Good morning, and welcome to the Xilio Therapeutics conference call. Currently, all participants are in a listen-only mode. Following the formal remarks and presentation, we will open the call up for your questions. Please be advised that this call is being recorded. At this time, I would like to turn the call over to your host, Stacey Davis at Xilio Therapeutics. Good morning, everyone. I'm Stacey Davis, Chief Business Officer of Xilio Therapeutics, and I'd like to welcome you all to our pipeline progress and SITC update call. Today, we'll be reviewing progress across our clinical pipeline, including the initial phase I-II clinical data presented at SITC last week for XTX202, our tumor-activated engineered beta gamma IL-2. On Friday, we issued a press release announcing the XTX202 data reported at SITC. You can access the press release and slides from today's presentation by going to the Investors and Media section of our corporate website. 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 Factors 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 date. We specifically disclaim any obligation to update or revise any forward-looking statements. On today's call, I'm joined by René Russo, our President and Chief Executive Officer, Uli Bialucha, our Chief Scientific Officer, and Katarina Luptakova, our Chief Medical Officer. In addition, we're pleased to be joined by Dr. Howard Kaufman from Massachusetts General Hospital. Dr. Kaufman is an investigator in our clinical trial for XTX202, our IL-2, and a leading authority on cancer immunotherapy. His clinical practice at Massachusetts General Hospital is focused on patients with cutaneous malignancies. Today, we'll be covering our two lead clinical programs, XTX101, our novel Fc- enhanced tumor-activated anti-CTLA-4, including phase I clinical data reported in August, and our development plans for XTX101 in combination with atezolizumab in advanced microsatellite stable colorectal cancer, commonly referred to MSS CRC. xtx202, our tumor-activated engineered beta gamma IL-2, including the initial phase I-II clinical data presented at SITC and remarks from Dr. Kaufman, as well as an overview of our plans for next steps in development. After the formal presentation, there will also be a Q&A session. I'd now like to turn it over to René Russo to kick off today's presentation. Thank you, Stacey. The field of immuno-oncology, or IO, has had a transformational impact for some patients with advanced cancers, including the potential for long-term durable cures. However, many exciting IO targets have been limited because their potent tumor-fighting immune effects that we want inside the tumor can also drive systemic immune-related toxicity. This can wreak havoc throughout the body and affects healthy tissues and cells. This systemic toxicity not only limits doses and duration of treatment, but also limits opportunities for combination therapy, ultimately impeding the potential for many promising IO therapies. At Xilio, we believe there's a smarter way to deliver potent IO medicines, to focus and concentrate their activity in the tumor microenvironment where we want it. Our molecules are designed to utilize the tumor's own dysregulated biology against itself, to trick tumors, essentially, into activating their own treatments locally inside the TME, while simultaneously sparing healthy tissues and cells. We call this approach tumor-selective activation. The dysregulated tumor biology that we exploit to turn on our molecules in the tumor microenvironment is the unchecked activity of matrix metalloproteases, or MMPs. MMPs are uniquely dysregulated inside solid tumors, contributing to the progression and metastasis of cancer. Our molecules are designed to harness this dysregulated biology by leveraging the MMPs in the tumor to activate a switch that turns on our molecules to deliver the active agent inside the tumor. Using our proprietary protein engineering technology, we built a pipeline of novel tumor-activated antibodies, cytokines, and bispecific biologics that are designed to optimize the therapeutic index for patients. The way we accomplish this is through a number of components. First, you'll see here the effector domain in yellow on the right-hand side. This is the active IO molecule that we often boost the potency of through engineering. Second, we design tightly regulated protein engineered masking domain, seen here in orange, to minimize or eliminate activity when the molecule is circulating outside of the tumor. And third, we design the equivalent of a switch, called a protease cleavage site, seen here in green, that releases the masking domain and turns on the molecule's activity, but only once it's inside the tumor microenvironment. We're currently advancing three clinical-stage activated IO molecules. XTX101 is our tumor-activated, high-affinity, Fc-enhanced anti-CTLA-4. And as previously announced, we've completed the phase I monotherapy dose escalation for XTX101, and we've selected a recommended phase II dose.... We plan to develop XTX101 in combination with atezolizumab under a co-funded clinical collaboration with Roche in patients with metastatic microsatellite stable colorectal cancer, MSS CRC, including patients with metastatic disease in the liver. XTX202 is our second program, a tumor-activated beta gamma engineered IL-2. Today, we'll review the initial phase I-II clinical data we announced last week at SITC, as well as plans for further phase II development at a dose of 4 milligrams per kilogram in patients with renal cell carcinoma and melanoma. While not our focus for today, we have two additional programs in the pipeline. XTX301 is our tumor-activated engineered IL-12, currently in phase I dose escalation, and we anticipate sharing initial safety data into the third dose level later this year. I'd also like to mention our preclinical bispecific tumor-activated PD-1/IL-2 molecule. This molecule is designed to deliver a synergistic combination of a full-dose PD-1 and a full-dose IL-2, directly targeted to the right immune cells in the tumor microenvironment, while also taking advantage of our tumor-activated approach so that the IL-2 component is designed to remain inactive until it is unmasked locally in the tumor microenvironment. I'm now going to turn it back over to Stacey Davis, our Chief Business Officer, who will highlight the opportunity for XTX101 in combination with atezolizumab and MSS CRC. Thank you, MSS CRC is the first of what we believe are multiple potential indications for our