I'm Dr. Jamie Montgomery, an associate biotech research analyst at the firm, and I'd like you to please join me in welcoming Sean McCarthy, CEO of CytomX Therapeutics, an oncology-focused biopharmaceutical company developing novel cancer biologics. Sean?
Great. Thank you very much, for the invitation to be here. It's a pleasure to be able to share, in the next, nineteen and three-quarter minutes, the CytomX story, so this will be a little bit of a whistle-stop tour, so starting with, the work that we're doing at CytomX, which is to build a multimodality Probody therapeutic pipeline with a, an intense focus on, major unmet needs in oncology. I will, over the course of the next few minutes, be making certain forward-looking statements. I refer you to our regulatory filings, so as I mentioned, CytomX is highly focused on oncology in areas of major unmet medical need. We have been a leader in the field of what we call conditional activation of biologics for the last decade or more.
We have developed, and, well, conceived of and developed the Probody therapeutic platform. This is a unique strategy for masking antibodies and antibody-like modalities in a protease-dependent manner, allowing us to improve and enhance therapeutic window for a wide range of modalities. We currently have a broad pipeline with more than fifteen active programs. We have three lead programs that I'll briefly cover today in the clinic, CX-904, CX-2051, and CX-801. We have been very successful over the years in formation of major alliances. We currently have highly productive collaborations with Bristol Myers Squibb, Amgen, Astellas, Regeneron, and Moderna. These alliances, together with our strategic capital-raising activities over the years, have maintained us in a consistently strong cash position.
We most recently reported at the end of Q2, $137 million on the balance sheet, with runway comfortably to the end of 2025, and this excludes any additional milestones under existing deals or of course, any new business development or financing. We have a terrific team based in South San Francisco, more than 120 employees with many, many years of collective experience in drug research, development, and commercialization. So today, I'll talk about three programs that each address major opportunities in the oncology landscape, and each of which reflects a different application of our technology.
You know, we have seen a number of other companies come into this space, since we conceived of it, this conditional activation space, and we continue to be differentiated from all other players, not only by being the leader with the deepest technology, deepest know-how, but also prosecuting a multimodality pipeline across T-cell engagers, antibody drug conjugates, and Probody masked cytokines. So taking these programs in order, and actually also in order of their status in the clinic, CX-904 is our first T-cell engaging bispecific antibody. It is indicated for broad applicability in EGFR-positive tumors, and that's regardless of mutational status. The vision here is to use our masking technology to open a therapeutic window for this previously undruggable target combination of EGFR and CD3, and to redirect T-cell-mediated killing of cancer cells in an EGFR-dependent manner.
That program is in phase I. We presented initial phase I-A data earlier this year, and I'll review that data with you in just a moment. Moving to our work in antibody-drug conjugates, this is a field that we've been active in for multiple years now, and the current leading edge of our antibody-drug conjugate work is CX-2051. This is a masked ADC targeting epithelial cell adhesion molecule. The opportunity here is in EpCAM-positive tumors. EpCAM is one of the very first pan-tumor antigens to ever have been described some decades ago. It has tremendous opportunity across many different EpCAM-positive tumors, including colorectal cancer, where the target is particularly highly expressed. We just advanced CX-2051 into phase I, and we're in the midst of dose escalation. That is a wholly owned program.
I should have said regarding 904, of course, that program is partnered with Amgen in a global co-development collaboration. And then moving to the most recent entry into the clinic, we just announced, earlier, actually last week, we announced the advancement of CX-801 into the clinic. We treated our first patient with CX-801. This is a masked version of interferon alpha-2b, which is designed to be a potential cornerstone of combination immunotherapy moving forward. So very excited about where the clinical pipeline is, multiple assets, a diversified set of assets across multiple masked modalities. We are entering a data-rich period.
