Good afternoon, everyone. We're now on the third day of the SVB Securities Global Biopharma Conference. I'm Ken Shields, Vice President of Equity Research helping to cover the targeted oncology universe of companies. I'm excited to have Exelixis join us, and we have Chris Senner, Executive Vice President and Chief Financial Officer, and Peter Lamb, Executive Vice President of Scientific Strategy here. Thank you both for spending some time with us. Thanks for having us. As a quick reminder to those tuned in, we have a chat box below where you can ask questions in real time, and we will try to get them asked and answered, if appropriate or as time permits so j ust jumping right in, perhaps you guys can start with a brief overview of Exelixis and help refresh those in the audience that may not be as familiar with the business. Thanks. Okay. Yeah, thanks for having us a nd, Ken, thanks for the opportunity to talk here. I'll start from a Exelixis perspective. You know, we're a commercial stage oncology company. You know, we had product revenue last year about $1.4 billion, primarily related to Cabometyx, which we launched back in April of 2016. You know, we're a research-based company. We have about 1,200 employees globally. You know, we've got many clinical trials ongoing for both Cabo, you know, contact, CONTACT-02, CONTACT-03, and also, cosmic, COSMIC-313. We also have, you know, other products in the pipeline, XL092, which is Zanzalintinib, XB002, which is tissue factor ADC. We've also done recently some business development deals, and actually historically, but more recently at the end of last year, some larger business development deals to continue to bolster that pipeline. That's part of our strategy, both internal discovery, but also bringing external innovation, t rying to think of anything else that I might have forgot. No, that was good. That's it. All right. Okay, great. Thanks for that introduction. Cabometyx, your lead product, had a strong year commercially in 2022. As you mentioned, $1.4 billion in sales, which is, you know, roughly 30% of an increase relative to 2021. What were the primary growth drivers for Cabo last year, and what do you see as the key sources going forward to continue that growth for the franchise? Yeah. We've actually grown pretty steadily since January of 2021 when the aRCC indication, the CaboNivo indication was approved. We've actually seen almost a doubling of revenue since then. We're about $750 million back in the end of 2020. You know, as I talked about, you mentioned $1.4 billion at the end of 2022. The vast majority of that growth is coming from that aRCC indication and the fact that patients are on drug a lot longer than they were just on the single agent Cabo. I think the PFS for the CaboNivo indication is around 18 months. That long duration of therapy, we get the patients continue to stack up as they stay on therapy longer. That drove our sales both in 2021 and 2022. Actually, when you think about our guidance, which we put out guidance at earnings last week, but really initially at J.P. Morgan at the beginning of the year, we're looking at $1.575 billion to $1.675 billion of product revenue, primarily coming from Cabometyx in 2023. That growth continues on both continue stacking patients, caused by the duration of therapy, but also to a lesser degree, that new patient starts that come through as new patients come on therapy as a first-line therapy. Okay. That's definitely helpful so j ust jumping a bit ahead, you have some data readouts for 2023. You know, some ongoing phase III trials, as you mentioned in the introduction, the COSMIC-313 in first-line setting, CONTACT-02 study in prostate cancer, and then obviously the second-line CONTACT-03 study. Can you provide a status on these readouts? How should we think about how they will layer into the growth and what it could mean for the Cabo franchise? Thanks. For COSMIC-313, we expect the second interim analysis to, which is OS, to read out sometime this year. Based on those data, we'll discuss any potential regulatory pathway with the FDA. For CONTACT-02, we're expecting enrollment completion this year. That is the prostate trial a nd top-line readout of PFS, which is the primary endpoint sometime in the second half of 2023. CONTACT-03, you're looking at, which is, cabo/Atezo, post an ICI, in RCC. We expect that readout to be, you know, sometime in the first half of 2023. Looking forward to all, you know, the potential for all those indications with positive data. Okay. Is there any that you feel particularly confident in or could provide, you know, the biggest upside in terms of these different opportunities? You know, it'll all depend on the data. I mean, we're excited about all of them. Obviously, you know, CONTACT-02 is in