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Good afternoon, everyone. Thank you for standing by. Welcome to the CytomX Therapeutics Second Quarter 2025 Financial Results 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, CytomX' Chief Financial Officer. Please go ahead.

Thank you. Good afternoon, 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 are 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. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments or otherwise. Earlier this afternoon, we issued a press release that includes a summary of our second quarter 2025 financial results and highlights recent progress at CytomX. We encourage everyone to read today's press release and the associated materials, which have been filed with the SEC. Additionally, the press release, 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 is Dr. Sean McCarthy, CytomX' Chief Executive Officer and Chairman. Sean will provide an update on our pipeline and company progress before I cover the financials for the quarter. We will then conclude with a Q&A session. With that, I'll now turn the call over to Sean.

Thanks, Chris, and good afternoon, everyone. We're thrilled to be here today to review our progress for the second quarter, highlighted by the exciting clinical data we announced in May for CX-2051, our PROBODY antibody drug conjugate targeting EpCAM, which we view as having significant potential in colorectal cancer and potentially many other tumor types. We're also making great progress with our second current clinical program, CX-801, that I'll come to a little later. I'll focus initially today on CX-2051 and our work in colorectal cancer, which I'll refer to from here on as CRC. CRC remains one of the biggest unmet needs in oncology with approximately 1.9 million patients diagnosed per year on a global basis. 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 death by cancer worldwide. Despite many advances across many other cancer types in recent years, CRC has seen little impact from innovation over this period of time, resulting in current 5-year survival rates in metastatic CRC of about 13%. New treatments like antibody drug conjugates are urgently needed to treat this cancer. In other solid tumor types, ADCs such as ENHERTU, TRODELVY and ELAHERE have made a big difference for patients, but ADCs have yet to break through in CRC, representing a major scientific, clinical and commercial opportunity. At CytomX, we have intentionally designed CX-2051 to address this opportunity, building on years of experience in how to optimally leverage our PROBODY technology for the maximum benefit of cancer patients. Let me recap the key design elements of CX-2051. EpCAM is a very highly expressed target in CRC, making it very attractive for an ADC. The payload on CX-2051 is a topoisomerase-1 inhibitor, which is ideally matched to CRC, where the Topo-1 inhibitor, irinotecan, has been a core component of the standard of care for many years. And thirdly, critically, CX-2051 uses CytomX PROBODY masking technology to limit binding in normal tissues, something that has thwarted previous attempts to drug EpCAM. Our initial experience with CX-2051 in the clinic announced in May is very encouraging. We have focused our Phase I clinical evaluation exclusively in CRC with the goal of delivering clear clinical proof of concept in this high area of unmet need. I'd like to briefly recap the CX-2051 initial Phase I data from May. For context, CX-2051 has initially been studied in a fifth-line CRC patient population where approved standard of care therapies are typically associated with 1% to 2% response rates and progression-free survival of only 2 to 3 months. In comparison to these benchmarks, CX-2051 has demonstrated robust clinical activity with a 28% confirmed overall response rate, 94% disease control, and 5.8 months of preliminary progression-free survival in the first 18 efficacy evaluable patients at relevant dose levels. We're also encouraged to have observed clinical activity, including confirmed objective responses across a relatively wide range of doses. Our initial data has also validated that EpCAM expression is abundant in late-line CRC with every evaluable patient having high target levels. This is important because it suggests that CX-2051 may broadly address CRC and may not require patient selection, potentially a significant commercial advantage. Furthermore, our CX-2051 masking strategy has succeeded in avoiding classic EpCAM toxicities such as pancreatitis that have impeded the successful development of drugs against this target previously. In terms of next steps, we have initiated dose expansions at doses of 7.2, 8.6 and 10 milligrams per kilogram administered every 3 weeks, and we are targeting enrollment of approximately 20 patients at each dose level. Enrollment is going well, and we remain on track for an updated data set from a total of about 70 patients in Q1 2026. Our goals for the dose expansions are to more fully characterize the dose response of CX-2051, both in terms of clinical activity and safety with the goal to inform dose selection for Phase II. In terms of safety, the most common adverse events in the interim Phase I data were diarrhea, nausea, vomiting and anemia. In the expansion phase, we're paying particular attention to management of diarrhea using prophylactic medications, and we'll continue to iterate and refine our AE management strategies to best position CX-2051 for Phase II and beyond. In parallel to enrolling the expansion cohorts, we are in the process of developing our Phase II strategy in late-line CRC and planning for potential initiation during the first half of 2026. While detailed next steps will, of course, be data dependent, our current view is that the next study would likely evaluate CX-2051 monotherapy in fourth-line CRC based on the high unmet need, the potential speed to market and the multibillion-dollar market opportunity we see in this treatment setting. Looking out to the longer term, CX-2051 is also anticipated to have potential in earlier lines of CRC therapy and ultimately may be positioned, we believe, to replace irinotecan as a foundational component of CRC treatment. In support of this strategy, we anticipate starting combination studies in CRC in 2026. Now turning to CX-801, our masked interferon alpha-2b program that we're developing in combination with the PD-1 inhibitor, KEYTRUDA. Interferon alpha is a powerful immune system modulator with known anticancer activity across multiple tumor types, including renal cancer, bladder cancer and melanoma. But it's fallen out of clinical use in oncology due to its poor tolerability. We designed CX-801 to really clamp down on the undesired broad systemic activity of interferon and localized activity to the tumor microenvironment. In May of 2025, during Q2, we dosed the first patient in the combination arm of our Phase I study with KEYTRUDA. This study is focused in metastatic melanoma, and we're targeting initial data for the combination in 2026. In the fourth quarter of this year, we anticipate providing a first look at translational data for monotherapy CX-801 impaired tumor biopsies and specifically how it's modulating the tumor microenvironment, including potential upregulation of interferon stimulated genes like PD-L1. Positive early results here would provide evidence that the mechanism of action is working as designed, underpinning our rationale for the KEYTRUDA combination and supporting our vision of turning cold tumors hot with this novel immunotherapy. We look forward to providing this initial CX-801 translational update in Q4 this year. With that, let me turn the call over to Chris for updates on our finances.

