CytomX Therapeutics, Inc.

Good morning, everyone, and thank you for standing by. Welcome to the CitumX Therapeutics CX2051 Phase 1 Interim Clinical Data Call. Please be advised that today's call is being recorded. I would now like to hand the call over to your host for today, Chris Ogden, CitumX's Chief Financial Officer. Please go ahead.

Thank you. Good morning, and thank you for joining us. Before we begin, I would like to remind everyone that during this call we were making forward-looking statements. Because forward-looking statements relate to the future, they're subject to inherent uncertainties and risks that are difficult to predict and many of which are outside of our control. Important risks and uncertainties are set forth in our most recent public filing with the SEC at sec.gov. We undertake no obligation to update any forward-looking statements whether as a result of new information, future developments, or otherwise. Earlier today, we issued a press release that includes a summary of our first quarter 2025 financial results and highlights recent progress at Cytomix. Additionally, this morning, we are excited to announce both positive interim phase one data for CX2051 and advanced colorectal cancer, as well as a $100 million financing with a leading group of healthcare investors. The focus of our call today will be the phase one data for CX2051. For details on the company's financial results and pipeline updates, we encourage everyone to read today's press releases and the associated materials, which have been filed with the SEC. Additionally, the press releases A recording of this call and our SEC filings can be found under the Investors in News section of our website. With me on the call today are Dr. Sean McCarthy, Sytomix's Chief Executive Officer and Chairman, and Dr. Wayne Chu, Sytomix's Chief Medical Officer. Sean will provide introductory remarks regarding CX2051 design and clinical strategy. Wayne will then walk through the CX2051 phase one interim clinical results and next steps for the program. We will then wrap up with concluding remarks before we move to Q&A. With that, I'll turn the call over to Sean for opening remarks.

