Good day, and thank you for standing by. Welcome to the CytomX Therapeutics First Quarter 2024 Financial Results Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Chris Ogden, CytomX' Senior Vice President, Finance and Accounting. 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 first quarter 2024 financial results and highlight recent progress at CytomX. We also issued a press release today announcing positive initial Phase Ia dose escalation data for monotherapy CX-904, which will be the primary focus of today's call. We encourage everyone to read today's press releases and the associated materials, which have been filed with the SEC. Additionally, the press releases and recording of this call and our SEC filings can be found under the Investors and News section of our website. With me on the call today are Dr. Sean McCarthy, CytomX' Chief Executive Officer and Chairman, and Dr. Wayne Chu, CytomX' Chief Medical Officer. Sean will provide an update on the overall pipeline and also outline CytomX' broader strategy for masked T-cell engagers. Wayne will then give an update on the CX-904 Phase I dose escalation study before Sean provides closing comments and we open up the call for Q&A. With that, I'll now turn the call over to Sean.

Thanks, Chris, and good afternoon, everyone. It's a pleasure to be here today to share our considerable progress during Q1, including our initial findings from our Phase I study of our EGFR targeted Probody T-cell engager CX-904. CytomX is highly focused on addressing major unmet needs in oncology using our Probody therapeutic platform, a proprietary antibody masking strategy, designed to improve the therapeutic window for multiple antibody modalities through tumor-localized activation. We are leveraging our Probody therapeutic platform to discover and develop new cancer therapies based on masked T-cell engagers, masked ADCs and masked cytokines. Our broad and deep pipeline encompasses more than 15 active programs, including 3 clinical stage molecules and significant retained commercial rates. Strategic partnering is our long-standing components of our corporate strategy, and we're proud to be working closely with Bristol-Myers Squibb, Amgen, Astellas, Regeneron and Moderna on multiple Probody therapeutic programs. We continue to be in a strong financial position with $150 million of cash at the end of Q1, which provides cash runway to the end of 2025, not including any milestone payments under our existing collaborations or any potential new partnership funding. CytomX is very strong organizationally with integrated R&D capabilities, continued investment in our core technology and a deeply experienced team dedicated to our vision of transforming lives with safer, more effective therapies. Moving to Slide 6. The CytomX product design strategy using our Probody therapeutic platform is informed by more than a decade of experience and seeks to balance target selection, masking strategy and effective function to make meaningful impact in key areas of unmet need in oncology. CX-904 brings the EGFR target together with T cell engagement via CD3 with the goal of T cell-mediated killing of EGFR positive tumor types, potentially including those for which conventional antibodies have not…

Thanks, Sean, and thanks, everyone, for the opportunity to share our early clinical and translational observations in the ongoing dose escalation study. This slide summarizes the dose escalation scheme, key eligibility criteria and study objectives. Patients with tumors with known EGFR expression were enrolled. However, patients were not selected based on EGFR expression. Dose escalation was initiated using a non-step dosing schedule in which CX-904 was dosed once every 2 weeks, doses starting from 7 micrograms through 6 milligrams were tested. As we will discuss in the subsequent slides, dose escalation of CX-904 continued using a step-dosing schedule with an initial target dose of 5 milligrams. Various step-dosing schedules were tested, after which the target dose was administered every 2 weeks. The data presented today represents safety and efficacy data from a total of 13 dose escalation cohorts through the 10-milligram target dose. And as Sean mentioned, dose escalation continues with the current enrollment testing the 15-milligram target dose. Selected baseline characteristics for enrolled patients are shown in this slide. The majority of patients enrolled in non-step dosing escalation cohorts were those with microsatellite stable or MSS colorectal cancer, which I will term CRC from here on out, which has been demonstrated to be unresponsive to immune therapies such as immune checkpoint inhibitors. With step-dosing escalation cohorts, we have begun to focus on patients with tumors with early evidence of clinical activity as well as other tumor types with known EGFR expression. As a typical for a Phase I first-in-human dose escalation study, patients had advanced late-line disease, enrolled patients received a median of 4 prior cancer therapies, many were refractory to their last prior therapy and a considerable proportion received prior EGFR and/or PD-1 and PD-L1 directed therapy. Early clinical pharmacokinetic data from the non-step dosing schedule was consistent…

