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

Hello, everybody. Thank you for joining us at the Wells Fargo Healthcare Conference. It's a pleasure to have you all. I'm Jessica Boardman with the banking team. Today, I have the pleasure of introducing Cytomics. For those less familiar, Cytomics is really focused on Barsetta M and Epcam-directed ADC with promising, exciting clinical data and late-line CRC and broad potential across an array of tumor types. speaking on behalf of the company is Sean McCarthy, CEO and Chairman.

Thank you, Jessica, and thanks to the Wells Fargo team for their kind introduction to be here today. It's a pleasure to be here to share our latest progress at Cytomics Therapeutics. I will be making certain forward-looking statements in the course of my presentation today, and I refer you to our SEC filings. So I'll talk to you today about how we're unmasking advances in oncology using our proprietary pro-body therapeutic technology platform. This is a platform we've been working on for a number of years. We have pioneered the space of antibody masking now for more than a decade and applied it to a number of target strategies. And with the two programs that we're currently advancing, We have, I believe, really pinned down the combination of going after the right target, the right tumor type, and the right effector mechanism. And we really believe it's the combination of all three of these that are leading to our current success applying our unique technology. We currently have two programs in the clinic, Varseta Tug Mazatecan, otherwise known as Varseta M, formerly known as CX-2051. This is an EPCAM targeting masked antibody drug conjugate that we're developing initially in late-line colorectal cancer. We're also developing a pro-body masked version of interferon alpha-2b in melanoma. We are in a robust financial position. We reported recently more than $350 million of cash, including a significant influx of cash from an expansion of our longstanding collaboration with Regeneron. We are based in the San Francisco Bay Area, an integrated R&D company with about 90 employees. So speaking specifically and initially about Varsteta M, this is a drug we're very, excited about. As I mentioned, it's a masked antibody drug conjugate targeting EPCAM. This is the only EPCAM targeting ADC that we are aware of. So this is a first-in-class antibody drug conjugate. We believe with our technology, we're the first to unlock EPCAM as a drug target. The program thus far has been focused in late-line colorectal cancer, and I'm delighted to report that just a week or so ago we announced fast-track designation awarded by FDA in relapsed refractory metastatic CRC. We have shared very encouraging anti-tumor activity in late-line colorectal cancer most recently in an update in mid-March this year reporting a very significant overall response rate highly encouraging progression-free survival in an all-comer patient population in late-line colorectal. We've also reported an encouraging safety profile. Epcam has been a very difficult target to drug over the years. We've really broken through on this target, which is highly abundant in colorectal cancer. We have an attractive safety profile with low rates of hematologic toxicity, no measurable interstitial lung disease, no classic Epcam toxicities that have been a challenge with this target in the past. And the one adverse event of note we are learning more about all the time, which is a certain rate of high-grade diarrhea that we're learning about and learning to manage as we move through dose optimization. We're currently in the dose optimization stage of phase one with the goal of initiating our first pivotal study in the first half of next year. And I know I don't need to tell you that the colorectal cancer market is absolutely enormous. This is a huge unmet need on a global basis, and this is a strategic, highly strategic opportunity for us to move this drug forward in initially late-line colorectal and then subsequently bring the drug into earlier lines and further into additional tumor types beyond that. So it's a very exciting time for our company as we advance this drug candidate. So in terms of the program itself, it is both broadening and deepening in real time. As I mentioned, we're on track to initiate our first registrational study in the first half of next year. We're also expanding into combination studies. We have a combination, a phase one combination with bevacizumab underway with initial data anticipated in the first half of next year. We're also working towards initiating combination studies with chemotherapy and late-line colorectal. Also later this year, we've also recently announced expansion into three additional tumor types, gastric, gastroesophageal junction cancers, pancreatic cancer, and also biliary tract cancer. So as I said, the program is advancing and broadening very, very quickly. And in addition to that, the 801 program is also moving forward. So let me take a deep dive on Varsetta M and show you the context for this program, where we are and where we are headed. So as you all know, colorectal cancer has seen a real dearth of innovation really for more than a decade. It's a very, very difficult disease to treat, particularly in the late line setting. But with Varsteta-M, we can say today that the promise of antibody drug conjugates is coming to colorectal cancer. ADCs, of course, have broken through in a number of solid tumor types, following on from initial approval in multiple hematologic indications. And we're very thrilled to be at the leading edge of bringing ADCs to colorectal with Varsteta-M. And again, this is the only EPCAM targeting ADC in development that we are aware of. Colorectal cancer remains one of