Thanks, Chris. It's a real pleasure to be here today to share our exciting update on CX2051. This is a transformational moment for cytomics. We believe we've really broken new ground in colorectal cancer with this novel antibody drug conjugate that has been uniquely enabled by the Cytomix ProBody therapeutic platform. The results we're sharing today represent the integration of years of learning about our technology and importantly, how to best direct it to the maximum benefit for cancer patients. Before getting to CX2051, we're of course delighted to have also announced today As Chris just mentioned, $100 billion financing with a top tier syndicate of healthcare specialist investors. Their belief in cytomics truly underscores the importance of what we have achieved with 2051 and the potential of this product. This financing positions us extremely well to continue our determined and focused execution towards bringing transformational cancer therapies to patients. Turning now to CX2051. Colorectal cancer remains one of the biggest unmet needs in oncology today with approximately 1.9 million patients diagnosed each year on a global basis. And this disease burden is expected to increase considerably over the next couple of decades to more than 3 million and is currently the second leading cause of cancer death worldwide. This is a significant global health problem and despite many advances across many other cancer types in recent years, colorectal cancer has not seen very much impact at all from innovation over that period of time, resulting in a current five-year survival rate in metastatic colorectal cancer of only 13%. This dire situation is unfortunately really underscored by just how inadequate options are for the treatment of late stage CRC in the third and fourth line settings or later. Current standard of care therapies have poor response rates and limited survival benefit. There is enormous room for improvement. At Phytomics, we've taken this challenge head-on by designing a colorectal cancer-targeting antibody drug conjugate, CX2051. Antibody drug conjugates are transforming cancer care, making a really big impact in the treatment of many solid tumors, accruing benefit for many, many thousands of patients around the world. This class of differentiated targeted oncology therapeutics continues to build very substantial value. ATCs have yet to break through, however, in colorectal cancer. Our goal is to transform colorectal cancer care with CX2051, a first-in-class antibody drug conjugate that we have carefully designed to target a protein called EPCAM that is present at high levels in CRC. We've been highly focused on running a phase one clinical trial over the past year, entirely focused in CRC. This is a very tough cancer to treat, but we really wanted to do the killer experiment to see what CX2051 can do for these patients. Today, we are very excited to share positive phase one clinical data for CX2051. In our first 12 months in the clinic, we have demonstrated robust anti-cancer activity for CX2051 in metastatic CRC with a 28% confirmed overall response rate, a 94% disease control rate, and 5.8 months of preliminary progression-free survival. This strong anti-cancer activity offers the potential to position CX2051 as a new standard of care in late-line colorectal cancer. Regarding safety, CX2051 has shown a favorable safety profile to date, including no dose-limiting toxicities during dose escalation. We believe the safety profile we have seen to date in late-line CRC is strongly supportive of developing 2051 in earlier lines of therapy, including in combinations. Furthermore, our masking strategy has succeeded in avoiding classic EPCAM toxicities that have impeded the successful development of drugs against this target before. Additionally, we can say with some confidence that EPCAM has the potential to be a pan-CRC target since we have validated that the target is indeed present at high levels in all patients we have tested. Taken together, we see this as a very strong start to the CX2051 development program. Before I hand over to Wayne to walk through our exciting results, I'd like to make a few comments on the molecular design of CX2051 and our phase one clinical strategy. First of all, a few words on the target. EPCAM or epithelial cell adhesion molecule, we really believe is an ideal CRC target enabled by the Cytomix ProBody platform. EPCAM has high and uniform expression across colorectal cancer. And you can see here an immunohistochemistry image of a patient actually in our phase one clinical trial showing just how high EPCAM expression is in this cancer type. In fact, this patient has a maximum score, a score of 300 by this assay. Now, the challenge with EPCAM in the past has been its expression in normal tissues. And this is limited drug development due to toxicities that have emerged, including acute pancreatitis. So we have developed and designed CX2051 as a first-in-class EPCAM-targeting antibody drug conjugate. we really believe with this molecule we have the right target the right payload and the right tumor type and it's really how these three design elements come together that underscore the progress that we are sharing today with this really exciting program so 2051 is based on a high affinity anti-epcam monoclonal antibody that we have masked using our proprietary probody therapeutic platform, and the masking is designed to reduce epcam binding in normal tissues. The masks, however, are removed specifically and selectively within tumor tissue by tumor-associated proteases, resulting in anti-cancer activity within the tumor. We have empowered this mask antibody with the topoisomerase 1 inhibitor, CAMP59. which is a cytotoxic payload designed to kill cancer cells. The payload is linked to the antibody through a cleavable peptide linker optimized for what we call bystander effect, which is the ability of the drug to kill neighboring cancer cells. The drug antibody ratio for CX2051 is eight. Moving now to our clinical strategy, we commenced this phase one study just about one year ago, And we really have made terrific progress. We began dose escalation at the dose of 2.4 milligrams per kilogram administered every three weeks. And we have escalated through seven dose levels to date. The focus of today's update will be the first five dose levels where we have 25 safety-evaluable patients across the doses of 2.4 to 10 milligrams per kilogram. We have 23 safety-evaluable patients at the doses of 7.2, 8.6, and 10 milligrams per kilogram. And these three doses, we have already started to expand based on the exciting results we have already seen with 2051. We have 18 efficacy-evaluable patients across these three dose levels. And we do anticipate once these expansions are completed towards the end of this year, that our recommended phase two doses will come from among this broad dose range. I should also say that in this clinical study, every patient enrolled was a metastatic CRC patient. We didn't enroll any patients with any other tumor types. So this has been a highly focused study. And we did not select for EPCAM expression because of our expectation that the target would be highly expressed in all patients enrolled. And Wayne will update you on that in just a moment. So it's been a really strong year of execution, and I'll now hand over to Wayne to talk through our findings so far. Thanks, Sean.