prostate. It's a new indication. CONTACT-03, as I mentioned is in RCC post an ICI. You know, that could continue to expand our RCC, you know, our penetration in the RCC market, which, you know, we're excited about. It has the potential for creating longer duration of therapy, also in the second line, similar to 9ER, creating a longer duration in first line. You'd have the ability to potentially, based on data, create a longer duration as a second line therapy in combination with Tislelizumab. Okay, thanks. You know, sort of sticking with the pipeline a little bit. I mean, historically, you guys have been known for your small molecule expertise. But over the, you know, past few years, you've ventured a little bit into biologics, with the various BD deals you've done. I believe you have an ADC now. Can you maybe talk about this transition and your expertise in that setting and where you see the balance of modalities within the company going forward? Yeah, absolutely. I mean, you're right, we've been a small molecule company by history for, you know, more than 20 years now. You know, with the initial success of Cabozantinib and, you know, having that revenue enable us to look at, you know, building a pipeline beyond Cabozantinib, we made the decision pretty quickly that, yes, of course, we were going to invest further in small molecules and rebuilding our own internal small molecule discovery group, which is ongoing. We very much wanted to have the ability to add biologics to the pipeline as well. There's a couple of reasons for that. You know, it just expands the universe of addressable targets, and we wanted to be able to match the kind of right therapeutic modality with the right target. Obviously, there's been a fair amount of success in terms of developing biologics and oncology. Many of the big oncology drugs that you know are biologics. As we looked at that, you know, in a little bit more detail, you know, biologics can cover a lot of ground there. We ended up focusing in on ADCs, primarily, but also bispecifics. There's a reason for that as well. I mean, the ideas behind ADCs and bispecifics have been around for, you know, 25 plus years. If you look at the history of ADCs, there was some initial success, you know, Mylotarg against Sila type approvals, but then a lot of failure, clinically, usually around lack of a recent therapeutic index. ADC just weren't tolerated. A lot has been learned from that, in terms of how to mitigate some of those issues, with exactly how you build the ADC. That's obviously resulted, I think, in a pretty clear renaissance in the whole field, with I figure, about dozen approvals, I think, over the last three years. We very much want to be part of that wave. XB002, which is our tissue factor targeting ADCs, our first foray into biologics. It's an agent that we licensed. It's a clinically validated target, tissue factor, just sort of map it with open from Seagen, has approval in cervical carcinoma. We felt there was space for a next gen agent which improved upon the properties of TIVDAK. We're excited about that one. We had some data come out late last year. I think, you know, there's an emerging profile, I think, that really gives one kind of belief that molecule could be advanced potentially in multiple different solid tumor types, you know, ones beyond cervical carcinoma. If you look back at the pipeline, you can kind of see the kind of emerging set of biologics coming. We've got a couple of other ADCs in the pipeline preclinically right now, a 5T4 targeting ADC and then a kind of next version of a tissue factor-targeting ADC, but this time with a different payload. Ultimately, we want to be able to match the tumor type with the payload that we believe it'll be most sensitive to, and a couple of bispecifics as well, PD-L1 CD47 and a PD-L1 NKG2A in pre-clinical development. We've done the biologics effort largely through collaborations. We didn't feel it was worth kind of setting up our own in-house antibody discovery, for example. There's a lot of that expertise out there. We partnered with folks who can provide us with an ongoing libraries of antibodies. We partnered with people who have, you know, cutting-edge site-specific conjugation technologies to enable us to control exactly how we're making the ADCs. And also partnered with folks who's given us a range of different payloads that we can add and mix and match. As time goes on, expect the pipeline, in general, will be a mix of both small molecules and biologics. We'll see how it goes, but I expect both of them to be in there for the long term. Okay, thanks so j ust diving a little deeper on XB002. I mean, you mentioned the comparison to Seagen's TIVDAK. Can you talk a little bit about the differentiation there? I know that drug has