Great. Thanks, Wayne. So staying with CX-904 for a moment, we're excited by our progress to date, developing this very novel drug candidate. EGFR is such a high potential target with expression of many tumor types. And we're just at the beginning of learning what CX-904 can do for patients. We clearly have a drug candidate with confirmed monotherapy activity and we're redoubling our efforts to generate data in additional tumor types as we more broadly explore in 904. Our data also unlocks potential strategies for future combinations, as Wayne mentioned. Focusing for a moment on pancreatic cancer. This is one of the greatest areas of unmet needed oncology today, and it's notoriously difficult to treat. Second-line response rates were in the single digits, mPFS and overall survival is just a matter of months. To reiterate the importance of our data shared today, pancreatic cancer does not respond to either anti-EGFR antibodies or to immunotherapy alone. What we have shown today is that when we combine these 2 powerful strategies in bispecific form, enabled by our Probody masking technology, we can elicit meaningful responses in late-stage pancreatic cancer patients. CX-904 brings these 2 mechanisms together into an integrated and unique pharmacology that could impact this very difficult-to-treat disease, showing how masked Probody T-cell engagers can be a new frontier in the war on cancer. These results are the embodiment of exactly what CX-904 was designed to do, and we plan to aggressively pursue the signal for the benefit of people afflicted with this devastating tumor type. Now zooming back out to our full pipeline and looking also into 2025, we anticipate a great deal of additional progress at CytomX. We see the data we're showing today on 904 as a promising initial step in developing this asset and also our…

[Operator Instructions] Your first question, it comes from the line of Peter Lawson from Barclays.

Really exciting. The masking benefit you've seen, do you think that can also extend to other T-cell engagers. And then the responses you've seen so far -- do you think there's something special about pancreatic cancer? Or do you think you can get deeper responses in other tissues as well?

Yes, Peter, great questions. Thanks. Regarding the extension and the read-through to other programs, we're obviously very optimistic that, that will be the case. You've got to start somewhere, and 904, I think it's a very strong start for us. We've learned a lot with this one in the clinic. And as we've mentioned, both internally and with our partners, we're doing a lot of work in T-cell engagers. We've got multiple programs. In fact, the majority of our partnered work is in T-cell engagers. So we would expect to make substantial additional progress here over the next few years. In terms of pancreatic, I think it's a great question. It's been interesting to see -- we've done a lot of thinking about this, obviously. And pancreatic is typically thought of as an immunology cold tumor or an immunologic desert, if you like. But actually, evidence is beginning to -- I'm not suggesting that, that might not be the case. If you look at the Roche BioNTech vaccine data, most recently updated at AACR. It's really interesting. It suggests that there are neoantigens in pancreatic cancer that there is some immunologic microenvironment. And it looks like with this combination of each -- well, there's also EGFR, of course, there. But no one has been able to break through with an anti-EGFR directed therapy. So we think that could be something very unique about EGFR and CD3 in this particular tumor type. But it absolutely does not indicate that others would not respond to 904. We're still very early in this study. As Wayne mentioned, the colorectal data is interesting. They're all MSS patients that we're showing today. That's another cold tumor. Not a lot of progress has been made with T-cell engagers yet in CRCs, so we would be looking to combination strategies there. As far as the other tumor types are concerned, it's just very, very early days. For example, just like I'd lung, where we have 2 patients in the dose escalation study to date. One of those was treated at a very low dose, so probably not relevant. We've already only -- we just haven't done the experiment yet. So we're going to keep enrolling across multiple tumor types in Phase Ia as we continue to pursue both the pancreatic signal and define the activity of the drug across hopefully multiple tumor types over time.

