CytomX Therapeutics, Inc. (CTMX) September 2026 Conference Transcript

Great. Afternoon, everybody. We're pleased to have Cytomics with us for the next fireside. Chris, I'm going to turn it over to 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 Cytomics. Just before starting, I will be making forward-looking statements, so I'll refer you to our SCC filings for those disclosures. Just to start, Cytomics is an oncology-focused company, and really we refer to Cytomics as the original masking company. We really invented the field of mask biologics. And what we mean by masking is we essentially have a technology where we can limit binding, really designed to limit binding of target biologic formats in healthy tissue, but activate those therapeutics preferentially in tumor cells. So what that allows us to do from a design perspective is to really go after targets that other companies can't drug. And so 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. So I think we'll talk much more about those, but that's really the focus of the company.

Perfect, wonderful. So maybe two sort of overarching questions, and then we can obviously get into Varsetta, which is the program that I think people are focused on. But first one is, right, so the target for Varsetta is FCAM. You know, as you talked about, masking is important there because that target is pretty widely expressed. So can you just talk a little bit about, you know, know, how you've designed this agent to be able to, you know, hit that target and, you know, just a little bit of history in the field because others have obviously tried this target, you know, why you think you're seeing a different result.

Yeah, I mean, first and foremost, for the target, so 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's 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's been attempted to be drugged before in monoclonal antibodies. There's been T-cell engager formats, and they've all run into toxicity due to expression, presumably in, you know, non-tumor tissues. And so the toxicities that have really limited therapies before are pancreatitis. So all the first, you know, antibodies saw pancreatitis quite early in dose finding, and also liver tox was a challenge. GI has also been something that's confronted that we'll 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. So first we thought this target, if you can create a therapeutic window, could make a big difference in colorectal cancer. And so 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 Matanzine payload that actually we could have advanced on a faster timeline, but we made the choice to switch out that payload with a TOPA1 payload because that mechanism is known to be active in colorectal cancer. Irina-Tecan, which is a Topo-1 inhibitor, is a key part of standard of care in CRC. And so the design, including EPCAM is a great target that we can unlock through masking, paired with a Topo-1 payload for CRC, has really been the focus of this program. And we think, you know, 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 mean, I would say when we did the work going back today with Immunogen, it is a DAR-8 ADC. and we benchmarked the payload to direct TECAN, the payload on in HER2. So in terms of the design and the preclinical work, we thought about this as really in HER2 for EPCAM. That was the design principles. And so when you think about the payload potency and those types of things, potential bystander effect, those were all benchmarked to in HER2, which was, you know, emerging at that time as a best-in-class ADC and has proven to be.

So why don't we talk a little bit about where you are with Varsetta, and then we can obviously talk about where you're going. Maybe first thing, you know, the sort of initial market where you've started to get some data, right, as 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, you know, what's available right now, what sort of standard of care for third line, and, you know, 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, you know, it's one of the, if not the most urgent health crisis 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. And so when we think about, you know, our place in the industry and the chance to make a difference there, I think it'll, you know, that perspective will be highlighted in how we're thinking about the initial development and how much unmet need there is for these patients. And to your question in the context of third line plus, first of all, I would just say it's unfortunately a big market. And so 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, so 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. And so in the context of that pretty poor set of outcomes, we've been very pleased with what we've seen with Varsetta and the chance to make a difference and improve upon those benchmarks. So our patient population has been really fourth line or later. It's 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% to 30% range. Again, that compares to 1% to 2% benchmarks. And our estimated progression-free survival of 6% to 7 months, again, comparing to just a few months in standard of care. And 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. And so 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 delayed phase development.

So 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. GI tolerability is probably the key focus from a tolerability standpoint. What have you seen so far? And 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, so GI toxicity has been the key adverse event that's popped out in the Phase I work, in particular, diarrhea. So, you know, over the course of Phase I, we've seen Grade III diarrhea rates that can exceed 20% at the higher doses into the 30% range for grade 3. So as this observation has 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. and we've optimized that prophylaxis over the course of the phase one 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 and 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 the early part of the study. So that was two months of follow-up, so it was a good start. We're continuing to follow up on those data, including with additional patients enrolled and more follow-up time. And so we're looking to continue to manage that rate of grade 3 diarrhea between 10% and 20%. We really think, based on the work we've done with physicians and thought leaders, that that will be an attractive risk-benefit in the context of the efficacy we're providing. The other thing we've implemented really to really fine-tune the exposure delivered of the drug is we've 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. and we provided some data, you know, on CMAX and PK in our presentation. And those patients, some of them had more challenges with GI. So we think tightening the exposure range and the outliers may help in those patients, the high BMI, and then the prophylaxis is an additional measure.