tumor-activated anti-CTLA-4 XTX101. Globally, colorectal cancer is the third largest cancer in terms of number of patients diagnosed annually, behind only breast and lung cancer, and colorectal cancer is the second largest cause of cancer-related deaths. In the US, we're seeing a trend towards younger patients diagnosed with colorectal cancer, and strikingly, it has become the leading cause of cancer-related deaths in men under the age of 50. More than 150,000 patients are diagnosed annually in the United States, with many of these patients presenting with stage 4 metastatic disease, who are not candidates for surgery. Chemotherapy and radiotherapy are often used, but with mixed results, leaving a significant unmet need in the metastatic setting. IO treatment with checkpoint inhibitors has shown promise, but only for the less than 5% of patients whose metastatic CRC is MSI-High. In the United States, over 95% of patients with metastatic CRC are classified as having microsatellite stable disease MSS CRC. this is a clear example of a cold tumor type characterized by weak immunogenicity and limited immune cells. These patients, approximately 85,000 in the US alone, with stage 4 MSS CRC, are not candidates for any approved IO agents today. Furthermore, an estimated 70% or 60,000 patients present with liver metastases as part of their disease, which are notoriously difficult to treat and are often excluded from clinical trials. The worldwide burden MSS CRC is staggering, and yet there are no approved IO options for patients today. MSS CRC patients are typically treated with older agents or chemotherapy, with little to no benefit. Checkpoint inhibitors have not been successful to date, with response rates for PD-1 alone or in combination, only in the 0%-5% response rate range. As dire as the situation currently is for patients MSS CRC, there is a new paradigm emerging around CTLA-4, with next generation Fc enhanced molecules that can cause Treg depletion, showing promise in tumors that have historically been unresponsive to checkpoint inhibitors alone or in combination, MSS CRC. i'll now turn it over to Uli, Uli Bialucha, our Chief Scientific Officer, to share the design of our XTX101 molecule and some of the data supporting this combination. Thank you, Stacey. Shown here are the key design features of XTX101, our next-generation tumor-activated anti-CTLA-4 antibody. XTX101 is a novel CTLA-4 antibody with tenfold higher affinity for CTLA-4 compared to ipilimumab. We then use our platform to design a unique and customized mask, highlighted here in orange. This peptide mask is designed to block the molecule's activity when circulating outside the tumor. The switch that we use to turn on the molecule through MMP activity inside the tumor microenvironment is seen here in green. We call this the protease cleavage element. The final feature of this distinguishes this molecule from ipilimumab and the other first-generation CTLA-4 antibodies, is that we incorporated mutations in the Fc domain of the antibody that enhance the affinity of... specific molecules. We believe that these unique features of XTX101 may allow us to concentrate its activity in the tumor microenvironment, including in primary tumors, but also in metastatic lesions, such as the liver. This increases the antibody's affinity for activating Fc gamma receptors and enables the antibody to elicit enhanced antibody-dependent cell-mediated cytotoxicity or ADCC. For XTX101, the enhanced ADCC drives potent Treg depletion, which is important because Tregs are immune suppressive in the tumor microenvironment. The Fc enhancement also potentiates priming of T cells through stronger interactions between antigen-presenting cells and T cells. Combined with XTX101's potent CTLA-4 checkpoint blocking function, this gives XTX101 multiple mechanisms of action to drive activity in settings typically insensitive to immunotherapy. In fact, recent clinical data for a systemically active Fc-enhanced anti-CTLA-4 antibody combined with an anti-PD-1 antibody reported greater than 20% response rate in microsatellite stable colorectal cancer, a cold tumor type where current checkpoint therapies simply do not work. We believe our approach with XTX101, which is masked to limit off-tumor toxicity, has the potential to deliver the potency of an Fc-enhanced anti-CTLA-4, concentrate its effects both in primary and metastatic lesions, and deliver a much improved safety profile over systemically active molecules. I will now turn it over to our Chief Medical Officer, Katarina Luptakova, to walk you through the clinical data from our phase I clinical trial for XTX101. Thank you, Uli. In August, we reported updated data from our phase I study for XTX101. As you can see here, the data included 29 patients with a broad range of advanced treatment-refractory solid tumors, which were primarily cold tumors. In addition, over 75% of these patients received three or more prior lines of therapy, and about half had failed prior immunotherapy. Overall, we observed a meaningfully differentiated safety profile from what would typically be expected of a potent, systemically active anti-CTLA-4. In particular, no Grade 4 or 5 treatment-related adverse events were observed at any dose level, and there were no discontinuations due to immune-related adverse events. Notably, there were no endocrine-related AEs, which are commonly associated with systemically active anti-CTLA-4 agents. Throughout the study, there was only a single case of dermatitis, and this was striking, as skin-related adverse events are the most common toxicity. In fact, it occurs early in the treatment and in almost one-half of the patients with ipilimumab, a systemically active anti-CTLA-4. Importantly, patients were able to tolerate repeat dosing with XTX101 successfully up to 42 weeks in the study. Looking at the data on the right-hand side, you see the safety profile for the recommended phase II dose, a dose of 150 mg once every six weeks. It is clearly differentiated from that of systemically active anti-CTLA-4s and consistent with the tumor-selective design of the molecule. Again, there were no discontinuations due to any treatment-related AEs. In addition, there was a low incidence of. All of the liver lesions have completely resolved on CT and had not recurred through week 36. This was very surprising to see with monotherapy XTX101, given that the liver mets are notoriously refractory to IO therapy, and even potent IO combinations often do not have activity in liver mets. Overall, this