Great. And then the depth of the responses. Is that correlated with EGFR expression or is it tumor microenvironment?

One thing we have not shown as -- that's shown in this presentation, but we continue to evaluate is the level of EGFR expression as assessed by immunohistochemistry assay. And we've been doing this on a retrospective basis for all the patients that have enrolled. To date, based on our early data with eGFR by this IHC assay, we have not seen a clear association between EGFR expression and the depth of the response. And just as an example, the 2 patients in pancreatic cancer who had the confirmed partial response. One patient had a moderately high level of EGFR expression by IHC, but the other patient had a very low level of EGFR expression, and it's actually the patient who had the 83% reduction in measurable tumor burden that has the low level of EGFR expression.

I think more -- yes, more work to be done there. But Peter, a lot of it depends also on the assay itself. So we'll continue to look at that relationship.

Your next question comes from the line of Roger Song from Jefferies.

A few questions from us. The first one is related to the dose relationship since the efficacy or antitumor activity is not clearly correlate with the dose level. My question is, how do you think about as you dose higher -- even beyond 10 mg, now you're at 15. How do you think about the balance between the efficacy and CRS, ICANS, more CD3 or EGFR-related tolerability profile, how confident you are you can keep dosing higher?

Yes. Thanks, Roger. Let me kick that one off. I'd say that there is a dose response in that the responses that we're seeing, the confirmed RECIST responses, we've seen at 5 and 6 milligrams. Remember that we began this dose escalation at 7 micrograms. So the range of doses where we're seeing activity is actually really consistent with our predictions from modeling of where the biologically effective range would be. So we think we're in the zone. We do believe, however, because of the safety profile, we can dose higher. Whether that will help or not, I don't think we know. I think all of us, in the T-cell engager field, are kind of trying to figure this out. And if you look at Amgen's tarlatimab, I mean, they went all the way to 100 and concluded in the end that 10 milligrams was the dose to move forward because the 100 didn't give significant additional efficacy. So I think we've got to learn more, but we're very encouraged that we have this clean safety profile with EGFR, I think it exceeded our expectations and it will allow us to dose escalate further, and we'll do that and we'll see where it takes us.

Got it. My follow-up question is related to your partner, Amgen. So this data, have you shared with the partner? And if so, any initial feedback and also understanding you will give an update by the end of the year, what you are looking for in order for both of you 2 parties to make the Phase Ib study design and the decision?

Yes, great questions. So with Amgen, let's take a little step back and talk about we just recap the agreement that we have with Amgen. So we're obviously running the Phase Ia study. And we do share data with them as it emerges. We are also responsible for running the Phase Ib once we get that up and running. And the transition from Phase II to Phase Ib is a decision that we'll take jointly with Amgen. And of course, the goal would be to in Phase Ib to enroll specific EGFR positive tumor type, for which one now, quite obviously, would be pancreatic. We would assume based on this exciting signal that we've seen. So we -- because we -- the way that enrollment has unfolded, we still have just not enrolled many patients in lung or head and neck, for example, -- we do want to bring in a few more patients to get some additional experience in those tumor types. Before we have the conversation with Amgen later in the year about what the Phase Ib strategy would be. So the update later this year could be a couple of things. It could be additional data from -- we would ballpark -- we should have by end of year, another 10 or so patients of data. It could also be an operational update that we've agreed with Amgen on the next steps. We just have to have that dialogue with them. But in terms of their perspective on the data, I think that's a question best asked from them at this point in time. But obviously, we're really excited by our progress.

Your next question, it comes from the line of Joe Catanzaro from Piper Sandler.

I guess maybe first one on the EGFR-mediated tox that you're seeing, I guess my question is like what do you think is happening? Is that some small amount getting unmasked in periphery or maybe a small amount getting unmasked in the tumor and then reentering circulation? And is that tox that you're seeing typical of sort of historical EGFR experience, say, cetuximab? Or is there anything indicative that it's T cell targeting of EGFR on normal tissue, and I may have 1 follow-up.