So we feel like we're making good progress and we'll have additional data, you know, following that up later this year. and I think you know one of the questions probably people focus on here is obviously the efficacy data that you've reported from multiple scans of patients and you say have a good sense of that the safety data where you've changed sort of the dose regimen is early and so we don't have the efficacy from those patients can you just talk about why you're confident about maintaining the efficacy that we've seen with this sort of newer dosing regimen yeah I mean I think the, you know, big picture, what we've seen across the phase one study to date suggests

that Varseta is active in late-line CRC, you know, and across the 8.6 and 10 dose range, which, you know, was dosed at actual body weight, you know, we're seeing response rates in PFS where we think there's room to operate. And so, you know, I think overall our view is, you know, the drug's behaving, you know, fairly consistently across this dose range. And so, you know, really this is about optimizing the therapeutic window within a, you know, compelling overall profile that we've seen to date. And, of course, we need to see that data through and see what we get, but that's, you know, the view based on the steps taken to date.

Okay, perfect. So from a next step standpoint, I think there are two things going on. So one, I think you've committed to sort of talking about what a registration program may look like here. And then 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, you know, 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 Optimist and making sure they're comfortable around whatever dose is chosen. And then 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 Varsetta into late-phase development. And so the context for all the data that's being generated is to make the dose and registrational decision. And so 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.

And so just to be clear, we should expect to get all of that at the same time is what you're saying.

Well, that's our base plan. Yeah, of course, in the context of things like FD interactions, we need to make sure those things stay on track. But our base plan is to provide next steps and data together.

And can you talk a little bit about, obviously, you don't know what that is yet, but can you give people a sense of sort of what the guardrails of that may look like? I mean, is this going to be a, you know, should people be thinking fourth line only? Can there be a possibility to include earlier patients or, you know, combinations? Or what should people be thinking about here in terms of, you know, what the guardrails look like? For the first study?

Yeah, I mean, we haven't made any decisions. I mean, for the first study for monotherapy, I would first say that our basic 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, for example, single-arm studies. And so with that context, we're likely looking at either a monotherapy study in the late line, which would include comparators such as friquitinib, regorafinib, maybe single-agent long surf, or the third line, which is a combination, the standard of care is a combination of Bevacizumab and Launcer. And so we haven't made any decision on which. We think both are attractive from an unmet need and market uptake perspective, most likely. And in any case, this is a first step. And to your point on combinations, you know, in parallel, we've kicked off combination work with Bevacizumab, which could unlock third or second line as we move up the treatment paradigm. And then also in Q4, we plan to start a combination with Varseta, Bevacizumab, and 5-FU, which is really our strategy to replace Rhinotecan in the Fulferi plus Bev regimen, which could unlock second line, and then that regimen is also used in first line. And so those things are all, you know, underway. way. And so in any case, the first step at monotherapy is just that in our view. And this drug has potential in multiple lines of therapy.

And can you just talk a little bit about how you think about market opportunity here? I know you talked about 40,000 patients. You know, if you do have a third line label versus a fourth line label, like how does that change your thinking at all in terms of initial opportunity here?

Yeah, I mean, I would say at a strategic level over the medium term, I'm not sure it changes the overall potential of Varsetta, to be quite honest with you. We're focused on continuing to move up. I think pragmatically for the first launch, third-line versus Fortifine, Fortifine would be more focused, right? So right now, you know, the $35,000 to $40,000 in third line, you know, a lot of patients in fortifying forego therapy or go on to a clinical trial. So we think that market's larger than, for example, what you see in the sales figures because the outcomes are just not that great. Duration therapy is short. and so we think there's 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 and so how that plays out in terms of timing of launch and competitive dynamics I think to be determined but I would just emphasize we're in the lead pack of ADCs for colorectal There's really only two of their competitors, which are much bigger. And 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.

You talked about competition. I want to talk about the combination studies you're 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, so the two competitors we're focused on, one is AbbV400, which is a CMET-targeted Topo 1 ADC, and then the other competitor is a C-Cam 5-targeted Topo 1 ADC from Merck Serono. You know, first I would say that we do believe, and we'll have to see over a long period of time, but we think Epcam, if it's not the best target, we think it's an ideal, one of the ideal targets for CRC. We believe it will continue to be highly expressed in nearly every patient that we won't need to select patients. And so I think when you're trying to change the treatment paradigm, that is a huge advantage. You know, I think in these early days, after the early phase one data across the class, you know, I would say all look compelling relative to what other modalities are. And so probably too early to say on the overall efficacy profile. And then 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, AbbVie has higher grade 3 anemia, which will need managed, both in terms of mono but potentially in combinations. And then Merck KGA has higher neutropenia. Same thing, will likely need managed. And so I think, and of course, you know, not being critical there, but those are considerations for patients depending on their overall health and baseline fitness. And so I think you're already seeing differences emerge, and as larger clinical studies play out, I think, you know, 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, you know, a year behind or so. Those competitors are further ahead on the Bev-Acizumab combinations and are using those combinations as their principal strategy in third line. And so, you know, we have an aim to catch up there.

Perfect. So combinations are obviously an important part, as you mentioned, of the development strategy here. You obviously have the Bev combinations ongoing. You know, when is that data coming? What does that unlock for you in terms of next steps after that?

