CytomX Therapeutics Q1 2025 Earnings Call Transcript

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Provided by Quartr
May 12, 2025

There are 7 speakers on the call.

Operator

Good morning, everyone, and thank you for standing by. Welcome to the Citemx Therapeutics CX 2,051 phase one 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, CitemX's chief financial officer. Please go ahead.

Speaker 1

Thank you. Good morning, and thank you for joining us. Before we begin, I would like to remind everyone that during this call, we will be 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 filings with the SEC at sec.gov.

Speaker 1

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 twenty twenty five financial results and highlights recent progress at CytomX. Additionally, this morning, we are excited to announce both positive interim phase one data for CX-two thousand and fifty one in advanced colorectal cancer, as well as a $100,000,000 financing with a leading group of healthcare investors. The focus of our call today will be the phase one data for CX-two thousand and fifty one. 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.

Speaker 1

Additionally, the press releases, a recording of this call, and our SEC filings can be found under the Investors and News section of our website. With me on the call today are Doctor. Sean McCarthy, CytomX's Chief Executive Officer and Chairman, and Doctor. Wayne Chew, CytomX's Chief Medical Officer. Sean will provide introductory remarks regarding CX-two thousand and fifty one design and clinical strategy.

Speaker 1

Wayne will then walk through the CX-two thousand fifty one phase one interim clinical results and next steps for the program. We will then wrap up with concluding remarks before we move to Q and A. With that, I'll now turn the call over to Sean for opening remarks.

Speaker 2

Thanks, Chris. It's a real pleasure to be here today to share our exciting update on CX-two thousand and fifty one. This is a transformational moment for CytomX. We believe we've really broken new ground in colorectal cancer with this novel antibody drug conjugate that has been uniquely enabled by the CytomX 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.

Speaker 2

Before getting to CX 02/1951, we're of course delighted to have also announced today, as Chris just mentioned, $100,000,000,000 financing with a top tier syndicate of health care specialist investors. Their belief in CytomX truly underscores the importance of what we have achieved with 02/1951 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 CX-two thousand and fifty one. Colorectal cancer remains one of the biggest unmet needs in oncology today with approximately one point nine million patients diagnosed each year on a global basis.

Speaker 2

And this disease burden is expected to increase considerably over the next couple of decades to more than three 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 thirteen percent. The current 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.

Speaker 2

There is enormous room for improvement. At CytomX, we've taken this challenge head on by designing a colorectal cancer targeting antibody drug conjugate CX-two 51. Antibody drug conjugates are transforming cancer care, making a really big impact in the treatment of many solid tumors accruing benefit from many, many thousands of patients around the world. This class of differentiated targeted oncology therapeutics continues to build very substantial value. The ADCs have yet to break through, however, in colorectal cancer.

Speaker 2

Our goal is to transform colorectal cancer care with CX-two thousand and fifty one, 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 I 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 CX-two thousand and fifty one can do for these patients. Today, we are very excited to share positive Phase I clinical data for CX-two thousand and fifty one. In our first twelve months in the clinic, we have demonstrated robust anticancer activity for CX-two thousand and fifty one in metastatic CRC with a twenty eight percent confirmed overall response rate, a ninety four percent disease control rate, and five point eight months of preliminary progression free survival.

Speaker 2

This strong anticancer activity offers the potential to position CX-two thousand and fifty one as a new standard of care in late line colorectal cancer. Regarding safety, CX-two thousand and fifty one 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 two thousand fifty one 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.

Speaker 2

Taken together, we see this as a very strong start to the CX-two 51 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 CX-two 51 and our Phase I clinical strategy. First of all, few words on the target. Or epithelial cell adhesion molecule, we really believe is an ideal CRC target enabled by the CytomX Probody platform. EpCAM has high and uniform expression across colorectal cancer.

Speaker 2

And you can see here an immunohistochemistry image of a patient actually in our Phase I clinical trial showing just how high EpCAM expression is in this cancer type. In fact, this patient has a maximum a score of 300 by this assay. Now, the challenge with ETCAM 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 CX-two thousand and fifty one as a first in class FCAM targeting antibody drug conjugate.

Speaker 2

And 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, two thousand fifty one 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 anticancer activity within the tumor.

Speaker 2

We have empowered this MASP antibody with the topoisomerase one inhibitor, CAP59, 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 CX-two 51 is eight. Moving now to our clinical strategy. We commenced this Phase I study just about one year ago, and we already have made terrific progress.

Speaker 2

We began dose escalation at the dose of two point four 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 two point four to ten milligrams per kilogram. We have 23 safety evaluable patients at the doses of seven point two, eight point six, and ten milligrams per kilogram. And these three doses we have already started to expand based on the exciting results we have already seen with 2,051.

