Chris Ogden; Chief Financial Officer; CytomX Therapeutics Inc
Sean McCarthy; Chairman of the Board, Chief Executive Officer; CytomX Therapeutics Inc
Roger Song; Analyst; Jefferies
Joseph Catanzaro; Analyst; Piper Sandler Companies
Peter Lawson; Analyst; Barclays
Operator
Good afternoon, everyone. Thank you for standing by. Welcome to the CytomX Therapeutics fourth-quarter 2024 and 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.
Chris Ogden
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 2024 full-year financial results and highlight 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 recorded on 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 walk through the financials for 2024. We will then conclude with a Q&A session.
With that, I'll now turn the call over to Sean.
Sean McCarthy
Thanks, Chris, and good afternoon, everyone. We're very pleased to be here with you today to provide updates on our continued progress at CytomX 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're 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 effector 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.
CX-801 is a mass version of interferon alpha with, we believe, broad potential as a next-generation targeted immunotherapy. 2025 promises to be an exciting year for CytomX, 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 Chris, who will review our financials.
I'll start with our lead program, CX-2051, our first-in-class masked ADC targeting epithelial cell adhesion molecule. We are the only organization to our knowledge, addressing this target in this unique way. EpCAM has been viewed as a high potential opportunity for many years due to its pan tumor expression and it's particularly high expression in colorectal cancer.
However, EpCAM is also expressed at moderate to high levels in normal tissues which has prohibited the successful development of systemic therapeutics against this target. The strong evidence, though that EpCAM targeting with locally delivered approaches can achieve clinical anticancer activity, including the multi-specific antibody, Korjuny, that is currently being relaunched in the EU for the localized treatment of intraperitoneal malignant ascites.
Despite success with localized therapies, however, prior systemic EpCAM-targeting strategies have not been able to reach therapeutically active drug levels in patients. And these include the T cell engager, solitomab, and other antibody approaches, which showed early promise but were unable to deliver a viable therapeutic window due to dose-limiting toxicities in the pancreas, liver and gastrointestinal tract.
CX-2051 is a Probody ADC comprising a high-affinity EpCAM antibody with a peptide mask and a protease-cleavable mask linker that has been validated in prior clinical work by CytomX. In designing CX-2051, our goal is to mitigate potential on-target EpCAM toxicities and to localize CX-2051 preferentially to tumor tissue. Preclinically CX-2051 has shown a wide potential therapeutic index and potent anticancer activity in multiple EpCAM-expressing indications.
The payload on CX-2051, CAMP59, is a topoisomerase-1 inhibitor selected specifically to treat topo-1-sensitive tumors, and in particular, colorectal cancer. The topo-1 inhibitor irinotecan is, of course, a key component in the treatment of metastatic CRC in the first and second-line settings. And so it's well established that this cancer can respond well to this class of drug. The global unmet need in colorectal cancer is one of the most significant in oncology with more than 1.9 million new cases annually and limited new treatments emerging for patients over the last two decades.
Unfortunately, there's also an increasing percentage of new CRC cases diagnosed as metastatic and a concerning trend of growing incidents in younger patient populations. First- and second-line treatment to metastatic CRC are still primarily based on systemic chemotherapy regimens that include irinotecan or oxaliplatin. In the later-line setting, patient options remain highly inadequate in patients that have generally had three or more prior lines of therapy, current standard of care only achieves low to mid-single-digit objective response rates and median progression-free survival of only two to four months.
We advanced CX-2051 into the clinic in Q2 last year, and we have been pleased with the execution and enrollment in the study to date. We are currently focused in late-line CRC with enrolled patients generally having received at least three prior systemic therapies. Given the consistently high levels of EpCAM expression in CRC, we are not preselecting patients for EpCAM expression in our Phase 1 study or for disease characteristics such as KRAS mutational status or liver metastases.
In dose escalation thus far, we've been encouraged by the CX-2051 safety profile, having successfully dose escalated to levels that we predict based on preclinical modeling to be biologically active and that we're confident could not be achieved with an unmasked ADC. As we continue in dose escalation, our expectation is that the maximum tolerated dose of 2051 will be largely driven by the cytotoxic payload.
