Great. Well, welcome, Sean McCarthy, Chief Executive Officer and Chairman of CytomX Therapeutics to Goldman Sachs Healthcare Conference. First, welcome. To start things, for those in the audience and listening who may be newer to the CytomX story, can you give a brief overview of Probody therapeutic platform, your masking technology, and why you think it's differentiated? Well, thanks so much for the invitation to be here. It's great to be at the conference. This is a very exciting time for our company, CytomX Therapeutics, and the core technology that we have been working on now for a number of years is a platform we call the Probody therapeutic platform. It's a strategy for taking biologics, such as antibody therapeutics, and engineering them to be masked in a way that allows for unmasking in the tumor microenvironment. The unmasking happens specifically and selectively within tumor tissue due to the presence of active proteases. Protease biology is a phenomenon that's turned on in tumor tissue to enable tumor cells to invade, migrate, and metastasize. We take advantage of this differential between protease activity in normal tissue versus tumor tissue to unmask these masked biologics and improve, or in some cases, as we're doing with our current drug, Varseta-M, the EpCAM ADC, to actually create a therapeutic window for the first time. Great. Before we get into Varseta-M, regarding the platform, you announced a pretty significant expansion of your existing collaboration with Regeneron. Can you talk a little bit about the scope of the agreement and what led to the expansion? Well, one thing about the Probody platform that we realized very early on in the company's history was that it really offered opportunities to form broad-based partnerships to fully explore the potential of the technology, and also quite importantly over the years, to act as a source of non-dilutive funding for the company as well. The Regeneron deal, we're super excited to have expanded it recently. It's a deal that we first entered into in 2022. It's focused in the field of bispecific immunotherapies, such as, for example, T-cell engagers, where there's enormous opportunity to improve therapeutic window for these highly potent immunotherapies by masking. In fact, we've shown previously with our own T-cell engager work in the clinic that masking can, for example, significantly reduce phenomena such as cytokine release syndrome. The strategy with Regeneron is aimed at in various bispecific constructs to improve tolerability, maximize antitumor efficacy, and really make a new generation of immunotherapies to really push the whole field forward. It's a very natural application of our technology, and it's also one that since most of our work internally at the moment is focused in ADCs, which we'll come to in a moment, partnering on the immunotherapy side makes a lot of sense. As you mentioned, we've received a significant additional upfront payment from Regeneron, $37 million, for the selection of two additional targets, and they also have an additional six target picks over the next while, for which they'll pay additional upfront funds and, of course, substantial milestones and ultimately royalties. That doubled the size of the deal from a $2 billion deal to a $4 billion deal. Just really excited, but really mostly excited about the science that we're doing with them. It's just really been terrific collaborating with their team and just doing some really cool stuff in the lab. That's great. Turning to Varseta-M, as you mentioned earlier, targets EpCAM, a target that historically has been very difficult to target given on-target off-tumor effects. Can you talk a little bit about how the Probody platform allowed you to essentially expand the therapeutic window and make it a viable drug? We've had a longstanding interest in EpCAM at CytomX, and it has been a target that has been around quite a long time. In fact, the protein was first described as long ago, believe it or not, as 1979, and I think that shows just how much of it there is on colorectal cancer cells. It was quite easy to find, even with the tools that were available way back then. It's very highly expressed on colorectal cancer. Pretty much every patient expresses high level EpCAM. It's also present on just about every other solid tumor. And for that reason, there have been multiple approaches, multiple attempts to turn EpCAM into a viable cancer drug target over the years, and none of them have worked with systemic therapeutics. Why is that? The first approaches that were naked antibodies encountered quite early in their development a significant tox road block of acute pancreatitis. Subsequent approaches with higher affinity or empowered anti-EpCAM antibodies, for example, an EpCAM CD3 T-cell engager, showed additional toxicities, including liver toxicity and some GI tox. And these drugs didn't get close to exposures in patients. They just could not achieve exposures in patients that resulted in significant anti-tumor activity. The experiment was never really done until our masking strategy came along. But what encouraged us to use masking to unlock EpCAM as a target was some really important clues from locally administered anti-EpCAM strategies. For example, there's a drug, an anti-EpCAM CD3 T-cell engager that when given locally into the peritoneum, actually can do quite remarkable things in shrinking peritoneal