Good afternoon, everyone. Thank you for standing by. Welcome to the CytomX Therapeutics, Fourth Quarter 2024 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's Chief Financial Officer. Please go ahead.

Thank you. Good afternoon, and thank you for joining us. Before we begin, I'd 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 2024 full-year financial results and highlights recent progress at CytomX Therapeutics, Inc. 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's Chief Executive Officer and Chairman. Sean will provide an update on our pipeline and company progress before I walk through the financials for 2024. We will then conclude with the Q&A session. With that, I'll now turn the call over to Sean.

Thanks, Chris, and good afternoon, everyone. We are very pleased to be here with you today to provide updates on our continued progress at CytomX Therapeutics, Inc., towards our mission of urgently advancing our probody therapeutic pipeline for the maximum benefit of cancer patients. As a pioneer in the field of antibody masking and conditional activation, we continue to direct our powerful technology platform towards major unmet needs in oncology. We are seeing broad strategic interest in antibody masking and CytomX is uniquely positioned with expertise and capabilities to deliver novel, masked therapeutics across multiple treatment modalities, including antibody-drug conjugates, T cell engagers, and cytokines. Our current clinical programs have been built on over a decade of scientific and clinical expertise and follow clear design principles aimed at optimally selecting the cancer type of interest, the tumor target, and the relevant effective function in order to deliver differentiated cancer therapies. 2024 was a very productive year for us, including the advancement of two new programs into the clinic, CX-2051 and CX-801. In January 2025, we announced the prioritization of these programs and the streamlining of our organization, extending our cash runway to Q2 of 2026, supporting our ability to deliver upon key clinical milestones. We see our lead program, CX-2051, as a highly differentiated first-in-class ADC that is designed to address a large unmet need in colorectal cancer and build significant value for CytomX Therapeutics, Inc. CX-801 is a masked version of interferon alpha with, we believe, broad potential as a next-generation targeted immunotherapy. 2025 promises to be an exciting year for CytomX Therapeutics, Inc. where we expect to generate initial clinical data for both CX-2051 and CX-801 that we believe could drive significant near-term value creation. I'd like to cover recent progress in our pipeline before handing over to…

Throughout 2024, we remain disciplined in our capital allocation. With a focus on progressing our clinical pipeline for the initial Phase one data. Entering 2025, we are now positioned to achieve initial data readouts for CX-2051 and CX-801. As Sean highlighted earlier, in January of this year, we made a focused set of trade-offs that extend our cash runway and direct capital primarily to our lead programs CX-2051, and CX-801. So now I'll turn to our 2024 financial results. As of December 31, 2024, we ended the year with $100.6 million in cash, cash equivalents, and investments. Compared to $174.5 million in cash at the end of 2023. With our prioritization efforts, we expect that our cash balance will continue to fund CytomX Therapeutics, Inc. operations into the second quarter of 2026. Consistent with our prior approach to cash runway guidance, our cash guidance does not assume any additional milestones from existing collaborations. Or any new business development. Which we have a strong track record of achieving. As Sean mentioned earlier, we recently achieved a $5 million milestone in our Stellus T cell engager collaboration, and we are funded to continue to execute programs under our research alliances. Turning to revenue and operating expenses for the year. Total revenue was $138.1 million compared to $101.2 million for the corresponding period in 2023. Increased revenue was attributed to our BMS collaboration as well as our collaborations with Moderna, Estella, and Regeneron. Total operating expenses for the full year were $113.1 million compared to $107.7 million in 2023. 2024 operating expenses increased $5.4 million primarily due to a $5 million milestone payment to AbbVie, for initiation of phase one for CX-2051. Excluding this milestone, operating expenses were essentially flat to 2023. R and D increased by $5.7 million from last year to $83.4 million in 2024. Also driven by the milestone payment for CX-2051 Phase one start. G and A expenses were essentially flat during 2024, decreasing by $0.3 million to $29.7 million for the year ended December 31, 2024. We remain committed to disciplined capital allocation and resource management. And we believe we are well positioned to progress our promising pipeline, deliver value to shareholders, and, ultimately, bring new treatment options to cancer patients. With that, I'll turn the call back to Sean for closing remarks.

Thanks, Chris, and thanks everyone for joining us today. We look forward to sharing additional updates in the coming months including the first look at how CX-2051 is performing in colorectal cancer. To close out, I want to recognize and sincerely thank the patients who join our studies, their families, our clinical investigators, and our dedicated team here at CytomX Therapeutics, Inc. We've never been more committed to our vision, mission, and values at CytomX Therapeutics, Inc., so we look forward to an exciting year ahead. With that operator, let's go ahead and open up the call for Q and A.

