EXELIXIS, INC. — Call Transcript 2026

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. 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. 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. Personally, I'm excited to have this conversation today. I worked with your company back when I was at Bristol Myers Squibb, so know Exelixis well from my time. That's right. Yeah. as a drug developer. Collaborators. Yes, collaborators. That's right. Dual LAG program. Look forward to a nice conversation and love to hear about your strategy and what you're thinking. Maybe just as a high level to kick us off, maybe just give an overview of Exelixis' multi-franchise strategy approach. Yeah, for sure. 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 two 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. Yeah. We want to help patients. I think we have an overriding focus on improving the standard of care for patients with cancer. 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. Yeah. Other times it can be relatively straightforward. A p-value and a successful pivotal trial doesn't necessarily mean you're going to be a commercial success. The way you drive commercial success is you basically change standard of care. You make it such that you're 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. We've done that, I think pretty well with cabo. 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. It's really franchises. As we talked about previously, we made it our big focus of our R&D day back in December. We really think about that in terms of different dimensions 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. We don't even focus on all of solid tumors, but we're really focused on moving the needle for GU and GI. Yeah Patients with cancer. We have, I think a pretty, not strict, but focused view on modalities. Yeah. We want to be able to put basically drug product into a bottle. Make that bottle available commercially. 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. We have to stay focused. That's, I think one of the things that we've tried to strive as a management team, is to really focus and prioritize. Strategy often comes down to not really so much what you're doing, but what you choose not to do. Right. 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. 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 excuse me, combine with relative to indications that we want to pursue within the GU and GI space. We obviously have some flexibility. Yeah. 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 strict category, but we have such interesting potential and activity that we can flex a little bit. Again, look for data in kind of a surveying effect and go. 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 and the pipeline and assets that we can find from external sources. That's great. You've 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? Yeah. I would say, I think that they're all interrelated, right? You really have to be able to, in the most simplistic terms, kind of the Venn diagram view of the world. The more overlap, the better, right? 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 of where sometimes we collaborate, sometimes we compete, sometimes we're collaborating with the competition. Yeah 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. I think with that focus on, again, we're not looking at nano niche indications because. Yeah I think history has shown that can certainly help a small number of patients, but the upside can be limited to a certain degree. Again, we're focused on big indications in both the 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. Yeah. I've seen the collaboration firsthand and think it's a great part of Exelixis. In terms of collaboration, anything that you look for, anything in terms of the benefits that the company has from that? When you think to collaborate with other companies, what are some of the things that you're looking to achieve? Yeah. 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. 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. Yeah Even to operate in a way that, again, allows you to move in. I think 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 + 1 = 5 as opposed to two 1.5, which is often the case. 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, two leading single agents that actually had initial single-agent top line data literally on the same day. Yeah. 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 move the needle for patients, what happens when you combine them? It was certainly a very rewarding process then. Yeah Collaborate between the two companies, the top KOLs, in a way that 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 continue to move cabo up in terms of being a market leader for RCC. Yeah. We're super excited about that, and I think that's success, and that comes after the typical kinds of failures that happen in this game. Yeah. It's fine. 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. Yeah. Done that with cabo. It's a molecule that has, I think, eight different indications or eight 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 enhancing overall survival. That comes on the back of four failed checkpoint-based trials. 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. Oh, congratulations. 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. Yeah. 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, you know, where you're in hypercompetitive space, indication-wise, versus maybe what's kind of wide open right now and pushing that envelope. Yeah It is 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 than 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 seven ongoing or soon-to-start pivotal trials with the first wave. Yeah I think the next wave kind of forming as we speak. 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? Yeah. What's the fourth franchise molecule? In our view, that's how you build really important growth in the story. How you kind of change the vector each time in terms of growth in terms of impact on patients, in terms of revenue, in terms of market cap can be. That's the focus. Team is 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. On the point where you ended, 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? Yeah. We have four molecules in the clinic now. We've got a few more on the way. Obviously zanza is leading the charge. We've stopped really investing in cabo per se, and we've talked about that for the last few years now, why we're doing that. 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- Yeah to how we're doing it. 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. Yeah Invest in and run, execute on pivotal trials. Yeah. That's the only way, the p-values that you hope to get are the only way to move the needle. The attention of regulators and payers and HCPs down the table. A lot of companies, certainly in where we were 10 years ago, were hesitant to do that because it's a big gulp moment in terms of do I really want to spend $100, $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 understand you've got to be able to put that risk capital to work. Yeah to be able to generate value for patients. 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. It's picking your fights to a certain degree, right? Yeah. Obviously we're a leader in renal cancer with cabo, and we certainly plan to try to maintain that. Yeah. With zanza, we've got three 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. Yeah The STELLAR-303 success really underscores that. We have a trial called STELLAR-316 looking at. Right Really post-adjuvant kind of therapy for high-risk patients based upon the Signatera technology, where you can pre-select high-risk patients based upon their MRD status. Again, there's no standard of care for those patients there. Yeah. They just kind of 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? If there's a way you can identify, pre-select 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. Yeah. 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. 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 investing in a very thoughtful, pragmatic way. Yeah. 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. Yeah. 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. The pipeline is full. Early stage, we have four compounds in phase I, phase I-B a couple of ADCs, a USP1 inhibitor. Bispecific XB628 that we're just starting to look at zanzalintinib combinations with. That's super exciting. Looking to do more. We've got a couple of INDs kind of on the way. Yeah with DLL3 and an oral SSTR2 antagonist. Great at the IND stage this year. We're looking, I think, pretty aggressively for potentially later-stage assets in the GU/GI space. Wow. We've got a great balance sheet, again, we're profitable. Yeah. Lots of cash flow. We have room to maneuver there as well. Again, 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. I think more often than not, we're going to be successful. Yeah. Any of those ADCs in particular that you want to highlight or that you're excited about? Yeah, I think they're both really interesting. There's more on the way. I think XB371 is tissue factor targeting ADC with a topo warhead. It's designed kind of de novo to play in the CRC, in the colon cancer space, where we want to build. Yeah. You can imagine getting to a point where, whether we have single agent or we have combinations with zanza, combinations with zanza and a checkpoint, just building off the foundation of 303. Yeah That's how building a franchise and that indication across molecules. Yeah It's that kind of multifactorial view of what's the best way to bring value, additional value, change standard of care for patients. Again, part of it's obviously empirical. You've got to generate data. Part of it is very clear looking at if you looked at that example of 371, zanza, and say, a checkpoint, right? You've got three orthogonal MOAs. Yeah. Which arguably, kind of least de facto should have minimal AE overlap liabilities. The question is, are you picking the right pathways? Are you picking the right, if you will, warheads of the right agents to be able to bring maximal benefit at the right level of therapeutic index, right? Yeah. It's theoretical. You look at the situation, you look at the genetics, you look at the evolution of how that indication is actually standing from a standard of care point of view. Yeah How it's treated, and then you've got to look downfield two years, five years, 10 years and say, "Okay, how am I going to move the needle in that timeframe?" It's a bit of putting the Carnac hat on some important kind of forward-looking questions. We're not doing anything to change standard of care today. It's always what happens three years, five years down the road. Yeah. Everything is moving so quickly. You've got to almost pre-select where you think the bar is going to be, and then try to beat that, right? Yeah, 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. Wow. That the structural team is just, 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, it's amazing to be able to. Yeah have an idea, make a molecule, get some data, solve the structure, say, "Oh, well, I guess I was wrong on that, but it does bind. It just binds this way or that way. Yeah. Then be able to modify your thinking and then go forward. It's a full court press and with multiple inputs from multiple, if you will, perspectives. 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. Yeah. You've talked a lot about CRC so far and RCC and also neuroendocrine is a focus. Right just curious what you're thinking for your SSTR2 and your DLL3. Yeah small cell neuroendocrine type focus. Yeah. Maybe you could just expand just in general neuroendocrine, about those targets. Yeah. Exactly. That's a franchise, and 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. Currently recruiting, looking at zanza compared directly to everolimus, which is kind of standard of care, second-line plus, first line plus. Yeah In that situation as usually before cabo, the first oral therapy that was used. CABINET looked at cabo against placebo in later line patients. Yeah. This is going one or two steps up in terms of line of therapy, but also against an active control. You would imagine if that wins, that really kind of opens up a lot of additional leeway for us in terms of how that might be used, right? Yeah. The mainstay of neuroendocrine tumors is really SSAs. Yeah Somatostatin agonists, 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. They're big needles, can be painful. To be able to have an oral therapy that they can take once a day. Yeah 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. I guess that's a good example of it's still early. Yeah Wrapping up GLP tox, and hopefully we'll be in man later this year, but it really shows to us the important perspective we have from a commercial point of view which very few biotech companies have, unless you've got a big commercial molecule. Yeah 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? Yeah. 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? I think that's a good example that it's actually a really big indication. Yeah. 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 says that it could double or triple in size. Yeah over the next 10 years. We want to be part of that growth. If we're successful in helping that indication grow, then it means we're helping a lot more patients. Yeah. If we can do that with more than one molecule, if 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. Yeah 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. We can then take those revenues and reinvest those in R&D. Yeah Really move the next generation forward. Because from our point of view, value creation is all about building franchises. Building one after another. Two is better than one, four is better than three. The math just kind of gets very, very appealing after a while. Yeah. The core of Exelixis, I think also RCC is at the core and as a starting point, maybe going back to that, what do you see as key highlights, key next steps as you expand and grow within RCC? Yeah Sort of take it from where you were? Yeah, 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. Definitely some very fundamental questions about tumor biology at the most basic level, simply asked the question with cabo, can you inhibit the primary driver of tumor angiogenesis and the resistance mechanisms at the same time? Okay. It was a simple hypothesis, right? We were able to make the molecules that did that. As we've profiled them further, we learn more about their direct anti-tumor activity. We learn more about their impact on both sides of the immune system. 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 as kind of by accident, it came along with the ride. I think that serendipity and that empiricism is an important part of the process. People don't like talking about that, but that's just the reality of the situation. Yeah. You know that from your days, right? Absolutely. In pharma. Absolutely. We just went from there, right? Yeah. We did a lot of work ourselves, a lot of work in collaboration with other companies. got some great collaborations as part of our credo with the NCI. Fast forward, we have cabo's 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 and second-line plus NET because we've been able to generate kind of standard of care moving data. Yeah Be able to monetize that and kind of make that happen from the standpoint of our commercial depth and heft. That's something that we're focused on. Obviously, zanza, we've got a lot going on there. The STELLAR-304 trial is looking at non-clear cell. RCC in combination with nivo, no one's ever done a pivotal trial in that subpopulation of RCC. Yeah. 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- and third-line plus patients in both combination with belzutifan. We're very, very focused on being able to come up with approaches for frontline RCC as well. Yeah. I think that's 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. Yeah. 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? Yeah. Where we've got PDL1 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. Yeah. If you're talking about, again, we and others together the whole industry-wide effort, we've really moved the needle, right? Yeah. In terms of patient benefit for RCC, right? By looking at new MOAs, new ways of approaching the problem, and then doing the right combinations. This is then going the next level. You're working at a much higher base- Yeah than you were before, right? Absolutely. You've got to really thread the needle. Whatever you do has to have the tolerability and the activity for going to the next big increment in terms of, it be PFS and/or OS, right? It's a heavy lift and as we've seen with IO in general, right? Yeah. These things there can be a long increment between. Absolutely breakthroughs, right? Yeah. You have IL-2, and then you wait 25 years and you have PD-1s and CTLA-4s. Waiting 15 years Yeah People are trying a lot of stuff. Yeah. It's all great science, it just hasn't worked out, right? Yeah Every time you improve standard of care, it actually gets more difficult. Yeah Which is why for us, 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 costs, if you will. Yeah With our collaborator. We're also looking, in areas like NET, like CRC, melanoma, whatever, that kind of spreads the risk and has significant upside all by itself. Yeah. Again, before the fact, and we've seen this with cabo. You can design trials that you think are going to work. Yeah. Most of them do work. Yeah. Some of them are commercial blockbusters. Yeah Others are a little bit less compelling. Doing that all before the fact, there's 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. When you do see breakout data, you've got to capitalize on that with great speed and great conviction. Absolutely. Just hearing you talk about the bar and thinking about this is where KEYTRUDA/Pembro, how it evolved going against chemotherapy, it was a lower bar, and now, as you say, we waited a long time to see what can now go head to head and beat. Yeah KEYTRUDA. 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. Yeah. What do you do, what do you think to really increase your PTS? Nothing's ever de-risked, but just curious. Yeah What you think about that? It's a combination of both. I think we're a thinking, learning, self-reflecting organization. I think the part of the charm that we, I think, have been able to execute on is looking at what has worked. What hasn't worked, and then ask some of the hard questions about, okay, what have we learned in both? Yeah. Because you can learn a lot more from a failure than you can from a success sometimes, right? Yeah Not totally myopic, right? I think that's where the asking the right question around. Combinations is so important. Yeah. 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 squamous population post basically chemo pembro. I think that's a good example where, could we actually improve patient outcomes in the maintenance phase by combining with pembro. Yeah. 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? Yeah. Well, with zanza, maybe we have the opportunity, instead of trying to beat docetaxel head to head which is still used a ton. Yeah All kinds of different tumor types because it's really hard to beat. Yeah. It's really standard of care. Do we have the right molecule with zanza from a activity tolerability point of view that we can actually combine with docetaxel? That doublet against docetaxel, it could be a really interesting way to go. Yeah. That's part of the next wave, and 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. You can imagine if we can actually see benefit there. Yeah. That could apply to prostate cancer, that could apply to second-line, non-small cell lung cancer. We could ask the question, could you combine, say, zanzalintinib with standard chemo in front line CRC? kind of reinforcing this whole paradigm around building franchises across lines of therapy. Like we've done with cabo and RCC. 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. Yeah. Yeah. 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 running Exelixis? Anything that you are maybe happy you didn't wade into, whether you were considering it or not? Things that you feel- maybe weren't? It's a great question. 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? Yeah. 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. Yeah. 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. Yeah. To redouble down where we're active, where we're successful, it makes a lot of sense. 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. Yeah. 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, improve standard of care? 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 tougher go in terms of both pharmacodynamics, right? In terms of genetics, certainly then in terms of the actual pharmacology you're trying to impart there. I think that's the right move. Lots of important work's been done in thoracic oncology, 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 broadly based, right? Yeah. Look, we'll double down. 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. Yeah. Part of it is opportunistic, part of it is mechanistic. Nothing stops us from doing that, but I think to keep everybody focused on what we're trying to do, because there's literally millions of patients in this subsection that. Yeah 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. Focus is a good thing for us, for sure. Absolutely. Maybe just thinking forward-looking, what do you see of success for Exelixis in maybe a five-year timeline? Whatever that metric looks like, what do you sort of look forward and say, "I'm happy with this if this happens? Yeah. 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. That from the standpoint of any kind of quantitative metric, numbers of patients you treat, patient years. You can improve upon. All that drives revenue. It's the big circle, one drives the other. Again, I think the multi-franchise pipeline or franchise molecules kind of plays to that theme, right? Yeah. 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. That's the way you bring value to shareholders. The two are intimately connected in a way that one goes with the other. Yeah The value isn't just another molecule but it is mproving standard of care. For me, again, I'm not an oncologist, I'm a scientist by training. Over the years, that's become kind of a 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, right? Yeah. Why are we doing it? What are we doing? Do we want to invest here or someplace else? Ultimately, that's the goal. If we do that well, everything just kind of flows from there. Yeah. That's true, I would say, in general, within the industry, right? Oh, for sure. You change checkpoints. They dramatically change standard of care. Yeah. Now, it's taken another 15 years to go to the next level, and that's the business we're in, right? This is a tough business, right? Yeah. Everybody who plays in this space can appreciate that on a very, as I know you can, a very personal level, because it's hard. Yeah. You fail more than you succeed. You understand less than you think. Yeah. The factors at play. When I was dabbling in antibiotics or antivirals from a pure genetic point of view compared of what's happening with solid tumor oncology, where you can have, in one organ, and this has been proven by autopsy, you can have a liver post-resection that has got 10 different tumors with 10 different genotypes, right? Yeah. It's tough. You really need to bring every MOA to bear, every approach to bear, sometimes every modality to bear, to move the needle. I think any success you have to be humble about. Yeah It's tough. Yeah Success was hard earned. 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. Yeah Bring more success to patients. Yeah, for sure. That's wonderful. We've talked a lot with RCC, talked about neuroendocrine. Maybe just give a little bit of time for CRC, too. When you think of your strategic vision for CRC? Yeah The trials and the things that you'd like to do there, anything you'd like to highlight or? Yeah, 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. That's been an area that's been heavily invested in by a number of companies, all met with lack of success. Yeah. Because it's just a tough place to play. 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. Yeah. 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? Yeah. Patients with metastatic disease that you can see radiographically. Can you go up in the line of therapy to this? Yeah. To the 316 opportunity where you've got basically no metastatic, no visible, immeasurable metastatic disease. You have high-risk patients post-surgery in chemo who are bound to progress based upon kind of longitudinal data within six or so months, right? The question is, will the same MOAs that appear to work in measurable disease work in tumors that micro-metastases. Yeah that you can't visualize radiographically? Yeah. Right. I think it's a fascinating kind of connection between those two ends of the spectrum. The fact that we had success with zanza checkpoint, 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? Not everybody needs this. A lot of patients are cured with surgery and chemotherapy. That's fantastic for them. Those that aren't, we need to get in there, and for whatever reason, genetically, they need an extra boost. Yeah If we pick the right combinations and right kind of details around how that works, can we convert what is a relatively short time period to them, kind of real problems in terms of metastatic disease? Can we lengthen that? Look, for me, that's a noble enterprise, and obviously we're in it to run a business and ultimately drive shareholder value. There's a lot of patients, there's thousands of patients every year that could benefit from that. That's a big benefit both physically and, I mean, think about it, psychologically. Absolutely. They're just waiting. There's no standard of care for that right now for those high-risk patients post-surgery and chemotherapy. To be able to, if we're successful, have something to offer them, I mean. Yeah That's very motivating and inspiring for everybody at the company. 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 and 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 any other modalities that you think we haven't talked about enough. Yeah, let's move to the modalities. I think that's actually a good time. We talked about ADCs, right? Yeah. We obviously have a strong small molecule approach, bispecifics. I think one of the things that we've done over the last few years is we were traditionally a small molecule-focused shop. Yeah. On the restart of our discovery efforts understood that the more breadth we could bring into our discovery world and 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. That's 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. We've been able to transition that from small scale to at scale for GLP. Yeah GMP applications. That's all happened in a very seamless, focused fashion. The team is 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. I'm really pleased about that, and it just gives us that much more kind of therapeutic and pharmacological breadth. Yeah To be able to ask important questions, right? Now unlike a couple of years ago, pre-expanding into these biologics, we were like, "Okay, 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? We can do that as well as anybody, right? Yeah. The scale up, 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 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. You talked earlier. Excuse me. In our last couple 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've mostly focused on drug development. Maybe just in the last couple of minutes, anything from the commercial side, financial side that you think is important to talk about the strategy and how you execute? Yeah, 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. Everything works together in 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? That's the way it has to be, right? Having people in silos sitting in their offices- Yeah drawing structures and thinking about whatever, that doesn't work, right? Yeah. 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. 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? Yeah. To be able to have that depth and that breadth and having that mindset that says, "Good idea, but a tiny indication," or, "Good idea, but don't forget about this competition," or, "Not so good idea." I mean, having that analysis, it happens automatically almost. I don't need to organize it just happens when the people are talking, and there's the right level of engagement and accountability about making that work. In that regard, it's super fun to watch. It's that easy. Yeah. Sometimes there's just things we don't know, and we have to be able to model effectively and then we're paid to make decisions without having perfect insight into all the different variables, and that's part of the job too. 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. 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. Thank you for sharing your strategy, your future vision, and really appreciate your time today. Fantastic. It's been a great day. Appreciate the invite and look forward to seeing you again.