Thank you, Sean. Echoing Sean's earlier comments, the second quarter was important as we presented initial CX-2051 Phase I data that informed clear next steps for the program. From a capital formation standpoint, we are pleased to have completed a $100 million follow-on offering with a top-tier group of shareholders, further underscoring CX-2051's potential. Following the execution of the financing, CytomX is in a strong financial position with projected cash runway to the second quarter of 2027. Of note, our cash guidance does not assume any additional milestones from existing collaborations or any new business development. Outside of CX-2051, we will continue to employ a focused capital allocation approach, including for CX-801, where we are aiming to deliver initial proof of concept in combination with KEYTRUDA in melanoma. In terms of our research collaborations, we continue to view partnering as a capital-efficient way to extend the reach of our technology and drive increased long-term value. A key current focus in our collaborations is T-cell engagers, where, for example, we have momentum with partners, Regeneron and Astellas and have the potential to earn milestones over the next 1 to 2 years. With that, I'll walk through our second quarter financial results. As of June 30, 2025, we ended the quarter with $158.1 million in cash, cash equivalents and investments versus $79.9 million in cash at the end of the first quarter of 2025. Total revenue was $18.7 million compared to $25.1 million in the second quarter of 2024. The lower revenue was driven by the completion of our performance obligations in the BMS and Amgen collaborations as well as decreased activity with Moderna. Operating expenses for the second quarter were $19.9 million compared to $33.6 million in the second quarter of 2024. R&D expenses were $13.3 million during the second quarter, representing a decrease of $11.9 million versus the second quarter of 2024. General and administrative expenses also decreased by $1.8 million during the 3 months ending June 30, 2025, to $6.6 million compared to $8.4 million for the corresponding period in 2024, driven by lower personnel costs and lower legal and patent expenses. Overall, we will continue to maintain a disciplined data-driven capital allocation approach in order to advance the most promising opportunities in our pipeline. With that, I'll turn the call back to Sean for closing remarks.