deep and durable partial response in the PD-L1 negative non-small cell lung cancer patient with liver metastases, as well as the lack of immune-related adverse event in this patient, was a great indication that XTX101 was doing what it was designed to do in this patient: tumor-specific activation. I will now turn it over to Uli to share some direct evidence for intratumoral activation of XTX101 from the study that further supports tumor-specific activity enabled by our approach. Thanks, Katarina. Before we move on to the tumor activation data, I'd like to point out a few things about the exciting monotherapy activity of XTX101 in liver metastases. We believe there are a few reasons for this. First, the fact that the liver metastases have high levels of Tregs, and we can specifically address this through the Treg depletion mechanism of an Fc enhanced CTLA-4. Second, we believe our approach lends itself well to activation in liver metastases because liver metastases have high MMP activity, and therefore should readily activate our molecules very efficiently. Moving on to the intratumoral data, as Katarina mentioned, we now have direct proof of XTX101 activation in the tumor in actual patients. We were able to collect two individual patient tumor biopsies during the trial and directly measure activation of XTX101 using mass spectrometry. One biopsy was from a patient with melanoma, and the second was from a patient MSS CRC, specifically a biopsy from a liver metastasis. In both cases, we saw significant activation of XTX101 in the tumor at very high levels, 96% in the melanoma lesion and 73% in MSS CRC liver metastases. In both patients, we also measured 13% activation of XTX101 in plasma, which is consistent with the molecule design to have some peripheral activity to co-cover draining lymph nodes, which we believe is important for the anti-CTLA-4 mechanism. Overall, these data are very exciting and well beyond what has been observed with masked antibodies previously. Stacey will now briefly cover the design of the XTX101 combination trial with atezolizumab and plans for next steps for our anti-CTLA-4 program. Thanks, Uli. As René mentioned at the top of the call, our next step with XTX101 will be to study it in combination with atezolizumab in patients with MSS CRC, including patients with and without liver metastases. Roche is our collaborator on this trial, and they are co-funding the trial and providing atezolizumab. We'll start with a combination dose escalation, referred to as Part 1C, and plan to have sites activated this quarter, and to enrich for CRC patients during dose escalation. Subject to the results of the dose escalation and sufficient additional capital, we plan to initiate a phase II trial for XTX101 in combination with atezolizumab in patients with MSS CRC. We would plan to report phase II proof of concept data for the first 20 patients in Q4 of 2024, followed by an additional 20 patients in Q1 of 2025. The trial is designed to enable us with the potential to move into a phase II pivotal trial in approximately 200 patients with MSS CRC, including the 40 patients from the initial phase II trial. As I showed earlier, there currently are no IO therapies approved for MSS CRC patients with or without liver metastases, and we believe the potential to include patients with liver metastases in our planned phase II trial is differentiating from other current anti-CTLA-4 approaches. We're very encouraged by the totality of the data for XTX101, our tumor-activated Fc enhanced anti-CTLA-4 molecule, demonstrating the first clinical validation of our platform, including safety, PK, PD, and anti-tumor activity, consistent with tumor-selective activation. We look forward to initiating dose escalation for XTX101 in combination with atezolizumab. We'd now like to turn to our second clinical stage molecule, XTX202, our tumor-activated beta/gamma-biased IL-2. Uli will start us off with a brief overview of the molecule design, and then Katarina will review the clinical data just reported at SITC. Thanks, Stacey. Shown here is an illustration of XTX202 in its inactive state on the left and in its active state on the right. We have a beta/gamma-biased IL-2 effector design to avoid Treg stimulation associated with alpha binding. XTX202 has a protein-based masking domain, which is held in place via a linker sequence that contains a protease cleavage site, shown here in green.... You will recall that this is the switch that turns on the molecule's activity inside the tumor microenvironment, both in primary tumors as well as in metastatic lesions. A key feature of our design is that XTX202 retains the Fc domain post-activation, as shown on the right in white, to extend half-life and residence time in the tumor. We believe the beta gamma design with the Fc domain is a better way to increase residence time of IL-2 in the tumor, rather than resorting to the use of wild type cytokine, which is burdened by significant Treg activation. The high level of alpha subunit expression on Tregs creates a sink for IL-2 and deprives effector cells in the TME of IL-2 signaling. Additionally, the Fc domain is not fully silenced, and it's still capable of binding the high-affinity Fc gamma R1 receptor, which allows for cross-presentation by monocytes and macrophages. In short, XTX202 is uniquely designed to enable high tumor exposure and residence time without taking on the potential liability of Treg stimulation. I'll now hand it over to Katarina to discuss the XTX202 clinical trial data presented at SITC. Thank you, Uli. As of the October 25th data cut-off date, 54 patients were enrolled in phase I dose escalation and dose expansion, and eight patients were enrolled in phase II. The phase I population was in a range of advanced solid tumors, including a number of cold tumors. Notably, these patients were heavily pretreated. 