Yes. Joe, thanks for the question. Well, first of all, let me say that we're really, really pleased with the very low incidence of Grade 3 rash in this study. We only have 1 patient over the 35 patients with a Grade 3 treatment-related rash. That's a significant achievement, we think, because it unlocks the opportunity to use this mechanism to shrink tumors that otherwise couldn't be shrunk with the EGFR. So we're very pleased about that. Obviously, early days, more work to do, but we're encouraged. With any drug, you're going to see some -- you're going to see AEs, it's very hard to say what are they -- where they're coming from? Is it local? Is it systemic? We don't know and we may never know and in a way might not matter that much because it's all about the risk benefit profile, and we're obviously delivering something we think very important here -- at least initially for patients with very late-stage pancreatic cancer. I would say -- on the type of rash that we see cetuximab rash is typically the acneiform rash, we see some of that Grade 1, Grade 2. They're also, as Wayne mentioned, maculopapular rashes, which are maybe more T cell -- involved T cells. So I think we're going to have to learn more about it, but we're not worried about it because it's mostly Grade 1, 2 effect across the entire study, the incidence of rash across the entire 35 patients was 40% and just about all Grade 1, 2 and manageable. So we're really encouraged by the AE profile here. Not to mention the CRS profile, which really quite frankly surprised us to the upside.

Yes. That's helpful. I guess my follow-up for the pancreatic cancer patient that had that deep response and then subsequent progression. Wondering if you could maybe elaborate a little bit more on that progression event. Was it a new lesion, growth of a target lesion. If it was a new lesion, maybe we were able to sort of profile it and see what's going on. Just anything you could say there, I guess, would be interesting.

Yes, I could provide some details on that. This is a patient that was treated with the 6-milligram non-step dosing had a confirmed partial response that strikingly with an over 80% reduction in measurable tumor burden. The patient did progress based on growth of the target lesion from the [indiscernible] as well as the appearance of, I think, of 1 new target lesion -- on -- sorry, on new lesion. So that was the nature of the progression on that particular patient. But all through that treatment course, the patient did quite well clinically. It was just based on the radiographic progression that...

Okay. And then maybe if I could just squeeze in 1 more, quick one, maybe going back to an earlier question. Just if you could maybe speculate more on what you think is maybe going on in MSS CRC. It seems mechanistically like you're seeing T cell infiltration, but that's not translating to tumor reduction. So I'm wondering if you have any other sort of hypotheses of what may be going on in those patients?

I think mechanistically, it's really interesting when we think about how T-cell engagers work overall, right? CD3 combined with the tumor antigen, we think that these typically as being MHC nonrestricted mechanisms. That may very well be what's going on. But there could be more necessary to really mount an antitumor response. I think we're again, in the field, I think there's more to be learned about specifically how CD3 T-cell engagers kill cancer cells. Clearly, we're doing it in pancreatic cancer. We're getting the T cells there in CRC, but it draws one's attention to think about what combination strategies could get you to actual objective tumor responses. So I think more work to do there in some of the basic science and then also clinical work that we can do in terms of clinical combinations. It's quite intriguing.

Your next question, it comes from the line of Etzer Darout from BMO Capital Markets.

Just wondering if you could maybe talk through your current thoughts on sort of the step versus the non-step dosing, particularly in the pancreatic patients that sort of had the response and how you're kind of thinking about potentially moving 1 or the other option for it as you sort of expand the patients? And then I don't know if you said this specifically but about sort of the EGFR expressions across sort of the patients that you've seen so far? Is it that you're going to -- moving forward, you will look at EGFR expressions? Or is there an opportunity to kind of look at EGFR expression across the folks that you've already sort of enrolled in the study. I don't know if I caught that correctly.

