Great. Afternoon, everybody. We're pleased to have CytomX with us for the next fireside. Chris, I'm going to turn over you to maybe make some opening comments, and then we can jump into it. Yeah. Hi, everyone, and thank you, Matthew, and the Morgan Stanley team for inviting us this year. I'm Chris Ogden, Chief Financial Officer of CytomX. Just before starting, I will be making forward-looking statements, so I'll refer you to our SEC filings for those disclosures. Just to start, CytomX is an oncology-focused company, and really, we refer to CytomX as the original masking company. We really invented the field of masked biologics. What we mean by masking is we essentially have a technology where we can limit binding. We designed to limit binding of target biologic formats in healthy tissue but activate those therapeutics preferentially in tumor cells. What that allows us to do from a design perspective is to really go after targets that other companies can't drug. From our perspective, that's led to clinical programs that are highly differentiated and are really enabled by our technology. We'll talk more about those, but our two clinical programs, one is an ADC for colorectal cancer, the principal indication, and the other is a cytokine program focused in melanoma. I think we'll talk much more about those, but that's really the focus of the company. Perfect. Wonderful. Maybe two overarching questions, and then we can obviously get into Varseta-M, which is the program that I think people are focused on. But first one is the target for Varseta-M is EpCAM. As you talked about, masking is important there because that target is pretty widely expressed. Can you just talk a little bit about how you've designed this agent to be able to hit that target and just a little bit of history in the field because others have obviously tried this target, why you think you're seeing a different result? Yeah. First and foremost, for the target, EpCAM, epithelial cell adhesion molecule, it was really discovered as a CRC cancer antigen quite some time ago. The reason it was discovered a couple of decades ago is it is just so highly abundant in tumor cells that it really pops out as potentially an ideal target for a colorectal cancer therapy. To your point, it has been attempted to be drugged before in monoclonal antibodies. There have been T-cell engager formats, and they have all run into toxicity due to expression, presumably in non-tumor tissues. The toxicities that have really limited therapies before are pancreatitis, so all the first antibodies saw pancreatitis quite early in dose finding, and also liver tox was a challenge. GI has also been something that has confronted, and we will talk more about, but I believe we have a therapeutic window in that context as well. In terms of our design, I would say it really starts with the end in mind. First, we thought this target, if you can create a therapeutic window, could make a big difference in colorectal cancer. From that perspective, we went about designing the other components of the drug, including the payload, which was developed and licensed from ImmunoGen, but we did have a former program with a maytansine payload that actually we could have advanced on a faster timeline. But we made the choice to switch out that payload with a Topo I payload because that mechanism is known to be active in colorectal cancer. Irinotecan, which is a Topo I inhibitor, is a key part of standard of care in CRC. The design, including EpCAM, is a great target that we can unlock through masking, paired with a Topo I payload for CRC, has really been the focus of this program, and we think all the components really lined up for us to make a difference here in CRC with our technology and this target. Any other thing you would highlight from a design standpoint, DAR, or any of the other factors that have been important as you think about therapeutic window here? Yeah. I would say when we did the work, going back today with ImmunoGen, it is a DAR8 ADC, and we benchmarked the payload, DXd, the payload on ENHERTU. In terms of the design and the preclinical work, we thought about this as really ENHERTU for EpCAM. That was the design principle, and so when you think about the payload potency and those types of things, potential bystander effect, those were all benchmarked to ENHERTU, which was emerging at that time as a best-in-class ADC and has proven to be. Perfect. Why don't we talk a little bit about where you are with Varseta-M, and then we can obviously talk about where you're going? Maybe first thing, the sort of initial market where you've started to get some data is in a third-line-plus patient population. Outcomes are pretty poor for those patients. But maybe just so we're all on the same page, what's available right now? What's sort of standard of care for third line, and what does that look like? Yeah. No, it's an important question. Before doing that, I do want to just zoom out. I think most investors and people in the audience will appreciate this, but when we think about the context of colorectal cancer, the way we think about it at the company is it's one of the, if not the most urgent, health crises in oncology. It's the second leading cause of death in the U.S. It's the leading cause of death in patients under 50, and as you've seen in the news, growing at an alarming rate. When we think about our place