the biggest unmet needs in oncology. The numbers are very large. The number of patients on a global basis is in the millions. It's the second leading cause of cancer death worldwide. Five-year survival is a dismal 13%. And rather alarmingly, colorectal cancer is growing in incidence in younger patients. So this indeed could be considered an emerging global health crisis. New solutions are needed. From the commercial point of view, it's an absolutely enormous market on a global basis. In the late line alone, this is a multi-billion dollar opportunity. And as we march earlier into third line, and ultimately our goal is to bring this drug into the front line in colorectal, the numbers get very large very quickly. So from a value creation standpoint, certainly from where we stand today, this represents a huge opportunity for value build in cytomics in the near, medium, and longer term. The design of Varseta M has been highly intentional. epcam is a protein it's a target that we've known about since 1979 it's such an abundant antigen it was one of the first colorectal cancer antigens to ever be described and ever since that time many institutions and companies have tried to target epcam given its high level of expression the challenge has been that epcam as the name suggests epithelial cell adhesion molecule is also present on many normal epithelial tissues and that has led to systemic toxicities for a wide range of different approaches that have been taken to try to target epcam previously so it's previously been impossible to open a therapeutic window for this target whether with an antibody whether with a t-cell engager certain conjugate structures no one has been able to achieve therapeutically active levels of a systemically administered drug targeting epcam we do know however that if you can locally target epcam you actually can induce anti-tumor responses and this has been shown by two two agents one of which was recently reapproved in Europe it's called Corjuni it's an anti-epcam targeting tri-specific antibody which is effective in the treatment of malignant ascites, but the drug has to be administered intraperitoneally because it has too many systemic side effects. But that is an important clue. It shows that if we get an empowered antibody actually to the target, to Epcam, we can induce, it is possible to induce anti-tumor responses. So how have we approached and how have we solved this problem at Cytomics? Well, we've brought our masking technology to bear, our probody therapeutic masking strategy. First of all, we made an antibody to Epcam, a high affinity antibody. We then used our protease dependent masking to engineer what we call a pro-body version of that antibody so that the pro-body has limited ability to bind to target until the mask is removed. And the mask is removed specifically and selectively within cancer tissue by tumor associated proteases. This is the core of our platform. Tumor-associated proteases, which are switched on in cancer, clip off the mask, allowing the antibody to recognize and bind its target and elicit its therapeutic effect. The therapeutic effect of Varseta M is mediated by the cytotoxic payload that we have conjugated to this ADC. This payload is called CAP59. It's a novel topoisomerase 1 inhibitor. It now has a new generic name called Masatecan, and it's linked to the antibody through a tri-alanine cleavable peptide linker. So this is a novel, masked, Epcam-directed antibody drug conjugate. Right target, right tumor type, right payload. We chose to first study Varsetta M solely in colorectal cancer to really see what this drug candidate can do. And one of the main reasons for that is, first of all, the target is so highly expressed in CRC, that's what this drug was designed to do. But this slide shows the current standard of care in late-line colorectal. And you can see that the numbers are really pretty dismal in terms of response rates, progression-free survival, overall survival. Once patients have progressed in CRC through conventional chemotherapy in the first and the second line settings, their opportunities for treatment in the later line are really poor. And it's this problem that we're looking to solve with Varsetta M. In terms of development strategy, we have a multi-tiered strategy to walk through multiple lines of development over time. First of all, to generate proof of concept in late-line metastatic CRC and move towards our first registration in this setting. And we're on our way to do that, potentially launching our first study in the first half of next year, building on the 113 patient phase one study for which I'll show you an update in a moment. We then plan to bring the drug into earlier line settings, into second line and then ultimately into first line, through combination strategies. And then over time, and we've started already, we plan to expand into additional tumor types. Epcam is expressed not only in CRC, but actually on most other solid tumors as well. So in the long run, we think that Varsetta M has the potential to even reach a tumor agnostic pan-tumor label across multiple cancer types. But one step at a time, let's talk about where we are with the monotherapy in the late-line setting. Just to recap here, we do see a broad development opportunity in metastatic CRC. This slide shows the current treatment paradigm from early line to late line, from left to right, and it's those treatments in the third line or later that we'll be comparing ourselves against as we move into our first registrational study and then over time move the drug into the earlier line setting. I should also say here that over the years colorectal cancer in earlier line settings has become quite fragmented as the field has sought different biomarker and