All right. Hey, good morning, everyone. Welcome to day three of our Cantor Healthcare Conference. My name is Olivia Brayer. I'm one of the senior biotech analysts here at Cantor, and we're really excited to have with us from CytomX, we've got Chris Ogden, who's CFO. Thanks, Chris, for joining us. No, thanks. Thanks for having us. Thrilled to be here. So obviously, a lot of progress and some new data that's come out this year for the team. A lot's changing since we've had you up on stage last year. Maybe just give us a rundown, right, of where the company is today and the trajectory that you guys are headed. Yeah, first, just, an overview on CytomX. We're a clinical stage, oncology-focused company, and we really pioneered the field of masked antibodies. We were one of the first to bring this concept to the market, and we've been working on it for more than 10 years. And so we now are at the point where we have three clinical stage programs across multiple modalities. We'll talk, I'm sure, about more- Mm-hmm ... more about those, but T cell engagers, antibody-drug conjugates, and cytokines. We also have five large pharma partnerships, Regeneron, Moderna, BMS, Astellas, to name a few. And so the company's really well-positioned. We have cash through the end of 2025, and that's comfortably without any milestones or new BD into the company, so really, really well-positioned and excited about the next steps ahead. Yeah, and you mentioned, obviously, your antibody masking technology platform. I mean, maybe just give us kind of an overview of how your approach is differentiated. Yeah, I mean, I think first, we have been working on this longer than anyone else, and so, you know, the depth and breadth of the protease biology that we understand, how that translates into the linkers and substrates that hold the mask on when they interact with the tumor environment, you know, we have more experience than anyone in the field, both pre-clinically, but importantly, clinically. We've brought prior programs into the clinic, where we've learned from those, and then optimized future design of next generation masked therapeutics to really optimize a therapeutic window. I think where it shows up in two ways, first, in our partners. If you look at the breadth of what we're working on, just to use a couple of recent examples, in the last two years, we signed a partnership with Regeneron in T cell engaging bispecifics, which, you know, their scientific bar is extremely high, and so I think that speaks to the depth that we've built over time. And then in new frontiers, you know, we're working with Moderna on mRNA-encoded masked therapeutics, and I think without the, you know, experience and, breadth across multiple modalities over time, that would not occur. And then as it relates to our wholly owned programs, we can talk more about this, but we do think, based on our learnings prior, those are really optimized for higher probability of success than prior programs, you know, based on our past learnings, which is sometimes how the innovation cycle goes and how we see the current positioning of the company. Yeah, and then from a sort of strategic priority perspective, you do have a lot of different modalities that- Right ... that are either moving into the clinic, already in the clinic, you know, ADCs, TCEs, cytokines, et cetera. How do you think about prioritization of those programs? Yeah, so the first thing is we are quite intentional about what we keep wholly owned, and/or retained economic rights from a commercial perspective. So first, to start with the partners, most of our partnerships, and this is sometimes, you know, a bit misunderstood, those really start with, you know, novel kind of research and scientific ideas that we're collaborating on with the large pharma partner, and so we're not necessarily out-licensing a molecule or an asset. We have technologies that synergize to, you know, bring together to make a better therapeutic, you know, potentially for patients. And so I'd say most of the partnering we've done is in that vein, where it's really advancing the breadth of the technology. In terms of wholly owned, I mean, we're looking for killer applications of the technology, right? And so when we look at a target, perhaps that can't be drugged by other companies because of therapeutic window, we're really looking for the biggest unmet need and the best application of our technology, and we do think the multi-modality gives us some advantage there, 'cause you have more options, you have more tools to work with- Mm-hmm ... in the programs, and then we could be quite intentional about, for example, what effector, so what modality in ADC in terms of a payload or, you know, CD3 in terms of a T cell engager, what to bring to that specific, you know, target to really optimize the potential benefit for that indication and that patient. With all these partnerships, right? I mean, how do you think about which ones have necessarily been the most successful or productive, or maybe I'll ask you upfront, right? Like, which is your favorite partnership? Ah, well, that's like the favorite child- The favorite child. ... question. Quite honestly, I think we're proud of the body of work with partners. Especially if you look at the longevity of a number of them, that I think speaks to how we work with partners. I would highlight a couple examples just to maybe, you know, paint the picture of the potential