Good afternoon, everyone. Thank you for standing by. Welcome to the Cytomics Therapeutics Second Quarter 2025 Financial Results Call. Please be advised that today's call is being recorded. I would now like to hand the conference over to your host for today, Chris Arjun, 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 will be making forward-looking statements because forward-looking statements relate to the future they're 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 scc.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 second 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 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 thrilled to be here today to review our progress for the second quarter, highlighted by the exciting clinical data we announced in May for CX2051, our probody antibody drug conjugate targeting EPCAM, which we view as having significant potential in colorectal cancer and potentially many other tumor types. We're also making great progress with our second current clinical program, CX801, that I'll come to a little later. I'll focus initially today on CX2051 and our work in colorectal cancer, which I'll refer to from here on as CRC. CRC remains one of the biggest unmet needs in oncology, with approximately 1.9 million patients diagnosed per year on a global basis. This disease burden is expected to increase considerably over the next couple of decades to more than 3 million and is currently the second leading cause of death by cancer worldwide. Despite many advances across many other cancer types in recent years, CRC has seen little impact from innovation over this period of time, resulting in current five-year survival rates in metastatic CRC of about 13 percent. New treatments like antibody drug conjugates are urgently needed to treat this cancer. In other solid tumor types, ADCs such as Nhertu, Tredelvi, and Elahir have made a big difference for patients, but ADCs have yet to break through in CRC, representing a major scientific, clinical, and commercial opportunity. At Cytomics, we have intentionally designed CX2051 to address this opportunity, building on years of experience in how to optimally leverage our pro-body technology for the maximum benefit of cancer patients. Let me recap the key design elements of CX2051. Etcam is a very highly expressed target in CRC, making it very attractive for an ADC. The payload on CX2051 is a topoisomirase-1 inhibitor, which is ideally matched to CRC, where the topo-1 inhibitor, arenatecan, has been a core component of the standard of care for many years. And thirdly, critically, CX2051 uses Cytomics ProBody Masking Technology to limit binding in normal tissues, something that has thwarted previous attempts to drug Epcam. Our initial experience with CX2051 in the clinic, announced in May, is very encouraging. We have focused our Phase I clinical evaluation exclusively in CRC, with the goal of delivering clear clinical proof of concept in this high area of unmet need. I'd like to briefly recap the CX2051 initial Phase I data from May. For context, CX2051 has initially been studied in a fifth-line CRC patient population where approved standard of care therapies are typically associated with 1 to 2 percent response rates and progression pre-survival of only two to three months. In comparison to these benchmarks, CX2051 has demonstrated robust clinical activity with a 28% confirmed overall response rate, 94% disease control, and 5.8 months of preliminary progression-free survival in the first 18 efficacy-evaluable patients at relevant dose levels. We're also encouraged to have observed clinical activity, including confirmed objective responses across a relatively wide range of doses. Our initial data has also validated that EPCAM expression is abundant in late-line CRC, with every invaluable patient having high target levels. This is important because it suggests that CX2051 may broadly address CRC and may not require patient selection, potentially a significant commercial advantage. Furthermore, our CX2051 masking strategy has succeeded in avoiding classic EPCAM toxicities, such as pancreatitis, that have impeded the successful development of drugs against this target previously. In terms of next steps, we have initiated dose expansions at doses of 7.2, 8.6, and 10 milligrams per kilogram administered every three weeks, and we are targeting enrollment of approximately 20 patients at each dose level. Enrollment is going well, and we remain on track for an updated dataset from a total of about 70 patients in Q1, 2026. Our goals for the dose expansions are to more fully characterize the dose response of CX2051, both in terms of clinical activity and safety, with a goal to inform dose selection for phase two. In terms of safety, the most common adverse events in the interim phase one data were diarrhea, nausea, vomiting, and anemia. In the expansion phase, we're paying particular attention to management of diarrhea using prophylactic medications, and we'll continue to iterate and refine our AE management strategies to best position CX2051 for phase two and beyond. In parallel to enrolling the expansion cohorts, we are in the process of developing our phase two strategy in late-line CRC and planning for potential initiation during the first half of 2026. While detailed next steps will, of course, be data-dependent, our current view is that the next study would likely evaluate CX2051 monotherapy in fourth-line CRC based on the higher met need, the potential speed to market, and the multibillion-dollar market opportunity we see in this treatment setting. Looking ahead to the longer term, CX2051 is also anticipated to have potential in earlier lines of CRC therapy and ultimately may be positioned, we believe, to replace arinatecan as a foundational component of CRC treatment. In support of this strategy, we anticipate starting combination studies in CRC in 2026. Now turning to CX801, our masked interferon alpha-2b program that we're developing in combination with the PD-1 inhibitor, Keytruda. Interferon alpha is a powerful immune system modulator with known anti-cancer activity across multiple tumor types, including renal cancer, bladder cancer, and melanoma, but it's fallen out of clinical use in oncology due to its poor tolerability. We designed CX801 to really clamp down on the undesired broad systemic activity of interferon and localized activity to the tumor microenvironment. In May of 2025, during Q2, we dosed the first patient in the combination arm of phase one study with Keytruda. This study is focused in metastatic melanoma and we're targeting initial data for the combination in 2026. In the fourth quarter of this year, we anticipate providing a first look at translational data for monotherapy CX801 impaired tumor biopsies and specifically how it's modulating the tumor microenvironment, including potential upregulation of interferon-stimulated genes like PD-L1. Positive early results here would provide evidence that the mechanism of action is working as designed, underpinning our rationale for the key-truder combination and supporting our vision of turning cold tumors hot with this novel immunotherapy. We look forward to providing this initial CX801 translational update in Q4 this year. With that, let me turn the call over to Chris for updates on our finances.

