, big needles, can be painful. To be able to have an oral therapy that they can take once a day at breakfast or at night would certainly simplify -- not only simplify administration, but from a PK/PD point of view, really kind of even things out from the standpoint of getting away from some of the valleys that, in more advanced patients, can certainly cause problems from a symptoms point of view. So -- but I guess that's a good example of -- it's still early. We're still kind of wrapping up GLP tox and hopefully, we'll be in man later this year. But it kind of -- it really shows to us the important perspective we have from a commercial point of view, with very few biotech companies have unless you've got a big commercial molecule that can inform how you evolve your strategy quickly in terms of asking the right questions about where's the maybe either underappreciated or unexpected opportunity. And then what's the best way to navigate that and what's the best way to use our financial depth to be able to build a leadership position. So I think that's a good example that it's actually a really big indication. It's just kind of under the radar for a lot of big companies. And it's one that we think we can build. And I think the estimate is that it could double or triple in size over the next 10 years. So we want to be part of that growth because if we're successful in helping that indication grow, then we're -- means we're helping a lot more patients. And if we can do that with more than one molecule, it's cabo, if it's zanza, if it's the SSTR2 story, if it's DLL3, if we can be part of that and own pieces of that pie as opposed to one pie as it's growing and helping that many more patients, then we can check a lot of boxes in terms of we've helped patients. We've improved standard of care. We're driving value creation, and we can then take that -- take those revenues and reinvest those in R&D and really move the next generation forward because from our point of view, value creation is all about building franchises and building one after another. And 2 is better than 1, 4 is better than 3. I mean the math just kind of gets very, very appealing after a while.

Yes. I mean at the core of Exelixis, I think also RCC is at the core as the starting point. Maybe going back to that, what do you see as key highlights, key next steps as you expand and grow within RCC and sort of to get from where you were?

Yes. No, it's a really interesting kind of look back in terms of where it was back in the early teens. First-gen molecules, second-gen molecules were kind of percolating along. I think we really changed the landscape there by asking some very fundamental questions about tumor biology at the most basic level and simply ask the question with cabo, "can you inhibit the primary driver of tumor angiogenesis and the resistance mechanisms at the same time, okay?" That was a simple hypothesis, right, be able to make the molecules that did that. As we profiled them further, we learn more about their direct anti-tumor activity. We learn more about their impact on the -- on both sides of the immune system. And in some ways, we ended up with a molecule and a class of molecules that had an impact on literally every cell type in the tumor microenvironment. Part of it on purpose, part of it is kind of by accident. It came along with the right, but I think that serendipity and that empiricism is an important part of the process. People don't like talking about that, but that's the reality of the situation. You know that from the days, right, in pharma. So then we just went from there, right? And we did a lot of work ourselves, a lot of work in collaboration with other companies and got some great collaborations as part of our CRADA with the NCI. And fast forward, we have the leading -- cabo is the leading TKI for RCC. It's the leading TKI in frontline IO/TKI combinations. It's the leading TKI in second line plus -- leading oral therapy in second-line plus NET because we've been able to generate kind of standard of care moving data and then be able to monetize that and kind of make that happen from the standpoint of our commercial depth and heft. So that's something that we're focused on. Obviously, zanza, we've got a lot going on there. The 304 trials looking at non-clear cell RCC in combination with nivo. No one has ever done a pivotal trial in that subpopulation of RCC. So we're super excited about that. We've got a couple of different trials going with Merck now in terms of the zanza, belzutifan combination, looking at post-adjuvant patients as well as second- third-line plus patients in both combination with belzutifan. And we're very, very focused on being able to come up with approaches for frontline RCC as well. And I think that the learnings from all the different kind of competitive machinations over the last few months has really reinforced in our mind, certainly in my mind, the importance of I think asking the question a little bit differently is can we -- by doing a broad survey clinically, can we find orthogonal MOAs, mechanisms of action, that can give us arguably better activity with zanza in a checkpoint, either as a single-agent modality, so a triplet, or as part of a bispecific kind of like 628, right, where we've got PD-L1 and NKG2A, the natural killer cell ligand to be able to kind of find the right balance of additional potential activity, okay, without having a lot more tox. Because if you're talking about -- again, we and others together, whole industry-wide effort, we've really moved the needle, right, in terms of patient benefit for RCC, right? And by looking at new MOAs, new ways of approaching the problem and then doing the right combinations. And this is then going to the next level. But you're working at a much higher base than you were before. So you've got to really thread the needle. And whatever you do has to have the tolerability and the activity for going to the next big increment in terms of whether it be PFS and/or OS, right? So it's a heavy lift. And as you've seen with IO in general, right? I mean these things, there can be a long increment between breakthroughs, right? You have IL-2 and then you 25 years and you have PD-1s and CTLA-4s and now we've waited 15 years. And people are trying a lot of stuff and it's all great science. It just hasn't worked out, right? So every time you improve standard of care, it actually gets more difficult, so -- which is why for us, it's -- I think it's really important that we are committed to our leadership in RCC. We're investing there. We're doing it the right way in terms of sharing the cost, if you will, with our collaborator. But we're also looking in areas like NET, like CRC and a meningioma, whatever, that kind of spreads the risk and has significant upside all by itself. So again, before the fact -- and we've seen this with cabo, you can design trials that you think are going to work. Most of them do work. Some of them are commercial blockbusters. Others are a little bit less compelling. But doing that all before the fact, there are so many factors that you just can't control for, you've got to have the right mix of trials and combinations and lines of therapy to be able to cover all the bases. And then when you do see breakout data, then you've got to capitalize on that with great speed and great conviction.