Specifically, we will be fully characterizing the anticipated GI toxicities and cytopenias such as neutropenia and anemia that's are commonly associated with topo-1 inhibitors. We're currently evaluating the seventh dose level in our dose escalation, and we have also begun to selectively backfill at certain dose levels to gain additional experience with the drug. Overall, we believe our early clinical experience with CX-2051 is showing that this first-in-class ADC is performing as designed, underpinning its prioritization is the lead program for CytomX and our focus on bringing this therapy to patients as quickly as possible.
We remain on track to provide initial Phase 1a data in CRC in the first half of 2025, and we expect to be in a position to define next steps for the program in the second half of the year.
Now moving to CX-801, our masked Probody interferon alpha-2b which is also making good early progress in Phase 1.
Interferon alpha is a well-validated therapeutic and was one of the first immunotherapies to be approved for cancer treatment. Interferon has established single-agent anticancer activity in multiple tumor types, including renal cancer, bladder cancer, and melanoma. Over time, systemic interferon has fallen out of clinical use in oncology, primarily due to its poor tolerability arising from systemic toxicities. However, interferon alpha is a powerful driver of T cell activation and antigen presentation, making it an ideal combination agent with checkpoint inhibitors.
Similarly to EpCAM, it's been shown recently that localized interferon alpha-2b can be very effective as an anticancer therapy. Specifically, the recently approved gene therapy, Adstiladrin, encoding interferon alpha-2b achieved a 51% complete response rate in patients with bladder cancer, reaffirming that this potent cytokine can indeed achieve robust antitumor responses in patients.
It's also been showing that interferon can potentiate the clinical effects of PD-1 inhibition including a Merck sponsored study, demonstrating a 60% response rate with KEYTRUDA in combination with KEYTRUDA in combination with interferon alpha-2b in advanced PD-1 naive melanoma. This combination was not further developed, however, due to grade 3 or higher adverse events occurring at approximately 50% of patients.
801 is designed to harness the proven power of interferon alpha-2b by reducing systemic activity and localizing therapeutic activity to the tumor microenvironment. We initiated our Phase 1/2 escalation study of CX-801 in the third quarter of 2024, focused in the advanced metastatic melanoma setting. We've made very good progress to date in the study, and we're currently enrolling the fourth monotherapy dose escalation cohort.
Importantly, as of the third dose level, we had already achieved doses that surpassed the approved dose of unmasked interferon alpha-2b SYLATRON. Our translational science program for CX-801 is multifaceted and includes systemic and intratumoral analysis of PD biomarkers that will give us insight into molecular performance of the drug candidate, and we hope the induction of an inflammatory tumor microenvironment conducive to PD-1 combination therapy.
Our goal is to present initial Phase 1a translational data for 801 in the second half of this year. Based on our progress to date, we also anticipate initiation of combination therapy with KEYTRUDA in 2025 under the collaboration and supply agreement we secured with Merck last year. Overall, we believe CX-801 is well positioned to demonstrate clinical proof of concept in advanced melanoma where the unmet need remains very high.
Longer term, we see CX-801 as a foundational combination agent which can potentially address the large population of cancer patients who do not respond to checkpoint inhibitors or who are refractory to immunotherapy. Turning now to our research collaborations.
Our partnerships continue to be very important to us in 2024 and remain so in 2025. I'm very pleased to say that in February of this year, we achieved another $5 million milestone payment in our Astellas T cell engager collaboration as a result of Astellas selecting a collaboration clinical candidate to advance into GLP toxicology studies. We look forward to continued progress with Astellas as well as strong execution in our discovery programs with Bristol-Myers Squibb, Amgen, Moderna and Regeneron.
Right now, the majority of our partner discovery programs are masked T cell engagers, an area in which CytomX and our partners continue to see significant potential. Regarding our first partner T cell engager program entered into the clinic, CX-904, we communicated earlier this year a reduction in capital allocation to this program given our overall pipeline priorities and pending ongoing dialogue with our partner, Amgen, regarding potential next steps.
Based on CX-904 clinical observations to date and our respective priorities, CytomX and Amgen have jointly decided not to continue CX-904 development. We continue T cell engager discovery work with Amgen. We remain optimistic about the potential of future mass T cell engagers and really look forward to making additional progress on this modality within our partnerships.
With that, let me turn the call over to Chris for updates on our finances.