Speaker 1: 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. Hi, my name is Jeffrey Walch. hi my name is jeffrey walch I co-lead the U.S. biotechnology coverage at Bernstein. 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. 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. look forward to the conversation and thank you for attending

Speaker 2: All right. Great to be here. Thanks for the invitation today. 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. All right. all right Great to be here. great to be here Thanks for the invitation today. thanks for the invitation today We had a great day. we had a great day Looking forward to a great conversation. 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. 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

Speaker 1: That's perfect. 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. Personally, I'm excited to have this conversation today. I worked with your company back when I was at Bristol Myers Squibb, so know Exelixis well from my time. That's perfect. that's perfect Michael, really appreciate you and the team coming out today. 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. we've had you attend multiple of these conferences and really appreciate always hearing your story Personally, I'm excited to have this conversation today. personally i'm excited to have this conversation today I worked with your company back when I was at Bristol Myers Squibb, so know Exelixis well from my time. i worked with your company back when i was at bristol myers squibb so know exelixis well from my time

Speaker 2: That's right. Yeah. That's right. that's right Yeah. yeah

Speaker 1: as a drug developer. as a drug developer. as a drug developer

Speaker 2: Collaborators. Collaborators. collaborators

Speaker 1: Yes, collaborators. Yes, collaborators. yes collaborators

Speaker 2: That's right. That's right. that's right

Speaker 1: Dual LAG program. Look forward to a nice conversation and love to hear about your strategy and what you're thinking. Maybe just as a high level to kick us off, maybe just give an overview of Exelixis' multi-franchise strategy approach. Dual LAG program. dual lag program Look forward to a nice conversation and love to hear about your strategy and what you're thinking. look forward to a nice conversation and love to hear about your strategy and what you're thinking Maybe just as a high level to kick us off, maybe just give an overview of Exelixis' multi-franchise strategy approach. maybe just as a high level to kick us off maybe just give an overview of exelixis' multi-franchise strategy approach