growths that occur in patients with GI tumors. These growths, they're called malignant ascites. Anti-EpCAM CD3 can shrink malignant ascites in a very effective way, but the drug can only be given locally because it's too toxic systemically. Similarly, an anti-EpCAM bacterial toxin fusion called oportuzumab monatox several years ago was shown to have very robust activity in non-muscle invasive bladder cancer. But again, that drug has to be given locally into the bladder. What that told us was if you can get an empowered anti-EpCAM antibody to the right place in a cancer patient, it can live. We reasoned that, with our masking strategy, really exactly what masking is designed to do. It's designed to diminish activity in normal tissues, allow for activity in tumor tissue where we see unmasking, and that's what led to the concept of Varseta-M. We also reasoned that colorectal would be the place to start first because it's where the target is most consistently and abundantly expressed. It's where the unmet need is really, really high. To do this experiment, we empowered our masked antibody with a TOPO1 inhibitor payload to treat CRC because we know that CRC is responsive to irinotecan, so it should be responsive to other TOPO1 inhibitors. And that set up the clinical experiment that we've been doing now for the last couple of years, evaluating what we now call Varseta-M in late-line colorectal. And obviously, we're so excited at the company to have been able to report really unprecedented anti-tumor activity with this drug in late-line colorectal, showing that we've really broken through on EpCAM as a target for the first time and in a very unique way enabled by our platform. Maybe let's dig in a little bit on that data. You had shared encouraging phase I dose expansion data in late-line metastatic CRC earlier this year. Can you go in a little bit more detail on the data and importantly contextualize these results versus current standard of care and what patients are currently dealing with in late-line CRC? Yeah, absolutely. Maybe let's start with that last question in terms of what patients are currently dealing with in late-line CRC. The options available for patients after they've exhausted chemotherapy in the first and second line, the options available are dismal. The prognosis for patients is dismal, and we have a five-year survival in metastatic CRC of 13%. We must do better, and we reasoned that antibody-drug conjugate could bring unique in the setting of colorectal because it's a very difficult disease to treat, in no small part because it's a very heterogeneous disease. We have the colon, we have rectal cancer, so just there you've got two different cancers. We've got left side and right-sided tumors that we know the biology of can be quite different, and they behave in different ways and respond in different ways to therapy. We have patients with or without liver metastases and other remote metastases, where CRC can move to. We have various mutational strategies, BRAF mutated tumors, KRAS mutated tumors. It's become an increasingly complex landscape where, in an increasingly fragmented landscape in terms of the treatment paradigm, but EpCAM is present on every tumor. We took the view, well, we should be able to develop a drug for all of CRC, and wouldn't that be just amazing if we could do that? That's really always been the vision for Varseta-M, and that's why in our phase I study, we've enrolled all-comer CRC patients in the late line, regardless of any of those clinical characteristics. The activity that we've shown so far is independent of any of those clinical characteristics. We've demonstrated our most recent update in March this year. We showed an overall response rate of 32% in fourth/fifth line colorectal, and that compares to the current standard of care in that setting where response rates, if indeed there is a response rate, are in the 1%-2% range. We showed progression-free survival at the 10 milligram per kilogram dose level of seven months. That exceeds the overall survival of current standard of care in the fourth or fifth line setting, which is around four to five months. A very strong start with this drug. It's highly active, and that's across, again, all clinical characteristics. We have activity in patients with liver mets or without liver mets. We have activity in patients with KRAS wild type or KRAS mutant, left side or right side. That's one of the things that's been so exciting to our investigators, the pull from the clinical sites for the drug has been a function of the fact that it really can be a drug for all of late-line CRC. Really thrilled with what we're seeing so far in terms of the anti-tumor activity of Varseta-M. Right. Late-line CRC, obviously a very rapidly evolving landscape with a number of novel agents in the clinic right now, including different ADCs. How do you view Varseta-M, you mentioned maybe some of them, but how do you view the differentiation in this landscape? We're really excited to have Varseta-M as the first-in-class anti-EpCAM antibody drug conjugate being developed. We are a long way ahead of the field. We got here by taking, if you like, calculated risks over many years in terms of how to explore the platform and how to apply the platform and how to get to this real killer experiment in colorectal with Varseta-M. That is now putting us in a very advantaged place with the