So as Sean mentioned, we've exclusively focused enrollment of this study in patients with metastatic colorectal cancer, or CRC. So summarized here are the key baseline characteristics of this patient population. As is typical for a phase one trial, This represents a very heavily pretreated advanced CRC population, essentially a median fifth-line patient population, as evidenced by the median number of prior lines of cancer therapy of four. Relevant to the mechanism of action of 2051 as a topoifomerase I inhibitor, it is important to note that, as is expected for this late-line population of CRC patients, all received prior urin and TCAN. And in many cases, patients received multiple lines of erinotecan-containing therapy. Other key baseline characteristics that have been known to affect therapeutic selection and therapeutic outcomes of agents used in colorectal cancer include liver metastases and KRAS mutation status, which are observed in the majority of these patients. Finally, virtually all patients were micro-satellite stable, have micro-satellite stable disease, indicating that these patients are not, have tumors that are responsive to immune checkpoint therapy. Shown here is the waterfall plot illustrating the objective responses in patients enrolled at the three relevant doses of 7.2 to 10 milligrams per kilogram. Among the 18 efficacy-evaluable patients, a total of 5, or 28%, had a confirmed partial response by resist 1.1 criteria. And this included three of seven efficacy-evaluable patients at the 10 milligram per kilogram dose level. You can see the depth of the responses in the waterfall plot, including one patient who had a 100% reduction in measurable target lesions. I'll turn your attention to the table at the bottom of the waterfall plot, which indicates the specific baseline characteristics for each of these patients. And you can see that 2051 had activity in patients who had many lines of prior systemic therapy. Anti-tumor activity was observed in patients with KRAS wild-type tumors, as well as KRAS mutated tumors. And importantly, activity of 2051 was observed in patients whose disease has spread to other organs, specifically the liver. Finally, and importantly, as Sean mentioned, supporting the hypothesis of high and uniform levels of EPCAM expression in CRC, we tested baseline tumor biopsies for EPCAM expression using H-score, which captures the proportion and the intensity of EPCAM expression in tumor cells. And as you can see, all tumors that have been evaluated had near-maximal H scores, supporting the fact that 2051 is a therapy that will not require patient selection based on EPCAM expression. The spider plot on the next slide shows the evolution of antitumor responses over time. And I wanted to highlight two important observations. In addition to the confirmed partial responses, you can see in multiple examples of continuing evolution of anti-tumor activity over time, exemplified by patients who had a stable disease response assessment at the first tumor assessment, but with continued treatment with 2051 had conversion of that stable disease to a resist partial response. The second important observation is the disease control. In addition to virtually all patients, 17 out of 18 efficacy-valuable patients with disease control, which is resist stable disease or better, this disease control was durable. There were no examples of patients with rapid disease progression following an initial assessment showing either stable disease or an objective response. And this durability of disease control is highlighted by the individual patients treated at the 7.2 milligram per kilogram dose level, who was able to maintain that disease control in excess of nine months on therapy. So when you take into account the objective responses and the durability of disease control, this has allowed a preliminary estimate of the median progression-free survival of 5.8 months. 10 of the 18 patients who are efficacy-available continue on 2051 treatment, including three of the five patients who had a confirmed partial response who continue on treatment. Importantly, there were no discontinuations for ongoing treatment-related adverse events. And while some patients had dose delays and or reductions for the management of adverse events, this has not precluded patients continuing to derive clinical benefit from 2051 nor has it prevented patients from continuing 2051 treatment. I wanted to highlight an example of the activity that we've been observing with 2051 in this case study. This is a 46-year-old male with metastatic CRC, KRAS wild-type microsatellite-stable disease. And as is typical for patients with metastatic colorectal cancer, there are multiple lesions in multiple locations outside of the GI tract. Specifically for this patient, there were metastatic lesions in the lung, the lymph node, and as you can see by the example CT scan, multiple lesions in the liver. This patient received three prior therapies, and this represents the typical course of treatment for metastatic colorectal cancer, comprised of combinations of monoclonal antibody and systemic chemotherapy. And the last line of prior treatment was combinations of Bevacizumab and Longserve. The patient came on study, was treated with 2051 at a dose of 7.2 milligram per kilogram every three weeks. The patient tolerated 2051 extremely well. And as you can see by the CT scans on the right, at the first tumor assessment, the patient had a significant reduction in tumor burden, corresponding to a near 50% reduction in burden that corresponds to a partial response by resist criteria. In addition to the measurable lesions as indicated by the green arrow, the patient also had noticeable reductions in multiple liver metastatic lesions as indicated by the blue arrows. Importantly, in addition to the radiographic response of 2051 against patient's metastatic cancer, The patient also had significant clinical improvement, highlighted by the discontinuation of multiple medications for the management of cancer-related pain. This patient was able to maintain his postural response through six months of treatment, and this example nevertheless highlights the fact that the patient derived significant clinical benefit, where otherwise the patient would have received worse clinical benefit with standard of care therapies. Turning our attention to safety, this is a table of the treatment-related adverse events observed in more than one patient. And as Sean mentioned earlier, previous efforts to develop systemically administered EPCAM-directed anticancer therapies have been extremely limited by the evolution of dose-limiting toxicities in the absence of compelling efficacy. So in that context, wanted to mention multiple observations on this table. First, what is notable by its absence are number one, there were no dose-limiting toxicities observed on this trial to date. Number two, there were no grade four or five treatment-related adverse events. And number three, some of the key dose-limiting toxicities, specifically severe pancreatitis, that have hampered the development of other therapies were not observed in this study. Overall, the AE profile of 2051 is manageable and reversible. If you look at the hematologic adverse events of anemia and neutropenia, these have primarily been laboratory in nature, and there were no significant clinical sequelae such as febrile neutropenia or sepsis observed on the study. And with respect to non-hematologic adverse events, the profile is consistent with that of other topoisomerase inhibitors, and that the most frequently observed adverse events were gastrointestinal in nature, including diarrhea and nausea. Nevertheless, again, these AEs were generally manageable and reversible, and its overall profile, combined with the compelling efficacy that we discussed earlier, clearly indicates the presence of a robust therapeutic index.