in the industry and the chance to make a difference there, I think that perspective will be highlighted in how we're thinking about the initial development and how much unmet need there is for these patients. To your question, in the context of third line plus, first of all, I would just say it's unfortunately a big market. We think in the U.S., there's about 40,000 patients that progress to third-line or later colorectal cancer. If you look at the benchmarks in the latest line, which are single-agent TKIs for the most part, response rates are 1% to 2% progression-free survival. The amount of time a patient stays on therapy without the tumor growing is only a few months, and unfortunately, their overall survival is six to seven months. In the context of that pretty poor set of outcomes, we've been very pleased with what we've seen with Varseta-M and the chance to make a difference and improve upon those benchmarks. Our patient population has been really fourth line or later. This is a clinical study population, so we're getting very sick patients. What we've observed over the course of phase I or the last couple of years is response rates in the 20%-30% range. Again, that compares to 1%-2% for benchmarks and our estimated progression-free survival of six to seven months, again, comparing to just a few months in standard of care. We've not reported overall survival, but that is something now that we've been in the clinic for a couple of years; we do expect to have initial reads on later this year. Just getting back to how important this category and unmet need is, I think the data we have really underscore how much urgency we have to progress this to late-phase development. As part of that data package, obviously, there's a focus both on efficacy and tolerability, and you sort of highlighted this a little bit at the beginning. Yeah. GI tolerability is probably the key focus from a tolerability standpoint. What have you seen so far? You've obviously done some things in terms of dose optimization, et cetera, that you're thinking about to try and improve that tolerability. Can you just walk through sort of what the thinking's been and where you think you're going to end up from a tolerability standpoint? Yeah. GI toxicity has been the key adverse event that's popped out in the phase I work, in particular diarrhea. Over the course of phase I, we've seen grade 3 diarrhea rates that can exceed 20% and, at the higher doses, into the 30% range for grade 3. As this observation's been understood, a few things we've been focused on. One, we have instituted prophylaxis to try to minimize the number of patients who get into grade 3. We've optimized that prophylaxis over the course of the phase I study, and it includes dual prophylaxis with loperamide, which is an anti-motility agent, and then budesonide, which is an orally absorbed steroid in the GI tract. We were encouraged in our data update we provided in March that we had initial data after a couple of months of follow-up where the grade 3 diarrhea rate was 10% compared to about 30%, which we had seen with non-prophylaxis in early part of the study. That was two months of follow-up, so it was a good start. We will continue to follow up on those data, including with additional patients enrolled and more follow-up time. We are looking to continue to manage that rate of grade 3 diarrhea between 10% and 20%. We really think based on the work we have done with physicians and thought leaders, that that will be an attractive risk-benefit in the context of the efficacy we are providing. The other thing we have implemented to really fine-tune the exposure delivered of the drug is we have begun dosing patients based on adjusted ideal body weight, which really normalizes for patients with higher BMI, based on the observation that some patients with high BMI were seeing outlier levels of exposure. We provided some data on Cmax and PK in our presentation. Those patients, some of them, had more challenges with GI. We think tightening the exposure range and the outliers may help in those patients with high BMI, and then the prophylaxis is an additional measure. We feel like we are making good progress, and we will have additional data following that up later this year. I think one of the questions probably people focus on here is obviously the efficacy data that you have reported from multiple scans of patients, and you say have a good sense of that. The safety data where you have changed sort of the dose regimen is early, so we do not have the efficacy from those patients. Can you just talk about why you are confident about maintaining the efficacy that we have seen with this sort of newer dosing regimen? I think the big picture, what we have seen across the phase I study to date, suggests that Varseta-M is active in late-line CRC. Across the 8.6 and 10 dose range, which was dosed at actual body weight, we are seeing response rates in PFS where we think there is room to operate. I think overall our view is the drug is behaving fairly consistently across this dose range. This is about optimizing the therapeutic window within a compelling overall profile that we have seen to date. Of course, we need to see that data through and see what we get, but that is the view based on the steps taken to date. Okay, perfect. From a next-step standpoint, I think there are two things going on. One, I think