been a little bit limited by ocular toxicity. I think it has a black box warning. Can you maybe talk about how you see them competing commercially? What are the key differentiators? Yeah. Thanks. Yeah, absolutely. If you look at the profile of TIVDAK, I mean, clearly it is active in cervical carcinoma. You commented on the ocular tox, which sort of goes along with the kind of first gen auristatin payload that it has. Notably, you see a fair amount of bleeding. I think in the label, it's 62% of patients either get epistaxis or hemorrhage. That's a notable side effect from TIVDAK. Along with other side effects like, you know, alopecia, peripheral neuropathy, for example. When we're looking at XB002, it had been constructed somewhat differently. First, it's a different antibody, so it still binds the tissue factor, but it does it at a site which does not interfere with the binding of Factor VII. TIVDAK does block the binding of Factor VII. That interferes with coagulation and then results in bleeding side effects. While, 02 does not interfere with coagulation at all in multiple different preclinical assays. In the clinical data that we released last year, we've seen no bleeding to date. I think that's one clear point of differentiation. I think the other one is it looks like LO2 is a more stable molecule. The other piece of data we're particularly excited about is the initial PK. At a 2 mg per kg dose, which is the same dose as in the label for TIVDAK, we see twice the exposure of the intact ADC, but only 1/10 the exposure of the free payload. You know, I believe free payload, you know, can contribute to side effects. We think that differentiated PK profile, you know, should lead to a better therapeutic index. I think that gives us some confidence that, you know, we may have the ability then to move beyond cervical carcinoma in terms of different indications. In the initial phase I for TIVDAK, they did see some activity in other solid tumors, a few tumor shrinkages and I think a PR in lung, for example. It was fairly limited. We think with the extra intact ADC exposure, we'll be able to build on that and hopefully get some more impressive efficacy data beyond cervical carcinoma. That's the strategy. It's certainly a goal for us this year to push, you know, XB002 forward pretty hard. We're kind of in late dose escalation right now. The plan is to go once we have a dose, to go into 10 different expansion cohorts, multiple different solid tumors as a signal finding exercise. We've also initiated some combo studies with Nivolumab or with Bevacizumab. Again, we're able to do the Bevacizumab combo because we don't have the bleeding effects. I think it might be challenging to do that with TIVDAK just because of the overlapping side effects there. That's the plan for XB002, and the reason we're excited about it. Okay, very helpful. Shifting gears a little bit. Obviously one of the biggest overhangs on the stock right now is the ANDA. How is it important for you to get this resolved? What's the courage of your conviction about your patent estate and what's next to come with the trial in the fall of this year? Yeah. I mean, you're right. It's probably one of the biggest overhangs that we have right now is the ANDA and the upcoming trial we have in October of this year. It's very important to us to get that resolved, but appropriately, you know, and we're, you know, we're confident in the patents that we have at stake here. I mean, it's really around, you know, all the modeling we do internally is through 2030. We're confident in those patents and the patent estate that we have generally for Exelixis and, you know, it. Like I said, it's important for us to get that resolved but do it appropriately, so that, you know, either take it to trial or, you know, or other avenues of getting that resolved over the next, you know, year or so. I'm just looking at investor questions, on a related point. Is success in maintaining validation of one patent in either the Teva or the second MSN trial enough to keep all generics away until 2030? I can't tell you I know the answer to that question. Yeah. I can't tell you I know the answer to that question. Okay, no worries. Let's circle back. Can you talk a little bit about Zanzalintinib, formerly known as XL092? What was the rationale behind the design of this molecule? When we re-started doing internal small molecule drug discovery, we were looking for a first project. At the time, of course, we were sitting on a pretty expansive set of Cabozantinib clinical data. And, you know, what we'd seen there was it's a broadly active molecule. We've seen activity in about 20 different solid tumor types. Obviously, we haven't developed in all of those. We're focused on a few ones. We knew that the target profile