first-in-class anti-EpCAM ADC. We also think Varseta-M has the potential to be the best-in-class ADC for colorectal. There are two others in development, ABBV-400, which is AbbVie's c-Met targeting ADC, is making solid progress in colorectal, as is M9140, the CEACAM5 targeting ADC being developed by Merck Serono. They are a little ahead of us. They began their programs a couple of years before we did. They've both shown robust activity in late-line colorectal. They're both now in the early stages of their first pivotal studies in both cases. We believe Varseta-M has a very differentiated profile. First of all, we can treat all comers in the context of c-Met. c-Met is high only in about 25%-30% of patients. It remains to be seen with the AbbVie drug as to how important target selection may be in the long run. With Varseta-M, there is no need to select target because every patient has high-level EpCAM as measured by IHC. We also, with our drug, the safety profile we think is quite unique and very differentiated from the other agents. We see, in addition to not seeing any of the classic EpCAM toxicities like pancreatitis because our masking is delivering, we see low rates of hematologic toxicity, actually really unusually low rates of heme tox for an ADC and particularly for a TOPO1 ADC. I want to underscore that this is a novel linker and payload that we're using. This is the first time this tri-alanine camptothecin construct has been explored in the clinic. So far so good in terms of the heme tox profile. Low rates of neutropenia, anemia, and thrombocytopenia. For some reason, the AbbVie and Merck drugs do show significantly higher rates of hematologic toxicity in the form of all three of those heme tox profiles, that's clearly something to watch as those drugs develop. We think on top of that, it looks to us, a bit more work to do here, but we believe we may have the most active drug as well. We do see Varseta-M as being intrinsically differentiated from the other ADCs. There are, of course, other innovations coming in colorectal across the immunotherapies. We're obviously watching closely the Exelixis TKI in combination with the atezolizumab, which may come to the market before too long. Again, we just feel like the intrinsic activity, quite honestly, the remarkable activity of Varseta-M in late-line colorectal is highly differentiated, and we're just really excited to get the drug into its first pivotal study beginning next year. That March update you mentioned earlier, showed activity across the two prioritized doses, the 8.6 mg per kg and the 10 mg per kg. You've completed enrollment in your dose optimization cohort. How should investors think about the overall clinical profile? We're progressively and systematically developing Varseta-M, initially for late-line CRC. That systematic development plan has involved, of course, initially dose escalation, dose expansion, where we reported the results recently from the expansion of three doses, 7.2 mg, 8.6 mg, and 10 mg per kg given every three weeks. Those expansions led to the efficacy data that we just reported, again, remarkable anti-tumor activity in late-line colorectal, also taught us a lot about the integrated safety profile of the drug and how to further optimize dose as we move towards that first pivotal study. What we elected to do and what we're in the middle of right now is we've further narrowed the dose range to the top two doses from expansion, 8.6 mg and 10 mg per kg. We are now enrolling about 20 patients at each of those two dose levels in the dose optimization phase, where we've also evaluating the role of adjusted ideal body weight dosing to reduce the number of patients who, when they come into clinic, have high body weights, particularly patients who may be obese, where under conventional actual body weight dosing, they probably get a little too much drug, such that there's a risk of overexposure, and that can lead to increased toxicity. We're using, I say, exploring AIBW dosing to decrease the number of patients who get this outlier exposure. We believe all of these measures will go to further improving the safety profile of the drug and specifically the incidence of high-grade GI toxicity. That will allow us, in the context of the activity that we're looking at for these 2 dose levels, to then zero in on which of these two really great choices we've got, actually, for the pivotal study, which of these 2 doses we move forward into the first registrational design. Great. You've articulated publicly the vision of expanding in CRC through combos and early line development. Can you talk a little bit about that strategy, the combinations that you're starting to explore in earlier line? Yeah. I'd say there's a healthy debate out there right now in the investment community regarding, which we think is great, regarding Varseta-M. There's a lot of interest in this drug, a lot of interest in what we're doing, and a lot of questions being asked. One of them is our ability to bring Varseta-M earlier in the treatment paradigm. Let me tell you how we're going to progressively do that. Obviously, we're beginning in the late line. That's where the unmet need is the highest. That's where we've conducted our clinical work to date, and that's where we have unquestionable activity, and we believe a clear path to registering the drug in late-line colorectal. That doesn't seem to be much of a debate