Chris Ogden
Thank you, Sean. Throughout 2024, we remain disciplined in our capital allocation with a focus on progressing our clinical pipeline towards initial Phase 1 data. Entering 2025, we are now positioned to achieve initial data readouts for CX-251 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-251 and CX-801.
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 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 Astellas 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. The increased revenue was attributed to our BMS collaboration as well as our collaboration with Moderna, Astellas, 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 1 for CX-2051. Excluding this milestone, operating expenses were essentially flat to 2023.
The R&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 1 start. G&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.
Sean McCarthy
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. We've never been more committed to our vision, mission and values at CytomX, and we look forward to an exciting year ahead. With that, operator, let's go ahead and open up the call for Q&A.
Operator
(Operator Instructions) Roger Song, Jefferies.
Roger Song
Great. Maybe just one related to 2051. So given you're enrolling patients progressing and then how should we think about the first half data update in terms of the patient number and then what kind of data we're going to show, what's the expectation for the data readout for the first half?
Sean McCarthy
Yes. 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 or 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 from that standpoint, so far, so good. Of course, this initial update or first update -- first presentation of data will include an initial assessment of antitumor activity across these first few cohorts. And 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 RECIST responses in this very late-line CRC patient population, we would be absolutely thrilled.
Roger Song
Yes. Got it. And then in terms of 801, you will give us some update in the second half. And then also you will move -- you say you were moving to the pembro combination. So how should we think about the timing and the criteria moving to the prembro before or after you gave us some data update.
Sean McCarthy
Yes, great question. So as I mentioned, as with 2051, we've been pleased with the operational execution in the 801 study so far, having really just started that, that Phase 1 study and already now being in the fourth dose level. And 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 the approved dose of unmasked interferon alpha.
So that's encouraging. And because we've been able to quickly go through those initial cohorts, we do see the potential to -- those first two dose levels, we do see the potential to initiate the KEYTRUDA combo in second half. 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 be sharing some initial data by the end of the year.
Operator
Joe Catanzaro, Piper Sandler.
Joseph Catanzaro
Great. Maybe a couple on 2051. 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 seven-dose cohorts. 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 category.
Sean McCarthy
Yes, so the first couple of cohorts, as we've disclosed previously, were single patient doses -- single patient cohorts at doses that we would predict to be outside of the therapeutic active range. But entering dose level 3, we would predict again, based on the animal modeling that -- and based on what's generally known about Topo-1 ADCs that we will be starting to get into that range.
And of course, that would increase as we've continued the escalation. So I think a significant number of patients by the time we're ready to share data will have been treated with doses in that range. Of course, I want to emphasize again that this is a late-line patient population. We're enrolling predominantly patients who have had at least three prior lines of systemic therapy. And so we think the bar is fairly low here for actual clinical activity.
Joseph Catanzaro
Okay, great. And maybe a follow-up. So I think you noted not enrolling based on KRAS status or liver mets. 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 mets or maybe even anything else that you're thinking of.
Sean McCarthy
Yes, there's no obvious biology that would suggest that EpCAM, well, let me start by saying EpCAM expression or just reiterating that EpCAM expression is high in more than 90% of CRC patients. And we've validated that with 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, an EpCAM or livers mets in EpCAM. The point we're making is that we're enrolling the full patient population at this time to characterize the drug across the full CRC population.
And we'll see what we get. I mean if it turns out that we get data that suggests that the drug is more suited to a particular subset than we may investigate that. But at this point, we're enrolling a broad patient population.
Operator
Anupam Rama, JPMorgan.
This is Priyanka on for Anupam. Just kind of following up on the previous line of questions, since the enrolled patients in the CX-251 Phase 1 trial is now being preselected for EpCAM expression, is there a published literature, for example, to help guide what level of expression would be beneficial?
Sean McCarthy
Yes. There's a broad literature EpCAM expression across most tumors, including colorectal. And I think it's well established that EpCAM 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 kind of expresser in most patients.
And I anticipate that our clinical results will validate that.
Operator
Peter Lawson, Barclays.
Peter Lawson
Just on the prioritization of CRC for your EpCAM ADC. Is that driven by the expression levels you kind of talked about and just kind of well known within the space or you've already seen signals there. And you've also seen any signals outside CRC to date.