Absolutely. I mean you're just hearing you talk about the bar and thinking about this is where KEYTRUDA and KEYTRUDA/pembro, how it evolved going against chemotherapy, with a lower bar. And now as you say, we're waiting -- we waited a long time to see what can now go head-to-head in KEYTRUDA. And on that point, when you think about the trials you guys are conducting, how do you sort of stack the deck? You've got great data. You're now thinking what trial to do. What do you do? What do you think to really increase your PTS? Nothing has ever de-risked, but just curious about that.

Well, it's a combination of both. And I think we're thinking, learning self-reflecting organization. And I think the part of the charm that we, I think, have been able to execute on is looking at what has worked and what hasn't worked and then ask some of the hard questions about, okay, what have we learned because you can learn a lot more from a failure than you can from a success sometimes, right, if you're not totally myopic, right? So -- and I think that's where the -- asking the right question around combinations is so important. So we have a Phase II that we talked about, Dana talked about on earnings about a month ago in terms of looking at a second-line maintenance of zanza plus pembro in a squam population post basically chemo, pembro. And I think that's a good example where could we actually improve patient outcomes in the maintenance phase by combining with pembro. Same thinking goes. We've done a lot of work, say, in prostate cancer with cabo. We had a trial in second-line lung cancer with cabo and atezo. Those have all failed. What have we learned from that? Well, with zanza, maybe we have the opportunity instead of trying to docetaxel head-to-head, which is still used a ton in all kinds of different tumor types because it's really hard to beat. It's truly standard of care. Can we -- do we have the right molecule with zanza and from an activity tolerability point of view that we can actually combine with docetaxel? And so that doublet against docetaxel could be a really interesting way to go. So that's part of the next wave. And we're doing -- we actually have a trial going right now looking at that combination in later-line prostate cancer to understand tolerability and PK and those kinds of things and initial activity. But you can imagine if we can actually see benefit there so that could apply to prostate cancer, that could apply to second-line non-small cell lung cancer. That could -- we ask the question, could you combine, say, zanza with standard chemo in frontline CRC. So kind of reinforcing this whole paradigm around building franchises across lines of therapy and like we've done with cabo and RCC. So it's a constant, I think, examination of what's the best place to put our efforts to make our investments based upon the data, based upon our vision for how things will evolve over time.

Yes. Earlier in the conversation, you mentioned how strategy isn't just what you choose to do. It's the things that maybe you don't do, things that you sort of either avoided or didn't dive too deep into. Is there anything that as you reflect on your time that you're running Exelixis, anything that you are maybe happy you didn't wait into, whether you were considering it or not, things that you feel maybe worth it?

Yes. Well, I would say the -- it's a great question. So I'm -- I think I've been in terms of my scientific career, more tend to focus than be broad because I think that's always the best way to marshal the resources you've got the critical thinking, you have access to either internally or externally, KOLs or through collaborations. I think the focus that we've done has been partly organic, right? We have activity in GU and GI cancer. So let's double down there. We've got a commercial organization that's built to excel in GU and GI. So it makes sense to build in there, right? We've dabbled in other areas with cabo in the past, other molecules in the past as we were signal searching and those did not work out as well as we would have liked for them to we've double down where we're active, where we're successful and it makes a lot of sense. But I think that one of the most important things we did early on was not looking at heme/onc and saying heme is so competitive. They're so deep there. The combination approach is so successful, really asking the question, what do we have to offer there that could be different and could, again, an improved standard of care. And I think the conclusion that we made was probably not a lot. Let's focus in on solid tumors where it's just a much, much tougher go in terms of both pharmacodynamics, right, in terms of genetics and certainly then in terms of the actual pharmacology you're trying to impart there. So I think that's the right move. Lots of important work has been done in thoracic oncology and breast cancer, those kinds of things, I don't think we could be as effective as we are in GU and GI if we were more broadly based, right? So look, we'll double down. always -- we always have the option if our MOAs and our pharmacology overlaps with biology and another tumor type, we can always go there. We're doing that now. And part of it is opportunistic, part of it is mechanistic. So nothing stops us from doing that. But I think to keep everybody focused on what we're trying to do because, I mean, there's literally millions of patients in this subsection that if we're successful, we can bring a lot of value to and can, again, grow the company and build shareholder value with as we go forward. So focus is a good thing for us for sure.