We are working hard on generating the next data set for CX-904 and, in particular, towards working with our partner, Amgen, on the definition of our phase I-B strategy, with the goal of launching phase 1b expansion cohorts in 2025. We're aggressively escalating CX-2051 in phase I, with our goal of initial data in the first half of 2025, and CX-801, as I just mentioned, just entering the clinic, and we expect to have an initial update on the phase I progress by the end of 2025. We're also making a lot of progress across those multiple research collaborations that we have, including earlier this year, earning $10 million of milestones from our highly productive collaboration with Astellas, which is focused in the field of T-cell engagers.
We have more than 10 ongoing preclinical programs with our partners and additional research milestones that we would anticipate over the course of the cash runway that I mentioned earlier on. Let me move then briefly to cover CX-904, our masked Probody T-cell engager targeting EGFR and CD3. The concept here, and as we all know, there are enormous opportunities for advancing T-cell engagers into the realm of solid tumors. We've seen some big advances over the last 12 to 18 months, not least of which has been Amgen's approval of Imdelltra, tarlatamab, in small cell lung cancer targeting DLL3. There are very few good targets for solid tumor T-cell engagers. By good target, what do I mean? I mean a target that is restricted almost solely to tumor tissue. There, that list is very short.
What we aim to do with our technology is to open the target landscape by using masking to go after highly expressed tumor antigens, regardless of their presence in normal tissue, and EGFR clearly fits that bill. So CX-904 is designed to be a T-cell engager to address solid tumors, and we have a single EGFR binding arm and a single CD3 binding arm, and each of those arms is masked in a protease-dependent manner. So the design strategy here is that in the circulation, in the absence of proteolysis, because proteases are quiescent in normal tissues, the mask stays on, and the construct cannot bind EGFR or CD3 to significant degrees outside of the tumor. Once 904 migrates into the tumor, tumor-associated proteases cleave off the masks, allowing EGFR-dependent T-cell activation and subsequent T-cell-mediated killing of tumor cells.
We were very pleased to give a first look in May of this year at our initial data from dose escalation of CX-904. We had made a lot of progress up to that time point, having escalated through initial non-step dose cohorts into step dosing cohorts to a target dose. At the time, we reported up to 10 milligrams, and we continued at that time and still continue to dose escalate at the 15 mg level and hoping to go beyond that in the coming months. The patient population enrolled, we enrolled 35 patients at that time through the 10 mg step dosing cohort. You can see about half of the patients enrolled were in colorectal cancer, about 20% in pancreatic, and then a handful of additional tumor types, including lung, head and neck, gastric, and esophageal.
So, a pretty mixed bag of EGFR-positive tumor types selected to initially assess the safety of the masking strategy of CX-904. Our experience is shown here in terms of our initial non-step dosing cohorts. So our flat dosing progressed very well. We saw very low levels, in fact, no cytokine release syndrome in non-step dosing up to three milligrams. We saw an attractive safety profile overall. The MTD of non-step dosing was 6 mg . That's total dose, 6 mg given to a patient, and at that dose, we did hit a couple of grade three DLTs, one grade three rash, one grade three tenosynovitis, and that was the trigger to then, as is typical for T-cell engagers, moving into step dosing cohorts. Step dosing progressed very, very well.
We were able to quickly escalate beyond that six-milligram non-step MTD to a 10 mg target dose. And rather remarkably, in this step dosing, first step dosing experience, we saw zero cytokine release syndrome. This is unprecedented for a T-cell engager for solid tumors, and it really shows the power of masking to minimize systemic side effects. Other adverse events that were of note were manageable and low grade, including rash, as expected for an EGFR targeting CD3 T-cell engager. But I want to emphasize that across the entire thirty-five patients enrolled up to this data cut, we saw only one grade three rash. That's a significant achievement. So taken together, a very attractive safety profile for this previously undruggable target combination of EGFR and CD3.