of Cabozantinib was driving broad efficacy, and we also knew that it had great potential in terms of being combined with immune checkpoint inhibitors. We like that pharmacology a lot. We wanted to see if we could come up with a next generation version of Cabozantinib essentially. The one thing that we keyed in on was the pharmacokinetics. Cabozantinib has a 100-hour half-life. When patients initially come on, the drug accumulates for about three weeks. You know, we have to, you know, advise physicians, for example, that if patients start getting adverse events during that three-week period, that they have to sort of be on top of giving, you know, initiating dose holds or dose reductions to let the drug wash out. Likewise, you know, in the general course of treatment, if a patient needs to be dose held, there's a washout period that they need to go to before they can come back on treatments. We think that provides some inertia essentially whereby a patient can decide during that period of they want to switch to a different drug. They, you know, come on Cabozantinib for a week or two, and then they want to go back on something else. They may be going on something different. We really wanted a version where we thought the AE management side of things would be easier. We wanted to keep the same target profile that Cabozantinib has but reduce the PK half-life. That was the goal with Zanzalintinib. Happily, the data that we put out late last year, I think fairly clearly demonstrates that we've achieved that. Target profile's the same and the half-life's around about 20 hours, and it really doesn't accumulate that much during the initial dosing. You know, we think that's going to help from a compliance point of view. We think i t could be a bit of a friendlier combination partner going forward as well. That was the thinking behind that one. Okay. I believe you've initiated two pivotal phase III studies so far, and guided to multiple additional phase IIIs coming online this year. Is there any color you can provide at this point on which indications you're looking at for the next wave of pivotals? Yeah. Generally speaking, what we're looking to do, it's not we're not really looking at this as just a drop-in replacement for Cabozantinib. We're really looking to expand on the kind of universe of things where a Cabozantinib-like profile, we think will provide benefit. We're really trying to fill in the white space where we didn't go with Cabozantinib from a registrational trial point of view, but it's all based on data that we have from, you know, earlier stage studies that were run with Cabozantinib. First trial, you know, 303, for example, STELLAR-303, this is in colorectal carcinoma. We had data with cabo/Atezo in CRC, which, you know, gave us some confidence that we see a reasonable activity profile. We like, you know, obviously once you get into sort of third line CRC, options are limited. We're going up against Regorafenib, which, you know, has a fairly modest PFS and OS benefit. I think PFS benefit for regorafenib in that setting's around, you know, two months or less. To us that, you know, I think that's a great example of going into a different tumor type where we didn't get registrational data with Cabo, but we can go there with Zanza now, but based on what we knew about the Cabo profile. More broadly, I think the other thing we're looking to do obviously is use Zanza as a background for putting together some novel combinations. You know, we've initiated certainly the combination with Nivo, with the new checkpoint inhibitors, but again, we're looking to then add onto that, in indications like RCC, for example. You know, we're also looking at combining in with Relatlimab, the LAG-3 antibody from BMS. Again, it's not just going to be carbon copying of the same trial that we run, we run with Cabo. We then have to go up against Cabo. That doesn't make any sense. We're looking to build to provide additional benefit with either novel combinations or new tumor types. That's very helpful. Just pulling for some investor questions here. We have one. What is the physician feedback for the three-year CM9 ER data? How is that being received? Well, we'll find out this weekend. I mean, you know, it's getting presented at ASCO GU. I think it's certainly a, you know, it's a strong dataset. We've got 44 months follow-up now. It's pretty much, I think, the longest follow-up from, you know, any of the, any of the competing kind of trials. The overall survival data has matured really quite nicely. We're getting about an extra year of benefit from the last analysis. Our view certainly is that this adds, you know, just to the whole story around the cabo/nivo combination in terms of the strength of the dataset and the amount of benefit that it's