Few words on PK.

We continue to evaluate pharmacokinetics, and shown here is a summary of interim analysis of cycle 1 PK. Overall, CX2051 is behaving as expected for an antibody drug conjugate. Importantly, the rate of payload deconjugation was low and in line with other topo1 inhibitor ADCs, as you can see by the low levels of the free linker payload. In addition, CX2051 remained masked in circulation, as evidenced by the superimposable PK curve for intact 2051 and total 2051, which represent masked and masked and unmasked 2051, respectively. The half-life of 2051 is approximately six days, and based on its early analysis of cycle 1 PK, 2051 showed dose linearity with respect to both AUC and Cmax. So when you take the clinical data together with respect to safety and with the efficacy, and then compare what we've observed with 2051 with other standard care therapies and late-line metastatic CRC, it is already evident based on this early data set that with respect to key efficacy-based endpoints, including objective response rate, disease control rate, and median PFS, that 2051 compares very favorably for the standard of care. We have potential to establish 2051 as the new standard of care in the late-line CRC setting. As the data continue to mature with respect to the number of patients and longer follow-up, we are optimistic that this efficacy endpoint will continue to be maintained, if not improved. As far as our plans going forward, as Sean mentioned, we continue to expand At the relevant dose levels of 7.2, 8.6, and 10 milligrams per kilogram, we are expanding each of the three dose levels to a total of 20 patients, such that by the time of Q1 2026, we'll have a robust data set across these three dose levels, corresponding to approximately a total of 70 patients of phase one data that we will update. Furthermore, the data from these dose expansions will be the basis of a go-forward plan regarding phase two design, which we also anticipate to initiate in the first half of 2026. So with that, I will turn it back to Sean for concluding remarks.