Thank you, Sean. Echoing Sean's earlier comments, the second quarter was important as we presented initial CX2051 phase one data that informed clear next steps for the program. From a capital formation standpoint, we were pleased to have completed a $100 million follow on offering with a top tier group of shareholders, further underscoring CX2051's potential. Following the execution of the financing, Citomex is in a strong financial position with projected cash runway to the second quarter of 2027. Of note, our cash guidance does not assume any additional milestones from existing collaborations or any new business development. Outside of CX 2051, we will continue to employ a focused capital allocation approach, including for CX-801, where we are aiming to deliver initial proof of concept in combination with Keytruda in melanoma. In terms of our research collaborations, we continue to view partnering as a capital-efficient way to extend the reach of our technology and drive increased long-term value. A key current focus in our collaborations is T-cell engagers, where, for example, we have momentum with partners Regeneron and Astellas and have the potential to earn milestones over the next one to two years. With that, I'm going to walk through our second quarter financial results. As of June 30th, 2025, we ended the quarter with $158.1 million in cash, cash equivalents, and investments versus $79.9 million in cash at the end of the first quarter of 2025. Total revenue was $18.7 million, compared to $25.1 million in the second quarter of 2024. The lower revenue was driven by the completion of our performance obligations in the BMS and Amgen collaborations, as well as decreased activity with Moderna. Operating expenses for the second quarter were $19.9 million, compared to $33.6 million in the second quarter of 2024. R&D expenses were $13.3 million during the second quarter, representing a decrease of $11.9 million versus the second quarter of 2024. General and administrative expenses also decreased by $1.8 million during the three months ending June 30, 2025, to $6.6 million compared to $8.4 million for the corresponding period in 2024, for, driven by lower personnel costs and lower legal and patent expenses. Overall, we will continue to maintain a disciplined, data-driven capital allocation approach in order to advance the most promising opportunities in our pipeline. With that, I'll turn the call back to Sean for closing remarks.

Thanks, Chris, and thanks, everyone, for joining us today. Cytomics made tremendous progress during Q2, and we look forward to the second half as we set our sights on 2026 and, in particular, next steps for the CX2051 program. With Etcam, we believe we have unlocked a new approach to the treatment of late-stage CRC, leveraging our proprietary platform technology and prior experience with mass ADCs. We view CX2051 as a first-in-class and highly differentiated asset with broad scope for value creation. Based on the interim phase one dose escalation results disclosed to date, we see a clear path forward to develop CX2051 in late-line CRC, and we plan to execute against this opportunity as our top near-term priority. We're excited to see Phase 1 results in Q1 of 2026, together with our next steps for the program. Regarding CX801, we're executing a similarly focused strategy to CX2051 in melanoma in order to generate proof of concept for the Keytruda combination. Positive data here would reestablish interferon as a potential new centerpiece of combination immunotherapy with broad potential across many immunologically cold tumors or for patients who become refractory to checkpoint inhibition. We look forward to advancing CX801 towards this vision. Before I wrap up today's call, I want to sincerely thank and honor the patients who join our studies, their families, our clinical investigators, and our dedicated team here at Cytomics. Your Your collective contributions are responsible for our advancements, and we're grateful for your help in getting us to where we are today. With that, operator, please go ahead and open up the call for Q&A.