Sean McCarthy
Yes. Peter, that's helpful to help me clarify and reiterate that this Phase 1 study of 2051 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 patient population that we're seeing that we're treating are for the most part, have, for the most part, been treated with at least three prior lines of systemic therapy. .
So the question is, okay, why? Why focus in CRC, several answers to that. First of all, when you just look at EpCAM biology and the target itself, CRC is really the indication that jumps out with the highest, broadest, most consistent, most homogeneous expression from patient to patient. And as I said, it's actually where EpCAM was first described as a tumor marker. That said, EpCAM is highly expressed in most other solid tumors.
So this is a pipeline in a product opportunity in the long run if we see a signal in CRC.
There's no question about that. The other reason to select CRC is the unmet need, the unmet need is just huge. And so it's an area where patients need new treatments. They've been waiting for them for decades, and we're trying to make a difference here. And then the third is that this drug candidate with a topo-1 inhibitor was really always designed with colorectal cancer in mind is the first place to go because there's not much -- that's been -- it's kind of a wide open field, ADCs in colorectal cancer, and we know that CRC responds to topo-1 inhibition.
As I mentioned in my prepared remarks, irinotecan is a component of standard of care therapy in the first and/or second line on a global basis is quite effective in the earlier stage of treatment of CRC. So we know that CRC can respond to topo-1 inhibition. So we think for this particular program, we think the combination of the tumor type of interest, the target selection and the effective mechanism, the payload has really been optimized and delivers, I think, compared to some of our prior work with ADCs a higher overall probability of technical success.
Just again, to be really clear that if we are fortunate enough to see a signal in CRC, then that would ungate many other tumor types that are known to be responsive to topo-1 inhibition but also express EpCAM at high levels.
Peter Lawson
Got you. Okay. And then just as we think about as you move forward, kind of what's the real bar for success? And are you thinking -- is it third line, fourth line, CRC?
Sean McCarthy
Well, in the fourth line, unfortunately, for patients, the bar is low. I mean you've got response rates in the single digits to drugs like Lonsurf, Lonsurf even in combination with bevacizumab, fruquintinib, regorafenib with just a few months of PFS. And so this is a very underserved highly underserved patient population in the fourth line.
It's also what we hear from our advisers and investigators and KOLs is that even in the third-line setting, the current standard of care, which is for the most part, bev-Lonsurf, is also highly inadequate and it's so inadequate that many, many patients in the third-line setting go on to trials or being held on therapy there as a precursor to going on to trials. And so I think that really underscores, number one, how high the unmet need is and really how low the bar is.
Obviously, we have high ambitions for this drug, but we think for this initial look in this late-stage patient population, we think, quite frankly, any evidence of RECIST responses would be a real win.
Peter Lawson
Got you. And so that initial look at that Phase 1/2 data, do you want to see tumor shrinkage? What's the bar there, you think, for success in your mind?
Sean McCarthy
Yes. As I already mentioned, I think we're looking at a number of things. We're looking at evidence of pharmacodynamic activity in tumor biopsies, evidence of tumor stabilization because 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 PFS-type measures because it's very difficult to achieve objective responses in this patient population.
So if you can keep patients from progressing that in and of itself is a success. So evidence of tumor stabilization, evidence of tumor shrinkage and then, of course, the Holy Grail for us in the 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 RECIST responses.
Operator
(Operator Instructions) Mitchell Kapoor, HC Wainwright.
This is Dan on for Mitchell. 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, how many more dose levels do you plan to test and where does the seventh dose level compared to the nonhuman primate preclinical tox.
Sean McCarthy
Yes. Thanks for the questions. In terms of where to present, we're keeping our options open there. So we'll provide further guidance into in due course. In terms of the escalation, 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 escalate. We'll have to see how that goes.
So at this point that's where we are, and we'll have to see. I would say that the -- when we talk about predictive active range of the drug, that is based on modeling that is including our experience from mouse and cynomolgus monkey experiments together with understanding in general of other topo-1 ADCs and what experience others have had in the clinic with this type of strategy.
Operator
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.
Sean McCarthy
Well, thanks, everyone, for joining us today. We look forward to providing additional updates throughout the year, and I hope you all have a good rest of the day.
Operator
This concludes today's conference call. Thank you for participating. You may now disconnect.