Speaker 2: Yeah, for sure. 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 two 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. Yeah, for sure. yeah for sure 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 two in terms of how we approach really every aspect of biotech R&D, commercialization, the intersection of all those different aspects together. 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 two 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. look we're all in the same business to a certain degree

Speaker 1: Yeah. Yeah. yeah

Speaker 2: We want to help patients. I think we have an overriding focus on improving the standard of care for patients with cancer. We want to help patients. we want to help patients I think we have an overriding focus on improving the standard of care for patients with cancer. i think we have an overriding focus on improving the standard of care for patients with cancer 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. That is largely informed by the success of cabo that we've had over the years. 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. getting a p-value can sometimes be really challenging

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Other times it can be relatively straightforward. A p-value and a successful pivotal trial doesn't necessarily mean you're going to be a commercial success. The way you drive commercial success is you basically change standard of care. You make it such that you're 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. We've done that, I think pretty well with cabo. 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. It's really franchises. Other times it can be relatively straightforward. other times it can be relatively straightforward A p-value and a successful pivotal trial doesn't necessarily mean you're going to be a commercial success. a p-value and a successful pivotal trial doesn't necessarily mean you're going to be a commercial success The way you drive commercial success is you basically change standard of care. the way you drive commercial success is you basically change standard of care You make it such that you're 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. you make it such that you're 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 We've done that, I think pretty well with cabo. we've done that i think pretty well with cabo We've learned a lot. we've learned a lot We've done 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. 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 It's really franchises. it's really franchises As we talked about previously, we made it our big focus of our R&D day back in December. We really think about that in terms of different dimensions 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. We don't even focus on all of solid tumors, but we're really focused on moving the needle for GU and GI. As we talked about previously, we made it our big focus of our R&D day back in December. as we talked about previously we made it our big focus of our r&d day back in december We really think about that in terms of different dimensions in terms of how we view a franchise. we really think about that in terms of different dimensions in terms of how we view a franchise Obviously, you can have a franchise within a single molecule like cabo. obviously you can have a franchise within a single molecule like cabo You can reinforce franchises in indications. you can reinforce franchises in indications We focus in the GU and GI space. we focus in the gu and gi space We don't focus on all of heme. we don't focus on all of heme We don't even focus on all of solid tumors, but we're really focused on moving the needle for GU and GI. we don't even focus on all of solid tumors but we're really focused on moving the needle for gu and gi

Speaker 1: Yeah Yeah yeah

Speaker 2: Patients with cancer. We have, I think a pretty, not strict, but focused view on modalities. Patients with cancer. patients with cancer We have, I think a pretty, not strict, but focused view on modalities. we have i think a pretty not strict but focused view on modalities

Speaker 1: Yeah. Yeah. yeah

Speaker 2: We want to be able to put basically drug product into a bottle. Make that bottle available commercially. 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. We have to stay focused. That's, I think one of the things that we've tried to strive as a management team, is to really focus and prioritize. Strategy often comes down to not really so much what you're doing, but what you choose not to do. We want to be able to put basically drug product into a bottle. we want to be able to put basically drug product into a bottle Make that bottle available commercially. make that bottle available commercially It really focuses where we want to play relative to the modalities from a manufacturing point of view. 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're a relatively small company We can only do so much heavy lifting from a manufacturing point of view. 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. we obviously have great depth and expertise in small molecules and now biologics as we've moved in that direction We have to stay focused. we have to stay focused That's, I think one of the things that we've tried to strive as a management team, is to really focus and prioritize. that's i think one of the things that we've tried to strive as a management team is to really focus and prioritize Strategy often comes down to not really so much what you're doing, but what you choose not to do. strategy often comes down to not really so much what you're doing but what you choose not to do

Speaker 1: Right. Right. right

Speaker 2: 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. 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 excuse me, combine with relative to indications that we want to pursue within the GU and GI space. We obviously have some flexibility. 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. 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 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 excuse me, combine with relative to indications that we want to pursue within the GU and GI space. 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 excuse me combine with relative to indications that we want to pursue within the gu and gi space We obviously have some flexibility. we obviously have some flexibility

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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 strict category, but we have such interesting potential and activity that we can flex a little bit. Again, look for data in kind of a surveying effect and go. 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 and the pipeline and assets that we can find from external sources. 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 strict category, but we have such interesting potential and activity that we can flex a little bit. 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 strict category but we have such interesting potential and activity that we can flex a little bit Again, look for data in kind of a surveying effect and go. again look for data in kind of a surveying effect and go 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 and the pipeline and assets that we can find from external sources. 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 and the pipeline and assets that we can find from external sources

Speaker 1: That's great. You've 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? That's great. that's great You've said before that sort of you have this product strategy, the modality strategy, the tumor franchise strategy. you've 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? what would you say sort of distinguishes your approach between the three How are they similar? how are they similar How are they different? how are they different How you approach each of these three? how you approach each of these three

Speaker 2: Yeah. I would say, I think that they're all interrelated, right? You really have to be able to, in the most simplistic terms, kind of the Venn diagram view of the world. Yeah. yeah I would say, I think that they're all interrelated, right? i would say i think that they're all interrelated right You really have to be able to, in the most simplistic terms, kind of the Venn diagram view of the world. you really have to be able to in the most simplistic terms kind of the venn diagram view of the world The more overlap, the better, right? The more overlap, the better, right? the more overlap the better right 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 of where sometimes we collaborate, sometimes we compete, sometimes we're collaborating with the competition. 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? 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 of where sometimes we collaborate, sometimes we compete, sometimes we're collaborating with the competition. we've talked about this in bms i mean that interaction that collaboration which goes back for literally decades is a good example of where sometimes we collaborate sometimes we compete sometimes we're collaborating with the competition

Speaker 1: Yeah Yeah yeah

Speaker 2: 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. I think with that focus on, again, we're not looking at nano niche indications because. In terms of, say, some of the early cabo-nivo work. 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. 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 I think with that focus on, again, we're not looking at nano niche indications because. i think with that focus on again we're not looking at nano niche indications because

Speaker 1: Yeah Yeah yeah

Speaker 2: I think history has shown that can certainly help a small number of patients, but the upside can be limited to a certain degree. Again, we're focused on big indications in both the 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. I think history has shown that can certainly help a small number of patients, but the upside can be limited to a certain degree. i think history has shown that can certainly help a small number of patients but the upside can be limited to a certain degree Again, we're focused on big indications in both the 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. again we're focused on big indications in both the 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

Speaker 1: Yeah. I've seen the collaboration firsthand and think it's a great part of Exelixis. In terms of collaboration, anything that you look for, anything in terms of the benefits that the company has from that? When you think to collaborate with other companies, what are some of the things that you're looking to achieve? Yeah. yeah I've seen the collaboration firsthand and think it's a great part of Exelixis. i've seen the collaboration firsthand and think it's a great part of exelixis In terms of collaboration, anything that you look for, anything in terms of the benefits that the company has from that? in terms of collaboration anything that you look for anything in terms of the benefits that the company has from that When you think to collaborate with other companies, what are some of the things that you're looking to achieve? when you think to collaborate with other companies what are some of the things that you're looking to achieve

Speaker 2: Yeah. 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. 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. Yeah. yeah It's always the common language of our, do we have aligned goals and philosophies around what success looks like, number one? 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 t hat 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. do we have the right scientific i would say both overlap and complementarity t hat 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 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. 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

Speaker 1: Yeah Yeah yeah

Speaker 2: Even to operate in a way that, again, allows you to move in. I think 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 + 1 = 5 as opposed to two 1.5, which is often the case. 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, two leading single agents that actually had initial single-agent top line data literally on the same day. Even to operate in a way that, again, allows you to move in. even to operate in a way that again allows you to move in I think 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 + 1 = 5 as opposed to two 1.5 , which is often the case. i think 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 + 1 = 5 as opposed to two 1.5 which is often the case 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, two leading single agents that actually had initial single-agent top line data literally on the same day. 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 two leading single agents that actually had initial single-agent top line data literally on the same day

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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 move the needle for patients, what happens when you combine them? It was certainly a very rewarding process 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 move the needle for patients, what happens when you combine them? 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 move the needle for patients what happens when you combine them It was certainly a very rewarding process then. it was certainly a very rewarding process then

Speaker 1: Yeah Yeah yeah

Speaker 2: Collaborate between the two companies, the top KOLs, in a way that 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 continue to move cabo up in terms of being a market leader for RCC. Collaborate between the two companies, the top KOLs, in a way that really allowed us to move quickly and dramatically and to win on response rate, PFS, overall survival, and quality of life together. collaborate between the two companies the top kols in a way that 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 continue to move cabo up in terms of being a market leader for RCC. set us up really well to continue to move cabo up in terms of being a market leader for rcc

Speaker 1: Yeah. Yeah. yeah

Speaker 2: We're super excited about that, and I think that's success, and that comes after the typical kinds of failures that happen in this game. We're super excited about that, and I think that's success, and that comes after the typical kinds of failures that happen in this game. we're super excited about that and i think that's success and that comes after the typical kinds of failures that happen in this game

Speaker 1: Yeah. It's fine. Yeah. yeah It's fine. it's fine

Speaker 2: 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. 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. 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

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Done that with cabo. It's a molecule that has, I think, eight different indications or eight 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 enhancing overall survival. That comes on the back of four failed checkpoint-based trials. 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. Done that with cabo. done that with cabo It's a molecule that has, I think, eight different indications or eight successful pivotal trials that led to a very broad label. it's a molecule that has i think eight different indications or eight successful pivotal trials that led to a very broad label Obviously, it's a commercial success across different indications. 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. 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 enhancing overall survival. first trial in third-line plus crc was successful in enhancing overall survival That comes on the back of four failed checkpoint-based trials. that comes on the back of four failed checkpoint-based trials Different kind of clinical phenotype, if you will, getting a lot of positive feedback. 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. in terms of the market potential and we're under review right now

Speaker 1: Oh, congratulations. Oh, congratulations. oh congratulations

Speaker 2: 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. 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. 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

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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, you know, where you're in hypercompetitive space, indication-wise, versus maybe what's kind of wide open right now and pushing that envelope. It's indicative of how we think about building a franchise, right? 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, you know, where you're in hypercompetitive space, indication-wise, versus maybe what's kind of wide open right now and pushing that envelope. the right combinations the right indications the right lines of therapy really pushing the needle in terms of, you know where you're in hypercompetitive space indication-wise versus maybe what's kind of wide open right now and pushing that envelope

Speaker 1: Yeah Yeah yeah

Speaker 2: It is 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 than 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 seven ongoing or soon-to-start pivotal trials with the first wave. It is 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. it is 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've been profitable i think since 2017 or so We're very convinced that buying back shares right now makes a lot of sense than we have for the last several years because we just think we're undervalued based upon how the Street views zanza currently but w e think over time that will change. we're very convinced that buying back shares right now makes a lot of sense than we have for the last several years because we just think we're undervalued based upon how the street views zanza currently but w e think over time that will change We have seven ongoing or soon-to-start pivotal trials with the first wave. we have seven ongoing or soon-to-start pivotal trials with the first wave

Speaker 1: Yeah Yeah yeah

Speaker 2: I think the next wave kind of forming as we speak. 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? I think the next wave kind of forming as we speak. i think the next wave kind of forming as we speak 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? 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

