Good afternoon, and thank you for joining Xilio Therapeutics' Conference Call and Webcast. At this time, all participants are on a listen-only mode. Following management remarks, we will hold a question-and-answer session. At that time, lines will be open for you. I would now like to turn the call over to Ruth du Moulin from Xilio Therapeutics. Please go ahead. Good afternoon, everyone, and thank you for joining today's call to discuss Xilio's key data updates presented at the Society for Immunotherapy of Cancer, or SITC, conference last week. The press releases reporting the details of our SITC presentations can be found on the investor relations section of Xilio's website. Joining today's call from Xilio are Dr. René Russo, our President and Chief Executive Officer; Dr. Katarina Luptakova, our Chief Medical Officer; and Chris Frankenfield, our Chief Financial and Operating Officer. In addition, we are joined by two clinical investigators from our plasterboard study: Dr. Aparna Parikh, Associate Professor of Medicine at Harvard Medical School; and Dr. Diwakar Davar, Associate Professor of Medicine at UPMC Hillman Cancer Center. Before we get started, I'd like to remind everyone that the statements we make on this conference call will include forward-looking statements. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties, and other factors, including those set forth in the risk factor section of our SEC filings, including our most recent Form 10-Q and any other filings that we have made or may make with the SEC in the future. In addition, any forward-looking statements made on this call represent our views only as of today and should not be relied upon as representing our views as of any subsequent dates. We specifically disclaim any obligation to update or revise any forward-looking statements. A replay of this call will be available on our website following the presentation. At the SITC Conference, we presented data from across our pipelines that continue to underscore the transformational potential of our masking technology. On today's call, we'll walk through these data updates with a focus on our late-breaking poster presentation of exciting new clinical data for Vilastobart, in combination with Atezolizumab in microsatellite stable colorectal cancer, or MSS CRC, an area of growing and unmet medical needs. For today's agenda, Rene will begin with a brief review of our technology and the differentiated clinical activity and safety profile demonstrated for Vilastobart to date, as well as the meaningful opportunity for a biomarker-guided approach to MSS CRC. Katarina will then review the new phase II data for Vilastobart in combination with Atezolizumab in patients with MSS CRC with high plasma tumor mutational burden, or TMB, which were presented in a late-breaking presentation at SITC. We will then hold a mini fireside chat with Dr. Parikh and Dr. Davar to discuss what these new data may mean for patients with MSS CRC and the potential role for plasma-based TMB in predicting response to the combination of Vilastobart and Atezolizumab. Finally, Chris will review additional data updates presented at SITC from across our pipeline. With that, I'm pleased to turn the call over to René. Thank you, Ruth, and thank you, everyone, for joining us today. At Xilio, we've used our proprietary protein engineering technology to build a broad pipeline of novel masked biologics, and we've successfully attracted multiple tier pharma partnerships, including with Gilead, AbbVie, and Roche. Our most advanced clinical programs utilize our unique masking technology to improve the therapeutic index of validated monoclonal antibody and cytokine targets, including Vilastobart, our FC-enhanced tumor-activated anti-CTLA-4, and Efarindodekin Alfa, our tumor-activated IL-12. We believe our platform is robust and clinically validated, supported by data in approximately 300 patients treated across our clinical stage programs that demonstrate a number of key findings. First, these molecules have demonstrated monotherapy efficacy in the clinic. Second, they've demonstrated consistent selective activation of these molecules in patient tumors. Third, they've demonstrated a differentiated safety profile driven by low systemic exposure of the activated or unmasked molecule. We believe this successful clinical translation for our most advanced programs underscores our ability to apply our unique masking approach to deliver on the next wave of more complex, multi-targeted molecules in our pipeline, including XTX501, our masked PD-1/IL-2, and our ATACR and SEECR masked T-cell engager formats. Now let's turn our attention to Vilastobart, a high-affinity FC-enhanced tumor-activated anti-CTLA-4, which is designed to achieve maximum potency in the tumor without systemic toxicity. As background, let's run through the clinical data reported to date for this program. First, from a mechanistic perspective, we've demonstrated tumor-selective activation of Vilastobart in patients with 70%-90% of the molecule activated in patient tumors and minimal systemic activation of only about 15%, confirming that the masking is working as designed in patients. In phase I, we saw confirmed responses in both the monotherapy and combination settings, along with a differentiated safety profile consistent with the 15% of active drug in peripheral circulation. Most recently, at ASCO in June, we shared the first phase II data for Vilastobart in combination with the Atezolizumab, demonstrating a meaningful 26% response rate in late-line metastatic MSS CRC without liver mets. This was with a differentiated safety profile, once again consistent with the masking design. Now let's turn to the treatment landscape for microsatellite stable, or MSS colorectal cancer, which makes up 95% of all colon cancers. First off, colon cancer continues to increase in incidence at a concerning rate. By 2028, it is projected to become the leading cause of cancer-related death in both men and women under the age of 50. Many patients are being diagnosed late with advanced metastatic disease, especially younger patients who are below the age of screening. This makes