Yeah, so we're focused on dose finding and safety right now in the Bevacizumab combination with Verceta. We started late Q1 or Q2 of this year. We expect to have initial data in the first half of 2027. So 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 full theory, so it includes 5FU, but with a targeted ADC, you may be able to improve around it. So what I think about it is it's the initial unlock of moving upstream, and that helps us ungate, I would say, with confidence, the work on the triplet, which would be Varseta plus Bevacizumab and 5-FU, which the aim there is to replace urinatecan in the full theory plus Bev study.

Two things maybe on that. So first, why is it helpful to replace urinatecan with 5-FU just for people so they understand what that can achieve. And then the second question, 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? When will you start to do that?

Yeah, so first on the strategic importance. So replacing or in a T-can with Varsetta, I think based on the activity and the targeted nature of an ADC, we think it has the potential to dramatically improve standard of care. I mean, a RIN-TECAN, systemic chemotherapy, but it's around for decades. And so we think the risk-benefit and, importantly, hopefully the efficacy over time, that's a central component of our strategy. And if you think a bit longer term, if we can replace a chemotherapy option, then Varsetta 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, so that will take work and some time. We are carrying forward the learnings from monotherapy into the combinations, so we do think adjusted ideal body weight dosing is a better way to, again, deliver the targeted exposure in patients 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. And we'll continue to learn over time as we have experienced the versetta, 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? You know, does that look dramatically different than what you've looked at in monotherapy?

Yeah, I mean, we have gotten going on the BEV 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 the every two-week schedule. And then ultimately the chemo combination will also be, 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. And so that will take a little bit of work because we've been studying the drug as a Q3 week, every three-week monotherapy. So, but we think long-term that that's the right play just to make sure that patient and physicians have a good experience.

Okay, perfect. So Epcam is obviously expressed across a lot of tumors, right? Some more than others, right? And CRC makes sense. That's why you started there because it's most expressed. What are the other tumors, you know, think you think make the most sense to go after and how should people think about, you know, potential data generation there?

No, we're really excited about the work outside of CRC. We've been intentionally focused, and I would say quite patient to do work outside, but we did announce on our Q3 earnings call we are going to do phase one cohorts for three additional indications. So we're going to do gastric and GEJ, and we're not going to select patients because we think most will have, the vast majority will have high up-cam expression. We are going to do pancreatic, and we're going to do biliary tract. We think basically these three indications, one, unmet need, and second line plus or third line is still very high. There really isn't significant development of other ADCs. There's some, but nothing that's really broken through. And long-term, we're focused on building a commercial GI franchise for cytomics, obviously starting in CRC, but these three tumor types, you know, if we were to see signals, you know, in the later line, could be additional fast-to-market potential and I think really also point the way to the, you know, pan-tumor potential of Epcam as a target. So, and we are, 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 haven't needed to do that in CRC. We don't think we need to in gastric. But in those two indications, you know, roughly a half of patients, half of patients we think will be high. And in terms of, like, generating the most meaningful data set, we think that's the right initial strategy, and then we can build from there.

And from a, you know, trial standpoint, I mean, do you need the data from the optimized monotherapy cohorts here to start in these patients? How are you thinking about, you know, the data that you have in CRC giving you dose and schedule in these other tumors?

I mean, we feel like we're 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, you know, and will inform what we do in the non-CRC indications. That said, there's precedent across the ADCs where different tumor types can have different doses. I think in HER2 is an example of this, for example, in gastric. And so we don't 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 alpha. You know, what are the next steps for that program and why you're excited?

Yeah, I mean, I think interferon alpha just, you know, at a high level, one, I would just say it's a mass cytokine, so interferon alpha-2b. Interferon alpha-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's severely toxic. Patients get severe flu-like symptoms. They're not able to tolerate it well, But it's 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. And we're really looking to do this initially in refractory melanoma. so PD-1 refractory melanoma, where, you know, patients really don't have additional options. And we're going to combine with K-TRUDA initially for proof of concept. And so the way we think about this setting is patients who get, for example, a PD-1 re-challenge or checkpoint re-challenge, you know, typically don't have great response rates. Some of the literature suggests 7% to 10%, and so we're looking to generate a signal that's significantly above that as a proof of concept. And, you know, if that were to work, I think we'd have a number of options to develop this in, for example, late-line melanoma, potentially earlier lines. And then, you know, the mechanism should work more broadly across PD-1 refractory populations, renal, bladder. There's a number of areas we could go. So I think, you know, we know we need to do the work, generate the proof of concept. We think, you know, this could be quite a broad and potentially important opportunity as well.

And what's timing there in terms of?

Yeah, so we're in dose escalation. We expect to have an initial data set by the first half of next year.

And then maybe just last question, which everybody always wants to know, is, you know, how do you think about your funding right now and what does that give you in terms of milestones?

Yeah, so 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's runway to at least the second half of 28. 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'll get within that runway. And 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. We appreciate it. I appreciate it.