All right. Good afternoon, everyone. My name is Roger Song, one of the senior analysts covers mid-cap biotech at Jefferies in the U.S. Our next company is CytomX Therapeutics. Welcome, Sean. Thanks very much. Hi, Roger. Good to be here. Thanks for the invitation. Absolutely. Okay, so maybe to set the level, what is your updated elevator pitch for investors, for CytomX with the recent updates? Yeah. So, CytomX Therapeutics, we're developing a deep and diverse pipeline of oncology therapeutics based on our Probody therapeutic platform. This is a conditional activation strategy that we've pioneered at the company for more than a decade now. We've had a very strong year. This really has been a year of very focused execution for the company. First of all, let me start with some of the financial parameters. We've been successful thus far in navigating this downturn by bringing additional capital into the company. We've raised $100 million over the last year from various sources, including upfront payments from Regeneron and Moderna into really exciting new alliances that we formed, and also financing, a PIPE financing with the Biotech Value Fund, BVF Partners midyear, and a $5 million milestone payment from our partner, Astellas, for the selection of the first clinical candidate in that T cell engager collaboration. So a lot of progress on the financial front. We just reported $194 million of cash on the balance sheet at the end of Q3. That funds us, you know, comfortably into the second half of 2025, and that's through a number of key milestones coming up in the pipeline over that time period. So, as I said, this has been a year of highly focused execution towards these upcoming milestones. The most proximal milestone on the horizon will be Phase Ia data for our CX-904 program. That's our EGFR CD3 Probody bispecific, where we're Phase I dose escalation. We're also filing two new INDs by the end of this year. One is for CX-2051, which is an EpCAM-targeted Probody ADC. So super excited about that. We think that program has a ton of potential across multiple tumor types. I'm sure we'll get into that in a few minutes. And then the second IND that we're filing, the team's very busy right now, writing two INDs in parallel, is for CX-801, which is a conditionally activated masked version of interferon alpha-2b. This is our first entry into the cytokine field. Those two programs, 2051 and 801, are both wholly owned. The 904 program is partnered with Amgen. The fourth potential milestone on the horizon is with our partner, Bristol Myers Squibb, who we've been working with for a long time on CTLA-4 strategies, focused on improving the therapeutic window of CTLA-4 inhibition. The collaboration is currently at a very exciting point, where they're running Phase I trial in MSS CRC with a non-fucosylated version of Ipi, to which our Probody technology has been applied, with the goal of making a safer, more effective version of Ipi in multiple tumor types, including CRC and lung, where they're Phase I proof of concept studies. They are anticipating data in 2024. So, you know, we've really been heads down this year, executing. We've been financing and driving towards those upcoming milestones, and we feel like we've got a very exciting 12-24 months ahead of us. Excellent. I have to say, you know, in the biotech world, and right now, you have such long cash runways, enviable kind of position. You can put the heads down and deliver the catalyst. So before we talk about each individual programs, as you mentioned, CytomX is built off of a conditional activating kind of a platform, and we recently see a couple clinical data readout from the space. And Sean, maybe the question is, how and why you will think, you know, CytomX's position in this space, particularly with the data you have generated and all the technology you are being developed? Yeah. So first of all, it's just been great to see additional progress in this broad field that, you know, that we've already kicked off with our technology. So we're excited to see other entrants into the space. And a couple of things about CytomX that I think is still very differentiated. First of all, we're taking a multimodality strategy, so we're active in many of the key areas of oncology R&D today. So, for example, coming out of ESMO, two of the biggest areas of news from ESMO were, of course, the progress in T cell engagers and the progress in ADCs, with the incredible data in, you know, frontline urothelial cancer in combination with PD-1 for Padcev. We're right in the middle of those spaces, so we're applying the technology to T cell engagers, to ADCs, also to cytokines. The breadth of investment we've been able to make over the years in the pipeline, and the technology continues to differentiate us, I think, just in terms of the breadth and range of what we're able to do. Secondly, really, CytomX has achieved every first in this field. So