treatment challenging. Unfortunately, approved therapies have little to no efficacy in this late-line metastatic setting, with response rates reaching only 6%, including the current standard of care for third-line patients. In contrast, new and emerging combination treatments with next-generation anti-CTLA-4s in development have shown encouraging clinical efficacy in this late-line metastatic setting, specifically in patients without liver mets. This includes Vilastobart, which, as I mentioned, has shown a 26% overall response rate in combination with the Atezolizumab in this setting. For context, the Atezolizumab has been extensively studied in this population and has shown only a 2% overall response rate as a monotherapy. While this 26% overall response rate achieved with Vilastobart combination therapy was certainly a meaningful improvement over the 0%-6% response rate seen previously with approved IO therapies and IO combinations, we looked further to identify a biomarker that would predict an even higher response in this population. Tumor Mutational Burden, or TMB, was a biomarker of interest to us that historically had been shown to enrich for IO responses in certain tumor types, such as non-small cell lung cancer, at a level defined as greater than 10 mutations or more per megabase, or high TMB. Unfortunately, historically, tissue-based high TMB has not been predictive of IO responses for MSS colorectal cancer. In addition, high tissue TMB represented only about 5%-10% of the MSS CRC population historically. For these reasons, tissue TMB has not been a useful biomarker of IO response in MSS CRC. As a result, in our phase II trial in MSS CRC patients, we implemented a new type of TMB assay from Guardant that uses plasma rather than tissue. This plasma-based TMB assay delivers a more sensitive result and is better able to provide a comprehensive assessment of mutational load that accounts for tumor heterogeneity. Because it is a simple and readily available test, it provides clinicians with the ability to determine TMB status at the time of the treatment decision. In contrast, historical tissue-based assays require a tumor biopsy procedure and are limited to that single-site biopsy specimen, which is typically taken only once at the time of initial diagnosis and does not account for tumor heterogeneity or changes in TMB over time. Using the Guardant plasma-based TMB assay as a biomarker for response, the Xilio team analyzed the data as part of a pre-specified analysis per protocol and found what we believe are important and striking new insights, including a clear correlation between high plasma TMB and overall response rate to combination treatment with Vilastobart. Additionally, our late-breaking presentation at SITC shared another new finding that approximately 55% of all MSS CRC patients have high plasma TMB, which is greater than 10 mutations per megabase. This is based on data from a real-world clinical genomic database in approximately 8,000 MSS CRC patients who received Guardant's plasma TMB assay. These data support a meaningful patient population that could potentially benefit from combination treatment with Vilastobart using this novel biomarker-driven strategy. I'll now turn it over to Katarina to review the data presented in our late-breaking poster at SITC. Thank you, René. As a reminder about our study design, eligibility criteria for our phase II study required that all patients had to be microsatellite stable, or MSS, based on standard local assessment, and the MSS status for every patient was further centrally confirmed using the Guardant plasma-based assay. As René mentioned, using the newer plasma-based TMB approach in these heavily pretreated MSS CRC patients, there was a meaningful and statistically significant correlation between high plasma TMB status of at least 10 mutations per megabase and best overall response to the combination of Vilastobart and Atezolizumab in patients without liver metastases. In this biomarker-defined population, shown in purple on the waterfall plot, we demonstrated a 40% ORR representing a meaningful response rate that has not been achieved before in this setting. Responses were deep and durable, with reductions in target lesions of up to 71% from baseline. The majority of the responding patients are continuing on therapy. Therefore, we have not yet reached the median duration of response, and the treatment duration for these patients ranges from over 10 to over 14 months at this time. All TMB-available patients with a partial response had a plasma TMB greater than 10; in other words, they were plasma TMB high. There were no responders among the plasma TMB low population, which is depicted in orange in the waterfall plot. This correlation between response and plasma TMB status was statistically significant, with a p-value of 0.05. Importantly, in terms of prevalence, the proportion of TMB high patients in our study was approximately 63%. This is in line with the data from Guardant real-world data set of over 8,000 patients. As noted before, 55% of MSS CRC patients had a plasma TMB value greater than 10. Now let's turn to the safety data. While we have seen encouraging signals for next-generation FC-enhanced anti-CTLA-4 combination, the tolerability remains a challenge for systemically active agents. In contrast, Vilastobart is masked. Only about 15% of the active drug is circulating in peripheral blood, while over 70% is activated in the tumor once Vilastobart becomes unmasked. This has resulted in a safety profile that is consistently improved over systemically active anti-CTLA-4 agents. The phase II safety profile demonstrated here for Vilastobart in combination with Atezolizumab looks similar to the adverse event profile of monotherapy at Atezolizumab, meaning we saw minimal additional or new toxicity from the combination outside of colitis, which is a hallmark toxicity seen with anti-CTLA-4 mechanism. Given the low systemic exposure of Vilastobart achieved with masking, the observed rate of colitis of any grade was only 7%, which is about half the incidence seen with systemically active anti-CTLA-4 combinations. In addition, the