Speaker 2

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.

Speaker 2

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.

Speaker 1

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 2,051 as a topoisomerase one inhibitor, it is important to note that as is expected for this late line population of CRC patients, all received prior irinotecan. And in many cases, patients received multiple lines of irinotecan containing therapy.

Speaker 1

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 microsatellite stable have microsatellite 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 seven point two to ten milligram per kilogram. Among the 18 efficacy evaluable patients, a total of five or twenty eight percent had a confirmed partial response by resist 1.1 criteria. And this included three of seven efficacy evaluable patients at the ten milligram per kilogram dose level.

Speaker 1

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 two thousand and fifty one had activity in patients who had many lines of prior systemic therapy. Antitumor activity was observed in patients with KRAS wild type tumors, as well as KRAS mutated tumors. And importantly, activity of 2,051 was observed in patients whose disease had spread to other organs, specifically the liver.

Speaker 1

Finally, and importantly, as Sean mentioned, supporting the hypothesis of high and uniform levels of F cam expression and CRC, we tested baseline tumor biopsies for F cam expression using H score, which captures the proportion and the intensity of F cam expression in tumor cells. And as you can see, all tumors that have been evaluated had near maximal each scores, supporting the fact that 2,051 is a therapy that will not require patient selection based on F cam expression. The spider plot on the next slide shows the evolution of anti tumor responses over time. And I wanted to highlight two important observations. First, in addition to the confirmed partial responses, you can see in multiple examples of continuing evolution of antitumor activity over time, exemplified by patients who had a stable disease response assessment at the first tumor assessment, but with continued treatment with 2,051 had conversion of that stable disease to a resist partial response.

Speaker 1

The second important observation is the disease control. In addition to virtually all patients, seventeen out of eighteen of 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 his durability of disease control is highlighted by the individual patient treated at the seven point two milligram per kilogram dose level, who was able to maintain that disease control in excess of nine months on therapy.

Speaker 1

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 five point eight months. Ten of the eighteen patients who are efficacy evaluable continue on 2,051 treatment, including three of the five patients who had a confirmed partial response to 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 two thousand fifty one, nor has it prevented patients from continuing 2,051 treatment. I wanted to highlight an example of the activity that we've been observing with two thousand and fifty one in this case study.

Speaker 1

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 long lymph node. And as you can see by the example, CT scans, 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.

Speaker 1

And the last line of prior treatment was combinations of bevacizumab and long serve. The patient came on study was treated at with two thousand fifty one at a dose of seven point two milligram per kilogram every three weeks. The patient tolerated two thousand fifty one 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.

Speaker 1

Importantly, in addition to the radiographic response of 2,051 against patients 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 partial 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 anti cancer therapies have been extremely limited by the evolution of dose limiting toxicities in the absence of compelling efficacy.

Speaker 1

So in that context, want 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 2000 50 1 is manageable and reversible.

Speaker 1

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, the again, these AEs were generally manageable and reversible. And this 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 at the summary of interim analysis of cycle one PK.

Speaker 1

Overall, CX two thousand and fifty one is behaving as expected for an antibody drug conjugate. Importantly, the rate of payload deconjugation was low and in line with other TOPO-one inhibitor ADCs, as you can see by the low levels of the free linker payload. In addition, CX2051 remained mass in circulation, as evidenced by the superimposable PK curve for intact 2,051 and total 2,051, which represent masked and unmasked 2,051, respectively. The half life of 2,051 is approximately six days. And based on this early analysis of cycle one PK two thousand and fifty one showed those linearity with respect to both AUC and Cmax.

Speaker 1

So when you take the clinical data together with respect to the safety and with the efficacy, and then compare what we've observed with two thousand fifty one with other standard of care therapies and late line metastatic CRC, it is already evident based on this early dataset that with respect to key efficacy based endpoints, including objective response rate, disease control rate, and mean in PFS, that two thousand fifty one compares very favorably to the standard of care. We have potentially potential to establish two thousand 50 one 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 endpoints 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 seven point two eight point six and ten 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 twenty twenty six, we will have a robust data set across these three dose levels, corresponding to approximately a total of 70 patients of seven phase one data that we will update.

Speaker 1

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 twenty twenty six. So with that, I will turn it back to Sean for concluding remarks.

Speaker 2

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 CX-two thousand and fifty one 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 anti cancer therapy for the first time. This is a highly differentiated program and very consistent with our overall philosophy at CytomX over the years of making a difference by being different.