74% had failed three or more prior lines of therapy, and 69% were IO refractory. More than two-thirds of the phase I patients had compromised ECOG performance scores, which represents a much sicker population than was reported in the pivotal studies of aldesleukin. This is significant, as a good performance status was a predictor of aldesleukin response in those studies. For phase II, we have limited data so far with six melanoma and two RCC patients treated at 1.4 mg/kg, the lower of the two doses we are studying in phase II. All of these eight patients progressed on prior immunotherapy. Here, we are showing our phase I dose escalation, including those patients in the expansion cohorts. It is important to note that when we initiated the study, we had estimated that the target dose would be somewhere in the 1-3 mg/kg range based on the preclinical data. However, our safety profile had supported escalating beyond this range, and we chose 4 mg/kg for our current phase II dose based on the totality of data, which we will outline throughout this discussion. We have been able to dose patients in the outpatient setting for more than 20 cycles on a once every three week dosing schedule, which translate to over one year of therapy or beyond, and is remarkable given how high we are dosing. To date, we have not yet hit a maximum tolerated dose. Across all dose levels, we have only observed a single dose-limiting toxicity at the 1 mg per kg dose level, and this was, an AE of elevated transaminase, which was transient, and the patient was able to continue on therapy with the dose reductions for five additional cycles without any further issues. In terms of the safety profile across all 62 patients treated between phase I and phase II, as well as a subgroup of patients treated in doses of 1.4 mg/kg and higher, as noted on the right side of the table, XTX202 was generally well-tolerated, and treatment-related adverse events were primarily Grade one or two. Importantly, no signs or symptoms of vascular leak syndrome have been observed at any dose level, including the highest dose of 4 mg/kg. As a reminder, vascular leak syndrome is a severe and life-threatening adverse event that is common with systemically active IL-2 molecules. In addition, no treatment discontinuation due to treatment-related adverse events occurred at any dose level, and there were no Grade five treatment-related AEs. Only two patients required dose reduction. The only Grade four treatment-related adverse events were two events of transient lymphopenia, each lasting less than three days. The only treatment-related adverse events occurring in at least 10% of patients include fatigue, fever and chills, and a transient decrease in lymphocyte count. Overall, I believe this is a remarkably remarkable initial safety profile for a high-dose IL-2, consistent with the tumor selective design of XTX202. Before reviewing the anti-tumor activity data for XTX202, I'll turn it over to Uli to discuss the clinical PK/PD data that we reported. Thank you, Katarina. To date, we've obtained four on-treatment paired tumor biopsies for pharmacodynamic analysis. The goal of this analysis was to look for evidence of IL-2 biology getting activated inside the tumor in patients on treatment with XTX202. These patients comprise the range of tumor types and dose levels. All of these patients had progressed on four or five prior lines of therapy and on prior IO, which is important to note because this is typically associated with a minimally inflamed or burned-out immune microenvironment at baseline, essentially a cold tumor microenvironment. We are therefore very pleased to see that in all four tumor samples, increases in CD8 T-cells were observed by immunohistochemistry, ranging from 20% increase to a 600% increase in CD8s from baseline. These data give us confidence that XTX202 is activating inside these tumors. We also wanted to directly measure XTX202 activation inside the tumor in a patient, and we were fortunate to obtain a fresh biopsy for this purpose. Consistent with the tumor PD data I just showed you, we now also have clinical evidence of tumor activation with XTX202, based on an analysis of a tumor biopsy from a patient treated at the 2.8 mg/kg dose level. The bioanalytical data for this patient demonstrated approximately 15% activated XTX202 in the tumor, which was approximately 40-fold higher compared to activation in plasma. Further, the actual concentration of XTX202 in the tumor, 7 nM, was high enough to enable activation of CD8 and NK cells, as predicted by in vitro concentration response curves generated with human immune cells. This suggests that at 2.8 mg/kg or higher dose levels, we are approaching the optimal range for intratumoral immune activation. Importantly, we saw essentially undetectable levels of activated XTX202 in peripheral blood, and this was also consistent with the molecule design, as well as the tolerability profile we've observed to date. This is a very tightly controlled molecule in the periphery, which is what we want, given the potential for toxicity with IL-2 molecules. Additionally, as shown here, when we look for PD markers, that's pharmacodynamic markers, in the peripheral blood, we saw robust evidence of CD8 and NK cell proliferation, as well as gene expression changes associated with CD8 and NK cell activation, showing clear dose-dependent effects consistent with the beta-gamma IL-2 design. Importantly, these increases in proliferating immune cells occurred in the absence of any signs or symptoms of VLS or any significant treatment-related AEs, which is consistent with a very low level of active XTX202 detected in the peripheral blood. We also wanted to pay close attention to Treg stimulation, that's regulatory T cell stimulation. We think this is actually an Achilles heel of wild-type IL-2 molecules and can impede both monotherapy anti-tumor activity and anti-tumor activity in combinations. Consistent with the beta-gamma design of XTX202, we observed profound dose-dependent increases in CD8 and NK cell numbers in the absence of any Treg changes, even up to the highest dose level of 4 mg/ kg, which you see here in the black line graph in the upper right of the slide. Keeping in mind, once again, that these changes in peripheral CD8 and NK cells were observed with a well-tolerated safety profile and in the absence of VLS. Importantly, we saw the same immune profile in our tumor biopsies across all dose levels, which you can see here in the graphs at the bottom of the slide. These are the same four tumor PD biopsies I showed you earlier with the immunohistochemistry data. You see here in the graph at the lower left, that all four samples showed increases in CD8 levels, and in the graph at the lower right, you see Tregs that essentially remain flat or decrease in three of the tumor biopsies. We saw a small bump in Tregs in one of the sample, but it was much less than the increase in CD8s observed, which is the key. Now I will turn it back to Katarina to review the anti-tumor activity data for XTX202. Thank you, Uli. We were pleased to see a clear dose-dependent increase in anti-tumor activity across a wide range of solid tumor types, and this