discontinuation rate for the combination was only 5%, which is meaningfully lower than the reported discontinuation rate for other next-generation anti-CTLA-4s in development. I'll now turn the call over to Rene to lead a discussion with Dr. Parikh and Dr. Davar. Thank you, Katarina. Thank you, Dr. Parikh and Dr. Davar, for joining us today. Let's first start with plasma TMB as a biomarker. A question for you, Dr. Davar. Could you please comment on the biological basis of tumor mutational burden and why TMB can predict for response to IO treatment? Mutation burden, or TMB, is a surrogate of the presence of neoantigen-specific T cells. neoantigen-specific T cells exist in all tumors, and this permits response or permits us to use immune-based modalities to target cancer cells. This was demonstrated more than a decade ago. Evidence shows that tumors with a higher neoantigen burden respond better to immune checkpoint inhibitors such as those directed against the CTLA-4 and PD-1 immune checkpoints. The TMB essentially is a surrogate of the total number of mutations in a tumor's coding region, typically expressed as a number of non-synonymous mutations per megabase. Higher TMB creates and implies the presence of more potential neoantigens for T cells to recognize, making tumors hotter immunologically and potentially more responsive to immune therapy. However, just merely quantifying the TMB in human tissue is a very, very 19th-century modality. Increasingly, given the well-understood heterogeneity of within-patient changes in tissue TMB, plasma-based TMB modalities represent a tremendous advancement in the field. This is because tissue biopsies only sample one area, missing mutations that are present in other regions of the tumor or distant metastasis, what is termed Spatial heterogeneity, and thus underestimate the true mutational burden of the patient. Secondly, tissue TMB is typically only assessed when tissue obtained at initial diagnosis does not capture any changes in the TMB that may occur over time, and particularly cannot easily be assessed in tissues that are in hard-to-biopsy areas, particularly of concern in patients with colorectal cancer. Plasma TMB, therefore, is a newer method with enhanced performance that can capture and mitigate the spatial heterogeneity and provides real-time tumor mutational status contemporaneous with treatment without an invasive biopsy needed to obtain a new TMB value. Thank you very much. As a follow-up question for both of you, and we'll start with Dr. Parikh. Sorry. These data that we presented today, they highlight a striking prevalence in terms of high plasma TMB in the MSS CRC population of 55% from the Guardant data. This is substantially greater than what we previously thought based on the tissue TMB. Could you comment on how meaningful this prevalence rate is in MSS CRC and the predictive value of plasma TMB in terms of immunotherapy response? Yeah, thanks, Nicole, for having us today. Just to rewind a little bit to a comment earlier in the discussion. Historically, when we look at tissue-based TMB, the TMB prevalence is low, so less than 10% of patients. The key point here is that patients, when you're doing tissue testing, are sampled with their tissue typically at the time of diagnosis, or if they were recurrent, they were oftentimes sampled at the time of their surgery and not necessarily sampled again in terms of their updated mutational profiling. In clinical practice, we see this. In contrast to that less than 10% rate that was tissue-based, the data that we see from this study, but also Guardant, is really consistent with what we see clinically. I and my practice tend to check serial TMB or serial Guardant plasma over time, and you see that mutational burden go up. This is very consistent with what we see clinically, but much higher than what is reported. The key distinction is that what is reported in the past is all tissue-based. What is also important to note is that when you look at prior data sets that highlight TMB being a poor prognostic biomarker, that is tissue-based TMB and lower TMB numbers as well. What we are seeing here is the ability to really assess, as Dr. Davar was mentioning, the spatial and temporal heterogeneity with patients that have been treated, and then giving them the appropriate therapy proximal to their testing, not remote from their testing. There actually has been some data sets, some data from Jonathan Loree and colleagues from the Canadian cooperative group did a study with Tremelimumab and Durva. In that data set, actually did show that, again, the plasma-based TMB versus tissue-based TMB actually was predictive of response to checkpoint inhibitors. I think consistent with what we see in a distinction, again, from tissue-based testing. Thank you, Dr. Parikh. Dr. Davar, do you want to add anything to that in terms of the prevalence that we saw here of the 55% high plasma TMB? I think to me, what is really exciting about this is that historically, as you heard from Dr. Parikh, the fact that less than 10% of patients have a TMB high tumor in colorectal cancer is definitely a concerning finding. I mean, it would suggest that this is not a disease in which one would historically go in. However, what is most exciting to me is that the value of this, particularly over time, suggests that, one, this biomarker, especially real-world, reproducible, easily obtained, and something that is obtained with a circulating assay and not a biopsy. Two, the prevalence, particularly in this case, indicating that it's north of not just 10% or 15%, but north of 55%. In fact, the Vilastobart data set was 63% being TMB high. This is extraordinarily valuable because it suggests that there's a strategy that potentially allows us to identify the patients who are benefiting. Very importantly, as you've highlighted, we didn't just identify half the patients who benefited. We were able to identify, your team was able to identify, all the patients who benefited. That is very, very valuable. Thank you both. I appreciate that. With that background in mind, I'd like to move to the impact of some of the new data we shared for Vilastobart in