Speaker 2

Looking ahead, we see a very broad development opportunity for CX-two thousand and fifty one. We will be highly focused on advancing two thousand fifty one in late line CRC towards approval as rapidly as we can, as fast as we can. We see tremendous opportunities to advance the 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.

Speaker 2

In addition to the late line setting, of course, we see enormous opportunities to bring CX-two thousand and fifty one forward in the treatment paradigm for colorectal cancer. Indeed, our vision for 02/1951 has always been based on using a TOPOL-one 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 I data showing just how effectively the drug is performing in the metastatic CRC setting. We, of course, 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.

Speaker 2

This presents a very large opportunity for expanding the 2,051 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, are super excited about this first look at 2,051. We have shown today clinical proof of concept for ETCAM targeting TOPO-one ADC, and this really is a big landmark for CytomX and the pinnacle achievement for our technology platform to date. This first in class antibody drug conjugate represents a multibillion dollar annual sales opportunity on a global basis, and that's in late line CRC alone.

Speaker 2

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 2,051 earlier in the treatment paradigm while starting to explore additional opportunities for this exciting drug. Now, 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 CytomX, 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 CytomX, we've never been more committed to our vision, mission, and values, and we look forward to great things to come.

Speaker 2

So with that, operator, let's go ahead and open up the call for Q and A.

Operator

Our first question comes from Roger Song with Jefferies. Your line is open.

Speaker 3

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 patient different between the stable disease versus responders in terms of the baseline, maybe the response from the prior lines?

Speaker 3

That's the first part of the question. Second part, how likely this entire tumor activity will deepen over time given you have ten of eighteen patients still to ongoing? Thank you.

Speaker 2

Yeah, thanks Roger for the questions. So, we're absolutely delighted with the overall profile of two thousand and fifty one after this first year of work in the clinic. The disease control rate is indeed impressive. We believe the 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.

Speaker 2

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 five point eight months so far. 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.

Speaker 3

Great. Thank you. If I may just add one more question related to the next step. This is late line. You say you will move this forward as quick as possible.

Speaker 3

Can you just what is the current development strategy in terms of the pivotal endpoint? And then also how you will move into this earlier line with some early work along with the later line? Thank you.

Speaker 2

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 CX-two thousand and fifty one 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 twenty twenty six.

Speaker 2

We will be discussing towards the end of this year. We expect with the regulatory authorities to ask and answer that exact question as to what is the optimal path forward for Phase II, potentially Phase IIIII 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 enable to start to enable bringing the drug into earlier lines of therapy.

Speaker 3

Great. Congrats again.

Operator

Thank you. Our next question comes from Anupam Rama with JPMorgan. Your line is open.

Speaker 4

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 I update is expected in the first quarter of twenty twenty six.

Speaker 4

Are there any plans on presenting the data at a scientific or medical forum between now and the next data update? Thanks so much.

Speaker 2

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 02/1951 is that we have 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.

Speaker 2

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 CytomX right now is planned for Q1 of twenty twenty six. That will be data from the expansions. We would expect it to be about a seventy plus patient update, including sixty patients across the dose levels of seven point two, eight point six and ten mgs per kg. And we have not yet decided exactly the venue to present or share that data.

Speaker 2

That will come over time.

Speaker 4

Thanks so much for taking our question.

Speaker 2

You're welcome.

Operator

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

Speaker 2

Great, thank you so much.

Speaker 5

Thanks for taking my questions and congrats on the data. Just I guess further questions are just around the potential, Phase II, you know, so that's going be a registrational study. If you've had discussions around, accelerated development or breakthrough designations, and then if there's, I guess, the the ability to include prophylactic strategies with, to help reduce GI toxicities? And then I guess the other follow-up around that is just around the comparator arm, whether it's a single arm study, kind of how you're thinking about that phase two. Thank you.

Speaker 2

Thanks, Peter. Let me address 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 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.

Speaker 2

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 regulatory environment. We are exploring multiple doses, of course, Project Optimus very much in mind. And we do see tremendous opportunities for demonstrating the full power and potential of 02/1951 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 on the prophylaxis side.

Speaker 2

Again, we're really encouraged by the AE profile of 2,051. I want to underscore that this is the first in human study for this payload, CAP59. This is a novel captopisin based turquoise omurice one inhibitor that we licensed from Immunogen. And we're very pleased with how this linker and payload is functioning. And when we look at the AE profile overall, it looks to us very much like other TOPO-one inhibitors.

Speaker 2

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 TOPS to manage, but we have a very good plan.

Speaker 1

Yeah. So regarding the GI talks, as we continue to get more experience with 02/1951, 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 for diarrhea, we have implemented the use of prophylactic medications, specifically prophylactic roperamide for to prevent the onset and prevent the onset of severe diarrhea. This was only recently implemented.