Thank you. Ladies and gentlemen, to ask a question, please press star 1-1 on your telephone, then wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Edward Tenhoff with Piper Sandler. Your line is open.

Thank you very much. And congrats on all the progress this year. So my question has to do with the potential to move into earlier lines of colorectal therapy. What's going into those decisions and, you know, how do you envision sort of announcing those trials?

Yeah, thanks for the question. So, as I mentioned, first of all, first and foremost, we're super focused on executing towards the late line opportunity. We see a terrific opportunity there to move really quickly in fourth line. Coming into the early lines, obviously, is a key, will be a key focus for us over time to really broaden the opportunity. that will require combination studies to assess the doses that we ultimately select for the phase two for the monotherapy in the context of certain combinations to come into, well, into third line, and then, of course, into second line, where the vision would be to replace irinitikan. So one, you know, clear opportunity there in terms of combinations, given the extent of its use in treatment of CRC is to evaluate the combination with bevacizumab, and that's something that we're looking at carefully, and we will be doing, I'm pretty sure, in the future, we need to obviously round out the phase one study and select our doses.

Excellent. That makes a lot of sense. Really helpful. Looking forward to it.

Thank you.

As are we.

Please stand by for our next question. Our next question comes from the line of Nabil Nassar with Jeffries. Your line is open.

Hi, team. This is Nabil on for Roger. Thanks for the updates. Quick question regarding the rationale for value creation of Fcam beyond CRC. Are we approaching this with partnerships, and what is the strategy? Are we looking for a particular cam, or is there a particular tip for indication that would fit better with your technology? Thank you.

Thanks for the question. It's a terrific opportunity, you know, to broaden the 2051 development program outside of CRC. We do, of course, currently have our hands rather full with the scope and scale of the opportunity in colorectal alone. But just to just to restate, Epcam is expressed in most solid tumors and in many of them at high levels. So for example, lung, pancreatic, gastric, endometrial, breast cancer. So there's an enormous opportunity here now that we have initial proof of concept in colorectal. So it is the kind of drug, the kind of profile of drug that over time could very well benefit from a partnership. You know, we'll get there when the time is right. As I've said many times on these calls, we'll do the right deal or right deals at the right time. But, you know, that could certainly make sense in the future for value creation. But again, right now, over the next few months, I think it's important for us to be laser-focused on really building value initially through the CRC opportunity.

Got it. Thank you.

Please stand by for our next question. Our next question comes from the line of Matt Beegler with Opco. Your line is open. Hi, guys. Thanks for the question and for the update.

What do you think is the bar for accelerated approval in CRC right now, assuming you do go forward with like a monotherapy fourth line? I think obviously like the rule of thumb that the buy side loves to point to is the 30% OR, but we've recently seen an ESMO working group come out advocating as low as 20%, I think, like given how poor salvage therapies work in this setting. So I'm just kind of curious if you had any thoughts on that or whether you think ORR is even the most relevant outcome, you know, versus PFS or OS or something like that.

Yeah, thanks, Matt. Great, great question. And, of course, an exceedingly difficult one to answer at the moment. But given the activity that we've seen so far and the performance of 2051 in this area of such enormous unmet medical need, we, of course, have to be thinking about strategies that could lead to an accelerated approval. We want to get this drug to patients as quickly as we possibly can. That said, there are two major considerations as we develop that strategy. One, there's not precedent for accelerated approval in the CRC setting based on ORR. As you know, that would be breaking new ground. More typically, we're looking at a patient population in a clinical setting where we're relying on PFS and, of course, ultimately OS endpoints. That said, the scope of the unmet need, the nature of the unmet need here is so high, and our activity is so encouraging that we are considering it, and we will at the right time have discussions with FDA. The second thing, of course, is just the overall regulatory uncertainty at the moment, which none of us can ignore. But just to reiterate, of course, we're all So we're all aligned here in wanting to get this drug to patients by the fastest possible

Makes sense. Appreciate it.