with the partnerships. One, the molecule I think we're going to talk more about, CX-904, T cell engager with Amgen. That was, you know, developed in the context of a very early research partnership, bringing together our experience in masking with Amgen's experience in EGFR, and also T-cell engagers. And really, so I mean, that's an example of an area where we made progress because we did it together. It would've been hard- Mm-hmm. For us to progress that project, you know, in 2016, 2017, based on where T-cell engagers were more broadly, and so that's a very successful one, right? That we're making clinical progress. And then I would highlight just this year with Astellas, we've earned two preclinical milestones, but for programs that are now, you know, into potential IND-enabling studies, and those are also in bispecific immunotherapies. You know, those have the example of, you know, the potential to bring a lot of economics to the company. We actually have some opt-in rights commercially on some of those programs, so it's really built for the long term, and we do, you know, I believe the partnerships are underappreciated. Yeah, and you mentioned CX-904, obviously your, you know, lead program, a lot of interest, a lot of engagement around it this year. You did have some data. That is the T-cell engager, you know, EGFR CD3 for the audience. Can you just kind of run us through your conviction in that program, maybe some of the high-level takeaways from the data set, and where- Yeah. Where do you go from here with it? Yeah, great question. I mean, first, just to paint the picture, maybe level set. So EGFR CD3 is a really unique mechanism of action. We're looking to use the EGFR target antigen as an address to really redirect the T cells to identify the tumor and kill the tumor. So it's very different than a traditional EGFR, you know, monoclonal. So the biology is unique. The other thing I'll say is just preclinically, and I think it's good to back up, no one's brought this mechanism into the clinic prior to this in an unmasked form, 'cause you'd expect it to be highly toxic, both skin- Mm-hmm ... related toxicity, immune-related toxicity, and probably the combination of those would be severely toxic. Amgen had a program a number of years ago that they did not advance past preclinical for that exact reason through their Micromet acquisition. So with that context, the initial data update, you know, in 35 patients, where we, you know, escalated up to a step target dose of 10 milligrams and continued to be dose escalating, the safety profile from our view is highly encouraging. We saw very little cytokine release syndrome, which is the key toxicity that's really held back this class for solid tumors. In step dosings, we saw no cytokine release syndrome. Mm-hmm. And so we've definitely got room to operate in terms of the continued exploration of the drug. That's a big win for us when you think about the context of an undruggable target. And then on EGFR-related toxicities, they look very manageable, mostly low grade. We had one Grade 3 rash out of 35 patients, so again, looks manageable overall. And then on efficacy, it's early, it's dose escalation, so again, focused on safety, but we were pleased to see, you know, confirmed partial responses. So tumor shrinkage at you know, two scans out to 12 weeks in pancreatic cancer was the signal that jumped out. It was, you know, an N of six, six patients, but to see those responses and the rest of the patients with at least stable disease, was highly encouraging that we potentially have, you know, an active drug that looks safe in an area of very high unmet need. We didn't see a lot of activity in other tumors. The one we principally studied was colorectal cancer. We had about half the patients in colorectal cancer. We saw some some tumor shrinkage, but nothing meaningful there. So I think it's a really interesting early signal. We're gonna do more work, enrolling pancreatic cancer- Mm-hmm ... as we progress through the back half of this year, and then also explore the drug in more, you know, known EGFR tumors that are traditionally sensitive, like head and neck, and lung cancer, which we think the drug has, you know, potential in as well. Yeah, I mean, any thoughts on why you didn't necessarily see some of those responses in some of those other indications, like lung cancer, for example? Yeah, so I think on, on lung cancer and head and neck, our view, we really just haven't done the experiment. We had a couple of patients- Mm-hmm ... for each of those indications. You know, since it's phase I, mostly focused on safety, that just was not where we saw robust enrollment. We're now focused there, now that we've got an initial profile that you know has you know proof of some efficacy- Mm-hmm ... and so enrollment there is a priority. On colorectal versus pancreatic, I think there's a number of things to note there. You know, one, just starting with colorectal, we of course would've loved to see some more activity. That tumor type has, I think, traditionally been just very difficult, you know, including. You know, I think there's been updates since ours on EGFR CD28 in combination with PD-1, for example, in the field that, you know, showed pretty modest activity. So it's possible that in colorectal you need multiple signals. In pancreatic cancer, since our update, there's been another T cell bispecific, CD3 targeting a different