we're the first company to have shown that a masked antibody can be stable in the plasma of oncology, of cancer patients. The first company to show direct evidence of intratumoral activation and unmasking of a Probody therapeutic. The first company to show anti-cancer activity of a Probody or a MAST therapeutic, and also the first to show an improved safety advantage. So it's been really, interesting and actually really great to see, many of these other companies really following our playbook. And you see in their data sets similar kind of box checking, where they're looking at intratumoral activation, looking at plasma stability, looking of course, for early signs of, tumor activity. And I would cite, you know, data that, that we've seen for, MAST IL-2 as being, you know, directionally interesting and encouraging, for MAST, CD3 PSMA bispecifics, in prostate cancer, looking interesting as well. So I think this field, you know, we're doing something really important. I think CytomX and others, we're all, driving to the same goal and the same vision really, which is that we, we see localization of biologics as really being the future of biologics. which makes so much sense, and it allows us to go after a whole new set of targets across multiple different modalities, and of course make a huge difference for patients. So we're really quite. I've never been more excited about where the field is. Oncology is such a tough space, but also a ton of opportunities, I think, conditional activating across different modalities, that makes a lot of sense to be able to localize the therapy into the tumor. Okay, so then we talk about a few. I think you have a couple in the clinic, but I think the lead program right now is CX-904 for the EGFR. So tell us how do you see the enrollment so far, and I believe you will start to announce the initial data first half next year. What should we expect from there? What's your goal to achieve in the initial data readout? Yeah. Well, first of all, let's just spend a few moments on technically what we're trying to do here, because it's a big idea, like a lot of what we do at CytomX. So we're taking EGFR and CD3, we're masking the bispecific on both arms with the goal of opening a therapeutic window for this particular target combination. EGFR, of course, is a very well understood, very well precedented, highly validated oncology target that's expressed in most solid tumors. And its potential is really far from being realized. Until you look at how broadly expressed the EGFR is, but still how limited EGFR biologics are in their commercial application. There's a ton of room for innovation and, you know, opening up new avenues for treating patients. And we think that EGFR CD3 is a great idea. So what we're trying to do, of course, is bring the immune system to EGFR-positive tumors. The goal of our Phase I study is, of course, safety first. So what are we looking for in particular in Phase I dose escalation? Two main things. First of all, the extent to which our masking on CD3, which is intended to reduce systemic CD3 engagement, allows us to manage and mitigate CRS. CRS being, of course, one of the major limiting factors in bringing T cell engagers into the world of solid tumors. I'll make a few comments in a few moments on the ESMO data from Amgen and Regeneron. I think it's very pertinent. But CRS has been a significant limitation in moving this highly potent modality into solid tumors. The other thing we're looking for, of course, is the degree to which masking on the EGFR binding arm can help us mitigate and manage what might be expected to be EGFR-driven toxicities. And so we know that EGFR causes various dermatologic skin toxicities, gastrointestinal toxicities. So we'll be looking for evidence that masking is allowing us to to get to dose levels by masking that are reaching the therapeutically active range of this novel drug, as predicted by our quantitative systems pharmacology modeling. So let's go to ESMO and just talk a little bit about what we learned from some great updates from Amgen and Regeneron. I think a few things there. First of all, these are very active drugs. They're very, very potent, and you need to be very thoughtful about your Phase I to ensure that you explore a wide range of doses and schedules to make the best decision you can when you move forward into later stages of clinical Phase Ib, and Phase I. and you can see in particular for the Amgen DLL3 program, tarlatamab, it took a while, but they have reached an incredible milestone now with the Phase I readout, and now have advanced into a registrational study. So our goals for 904 are initially in Phase Ia, dose range, look at safety, look for... as we get to the upper, upper dose ranges, look, of course, for evidence of antitumor activity in the form of tumor stabilization, tumor shrinkage, and the totality of that data will then be used to devise our strategy for