included several cold tumors, with stable disease of at least nine weeks duration in 13 patients. This dose-dependent increase is in line with the pharmacodynamic data just presented by Uli. Among the six response-evaluable patients treated at the 2.8 mg/kg dose level or higher, we saw a disease control rate of 50%, and among 42 response-evaluable patients treated at all dose levels, we saw a disease control rate of 31%. Importantly, several of these patients had long-term stable disease, and two patients who have been on treatment for more than one year. One of these patients was a treatment-refractory microsatellite stable colorectal cancer patient, and the other was a renal cell carcinoma patient, suggesting XTX202 was well-tolerated with a repeated long-term dosing in these patients. Here, we are showing additional details on the patient with MSS colorectal cancer, who has been on treatment for more than one year and has stable disease. Recall that MSS colorectal is a cold tumor. As Stacey shared earlier in this call, monotherapy IO agent historically has shown essentially no efficacy in this tumor type. This patient had failed three prior lines of therapy before enrolling in our study. They had extensive disease, including target lesions in the liver, adrenal gland, lung, and thoracic lymph nodes. They have received a total of 21 cycles of XTX202 at doses between 0.53 and 1.4 mg/kg and have not experienced any treatment-related adverse events. Despite having a cold tumor and progressive disease after prior therapy, this patient has remained stable on XTX202 for over a year, with resolution of three out of four non-target lesions in the lung, thoracic lymph nodes and overall, they are clinically doing very well. I'd now like to turn it over to Dr. Howard Kaufman from MGH, one of our lead investigators on the XTX202 trial, to talk about his experience to date and what he is seeing with his patients. Yeah, thank you, Katarina. I am really happy to be able to give you my sort of take on this. The last patient I treated, I think, is a really good example of the kind of things that we've been seeing. This is a 75-year-old gentleman who initially presented to me with an acral lentiginous melanoma in his right foot. For those that don't know melanoma, this is a particularly aggressive variant of melanoma that often doesn't respond as well to kind of standard therapies. We had treated him previously with pembrolizumab, which is an anti-PD-1. We also treated him with T-VEC, and he basically progressed through that, developing multiple in-transit lesions, eventually developing inguinal nodes in the right groin, and really started with what appeared to be 3 small liver metastases. So I knew I had to get him onto some other therapy. He was starting to have some edema, as well as pain in the lesions in his foot as well. We enrolled him onto the XTX202 study, and he received the 4 mg/kg dose. He actually tolerated it fairly well. He did have some fever and chills, which you heard about, but we were really able to control those with you know, anti-fever medications like Tylenol and nonsteroidals. These were generally self-limited to about a day or so after the treatment. He noticed early on, I think, one of the first signs that he was responding was that the pain went away. And then the lesions began to morphologically change a little bit, and while we could still measure them, they were a little bit flatter. They were just looking a little bit different. And on his first initial scan, the radiologist actually called me because the liver metastases seemed to be really regressing significantly, and everything else appeared to be remarkably stable. So anyway, he's continuing on treatment, and he's, you know, now into the second major course of treatment, and we're gonna continue to follow him. He's the primary caretaker for his wife, who is sick, and he's been really able to tolerate and have a very good quality of life while on this medication. So, I'm very much looking forward to putting more patients onto this study. I'll hand it back to you, Katarina. Thank you, Dr. Kaufman. As you have seen today, the clinical data to date for XTX202 demonstrates a number of key findings. First, we have observed tumor-selective activation of XTX202 in a patient tumor. Second, we have observed tumor-selective increases in CD8 and NK cells without Treg increases in three patients. Third, the safety data for XTX202 demonstrate a differentiating tolerability profile at high doses. And fourth, we observed a clear dose-dependent increase in disease control rate, including two patients with long-term treatment for more than one year. Overall, we are encouraged by what we have seen so far and recently opened enrollment at the second dose level of 4 mg/kg in the ongoing phase II monotherapy study for XTX202. I'll now turn the call over to René, who will provide closing remarks. Thank you, Katarina. So as you've heard today, we're very excited about the potential for our tumor-activated platform based on now the initial clinical validation demonstrated by our two lead clinical programs, XTX101 and XTX202. Importantly, each of these molecules has now demonstrated tumor-selective activation in patients, monotherapy anti-tumor activity, including in cold tumors, differentiated safety profiles at high doses, and the ability to dose patients over long durations. In terms of key upcoming milestones for each of our clinical stage programs, for XTX101, our tumor-activated Fc- enhanced anti-CTLA-4, we plan to have sites activated this quarter for the phase I combination dose escalation of atezolizumab under our co-funded clinical collaboration with Roche. For XTX202, our tumor-activated engineered IL-2, we're encouraged by what we have seen so far, including a clear dose-dependent increase in disease control rate, and we've recently opened enrollment at the 4 mg/kg dose level. For context, that would translate to a 280 mg dose in a 70-kg patient, and this is in our ongoing phase II monotherapy trial for XTX202. Finally, for XTX301, our tumor-activated engineered IL-2, we're currently enrolling patients in phase I dose escalation, and we believe IL-12 has significant potential as an IO agent for both cold and hot tumor types, but the severe toxicity of IL-12 has significantly limited its clinical application to date. We look forward to reporting preliminary phase I safety data for XTX301 into the third dose level at the end of this year. Subject to obtaining sufficient additional capital, we anticipate