Thank you.

You're welcome.

Please stand by for our next question. Our next question comes from the line of Anupam Roma with J.P. Morgan. Your line is open.

Hey, guys. Thanks so much for taking the question. So on the preliminary 801 monotherapy data here in the fourth quarter, what are you looking for that might give you confidence in sort of the combination and potential of this product with Keytruda and melanoma? And I guess any thoughts on any risks of overlapping tox that you're going

to be monitoring for? Thanks so much. Yeah, hey, Aniphan, great question. I'm happy to talk about 801 a little bit more. So first of all, there's actually very good precedent for mechanistically for PD-1, specifically Keytruda, and interferon alpha-2b, having very powerful combination activity in melanoma. That's been shown by Merck in a somewhat earlier setting, patient setting, than we're currently working in. But nonetheless, they showed robust activity, but it was limited by significant incidence of grade 3 adverse events of various kinds, particularly immune adverse events. But so we do know that this combination can be very effective in melanoma as a starting point. In terms of, you know, the progression of our development plan for 801, we're being very deliberate about it. We've escalated through several cohorts already of monotherapy, just in a handful of patients to get initial experience with the drug. In that escalation, we've reported previously, we've already exceeded the clinically approved dose and clinically utilized dose of interferon alpha. So we've already made progress, which is consistent with masking, showing an overall tolerability benefit. Most importantly, though, that initial experience with just a few monotherapy patients ungated our ability to start the combination, which we did during Q2, as we just mentioned. And that really is the drug here. So we see the drug ultimately as being 801 plus Keytruda, and we're now going to aggressively enroll that arm of the study, and that data will be reported next year. So the safety and efficacy data from the combination will come in 2026. In the meantime, with this handful of monotherapy patients that we've treated, we have been studying and we'll continue to study a series of paired tumor biopsies to interrogate the immune tumor microenvironment to look at how in the microenvironment the unmasked interferon is modulating immune cells and also inducing what we would expect it to do, which is to induce interferon-regulated genes, which include PD-L1, which really underscores the rationale for the combination with a checkpoint inhibitor like Keytruda. So the data that we're planning to share in Q4 will be from a handful of patients. It will be biopsy data initially. You know, we're not expecting in this initial like small number of patients to have any kind of initial ORR assessment. It's going to be translational data, but very important and hopefully very informative data that shows us that at the molecular level, the drug is behaving as we've

designed it. Thank you so much for taking our question. Thank you. You bet. Please stand by

for our next question. Our next question comes from the line of Peter Lawson with Barclays. Your

line is open. Great, thank you so much. I apologize if this has been asked, I've joined late. On the EPCAM ADC, so we've got the phase one update in Q1, kind of just if you could talk through the the size of the data set we see and the scope of it and kind of we should expect to see you know

durability and and also biomarker data yeah thanks peter thanks for giving me the opportunity to to recap some of our earlier comments um in the on the call um it's very important so uh as we said we're super focused on generating this next data set for 2051 we anticipate that in Q1 2026, we'll have 70, maybe a few more patients who have experienced with the drug compared to the update, the initial disclosure in May, which was 25 safety-available patients and 18 efficacy-available. So by the time we get to Q1, that data set should be quite a bit larger and predominantly across three dose levels, 7.2, 8.6, and 10 mg per gig, each of which were doses that we saw clinical activity for in that initial disclosure. So by then, yeah, we would expect to have reasonable follow-up on the majority of those patients. And the other element of that update will be the integration of that data into our go forward plan for phase two. So that's our current plan, is that the Q1 update will be a rounded out phase one data set, plus our strategy for moving forward into phase two. That's the current plan.

And that phase two, would that have a randomized component to it?

I think that's most likely. Yeah, we're still obviously collecting data from the phase one, so no decisions made yet. But we are of the general view that the next study would be randomized to a component or components of current standard of care in the fourth line, where, you know, unfortunately for patients today, the bar is very low. So, you know, we think that 2051 is very well positioned against those comparators. And, you know, we'll also be thinking through, in the context of Project Optimus, and also of course based on the full phase one data set that we analyze later this year, and into Q1, whether that's one dose of 2051 or maybe two. That remains to be decided. Great.

Thank you so much. Thanks for taking the questions. Thanks for the update.

You're very welcome.

Thank you.