entering Phase Ib in EGFR in specific EGFR-positive tumor types. It's important to note that right now, in Phase I dose escalation, we're in essentially a phase, an EGFR all-comer setting. And this is a little bit different to what Amgen did with DLL3, where they began in small cell from the outset. It's a little different from what they did with STEAP1, where they began in prostate from the outset, and it's even different from what Regeneron's done with MUC16, beginning in ovarian. For us, because EGFR has got so much potential across so many tumor types, we're escalating. We're agnostic of tumor type Phase I, but that means that it won't be Phase Ib that we're exploring specific tumor types and really probing for robust clinical activity. So that's how we view the program. The main goal really for next year for us will be to sit down with Amgen, review Phase Ia data as it stands at that time, and devise and develop Phase Ib program, which CytomX will still run. So we're Phase Ia, we've Phase Ib is complete, the program goes back to Amgen to run global registrational studies. So that's kind of high level how we think about 904. The space in general, I don't think has ever been more exciting based on the progress that's being made. The last thing I would note is that just to compare and contrast again to the Amgen and Regeneron data from ESMO, is that EGFR is a much more broadly expressed target on normal tissues. DLL3, STEAP1, MUC16, these are pretty restricted targets. DLL3 is highly expressed in small cell lung cancer. It's pretty low in normal tissues, actually very low in normal tissues. So it's a good target for an unmasked T cell engager, but EGFR, you couldn't do an unmasked T cell engager. No one's taken that to the clinic because all the preclinical results would suggest it would be severely toxic. So we bring, we believe, you know, enormous value with our technology through masking these broadly expressed antigens to open a therapeutic window and then go into multiple tumor types in the future. Excellent. So the initial data will be 1/2, and the focus on the safety, potentially you will have some, you know, biomarker PK data. Ideally, you will see some initial clinical activity, and then you will sit down with the, with Amgen to talk about the next step. Maybe based on current thinking, what is the key considerations to moving to the expansion? Do you need to? What kind of signal you need to see before you can move into the EGFR positive population for the Phase Ib? Yeah, it's pretty much what I've already laid out. So it's, you know, really having a good feel for being in the appropriate dose range, where based on everything we know from a modeling and preclinical study standpoint, that these doses and schedules are where the drug should declare its activity, but also, of course, to have seen some level of activity Phase Ia. that will be important to moving Phase Ib. but because of the mixed patient population that we're in, I don't think it needs to be very much, right? That's because we're in this EGFR all-comer setting. And then the other thing to emphasize is that this mechanism of T cell engaging strategies and bispecifics, of course, requires that the tumor has some level of immune competence already. It may be that, I mean, EGFR positivity, of course, will be important, ultimately, because that's the target that the construct binds. But it wouldn't be surprising if some level of immune competence was important as well. That's something that we're paying close attention to, particularly with our biomarker strategies, as we're looking at how cytokines are moving, we're looking at on-treatment biopsies to really measure and monitor the TME and the relationship between the TME and what we're actually seeing from a PK/PD and ultimately clinical efficacy standpoint. Okay, good. Before we move on to your earlier IND and the earlier pipeline, so anything else you wanna discuss on the nine oh four, kind of upcoming kind of data readout and the plan maybe, you know? Fair question is, will be the for the expansion, what are the tumor type you will be considering? What's the potential design will look like? I think you mentioned EGFR positive and maybe some tumor type and the size of the population. Yeah, I think it's really too early to comment on that. I think we'll have a much better view as we continue to collect data Phase Ia. so, you know, that type of roadmap for the next stage of development is something that we'll lay out once we're ready to communicate the initial data from Phase Ia dose escalation. That's fair. Okay. So, outside of CX-904, you have two IND plans for the rest of the year. As you said, you're in parallel to IND, that's not too common for a small kind of company. And, what, what's the status over there for those two INDs? And, what are the key gating factors before you can file the IND? Yeah, so like I said, the team is very busy