multiple meaningful data readouts across our clinical stage programs in 2024. Most importantly, we wanna thank the patients who are participating in our trial, their families who are supporting them in this, caregivers, the investigators, and study site staff for their commitment to our trials, as well as all of the Xilio employees for their passion and urgency that they're bringing to our mission every day. We're excited for the potential across our pipeline as we develop tumor-activated IO molecules designed to improve the therapeutic index and overcome limitations of current IO treatments. Thank you for your attention. We'll now open the call for questions. Operator, please. Thank you. At this time, we'll begin conducting our Q&A session. As a reminder to the audience, you may submit questions through the Q&A portal below the webcast player. To our analysts, please raise your hand to indicate you would like to join the queue. With that, we'll take the first question from Mike Ulz at Morgan Stanley. Yep. Good morning, everyone, and thanks for taking the question. So maybe a couple just on 202. Just want to get a little bit more clarity on what patients you've treated so far at that 4 mg dose, since that's the dose you plan to add to the phase II. So I guess in the phase I, maybe you can talk about how many patients were treated at that dose, and what type of tumor types were included, and specifically, any melanoma or RCC patients? And then just on safety, maybe a similar type question in terms of how long those patients have been followed up, and are they beyond the window of when we would expect to see potentially vascular leak syndrome, or are we well past that at this point? Thanks. Thanks, Mike. It looks like we have a little feedback on the line. Sorry about that. So I think a couple of things I'll point out, and then I'll turn it over to Katarina and also Dr. Kaufman, who has treated a patient at 4 mg/kg in terms of the safety profile so far. So the 4 mg/kg dose is a recent dose level that we just opened up in the phase II trial, and we did enroll some patients at 4 mg/ kg in the phase I as well, and we have some follow-up on those patients. So let me turn it over to Katarina to answer your specific questions. Thank you. So far, the 4 mg/kg dose level has been administered in the phase I study only, as we just opened the phase II. And therefore, it included a variety of different tumor types. A total of nine patients to date, and of those, there was 1 patient with melanoma and no patients with renal cell. The second part of the question was about safety? Yeah, the second part of the question was, have they been treated long enough to really determine if VLS might be an issue? Thank you. Typically, VLS would be expected to occur immediately after dosing. As you know, for all those looking, patients are brought to the hospital, and in fact, to the intensive care unit to get administration of recombinant human high-dose IL-2. We have observed patients well through multiple cycles of therapy, as you heard during the presentation, some patients staying on treatment for well over a year. Specifically at the highest dose level, we are now past cycle four or five of treatment, and again, this is well beyond the window to expect vascular leak syndrome. Yeah, I would agree. Usually, you would see that early on, and we just haven't seen anything like that. I think the main thing we're seeing are these fever and chills, and that's consistent with immune activation. And as mentioned, it seems to be also a very brief duration and responsive to, you know, premedication. Great, thanks for taking our questions. Thank you. The next question comes from Marc Frahm at Cowen. Hey, thanks for taking my questions. Maybe following up on Mike's question about kind of the, those higher dose levels. In the safety table, I think you break down the safety by 1.4 mg. Can you maybe speak to the rates of AEs you are seeing at maybe at the 2.84, where, you know, the PD data is really showing you're, you're really moving up the, the potential efficacy curve? Yeah. Thanks for your question, and good morning. So we have limited data at the higher doses yet, but Katarina can speak to what... the safety profile, what does it look like so far, and what are we seeing there? Thank you. Overall, we obviously did look at this, and the safety profile is very comparable. Perhaps a slight increase in the incidence of fevers and chills, however, no change in terms of their severity. They are primarily low-grade events. And even at the higher dose level, not every patient would experience this. I would also say the lymphopenia that's been reported is also consistent with the normal mechanism of IL-2. So we actually think that what happens is IL-2 induces recruitment of these lymphocytes to the tumor, so that you do see this transient decrease in the peripheral blood, and there's often a rebound later after stopping the IL-2. Great, that, that's very helpful. Then maybe just looking a little more forward-looking, can you talk about kind of recent enrollment pace, particularly, you know, as you are starting to show these kind of improvements on the PD side? And therefore, the kind of level of confidence you have that you can get these 20 patients enrolled quickly, on the 4 mg dose. Yep. Thanks, Mark. Yeah, I would say we do have increased interest from investigators in the trial now that they're seeing the data, and even as recently as our SITC poster on Friday, I think a lot of interest. So I'll turn it over to Katarina to talk about that in more detail. Thank you. I would say that, as we started to see our pharmacodynamic data, you could see the fast pace of enrollment. As you know, we have enrolled 62 patients overall to date, and most of that is coming in the last few months. And now, obviously, that we have declared a second dose in phase II at SITC. I have been approached by our investigators already about, "These are the patients I have, you know, can you, can you make sure that we can get them on? Thank you. Okay, great. Thank you. Thank you. The next question comes from Paul Jeng at Guggenheim. ... Hi, yeah, this is Paul Jeng from Guggenheim, from Michael Schmidt's team. So thanks for taking our question and hosting the event today. So yeah, maybe just a quick one on XTX202. You know, what is your confidence level that sort of the dose response to disease control you observed at lower doses will translate to the clinical responses at 4 mg/kg, as opposed to perhaps, you know, very extensive