antigen. Mm-hmm. Claudin-18.2, that actually showed about a 30% response rate in a phase I study, about 30 patients, suggesting that maybe we're not alone in terms of pancreatic potentially being responsive to this type of immunotherapy. It hasn't been to checkpoint, but maybe there's something unique about the biology, and we'll do more work to see if that you know firms up over time. Right, and durability of response is obviously very important, too, right? And I know there's been a lot of, you know, conversations just around DOR and the importance of that- Yeah ... in your data set. I mean, what do you guys make of the responses that you saw in terms of the durable effect and, you know, what gives you the confidence in your program going forward that you will have deep and durable responses? Yeah, great question. I think in general, in phase Ia at this stage, it is early. Yeah. So I don't think we, you know, have enough information to make a definitive judgment. I will say, in the context of pancreatic cancer, just given, how high the unmet need is and unfortunately, how poor the duration of responses are in really third line plus- Mm-hmm. ... we're talking about a couple months of progression-free survival. Having confirmed responses out to twelve weeks and, you know, and beyond is a start. It's not... We obviously need to learn more, but it's a start. The other thing I would say is if you looked at probably the best example in the field for T cell engagers, which is Amgen's Imdelltra, which is a small cell lung cancer drug, targeting DLL3, you know, they have a profile that looks like it's driving durable responses. So I would say, you know, writ large on the field, with that being probably the biggest body of evidence, it looks like this mechanism can work early in terms of- Mm-hmm ... driving responses and can drive durability. We'll have to obviously understand, you know, how our drug looks in that context over time. Yeah, and Amgen is your program, obviously, or, sorry, Amgen is your partner, obviously, in this program. What have the conversations with Amgen been like since the data readout? Yeah, a great question. So we have regular updates with them in the context of the alliance. Mm-hmm. You know, collectively, we view this as an important first step, so we're encouraged, you know, where we are. You know, in terms of specific comments beyond that, I can't speak for them, but you know, big picture, you know, we feel quite fortunate that they're a great partner on this, as I just spoke to the Imdelltra example. Mm-hmm. But, you know, world leader in T cell engagers from our view at this standpoint, and, you know, we think the discussions as we progress into the back half of the year, you know, we're looking forward to those, and hopefully get to alignment, you know, as we come into the back half of the year. Yeah, and so in terms of next steps, I mean, walk us through that. What does that look like? Is there sort of a timeframe that Amgen has to make a decision about opting in? What about phase 1b starting up? How are you guys thinking about those timelines? Yeah. So, we're in control of the program and the development right now in phase Ia. Amgen does have an option to opt in to the global co-development as we move to phase 1b. Mm-hmm. There's no set timetable on that. It's really based on when we feel we're ready to make those decisions and, you know, in consultation with them, 'cause obviously we'd want to be in alignment in that context. You know, we'd make that decision together, and then we'd continue to run the phase 1 portion, so the phase 1a- Mm-hmm ... Ib. Amgen Ib. Amgen Ib. Amgen takes over after phase II, and there's a co-funding arrangement where we retain, you know, material U.S. commercial rights. So really the, you know, next step is generate data in the back half of this year, again, focused on dosing schedule, pancreatic, head and neck, and lung. Mm-hmm. And then by the end of the year, we think we'll be in a good position to have a robust discussion on next steps. Yeah, and those data that we will get, remind me, that'll be publicly announced by the end of the year, or that'll be something that you'll have in-house and maybe could be an early 2025 readout? Right. We'll give a program update by the end of the year- Okay ... as it relates to where we think we're headed with the drug, in the context of the alliance, with Amgen and more broadly. The data that underpins that decision, likely in 2025 to follow. Mm-hmm. Likely first half of 2025. Okay, understood. And then for those data, once those are, you know, publicly disclosed, maybe just give us a sense of what we could see, right, in terms of potential patient numbers. I mean, it sounds like pancreatic, lung, head and neck are all very likely indications that we'll see. You know, will it be more patient numbers? Will it be longer, you know, duration of follow-up? I mean, what kind of granularity can you give us around what we should expect next year for those data? Yeah, I mean, without... We're not speaking to patient numbers, just given, you know, that's. We'll see how that plays out. In general- I had to try. Yes. In general, though, in terms of what we'd want to update on, you know, first dosing schedule- Mm-hmm ... you know, as discussed, we were at a 15-milligram target dose. If we clear that, we would, you know, potentially have data in that higher doses and potentially go beyond that. So dosing schedule