at the moment, and actually beyond those two INDs, across the pipeline, we have more than 15 active programs at the moment, both ourselves and with our partners. So, you know, we've continued to build a broad, deep, multi-modality, diversified, and we believe risk-balanced pipeline, that really gives us a lot of opportunity to make progress over the next, 1 to 2 years. So, maybe we can come back to the partnerships if we have time. I know time's flying. But, CX-2051, you know, we're— Well, both of them are on track with manufacturing, with GLP tox is complete. It's really assembling the various sections of the IND, getting it filed, getting them both filed. We've had for CX-2051, as we think about starting dose, we've seen that as pretty straightforward because we've done a lot of work with ADCs in the past. And, you know, the framework around which one thinks about starting dose for ADCs, even for masked ADCs, in our experience, is relatively straightforward. For CX-801, as an immunotherapy, and thinking about our experience with CX-904, where because of the potency of the T-cell engagers, we began at a very low dose, which is again, typical. If you look at the data from other parties, T-cell engagers, you're typically starting at very low doses. CX-801 is also an immunotherapy, so we have had some very productive pre-IND interactions with FDA around starting dose, around clinical design. And that's given us really great input, and that's now being factored into the IND. So again, teams are doing a terrific job, and we're on track to get these both filed and up and running in the clinic in 2024. Okay, good. Any other comments? You mentioned the starting dose. Any other comments you can mention for the study design for those two Phase I? Well, for CX-2051, the target EpCAM is such a fantastic target. It's and it's a... You know, you talk to many in the oncology field, they'll, they'll tell you that it's, it's a great target, we wish we could drug it. And so this is what we're, what we're doing at CytomX with CX-2051. And why is it considered to be such a great target? Well, its expression is really, really broad. So we think there are upwards of about 300,000 patients that could be treatable with an EpCAM ADC, across many tumor types, including CRC, lung, ovarian, breast cancer, endometrial, GI, stomach cancer, esophageal. So Phase I, with all that said, Phase I, we do plan to focus, not entirely, but certainly bias enrollment to CRC. This is partly because EpCAM is really, really highly expressed in CRC, and the payload that we have on CX-2051 is a camptothecin class, topoisomerase-1 inhibitor, of course, which is in the same general class as irinotecan, which is frontline and/or second-line therapy for, you know, CRC on a global basis. Now we know that CRC in the third-line setting can respond to irinotecan-type regimens. We've also shown preclinically that CX-2051 is active in irinotecan-resistant CRC. And so we see a great opportunity with this drug candidate to quickly look for a signal in the third-line CRC setting, where, of course, there's enormous benefit that we could bring to patients and an enormous value that we could create. It doesn't mean that we're only going to enroll in CRC, we will include other tumors, but we wanna move this study really quickly. Based on, I think everybody's experience Phase I studies, you know, CRC patients tend to come in pretty quickly. So, that's Phase I strategy for 801. Sorry, for 2051. 801, a couple of things to say there. First of all, we'll focus in tumor types where interferon alpha is already known to be active, and this goes back to when interferon was first approved in 1986, right? We know that interferon alpha is active in melanoma, in renal, in certain head and neck cancers, and so there are some obvious places to go Phase I dose escalation. Again, it'll be a multi-tumor escalation, but most likely biased towards those types of immune-competent tumors, where we're more likely to see single-agent activity. And the other thing with eight oh one is we'll want to quickly get into combination settings. So the whole mechanism of eight oh one, you know, interferon was first described as a central mediator of antigen presentation in the context of viral infection. Of course, it promotes antigen presentation in the context of immune cell recognition of tumor cells, which is why we're developing it as an immunotherapy. In that regard, it makes total sense to get it into a combination with a checkpoint inhibitor, where we've shown preclinically, including most recently at SITC, just a couple of weeks ago, very potent combination activity when we combine PD-1 with our masked surrogate of 801. So we think the stage is set for a really Phase I study for 801 as well. So we're gonna get those INDs filed for the co-initiation in 2024. Obviously, way too early to guide to it... Before you ask me, way too early to guide to data