Thanks, Chris, and thanks, everyone, for joining us today. CytomX made tremendous progress during Q2, and we look forward to the second half as we set our sights on 2026 and in particular, next steps for the CX-2051 program. With EpCAM, we believe we have unlocked a new approach to the treatment of late-stage CRC, leveraging our proprietary platform technology and prior experience with masked ADCs. We view CX-2051 as a first-in-class and highly differentiated asset with broad scope for value creation. Based on the interim Phase I dose escalation results disclosed to date, we see a clear path forward to develop CX-2051 in late-line CRC, and we plan to execute against this opportunity as our top near-term priority. We're excited to see Phase I results in Q1 of 2026, together with our next steps for the program. Regarding CX-801, we're executing a similarly focused strategy to CX-2051 in melanoma in order to generate proof of concept for the KEYTRUDA combination. Positive data here would reestablish interferon as a potential new centerpiece of combination immunotherapy with broad potential across many immunologically cold tumors or for patients who become refractory to checkpoint inhibition. We look forward to advancing CX-801 towards this vision. Before I wrap up today's call, I want to sincerely thank and honor the patients who joined our studies, their families, our clinical investigators and our dedicated team here at CytomX. Your collective contributions are responsible for our advancements, and we're grateful for your help in getting us to where we are today. With that, operator, please go ahead and open up the call for Q&A.

[Operator Instructions] Our first question comes from the line of Edward Tenthoff with Piper Sandler.

Congrats on all the progress here. So my question has to do with the potential to move into earlier lines of colorectal therapy. What's going into those decisions? And how do you envision sort of announcing those trials?

Ted, thanks for the question. So as I mentioned, first of all -- first and foremost, we're super focused on executing towards the late-line opportunity. We see a terrific opportunity there to move really quickly in fourth line. Coming into the earlier lines, obviously, is a key -- will be a key focus for us over time to really broaden the opportunity. That will require combination studies to assess the doses that we ultimately select for the Phase II for the monotherapy in the context of certain combinations to come into -- well, into third line and then, of course, into second line, where the vision would be to replace irinotecan. So one, clear opportunity there in terms of combinations, given the extent of its use in treatment of CRC is to evaluate the combination with bevacizumab. And that's something that we're looking at carefully. And we will be doing -- I'm pretty sure in the future, we need to obviously round out the Phase I study and select our doses.

Our next question comes from the line of Nabeel Nissar with Jefferies.

This is Nabeel on for Roger. Thanks for the updates. Quick question regarding the rationale for value creation of EpCAM beyond CRC. Are we approaching this with partnerships? And what is the strategy? Are we looking for a particular TAM? Or is there a particular tumor indication that would fit better with your technology?

Thanks for the question. It's a terrific opportunity to broaden the 2051 development program outside of CRC. We do, of course, currently have our hands rather full with the scope and scale of the opportunity in colorectal alone. But just to restate, EpCAM is expressed in most solid tumors and in many of them at high levels. So for example, lung, pancreatic, gastric, endometrial breast cancer. So there's an enormous opportunity here now that we have initial proof of concept in colorectal. So it is the kind of drug or the kind of profile of drug that over time, could very well benefit from a partnership. We'll get there when the time is right. As I've said many times on these calls, we'll do the right deal or right deals at the right time. But that could certainly make sense in the future for value creation. But again, right now, over the next few months, we're -- I think it's important for us to be laser focused on really building value initially through the CRC opportunity.

Our next question comes from the line of Matt Biegler with Opco.

What do you think is the bar for accelerated approval in CRC right now, assuming you do go forward with like a monotherapy fourth line? I think obviously, like the rule of thumb that the buy side loves to point to is a 30% ORR, but we've recently seen an ESMO working group come out advocating as low as 20%, I think, like given how poor salvage therapies work in this setting. So I'm just kind of curious if you had any thoughts on that or whether you think ORR is even the most relevant outcome versus PFS or OS or something like that?