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

Great. Thanks for taking the question. Maybe just one related to 2051. So given your enrolling patient progressing, and then how should we think about the first half date update in terms of patient number and then what kind of data we're gonna show, what's the expectation for the data readout for the first half. Yeah. Hi, Roger. Thanks for the question.

Well, we're expecting it to be a meaningful update. We do anticipate this initial look will include an initial characterization of the safety profile of the drug, up to and including doses as we said that we are predicting based on our preclinical work in the therapeutically active range. We've been pleased with the escalation so far given the prior history with other systemic EPCAM strategies having hit roadblocks very early in dose escalation. So you know, so from that standpoint, so far so good. Of course, this initial update will all will will will first update first presentation of data will include an initial assessment of antitumor activity across these first few cohorts, and, you know, that activity data could take the form of pharmacodynamic markers, tumor stabilization, of course, potentially tumor shrinkage, and, of course, if we see anything approximating or equivalent to resist responses in this very late line CRC patient population, we would be absolutely thrilled.

Yep. Got it. And then in terms of the a o one, I You will give us some update in second half, and then also you will move you say you were moving to the Pembroke combination. So how should we think about the timing and then criteria moving to the Pembro before or after you give us the Did update. Thank you.

Yes. Great question. So as I mentioned, as we're twenty fifty one, you know, we've been pleased with the operational execution in the eight zero one study so far having really just started that, that phase one study and already now being in the fourth dose level and the the starting dose was pretty decent, and that's allowed us to go pretty quickly to now be treating patients with doses that are higher than than the approved dose So unmasked into parenthesis. So so that's that's encouraging. And because we've been able to quickly go through those initial cohorts, we do see the the potential to those those first two dose levels we do see the potential to initiate the KEYTRUDA combo in second half. If if I had to guess, I'd say that the sequencing would be the combo initiation would proceed any data presentation, but we do remain on track. Based on our ongoing translational work looking at tumor biopsies to to be sharing some initial data by the end of the year.

Excellent. You.

You're welcome.

Thank you. Our next question comes from Joe Catanzaro with Piper Sandler. Your line is open. Great. Hey, everybody. Thanks for taking my question. Maybe a couple on two thousand and fifty one. So I think you've been saying for a little while now that you've entered therapeutically active doses based on preclinical data. Today, you're saying you're in the seventh dose cohort. So wondering how many of those seven dose cohorts sort of fall into that category of predicted to be within therapeutic the active doses. I guess I'm just trying to get a sense of sort of what percent in this initial disclosure will fall within that that category. Thanks.

Yeah. Hi. Hi, Joe. So the the first couple of cohorts as we've disclosed previously were single patient doses single patient cohorts, excuse me, at doses that we would predict to be outside of the therapeutic active range. But entering dose level three, we would predict Again, based on the animal modeling that and based on what's generally known about Topo one ADCs, that we will be starting to get into that range and, of course, that would increase as we've we've continued the escalation. So I think a significant number of patients by the time we're ready to share data we'll have been treated with doses in in that range. Of course, I wanna emphasize again that this is a a late line patient population We're enrolling predominantly patients who have had at least three prior lines of systemic therapy. And, you know, so we think the the the the bar is fairly low here for actual clinical activity.

Okay. Great. And then maybe a maybe a follow-up. So you noted not enrolling. Based on KRAS status or or LiverMed. So so I'm wondering if any expectations whatsoever potentially seeing differential activity as it relates to some of those features like KRAS status or presence, absence of liver meds or or maybe even anything else that you're thinking of. Thanks.

Yeah. There's there's no obvious there's no obvious biology you know, that would you know, suggest that ATCAM well, let me start by saying, ATCAM expression or just reiterating that Atcam expression is high in more than ninety percent of CRC patients. And, yeah, we've validated that with our our own work, and we're measuring EPCAM levels, of course, in every patient that we treat. So, we'll have that data for this study. There's no reason to suggest that there's a connection between KRAS mutational status a Netcam, or LiverMax and Netcam. It's it it the point we're making is that, we're enrolling the full patient population this time to characterize the drug across the full CRC population. And we'll we'll see what we get. I mean, if if it turns out that we get, you know, data that suggests that suggest that the drug is more suited to a particular subset then we may investigate that. But at this point, we're we're enrolling a broad patient population.