this population. Question for you, Dr. Parikh. Could you comment on the clinical significance of this 40% overall response rate in this biomarker-selected population versus the expected response rate for currently available therapies or even therapies in development? This response rate is really notable and extremely exciting. To put this in context, when you look at our approved therapies in refractory metastatic colorectal cancer, response rate, single-digit response rate is generous. We just do not see responses. Even with the newer checkpoint inhibitor combination studies that we are seeing, we really have not moved the needle beyond 20% or so, in that 20%-definitely less than 30% range. Fortunately, with this combination, toxicity is certainly manageable. I think it has been a pleasant surprise after other CTLA-4s. That being said, any biomarker where you are seeing this really clean separation of responses and no patients that were low TMB in the plasma responding is really exciting because not only is it dramatically improving the ORR, it is giving us a tool to better select patients who are most likely to benefit. I think we just haven't seen north of 30% response rate to date, which is really great. Thank you. Maybe a follow-up question. I think you touched on this a little earlier, Dr. Parikh, regarding your current clinical practice. Generally, how often are you assessing plasma TMB in cancer patients? Related to that, is this type of testing very accessible, easy to obtain, and is it something you might be considering now for MSS CRC specifically? Absolutely. Just to make a point, the plasma-based TMB is not yet a test that you're doing independently. It is incorporated into many of the blood-based diagnostic tools that clinicians are using. It is nice because you don't have to order a separate plasma-based TMB testing. You're getting that as you're doing your molecular-based, blood-based testing for patients. Very easy to obtain, and your turnaround time is sometimes even faster than a week. You're getting the information back really quickly, about as real-time as you can, I think, as you can get for a send-out test. I think we've always tried to treat patients smartly. I think having this data, even as I'm thinking about clinical trials for patients, will be helpful for me to be able to better select who I think might benefit from a certain clinical trial more so than other patients. I think we're not yet—I wouldn't say we're using this yet clinically as standard of care. I think in the modern IO era, where there are many clinical trials available too, I think certainly an incredibly useful tool to have this data to better inform patient care and patient decision-making. Thank you. Dr. Davar, anything you would like to add on how you're using plasma-based TMB in your patients? In the context of cutaneous melanoma, we generally have a tumor that essentially is high TMB, as generally defined, in most of our patients. One very important thing about serial TMB, which Dr. Parikh alluded to, is that it is very important to underscore that TMB is not a static measurement. This does and is well known increasingly to change over time. Just at the last ASCO annual—a couple of the last ASCO annual meetings, we have seen data from cancers, including melanoma, non-small cell lung cancer, even prostate cancer, demonstrating that the temporal change of TMB over time happens because patients progress through different lines of therapy and that selection pressure exerted by treatment can sometimes result in an increase in TMB. Firstly, therefore, this implies that as patients potentially become more TMB high, that one can result in them becoming candidates for a novel therapy, particularly an immune checkpoint blockade. Two, a TMB high tumor is particularly sensitive to an agent that recognizes neoantigens such as a CTLA-4 inhibitor, and particularly one that is potentially less toxic, such as Vilastobart. Thank you. Let's continue, Dr. Davar, with you. Thinking beyond MSS CRC, do you see potential for plasma TMB as a selection biomarker for Vilastobart in other cancer types beyond colorectal? Absolutely. I think to me, the most interesting thing about TMB is beyond identifying a biomarker that potentially selects activity, this is a biomarker that actually makes sense. The presence of TMB is synonymous with the nature of a CTLA-4 inhibitor. After all, a CTLA-4 inhibitor is an immune checkpoint that recognizes neoantigens. Therefore, the fact that a TMB is the biomarker is not surprising because this is a method of quantitating neoantigens, except that this is doing so peripherally. Two, right now, there are something like 19 different indications for a PD-1 inhibitor and only four indications for a CTLA-4 inhibitor in combination with a checkpoint: microsatellite high, melanoma, kidney cancer, and hepatocellular carcinoma. What this implies is that there are a whole slew of indications wherein checkpoint PD-1 blockade potentially could be effective, but we have not bothered to add a CTLA-4 inhibitor historically for concerns over toxicity. We now have an option to study a safe CTLA-4 inhibitor in combination with an easily obtained biomarker with a rapid turnaround. This idea of using a CTLA-4 inhibitor such as Vilastobart with a biomarker to select patients with the best chance of benefiting can firstly guide treatment development plans, but also potentially allows us to extend from the already very large CRC patient population to patient populations beyond colorectal cancer, such as at the very least melanoma, kidney cancer, non-small cell lung cancer. Potentially, the other 13 indications where a checkpoint inhibitor is approved without a companion CTLA-4 inhibitor concomitantly. In addition, we can start thinking about other PD-1 CTLA-4 backbones, including the new checkpoint inhibitor variants that are the PD-1 cis IL-2s as well as the PD-1 VEGF bispecifics. Thank you. So a final question from us, at least. There will be questions at the end from the audience. Final question from us for both Dr. Parikh and Dr. Davar. You are both investigators on the Vilastobart clinical trial. What