Great. Thanks, Wayne. Well, based on this really exciting data that we're absolutely thrilled to share with you all today, I believe we can say that CX2051 is functioning exactly as we have designed it. We've broken new ground for EPCAM and colorectal cancer with our masking strategy, unlocking EPCAM as a viable therapeutic target for systemic anticancer therapy for the first time. This is a highly differentiated program and very consistent with our overall philosophy at Cytomix over the years of making a difference by being different. Looking ahead, we see a very broad development opportunity for CX2051. We will be highly focused on advancing 2051 in late line CRC towards approval as rapidly as we can, as fast as we can. We see tremendous opportunities to advance a drug in the third line or later setting based on these groundbreaking results that we've shared today. As I mentioned earlier, the current standard of care, as Wayne just reviewed, the current standard of care in the late line setting is highly inadequate, and we believe we've got something really valuable that can make a big difference for patients. In addition to the late line setting, of course, we see enormous opportunities to bring CX2051 forward in the treatment paradigm for colorectal cancer. Indeed, our vision for 2051 has always been, based on using a topo1 payload, that we could bring it to earlier lines, potentially replacing Irinotecan in earlier line regimens. and perhaps even more broadly, replacing chemotherapy in the treatment and management of earlier line CRC. So this drug has, we believe, transformational potential based on this early look at our phase one data showing just how effectively the drug is performing in the metastatic CRC setting.

We, of course, are also

We also note that in having done the CRC experiment, in a way, we've done the hardest experiment first. FCAM is not only very highly expressed in colorectal cancer, but it is an antigen that is present on most solid tumors at high levels. This presents a very large opportunity for expanding the 2051 program into multiple other solid tumors. over time and we really believe that in addition to being a pan crc target this is a potential pan tumor target with tremendous value creation opportunities for cytomics over time so to summarize again we are super excited about this first look at 2051 we have shown today clinical proof of concept for EPCAM targeting TOPA1 ADC, and this really is a big landmark for cytomics and the pinnacle achievement for our technology platform to date. This first-in-class antibody drug conjugate represents a multi-billion-dollar annual sales opportunity on a global basis, and that's in late-line CRC alone. Our top priority is to advance now towards the potential first approval in late-stage metastatic colorectal cancer, while also advancing in parallel into combination regimens to bring 2051 earlier in the treatment paradigm while starting to explore additional opportunities for this exciting drug. Now, before opening up to questions, I want to recognize and sincerely thank the patients who join our studies, their families, our clinical investigators, and our highly dedicated team at Cytomix, including present and past employees. This team has been through many ups and downs, but to a person has stayed laser focused on execution for the benefit of patients. I want to also thank our board of directors for their continued belief and support, and also our investors, including the new investors that we're welcoming to the company in today's financing. At Cytomics, we've never been more committed to our vision, mission, and values, and we look forward to great things to come. So with that, operator, let's go ahead and open up the call for Q&A.

To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from Roger Song with Jefferies. Your line is open.

Excellent. Congrats for the data. Really impressive. And then thank you for taking our question. A couple from us. So the number one is you have a very high disease control and then also very meaningful partial response patient. Just curious about what do you see for those patients different between the stable disease versus responders in terms of the baseline, maybe the response from the prior lines? That's the first part of the question. Second part, how likely this entire tumor activity will deepen over time given you have 10 of 18 patients still ongoing. Thank you.

Yeah, thanks, Roger, for the questions. So, look, we're absolutely delighted with the overall profile of 2051 after this first year of work in the clinic. The disease control rate is indeed impressive. We believe that response rate across this dose range that we're advancing into expansions is also impressive in this very difficult to treat tumor type. In terms of patient characteristics that could determine response versus stable disease, I think that's something we'll continue to look at, but we just think this overall level of activity in an unselected patient population, not just unselected for EPCAM, but also unselected for other clinical characteristics like KRAS mutation or liver metastases is just really impressive and, quite frankly, surpassing our expectations. In terms of improvement over time, I think on that point, I'm sure Wayne would say the same, that we would point to the emerging preliminary progression-free survival. where we see, you know, 5.8 months so far. You know, there is, of course, a confidence interval on that. This is an early data set. But we do have many patients still on study as of the data cutoff, and we have good reason to believe that that PFS number will improve over time.