Speaker 1

So the data that we showed today was actually in all patients were not were in patients who are not a prophylaxis loperamide. And as you probably are aware, the experience of prophylactic loperamide was explored with other ADCs, namely, Trodelvy in the context of a clinical trial, where they were able to demonstrate a notable reduction in the incidence of grade three diarrhea with loperamide prophylaxis. So moving forward, we will implement similar strategies for patients coming on the 02/1951 studies are expectation and we're very optimistic that those rates of diarrhea will change and change for the better.

Speaker 5

Great. Thank you so much.

Operator

Thank you. As a reminder, to ask a question, please press 11 on your telephone. Our next question comes from Robert Driscoll with Wedbush. Your line is open.

Speaker 6

Thanks. Good 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.

Speaker 6

Is there kind of evidence that 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?

Speaker 2

Yeah. Hi Robert. Thanks for the questions. So EpCAM 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.

Speaker 2

So, 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 ETCAM, although it's been around a long time, its actual biological function is still not that well characterized. And we haven't really focused on that as anything that relates to the design of 02/1951. There's so 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 VetCAM in CRC is similar to HER2 in breast cancer.

Speaker 2

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.

Speaker 6

Got it. Thanks. And maybe just one more. In terms of the doses selected go forward here, any plans to go higher in dosing just kind of given that emerging signal of maybe a higher response in the ten mgkg dose?

Speaker 2

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 in this patient population, it really is a we think a really significant achievement. We have escalated, as I mentioned in my presentation, to 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 dose.

Speaker 2

So, 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 twenty twenty six. But right now, we feel like the dose range that we're expanding seven point two, eight point six, and 10 gives us a lot of room to maneuver.

Speaker 6

Perfect. Thanks very much and congrats again guys.

Speaker 2

Thank you.

Operator

Thank you. Our next question comes from Mitchell Kapoor with H. C. Wainwright. Your line is now open.

Speaker 1

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 worked most optimally with the Eptam strategy versus with prior strategies in the past?

Speaker 1

And 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.

Speaker 2

Yeah, thanks, Dan. That's a terrific question. And this data is obviously super exciting, and it absolutely is showing the power of our Probody therapeutic masking platform. And many of you will be aware, of course, that CytomX 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.

Speaker 2

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 TURPA1 inhibitor, CAP 59.

Speaker 2

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, 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. 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.

Speaker 2

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 Probody therapeutic candidates across our pipeline as we build the company for the long term. But thanks for the question. It's a terrific question.

Speaker 1

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 at the basket study? Are you thinking of targeting those indications piecemeal? And given the exceptional levels of FCAM expression in CRC versus other solid tumors, which they still have high levels, but CRC is the highest, would you lean towards identifying high FCAM positive patients in the other solid tumors, or are you thinking of going in an agnostic approach there?

Speaker 1

Thank you.

Speaker 2

Yeah. Well, clearly, a lot of ground to explore with 2,051 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.

Speaker 2

Now that it's delivering, it opens up a multitude of opportunities across other cancer types. 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 02/1951 as we get this drug to the market.

Speaker 2

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.

Speaker 2

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.

Speaker 1

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

Operator

Thank you. 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 Doctor. Sean McCarthy, Chairman and CEO for closing remarks.

Speaker 2

Well, thanks everyone for joining us today. It's obviously a very exciting day for all of us here at CytomX 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.

Operator

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

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Key Takeaways

  • CytomX announced positive interim Phase I data for CX-2051 in metastatic colorectal cancer, demonstrating a 28% confirmed overall response rate, a 94% disease control rate, and a preliminary median progression-free survival of 5.8 months.
  • The Probody-masked EpCAM-targeting antibody-drug conjugate exhibited a favorable safety profile with no dose-limiting toxicities or severe EpCAM-associated toxicities, supporting development in earlier treatment lines and combination regimens.
  • Baseline tumor biopsies revealed uniformly high EpCAM expression across all patients, indicating CX-2051 may not require target-based patient selection and could serve as a pan-CRC therapy.
  • The company secured $100 million in financing from leading healthcare investors to advance the CX-2051 program and its broader pipeline, bolstering its resources for focused execution.
  • CytomX is expanding three dose levels (7.2, 8.6 and 10 mg/kg) to 20 patients each, plans a Phase I data update in Q1 2026, and aims to initiate Phase II in H1 2026 while exploring later-line and earlier-line treatment opportunities.
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Earnings Conference Call
CytomX Therapeutics Q1 2025
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