Absolutely. And maybe just thinking forward-looking, what does -- what do you see your success for Exelixis in maybe a 5-year time line? Whatever that metric looks like, what would you sort of look forward and say, if I'm happy with this.

Yes. No, it's a good question. It's something that we think about a lot. I think about success on a log scale, not a linear scale. And that from the standpoint of any kind of quantitative metric, patient numbers of patients you treat, patient years, you can improve upon all that drives revenue, and it's the kind of the big circle one drives the other. But again, I think the multi-franchise pipeline of franchise molecules kind of plays to that theme, right? We want to jump up in half log units as quickly and as often as we can because that's the way you bring value to patients, and that's the way you bring value to shareholders. The two are intimately connected in a way that one goes with the other. And the value isn't just another molecule, but it's improving standard of care. So for me, again, I'm not an oncologist, I'm a scientist by training, over the years, that's become kind of a very, very clear guide for me. If we're not actively changing standard of care, then we need to ask the question, what are we doing? Why are we doing it? What are we doing? Do we want to invest here or someplace else? Because that's -- ultimately, that's the goal. If we do that well, everything just kind of flows from there. And that's true, I would say, in general, within the industry, right? You change checkpoints. I mean they dramatically change standard of care. Now it's taken another 15 years to go to the next level, and that's -- but that's the business we're in, right? It's a tough business, right? Anybody who plays in this space can appreciate that on a very -- as I know you can, a very personal level because it's hard. You fail more than you succeed. You understand less than you think the factors at play. When I was dabbling in antibiotics or antivirals from a pure genetic point of view compared to what's happening with solid tumor oncology where you can have in 1 organ, and this has been proven by kind of autopsy, you can have a liver post-resection that is -- has got different -- 10 different tumors with 10 different genotypes, right? I mean it's just -- it's tough. And you really need to bring every MOA to bear, every approach to bear, sometimes every modality to bear to move the needle. So I think it's with a great -- any success you have to be humble about because it's tough. And that success was hard-earned and maybe a little bit of luck was involved as you go, but you've got to be able to capitalize that and build foundations that you can then build companies and bring more success to patients. Yes, for sure.

And that's wonderful. And we've talked a lot with RCC. You talked about neuroendocrine. Maybe just give a little bit of time for CRC, too, is that when you think of your strategic vision for CRC and the trials and the things that you'd like to do there, anything you'd like to highlight?

Yes. So we talked about that a lot already. I think that certainly having a foundation of success with 303 in a later-line population, checkpoint-based kind of regimen along with zanza, really interesting. Again, that's been an area that's been heavily invested in by a number of companies, all met with lack of success and because it's just a tough place to play. So we're very fortunate to be able to win there. We have some data at ASCO, which I think is going to be pretty interesting around contribution of components that I would refer people to because it really highlights, I think, some of the way we view science in a way that I think is very novel as well. Yes. So the foundation of success there, can we take the same general approach where we have activity in terms of improving survival with measurable tumors, right? Patients with metastatic disease, as you can see radiographically. And can you go up in the line of therapy to the 316 opportunity where you've got basically no metastatic, no visible imageable metastatic disease, but you have high-risk patients post-surgery and chemo who are bound to progress based upon kind of longitudinal data within 6 or so months, right? So the question is, will the same MOAs that appear to work in measurable disease work in tumors that you can't -- that micro metastases that you can't visualize radiographically, right? So I think it's a fascinating kind of connection between those 2 ends of the spectrum. The fact that we're -- we had success with zanza checkpoint that I think gives us a lot of confidence using, again, as I mentioned before, using the Natera technology to select the right patients is the way to play the game, right? You want to -- not everybody needs this. A lot of patients are cured with surgery and chemotherapy. And that's fantastic for them. But those that aren't, we need to get in there. And for whatever reason, genetically, they need an extra boost. And if we pick the right combination and the right kind of details around how that works, can we convert what is a relatively short time period to then kind of real problems in terms of metastatic disease? Can we lengthen that? So that's a -- look, for me, that's a noble enterprise. And obviously, we're in it to run a business and ultimately drive shareholder value, but there's a lot of patients. There's thousands of patients every year that could benefit from that. And that's a big benefit, both physically and I think about it psychologically. There's no -- I mean, they're just waiting. There's no standard of care for that right now post -- for those high-risk patients, post-surgery and chemotherapy. So to be able to -- if we're successful, have something to offer them, I mean, that's very motivating and inspiring for everybody at the company. So we're serious about this stuff. We understand the stakes that are there for patients, and we're doing everything we can to move the needle quickly and confidently with high quality every single day.