Speaker 1: Yeah. Yeah. yeah

Speaker 2: What's the fourth franchise molecule? In our view, that's how you build really important growth in the story. How you kind of change the vector each time in terms of growth in terms of impact on patients, in terms of revenue, in terms of market cap can be. That's the focus. Team is 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. What's the fourth franchise molecule? what's the fourth franchise molecule In our view, that's how you build really important growth in the story. in our view that's how you build really important growth in the story How you kind of change the vector each time in terms of growth in terms of impact on patients, in terms of revenue, in terms of market cap can be. how you kind of change the vector each time in terms of growth in terms of impact on patients in terms of revenue in terms of market cap can be That's the focus. that's the focus Team is 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. team is 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

Speaker 1: Absolutely. On the point where you ended, 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? Absolutely. absolutely On the point where you ended, what do you think of how the pipeline is situated for future pan-tumor leadership? on the point where you ended what do you think of how the pipeline is situated for future pan-tumor leadership Anything in particular you want to highlight? anything in particular you want to highlight Anything you'd like to talk about? anything you'd like to talk about

Speaker 2: Yeah. We have four molecules in the clinic now. We've got a few more on the way. Obviously zanza is leading the charge. We've stopped really investing in cabo per se, and we've talked about that for the last few years now, why we're doing that. 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- Yeah. yeah We have four molecules in the clinic now. we have four molecules in the clinic now We've got a few more on the way. we've got a few more on the way Obviously zanza is leading the charge. obviously zanza is leading the charge We've stopped really investing in cabo per se, and we've talked about that for the last few years now, why we're doing that. we've stopped really investing in cabo per se and we've talked about that for the last few years now why we're doing that 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- 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-

Speaker 1: Yeah Yeah yeah

Speaker 2: to how we're doing it. 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. to how we're doing it. to how we're doing it 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. 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

Speaker 1: Yeah Yeah yeah

Speaker 2: Invest in and run, execute on pivotal trials. Invest in and run, execute on pivotal trials. invest in and run execute on pivotal trials

Speaker 1: Yeah. Yeah. yeah

Speaker 2: That's the only way, the p-values that you hope to get are the only way to move the needle. That's the only way, the p-values that you hope to get are the only way to move the needle. that's the only way the p-values that you hope to get are the only way to move the needle The attention of regulators and payers and HCPs down the table. A lot of companies, certainly in where we were 10 years ago, were hesitant to do that because it's a big gulp moment in terms of do I really want to spend $100, $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 understand you've got to be able to put that risk capital to work. The attention of regulators and payers and HCPs down the table. the attention of regulators and payers and hcps down the table A lot of companies, certainly in where we were 10 years ago, were hesitant to do that because it's a big gulp moment in terms of do I really want to spend $100, $200 million doing this? a lot of companies, certainly in where we were 10 years ago, were hesitant to do that because it's a big gulp moment in terms of do i really want to spend $100 $200 million doing this We do that readily. 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 understand you've got to be able to put that risk capital to work. 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 understand you've got to be able to put that risk capital to work

Speaker 1: Yeah Yeah yeah

Speaker 2: to be able to generate value for patients. 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. It's picking your fights to a certain degree, right? to be able to generate value for patients. to be able to generate value for patients 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. 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 It's picking your fights to a certain degree, right? it's picking your fights to a certain degree right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Obviously we're a leader in renal cancer with cabo, and we certainly plan to try to maintain that. Obviously we're a leader in renal cancer with cabo, and we certainly plan to try to maintain that. obviously we're a leader in renal cancer with cabo and we certainly plan to try to maintain that

Speaker 1: Yeah. Yeah. yeah

Speaker 2: With zanza, we've got three 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. With zanza, we've got three pivotal trials going right now, and probably we'll have more on the way in the future. with zanza we've got three 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. we think colon cancer is another good example of an indication that is ripe for innovation

Speaker 1: Yeah Yeah yeah

Speaker 2: The STELLAR-303 success really underscores that. We have a trial called STELLAR-316 looking at. The STELLAR-303 success really underscores that. the stellar-303 success really underscores that We have a trial called STELLAR-316 looking at. we have a trial called stellar-316 looking at

Speaker 1: Right Right right

Speaker 2: Really post-adjuvant kind of therapy for high-risk patients based upon the Signatera technology, where you can pre-select high-risk patients based upon their MRD status. Again, there's no standard of care for those patients there. Really post-adjuvant kind of therapy for high-risk patients based upon the Signatera technology, where you can pre-select high-risk patients based upon their MRD status. really post-adjuvant kind of therapy for high-risk patients based upon the signatera technology where you can pre-select high-risk patients based upon their mrd status Again, there's no standard of care for those patients there. again there's no standard of care for those patients there

Speaker 1: Yeah. Yeah. yeah

Speaker 2: They just kind of 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? If there's a way you can identify, pre-select 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. They just kind of 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? they just kind of 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 If there's a way you can identify, pre-select these high-risk patients as has been done recently in, say, bladder, with a very well, I think, just elegant technology. if there's a way you can identify pre-select 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. it really brings potentially a lot of value to patients

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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. 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 investing in a very thoughtful, pragmatic way. 303 and 316 kind of travel together. 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. we're constantly getting talk about one with a cabo and the other one comes up and vice versa 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 investing in a very thoughtful, pragmatic way. 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 investing in a very thoughtful pragmatic way

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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. 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. 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

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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. The pipeline is full. Early stage, we have four compounds in phase I, phase I-B a couple of ADCs, a USP1 inhibitor. Bispecific XB628 that we're just starting to look at zanzalintinib combinations with. That's super exciting. Looking to do more. We've got a couple of INDs kind of on the way. 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. 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 The pipeline is full. the pipeline is full Early stage, we have four compounds in phase I, phase I-B a couple of ADCs, a USP1 inhibitor. early stage we have four compounds in phase i phase i-b a couple of adcs a usp1 inhibitor Bispecific XB628 that we're just starting to look at zanzalintinib combinations with. bispecific xb628 that we're just starting to look at zanzalintinib combinations with That's super exciting. that's super exciting Looking to do more. looking to do more We've got a couple of INDs kind of on the way. we've got a couple of inds kind of on the way

Speaker 1: Yeah Yeah yeah

Speaker 2: with DLL3 and an oral SSTR2 antagonist. with DLL3 and an oral SSTR2 antagonist. with dll3 and an oral sstr2 antagonist

Speaker 1: Great Great great

Speaker 2: at the IND stage this year. We're looking, I think, pretty aggressively for potentially later-stage assets in the GU/GI space. at the IND stage this year. at the ind stage this year We're looking, I think, pretty aggressively for potentially later-stage assets in the GU/GI space. we're looking i think pretty aggressively for potentially later-stage assets in the gu/gi space

Speaker 1: Wow. Wow. wow

Speaker 2: We've got a great balance sheet, again, we're profitable. We've got a great balance sheet, again, we're profitable. we've got a great balance sheet again we're profitable

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Lots of cash flow. We have room to maneuver there as well. Again, 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. I think more often than not, we're going to be successful. Lots of cash flow. lots of cash flow We have room to maneuver there as well. we have room to maneuver there as well Again, 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. again 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 I think more often than not, we're going to be successful. i think more often than not we're going to be successful

Speaker 1: Yeah. Any of those ADCs in particular that you want to highlight or that you're excited about? Yeah. yeah Any of those ADCs in particular that you want to highlight or that you're excited about? any of those adcs in particular that you want to highlight or that you're excited about

Speaker 2: Yeah, I think they're both really interesting. There's more on the way. I think XB371 is tissue factor targeting ADC with a topo warhead. It's designed kind of de novo to play in the CRC, in the colon cancer space, where we want to build. Yeah, I think they're both really interesting. yeah i think they're both really interesting There's more on the way. there's more on the way I think XB371 is tissue factor targeting ADC with a topo warhead. i think xb371 is tissue factor targeting adc with a topo warhead It's designed kind of de novo to play in the CRC, in the colon cancer space, where we want to build. it's designed kind of de novo to play in the crc in the colon cancer space where we want to build

Speaker 1: Yeah. Yeah. yeah

Speaker 2: You can imagine getting to a point where, whether we have single agent or we have combinations with zanza, combinations with zanza and a checkpoint, just building off the foundation of 303. You can imagine getting to a point where, whether we have single agent or we have combinations with zanza, combinations with zanza and a checkpoint, just building off the foundation of 303. you can imagine getting to a point where whether we have single agent or we have combinations with zanza combinations with zanza and a checkpoint just building off the foundation of 303

Speaker 1: Yeah Yeah yeah

Speaker 2: That's how building a franchise and that indication across molecules. That's how building a franchise and that indication across molecules. that's how building a franchise and that indication across molecules

Speaker 1: Yeah Yeah yeah

Speaker 2: It's that kind of multifactorial view of what's the best way to bring value, additional value, change standard of care for patients. Again, part of it's obviously empirical. You've got to generate data. Part of it is very clear looking at if you looked at that example of 371, zanza, and say, a checkpoint, right? You've got three orthogonal MOAs. It's that kind of multifactorial view of what's the best way to bring value, additional value, change standard of care for patients. it's that kind of multifactorial view of what's the best way to bring value additional value change standard of care for patients Again, part of it's obviously empirical. again part of it's obviously empirical You've got to generate data. you've got to generate data Part of it is very clear looking at if you looked at that example of 371, zanza, and say, a checkpoint, right? part of it is very clear looking at if you looked at that example of 371 zanza and say a checkpoint right You've got three orthogonal MOAs. you've got three orthogonal moas

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Which arguably, kind of least de facto should have minimal AE overlap liabilities. The question is, are you picking the right pathways? Are you picking the right, if you will, warheads of the right agents to be able to bring maximal benefit at the right level of therapeutic index, right? Which arguably, kind of least de facto should have minimal AE overlap liabilities. which arguably kind of least de facto should have minimal ae overlap liabilities The question is, are you picking the right pathways? the question is are you picking the right pathways Are you picking the right, if you will, warheads of the right agents to be able to bring maximal benefit at the right level of therapeutic index, right? are you picking the right if you will warheads of the right agents to be able to bring maximal benefit at the right level of therapeutic index right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: It's theoretical. You look at the situation, you look at the genetics, you look at the evolution of how that indication is actually standing from a standard of care point of view. It's theoretical. it's theoretical You look at the situation, you look at the genetics, you look at the evolution of how that indication is actually standing from a standard of care point of view. you look at the situation you look at the genetics you look at the evolution of how that indication is actually standing from a standard of care point of view

Speaker 1: Yeah Yeah yeah

Speaker 2: How it's treated, and then you've got to look downfield two years, five years, 10 years and say, "Okay, how am I going to move the needle in that timeframe?" It's a bit of putting the Carnac hat on some important kind of forward-looking questions. We're not doing anything to change standard of care today. How it's treated, and then you've got to look downfield two years, five years, 10 years and say, "Okay, how am I going to move the needle in that timeframe?" It's a bit of putting the Carnac hat on some important kind of forward-looking questions. how it's treated and then you've got to look downfield two years five years 10 years and say "okay how am i going to move the needle in that timeframe?" it's a bit of putting the carnac hat on some important kind of forward-looking questions We're not doing anything to change standard of care today. we're not doing anything to change standard of care today It's always what happens three years, five years down the road. It's always what happens three years, five years down the road. it's always what happens three years five years down the road