Okay. Got it. That's helpful. Thanks for taking my questions. Okay.

You're welcome.

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

Hi, guys. This is Priyanka on for Anupam Just kind of following up on the previous line of questions. Since we enrolled patients in the CX two thousand and fifty one phase one trial, it's not being preselected for AbbViec expression. Is there published literature, for example, to help guide what level expression would be beneficial?

Yes. There's a there's a broad literature on f chem expression across most tumors including colorectal, and I think it's Well established that EPKAM is is highly expressed in this tumor type. In fact, EPCAM was first described as a colorectal cancer marker, a very long time ago, actually. So, yes, I think it's pretty well established that CRC is a high account exporter in most most patients, and I I I anticipate that our clinical results will will will validate that.

So much for taking my question.

You're welcome.

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

You so much. Thanks for taking the questions. Just on the prior authorization of CRC for your EPCAM, Eighty c. Is that driven by the expression levels you kinda talked about and just kinda well known within the space. So you've already seen signals there. And also seen any signals outside CLC to date?

Yeah. Hi, Peter. That's helpful to help me help me clarify and and reiterate that this phase one study of two zero five one is being conducted entirely in the CRC setting. So we're only enrolling metastatic CRC patients. And as I mentioned, patients who have been treated the the the patient population that we're that we're seeing, that we're we're treating are for the most part, have have, for the most part, been treated with three at least three prior lines of of systemic therapy. So so the question is, okay. Why why focus in CRC? There's several answers to that. First of all, when you just look at EPCAM biology and the the target itself, CRC is really the indication that jumps out as, you know, with the highest broadest, most consistent, most, homogeneous expression from patient to patient. And as I said, it's actually where where EDCAM was first described as a tumor marker. That that said, EDCAM is highly expressed in in most other solid tumors. So this is a you know, pipeline, you know, product opportunity in the long run if we see a signal in CRC. There's no question about that. The other the other reason to select CRC is, you know, the unmet need the unmet need is just is is just huge. And so, you know, a scenario where Patients need new treatments. They've been waiting for them for decades. And we're we're trying to make a difference here. And then the third is that this drug this drug candidate with a TOPO one inhibitor was was really always designed with colorectal cancer in mind is the first place to go because you know, there's not much There's been it's kind of a wide open field. The ABCs in colorectal cancer And…

Yeah. As I as I as I already mentioned, I think we're looking at a number of things. We're looking at you know, evidence of you know, pharmacodynamic activity in tumor biopsies evidence of tumor stabilization because, you know, CRC approvals those drugs I mentioned earlier on that have been approved in the third line setting, third and or fourth line, for the most part, have been approved based on On PFS, type measures because it's very difficult achieve objective responses in this patient population. So if you can keep patients from progressing, that in and of itself is a is a success. So evidence of tumor stabilization, evidence of tumor shrinkage, and then, of course, you know, the the the the holy grail for us in this study is if we can see in this early first look in this late line patient population is to see if we can deliver objective resist responses. Perfect. Thank you so much. Thanks for taking the questions.

Thank you. As a reminder, to ask a question, please press star one one on your telephone. Again, that is star one one to ask a question. Our next question comes from Mitchell Kapoor with H. C. Wainwright. Your line is open.

Good afternoon. This is Dan on for Mitchell. Thanks for taking our questions. We wanted to ask where you might present the Phase 1a CRC data Would this likely be a press release event, any lean towards first quarter or second quarter, And then jumping on the therapeutic active range kind of discussion, many more dose levels do you plan to test, and where does the seventh dose level compare to the nonhuman primate clinical talks. Thank you.

Yeah. Thanks for the questions. In terms of where to present We're keeping our options open there. So we'll provide further guidance in due in due course. In terms of the you know, the escalation, The the the second and third questions are, of course, connected. The escalation into the seventh dose level, obviously, if we clear that dose level, we'll continue to we'll continue to escalate. We'll have to we'll have to see how that goes. At this point, That's where we are, and we'll we'll we'll have to see. I I would say that the the the you know, when we talk about predictive active range of the drug, that is Based on modeling, that is including our experience from mouse and cinemologist monkey experiments, together with understanding in general of other topa one ADCs and what experience others have had in the clinic with with this type of Thank you.

You're welcome.

Thank you. I'm not showing any further questions in the queue. 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. We look forward to providing additional updates throughout the year and hope you all have a good rest of the day.

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