Good afternoon, everyone. Thank you for standing by. Welcome to the Cytomics Therapeutics Third Quarter 2025 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, Cytomics' Chief Financial Officer. Please go ahead.

Thank you. Good afternoon, and thank you for joining us. Before we begin, I'd like to remind everyone that during this call, we'll 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 third quarter 2025 financial results and highlights recent progress at Cytomics. We encourage everyone to read today's press release and the associated materials, which have been filed with the SEC. Additionally, the press release recording of this call and our SEC filings can be found under the Investors, and news section of our website. With me on the call today is Dr. Sean McCarthy, Cytomics' Chief Executive Officer and Chairman. Sean will provide an update on our pipeline and company progress before I cover the financials for the quarter. We will then conclude with a Q&A session. With that, I'll turn the call over to Sean.

Thanks, Chris, and good afternoon, everyone. We're very pleased to be here today to provide an update on our third quarter developments and our strong continued company momentum at Cytomics. I'd like to start by welcoming Rachel Lester to the team as Chief Business Officer. Rachel's broad strategic planning and business development experience will be highly valuable as we shape our pipeline and corporate development strategy towards realizing our ambition of building Cytomics to commercial stage. Rachel's a terrific addition to a wonderful team that I'm privileged to work with every day. Our goal at Cytomics is to make innovative medicines for people with cancer that are substantially more effective than currently available treatments. Our most advanced drug candidate, CX2051, is currently focused in colorectal cancer, one of the biggest unmet needs in oncology today, with more than 1.9 million new cases annually worldwide, expected to exceed 3 million by 2040. I'll refer to colorectal cancer as CRC from here on. CRC is also increasing in younger patients and is the second leading cause of cancer death. Five-year survival for metastatic CRC is only 13%. At Cytomics, we have used our proprietary pro-body therapeutic platform to attack this problem in a new and different way. The pro-body approach is a masking technology that allows us to hit cancer cells hard and with stealth, sparing normal tissues, opening up therapeutic strategies that were previously impossible. Specifically, with CX2051, we have deployed our platform to bring the power of an antibody drug conjugate to the treatment of CRC. ADCs are transforming the treatment of many cancers. There are currently more than a dozen approved in the United States, but thus far, ADCs have not broken through in CRC, a notoriously difficult cancer to treat. There's an enormous opportunity here to meaningfully impact patient lives and access a global multi-billion dollar market, and our ambition at Cytomics is to build an integrated commercial stage organization around this exciting opportunity. CX-2051 is a masked pro-body ADC targeting EPCAM. This drug candidate has been intentionally designed by selecting the optimal target, tumor type, and cell killing mechanism to deliver potent anti-cancer activity. CX2051 is, we believe, a truly differentiated molecule, being the first and only EPCAM-directed ADC in development. EPCAM is a very highly and consistently expressed target in CRC. While certain locally administered EPCAM strategies have shown promise in cancer treatment, systemic approaches have consistently failed due to toxicities in normal tissues where EPCAM is also expressed. To solve this problem and realize the potential of EPCAM, CX2051 leverages our masking strategy to reduce normal tissue binding and maximize activity within tumor tissue. The CX2051 payload is a topoisomerase 1 inhibitor, known as CAP59, selected because of the well-established responsiveness of CRC to this mechanism of cell killing, underscored by the widespread use of orinotecan in CRC therapy. Our CX2051 product design strategy was quickly validated with our positive interim phase one data reported in May this year from a highly focused dose escalation study in late stage, unselected metastatic CRC. This first look at data from our phase one study demonstrated robust clinical activity and the potential, we believe, for CX2051 to become a new standard of care in this setting. To briefly recap the data, CX2051 demonstrated meaningful tumor reductions, including confirmed objective responses or disease control in nearly every patient, as well as preliminary median progression-free survival of 5.8 months, a potentially substantial improvement over currently available treatments for late-stage CRC that provide only two to three months of benefit. Patients included in this initial data set had a median of four prior lines of therapy, with all patients previously having been treated with Irina-Tcan. Encouragingly, anti-cancer activity was observed across a wide range of clinical characteristics, including in patients with liver metastases and KRAS mutations. The activity we've seen across this broad late-stage patient population, together with the fact that we don't need to select for EPCAM expression in CRC, suggests that CX2051 could become a pan-CRC drug. CX2051 was generally well-tolerated, including a notable absence of safety events such as pancreatitis and liver toxicity that have limited prior EPCAM therapies, strongly suggesting that our masking technology is working as designed. We were encouraged with the hematologic safety profile of CX2051, which