has been your hands-on experience in terms of depth and durability of response in your patients, as well as safety and tolerability? Yeah. As an investigator in the GI cancer space, it's not often that we get to see really great responses. This time, I got lucky with many of my patients who were on this trial being the ones to derive significant benefit. One of the patients that I think is most remarkable and just kind of shows with appropriate patient selection and treatment how you can allow patients to derive benefit from immunotherapy was a patient that actually had a history of liver metastases. Remember that this trial did not allow active liver mets on study, but it did allow patients that had treated liver mets that were stable to go on. This patient had previously—we had treated the liver metastases with no active liver disease at the time of study entry. That patient has been on therapy for a substantial amount of time, as well as several other patients. We, in terms of tolerability, again, having had experience with several other CTLA-4s, I think went into the study a little bit nervous around how much immunomodulation we were going to be having to give again, akin to past experiences. Quite to our surprise, treatment was incredibly well tolerated with some low-grade IRRs, but entirely manageable. None of our patients actually had to come off therapy due to toxicity, which is fantastic. Thank you, Dr. Parikh. Dr. Davar, would you comment on your experience as an investigator on the trial? I think the anecdote that Dr. Parikh provided, I think, is very illustrative of the patients that I've treated. The one point that I would add in addition to that is that I've been an investigator in many of the other FC-active CTLA-4 programs. What is striking to me is the absolute lack of significant serious toxicity in these patients treated with Vilastobart. Oftentimes, when giving somebody an FC-active CTLA-4 inhibitor, we see a lot of Grade 3 or higher toxic rates: hepatitis, certainly colitis, other neurological side effects as well. We are able to treat those patients with immunosuppressive agents such as vedolizumab or infliximab. However, the use of the secondary biologics is not ideal because these biologics, one, cost money, two, they're difficult to obtain from insurance, and three, they're actually directly counteracting the mechanism by which you select and produce an immune response. Therefore, identifying a CTLA-4 that is particularly FC enhanced, but also permits tumor microenvironment selective activation, is potentially highly beneficial because you do not see these high grades of toxicity and do not have to use these counteractive medicines. That potentially is very beneficial for both patients, health systems, but also drug development as a whole. Thank you, Dr. Parikh and Dr. Davar, for that commentary. We are very encouraged by these new data demonstrating a 40% overall response rate in heavily pretreated patients with MSS CRC without liver mets and high plasma TMB, as well as a statistically significant correlation between plasma TMB and response. These data support the promising opportunity to use plasma TMB as a predicted biomarker to identify patients who may benefit from combination treatment with Vilastobart. In addition, the prevalence of patients with high plasma TMB in our study, which is consistent with the approximately 55% prevalence in the real-world setting using Guardant Health's plasma-based assay, further supports the meaningful opportunity in patients with this high unmet medical need. Based on these promising data, we are continuing to actively seek a partner to develop Vilastobart in combination with PD-1, PD-L1, or newer PD-1 bispecifics, as you mentioned, Dr. Davar, such as PD-1 VEGF, both in MSS CRC as well as other tumor types. In parallel, we also plan to assess the appropriate regulatory path for future development with this novel biomarker. Before we open the call to Q&A, I'd like to turn it over to Chris to touch on several additional presentations from SITC and key upcoming milestones across our pipeline. Thank you, René. Starting with our clinical programs, we presented phase I data for Efarindodekin Alfa, our tumor-activated IL-12 program, demonstrating deep monotherapy responses in difficult-to-treat tumors, a well-tolerated safety profile, and consistent interferon gamma signaling without evidence of tachyphylaxis with repeat dosing. In addition, pharmacodynamic data demonstrated robust immune cell infiltration and PD-1, PD-L1 upregulation. These data further demonstrate the tumor-selective activation of Efarindodekin Alfa and we're currently advancing this program in phase II. Continuing on the theme of biomarkers correlated to response, we also presented phase II data for Vilastobart assessing plasma-circulating tumor DNA, or ctDNA. These data showed radiographic responses were accompanied by deep reductions in ctDNA, which generally occurred before the radiographic responses. ctDNA reductions were significantly associated with best overall response. In addition, we reported two patients with endoscopic complete responses accompanied by reductions in ctDNA to undetectable levels. Turning to the next wave of innovation leveraging our clinically validated masking technology, we presented preclinical data for our masked T-cell engagers, demonstrating the broad applicability and best-in-class potential of our masked T-cell engager formats across a diverse range of targets. As a reminder, our masked T-cell engager programs include bispecific molecules designed using our advanced tumor-activated cell engager, or ATACR format, which consists of a T-cell engager with a masked CD3 targeting domain, and trispecific molecules designed using our selective effector-enhanced cell engager, or SEECR format. The SEECR format builds upon the ATACR format by adding co-stimulatory signaling designed to further enhance the potency and durability of T-cell activation. In particular, our new data showed our T-cell engager formats demonstrated potent anti-tumor activity with evidence of reduced systemic toxicity in murine models. The incorporation of co-stimulatory