stable disease? And then for the 20 patients at the 4 mg/kg dose, is your bar still in the sort of 10%-15% response range, or is, you know, maybe one good response and high levels of disease control also sort of a favorable outcome from a go/no-go perspective on monotherapy? Hey, Paul, good morning. Thanks for your question. So I think your question is, you know, this DCR, the dose-dependent DCR we're seeing primarily in the phase I, how do we think that will translate now in a phase II population? I think it's important to point out a couple things. Our phase I, we chose to go after all comers, so we had heavily pretreated diverse tumor types, including a lot of cold tumors. We did still see this dose-dependent disease control rate, which we think is encouraging. Second, we are seeing the durability that you mentioned. So the DCR rate we observed included, you know, several patients that had very long-term stable disease, even with cold tumors, like the MSS CRC patient, stable for over a year with a resolution of three of four non-target lesions, without treatment-related AEs, which is a good sign. And third, I think the beta gamma design, what we're seeing, it's consistently demonstrating the CD8 and NK activation in the tumor peripheral blood, but without Treg stimulation. And we think this is important ultimately, you know, for long-term sort of prediction of response, right? As Treg activation can inhibit the antitumor activity, and we'd worry about that, you know, in combination with PD-1, that can inhibit the combination. So we're very happy with the profile and seeing that Treg levels stay low. I would mention also, for now, given the tolerability we're seeing at these high doses and the tumor bioanalytical data, right, that demonstrated we see sufficient activation in the tumor at 2.8 mg/kg. This all kind of leads us to believe that the plan is Study 202 at 4 mg/kg in an IO-sensitive population. phase II population will be the right next step to determine that monotherapy response rate in renal, melanoma. So we would, we would expect that, you know, to be sort of the right next step to answer the question. And then in terms of what, you know, what's the bar for 20 patients in melanoma and renal? You know, historically, we've all sort of been anchoring on aldesleukin data. You know, something around a 15% response rate in monotherapy. But I think it's important to point out, right? That isn't a population that had better ECOG scores, and that response rate was in patients who did not see prior IO. That said, I think that is still the bar we'd like to hold ourselves to for monotherapy for this agent, again, at this high dose of 4 mg/ kg. So long answer, but I think we're on the right track, and I think the data's pointing us, you know, now with the intratumoral PK pointing us to 4 mg/ kg as the right dose. This is my personal comment as a physician, and I say this from the cutaneous malignancy perspective. You know, we're using checkpoint blockade now more in neoadjuvant and adjuvant setting, and it's actually creating a new patient population with Stage IV disease that have already seen checkpoint blockade. And so we really need new therapeutics here. And so I think if we had an agent like this that could get us a 15%-20% response rate, I think that would be extremely valuable. And, you know, I think we're gonna be seeing this across tumors, but it's certainly melanoma's taken the lead in this, where a lot of these Stage IV patients now, you know, really need some therapy that's not checkpoint blockade. Great. Thank you. And then maybe just, one on XTX101. You mentioned sort of enriching for colorectal cancer during the phase I dose escalation. Is there a target minimum number that you're hoping to reach in that basket of solid tumors? And is there any chance we can see some early phase I data for those patients, next year as you reach the RP2D? Thank you. Yeah. Thank you. Yeah, I think what's what we're seeing, and Katarina can speak to this more, right? There is just a natural interest of investigators and, frankly, patients MSS CRC to now begin to seek out our trials. We saw this even toward the end of the phase I, given some of the data with Fc-enhanced molecules MSS CRC. so we will be looking to enrich. We don't have a target number of patients in mind. I think we wanna move quickly through the dose escalation. But we will be looking, you know, at the totality of the data as we make the decision to move into the phase II. I don't know if you wanna add anything to that. I would just add that while we don't have a predetermined number of patients with colorectal in this dose-finding study, I am very confident that there's going to be a natural enrichment based on where the field is now, and we have already seen it in monotherapy. Thanks, Katarina. Great. Thank you so much. All right, and the last verbal question will come from Laura Prendergast at Raymond James. Yes, thanks for taking today and taking my questions. I'm just curious, piggybacking off that last question, do you guys have an internal bar set for what you wanna show in colorectal cancer? You know, or are you just, you know, trying to beat previous, what previous studies have shown? Which, you know, really isn't much response on the response side. But if you could just provide any extra color, that would be much appreciated. Thank you. Sure. Thanks for your question. So I think it's important to point out there's essentially two different patient populations we'll be studying in MSS CRC, phase II program, with the combo. We'll be looking at patients without liver metastases, for which we know there is prior, data with another Fc-enhanced anti-CTLA-4 that's systemically active in combination with PD-1, where we saw over a 20% response rate, which is really meaningful, right? Given what we've seen historically with IO is 0%-5%. So I think in patients without liver metastases, you know, that would be, what we would be aiming to see as well. But also with the tumor selective activation, we're hoping that we can see that with a safety profile that's aligned with what we saw in phase I. In terms of patients with liver metastases, these patients are often excluded from these trials MSS CRC. we don't know what the right bar might be there for efficacy, but I think any meaningful efficacy, especially with a well-tolerated regimen, will be meaningful, and that's something we would certainly continue to talk to regulators about as we develop that data. So I would think about those two data