giving. Again, certainly the physicians we, you know, we've talked to to date have been pretty enthusiastic about it. Okay, thanks. Okay, maybe we can talk a little bit about XL102, the covalent CDK7 inhibitor. Seems to be a little bit different from Zanza and XB002, and that the target and pathway aren't as clearly validated. Can you provide some insight into why you chose to take this approach to targeting CDK7, and what are your expectations for the program? Yeah, absolutely. You're exactly right. It did. Like, I would put it in a different bucket. I think as we combine it with XB002, there's some clinical validation for targeting tissue factor with an ADC. Obviously with Zanza, there's clinical validation from the Cabozantinib dataset. Again, CDK7's a much newer kind of agent on the block. It's still relatively early days in terms of clinical development of CDK7 inhibitors, so there isn't clinical proof of concept at the moment. I think generally speaking from a pipeline point of view, we're going to be developing both kinds of agents. You know, when we can do, you know, next-gen versions of things, I think that's always attractive, and we're certainly going to be doing more of that. Yeah, we also want to advance the more novel types of mechanisms of action really to try and expand the, you know, types of therapies that are available in various tumor types. You know, CDK7 had popped up as a target of interest for a number of reasons. It's certainly come out of a lot of kind of, you know, genetic screens for what cancer cells rely on in order to grow. It sits upstream of CDK4/6, so that's probably the closest kind of, you know, drug interaction there. Obviously there is some precedent for being able to get CDK4/6 inhibitors approved. It has a role in controlling the cell cycle from that point of view, which means it may have the potential at least to have broad activity. It also controls aspects of transcription and transcriptional response, particularly in the context of nuclear hormone receptors, specifically estrogen receptor and androgen receptors. Combinations with Fulvestrant or Abiraterone in breast and prostate respectively, you know, make a lot of sense. With XL102, we wanted a compound that was obviously potent, we want it to be very selective. We really didn't want any significant spillover into other CDKs. That's what the profile is. We actually went with a covalent inhibitor, you know, it binds to CDK7 covalently and then sits there until the protein turns over. We also went with a compound that has a relatively short plasma half-life, it kind of washes out of the circulation fairly fast. That's really intended to maximize the pharmacodynamic, you know, duration of action at the target whilst minimizing the opportunity in a sense to have off-target activities in tissues outside the tumor. You know, again, we published some initial phase I data last year on this compound, basically showing that profile. Dose escalation's ongoing but, you know, I think the data that we have now says that we have a really good tool, a really good probe, essentially, to explore the pharmacology of CDK7 inhibition in cancer. Okay. That's very helpful. Maybe we can talk a little bit about the recent clinical option agreement with Cybrexa and Sairopa announced in November. Can you talk about why you're excited about the deal and CBX-12 as well as ADU-1805? What drove your interest in these assets? Yeah. Well, we've been obviously looking to build our pipeline, not only through internal kind of activities, but also through, you know, collaborations, partnerships, in-licensing type deals. We've been looking very intensively over the last couple of years at a broad array of agents, both biologics and small molecules that are, you know, late preclinical, early clinical. You know, we certainly looked at later clinical as well. That's a smaller space. And, you know, really based on that, w e really like the kind of option way of doing this 'cause it means we don't have to just, you know, rush in and buy the agent upfront with that when it's in phase I with really very limited data. I mean, failure rates from phase I in oncology are still pretty high. This way, we get to, you know, potentially stack together a whole series of these kind of option deals exploring different mechanisms of action where we're not committing that much money up front, but we have the option to buy in once an agreed upon package of clinical data is assembled. For those agents specifically, CBX-12 is in a sense you can view it as an extension of the ADC approach. It's actually a peptide drug conjugate. The payload here is Exatecan. The pH, the peptide is a pH-sensitive agent. Normally in circulation, you know, whatever pH 7.2, it's not structured. As it gets near