signaling in our SEECR format enhanced durability of anti-tumor activity compared with T-cell engager molecules that lacked co-stimulation. We believe the data we've shared today position Xilio well to execute on several potential value drivers across our pipeline. For Vilastobart, we plan to report additional phase II data in MSS CRC, including in the high plasma TMB population in the first half of 2026. For Efarindodekin Alfa, we're advancing our phase II trial with the goal of delivering a phase I two option data package to Gilead. As a reminder, we recently received a $17.5 million development milestone in connection with phase II initiation. If Gilead exercises its option for the program, we'll receive a $75 million option fee. For XTX501, our bispecific PD-1 IL-2, we're on track with plans to submit an IND in mid-2026. We're very encouraged by meaningful clinical efficacy shown with other non-masked PD-1 IL-2s in hard-to-treat tumors, coupled with the recent BD activity in this space, which further validates this PD-1 targeted approach. We believe our molecule has the potential for significant differentiation with more potent co-stimulatory signaling and a wider therapeutic index enabled by masking the IL-2 component. Finally, we look forward to sharing more updates in early 2026 for our masked T-cell engager molecules targeting PSMA, CLDN18.2, and STEAP1. With that, I'll hand the call over to the operator to open it up for questions. Thank you. Ladies and gentlemen, as reminded to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. One moment for our first question. Now, first question coming from the line of Daina Graybosch with Leerink Partners, the Atlantis Melvin. Hi. I have many questions, but I'll try to prioritize. Congratulations on the data, and thanks for hosting this event with the KOLs. I think the initial question I had was remembering that Pembro has a tissue-agnostic label or indication-agnostic label for tissue-based TMB. I wonder with this plasma-based high TMB whether these patients might have responded with Pembro alone or what's the contribution of Vila. I wonder for the two doctors if you have any data or feeling or experience from your own practice or other trials with PD-1s, what the sort of baseline activity with PD-1 or PD-L1, Atezo in this case, might be for these patients versus the contribution of Vila. If you'll allow me, I'll have a separate follow-up. Sure. Thank you, Daina. We'll come back to you for your separate follow-up. Just to make sure we understand the question, understanding Pembro's historical tissue-based tissue-agnostic label for the tissue-based high TMB, you're wondering if there is any data on whether Pembro alone or any clinical experience from our KOLs, whether Pembro alone would be expected to work in this 55% of the population with high plasma TMB. Correct. Okay. Let me, let's start with Dr. Davar. Okay. The way I would break the question down is as follows. One, Pembro is very effective in TMB high tumors. TMB high in this case is defined as 10 with a cutoff on Foundation. That is assessed in tissue, not plasma. What we do know is that if you took Pembro and you took the same assay, in this case, a circulating tumor-based TMB, and you did that study, you'd probably find a response rate that is fairly similar. Let's keep in mind that in this case, this study comes from Keynote 158. The response rate in Keynote 158 was, firstly, only Keynote 158 enrolled about 1,000 patients. Of those 1,000 patients, not all of them were evaluable for TMB. You know why? Because we couldn't get biopsies. In the study that was designed to look at TMB, only 75-odd% of patients, 800 of the 1,000, could even get TMB because we did not have a good way of looking at it. Of those patients, the proportion of patients who had a TMB high status was only about 15%. I think it is 100 out of the 1,000. In those patients who had a high TMB, the response rate was about 30 or so%. Do I think we will see the same results if this study, if you used Vilastobart with tissue high TMB? I think we would actually see better results. The reason is because Vilastobart essentially is, it is a CTLA-4 inhibitor that sort of primes the T-cell response. That is how CTLA-4 inhibitors work. They prime immune responses, whereas checkpoint inhibitors, PD-1 inhibitors, essentially reverse PD-1, PD-L1 mediated tumor exhaustion that is within the tumor microenvironment. Ideally, what you need is a PD-1, CTLA-4 combination. If you did that using a blood-based assay, you'd probably find a very, very high response rate. If you did Vilastobart monotherapy, you'd probably see the same response rate that you saw with the CTLA-4 exposure in cutaneous melanoma. Response rates would be about the 15% or so in highly inflamed tumors. To answer your question, I think if you utilize the same assay, you'd probably see a response rate that is higher than that if you combine PD-1 with CTLA-4. If you studied CTLA-4 by itself in a PD-1 naive setting, you'd see response rates that are very similar to Ipilimumab that was observed in the melanoma frontline studies that were done in the 2012 and 2010 era. If you combine PD-1 with CTLA-4, I think you'd see very, very high response rates. Colorectal cancer in the 30%-40% response rates. Melanoma in the 50 or so% response rates in the frontline setting, meaning PD-1 naive setting. And potentially response rates that are north of 30%-40% in the PD-1 experienced setting in melanoma and other inflamed tumors. You sort of answered the exact opposite of what I asked. Can I clarify and maybe go back? Do you want me to clarify, Daina, for you? Yeah. I think, Daina, your question is. Yeah. Yeah. I'll bring it to Dr. Parikh because she can answer specifically for CRC in particular. I think your question was if we treated these patients with Pembro alone, in our study, these high plasma TMB patients, would we expect a similar response rate? Yeah. My sense is no. That is for a couple of reasons. I think when you look back at the history of kind of monotherapy trials with PD-1 alone, we really did not see any activity. It was only when we started to combine PD-1 