patient stratification approaches to target the right drug to the right patient. One of the hallmarks of Varseta-M is because the target is so abundantly expressed on every patient, we have actually been able to treat all patients in an all-comer setting in late-line colorectal. That's regardless of other clinical characteristics like KRAS mutations, BRAF mutations, left side or right side, whether or not the patients have liver metastases. And this has really helped with our rapid enrollment into the study. And we believe this drug will continue to show activity across this range of patients without the need to select. Neither have we had to select for target level because the target is highly expressed on more than 90% of patients. So in our phase one study to date, we have conducted the study in three stages. First of all, dose escalation, dose expansion, where we expanded at three dose levels, 7.2, 8.6, and 10 milligrams per kilogram administered on a Q3 week schedule. Again, this is in patients treated in the fourth line or later. So it's a late-stage patient population. And more recently, we moved two of those doses into dose optimization. These are the doses of 8.6 and 10 milligrams per kilogram, again administered every three weeks, but this time with an adjusted ideal body weight calculation of dose. And we also implemented upfront prophylaxis with loperamide and budesonide to attempt to manage and mitigate the onset of this one toxicity that we're paying close attention to, which is diarrhea. So the study has made terrific progress, 113 patients enrolled, and we're on track to present an update on the study by the end of this year, which will include data from the two dose optimization cohorts together with extended follow-up on the 73 patients that were enrolled in escalation and expansion, and that update will also include our first sharing of overall survival data from the escalation and dose expansion phase. So we're really excited to have this study has progressed to date and really looking forward to presenting this update from the phase one study later this year. We're also very active in bringing the drug into earlier lines through initially starting to combine with other agents. And as you know, bevacizumab is broadly utilized in colorectal cancer across really all lines of therapy. It's heavily used in the third line in combination with Lonsurf, in the second line in combination with Arunatecan containing regimens, and also in the first line setting. So it's really essential that we gain experience with combining Varseta M with Bev to enable coming into early aligned settings. This work is underway. We're in dose ranging, dose finding. We've treated our first patients and our goal is to share initial data from this combination in the first half of next year. This will be foundational, not only in potentially enabling a third line evaluation of Varseta-M in combination with Bev, but as I said, also in moving into earlier line settings. We're also actively combining, working towards starting to combine Varseta-M with chemotherapy, and particularly with the backbone of second line chemotherapy of metastatic CRC, which is 5-FU. So our goal towards the end of this year is to initiate a combination with Bevacizumab plus 5-FU, again as a stepping stone to reach into second line therapy with Varseta M. So that work and that planning is now well underway. We're also actively moving into additional tumor types. As I mentioned, Epcam is highly expressed in many other cancers, and we've selected certain GI indications initially to expand into because of their adjacency to colorectal. Our goal is to take Varsetta M all the way through to approval and launch ourselves. We absolutely see line of sight to doing that. And as we work towards building our commercial infrastructure to launch Varsetta M, it obviously makes sense to explore additional GI tumors initially to build into a potential GI commercial franchise. So those first tumors that we've selected for evaluating Varsetta M, R, gastric, GA, pancreatic, and biliary tract tumors. And in gastric, like in colorectal, we see no need to select patients for target expression. We validated ourselves, and this is known in the literature, that gastric highly expresses Epcam. More than 80% of patients express high levels of Epcam, so no need to select patients for target level there. In pancreatic and bilary tract tumors. About half of patients are high in Epcam, so we do plan to at least initially start in Epcam high pancreatic and Epcam high bilary tract tumors. These patients will be treated on a Q3 week adjusted ideal body weight schedule. We plan to enroll about 60 patients across these three tumor types, evaluate this initial data, and then determine potential steps forward to expansion and potential registrational studies in these new areas of medical need. So we have with the Varsetta M program multiple milestones anticipated over the course of the next 6 to 12 months. First of all additional data from the ongoing phase 1 study by the end of this year. Our goal is for this update to have two main components. First of all, to share the go-forward strategy for Varsetta M in terms of the structure and goals of that first registrational study that we aim to start in the first half of 2027. And of course, to report the underlying data from the escalation, expansion, and optimization phase that underpin the design of that first registrational study. We're also on track to communicate initial data for the bevacizumab combination in the first half of next year as we work in parallel to begin our work with the chemotherapy chemotherapeutic combination with 5-FU and our work in additional tumor types. So a very exciting time for the Varsetta M program. We