Yes. Thanks, Matt. Great question. And of course, an exceedingly difficult one to answer at the moment. But given the activity that we've seen so far and the performance of 2051 in this area of such enormous unmet medical need, we, of course, have to be thinking about strategies that could lead to an accelerated approval. We want to get this drug to patients as quickly as we possibly can. That said, there are two major considerations as we develop that strategy. One, there's not precedent for accelerated approval in the CRC setting based on ORR, as you know, that would be breaking new ground. More typically, we're looking at a patient population in a clinical setting where we're relying on PFS and of course, ultimately OS endpoints. That said, the scope of the unmet need, the nature of the unmet need here is so high and our activity is so encouraging that we are considering it, and we will, at the right time, have discussions with FDA. The second thing, of course, is just the overall regulatory uncertainty at the moment, which none of us can ignore. But just to reiterate, of course, we're all aligned here and wanting to get this drug to patients by the fastest possible means.

Our next question comes from the line of Anupam Rama with JPMorgan.

So on the preliminary 801 monotherapy data here in the fourth quarter, what are you looking for that might give you confidence in sort of the combination potential of this product with KEYTRUDA and melanoma? And I guess, any thoughts on any risks of overlapping tox that you're going to be monitoring for?

Anupam, great question. I'm happy to talk about 801 a little bit more. So first of all, there's actually a very good precedent for -- mechanistically for PD-1, specifically KEYTRUDA and interferon alpha-2b having very powerful combination activity in melanoma. That's been shown by Merck in a somewhat earlier setting -- patient setting than we're currently working in. But nonetheless, they showed robust activity, but it was limited by significant incidence of Grade 3 adverse events of various kinds, particularly immune adverse events. So we do know that this combination can be very effective in melanoma as a starting point. In terms of the progression of our development plan for 801, we're being very deliberate about it. We have escalated through several cohorts already of monotherapy just in a handful of patients to get initial experience with the drug. In that escalation, we've reported previously, we've already exceeded the clinically approved dose and clinically utilized dose of interferon alpha. So we've already made progress, which is consistent with masking showing an overall tolerability benefit. Most importantly, though, that initial experience with just a few monotherapy patients ungated our ability to start the combination, which we did during Q2, as we just mentioned. And that really is the drug here. So we see the drug ultimately as being 801 plus KEYTRUDA, and we're now going to aggressively enroll that arm of the study, and that data will be reported next year. So the safety and efficacy data from the combination will come in 2026. In the meantime, with this handful of monotherapy patients that we've treated, we have been studying and we'll continue to study a series of paired tumor biopsies to interrogate the immune tumor microenvironment to look at how in the microenvironment, the unmasked interferon is modulating immune cells and also inducing what we would expect it to do, which is to induce interferon regulated genes, which include PD-L1, which really underscores the rationale for the combination with a checkpoint inhibitor like KEYTRUDA. So the data that we're planning to share in Q4 will be from a handful of patients. It will be biopsy data initially. We're not expecting in this initial small number of patients to have any kind of initial ORR assessment. It's going to be translational data, but very important and hopefully very informative data that shows us that at the molecular level, the drug is behaving as we've designed it.

Our next question comes from the line of Peter Lawson with Barclays.

I apologize if this has been asked, I joined late. On the EpCAM ADC, so we got the Phase I update in Q1. Kind of just if you could talk through the size of the data set we see and the scope of it, and kind of if we should expect to see durability and also biomarker data.

Yes. Thanks, Peter. Thanks for giving me the opportunity to recap some of our earlier comments on the call. It's very important. So as we said, we're super focused on generating this next data set for 2051. We anticipate that in Q1 2026, we'll have 70 and maybe a few more patients have experience with the drug compared to the update, the initial disclosure in May, which was 25 safety evaluable patients and 18 efficacy evaluable. So by the time we get to Q1, that data set should be quite a bit larger and predominantly across three dose levels, 7.2, 8.6 and 10 mg per kg. Each of which were doses that we saw clinical activity for in that initial disclosure, right? So by then, yes, we would expect to have reasonable follow-up on the majority of those patients. And the other element of that update will be integration of that data into our go-forward plan for Phase II. So that's our current plan is that the Q1 update will be a rounded out Phase I data set plus our strategy for moving forward into Phase II. That's the current plan.

And that Phase II, would that have a randomized component to it?