Great. Thank you. If I may, just add one more question related to the next step. You know, this is a late line. You say you will move this forward as quick as possible. Can you just, what is the current development strategy in terms of the pivotal, the endpoint, and then also how you will move into this earlier line with some early work along with the later line? Thank you.

Yeah, thanks again, Roger. Obviously, we've got a lot of work to do in now thinking through the mid and late stage development strategy for CX2051 based on this very strong start. We are right now highly focused on generating data from the three expansion cohorts. We expect to have that data in Q1 of 2026. We will be discussing towards the end of this year, we expect with the regulatory authorities ask and answer that exact question as to what is the optimal path forward for phase two, potentially phase two, three, to get this drug to patients who need it as quickly as possible. We will, of course, be exploring the fastest possible routes to the market in the context of the current regulatory landscape, but these will be data-driven decisions, including generating additional data beginning in 2026 in the combination setting to start to enable bringing the drug into earlier lines of therapy.

Great. Congrats again.

Thank you. Our next question comes from Anupam Rama with J.P. Morgan. Your line is open.

Hey, guys. Thanks so much for taking the question and congrats on the data. Just two quick ones from me. Just in the adverse events that you saw, the serious adverse events that you saw in five patients, can you give us a little color on how these were managed by dose reduction or dose holiday? And then I know that the Phase 1 update is expected in the first quarter of 2026. Are there any plans on presenting the data at a scientific or medical forum between now and the next data update? Thanks so much.

Yeah, thanks, Anupam. Let me just make a high-level comment on the AESAE profile as reported today. I think as Wayne mentioned, our initial sense of the safety profile of 2051 is that we have a A great start here with a safety profile that is, we think, very encouraging and supportive of moving into earlier lines of therapy in potential combinations. The SAEs reported today are consistent with the overall adverse event profile, and we're not at liberty right now to really dig in patient by patient, as I'm sure you'll understand. In terms of presenting at a major medical meeting, the next update from Cytomix right now is planned for Q1 of 2026. That will be data from the expansions. We would expect it to be about a 70-plus patient update, including 60 patients across the dose levels of 7.2, 8.6, and 10 mg per kg. And we have not yet decided exactly the venue to present or share that data.

That will come over time. Thanks so much for taking our question. You're welcome.

Thank you. Our next question comes from Peter Lawson with Barclays. Your line is now open.

Great. Thank you so much. Thanks for taking the questions and congrats on the data. Just, I guess, further questions around the potential phase two, you know, so it's going to be a registrational study. You've had discussions around, et cetera, about settlement or breakthrough designations and then It is, I guess, the ability to include prophylactic strategies to help reduce GI toxicities. And then, like I said, the other follow-up around that is just around the comparison around whether it's a single-arm study, kind of how you're thinking about that phase two. Thank you.

Thanks, Peter. Let me address a couple of those questions, and then I'll hand over to Wayne to make a few comments on prophylaxis on the GI side. So obviously with this level of activity that we're seeing in this very late line patient population, it does, it should open avenues for moving quickly in mid and late stage development. Way too early to say exactly what they will be, but we will be discussing with the regulatory authorities to make sure we can move forward in the most expeditious way possible. We have not yet had dialogue with FDA. We believe that the expansion data across these three active dose levels will be, of course, important and very useful in those discussions at the right time. In terms of Comparator Arm, I mean obviously moving into the next stage of development, we're mindful of a number of things in the, you know, in the regulatory environment. We are exploring multiple doses of course to, you know, with Project Optimus very much in mind. And we do see tremendous opportunities for demonstrating the full power and potential of 2051 by potentially comparing it to one or more of the current standards of care in the third and fourth line setting, where I think we all agree there is substantial room for improvement in CRC. Just one comment on the overall TOPS profile before I hand over to Wayne on the prophylaxis side. Again, we're really encouraged by the the AE profile of 2051. I want to underscore that this is the first in human study for this payload, CAP-59. This is a novel Captathicin-based topoisomerase-1 inhibitor that we licensed from Immunogen. And we're very pleased with how this link room payload is functioning. And when we look at the AE profile overall, it looks to us very much like other TOCA1 inhibitors, and we would have expected with our masking working as well as it is to prevent Epcam toxicities like pancreatitis, we would have expected that the principal AEs would come from the payload because, of course, we're not masking the payload. So with that, I'll hand over to Wayne to talk about, you know, of course, that does leave us with some GI TOCs to manage, but we have a very good plan.