could be favorable for future chemotherapy combinations. The most common adverse event in early phase one was diarrhea, a known side effect of Topol1-based therapies such as Arunotica. We're currently focused on better characterizing and managing gastrointestinal adverse events as part of our ongoing development program. Based on these very promising initial results, we're now well into the expansion phase of the phase one study with our next data update planned for Q1 2026. With that, let's review our progress with CX2051 this quarter, as well as next steps. In August, we announced that the CX2051 dose expansion cohorts at the 7.2, 8.6, and 10 mg per gig doses had reached our enrollment goal of approximately 20 patients each. Since August, we've continued enrollment in the dose expansion cohorts, and we now expect total enrollment in the CX2051 Phase I study to be about 100 patients by our planned data update in the first quarter next year. As we work towards our goal of initiating a potential registrational study for CX2051 monotherapy in late-line CRC, we expect this expanded Phase I patient enrollment will further inform dose selection, including FDA dialogue regarding Project Optimus. Additionally, given the momentum within the program, we expect to initiate a Phase I-B study with the anti-VEGF antibody, Bevacizumab, in the first quarter of 2026. Bevacizumab is a core component of CRC therapy across multiple lines of treatment, and we anticipate this combination data will unlock broad additional potential. Beyond CRC, we continue to see potential for CX2051 across many other cancers, where APCAM is also expressed. Given our compelling initial results in CRC, we're currently assessing additional indications for future development, and we expect to provide an update on non-CRC indications in 2026. Now turning to CX801, our masked interferon alpha-2b program currently being developed in combination with Keytruda in advanced melanoma. The metastatic melanoma landscape continues to evolve rapidly, as checkpoint inhibition moves to earlier-stage treatment, leaving considerable unmet need in later-stage settings. Advances are being made, for example, with cell therapy and oncolytic virus strategies, but new approaches are urgently needed. We're very excited about the potential for CX801 in melanoma, as illustrated by the positive initial biomarker data we will present at CITSI this weekend. In designing CX801, we have applied a similarly focused set of design principles as we did with CX2051 by selecting a validated pathway, a potent effector mechanism, and a focused initial clinical development path centered on clear unmet medical need. Interferon Alpha 2b is a well-validated, powerful immune system modulator that has previously been approved for cancer therapy, but that has been limited in use due to poor tolerability. Our masking strategy for CX801 is highly novel and includes masks on both the cytokine domain and an FC masking domain to really minimize activity in the periphery, while directing activity towards the tumor microenvironment. Conceptually, what we're aiming for here is to harness the potent ability of interferon Alpha to selectively activate the tumor immune microenvironment, allowing for synergistic anti-tumor activity in combination with checkpoint inhibition. We treated our first patient in the CX801 Phase 1 study in September last year, and we've made excellent progress thus far in the clinic. Monotherapy dose escalation has reached the fourth dose level, including multiple dose levels that exceed the approved clinical dose of unmasked Interferon Alpha 2b. Now, this is important, since it already suggests that masking is working as designed. Our 60 presentation this weekend encompasses biomarker data from five melanoma patients treated with monotherapy. CS801 has been generally well-tolerated through the first three dose levels and is inducing robust interferon signaling within the tumor microenvironment. Specifically, our initial data includes gene expression analysis of pre- and post-treatment patient tumor biopsies, demonstrating consistently increased expression of interferon-stimulated genes, evidence of T cell activation, and upregulation of immune checkpoint inhibitors such as checkpoint genes, including PD-1 and PD-L1. We also observed evidence of sustained chemokine elevation in the tumor microenvironment with stable chemokine levels in the blood, suggesting preferential 801 activation in the tumor. Furthermore, CX801 is activating cell populations of both the innate and adaptive immune systems as anticipated and consistent with Interferon Alpha's broad mechanism of action. This initial progress with CX801 is exactly what we aim for in assessing the initial monotherapy performance, and it lays a strong foundation for the potential of the combination with Keytruda, which we initiated in May of this year. We currently expect initial data for the CX801 Keytruda combination by the end of 2026, and we look forward to sharing those results. Before handing over to Chris for financials, I'd like to also briefly highlight a second poster presentation we have at CITSI this weekend, introducing a new program at Cytomics, CX908, a masked T-cell engager targeting CDH3, also known as P-cadirin. In addition to our work on masked ADCs and cytokines, we continue to be active in the T-cell engager space, and this preclinical data highlights the power of masking to substantially widen therapeutic window for this modality. We also continue to be active in T-cell engagers and by specifics in our collaborations, including with Estellus and with Regeneron. With that, let me hand over to Chris.