I think that's most likely. Yes, we're still obviously collecting data from the Phase I. So no decisions made yet, but we are of the general view that the next study would be randomized to a component or components of current standard of care in the fourth line where, unfortunately, for patients today, the bar is very low. So we think that 2051 is very well positioned against those comparators. And we'll also be thinking through in the context of Project Optimus and also, of course, based on the full Phase I data set that we analyzed later this year and into Q1, whether that's a one dose of 2051 or maybe two, that remains to be decided.

Our next question comes from the line of Mitchell Kapoor with H.C. Wainwright.

You mentioned that there's quite a low bar for 2051. That makes a lot of sense. But thinking about what triggers a go/no-go move into the Phase II and fourth line as a monotherapy, can you just speak to what we should be looking for that would be indicative of a positive outcome that would immediately trigger looking to move into Phase II?

Yes. Mitch, thanks for the question. Well, again, just to recap our experience with the first 18 efficacy evaluable patients where across the three dose levels of 7.2, 8.6 and 10, we saw a confirmed ORR of 28%. So I think we all agree that that's very exciting and would set up a very clear go-forward decision into the fourth-line study. Number doesn't, of course, need to be as high as that to go forward. I don't think we're going to put a number on it today, but we've got a lot of room to maneuver, we think, with the data that we've already presented with CX-2051 as our data continues to mature.

Okay, great. And just one more on the CRC combos in earlier lines, would you potentially advance multiple combinations? And have any plans been discussed with the FDA on the combination strategy so far?

Multiple combinations are certainly on the table. We need to be mindful of our resources at this point in time. And as I mentioned, the place to start most likely would be the combination with bev. We have yet to have significant conversations with FDA relating to few go-forward study design. That will come, of course, as our Phase I data continues to mature.

Our next question comes from the line of Mayank Mamtani with B. Riley.

This is Jeff from B. Riley for Mayank. My first question is given that CX-2051's Grade 3 diarrhea rates exceeded those of other Topo-1 inhibitor ADCs. Will you explore alternative mitigation strategies such as specific protease inhibitors or microbial modulation rather than relying solely on loperamide. My second question is how much median follow-up are you expecting to have at 1Q update? And are you planning to present data at ASCO GI in January 2026?

Great. Thanks for the questions. So taking the first one relating to diarrhea. Yes, so as I mentioned on the call, that is one of the AEs that we're most focused on in this Phase I study. We've learned a lot about it in the context of the data that we initially disclosed. Just to recap what we're doing, as we've discussed before. In the earlier part of this study, of course, as we wanted to understand the overall AE profile of this drug, we have not implemented any prophylactic measures for management of diarrhea. But we did earlier this year around the March time -- March, April time frame around the time that we were beginning to gear up some of these expansion studies. And so we continue to be focused on the use of loperamide as a prophylactic measure. We're going to learn a lot about that as we continue to execute on the expansions. And in terms of the incidence of Grade 3 diarrhea in the study, about 20%. I want to remind everyone that in the early days of irinotecan development, that number was closer to 30% to 40%. And we do know that Topo-1 inhibitors in the context of ADCs can also induce significant levels of Grade 3 and higher diarrhea. So it's something we need to understand more about, something we need to manage. We're really exploring loperamide as a starting point. Your question on protease inhibitors, I think is an interesting one. At this point, that will be very exploratory, and we don't really have any evidence right now that protease biology is playing any role in the AE profile. So that may be something for future exploration. But thanks for the question. I think you had two more questions in terms of median follow-up. I guess there, what I would say is that, as I mentioned earlier, enrollment of the expansions has gone well. We're midway through 2025. So by the time we get to Q2 -- sorry, Q1 of next year, we'll have a pretty decent follow-up, we think, on the majority of these patients. So I can't give you a number. The study is still in progress. And of course, I can't comment on the ASCO GI 2026. We will plan to keep all of our options open in terms of where and exactly when we present data as is customary. But thanks for the questions.

Ladies and gentlemen, I'm showing no further questions in the queue. I would now like to turn the call back over to Dr. Sean McCarthy, Chairman and CEO, for closing remarks.

Thanks, everyone, for joining us today. It's been a pleasure to recap our tremendous progress during Q2 of 2025. We look forward to providing additional updates as we move through the second half of the year. So enjoy the rest of your day.