you've committed to talking about what a registration program may look like here. The second is obviously you have these optimized dose cohorts ongoing. Can you just talk a little bit about timing for when we might expect to hear from you? Yeah. What that additional data is, and then what the registration path may look like. Yeah, and it really starts with the latter, where the focus of the company around dose optimization is getting to dose selection, including discussions with FDA around Project Optimus and making sure they're comfortable around whatever dose is chosen. That decision, obviously in conjunction with based on the totality of our data, what's the first monotherapy registrational study? Again, just given the unmet need in late line, we think it's absolutely critical to get Varseta-M into late phase development. The context for all the data that's being generated is to make the dose and registrational decision. We will communicate those next steps and the data that underpins it. That's really how we're thinking about it and we think also most helpful to investors. Just to be clear, we should expect to get all of that at the same time, is what you're saying? Well, that is our base plan. Yeah, of course, in the context of things like FDA interactions, we need to make sure those things stay on track. Our base plan is to provide next steps and data together. Can you talk a little bit about, obviously, you do not know what that is yet, but can you give people a sense of what the guardrails of that may look like? Is this going to be Should people be thinking fourth line only? Can there be a possibility to include earlier patients or combinations, or what should people be thinking about here in terms of what the guardrails look like? For the first study? Yeah. Yeah. We haven't made any decisions. For the first study for monotherapy, I would first say that our base expectation is we do expect the initial study will be a randomized study with an overall survival endpoint. There aren't a lot of precedents, for example, single-arm studies. With that context, we're likely looking at either a monotherapy study in the late line, which would include comparators such as fruquintinib, regorafenib, maybe single-agent LONSURF, or the third line, which is a combination; the standard of care is a combination of bevacizumab and LONSURF. We haven't made any decision on which. We think both are attractive from an unmet need and market uptake perspective, most likely. In any case, this is a first step. To your point on combinations, in parallel, we've kicked off combination work with bevacizumab, which could unlock third- or second-line as we move up the treatment paradigm. Also in Q4W, we plan to start combination with Varseta-M, bevacizumab, and 5-FU, which is really our strategy to replace irinotecan in the FOLFIRI plus bev regimen, which could unlock second-line, and then that regimen's also used in first line. Those things are all underway. In any case, the first step at monotherapy is just that. Yep. In our view, this drug has potential in multiple lines of therapy. Can you just talk a little bit about how you think about market opportunity here? I know you talked about 40,000 patients. If you do have a third-line label versus a fourth-line label, how does that change your thinking at all in terms of initial opportunity here? Yeah. I would say at a strategic level over the medium term, I am not sure it changes the overall potential of Varseta-M, to be quite honest with you, we are focused on continuing to move up. I think pragmatically, for the first launch, third line versus fourth line, fourth line would be more focused. Right now, the 35,000 to 40,000 in third line, a lot of patients in fourth line forego therapy or go into a clinical trial. We think that market is larger than, for example, what you see in the sales figures, because the outcomes are just not that great, duration of therapy is short. We think there is a substantial launch opportunity, at least a billion-dollar-plus market in the fourth line, and we can launch the drug in a focused way while getting the appropriate combination data. How that plays out in terms of timing of launch and competitive dynamics, I think to be determined, but I would just emphasize, we are in the lead pack of ADCs for colorectal. There are really only two other competitors, which are much bigger. Our view is that ADCs are going to be an important modality in CRC, and so I think, in any case, the positioning could be quite good as long as we move quickly. Yeah. You talked about competition. I want to talk about the combination studies you are running, but maybe just quickly we could touch on how you see yourselves versus the competitors, either from a profile standpoint, but as well as a sort of timing standpoint. Yeah. The two competitors we are focused on, one is ABBV-400, which is a c-Met-targeted Topo I ADC, and then the other competitor is a CEACAM5-targeted Topo I ADC from Merck Serono. First I would say that we do believe, and we will have to see over a long period of time, but we think EpCAM, if it is not the best target, we think it is one of the ideal targets for CRC. We believe it will continue to be highly expressed in nearly every patient, that we will not need to select patients. I think from a, when you are trying to change the treatment paradigm, that is a huge advantage. I