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Everything is moving so quickly. You've got to almost pre-select where you think the bar is going to be, and then try to beat that, right? Yeah, 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. Everything is moving so quickly. everything is moving so quickly You've got to almost pre-select where you think the bar is going to be, and then try to beat that, right? you've got to almost pre-select where you think the bar is going to be and then try to beat that right Yeah, there's a lot going on, and it's fascinating to watch the technology advancements on the translational side c ertainly on the discovery side, we have our own cryo-EM. yeah there's a lot going on and it's fascinating to watch the technology advancements on the translational side c ertainly on the discovery side we have our own cryo-em

Speaker 1: Wow. Wow. wow

Speaker 2: That the structural team is just, 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, it's amazing to be able to. That the structural team is just, 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, it's amazing to be able to. that the structural team is just 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 it's amazing to be able to

Speaker 1: Yeah Yeah yeah

Speaker 2: have an idea, make a molecule, get some data, solve the structure, say, "Oh, well, I guess I was wrong on that, but it does bind. It just binds this way or that way. have an idea, make a molecule, get some data, solve the structure, say, "Oh, well, I guess I was wrong on that, but it does bind. have an idea make a molecule get some data solve the structure say "oh well i guess i was wrong on that but it does bind It just binds this way or that way. it just binds this way or that way

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Then be able to modify your thinking and then go forward. It's a full court press and with multiple inputs from multiple, if you will, perspectives. 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. Then be able to modify your thinking and then go forward. then be able to modify your thinking and then go forward It's a full court press and with multiple inputs from multiple, if you will, perspectives. it's a full court press and with multiple inputs from multiple if you will perspectives 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. 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

Speaker 1: Yeah. You've talked a lot about CRC so far and RCC and also neuroendocrine is a focus. Yeah. yeah You've talked a lot about CRC so far and RCC and also neuroendocrine is a focus. you've talked a lot about crc so far and rcc and also neuroendocrine is a focus

Speaker 2: Right Right right

Speaker 1: just curious what you're thinking for your SSTR2 and your DLL3. just curious what you're thinking for your SSTR2 and your DLL3. just curious what you're thinking for your sstr2 and your dll3

Speaker 2: Yeah Yeah yeah

Speaker 1: small cell neuroendocrine type focus. small cell neuroendocrine type focus. small cell neuroendocrine type focus

Speaker 2: Yeah. Yeah. yeah

Speaker 1: Maybe you could just expand just in general neuroendocrine, about those targets. Maybe you could just expand just in general neuroendocrine, about those targets. maybe you could just expand just in general neuroendocrine about those targets

Speaker 2: Yeah. Exactly. That's a franchise, and 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. Currently recruiting, looking at zanza compared directly to everolimus, which is kind of standard of care, second-line plus, first line plus. Yeah. yeah Exactly. exactly That's a franchise, and we talked about this in December, where we're just starting kind of scraping the surface with cabo. that's a franchise and 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. based upon the cabinet study we've got the stellar-311 study that's ongoing Currently recruiting, looking at zanza compared directly to everolimus, which is kind of standard of care, second-line plus, first line plus. currently recruiting looking at zanza compared directly to everolimus which is kind of standard of care second-line plus first line plus

Speaker 1: Yeah Yeah yeah

Speaker 2: In that situation as usually before cabo, the first oral therapy that was used. CABINET looked at cabo against placebo in later line patients. In that situation as usually before cabo, the first oral therapy that was used. in that situation as usually before cabo the first oral therapy that was used CABINET looked at cabo against placebo in later line patients. cabinet looked at cabo against placebo in later line patients

Speaker 1: Yeah. Yeah. yeah

Speaker 2: This is going one or two steps up in terms of line of therapy, but also against an active control. You would imagine if that wins, that really kind of opens up a lot of additional leeway for us in terms of how that might be used, right? This is going one or two steps up in terms of line of therapy, but also against an active control. this is going one or two steps up in terms of line of therapy but also against an active control You would imagine if that wins, that really kind of opens up a lot of additional leeway for us in terms of how that might be used, right? you would imagine if that wins that really kind of opens up a lot of additional leeway for us in terms of how that might be used right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: The mainstay of neuroendocrine tumors is really SSAs. The mainstay of neuroendocrine tumors is really SSAs. the mainstay of neuroendocrine tumors is really ssas

Speaker 1: Yeah Yeah yeah

Speaker 2: Somatostatin agonists, 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. They're big needles, can be painful. To be able to have an oral therapy that they can take once a day. Somatostatin agonists, which are all peptidic and parenterally administered. somatostatin agonists 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. 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. these are all subcu injections They're big needles, can be painful. they're big needles can be painful To be able to have an oral therapy that they can take once a day. to be able to have an oral therapy that they can take once a day

Speaker 1: Yeah Yeah yeah

Speaker 2: 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. I guess that's a good example of it's still early. At breakfast or at night would certainly simplify, not only simplify administration, but from a PK/PD point of view. 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. 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 I guess that's a good example of it's still early. i guess that's a good example of it's still early

Speaker 1: Yeah Yeah yeah

Speaker 2: Wrapping up GLP tox, and hopefully we'll be in man later this year, but it really shows to us the important perspective we have from a commercial point of view which very few biotech companies have, unless you've got a big commercial molecule. Wrapping up GLP tox, and hopefully we'll be in man later this year, but it really shows to us the important perspective we have from a commercial point of view which very few biotech companies have, unless you've got a big commercial molecule. wrapping up glp tox and hopefully we'll be in man later this year but it really shows to us the important perspective we have from a commercial point of view which very few biotech companies have unless you've got a big commercial molecule

Speaker 1: Yeah Yeah yeah

Speaker 2: 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? 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? 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

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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? I think that's a good example that it's actually a really big indication. 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? 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 I think that's a good example that it's actually a really big indication. i think that's a good example that it's actually a really big indication

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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 says that it could double or triple in size. 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 says that it could double or triple in size. 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 says that it could double or triple in size

Speaker 1: Yeah Yeah yeah

Speaker 2: over the next 10 years. We want to be part of that growth. If we're successful in helping that indication grow, then it means we're helping a lot more patients. over the next 10 years. over the next 10 years We want to be part of that growth. we want to be part of that growth If we're successful in helping that indication grow, then it means we're helping a lot more patients. if we're successful in helping that indication grow then it means we're helping a lot more patients

Speaker 1: Yeah. Yeah. yeah

Speaker 2: If we can do that with more than one molecule, if 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. If we can do that with more than one molecule, if it's cabo, if it's zanza , if it's the SSTR2 story. if we can do that with more than one molecule if it's cabo if it's zanza if it's the sstr2 story If it's DLL3. 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. if we can be part of that and own pieces of that pie as opposed to one pie as it's growing

Speaker 1: Yeah Yeah yeah

Speaker 2: 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. We can then take those revenues and reinvest those in R&D. 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. 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 We can then take those revenues and reinvest those in R&D. we can then take those revenues and reinvest those in r&d

Speaker 1: Yeah Yeah yeah

Speaker 2: Really move the next generation forward. Because from our point of view, value creation is all about building franchises. Building one after another. Two is better than one, four is better than three. The math just kind of gets very, very appealing after a while. Yeah. Really move the next generation forward. really move the next generation forward Because from our point of view, value creation is all about building franchises. because from our point of view value creation is all about building franchises Building one after another. building one after another Two is better than one, four is better than three. two is better than one four is better than three The math just kind of gets very, very appealing after a while. the math just kind of gets very very appealing after a while Yeah. yeah

Speaker 1: The core of Exelixis, I think also RCC is at the core and as a starting point, maybe going back to that, what do you see as key highlights, key next steps as you expand and grow within RCC? The core of Exelixis, I think also RCC is at the core and as a starting point, maybe going back to that, what do you see as key highlights, key next steps as you expand and grow within RCC? the core of exelixis i think also rcc is at the core and as a starting point maybe going back to that what do you see as key highlights key next steps as you expand and grow within rcc

Speaker 2: Yeah Yeah yeah

Speaker 1: Sort of take it from where you were? Sort of take it from where you were? sort of take it from where you were

Speaker 2: Yeah, 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. Yeah, no, it's a really interesting kind of look back in terms of where it was back in the early teens. yeah 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. first-gen molecules second-gen molecules were kind of percolating along I think we really changed the landscape there by asking. i think we really changed the landscape there by asking

Speaker 1: Definitely Definitely definitely

Speaker 2: some very fundamental questions about tumor biology at the most basic level, simply asked the question with cabo, can you inhibit the primary driver of tumor angiogenesis and the resistance mechanisms at the same time? Okay. It was a simple hypothesis, right? We were able to make the molecules that did that. As we've profiled them further, we learn more about their direct anti-tumor activity. some very fundamental questions about tumor biology at the most basic level, simply asked the question with cabo, can you inhibit the primary driver of tumor angiogenesis and t he resistance mechanisms at the same time? some very fundamental questions about tumor biology at the most basic level simply asked the question with cabo can you inhibit the primary driver of tumor angiogenesis and t he resistance mechanisms at the same time Okay. okay It was a simple hypothesis, right? We were able to make the molecules that did that. it was a simple hypothesis right? we were able to make the molecules that did that As we've profiled them further, we learn more about their direct anti-tumor activity. as we've profiled them further we learn more about their direct anti-tumor activity We learn more about their impact on both sides of the immune system. 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 as kind of by accident, it came along with the ride. I think that serendipity and that empiricism is an important part of the process. People don't like talking about that, but that's just the reality of the situation. We learn more about their impact on both sides of the immune system. we learn more about their impact on both sides of the immune system 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. 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 as kind of by accident, it came along with the ride. part of it on purpose part of it as kind of by accident it came along with the ride I think that serendipity and that empiricism is an important part of the process. i think that serendipity and that empiricism is an important part of the process People don't like talking about that, but that's just the reality of the situation. people don't like talking about that but that's just the reality of the situation

Speaker 1: Yeah. Yeah. yeah

Speaker 2: You know that from your days, right? You know that from your days, right? you know that from your days right

Speaker 1: Absolutely. Absolutely. absolutely

Speaker 2: In pharma. In pharma. in pharma

Speaker 1: Absolutely. Absolutely. absolutely

Speaker 2: We just went from there, right? We just went from there, right? we just went from there right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: We did a lot of work ourselves, a lot of work in collaboration with other companies. We did a lot of work ourselves, a lot of work in collaboration with other companies. we did a lot of work ourselves a lot of work in collaboration with other companies got some great collaborations as part of our credo with the NCI. Fast forward, we have cabo's 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 and second-line plus NET because we've been able to generate kind of standard of care moving data. got some great collaborations as part of our credo with the NCI. got some great collaborations as part of our credo with the nci Fast forward, we have cabo's the leading TKI for RCC. fast forward we have cabo's the leading tki for rcc It's the leading TKI in frontline IO TKI combinations. it's the leading tki in frontline io tki combinations It's the leading TKI in second-line plus leading oral therapy and second-line plus NET because we've been able to generate kind of standard of care moving data. it's the leading tki in second-line plus leading oral therapy and second-line plus net because we've been able to generate kind of standard of care moving data