We were also delighted to see in this early phase I work initial signs of anti-tumor activity, notably two confirmed partial responses in patients with late-stage metastatic pancreatic ductal adenocarcinoma. This signal was the most prominent signal. We saw evidence of tumor shrinkage and stabilization in several other tumor types, but the pancreatic signal is the one that initially jumped out at us from this first phase I work. We're very encouraged by these findings, and we continue to explore pancreatic now as we continue enrolling in this study in pancreatic cancer to continue to firm up that signal, and also now accelerating enrollment in other EGFR tumor types, notably squamous head and neck carcinoma and non-small cell lung cancer.
So our goal for this program between now and the end of the year is to generate a more robust dataset to take to our partner, Amgen, by the end of 2024, to engage in dialogue with them regarding the strategy for phase I-B expansions in one or more tumor types, potentially at one or more doses. And again, to emphasize, we continue to dose escalate, so we have not yet hit MTD for the step dosing, and we therefore do not yet have our RP2D that will come. And that's something we'll be discussing with Amgen later this year, and we do plan to provide a strategic update on the program by the end of 2024, with the data that underpins that conversation with Amgen likely being presented in the first half of 2025.
Great progress on our first T-cell engager. Let me now switch gears to our antibody-drug conjugate targeting EpCAM. Now, of course, ADCs need no introduction, but a real challenge in this space is that we need new targets. We need new solid tumor targets if we're really going to maximize the potential of antibody-drug conjugates across a wide range of cancer types. And that's what we're about at CytomX, using our masking technology to open therapeutic window for novel targets. And we're doing that with EpCAM, epithelial cell adhesion molecule, a very highly expressed, very well-characterized tumor antigen that is highly expressed on most solid tumors. As I mentioned, it's one of the first cancer antigens to have ever been described, and you can see here just how highly expressed it is in non-small cell lung cancer, triple-negative ovarian, and in colorectal.
Highly expressed on cancer cells, a functional role in cancer signaling, and also expressed, interestingly, on circulating tumor cells, for which there is an approved product on the market. Now, why hasn't EpCAM been successfully targeted previously? Well, because it is, as the target name suggests, present on many normal epithelial structures, notably the gastrointestinal tract. And you can see here at the bottom right, the expression of EpCAM is quite high in normal colon, and efforts to drug this target before with antibodies and also with T-cell engagers have hit a roadblock of gastrointestinal tox. But the target has enormous potential if we can find a way to open a therapeutic window, and that's exactly what we're doing with CX-2051. So this slide shows the optimized design of 2051.
It's a masked anti-EpCAM antibody conjugated to a novel topoisomerase I with a cleavable linker payload optimized for bystander activity. This drug is structurally and functionally you know somewhat analogous to Enhertu, has a drug-antibody ratio of eight with a topo -1 payload. It's really been designed with the activity in colorectal cancer in mind. CRC is the highest expresser of EpCAM, and that's where we're planning to dose escalate, where we are dose escalating in real time. First, a little bit of a deep dive on our preclinical findings with CX-2051.
We've shown that the masked antibody drug conjugate is equivalent in potency to the unmasked ADC, which is consistent with a large body of work we've done over the years to show that masked antibodies can be effectively and efficiently unmasked in tumor tissue, including in the clinic, where we've shown that for multiple programs. You can see on the right-hand side of this panel, the very significant improvement in tolerability we achieve by masking the antibody. CX-2051, we can achieve doses in excess of 60 mg per kilogram in cynomolgus monkeys, whereas only even 10 mg of unmasked ADC to EpCAM is not tolerated in cynos. The toxicity in question here, as predicted, is gastrointestinal tox. Masking, we believe, can open a window for this drug candidate in the clinic.