As a reminder, ladies and gentlemen, let's start 1-1 to ask the question. Please stand by for our next question. Our next question comes from the line of Mitchell Kapoor with H.C. Wainwright. Your line is open.

Hey, guys. Thanks for taking the question. You mentioned that there's, you know, quite a low bar for 2051. That makes a lot of sense. But thinking about, you know, what triggers and go, no-go move into the phase two and fourth line as a monotherapy, can you just speak to what we should be looking for that would be indicative of a positive outcome that would immediately trigger, you know, looking to move into phase two?

Yeah, hey, Mitch, thanks for the question. Well, again, just to recap our experience with the first 18 efficacy-evaluable patients, where across the three dose levels of 7.2, 8.6, and 10, we saw a confirmed ORR of 28%. So I think we all agree that that, you know, that's very exciting and, you know, would set up a very clear go forward decision into the fourth line study. Number doesn't, of course, need to be as high as that to go forward. I don't think we're going to put a number on it today, but we've got a lot of room to maneuver, we think, with the data that we've already presented with CX2051 as our data continues to mature.

Okay, great. And just one more on the CRC combos in earlier lines. Would you potentially advance multiple combinations? And have any plans been discussed with the FDA on the combination

strategy so far? Multiple combinations are certainly on the table. We need to be mindful of our resources at this point in time. As I mentioned, the place to start most likely would be the combination with Bev. We have yet to have significant conversations with FDA relating to go-forward study design. That will come, of course, as our Phase I data continues to mature. Great. Thank you. Thank you.

Please stand by for our next question. Our next question comes from the line of Mayak Mantani with B. Riley. Your line is open.

Hi, this is Jay from Birelli for Mayank. Thank you for taking the questions. My first question is, given that CX-2051's grade 3 diarrhea rates exceed those of other POP1 inhibitor ADCs, Will you explore alternative mitigation strategies, such as the SAC-specific protease inhibitors or microbiome modulation, rather than relying solely on rapamide? My second question is, how much median follow-up are you expecting to have as a 1Q update? And are you planning to present data at ASCO GI in January 2026? Thank you. Great.

Thanks for the questions. So taking the first one relating to diarrhea, yeah, so as I mentioned on the call, you know, that is one of the AEs that we're most focused on in this phase one study. We've learned a lot about it in the context of the data that we initially disclosed. to recap, you know, what we're doing, as we discussed before, in the earlier part of this study, of course, as we wanted to understand the overall AE profile of this drug, we had not implemented any prophylactic measures for management of diarrhea. But we did earlier this year, around the March time, March-April timeframe, around the time that we were beginning to gear up some of these expansion studies. And so we continue to be focused on the use of loperamide as a prophylactic measure. We're going to learn a lot about that as we continue to execute on the expansions. And in terms of the incidence of grade 3 diarrhea in this study, about 20%, I want to remind everyone that in the early days of arena tecan development, That number was closer to 30% to 40%. And, you know, we do know that topo-1 inhibitors in the context of ADCs can also induce significant levels of grade 3 and higher diarrhea. So, you know, it's something we need to understand more about, something we need to manage. We're really exploring loperamide as a starting point. Your question on protease inhibitors, I think, is an interesting one. you know, at this point, you know, that will be very exploratory, and we don't really have any evidence right now that protease biology is playing any role in the AE profile. So that may be something for future exploration, but, you know, thanks for the question. I think you had two more questions, but in terms of median follow-up, I guess there, what I would say is that, as I mentioned earlier, enrollment of the expansions has gone well. We're midway through 2025. So by the time we get to Q1 of next year, we'll have a pretty decent follow-up, we think, on the majority of these patients. So I can't give you a number. The study is still in progress. And of course, can't comment on ASCO GI 2026. We will plan to keep all of our options open in terms of where and exactly when we present data as is customary. But thanks for the question. Thank you. That's very helpful.

Thank you. Ladies and gentlemen, I'm showing no further questions in the queue. I would now like to turn the call back over to Dr. Sean McCarthy, Chairman and CEO, for closing remarks.

Thanks, everyone, for joining us today. It's been a pleasure to recap our tremendous progress during Q2 of 2025. We look forward to providing additional updates as we move through the second half of the year. So enjoy the rest of your day.

Ladies and gentlemen, that concludes today's conference call. Thank you for your participation. You may now disconnect.