Thank you, Sean. Reiterating Sean's earlier settlement, our third quarter was characterized by continued momentum with our clinical development programs, and we continue to drive towards our key milestones in a capital-efficient manner. Having completed a $100 million financing earlier this year with a strong group of investors, we are positioned to rapidly advance 2051 towards later phase development and build value in Cytomics over the near and long term. As Sean mentioned earlier, we are on track to provide a CX 2051 data update in Q1 of next year, and investing behind a potential first approval will continue to be our top capital allocation priority. We also will begin focused investments to drive additional value in CX 2051, including initiating accommodation study with bevacizumab in the first quarter of next year. And we are also in the process of evaluating additional FCAM expressing indications for CX-2051 development. With that, I'm going to walk through our third quarter financial results. As of September 30th, 2025, we ended the quarter with $143.6 million in cash, cash equivalents, and investments versus 158.1 million in cash at the end of the second quarter of 2025. We continue to project that our cash balance will be able to fund Citomex operations to at least the second quarter of 2027. As a reminder, our cash guidance does not account for any additional milestones from existing collaborations or any new business development And we continue to make progress with our partners and expect to remain active in business development to extend the reach of our technology. Looking at revenue and operating expenses for the quarter, total revenue was $6 million compared to $33.4 million in the third quarter of 2024. The decreased revenue was primarily attributed to the completion of our performance obligations in our Bristol-Myers Squibb collaboration. operation. Operating expenses for the third quarter were $21.7 million, compared to $29.3 million in the third quarter of 2024. R&D expenses were $15.3 million during the third quarter, representing a decrease of $6.1 million versus the third quarter of 2024, primarily due to a reduction in CX904 expenses, as well as reduced research expenses. G&A expenses decreased by $1.5 million during the three months ending September 30, 2025 to $6.4 million driven by lower personnel costs as well as patent and legal expenses. As we look ahead to 2026, we will continue to employ a disciplined approach to capital allocation, focus on delivering on our key program milestones for CX-2051 and CX-801 and advancing the pipeline towards later stage development. With that, I'll turn the call back to Sean for closing remarks.

Thanks, Chris, and thanks everyone for joining us today. 2025 certainly continues to be a highly productive year for cytomics. Our pro-body masking platform is really coming into its own with two exciting programs in the clinic that build on everything we have learned over more than a decade about how to optimally deploy this strategy that we have pioneered. CX2051 and CX801 both utilize validated mechanisms, and in both cases, the clinical problems we're addressing and the potential value we can create are very clear. We remain focused on our objective of building cytomics around these and future innovative programs and moving them further into development and ultimately to commercialization. Regarding CX2051, our planned Q1 2026 update will encompass broad progress with the program as we look to position the initial registrational path while initiating combination strategies to support use in earlier lines of CRC therapy. This is a major opportunity. CX801 is also off to a promising start, and we're excited to see Keytruda combination data in 2026 in melanoma. Before I wrap up today's call, I wanted to sincerely thank all cytomic stakeholders for your support. We are here to make the biggest difference we possibly can. With that, Operator, let's go ahead and open up the call for Q&A.

Thank you. To ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. We will now go to your first question. And your first question today comes from the line of Edward Tenthoff from Piper Sandler. Please go ahead.