think in these early days, I would say the early phase I data across the class, I would say all look compelling relative to what other modalities are, so probably too early to say on the overall efficacy profile. On safety, we talked about our profile, which really the one thing of focus is diarrhea. The two competitors have higher levels of hematologic tox; one with higher AB has higher grade 3 anemia, which will need managed, both in terms of mono, but potentially in combinations. Merck KGaA has higher neutropenia. Same thing, will likely need managed. Of course, not being critical there, but those are considerations for patients depending on their overall health and baseline fitness. I think you're already seeing differences emerge, and as larger clinical studies play out, I think each of these are likely to have a place in an underserved market that hasn't seen substantial innovation over a number of decades. On timing, I would say we're a year behind or so. Those competitors are further ahead on the bevacizumab combinations and are using those combinations as their principal strategy in third line. We have an aim to catch up there, so Perfect. Combinations are obviously an important part, as you mentioned, of the development strategy here. You obviously have the bev combinations ongoing. When is that data coming? What does that unlock for you in terms of next steps after that? Yeah. We're focused on dose finding and safety right now in the bevacizumab combination with Varseta-M. We started late Q1 or Q2 of this year. We expect to have initial data in the first half of 2027. That should give us an initial look on safety and dose and schedule and early efficacy of the combination. Depending on the data, that could enable growing our opportunity in the late line, for example, third line, to grow the addressable market, or potentially depending on the data over time, could be an opportunity in second line where the benchmarks and the standard of care does include FOLFIRI, so includes 5-FU, but with a targeted ADC, you may be able to improve around that. The way to think about it is it's the initial unlock of moving upstream, and that helps us un-gate. I would say with confidence the work on the triplet, which will be Varseta plus bevacizumab and 5-FU, which the aim there is to replace irinotecan in the FOLFIRI plus bev study. Two things maybe on that. First, why is it helpful to replace irinotecan with 5-FU? Just for people, so they understand what that can achieve. Then the second question is just, you talked about some of the steps you've taken to manage GI tox in the monotherapy study. Are you using those same procedures in the combination study? Or when will you start to do that? Yeah. First, on the strategic importance. Replacing irinotecan with Varceta, I think, based on the activity and the targeted nature of an ADC, we think has the potential to dramatically improve standard of care. I mean, irinotecan, systemic chemotherapy that it's around for decades. We think the risk-benefit and, importantly, hopefully the efficacy over time—that's a central component of our strategy. If you think a bit longer term, if we can replace a chemotherapy option, then Varseta-M becomes really a strategic piece of all combination therapies for other targeted agents that might emerge. For example, next-gen EGFR, PD-1, VEGF, as really one of the cytotoxic backbones that can improve outcomes for patients, including safety and efficacy. Now we will, to your point, have to do dose finding and make sure that it's tolerable and that we can find an optimized therapeutic window. That will take work and some time. We are carrying forward the learnings from monotherapy into the combinations. We do think adjusted ideal body weight dosing is a better way to, again, deliver the targeted exposure in ppatients and then the prophylaxis measures. Given what we've learned on diarrhea, we think that's a prudent thing to do, at least initially, as we try to optimize those combination profiles. We'll continue to learn over time as we have experience with Varseta-M, in particular in combination, and again, this is a long game; we think there hopefully is a path forward. Any comments, and maybe last on this before we talk about some of the other tumor types you might think about, but just any comments on the range of dose and schedule you're looking at in combination? Does that look dramatically different than what you've looked at in monotherapy? Yeah. I mean, we have gotten going on the bevacizumab combination. We haven't commented on the doses other than we haven't needed to go back to the start of dose escalation. So we do feel like we're starting at relevant exposures based on the doses that have been picked. We are looking at schedules that are twice a week and every four weeks, so Q2 and Q4, to sync up with the bevacizumab Q2 week, so that every two-week schedule. Ultimately the chemo combination, that's a Q2-week schedule. So we're looking at that every two-week interval to try to sync that up really for long-term success and patient convenience. That will take a little bit of work because we've been studying the drug as a Q3 week, every three-week monotherapy. But we think long-term, that's the right play, just to make sure that patients and physicians have a good experience. Yep. Okay, perfect. So EpCAM is obviously expressed across a lot of