is one thing to look for an update. The other thing is we'd expect to have enough patients in the three tumor types we mentioned, pancreatic, head and neck, and lung- Mm-hmm ... to, you know, draw at least early conclusions on whether there's signs of tolerability and efficacy to inform phase 1b. Mm-hmm. And so really I would focus on that dosing schedule, and then those three indications. Okay, understood. The dose that you do move forward with in phase 1b is still a little bit up in the air, right? Because we haven't actually seen that 15 mg dose level. Yeah, I mean, that's... We're still working through that. That is a key with this modality in general. Mm-hmm. If you look at updates at ESMO even, right, there's navigating that can take some time, and then also the discussions with Amgen will be really important, because they have a lot of expertise. And there looks like there is a dose response in this class more broadly, but it's not as linear as something like an ADC or a monoclonal antibody, and so it's, you know, I think more the scientific discussion on that will be important. Mm-hmm. Yeah, and you mentioned this earlier, but your safety to date has been very clean, the tolerability profile. I mean, how do you think about dose intensity, right? And you mentioned step-up dosing, but is non-step-up dosing something that you guys are considering as well? We're leaving all options on the table. We did see, you know, early activity at one of the flat doses, so one of our responses was at the highest flat dose in a pancreatic cancer patient, and we've seen, you know, responses and activity at the step-up doses, as you mentioned, with good tolerability, and I would say in general for the field, what seems clear is, one, responses do happen quite early with this modality. Mm-hmm ... you know, first or second scan, and so we do think, you know, the early dose intensity is important. How we get there, I think that's, you know, that is one of the things we're continuing to look at in terms of optimization. Yeah. Well, I know everybody in this room is looking forward to that progress. Yeah. I did wanna ask you a little bit about competition, right? Because there are other TCEs that are in development, that, of course, get investor attention as well. I mean, how are you guys just thinking about the landscape more broadly and how you guys really fit into this, you know, T cell engager class overall? Yeah, it's a great question. We're quite excited by the level of competition. Quite honestly, we think T cell engagers are at a moment in time where there's gonna be a lot more- Mm-hmm ... innovation and masking of T cell engagers, looks based on the work of us and other companies, to be a, you know, a key strategic approach to unlock new targets, open therapeutic window. And, we think competition in that context, based on T cell engagers still having a lot of room in solid tumors- Mm-hmm ... masking overall. While there's increased competition, there's not that many, many companies working on it, especially with our level of expertise. So we think the competition is gonna help us and the field, and quite honestly, we're rooting for success across multiple approaches and modalities because we think there's just a lot of green space as it relates to new targets and therapeutic window. Yeah, and then you obviously have a lot of other modalities in play, right? Maybe we'll talk about your ADC program. I mean, you- Yes ... you have an EpCAM, ADC. I think it's CX-2051? Yes. If I have that right. I mean, how big of a focus and just strategic priority is that program at this point? It's been a key strategic priority. Mm. If you go back two years, when we restructured the company, based on a phase 2 readout of a first generation ADC, we actually met the primary endpoint in that first generation ADC, but we were comparing and contrasting to the other opportunities in the portfolio and obviously thinking about capital allocation. You know, EpCAM, at that point, was the... That ADC was a key focus on why we were excited about what was coming next. So it's a key priority. It's wholly owned. We did license it from ImmunoGen, which, there's some history to that, which we can talk through. But there's a few reasons why we think it's, you know, really important. First, that it's a great target. It is a pan-tumor target. Mm ... that we view as having more validation than other targets we've worked on before. There's a number of examples of companies driving some activity through localized EpCAM approaches or even attempts to systemically drug it that have been limited by toxicity. The other thing is we've really designed this drug with the indication and patient end in mind, which is really focused on colorectal cancer. Yeah. If you look at the target, EpCAM is expressed in more than 98% of colorectal cancer. It's IHC 3+ in most of those patients. The payload we've put on this drug is a Topo 1 payload licensed from ImmunoGen that's very analogous to deruxtecan, which is the payload- Mm-hmm ... on in Enhertu. irinotecan, so this class is standard of care in CRC, so the payload really matches what's already standard of care in the field. And then there's evidence, you know, in the clinic from drugs like Enhertu in small patient populations. And AbbVie has a program targeting c-Met, that Topo 1 ADCs in late-line CRC can drive... you know, meaningful response rates much above the standard of care. And so