Yes. Thanks, Etzer. In terms of moving forward with step or non-step, we obviously haven't made a decision on that yet. But I would say based on our experience to date, more likely that our Phase Ib doses will be step strategies, because it's allowing us to get to significantly higher target doses. And we do think there's a dose response here of sorts. So more to be learned there will also likely take -- when you think about project Optimus considerations, we'll likely want to take more than 1 dose and schedule into Phase Ib to gain further experience of the drug candidate, not only in pancreatic, but also in other tumors as well. In terms of EGFR it's surprising actually -- how should I put this -- the available assay for EGFR or assays for EGFR by IHC, it's just that it's not perfect. And so we're not sure how much 1 would want to rely on it moving forward, particularly because it doesn't seem from our early data that this is a straightforward ADC type thing where you -- high target is required for activity. These drugs like T-cell engagers just would be predicted to be active at low target levels because of the mechanism of -- the amplified mechanism of tumor killing where 1 T cell can kill multiple tumor cells. So I think we've got more to do in there, and that's why we're -- we may not be needing or leveraging EGFR selection on a go-forward basis based on what we've seen so far.

Your next question, it comes from the line of Anupam Rama from JPMorgan.

Can you comment -- was there anything in the baseline characteristics, a number of prior treatments I think the PDAC case study that you said was 3 lines of therapy or otherwise, that might be predictive of a response. I think based on the first question, EGFR expression didn't correlate. And then can you comment, and I'm sorry if I missed this, the other 3 stable disease patients, what was their duration?

I'll take the first question in terms of which I think was anything in the patient characteristics that could have been predictive of response and I'd say, no, not really. Again, these are all pretty late-life patients. And aside from EGFR, we did show -- that said, Wayne showed a slide of a pretreatment biopsy of a patient with pretty high levels of pretreatment, CD8-positive cytotoxic T cells which is intriguing, and certainly could have contributed to the response. And so -- that's something that we have observed. We don't have that data systematically, across the whole study. That's difficult data to get for every patient, but it is intriguing. In terms of the stable disease, Wayne can address that question real quick.

Yes. So as we showed in the swim lane plot during the presentation, there were a number of patients who were able to maintain a stable disease through at least 1 tumor response and smattering -- that included a smattering of patients that had durable stable disease through tumor -- to tumor responses. But otherwise, patients were able to achieve a stable disease and then it was followed by progressive disease.

I do think it's important to reemphasize that these -- again, the pancreatic are very -- as everyone knows, it's a very rapidly progressing disease. These are patients who, for the most part, had 3 or 4 priors. And so this -- so yes, we think this is a really exciting data.

[Operator Instructions] Your next question, it comes from the line of Mitchell Kapoor from H.C. Wainwright.

Congrats on the positive data. I wanted to ask about the total 8 patients with tumor reductions the other -- well, I guess, if you could just broadly comment on what a slider plot for these patients might look like. Are you seeing a trend in depth of response over time? Or how are we seeing those tumor reductions evolve?

Yes. I mean it's early days. I think those 8 patients, obviously, 2 of them are the pancreatic patients, and you can see them in the waterfall plot. I think there's encouragement there in terms of the fact that escalation continues, we'll keep pushing the dose here. So at this point, I think it's fair to say the [ spider plot ] will be relatively immature.

Okay. And could you just comment on the other confirmed partial response patient? And how much duration of follow-up that patient ahead?

That patient, again, was treated at the 6-milligram non-step dosing schedule, had confirmed partial response, and that patient remained on study about -- on study treatment approximately 18 weeks before having progressive disease.

Thank you. And I'm showing no further questions. I would now like to turn the conference back to Dr. Sean McCarthy, CytomX' Chairman and CEO, for closing remarks.

Great. Thank you very much, and thanks, everyone, for listening in today. CytomX has made terrific progress so far in 2024, and we look forward to providing additional updates as the year proceeds. And as we continue to build our company for the long term to make the biggest difference we can for patients. And so thank you very much. Have a good evening.

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