Great. Thank you very much for taking the question. and really great update. I'm excited to hear all the progress for the 2051 and looking forward to the 801 and the new program at Tuesday this weekend. My question really has to do with respect to expectations for the 2051 readout, and I appreciate that you're up to around 100 patients. You know, what should we be expecting from an ORR? You know, is there a chance for that to deepen? And I know that the PFS was immature at 5.8 months. What do you guys sort of see as a win here for PFS? In these late-line pieces.

Yeah, hi, Ted. Thanks for the questions. So just to recap our data in May, which we were super excited about, as you know, across the three relevant dose levels that we're currently expanding, the 7.2, 8.6, and 10 mg per gig doses, we saw an integrated confirmed response rate of 28%, which very substantially beats the current standard of care in the late-line setting, whereas, you know, response rates are in the single digits. So, that gives us a lot of room to maneuver. Similarly, with progression-free survival. The 5.8-month preliminary estimate based on that early data set compares to two to three months in the late-line setting for current standard of care. So, you know, so our feeling is a lot of room to maneuver on the data set as it continues to mature from this larger expansion phase, and we're excited to have the update in Q1.

Yeah, and I totally agree with all that. And And quick follow-up question, will you break out dose, or will you break out efficacy by dose, and do you think you'll have enough data at that point to really select the dose or doses in phase three?

Yeah, we absolutely would expect to be breaking the data out by dose in this next update. I think that's going to be very important from an efficacy and safety standpoint as we continue to work towards dose selection for the next studies. Absolutely.

Great. Thank you.

You're welcome. Thank you. Your next question comes from the line of Roger Song from Jefferies. Please go ahead.

Hey, team. This is Nabil on for Roger. Thank you for the updates. Maybe two from us. Excited to hear about the enrollment picking up. What do you attribute that to? And is there any more feedback you have maybe from your trial partners in terms of what you're hearing from them and anything regarding the prophylaxis and how that's going? And then another follow-up would be just regarding the ESMO data that we saw from some other competitors that did not differentiate from standard of care, if you had any thoughts on that as well.

Yeah, great. Thanks for the questions. In terms of enrollment, I take you back to the comments we made during our August updates where, you know, we were able to rapidly increase enrollment during Q2 and Q3 after the initial May disclosure to 73 patients, and that really was a reflection of the high interest from our investigators and patients, you know, to come onto this study. And that's been continued in Q4. We continue to see a lot of demand for 2051, and we felt as we moved through this quarter that it would be helpful to continue to enroll patients and continue to gain additional experience with this drug as we work towards dose selection for our next stages of development in 2026. Regarding prophylaxis, that continues to be an important area of investigation. We are highly focused on really the one adverse event that we need to actively manage with the drug, which, as you know, is the diarrhea. We have implemented prophylactic measures at the early stages of the expansion phase, and we would anticipate that we will continue to learn about the AE management protocols over time. And we feel that, you know, we'll have a much better understanding of many aspects of this adverse event as we move into 2026. And I, you know, I can assure you that we are we're very much on it. In terms of ESMO, it was a busy conference, wasn't it? And there was quite a lot of news in CRC, you know, after such a long time of very little innovation in this space. It's really exciting to see, you know, multiple mechanisms, pathways, targets, strategies being used to try to, you know, make inroads into this very difficult to treat cancer. We didn't really see anything that gave us any concern. We continue to be strongly that 2051 is a highly differentiated molecule and approach, of course, as an antibody drug conjugate, is bringing the concept of the ADC into CRC, which we think is going to be really, really important. So we are as excited about 2051 as we have ever been.

Thank you.

Thank you. Your next question comes from the line of Olivia Brea from Cancer Fitzgerald. Please go ahead.

Hi, good afternoon, guys. Thank you for the questions, and congrats on all the great progress here. What is the strategy for the combination approach with BEV? Are you looking at enrolling third-line patients, or is it really more about exploring second line? And would you wait until the next CX2051 monotherapy update to actually inform a dose escalation strategy? for the combo? And then I've got one follow-up.