Yeah, so regarding the GI TOCs, As we continue to get more experience with 2051, we continue to optimize our management strategy. And so a lot of the actually all of the data that we presented today are just reflections of earlier efforts to manage talks. But specific to the question of prophylaxis for diarrhea, we have implemented the use of prophylactic medications, specifically prophylactic loperamide, to prevent the onset of severe diarrhea. This was only recently implemented, so the data that we showed today was actually in all patients who were not prophylactics with loperamide. As you probably are aware, the experience of prophylactic loperamide was explored with other ADCs, namely Tridelvi, in the context of a clinical trial where they were able to demonstrate a notable reduction in the incidence of grade 3 diarrhea with loperamide prophylaxis. So moving forward, we will implement similar strategies for patients coming on the 2051 study. So our expectation, and we're very optimistic that those rates of diarrhea will change and change for the better.

Thank you so much.

Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone. Again, that is star 1-1, ask a question. Our next question comes from Robert Driscoll with Wedbush. Your line is open.

Thanks for morning, guys. Congrats on the data here. Just a couple of questions from us. We're seeing very high expression of Epcam here in late-line patients. Is there kind of evidence for similarly kind of high and robust expression of Epcam in earlier-stage patients, just as you think you're going to, as you go to those earlier lines next year, potentially? And then anything about the biology of Epcam you think may be particularly attractive here in colorectal cancer and then potentially in other solid tumors?

Hi, Robert. Thanks for the questions.

So, you know, FCAM was first described quite some time ago as a CRC antigen. So it's been well established for decades, actually, to be a CRC target. And it is expressed throughout the natural history of the disease. So, you know, we feel confident about bringing EPCAM earlier in the treatment paradigm based on target expression and other aspects that we've discussed today. In terms of the biology of EPCAM, you know, although it's been around a long time, its actual biological function is still not that well characterized. And, you know, we haven't really focused on that as anything that relates to the design of 2051. There's just so much Epcam on CRC tumor cells that we've always thought of it as an address to target with this ADC. And just to put that in context, the expression level of Epcam in CRC is similar to to HER2 in breast cancer. So now we can't rule out that there's some biology here that blocking EPCAM is contributing to this really exciting clinical activity that we're seeing, but it's never been something that we've relied on or needed to invoke actually for the drug to work.

Got it, thanks. And maybe just one more, you know, in terms of the doses select to go forward here, any plans to go higher in dosing, just kind of given that emerging situation? signal of maybe a higher response in the 10 makes the kick dose?

Yeah, thanks. I'll start by saying we're already pretty excited about the response rate that we have across these three dose levels. And, you know, in this patient population, it really is, we think, a really significant achievement. We have escalated, as I mentioned in my presentation, through seven dose levels to date in the clinical study. We do anticipate that, although we haven't seen any dose-limiting toxicities in the execution of the study to date, but we do anticipate that at these upper dose levels, we will find our maximum assessed So, you know, we're not currently expanding those dose levels. We will present data from them when we present the overall update on the expansions in Q1 of 2026. But right now, we feel like the dose range that we're expanding, 7.2, 8.6, and 10, gives us a lot of room to maneuver.

Okay. Thanks very much, and congrats again, guys. Thank you.

Thank you. Once again, to ask a question, please press star 11 on your telephone. Our next question comes from Mitchell Kapoor with HC Wainwright. Your line is now open.