Speaker 1: Yeah Yeah yeah

Speaker 2: Be able to monetize that and kind of make that happen from the standpoint of our commercial depth and heft. That's something that we're focused on. Obviously, zanza, we've got a lot going on there. The STELLAR-304 trial is looking at non-clear cell. RCC in combination with nivo, no one's ever done a pivotal trial in that subpopulation of RCC. Be able to monetize that and kind of make that happen from the standpoint of our commercial depth and heft. be able to monetize that and kind of make that happen from the standpoint of our commercial depth and heft That's something that we're focused on. that's something that we're focused on Obviously, zanza, we've got a lot going on there. obviously zanza we've got a lot going on there The STELLAR-304 trial is looking at non-clear cell. the stellar-304 trial is looking at non-clear cell RCC in combination with nivo, no one's ever done a pivotal trial in that subpopulation of RCC. rcc in combination with nivo no one's ever done a pivotal trial in that subpopulation of rcc

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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- and third-line plus patients in both combination with belzutifan. We're very, very focused on being able to come up with approaches for frontline RCC as well. We're super excited about that. 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- and third-line plus patients in both combination with belzutifan. 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- and third-line plus patients in both combination with belzutifan We're very, very focused on being able to come up with approaches for frontline RCC as well. we're very very focused on being able to come up with approaches for frontline rcc as well

Speaker 1: Yeah. Yeah. yeah

Speaker 2: I think that's 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. I think that's 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. i think that's 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. the importance of i think asking the question a little bit differently

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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? 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? 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

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Where we've got PDL1 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. Where we've got PDL1 and NKG2A, the natural killer cell ligand to be able to kind of find the right balance of additional potential activity. where we've got pdl1 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. okay without having a lot more tox

Speaker 1: Yeah. Yeah. yeah

Speaker 2: If you're talking about, again, we and others together the whole industry-wide effort, we've really moved the needle, right? If you're talking about, again, we and others together the whole industry-wide effort, we've really moved the needle, right? if you're talking about again we and others together the whole industry-wide effort we've really moved the needle right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: In terms of patient benefit for RCC, right? By looking at new MOAs, new ways of approaching the problem, and then doing the right combinations. This is then going the next level. You're working at a much higher base- In terms of patient benefit for RCC, right? in terms of patient benefit for rcc right By looking at new MOAs, new ways of approaching the problem, and then doing the right combinations. by looking at new moas new ways of approaching the problem and then doing the right combinations This is then going the next level. this is then going the next level You're working at a much higher base- you're working at a much higher base-

Speaker 1: Yeah Yeah yeah

Speaker 2: than you were before, right? than you were before, right? than you were before right

Speaker 1: Absolutely. Absolutely. absolutely

Speaker 2: You've got to really thread the needle. Whatever you do has to have the tolerability and the activity for going to the next big increment in terms of, it be PFS and/or OS, right? It's a heavy lift and as we've seen with IO in general, right? You've got to really thread the needle. you've got to really thread the needle Whatever you do has to have the tolerability and t he activity for going to the next big increment in terms of, it be PFS and/or OS, right? whatever you do has to have the tolerability and t he activity for going to the next big increment in terms of it be pfs and/or os right It's a heavy lift and as we've seen with IO in general, right? it's a heavy lift and as we've seen with io in general right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: These things there can be a long increment between. These things there can be a long increment between. these things there can be a long increment between

Speaker 1: Absolutely Absolutely absolutely

Speaker 2: breakthroughs, right? breakthroughs, right? breakthroughs right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: You have IL-2, and then you wait 25 years and you have PD-1s and CTLA-4s. You have IL-2, and then you wait 25 years and you have PD-1s and CTLA-4s. you have il-2 and then you wait 25 years and you have pd-1s and ctla-4s

Speaker 1: Waiting Waiting waiting

Speaker 2: 15 years 15 years 15 years

Speaker 1: Yeah Yeah yeah

Speaker 2: People are trying a lot of stuff. People are trying a lot of stuff. people are trying a lot of stuff

Speaker 1: Yeah. Yeah. yeah

Speaker 2: It's all great science, it just hasn't worked out, right? It's all great science, it just hasn't worked out, right? it's all great science it just hasn't worked out right

Speaker 1: Yeah Yeah yeah

Speaker 2: Every time you improve standard of care, it actually gets more difficult. Every time you improve standard of care, it actually gets more difficult. every time you improve standard of care it actually gets more difficult

Speaker 1: Yeah Yeah yeah

Speaker 2: Which is why for us, 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 costs, if you will. Which is why for us, I think it's really important that we are committed to our leadership in RCC. which is why for us 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 costs, if you will. we're investing there we're doing it the right way in terms of sharing the costs if you will

Speaker 1: Yeah Yeah yeah

Speaker 2: With our collaborator. We're also looking, in areas like NET, like CRC, melanoma, whatever, that kind of spreads the risk and has significant upside all by itself. With our collaborator. with our collaborator We're also looking, in areas like NET, like CRC, melanoma, whatever, that kind of spreads the risk and has significant upside all by itself. we're also looking in areas like net like crc melanoma whatever that kind of spreads the risk and has significant upside all by itself

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Again, before the fact, and we've seen this with cabo. You can design trials that you think are going to work. Again, before the fact, and we've seen this with cabo. again before the fact and we've seen this with cabo You can design trials that you think are going to work. you can design trials that you think are going to work

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Most of them do work. Most of them do work. most of them do work

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Some of them are commercial blockbusters. Some of them are commercial blockbusters. some of them are commercial blockbusters

Speaker 1: Yeah Yeah yeah

Speaker 2: Others are a little bit less compelling. Doing that all before the fact, there's 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. When you do see breakout data, you've got to capitalize on that with great speed and great conviction. Others are a little bit less compelling. others are a little bit less compelling Doing that all before the fact, there's so many factors that you just can't control for. doing that all before the fact there's 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. you've got to have the right mix of trials and combinations and lines of therapy to be able to cover all the bases When you do see breakout data, you've got to capitalize on that with great speed and great conviction. when you do see breakout data you've got to capitalize on that with great speed and great conviction

Speaker 1: Absolutely. Just hearing you talk about the bar and thinking about this is where KEYTRUDA/Pembro, how it evolved going against chemotherapy, it was a lower bar, and now, as you say, we waited a long time to see what can now go head to head and beat. Absolutely. absolutely Just hearing you talk about the bar and thinking about this is where KEYTRUDA/Pembro, how it evolved going against chemotherapy, it was a lower bar, and now, as you say, we waited a long time to see what can now go head to head and beat. just hearing you talk about the bar and thinking about this is where keytruda/pembro how it evolved going against chemotherapy it was a lower bar and now as you say we waited a long time to see what can now go head to head and beat

Speaker 2: Yeah Yeah yeah

Speaker 1: KEYTRUDA. On that point, when you think about the trials you guys are conducting. KEYTRUDA. keytruda On that point, when you think about the trials you guys are conducting. 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. How do you sort of stack the deck? how do you sort of stack the deck You've got great data. you've got great data You're now thinking what trial to do. you're now thinking what trial to do

Speaker 2: Yeah. Yeah. yeah

Speaker 1: What do you do, what do you think to really increase your PTS? Nothing's ever de-risked, but just curious. What do you do, what do you think to really increase your PTS? what do you do what do you think to really increase your pts Nothing's ever de-risked, but just curious. nothing's ever de-risked but just curious

Speaker 2: Yeah Yeah yeah

Speaker 1: What you think about that? What you think about that? what you think about that

Speaker 2: It's a combination of both. I think we're a thinking, learning, self-reflecting organization. I think the part of the charm that we, I think, have been able to execute on is looking at what has worked. What hasn't worked, and then ask some of the hard questions about, okay, what have we learned in both? It's a combination of both. it's a combination of both I think we're a thinking, learning, self-reflecting organization. i think we're a thinking learning self-reflecting organization I think the part of the charm that we, I think, have been able to execute on is looking at what has worked. i think the part of the charm that we i think have been able to execute on is looking at what has worked What hasn't worked, and then ask some of the hard questions about, okay, what have we learned in both? what hasn't worked and then ask some of the hard questions about okay what have we learned in both

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Because you can learn a lot more from a failure than you can from a success sometimes, right? Because you can learn a lot more from a failure than you can from a success sometimes, right? because you can learn a lot more from a failure than you can from a success sometimes right

Speaker 1: Yeah Yeah yeah

Speaker 2: Not totally myopic, right? I think that's where the asking the right question around. Combinations is so important. Not totally myopic, right? not totally myopic right I think that's where the asking the right question around. i think that's where the asking the right question around Combinations is so important. combinations is so important

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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 squamous population post basically chemo pembro. I think that's a good example where, could we actually improve patient outcomes in the maintenance phase by combining with pembro. We have a phase II that we talked about, Dana talked about on earnings about a month ago in terms of looking a t a second-line maintenance of zanza plus pembro in a squamous population post basically chemo pembro. we have a phase ii that we talked about dana talked about on earnings about a month ago in terms of looking a t a second-line maintenance of zanza plus pembro in a squamous population post basically chemo pembro I think that's a good example where, could we actually improve patient outcomes in the maintenance phase by combining with pembro. i think that's a good example where could we actually improve patient outcomes in the maintenance phase by combining with pembro

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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? Same thinking goes, we've done a lot of work, say, in prostate cancer with cabo. 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. we had a trial in second-line lung cancer with cabo and atezo Those have all failed. those have all failed What have we learned from that? what have we learned from that

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Well, with zanza, maybe we have the opportunity, instead of trying to beat docetaxel head to head which is still used a ton. Well, with zanza, maybe we have the opportunity, instead of trying to beat docetaxel head to head which is still used a ton. well with zanza maybe we have the opportunity instead of trying to beat docetaxel head to head which is still used a ton

Speaker 1: Yeah Yeah yeah

Speaker 2: All kinds of different tumor types because it's really hard to beat. All kinds of different tumor types because it's really hard to beat. all kinds of different tumor types because it's really hard to beat

Speaker 1: Yeah. Yeah. yeah

Speaker 2: It's really standard of care. Do we have the right molecule with zanza from a activity tolerability point of view that we can actually combine with docetaxel? That doublet against docetaxel, it could be a really interesting way to go. It's really standard of care. it's really standard of care Do we have the right molecule with zanza from a activity tolerability point of view that we can actually combine with docetaxel? do we have the right molecule with zanza from a activity tolerability point of view that we can actually combine with docetaxel That doublet against docetaxel, it could be a really interesting way to go. that doublet against docetaxel it could be a really interesting way to go

Speaker 1: Yeah. Yeah. yeah

Speaker 2: That's part of the next wave, and 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. You can imagine if we can actually see benefit there. That's part of the next wave, and 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. that's part of the next wave and 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 You can imagine if we can actually see benefit there. you can imagine if we can actually see benefit there