We've shown, as shown here, that the payload that we're using is functionally equivalent to Deruxtecan. This is a novel payload we licensed from ImmunoGen. You can see that the EpCAM DXd conjugated Probody has equivalent potency here in animal models to CX-2051, which is the novel topo one payload. So again, this is a DXd-like ADC, and on the right-hand side here, we're showing that this drug has potent activity in irinotecan-resistant CRC models. This is particularly important in the clinic because as we escalate in colorectal cancer, most patients that come onto our study are likely to have seen irinotecan in either the first or second-line setting. But we're confident that this drug has the potential to work in the third-line setting in CRC. So we're in the clinic actively treating patients.
This slide just shows the breadth of the opportunity and the pan-tumor potential for EpCAM, highly expressed in more than 95% of colorectal cancer patients, but also expressed in many other tumor types, and we're excited to explore multiple cancer types over the next months and years, and almost three hundred thousand addressable patients, so you can see how this drug, which remains wholly owned, could translate into major market opportunities. Our dose escalation is proceeding well. We announced on our earnings call a few weeks ago, we've already reached our third dose level in dose escalation. I fully expect that we will be at predicted active dose levels of this drug by the end of the year, and we're on track to have initial phase I dose escalation data for CX-2051 in the first half of 2025.
And our goal would be to rapidly advance this program into potential expansion cohorts in colorectal cancer and beyond, in the second half of 2025. In the last few minutes, just briefly, let me touch briefly on our third clinical program, CX-801, which is our masked version of interferon alpha-2b. Interferon alpha is a very potent cytokine. Actually, it's the first immunotherapy to have ever been approved in 1986. It is well established to have single-agent anticancer activity in several tumor types, including melanoma. It is, however, a cytokine that has significant systemic liabilities, and it fell into disuse because of its very narrow therapeutic window. We really like interferon, though, because first of all, we think it's been a little bit overlooked by the community.
Secondly, it has orthogonal activity to IL-2, IL-12, and IL-15, and really, based on its activity in driving antigen presentation, it absolutely has the potential to synergize powerfully with checkpoint inhibition in the clinic. The design of CX-801 is shown here. It is a dual masked interferon alpha-2b with a peptide mask blocking the interferon domains, and then a steric Fc mask, which is also protease cleavable. So the vision is that these masks will be removed, the Fc mask and the peptide masks in the tumor, resulting in the localization of the powerful immune cell modulating activity of interferon within the tumor microenvironment. This program really builds on, as I said, more than a decade of experience that we have at CytomX in optimizing protease cleavable linkers to be active within the tumor microenvironment.
We're looking with this drug to really build on work done by others, including a very important clinical experiment performed by Merck here, where they showed combination of interferon with PD-1 in melanoma has profound anti-tumor activity, 60% overall response rate, but significant toxicity, with almost a 50% incidence of grade 3-4 adverse events, as the side effect profile of interferon unfortunately synergizes with the peripheral side effect profile of PD-1. So what we're looking to do with our masking of eight oh one is to reduce systemic toxicity, improve intratumoral exposure through systemic delivery, increasing therapeutic window, and improving combination, particularly with Keytruda, which we have a supply agreement for from Merck. We're in monotherapy dose escalation, and our goal is after a few initial cohorts of escalation in monotherapy, to quickly initiate combination escalation with Keytruda.
So very excited about this drug. And taken together, I hope you can see that the work that we continue to do at CytomX is broad, it's deep. We have a robust pipeline. We're very distinct, differentiated as the only company with a multimodality, conditional activation masking strategy. And we believe the outlook is very bright for our company as we move towards 2025 . Our vision is there to be realized in real time, transforming lives with safer, more effective therapies. And as we look to 2025 , we anticipate additional data and strategic updates on our partnership with Amgen for the nine oh four program, initial dose escalation data for our wholly owned anti-EpCAM ADC, CX-2051 in colorectal cancer, our initial data for CX-801 in the clinic as we escalate, monotherapy and combinations.
And we anticipate continued progress through our multiple collaborations and potentially ongoing business development. So thank you for your time. It's a privilege to lead this company and to be able to be here today to talk about the work that we're doing. Thank you very much.