the tumor and the pH drops because tumors like to excrete lactic acid, pH goes down. The peptide, kind of forms an alpha helix, which allows it to translocate across the membrane, and it drags the Exatecan with it. It's a way to enhance payload delivery to the tumors that depends upon the pH difference, not upon the expression of a particular tumor-specific protein, which is what ADCs rely on for the antibody to bind. It's potentially applicable to a really broad set of solid tumors. We like the concept a lot. It's novel. I think this is the first agent of this type that's gone into clinical trials. There was, you know, again, initial phase I data which published late last year. It's, you know, been exploring a number of different dose schedules, s tarting to see activity in solid tumors. Certainly a nice PR in breast at the 20 mg/kg weekly dose, which is a dose that's currently being or a schedule that's being further explored. Yeah, we're, you know, excited about that one just because of the broad potential. It sort of fits with the ADC approach, but is, you know, tumor antigen-agnostic. The Sairopa does a monoclonal antibody against SIRPα. SIRPα binds to CD47, which is, you know, the partner most people are familiar with. You know, at this point I think the kind of profile of CD47 binding agents of various kinds in the clinic has been pretty well established. There is a fair amount of CD47 certainly expressed on tumors, but also expressed in normal tissues. You know, what you tend to see is there's a PK sync, but you also get side effects of the CD47 directly, specifically anemia and thrombocytopenia, just because you're blocking the normal cycling of those particular cell types. The SIRPα approach is attractive because the expression of SIRPα is significantly more restricted. It's just expressed on myeloid cells. There is a SIRPα monoclonal that's already in the clinic, and what that's shown is, one, greatly reduced PK sync. Two, you don't get the anemia and thrombocytopenia. There's a clear differentiation from that point of view. It's also started to show efficacy, that particular antibody, whether as a single agent a little and in combination. One feature of that antibody, however, is it binds to only three of the 10 known SIRPα alleles. Patients have to be genotyped to come on study to make sure they actually have the appropriate allele. The Sairopa antibody, however, binds to all alleles, so there's no requirement for genotyping there. In a sense, we can follow what's going on with the antibody that's in the clinic and then just come in with an antibody that's probably, it's going to be applicable to a broader pool group of patients. Yeah, we're excited about that differentiated approach, and I think it was just a very well-constructed and kind of thought out antibody. IND for that's just been filed, so yeah, we look forward to starting to see clinical data over the next year or so. Okay, fantastic. Looks like we're coming up on time, but maybe we can just end with general theme of cash and capital allocation. I mean, there's also an investor question coming in here generally on how you're planning on returning shareholder value. Obviously you have strong balance sheet, over $2 billion in cash. How are you going to utilize this cash position to drive shareholder value? Are you thinking about buybacks? Maybe a special dividend? How are you thinking about returning shareholder value? Okay. Well, thanks for the final question there. yeah, I mean, w e have a little over $2 billion of cash. you know, we continue to look at ways to invest that cash in the pipeline. you know, we had several years where we didn't have a discovery organization. We're building out the pipeline for Exelixis. you know, Peter just talked about the Cybrexa and Sairopa deals, which are capital efficient, which allow us to put some capital at risk and ultimately get to a point where we can make a decision to make a decision on going forward with more data. We'll continue to do deals like that. We'll continue to look at larger deals that are, that may or may not be out there, and try to continue to grow the company, and that's the primary focus of our capital allocation. We do talk about buybacks internally here all the time. We just feel at this point in time that the investments between, you know, getting a decision on the end of that but also the building out the pipeline, that is the primary focus of our capital allocation for the company. We do look at other capital allocations, potential capital allocation opportunities. Okay. Well, with that, I think we're at time. You know, thanks for attending and giving this presentation. We enjoyed the conversation. It was very informative. With that, we'll end the webcast, so you can sign off. Thanks.