sets sort of distinctly, patients with and without liver mets. Thank you. Thanks. Thank you. I'll now hand the call back to Stacey for any additional questions that may have come through the web. Thank you, Sarah. We have one question in the chat right now, which I would direct to Uli. This is a question about the pharmacokinetics for XTX202. Could you talk a little bit about what we're seeing for this molecule as far as PK? Yeah. Thank you, Stacey. I think what we've seen in terms of PK is very consistent, that XTX101 ultimately is a monoclonal antibody. And so what we have seen at the Q six weeks is consistent with that. It's question 202, Uli. Sorry. I'm sorry. On XTX202. So XTX202, you can think of really as an Fc fusion protein, since it retains the half-life extension domain, both in its masked state as well as in the active state. So what we've seen there is, very much antibody-like behavior. We've seen a prolonged half-life in circulation. We've seen dose consistent with dosing. We have seen changes in the overall exposure. And then, as we've shown today, we're also able to measure the actual concentration of active XTX2 in tumors, and the concentration that we're able to achieve is consistent with activation of CD8 and NK. So I would say overall, we've been very encouraged by the pharmacokinetic profile of XTX202. I would just add, it's consistent, it supports the Q three-week dosing regimen that we have in place, and that's working well. Great. And then changing gears back to XTX101. Very encouraging profile that we shared on the lung cancer patient with resolution of liver metastases. Could you talk a little bit about why we would believe that it's plausible the activity we saw in lung liver metastases could translate MSS CRC patients with liver metastases? Yeah, great question. I'll kick us off, and then Uli can add. I think this is something that's been interesting to us overall with the platform, is how we're seeing this opportunity to help patients with liver mets translate, you know, from these tumor-activated molecules. What we believe is happening is based on the fact that liver mets tend to be highly proteolytic and have quite a lot of MMP activity. We believe this could be leading to getting really good tumor activation in liver mets. We saw that specifically and measured that in our XTX101 trial, in that tumor biopsy of a patient MSS CRC from a liver metastases, where we saw over 70% of the drug activated. But also I think the fact that liver mets are high in Treg is important component. I'll ask Uli to talk about how MSS CRC liver mets sort of compare to what we saw in this lung patient with liver mets, and can we make that leap of translation? Yeah, I think, I think there are a couple of reasons to believe that is the case. I mean, for one, we and others have shown that when you just look at gene expression and you begin to cluster just in an unbiased manner, there are clearly, features, molecular features, meaning gene expression patterns, that are shared between lung and CRC patients, meaning patients that have liver metastases with a primary in the lung or a primary in the colon. So there are features that are similar, and I think the other reasons to believe, in my mind, are what you highlighted: high MMP activity, as well as, the liver being a uniquely immune-suppressive environment that has high levels of myeloid-derived suppressor cells, as well as regulatory T cells. I think that combines quite well with the mechanism of XTX101, what we have built into the molecule. Great. Last question coming in through the chat is going back to XTX202. We've obviously spent a lot of time talking about the monotherapy data for 202 and how encouraging the dose response is there. This question is around combinations and the places that it might be possible that XTX202 could drive synergy with other mechanisms of action via combination. So maybe that's a question for Uli, and maybe Dr. Kaufman has a perspective on that as well. ... Thanks, Stacey. I'll just start off by saying I think the most important thing that we're excited to see that really drives the opportunity in combinations with this agent is the tolerability profile. The fact that we're seeing really differentiated tolerability at high doses in the outpatient setting for long-term use, I think is really encouraging generally for combinations. And that was sort of the key and the hope, right? That we set out with in designing a tumor-activated molecule. In terms of mechanistically, which combinations make most sense, maybe Uli, you kick us off. Yeah. I mean, one thought that I had on this, and I wanted to share is, you know, despite the fact that it's been challenging, you'd argue, to develop therapies for that harness the IL-2 mechanism, nothing has changed in the fact that the IL-2 biology is central to T, T cell biology. So to us, that actually highlights the broad potential for XTX202, because I think we're beginning to see that we're getting the biology, but importantly, with an acceptable safety profile. And that biology is ultimately what we wanna harness. We want to ensure that the T cells have the right level of fitness, that they're activated, that they're expanding, and that kind of feature is something that you would wanna combine broadly across immunotherapies. So that includes checkpoint therapies. I would argue it could include ADCC antibodies, but importantly, also cell engagers and cell therapies. So there's a broad potential. I'll also note, even preclinically, we've done some work that is supportive of this. And we have previously shown combination of XTX202, showing enhanced activity in combination with PD-1. But we've also done preclinical work that gives us confidence that this agent could be combined with cell engagers. And I think that's an exciting area, because clearly getting cytokine support on top of that, but in a tolerated manner, could be highly beneficial for patients. I agree with everything that's been said. IL-2 is key to getting these cells to proliferate, but they also, you know, induce NK cell proliferation. So I think the other thing to think about would be maybe combinations with cell therapies and NK cell therapy, which hasn't been that good in solid tumors, where this kind of approach might be really helpful. But I'm holding out for monotherapy activity. Thank you. That's everything coming in through the chat. Excellent. Thank you, Stacey. That concludes our call for today. Thank you all for your time and attention. And now we'll close the line.