Yeah, thanks, Olivia. Thanks for the question. So the strategy, initially, of course, we'll be beginning by looking at, you know, a few doses of 2051 to explore the combination with Bev as we, because we're beginning this study in Q1, we think it's important to get this study going. It's a crucial part of the development plan as we broaden out the 2051 strategy to bring the drug into earlier lines of therapy. But starting in Q1, it will be concurrent with continued evaluation of dose selection for monotherapy. So I anticipate that we'll be looking at more than one dose of 2051 with Bev. Obviously, the goal ultimately is to get into the second line setting, specifically which patients Once we enroll into the very earliest phases of the combination, that remains to be determined. In terms of the data update on the combo, too early to tell, we want to get the study going and we'll see how it's, you know, timing-wise, we'll see how it aligns with future updates on the monotherapy.

Okay. And then what can you tell us at this point just around percentage of patients who you actually expect to receive loperamide in the dose expansion phase for the monotherapy. Are there any parameters that you guys have put in place in terms of which patients can or can't receive it, or is it really truly at the investigator's discretion? And then just to kind of sneak in a point of clarification on that, can that loperamide regimen, can it actually be used both proactively for prevention, but also reactively at first onset of diarrhea?

I'll take the second question first, and the answer there is yes. I mean, Loperamide is a common drug to be used to manage diarrhea for any medicine that has that adverse event, so that's a very normal thing to do. But it's also been shown to be effective, as you know, for example, in the PRIME study with Tredelby, where upfront treatment of patients with the paramide was effective in reducing the rates of grade 3 diarrhea in patients treated with that particular TOPA1 ADC. In terms of our study, as we've said previously multiple times, we instituted the paramide prophylaxis in the protocol concurrent with initiating the expansions in April. We did leave the investigators some level of discretion there. Lipiramide, as we've commented before, does not come without its own side effects. And so it has to be used thoughtfully and deployed thoughtfully. And so we felt it was important to give investigators the flexibility because, of course, they're managing their patients on the ground, as it were. Over time, and again, just to really emphasize, we are laser focused on this question of learning more about the onset, the timing, the overall etiology of diarrhea in these patients, and learning how to get ahead of it with lapiramide. And over time, as we learn more, I would anticipate that our AE management plan will continue to evolve and continue to be refined as we move into 2026 and towards discussions with FDA relating to dose selection and, of course, navigating Project Optimus.

Great. Thanks so much.

You're very welcome.

Thank you. Your next question comes from the line of Matthew Biegler from Opco. Please go ahead.

Hey, guys. Thanks so much for the update here. I just wanted to ask a follow-up one on your current thinking of the regulatory strategy, particularly as in monotherapy. Do you think you can go head-to-head against BevLontsurf in the third line, or are you thinking monotherapy would more likely be a fourth-line trial against, I guess, physicians' choice? Thanks.

Yeah, thanks, Matt. Look, I think everything's still on the table. So, yeah, we're generating now an even more substantial data set with the continued enrollment into the phase one. And I think we feel, as we commented previously, pretty confident that the very first look at the profile of 2051 showed us that this drug has the potential to comprehensively beat standard of care in the fourth line. So that seems clear from the very, very early data set. In the third line, of course, we know that Bev Longsurf has a PFS of five and a half-ish months. And we need to see our data mature to have a better handle and understanding of how competitive monotherapy 2051 can be in the third line setting. So that remains to be determined, but it's very much still on the table. As we collect more data, we follow our patients for longer. And by the time we get to Q1 of 2026, just to further build on one of the earlier questions asked, we do anticipate that we'll have estimates of PFS at all three of the expansion doses. So that will be, I think, very helpful and informative in helping us lay out what our thinking is at that time about the go-forward potential registrational path.

Makes a lot of sense. Thanks.

You're welcome.

Thank you. Your next question comes from the line of Anupam Rama from JPMorgan. Please go ahead.

Hi, this is Joy Son for ANAPOM. Thanks for taking our questions. I understand there's a host of other tumor types outside of colorectal where 2051 could have potentially meaningful benefit. What are your thoughts on which tumor types you're most excited for, and then what should we expect in terms of timing or cadence next year of new proof-of-concept studies in these other tumors, and just how are you balancing that with your development plans and CRC?