tumors, right? Some more than others, right? CRC makes sense. That's why you started there, because it's most expressed. What are the other tumors you think make the most sense to go after, and how should people think about potential data generation there? Yeah. We are really excited about the work outside of CRC. We have been intentionally focused, and I would say, quite patient, to do work outside. We did announce on our Q3 earnings call, we are going to do phase I cohorts for three additional indications. We are going to do gastric and GEJ, and we are not going to select patients because we think the vast majority will have high EpCAM expression. We are going to do pancreatic, and we are going to do biliary tract. We think, basically, these three indications, one, the unmet need in second line plus or third line is still very high. There really is not significant development of other ADCs. There is some, but nothing that has really broken through. Long term, we are focused on building a commercial GI franchise for CytomX, obviously starting in CRC, but these three tumor types, if we were to see signals in the later line, could be additional fast-to-market potential. I think really also points the way to the pan-tumor potential of EpCAM as a target. I should mention that we get asked about target expression across indications. We are going to, for pancreatic and biliary tract, initially select patients for high EpCAM. We have not needed to do that in CRC. We do not think we need to in gastric. In those two indications, roughly half of patients we think will be high. In terms of generating the most meaningful data set, we think that is the right initial strategy, and then we can build from there. From a trial standpoint, do you need the data from the optimized monotherapy cohorts here to start in these patients? Just how are you thinking about the data that you have in CRC giving you dose and schedule in these other tumors? Yeah. We feel like we are in a close enough dose range that it makes sense to get going. To your point, as we get to final dose selection on CRC monotherapy, certainly the learnings will translate over and will inform what we do in the non-CRC indications. That said, there is precedent across the ADCs where different tumor types can have different doses. I think HER2 is an example of this, for example, in gastric. We do not want to necessarily go in dogmatic that it has to be the same dose, but certainly it will inform the work there. Perfect. I know we only have a couple more minutes, but maybe we could just touch on interferon alfa. Yeah. What are the next steps for that program and why you are excited? Yeah. I think interferon alfa, just at a high level, one, I would just say it is a masked cytokine, so interferon alfa-2b. Interferon alfa-2b is a well-validated immunotherapy. It was actually approved as a single agent a long time ago, as a monotherapy. It actually just fell out of use because it is severely toxic. Patients get severe flu-like symptoms and are unable to tolerate it well. It is a very potent cytokine, and we think a perfect application of our masking technology, which we can take the potent efficacy, try to detune that in the broader periphery of the patient's body and direct the activity more preferentially to the tumor. We are really looking to do this initially in refractory melanoma, so PD-1 refractory melanoma, where patients really do not have additional options. We are going to combine with KEYTRUDA initially for proof of concept. The way we think about this setting is patients who get, for example, a PD-1 rechallenge or checkpoint rechallenge typically do not have great response rates. Some of the literature suggests 7%-10%, and so we are looking to generate a signal that is significantly above that as a proof of concept. If that were to work, I think we would have a number of options to develop this in, for example, late-line melanoma, potentially earlier lines, and then the mechanism should work more broadly across PD-1 refractory populations, renal, bladder. There is a number of areas we could go. So I think we know we need to do the work, generate the proof of concept. We think this could be quite a broad and potentially important opportunity as well. What is the timing there in terms of— We are in dose escalation. We expect to have an initial data set by the first half of next year. Great. Then maybe just last question, which everybody always wants to know is, how do you think about your funding right now, and what does that give you in terms of milestones? We had $330 million of cash as of June 30th. We then expanded our Regeneron collaboration, which we received $37 million in July. So the pro forma cash, about $367 million. That is runway to at least the second half of 2028. That does contemplate, in a first registrational study, the combination work to proof of concept to inform next steps and the proof of concept work in non-CRC indications, as well as the interferon program. So we have a number of, I would say, important learnings we will get within that runway. As we hopefully pin down the first registrational study, I think we can provide additional perspective on what that means in terms of the overall run. But we are planning for a registrational study in that runway guidance. Perfect. Chris, thanks for being here. Thanks, Matthew. We appreciate it. Appreciate it.