VEGF, PD-1 with anti-EGFR chemo, and then PD-1 CTLA-4, where we started to see more of a signal. Actually, within the CTLA-4, there was variability based on the CTLA-4 of choice. For example, in Tremelimumab trials, not as good as we saw. That signal was, again, a modest, weak signal, but there was something. Where the field went, I think, as many of you know on the call, is entirely anchoring around the benefit seen in the non-liver met patients. I think what stumbled upon here was that this is, again, just another biomarker to really help even separate out that group. I think if you go, I mean, we do not entirely know because we did not select based on, even in that TMB that was tissue-based, no patients in that data set, if you pull out the MSI high patients, benefit from checkpoint inhibitors with Pembro alone. When you look at even metastatic immunotherapy in the MSI high patients, finally randomized data around dual checkpoint inhibitors versus monotherapy and a striking difference in cure with the addition of CTLA-4. My strong suspicion is no, based on where we have seen. Of course, we have not specifically looked at plasma TMB right before checkpoint monotherapy, but I would suspect that you really do need the CTLA-4. Daina, I'll just add because Katarina and I, we looked at this very mathematically. We asked ourselves the same question, right? We know historically PD-1 and PD-1 CTLA-4 combinations have been studied extensively in MSS CRC. The response rates are 0%-3%. In this population, obviously, if 55% of the population is high plasma TMB, you're not getting a high response rate. We decided, what if every one of those responders was, in fact, high plasma TMB? What would those response rates look like if we just assumed they were all high plasma TMB? What we get to generally, Katarina's. Single digits still. Still single digits. So that's kind of how we're looking at it because we're looking at the current 55% rate of this plasma high TMB and the historical response rates and just saying, let's assume they were all high plasma TMB. So we still are in that single digit range. And we did this across all of the studies. So we think this is something unique. We believe it's unique to these next generation CTLA-4s and certainly the plasma TMB also being contemporaneous with the treatment. I think that's key. Does that help? It does. Okay. Good. Sorry, I think you had a second question. Yeah. I think Dr. Parikh mentioned it, actually. Now that you have this result and we also have the non-liver met result, what do you, for everybody, think the best next approach is? Should the next study be looking at high plasma TMB regardless of stable or active liver mets? Because could you be picking up responses even in patients with active liver mets? Thank you. I'll give you a little bit of a sense of what we're thinking about from a development perspective and then turn it over to our KOLs to discuss what they think. Certainly, we all want to kind of go after the broader population, right, including patients with liver mets. What we would love to see is an earlier line study in the high plasma TMB population with this combination, potentially plus chemo, for example. Because what we've heard and seen, and you've heard of one of these examples from Dr. Parikh, is that previously treated liver mets, right, with chemo typically, are having responses to the Vilastobart combination that are durable and deep. I think if we can move earlier line, select high plasma TMB and include those liver met patients, but add in chemo, maybe it's VEGF. I think you need that additional therapy to really target and treat the liver met situation. It does seem like, based on a few cases we know of, that we can have those responses remain durable long term. Let me turn it over to Dr. Parikh. Yeah. I couldn't agree more. I think I've always felt like there was a little bit of a kind of signal there for these intermediate even TMB patients in earlier lines of therapy. Just to, I think, comment on another approach. This is not a particularly sexy approach, but it's an approach that I think the field felt was warranted. I have an NCI CTEP trial that is looking at actually actively treating the liver mets with radiation therapy and trying to eliminate that immunosuppressive tumor microenvironment because we didn't actually actively say this, but in colorectal cancer, around 70% of patients with metastatic disease, 60%-70% have liver mets. I think there's two options. One, you treat the liver mets with something and then you try to get response. B, you move it up in earlier lines of therapy, treat it with chemotherapy or, again, VEGF, PD-1, for example. Using this biomarker, is that another tool to really engender more responses? I think there are a couple of different ways to tackle it. I think, again, I am so thrilled that at least we are kind of using a biomarker because we have seen time and time again, too many trials where you see the signal and it just goes away without the biomarker. I think if plasma TMB is sufficient to, even without a local therapy, select for patients who are going to benefit, it will open the door for so many more patients who have the opportunity to benefit. Thank you. Dr. Davar, would you like to add anything about the liver mets? I would just add that the idea that the liver is an extraordinarily immunosuppressive tumor microenvironment for immune therapy is not unique to colorectal cancer. This has been demonstrated in multiple solid tumors across sort of the depth and breadth of checkpoint inhibitor therapy dating back to about 2012 or so. We've seen this in melanoma, lung cancer. It appears to be truly related to the liver being a sink for T-cells. I can expand more about this if needed, if asked. I think this is by no means sort of central to just colorectal cancer. This is a pan-tumor phenomenon. Thank you. Thank you, Daina. Did you have any other questions? I'll go back into the queue if it's not asked. Okay. Thank you. Thank you. Question coming from the line of Marc Frahm with TD Cowen. Your line is now open. Hi. Thanks for taking my questions. Maybe just picking up on some of those