Speaker 1: Yeah. Yeah. yeah

Speaker 2: That could apply to prostate cancer, that could apply to second-line, non-small cell lung cancer. We could ask the question, could you combine, say, zanzalintinib with standard chemo in front line CRC? kind of reinforcing this whole paradigm around building franchises across lines of therapy. Like we've done with cabo and RCC. 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. That could apply to prostate cancer, that could apply to second-line, non-small cell lung cancer. that could apply to prostate cancer that could apply to second-line non-small cell lung cancer We could ask the question, could you combine, say, zanzalintinib with standard chemo in front line CRC? kind of reinforcing this whole paradigm around building franchises across lines of therapy. we could ask the question could you combine say zanzalintinib with standard chemo in front line crc kind of reinforcing this whole paradigm around building franchises across lines of therapy Like we've done with cabo and RCC. like we've done with cabo and rcc 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. 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

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Yeah. Yeah. yeah

Speaker 1: 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 running Exelixis? Anything that you are maybe happy you didn't wade into, whether you were considering it or not? Things that you feel- maybe weren't? 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. 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 running Exelixis? is there anything that as you reflect on your time running exelixis Anything that you are maybe happy you didn't wade into, whether you were considering it or not? anything that you are maybe happy you didn't wade into whether you were considering it or not Things that you feel- maybe weren't? things that you feel- maybe weren't

Speaker 2: It's a great question. 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? It's a great question. it's a great question I think I've been, in terms of my scientific career, more tend to focus than be broad. 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. 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? i think the focus that we've done has been partly organic right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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. We have activity in GU and GI cancer, so let's double down there. 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. we've got a commercial organization that's built to excel in gu and gi

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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. It makes sense to build in there, right? 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. 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

Speaker 1: Yeah. Yeah. yeah

Speaker 2: To redouble down where we're active, where we're successful, it makes a lot of sense. 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. To redouble down where we're active, where we're successful, it makes a lot of sense. to redouble down where we're active where we're successful it makes a lot of sense 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. 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

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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, improve standard of care? 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 tougher go in terms of both pharmacodynamics, right? In terms of genetics, certainly then in terms of the actual pharmacology you're trying to impart there. I think that's the right move. Lots of important work's been done in thoracic oncology, 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 broadly based, right? They're so deep there. they're so deep there The combination approach is so successful. the combination approach is so successful Really asking the question, what do we have to offer there that could be different and could, again, improve standard of care? really asking the question what do we have to offer there that could be different and could again improve standard of care I think the conclusion that we made was probably not a lot. 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 tougher go in terms of both pharmacodynamics, right? let's focus in on solid tumors where it's just a much tougher go in terms of both pharmacodynamics right In terms of genetics, certainly then in terms of the actual pharmacology you're trying to impart there. in terms of genetics certainly then in terms of the actual pharmacology you're trying to impart there I think that's the right move. i think that's the right move Lots of important work's been done in thoracic oncology, breast cancer, those kinds of things. lots of important work's been done in thoracic oncology 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 broadly based, right? i don't think we could be as effective as we are in gu and gi if we were broadly based right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Look, we'll double down. 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. Look, we'll double down. look we'll double down We always have the option if our MOAs and our pharmacology overlaps with biology and another tumor type, we can always go there. 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. we're doing that now

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Part of it is opportunistic, part of it is mechanistic. Nothing stops us from doing that, but I think to keep everybody focused on what we're trying to do, because there's literally millions of patients in this subsection that. Part of it is opportunistic, part of it is mechanistic. part of it is opportunistic part of it is mechanistic Nothing stops us from doing that, but I think to keep everybody focused on what we're trying to do, because there's literally millions of patients in this subsection that. nothing stops us from doing that but i think to keep everybody focused on what we're trying to do because there's literally millions of patients in this subsection that

Speaker 1: Yeah Yeah yeah

Speaker 2: 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. Focus is a good thing for us, for sure. 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. 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 Focus is a good thing for us, for sure. focus is a good thing for us for sure

Speaker 1: Absolutely. Maybe just thinking forward-looking, what do you see of success for Exelixis in maybe a five-year timeline? Whatever that metric looks like, what do you sort of look forward and say, "I'm happy with this if this happens? Absolutely. absolutely Maybe just thinking forward-looking, what do you see of success for Exelixis in maybe a five-year timeline? maybe just thinking forward-looking what do you see of success for exelixis in maybe a five-year timeline Whatever that metric looks like, what do you sort of look forward and say, "I'm happy with this if this happens? whatever that metric looks like what do you sort of look forward and say "i'm happy with this if this happens

Speaker 2: Yeah. 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. That from the standpoint of any kind of quantitative metric, numbers of patients you treat, patient years. You can improve upon. All that drives revenue. It's the big circle, one drives the other. Again, I think the multi-franchise pipeline or franchise molecules kind of plays to that theme, right? Yeah. yeah No, it's a good question. no it's a good question It's something that we think about a lot. it's something that we think about a lot I think about success on a log scale, not a linear scale. i think about success on a log scale not a linear scale That from the standpoint of any kind of quantitative metric, numbers of patients you treat, patient years. that from the standpoint of any kind of quantitative metric numbers of patients you treat patient years You can improve upon. you can improve upon All that drives revenue. all that drives revenue It's the big circle, one drives the other. it's the big circle one drives the other Again, I think the multi-franchise pipeline or franchise molecules kind of plays to that theme, right? again i think the multi-franchise pipeline or franchise molecules kind of plays to that theme right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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. That's the way you bring value to shareholders. The two are intimately connected in a way that one goes with the other. 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. 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 That's the way you bring value to shareholders. that's the way you bring value to shareholders The two are intimately connected in a way that one goes with the other. the two are intimately connected in a way that one goes with the other

Speaker 1: Yeah Yeah yeah

Speaker 2: The value isn't just another molecule but it is mproving standard of care. For me, again, I'm not an oncologist, I'm a scientist by training. Over the years, that's become kind of a 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, right? The value isn't just another molecule but it is mproving standard of care. the value isn't just another molecule but it is mproving standard of care For me, again, I'm not an oncologist, I'm a scientist by training. for me again i'm not an oncologist i'm a scientist by training Over the years, that's become kind of a very clear guide for me. over the years that's become kind of a very clear guide for me If we're not actively changing standard of care, then w e need to ask the question, what are we doing, right? if we're not actively changing standard of care, then w e need to ask the question what are we doing right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Why are we doing it? What are we doing? Do we want to invest here or someplace else? Ultimately, that's the goal. If we do that well, everything just kind of flows from there. Why are we doing it? why are we doing it What are we doing? what are we doing Do we want to invest here or someplace else? do we want to invest here or someplace else Ultimately, that's the goal. ultimately that's the goal If we do that well, everything just kind of flows from there. if we do that well everything just kind of flows from there

Speaker 1: Yeah. Yeah. yeah

Speaker 2: That's true, I would say, in general, within the industry, right? That's true, I would say, in general, within the industry, right? that's true i would say in general within the industry right

Speaker 1: Oh, for sure. Oh, for sure. oh for sure

Speaker 2: You change checkpoints. They dramatically change standard of care. You change checkpoints. you change checkpoints They dramatically change standard of care. they dramatically change standard of care

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Now, it's taken another 15 years to go to the next level, and that's the business we're in, right? This is a tough business, right? Now, it's taken another 15 years to go to the next level, and that's the business we're in, right? now it's taken another 15 years to go to the next level and that's the business we're in right This is a tough business, right? this is a tough business right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Everybody who plays in this space can appreciate that on a very, as I know you can, a very personal level, because it's hard. Everybody who plays in this space can appreciate that on a very, as I know you can, a very personal level, because it's hard. everybody who plays in this space can appreciate that on a very as i know you can a very personal level because it's hard

Speaker 1: Yeah. Yeah. yeah

Speaker 2: You fail more than you succeed. You understand less than you think. You fail more than you succeed. you fail more than you succeed You understand less than you think. you understand less than you think

Speaker 1: Yeah. Yeah. yeah

Speaker 2: The factors at play. When I was dabbling in antibiotics or antivirals from a pure genetic point of view compared of what's happening with solid tumor oncology, where you can have, in one organ, and this has been proven by autopsy, you can have a liver post-resection that has got 10 different tumors with 10 different genotypes, right? The factors at play. the factors at play When I was dabbling in antibiotics or antivirals from a pure genetic point of view compared of what's happening with solid tumor oncology, where you can have, in one organ, and this has been proven by autopsy, you can have a liver post-resection that has got 10 different tumors with 10 different genotypes, right? when i was dabbling in antibiotics or antivirals from a pure genetic point of view compared of what's happening with solid tumor oncology where you can have in one organ and this has been proven by autopsy you can have a liver post-resection that has got 10 different tumors with 10 different genotypes right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: It's tough. You really need to bring every MOA to bear, every approach to bear, sometimes every modality to bear, to move the needle. I think any success you have to be humble about. It's tough. it's tough You really need to bring every MOA to bear, every approach to bear, sometimes every modality to bear, to move the needle. you really need to bring every moa to bear every approach to bear sometimes every modality to bear to move the needle I think any success you have to be humble about. i think any success you have to be humble about

Speaker 1: Yeah Yeah yeah

Speaker 2: It's tough. It's tough. it's tough

Speaker 1: Yeah Yeah yeah

Speaker 2: Success was hard earned. 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. Success was hard earned. success was hard earned 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. 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

Speaker 1: Yeah Yeah yeah

Speaker 2: Bring more success to patients. Yeah, for sure. Bring more success to patients. bring more success to patients Yeah, for sure. yeah for sure

Speaker 1: That's wonderful. We've talked a lot with RCC, talked about neuroendocrine. Maybe just give a little bit of time for CRC, too. When you think of your strategic vision for CRC? That's wonderful. that's wonderful We've talked a lot with RCC, talked about neuroendocrine. we've talked a lot with rcc talked about neuroendocrine Maybe just give a little bit of time for CRC, too. maybe just give a little bit of time for crc too When you think of your strategic vision for CRC? when you think of your strategic vision for crc

Speaker 2: Yeah Yeah yeah

Speaker 1: The trials and the things that you'd like to do there, anything you'd like to highlight or? The trials and the things that you'd like to do there, anything you'd like to highlight or? the trials and the things that you'd like to do there anything you'd like to highlight or

Speaker 2: Yeah, 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. That's been an area that's been heavily invested in by a number of companies, all met with lack of success. Yeah, we talked about that a lot already. yeah 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. 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. really interesting That's been an area that's been heavily invested in by a number of companies, all met with lack of success. that's been an area that's been heavily invested in by a number of companies all met with lack of success

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Because it's just a tough place to play. 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. Because it's just a tough place to play. because it's just a tough place to play We're very fortunate to be able to win there. 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. 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

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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? The foundation of success there. 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? can we take the same general approach where we have activity in terms of improving survival with measurable tumors right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Patients with metastatic disease that you can see radiographically. Can you go up in the line of therapy to this? Patients with metastatic disease that you can see radiographically. patients with metastatic disease that you can see radiographically Can you go up in the line of therapy to this? can you go up in the line of therapy to this