Yeah, thanks. Great question. And, you know, in a similar way to how we like to refer to 2051 as potentially being a pan-CRC drug, it really has pan-tumor potential, given the widespread expression of EPCAM on so many solid tumor types. We're eager to get going in additional cancers, and there are many of them, gastric, endometrial, uterine, pancreatic, lung. It's a long list. And, you know, so we're enthusiastic to get going at the same time. We've got so much work to do in colorectal that, you know, we need to be thoughtful of timing. But I do anticipate that we'll have updates on the initiation of additional cohorts and additional tumor types in 2026. We are working towards that.

Great. Thanks so much. Thank you. Your next question comes from the line of Etza Daru from Barclays. Please go ahead.

Great. Thanks for taking the question. Just a couple of ones for me. On the over-enrollment that you're seeing, just wondered if any of the additional enrollment is skewed to any of the three doses that you're exploring? And then of sort of this 100 patients or so, are we going to get a breakout maybe of maybe less pre-treated patients versus sort of the four median prior therapy patients we got in the initial update? Thank you.

Yeah, thanks, Ed, sir. So, in terms of enrollment, I mean, I can say that we're we're enrolling patients at similar dose levels within the same dose ranges that we've been expanding. Not quite ready to comment on specifically which doses that we're adding additional patients, but we're really thrilled that, you know, with the speed and rate of continued enrollment, you know, during Q4, it's going to give us a lot of additional information, important information as we move towards dose selection in the early part of next year. In terms of breaking out less or, you know, it's a really interesting question, you know, less heavily pretreated or more heavily pretreated. You know, we may look at that, but I can say that the patient population that we're continuing to enroll is pretty consistent with what we saw in the first 20 to 25 patients that we shared in May. So still pretty late line CRC. So if you're wondering whether we'd have, for example, you know, some initial suggestions of maybe some, you know, second line patients that may have squeezed into the study or a large number of third line, I don't anticipate that to be the case. I think we're really still going to be, at least for now, in the pretty late line setting. That said, of course, you know, So we always want to try to analyze and squeeze as much information out of every patient and data set as we can.

Right. Great. Thanks, Sean. You're welcome.

Thank you. As a reminder, if you would like to ask a question, please press star 1 and 1 on your telephone. We will now go to our next question. And the next question comes from the line of Mitchell Kapoor from H.C. Wainwright. Please go ahead.

Hi, team. Thanks for taking the questions, and congrats on the progress today. Just wanted to ask if you could elaborate on your interactions with the FDA so far and what they have indicated their feelings are about what would be registrational or positive in the fourth-line setting. Have they said anything like 20%, 25% or our six-month PFS would be, you know, impressive to them? Anything that you could say about, you know, what their alignment has been like with you all to date? And what was the last time you spoke with them about their registrational plans? Obviously, there's been a lot of changes at the FDA, but just want to know, you know, when the last communication was and when you plan to meet with them again.

Yeah, thanks. Thanks, Mitch. So, obviously, regulatory strategy is something we're going to be super focused on as we move into 2026. We anticipate those discussions to happen next year.

Okay, great. And then, just secondly, if you could talk about your updated thoughts on BioAtlas, FCAM by specific, what are the puts and takes there in terms of read-through, but also, you know, differentiation where we should think about your strategy in a different way?

Yeah, we think that it's an interesting strategy, the EPCAM CD3 conditional activation approach. We obviously all know there's a lot of EPCAM in colorectal cancer, and leveraging that particular effective strategy, I think, could make some sense. But we feel like at Cytomics, we really feel like the ADC strategy is the right one.

Thanks, guys.

You're welcome.

Thank you. I'm not showing any further questions in the queue. I would now like to turn it back over to Dr. Sean McCarthy, Chairman and CEO, for closing remarks.

Thanks very much. And thanks, everyone, for tuning in today. It's been great to give an update. We're super excited about our progress in 2025 and the direction that Cytomics is headed with our clinical programs and our platform overall and our collaboration. So thanks for your time and look forward to following up.

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