really think we've done something quite unique by using our technology to unlock EPCAM as an ADC target. And we really look forward to providing additional updates on this program in the coming months. Let me now switch gears to our second clinical program, which is CX801, our pro-body version of the cytokine interferon alpha 2b. So interferon alpha 2b is a well-known cytokine. It, in fact, was the first immunotherapy to ever be approved. some years ago. It's a powerful cytokine that regulates the immune system through multiple mechanisms, including the modulation of a whole host of different immune cell populations, including T cells, NK cells, Tregs, dendritic cells. And it's been shown to have single-agent activity, anti-tumor activity, against a variety of solid tumors, including melanoma, head and neck cancer, renal cancer, and bladder cancer. It really is a pleiotropic regulator of the immune system, but it's a tough drug to use because it has significant systemic toxicities. Patients treated with systemic interferon alpha show significant systemic flu-like symptoms. They develop immune-related adverse events. They develop certain neuropsychiatric disorders. And this has been a real barrier to the use of interferon alpha. But we know it's got such a powerful and unique way to activate the immune system. We've reasoned that we could potentially use our masking strategy to shut down the systemic activity of interferon alpha while maintaining the potent intratumoral activation of the immune system. So that's what we're doing with CX801. So the intentional design of 801 is shown here. The cytokine is shown towards the top of the slide, the dimeric structure in yellow. That is the cytokine, which as you can see, We have taken a dual masking approach to 801. We have a peptide mask that binds directly to the cytokine. We then have an FC mask, which also provides a steric blockade of binding to interferon receptors. And both of these masks are designed to be protease cleavable. So the strategy, similar to Varseta M, is that when first administered to a patient, CX801 has very low binding affinity. for interferon receptors. When it moves into the tumor, the masks are removed, the cytokine can bind interferon receptors and elicit its biological effect. So this is the strategy. So this is a high potential target with a masking strategy designed to localize the powerful immunobiology of interferon alpha into the tumor. We're initially focusing in late-line melanoma. So similarly to the Varseta M program, where we conducted our phase one entirely in colorectal cancer, with CX801, we're currently focused entirely in late-line melanoma, and specifically in melanoma patients that have progressed after dual checkpoint therapy. So what we're looking to do with the cytokine here is to reactivate the immune system in these late-line melanoma patients, and in particular, restore sensitivity to checkpoint inhibition, and specifically to PD-1. Late-line melanoma remains a significant unmet medical need. In fact, this is an unmet need that will continue to grow as checkpoint inhibitors continue to move earlier in the treatment paradigm being used increasingly in the neoadjuvant setting. And as vaccine approaches also come into the field, we anticipate that the size of the patient population in late-line metastatic melanoma will continue to grow. So this is an important area to be in and an area where we think we can make a difference. So we're currently in phase one. We're conducting a phase one dose escalation of both monotherapy CX801 and CX801 in combination with Keytruda in collaboration with Merck. We have successfully moved through now several dose levels in monotherapy dose escalation. We have already exceeded the approved dose of PEG interferon alpha in dose escalation, and the drug has been well tolerated to date. So we feel like our masking strategy is already opening possibilities by allowing us to get to doses that are higher, that have been evaluated before. And that's allowed us to open up the combination arm, where we're also stepping through multiple dose levels in combination with full dose Keytruda we're on track to have an initial data set to present in the first half of 2027 in across both arms across monotherapy and last year 2025 certain biomarker data that showed that in the first five patients treated with monotherapy we're seeing exactly what we wanted to see within the tumor micro environment 801 is activating immune-responsive gene expression, immune-regulated, interferon-regulated gene expression, including the induction of checkpoint proteins, PD-1, PD-L1, and LAG-3. It's also inducing chemokine expression within the tumor, and also as a result of that chemokine expression, which is directly interferon-regulated, leading to significant recruitment of T cells into the tumor bed. So the pharmacodynamics of 801 already look encouraging, and we're really excited to share our initial clinical safety and efficacy data, again, for both monotherapy and combination as we move into the first half of next year. So just to recap then, our milestones and outlook. Very excited about the our SETA-M program and where we go next an additional data update from the monotherapy phase one dose escalation expansion and optimization by the end of the year together with communicating our go forward plan for our first registrational study initiating work with combinations including bevacizumab and chemotherapy initiating work in real time with additional tumor types gastric gej pancreatic and biliary tract cancers while we also continue to make progress with CX801 in melanoma. So really exciting time for the company and very happy to be here today to have shared our progress. Appreciate you all taking the time.