Good morning. This is Dan on for Mitchell. Thanks for taking our questions and congratulations on the data. So, this data appears to be a very clear indicator that the ProBody masking technology is at work, especially slide 20. Why do you believe your ProBody masking work most optimally with the Epcam strategy versus with prior strategies in the past? And is there anything that's being done to enhance the ProBody platform to where future pipeline candidates may have better odds of success? And I'd like to ask a follow-up if I could.

Yeah, thanks, Dan. That's a terrific question. And, you know, this data is obviously super exciting and fascinating. It absolutely is showing the power of our pro-body therapeutic masking platform. And many of you will be aware, of course, that Cytomics is the company that really originated the whole concept of antibody masking to increase therapeutic index. In terms of why it's working so well, on this target. I've kind of always believed, as most of you will know, that our platforms always work. We've been in the clinic with multiple programs. We've shown a lot of really interesting clinical results over the years. I think we've come to the view that it's all about where you direct the power of the technology. And in this particular case, we have come to learn that And I think what we've really got right is the combination of the tumor type of interest and the clinical problem that we're trying to solve, the target, which of course is CRC, at least initially, the target, which is EPCAM, and the effector mechanism, which in this case is the cytotoxic payload, the TOPA1 inhibitor, the CAP59. I think you've got to get all three of those things right. and I think we have, to really nail it. In terms of the underlying technology, the protease cleavable substrate and the masking strategy, which is a peptide masking strategy that we've always employed and continue to employ, this is a strategy that has been validated previously in our previous clinical work. You know, so we're not surprised to see it doing so well in the clinic. It's worked before. It's just in this case, we really think we've got that combination of the tumor, the target and the effector. We've got it right. And that's just really exciting. And of course, that opens up now many new opportunities to go back and design the next generation of pro body therapeutic candidates across our pipeline as we build the company for the long term. But thanks for the question. It's a terrific question.

Yeah, excellent answer. Thank you. And thinking about on the PR for the pan tumor phase 1B study expected in 2026, do you intend on registering as a basket study, or are you thinking of targeting those indications piecemeal? And given the exceptional levels of Epcam expression in CRC versus other solid tumors, which they still have high levels, but CRC is the highest, would you lean towards identifying high Epcam positive patients than the other solid tumors, or are you thinking of going in an agnostic approach there? Thank you.

Yeah, well, clearly, a lot of ground to explore with 2051 across so many tumor types where there continues to be so much unmet medical needs. So we are working through our strategy for moving into those additional cancer types at the moment. As I mentioned, we've been really, really focused on CRC for the last year, and that's been very intentional. And we really wanted to do, as I said, in a way, kind of the hardest experiment first to really put this drug through its paces. Now that it's delivering, it opens up a multitude of opportunities across other cancer types. And the specific design of that phase 1B study, if that's what we call it, as a basket or looking in a more targeted way at specific tumor types is something we continue to discuss internally. In terms of selection of patients, again, one of the great features of CRC is we don't have to select patients. We don't think we're going to need to. And we think ultimately, commercially, that's going to be a huge advantage for 2051 as we get this drug to the market. But we have a terrific IHC assay. You've seen some of the results in this study. We showed one of our patients in our presentation today. And it may be helpful to select patients in these other tumor types. But I would say we're also early in, very early actually, in understanding any relationship between target level and response. We don't actually know how much target is necessary. So there's just a lot more to be learned about this drug and obviously a ton of potential. But thanks for the question.

Thank you so much, and congratulations again. Thank you.

Thank you. As a reminder, to ask a question, please press star 11 on your telephone. Again, that is star 11 to ask a question. Thank you. I'm not showing any further questions in the queue at this time. I would now like to turn it back over to Dr. Sean McCarthy, Chairman and CEO, for closing remarks.

Well, thanks, everyone, for joining us today. It's obviously a very exciting day for all of us here at Scythermics and a very important day for cancer patients. So thank you for your time, and we look forward to keeping you updated on our progress in the future.

This concludes today's conference call. Thank you for participating. You may now disconnect.