we think the program is really tailored- Mm. -to run that experiment, which is, you know, quite focused. And so we think that's an important, you know, program for us, especially as we look to first half of 2025. Right. So I mean, ADC in EpCAM, you think you have the right modality, could be the right target, obviously, colorectal cancer, all makes sense to me. So when you think about the bar for success for this program, you all will have data at some point next year, you know, just how are you thinking about internally, what you're looking to see from this program- Yeah -just to get you even more enthusiastic? Yeah, in terms of, of benchmarks, and we haven't commented on, like, you know, what our internal bar is. If, if you look at the third line plus or fourth line colorectal cancer, which is where- Mm-hmm ... you know, the initial phase I is gonna be studied. You know, single agent, very low single digit response rates, five months PFS, even in combination, you know, single digit response rates. So the bar, in terms of what's available for treatments today, is quite low. Mm-hmm. If you look at AbbVie's progress with the c-Met ADC, you know, in third line plus CRC, they had about a 20% response rate, you know, in that patient population, and then, you know, based on c-Met cutoffs, a bit higher from a- Mm ... retrospective perspective, and so we think that's interesting data, for sure. They're investing in that program quite aggressively, and so I think those are kind of a couple of, you know, contextual points to, you know, paint the landscape. Right. Oh, and you mentioned, you know, that there are some combination agents, right? And we have seen activity there. Would it make sense mechanistically to potentially combine your asset with another one? It- Or your modality with- Certainly down the line. We do think the drug is designed to work in late-line CRC. Mm-hmm. So that's the initial experiment. We also have preclinical data showing that, you know, post irinotecan, which is the frontline chemotherapy, that the drug works in those settings, whereas irinotecan does not, and the AbbVie data, you know, would support that the Topo 1 payload- Mm ... works as well. In terms of combinations, we certainly look at that as we get, you know, clinical proof of concept on single-agent activity. Mm-hmm. You know, AbbVie's expanding into the combinations with things like Avastin in earlier lines, and so, there's a number of different ways you could go, but certainly there'd be combination potential. The long-term play here, do you think you could eventually move upstream in the CRC market? Yes. I mean, I think the big, big picture. I think strategy for ADCs- Mm-hmm ... is to potentially replace earlier line chemotherapies, that could be a win-win for patients and also large market opportunity in terms of these novel mechanisms for ADCs. Yeah, and then you also have another program that recently entered the clinic, that's CX-801. And maybe just tell us a little bit about this program, and again, I mean, level of just enthusiasm and really, I'm curious if it's really on investors' radars at this point. Does it come up in many of your conversations? Great question. So first, we're very excited. It is a bit overlooked. Part of that is, you know, it is a mechanism that will take a bit more time to develop, so we're guiding to an initial update in the back half of 2025. But you know, interferon, we think, is overlooked in the cytokine field. There's a lot of companies working on IL-2, but interferon was actually an approved immunotherapy that was limited by tox and has proven single-agent activity, low-level single-agent activity. Mm-hmm ... and is a powerful presenter of tumor antigens to really drive more combination potential with PD-1. Merck ran an experiment with Keytruda with interferon, so unmasked, and saw a 60% response rate in melanoma, but had, you know, very high Grade III, IV AEs, 50% Grade III, IV AEs. So there's clear synergy from an efficacy perspective, but not developable due to AEs. So we've masked this quite efficiently, we think, and, you know, we think with, you know, focused development in combination with Keytruda, which we have a supply agreement, there's a, you know, quite interesting and large path forward, you know, in combination immunotherapy. And again, there's not a lot of competition. There is one other program that Jazz has licensed from Werewolf, but you know, we think this could really open up you know, quite a bit of potential in the cytokine field. Yeah, and I mean, you guys obviously have a lot of different readouts coming, let's say, in the next 12 or so months. Yeah. What are you most excited about, or what should we be paying most attention to? Yeah, I mean, we, we really are... We've built the company over the last two years to be at this moment in time. So the fact that we have, you know, three clinical stage programs that we think are differentiated with, you know, some competition, but we think- Mm-hmm ... lots of opportunity with real data on all those programs, you know, likely as you said in the next twelve to eighteen months, you know, we think the potential to deploy capital behind those as data matures is very significant and, you know, a great opportunity for shareholders and we think patients. So toward the position of where the company is over the next twelve months, very excited to see how these programs play out in the clinic and for-