on those programs. Unlikely to be 2024, because that's gonna be initiation. But as we move into 2025, and as I said, I really wanna emphasize for CytomX, this next, you know, six, 12, 18 month time horizon as a time period where we do expect it to be really quite data rich, with these programs. Yeah, I'm not gonna ask you the timeline, so I know the answer. Yeah. Okay. So last a couple of minutes, now you have been very successfully engaged or signed a lot of the partnership. I think, you know, across all the major pharmas, so who are interested in this space, probably already have the partnership with you. Maybe just give us updates among all the partnership, maybe start from the BMS, given it's pretty advanced, and also, you know, Regeneron, Cellectis, and Moderna. Yeah. So it's been a central component of our strategy from the early days. We realized very early on when we put CytomX together, that the breadth of the technology really would require partnering to really extend the reach, and also as a way to help fund the company. We knew we were gonna have to raise a lot of money. We have raised a lot of money for the company over the last 10 years, and that strategy has been very successful. So BMS really is our foundational partner. That alliance goes back to 2014. And as I said, we're still very active with them on improving the therapeutic window of CTLA-4 strategies. But we're also doing a lot of discovery work with BMS as well. We had a temporary, you know, pause in some of that work during the Celgene acquisition. But now, you know, we're back in full force and active on multiple programs across multiple modalities with BMS that we're very excited about. Astellas, we have a collaboration in T cell engagers. As I mentioned earlier on, this is a multi-target alliance. We achieved our first clinical candidate milestone with them earlier this year. Terrific collaboration, great, great collaborator, and making progress across multiple other programs as well. The way that that deal works is we're doing a lot of the preclinical work, Astellas will do the development, and we get milestones and royalties along the way, with the option to opt in to co-commercialize certain products in the US further down the road. So really excited about the progress on Astellas. Amgen, we've already mentioned, the leading edge of the Amgen bispecific alliance is 904. Also active with Amgen on the discovery side as well. And continuing on the theme of the T cell engagers, our most recent alliance in this space is with Regeneron, as you mentioned. With Regeneron, working on multiple bispecific immunotherapy strategies, you know, that deal I think is really a terrific illustration of the depth of our science and, in particular, the depth of our protease biology. We've really invested heavily in our understanding of the protease biology of the tumor microenvironment, and that really underpins everything we do in the design and optimization of masked protease activatable therapeutics, which is what the Probody platform is all about. So, you know, that brought Regeneron to the table, and, you know, we're up and running with those guys and doing some really, really cool science. And then speaking of cool science, we're working with Moderna, our most recent collaboration that we signed earlier this year. And this is, you know, as we said in the press release, an opportunity to really invest at the intersection between technology and biology, using mRNA to encode localized protease-activated biologics. And that's again a multi-target collaboration. So, really thrilled about the alliances. They not only are helping us further develop the technology, but also from a burn rate management standpoint, have been very valuable to us this year. As we announced on Q3 earnings, we only burned $17 million of cash in Q3. So we've really been thoughtful and I think very methodical and highly disciplined, not just in terms of how we're investing and spending money, but also how we're getting reimbursed for a lot of the early work we're doing on the platform by our partners. And this is allowing us to maintain this research engine, which is really the core of our company, for the long term. You know, not an easy thing to do in a financial environment like this, but the partnerships have helped us, helped us do that. The last thing I would say about the partners is that the cash guidance that we're giving, which is that with the $194 million as of end of Q3, that's funding into the second half of 2025. But that does not take into account any potential additional milestones under our collaborations, or of course, any potential new business development that we might do. You know, we continue to be looking for, you know, new opportunities. And as I've always said, you know, CytomX will do the right deals at the right time. Excellent. I think, that's about it. And, thanks, for coming. Thanks for having me.