last talking points about just the impact of liver. Obviously, it's not the focus of the presentation and the numbers aren't huge, but there were some of those people with history of liver mets, even if they're not active. Enrolled. Just any sense that TMB is also maybe effective in selecting responses there? Or is this really the selection strategy unique to this non-liver met population? Yep. A great question. I don't think, from Xilio's perspective, that we know the answer to that yet, but we certainly would like to look into it more. Let me turn it to Dr. Parikh to see if she has any thoughts. I don't have many additional thoughts except for, I mean, I think we investigators, even putting patients on immunotherapy trials, I think we're seeing more and more the opportunity to try to treat the liver with local therapies and then engender responses. That's our current, I think, thinking in the field. Thank you. Dr. Davar, anything you want to add on that? No. I think Dr. Parikh is completely right. I would point you guys towards a slightly different data set. That is, in color, we have been talking about colorectal cancer, but in a completely unrelated, even colder, more immunosuppressive tumor that is metastatic uveal melanoma, there is recently released a data set of essentially liver perfusion with chemotherapy. What you saw is that liver perfusion trial is when they synchronized liver perfusion with old-fashioned ipi-nivo in a disease in which ipi-nivo does not work particularly well, they were able to extend benefit. This is essentially perfusing the liver with heated Melphalan. My point here is that I think the idea that you need to treat the liver in order to get immunotherapy to work is a pan-cancer phenomena and potentially allows us to actually add to the benefit of immunotherapy in diseases where liver mets are present, as long as we're able to treat the liver mets and then we have an effective way of mobilizing the immune system, such as with a checkpoint inhibitor or checkpoint inhibitor combination. Thank you. Okay. That's helpful. Maybe just on this idea that the TMB level kind of evolves over time by line of therapy. Does that imply that maybe this drug's actually, unlike many other things, may be best suited for later lines of therapy once that accumulation has happened? Or do you think the biology, that there's something going on in the biology that predisposes the accumulation of mutations, but also the whole time will predispose that patient to a response? Yeah. I think that's definitely a question we're asking as well. What I can tell you is from our data set, we had responses in TMBs as low as 10. These are not, they're high TMB, but they're at the breakpoint. We're seeing responses even at a TMB of 10 in the plasma. I think that we do expect that TMB increases over time with other therapies. Moving earlier line may reduce the number of patients selected, but I would still expect that it would retain the response rate once you have that high TMB population selected. There may be fewer patients earlier line. Maybe it's not 55%, although this was all comers, this 55% in the 8,000 patients. I think we would still have the opportunity to be selecting for the ones that are going to respond. Again, we saw responses down to 10. Let me turn it over to Dr. Parikh to see if she has any additional thoughts there. No. I think that's exactly right. I think that we do, as you described eloquently earlier, you do see a clear increase with exposure to systemic therapies. Again, I think being an investigator who checks plasma, blood-based biopsies at even diagnoses, there are definitely patients, and I strongly believe that it's more than 5%-10% that even at the time of diagnosis are 10+. Yes, maybe it's not 20 or 30 or 40 quite yet, but I think that, to Rene's point, it may lower your end initially, but still hopefully will allow for more patients and then even more patients potentially over time. Okay. Thanks. Very helpful. Thank you. We have a follow-up question from Daina Graybosch with Leerink Partners, Your line is open. We've seen in these frontline trials, and you have brought up the VEGF combinations with chemo and PD-1 like Atezolizumab and POCHI, and there was one with Nivolumab presented at ESMO where they're using more complex biomarker scores for the immune system like Immunoscore to enrich for responses post-hoc, looking to see enrichment responses. Have you looked at the correlation of this plasma TMB with these other scores utilized in those other studies? Is this a simpler method of very good correlation overlap, or is this quite different? I can take, I mean, so Immunoscore has a kind of complicated history, right? I think for a brief period of time, actually, it was no longer even available as a test and then kind of only recently came to be. It requires tissue-based assessment and time and is not something that's sort of commercially actually available in the U.S. One of the studies, as you alluded to, Atezolizumab in Europe is using Immunoscore to select patients for the combination in colorectal cancer. It is not a test that is really commercially available or used. When we had access, it took time. It is tissue-based testing, so it does not really account at all for spatial or temporal heterogeneity. I'm not sure if, for example, the Canadian group who started to see some of the benefit with plasma TMB looked at Immunoscore in combination with that. Yeah. Yeah. Daina, we haven't looked at this correlation in our data, and we're not aware of Guardant having looked at this correlation yet. I think now that we see this, we'll be looking at how this correlates to everything, right? Because this is such a striking kind of finding. Thank you. As there are no more questions in the queue at this time, I'd like to turn the microphone back to Dr. Russo. Thank you, operator. Thank you, everyone, for joining our call today. We look forward to keeping you updated on our progress in the months ahead and certainly talking more about the high TMB population in the future. This concludes today's conference call. Thank you for your participation, and you may now disconnect.