at the moment. I think everyone is on board with that, yeah, this is an execution story now about getting the drug approved in late-line colorectal. We're confident in our ability to do that. In terms of bringing the drug into the earlier lines, we're also confident there. We need to do the work. What are we doing? Well, first of all, as I said, we're working very hard to further characterize the safety profile and very specifically reduce the rate of Grade 3 diarrhea that we see in patients treated with Varseta-M. We showed a very strong start in our March 16th update with the first 20 patients treated in dose optimization, where we had reduced the incidence of Grade 3 diarrhea to 10%. Our goal over time is to keep that rate in the 10%-20% range. That is going to be an acceptable range of Grade 3 that everyone we talk to in the clinical community says that will be manageable, particularly in the context of the incredible benefit that the drug is bringing to these CRC patients. In the context of that dose optimization work, we're beginning combination work, and we've started to combine Varseta-M with bevacizumab. That's an obvious choice, of course, because Bev is so frequently used really across the treatment paradigm in colorectal from early lines into the late line. We want to get that experience because we absolutely anticipate that the combination of Varseta-M and Bev will be a possibility in earlier lines of therapy. We're also in the second half of the year beginning combination work with chemotherapy. The reason to do that is it's a big step towards realizing our ultimate vision for Varseta-M, which is to replace irinotecan in the treatment paradigm. Irinotecan, TOPO1 inhibitor, has been well established in the treatment of CRC for many years now, and it's used often in the front line, more typically in the second line in the context of FOLFIRI plus bevacizumab. It's pretty effective in the second line setting. Our goal is to combine with the non-irinotecan components of the FOLFIRI regimen and, of course, to evaluate it with bevacizumab as we gain experience with that combination as well. We're laying the foundation for bringing the drug earlier to the treatment paradigm by, number one, improving how to predict and manage the safety profile and optimize the safety profile. Number two, pick the optimal dose for late-stage development. Number three, gaining experience with bevacizumab. Number four, gaining experience with chemotherapy. You can see in my comments how this program is broadening in real time. We are significantly broadening the scope of the Varseta-M program and really excited to see what we can deliver across the treatment paradigm for colorectal. Great. Talked about broadening in CRC. Let's talk about broadening outside of CRC. EpCAM, as you mentioned, expressed in many other tumor types. As you think about the potential to move into other tumor types, how would you prioritize where to go first? Well, with colorectal, we certainly feel like we've done the hardest experiment first. We really intentionally designed Varseta-M to be active in colorectal, and it is. It's highly active in colorectal. That was a big decision that we took as a company to focus our phase I study entirely in metastatic late-line CRC, and that decision, we believe, has really paid off because we've done the hardest experiment first, we are now very excited to move Varseta-M into other tumor types. There's a long list of cancers that we can potentially address. EpCAM is expressed in many, many other solid tumors, and we do plan to start that work in the coming months. We do like some of the other GI tumors, if you like franchise adjacent to colorectal, as being areas of significant unmet medical need, tumors that are, in many cases, responsive to TOPO1 inhibition, and where EpCAM is expressed at high levels. In some of those patients, it may require a patient selection strategy. We have a fully validated EpCAM selection IHC assay ready to go. That's something that we're looking at right now. We're working our way through a list of priorities, and we'll be sharing later in the year specifically what the first steps in our non-CRC strategy are going to be. Of course, our ultimate goal is to secure a pan-tumor label for EpCAM, given its broad expression. That'll take a while to get to, but these will be the first few steps along the way. Right. Shifting gears a little bit, there's a lot of, I think, very understandable investor focus on Varseta-M, but your second program, CX-801, is also in the clinic. You're advancing in dose escalation with pembrolizumab. Can you give a little bit of an overview of the program and what makes you excited about it? Absolutely. We've already touched on some of the immunotherapy applications of the Probody platform in the context of our ongoing and now expanded work with Regeneron in bispecific immunotherapies. As I said, we absolutely see those types of strategies as being very natural places to go to leverage the power of masking to improve therapeutic window. The cytokine field is another whole universe of application of the Probody strategy, and we're working on a number of cytokines in the company, and the interferon program is the most advanced. CX-801 is a dually- masked version of interferon alfa-2b. Interferon alfa actually was the first immunotherapy to ever be approved. It's a very powerful cytokine. It does