Speaker 1: Yeah. Yeah. yeah

Speaker 2: To the 316 opportunity where you've got basically no metastatic, no visible, immeasurable metastatic disease. To the 316 opportunity where you've got basically no metastatic, no visible, immeasurable metastatic disease. to the 316 opportunity where you've got basically no metastatic no visible, immeasurable metastatic disease You have high-risk patients post-surgery in chemo who are bound to progress based upon kind of longitudinal data within six or so months, right? The question is, will the same MOAs that appear to work in measurable disease work in tumors that micro-metastases. You have high-risk patients post-surgery i n chemo who are bound to progress based upon kind of longitudinal data within six or so months, right? you have high-risk patients post-surgery i n chemo who are bound to progress based upon kind of longitudinal data within six or so months right The question is, will the same MOAs that appear to work in measurable disease work in tumors that micro-metastases. the question is will the same moas that appear to work in measurable disease work in tumors that micro-metastases

Speaker 1: Yeah Yeah yeah

Speaker 2: that you can't visualize radiographically? that you can't visualize radiographically? that you can't visualize radiographically

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Right. I think it's a fascinating kind of connection between those two ends of the spectrum. Right. right I think it's a fascinating kind of connection between those two ends of the spectrum. i think it's a fascinating kind of connection between those two ends of the spectrum The fact that we had success with zanza checkpoint, 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? Not everybody needs this. A lot of patients are cured with surgery and chemotherapy. That's fantastic for them. Those that aren't, we need to get in there, and for whatever reason, genetically, they need an extra boost. The fact that we had success with zanza checkpoint, 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? the fact that we had success with zanza checkpoint 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 Not everybody needs this. not everybody needs this A lot of patients are cured with surgery and chemotherapy. a lot of patients are cured with surgery and chemotherapy That's fantastic for them. that's fantastic for them Those that aren't, we need to get in there, and for whatever reason, genetically, they n eed an extra boost. those that aren't we need to get in there and for whatever reason genetically, they n eed an extra boost

Speaker 1: Yeah Yeah yeah

Speaker 2: If we pick the right combinations and right kind of details around how that works, can we convert what is a relatively short time period to them, kind of real problems in terms of metastatic disease? Can we lengthen that? Look, for me, that's a noble enterprise, and obviously we're in it to run a business and ultimately drive shareholder value. There's a lot of patients, there's thousands of patients every year that could benefit from that. That's a big benefit both physically and, I mean, think about it, psychologically. If we pick the right combinations and right kind of details around how that works, can we convert what is a relatively short time period to them, kind of real problems in terms of metastatic disease? if we pick the right combinations and right kind of details around how that works, can we convert what is a relatively short time period to them, kind of real problems in terms of metastatic disease Can we lengthen that? can we lengthen that Look, for me, that's a noble enterprise, and obviously we're in it to run a business and ultimately drive shareholder value. look for me that's a noble enterprise and obviously we're in it to run a business and ultimately drive shareholder value There's a lot of patients, there's thousands of patients every year that c ould benefit from that. there's a lot of patients there's thousands of patients every year that c ould benefit from that That's a big benefit both physically and, I mean, think about it, psychologically. that's a big benefit both physically and i mean think about it psychologically

Speaker 1: Absolutely. Absolutely. absolutely

Speaker 2: They're just waiting. There's no standard of care for that right now for those high-risk patients post-surgery and chemotherapy. To be able to, if we're successful, have something to offer them, I mean. They're just waiting. they're just waiting There's no standard of care for that right now for those high-risk patients post-surgery and chemotherapy. there's no standard of care for that right now for those high-risk patients post-surgery and chemotherapy To be able to, if we're successful, have something to offer them, I mean. to be able to if we're successful have something to offer them i mean

Speaker 1: Yeah Yeah yeah

Speaker 2: That's very motivating and inspiring for everybody at the company. 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 and with high quality every single day. That's very motivating and inspiring for everybody at the company. that's very motivating and inspiring for everybody at the company We're serious about this stuff. 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 and with high quality every single day. we understand the stakes that are there for patients and we're doing everything we can to move the needle quickly and confidently and with high quality every single day

Speaker 1: 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 any other modalities that you think we haven't talked about enough. Well, we've talked about several different tumor types, CRC, RCC, neuroendocrine. 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? is there any other tumor type that you think would be worth highlighting If not, we can talk about maybe any other modalities that you think we haven't talked about enough. if not we can talk about maybe any other modalities that you think we haven't talked about enough

Speaker 2: Yeah, let's move to the modalities. I think that's actually a good time. We talked about ADCs, right? Yeah, let's move to the modalities. yeah let's move to the modalities I think that's actually a good time. i think that's actually a good time We talked about ADCs, right? we talked about adcs right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: We obviously have a strong small molecule approach, bispecifics. I think one of the things that we've done over the last few years is we were traditionally a small molecule-focused shop. We obviously have a strong small molecule approach, bispecifics. we obviously have a strong small molecule approach bispecifics I think one of the things that we've done over the last few years is we were traditionally a small molecule-focused shop. i think one of the things that we've done over the last few years is we were traditionally a small molecule-focused shop

Speaker 1: Yeah. Yeah. yeah

Speaker 2: On the restart of our discovery efforts understood that the more breadth we could bring into our discovery world and 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. That's 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. We've been able to transition that from small scale to at scale for GLP. On the restart of our discovery efforts understood that the more breadth we could bring into our discovery world and 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. on the restart of our discovery efforts understood that the more breadth we could bring into our discovery world and 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 That's 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. that's 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. 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 We've been able to transition that from small scale to at scale for GLP. we've been able to transition that from small scale to at scale for glp

Speaker 1: Yeah Yeah yeah

Speaker 2: GMP applications. That's all happened in a very seamless, focused fashion. The team is 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. I'm really pleased about that, and it just gives us that much more kind of therapeutic and pharmacological breadth. GMP applications. gmp applications That's all happened in a very seamless, focused fashion. that's all happened in a very seamless focused fashion The team is just first rate, right? the team is 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. 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 I'm really pleased about that, and it just gives us that much more kind of therapeutic and pharmacological breadth. i'm really pleased about that and it just gives us that much more kind of therapeutic and pharmacological breadth

Speaker 1: Yeah Yeah yeah

Speaker 2: To be able to ask important questions, right? Now unlike a couple of years ago, pre-expanding into these biologics, we were like, "Okay, 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. To be able to ask important questions, right? to be able to ask important questions right Now unlike a couple of years ago, pre-expanding into these biologics, we were like, "Okay, 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. now unlike a couple of years ago pre-expanding into these biologics we were like "okay 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 a small molecule This is an ADC. this is an adc This is a bispecific. this is a bispecific Let's go do it, right? We can do that as well as anybody, right? Let's go do it, right? let's go do it right We can do that as well as anybody, right? we can do that as well as anybody right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: The scale up, 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 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. The scale up, making things on a milligram scale can be easy. the scale up 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 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. making things on a kilogram scale you got to have the right people and the right opportunity with 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

Speaker 1: That's amazing. You talked earlier. That's amazing. that's amazing You talked earlier. you talked earlier

Speaker 2: Excuse me. Excuse me. excuse me

Speaker 1: In our last couple 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've mostly focused on drug development. Maybe just in the last couple of minutes, anything from the commercial side, financial side that you think is important to talk about the strategy and how you execute? In our last couple minutes here, you talked earlier about you have great financial position, stock buybacks. in our last couple 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. i mean we haven't talked too much about the financial commercial side of the company We've mostly focused on drug development. we've mostly focused on drug development Maybe just in the last couple of minutes, anything from the commercial side, financial side that you think is important to talk about the strategy and how you execute? maybe just in the last couple of minutes anything from the commercial side financial side that you think is important to talk about the strategy and how you execute

Speaker 2: Yeah, 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. Everything works together in 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? That's the way it has to be, right? Having people in silos sitting in their offices- Yeah, I would say at the highest level, it's all integrated. yeah i would say at the highest level it's all integrated We have one strategy. we have one strategy We have one focus. we have one focus Obviously, we have different groups and different responsibilities and accountabilities in terms of how that works. obviously we have different groups and different responsibilities and accountabilities in terms of how that works Everything works together in the way we're organized, the way we're co-located. everything works together in 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? the commercial people the competitive intelligence people the discovery people that leadership operation is talking on an hourly basis right That's the way it has to be, right? that's the way it has to be right Having people in silos sitting in their offices- having people in silos sitting in their offices-

Speaker 1: Yeah Yeah yeah

Speaker 2: drawing structures and thinking about whatever, that doesn't work, right? drawing structures and thinking about whatever, that doesn't work, right? drawing structures and thinking about whatever that doesn't work right

Speaker 1: Yeah. Yeah. yeah

Speaker 2: 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. 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? 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? 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. we need to have a full view of what the opportunity is 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? 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

Speaker 1: Yeah. Yeah. yeah

Speaker 2: To be able to have that depth and that breadth and having that mindset that says, "Good idea, but a tiny indication," or, "Good idea, but don't forget about this competition," or, "Not so good idea." I mean, having that analysis, it happens automatically almost. I don't need to organize it just happens when the people are talking, and there's the right level of engagement and accountability about making that work. In that regard, it's super fun to watch. It's that easy. To be able to have that depth and that breadth and having that mindset that says, "Good idea, but a tiny indication," or, "Good idea, but don't forget about this competition," or, "Not so good idea." I mean, having that analysis, it happens automatically almost. to be able to have that depth and that breadth and having that mindset that says "good idea but a tiny indication," or "good idea but don't forget about this competition," or "not so good idea." i mean having that analysis it happens automatically almost I don't need to organize it just happens when the people are talking, and there's the right level of engagement and accountability about making that work. i don't need to organize it just happens when the people are talking and there's the right level of engagement and accountability about making that work In that regard, it's super fun to watch. in that regard it's super fun to watch It's that easy. it's that easy

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Sometimes there's just things we don't know, and we have to be able to model effectively and then we're paid to make decisions without having perfect insight into all the different variables, and that's part of the job too. 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. 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. Sometimes there's just things we don't know, and we have to be able to model effectively and then we're paid to make decisions without having perfect insight into all the different variables, and that's part of the job too. sometimes there's just things we don't know and we have to be able to model effectively and then we're paid to make decisions without having perfect insight into all the different variables and that's part of the job too 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. 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 Great team. great team Everybody works together really well. 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. 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

Speaker 1: 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. Thank you for sharing your strategy, your future vision, and really appreciate your time today. Well, that's amazing. well that's amazing I mean, this has been a great conversation. 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. i really appreciate the chance to learn from you and i'm sure everyone else listening has as well Thank you for sharing your strategy, your future vision, and really appreciate your time today. thank you for sharing your strategy your future vision and really appreciate your time today

Speaker 2: Fantastic. It's been a great day. Appreciate the invite and look forward to seeing you again. Fantastic. fantastic It's been a great day. it's been a great day Appreciate the invite and look forward to seeing you again. appreciate the invite and look forward to seeing you again