Well, we've talked about several different tumor types, CRC, RCC, neuroendocrine. Is there any other tumor type that you think would be worth highlighting? If not, we can talk about maybe some -- any other modalities that you think haven't talked about enough.

Let's move to the modalities. I think that's actually -- it's a good time. And we talked about ADCs, right? We obviously have a strong small molecule approach, bispecifics. I think one of the things that we've done over the last 2 years is we were traditionally a small molecule-focused shop. And on the restart sort of our discovery efforts understood that the more breadth we could bring into our discovery world from a biologics point of view, the better in terms of covering more MOAs, getting away from potential overlapping toxicities of having small molecules kind of play in the same structural space, if you will. And that thing has been a real successful operation from the standpoint of -- we haven't invented new technologies, but I think we've aggregated technologies across the board. The execution has been absolutely phenomenal from a target identification to kind of drug elaboration, if you will, optimization, both with bispecifics as well as ADCs, for example. And we've been able to transition that from small scale to at scale for GLP and then GMP applications. So -- and that's all happened in a very seamless focused fashion. And the team is -- it's just first rate, right? We can go from concept to molecule to assays to scaling up either internally or externally and kind of turn that crank in a really impressive sort of way. So I'm really pleased about that. And it just gives us that much more kind of therapeutic and pharmacological breadth to be able to ask important questions, right? Now unlike a couple of years ago, pre-expanding into these biologics, we were like, okay, where do we -- who do we collaborate with to find this. Now we can say, okay, if we're looking at the biology correctly, we need something here and something here. This is a small molecule. This is an ADC. This is a bispecific. Let's go do it, right? And we can do that as well as anybody, right? So -- and then the scale up -- I mean, making things on a milligram scale can be easy, making things on a kilogram scale. You got to have the right people and the right opportunity with the right -- really, the right interest and the right vision to be able to get that done in real time. So I've been super pleased how fast we've built that and the expertise is just first rate.

That's amazing. And you talked earlier -- in our last couple of minutes here, you talked earlier about you have great financial position, stock buybacks. I mean we haven't talked too much about the financial commercial side of the company. We're mostly focused on drug development. So maybe just in the last couple of minutes, anything from the commercial side, finance side that you think is important to talk about the strategy and how you execute?

Yes. I would say, at the highest level, it's all integrated. We have one strategy. We have one focus. Obviously, we have different groups and different responsibilities and accountabilities in terms of how that works, but everything works together. And the way we're organized, the way we're co-located, the commercial people, the competitive intelligence people, the discovery people, that leadership operation is talking on an hourly basis, right? And that's the way it has to be, right? Having people in silos, sitting in their offices, drawing structures and thinking about whatever, just doesn't -- that doesn't work, right? You've got to have the right level of insight. And certainly, whether it be on internal programs, but also looking at external assets, right? We need to have a full view of what the opportunity is. And we're fortunate to have this fully enabled commercial team that has achieved and overachieved and competed with all the big guys all the time, right? So to be able to have that depth and that breadth and having that mindset that says, a good idea, but a tiny indication or a good idea, but don't forget about this competition and that's a good idea. I mean having that analysis is now just -- it's just kind of -- it happens automatically almost. I don't want to organize it. It just happens when the people are talking and there's the right level of engagement and accountability about making that work. So in that regard, it's super fun to watch. It's not easy. And sometimes there's just things we don't know, and we have to be able to model effectively and then make -- we're paid to make decisions without having perfect insight into all the different variables, and that's part of the job, too. So -- but I think from a financial point of view, the depth we've got and the modeling capabilities we've got really helps us do that a long way. So great team. Everybody works together really well. I'm super excited about where we're going, and we just need to continue to keep our heads down and just keep cranking, which we do.

Well, that's amazing. I mean this has been a great conversation. I really appreciate the chance to learn from you, and I'm sure everyone else listening has as well. So thank you for sharing your strategy, your future vision and really appreciate your time today.

Fantastic. It's been a great day. I appreciate the invite and looking forward to seeing you again soon.

Absolutely. Thank you, Mike.

Okay. Thank you. All right. Great.