multiple things in the tumor microenvironment to drive antigen presentation, T-cell activation. It actually has direct anti-tumor activity as well through interferon receptors expressed on the cell surface of tumor cells. For that reason, it's been utilized extensively in the clinic over many years and has been shown to have single-agent activity in a number of cancers, including in melanoma. Interferon fell out of use because it's very poorly tolerated when given systemically. It causes a range of significant debilitating side effects. Patients have a very poor experience on systemic interferon alfa, including fever, including chills, including neuropsychiatric challenges. The risk-benefit for unmasked interferon alfa has resulted in it falling out of use over the years. When we come back to its fundamental immunobiology and the way that interferon alfa modulates the tumor microenvironment and the inflammatory microenvironment, it does have all the hallmarks of a cytokine that can drive, or if you like, restore sensitivity in the post-checkpoint inhibitor setting to a wide range of cancer types. In fact, it was shown by Merck some years ago that the combination of interferon alfa-2b with PD-1 inhibition is highly active in melanoma. In fact, in frontline melanoma, has a 60-plus% overall response rate. The challenge is that combination is poorly tolerated with, again, conventional systemic interferon. The experiment that we're doing in the clinic in real time is focused in melanoma with our dually- masked interferon alfa-2b. We call it CX-801. It has a peptide mask on the cytokine. It has an Fc mask, both of which are protease cleavable. The combined effect of those two masks shuts down the peripheral activity of the cytokine by about 5,000-fold, so it's very, very quiet in the periphery. The goal is when it gets to the tumor, that those masks should be removed, and that should allow us to activate interferon biology in the tumor and then restore checkpoint sensitivity. As you know, this is one of the biggest questions in immunotherapy today. How do we restore activity in patients who have been on checkpoint inhibition, or how do we create activity in patients who are resistant or recalcitrant, non-responsive in the first place? We've been in the clinic now for about a year, and we have already reported some clinical data. Last year at SITC, we showed results in the first five patients treated with monotherapy CX-801. The data we shared was pharmacodynamic analysis of on-treatment tumor biopsies in the first five patients treated with CX-801, and it looks really exciting. Clearly, the drug is activating multiple layers of interferon alfa-2b biology in the tumor. We're activating interferon-responsive genes. We're inducing checkpoint proteins, including PD-1 and PD-L1. Really dramatically, we see profound infiltration of cytotoxic T cells into the tumor bed in conjunction with the activation of local chemokines. Mechanistically, the first few patients we've treated, the drug is working exactly as we've designed. It's also been very well tolerated. We've already achieved dose levels in the clinic that have exceeded the clinically approved dose of interferon alfa. At those doses, we're seeing this powerful intratumoral modulation of the immune system, which really sets up the perfect foundation for the real experiment that we're doing here in melanoma, which is to combine well into the combination escalation of 801 with KEYTRUDA. We're enrolling at our third dose level, and we're on track to have initial clinical data for CX-801 in a handful of melanoma patients by the end of this year to look at what kind of activity and tolerability we're seeing with the combination in this late-line post-checkpoint inhibitor metastatic melanoma patient population. Great. In our closing time, maybe taking a step back, looking forward to the next several years for CytomX, how do you see the company evolving as Varseta-M CX-801 evolves or continues in the clinic, as well as continuing to evolve the broader Probody platform? We're absolutely setting our sights on bringing Varseta-M to the market, building CytomX to commercial stage. Time will fly over the next few years, and we'll be there before we know it. We are well-funded at the moment. We raised, as you know, in mid-March on the heels of our March 16th update. We also, of course, had the cash infusion from the Regeneron expansion, which further strengthens the balance sheet and puts us in a robust position to continue to execute. Varseta-M monotherapy, driving that to its first approval based on the first pivotal study that we'll initiate first half of next year. Looking further down the road, bringing the drug into earlier line settings, and by the way, not just second line, we're also setting our sights on the potential of Varseta-M in the front line in colorectal. This market is absolutely enormous, and the unmet need is huge. A lot of work ahead of us there. Continuing to broaden the pipeline, both ourselves and with our collaborators, bringing CX-801 forward to clinical proof of concept, potentially bringing other ADCs into the clinic, and just continuing to build the company around this very unique technology that we've been working on for a number of years, which is now absolutely delivering for us in this most remarkable way. Fantastic. Well, thank you, Sean, for joining us today. Thanks for having me.