Good morning, and thank you for joining Xilio's Investor Conference call. At this time, all participants are in a listen-only mode. Following the management's remarks, we will hold a question-and-answer session. At that time, lines will open for you. If anyone should require operator assistance, please press star, then zero on your touch-tone telephone. I would like to now turn the call over to Scott Young, VP of Investor Relations from Xilio Therapeutics. Please go ahead, Scott. Thank you. Good morning. Welcome to the Xilio Therapeutics Investor Conference call. Today, we will review initial phase 2 data for vilastobart, also known as XTX-101, in combination with atezolizumab in patients with metastatic microsatellite stable colorectal cancer, or MSS-CRC. These data will be presented in a poster session at ASCO GI on Saturday, January 25th, 2025. Before we get started, I'd like to remind everyone that today's conference call will include forward-looking statements. Actual events or results could differ materially as a result of various risks and uncertainties. Please see the risk factor section of our current SEC filings, including our most recent Form 10-Q. 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. Following the completion of this call, a replay will be available on our Investor Relations website, which can be found at ir.xilio-tx.com. This morning, we are joined by Dr. Marwan Faqih from City of Hope, where he serves as a professor in the Department of Medical Oncology and Therapeutics Research and is the division head for GI Medical Oncology. Dr. Faqih is a principal investigator in our ongoing phase 2 trial of vilastobart and atezolizumab in MSS-CRC, and he's a renowned oncologist who has led numerous clinical trials, many of which focus on immunotherapy treatments for advanced colorectal cancer. From the Xilio leadership team, I am joined by Dr. René Russo, our President and Chief Executive Officer, and Dr. Katarina Luptakova, our Chief Medical Officer. In addition, Uli Bialucha, our Chief Scientific Officer, and Chris Frankenfield, our Chief Financial and Operating Officer, will both be available for the Q&A portion of the call. During today's presentation, René will provide a brief overview of Xilio's platform technology and pipeline progress, as well as the significant unmet need in colon cancer. Katarina will review the promising initial phase 2 clinical data for vilastobart in combination with atezolizumab in patients with metastatic MSS-CRC, and Dr. Faqih will share his clinical perspectives on these data and the important contribution of vilastobart to this combination. With that, I'm pleased to turn the call over to René. Thank you, Scott, and thank you all for joining us this morning. At Xilio, we've built a robust pipeline of tumor-activated immunotherapies. Our technology leverages dysregulated proteases in solid tumors to create molecules designed for tumor selective activation. Our molecules are designed each with its own unique components that are optimized for the specific target. Our platform has been successfully applied in a clinic with over 200 patients treated to date across diverse molecular structures and is now being applied to more complex, multi-specific molecules, including cell engagers. The focus of our call today is vilastobart, or XTX-101, our tumor-activated Fc-enhanced anti-CTLA-4, currently advancing in an ongoing phase 2 clinical trial in combination with atezolizumab in patients with microsatellite stable colorectal cancer, or MSS-CRC. This trial is part of a co-funded clinical collaboration with Roche. We have a number of additional programs advancing in development, including XTX-301, our tumor-activated IL-12, which is in a partnership with Gilead, XTX-501, our masked bispecific PD-1/IL-2, currently an IND-enabling, and multiple tumor-activated cell engagers, which we plan to unveil in more detail later this quarter. We'll now turn to vilastobart, our tumor-activated high-affinity binding Fc-enhanced anti-CTLA-4 antibody. vilastobart is tenfold more potent than ipilimumab and incorporates Fc mutations for enhanced effector function and Treg depletion. Consistent with its tumor-activated design, vilastobart has been shown to be over 70% activated in tumor biopsies from patients with less than 15% of the active molecule in peripheral circulation. In the clinic, vilastobart was well tolerated in phase 1 with a differentiated safety profile, including with long-term administration up to 18 months in the monotherapy trial. Vilastobart demonstrated monotherapy activity in phase 1, including a deep and durable PR in a PD-L1 negative non-small cell lung cancer patient with a complete resolution of multiple liver metastases, which are often resistant to immunotherapies, and finally, vilastobart has demonstrated activity in the combination setting, including partial responses in two patients with immunologically cold tumors in phase 1c, including MSS-CRC with liver metastasis and ampullary carcinoma, a difficult-to-treat pancreatic-like cold tumor. Vilastobart is currently being studied in MSS-CRC, an urgent area for clinical development given the significant and growing unmet need. Unlike many other cancers that are on the decline, the incidence of colon cancer is increasing, particularly in young people. Overall, colon cancer now ranks as the second leading cause of cancer-related death in the U.S. and ranks third in annual new cases worldwide, with approximately 900,000 deaths globally. Colon cancer is often asymptomatic and can go undetected, especially in younger patients who are not routinely screened. As a result, colon cancer is often diagnosed in late-stage, such as Stage 4, depicted here on the right. 95% of these late-stage colon cancers are defined as microsatellite stable, or MSS, which is historically resistant to treatment with immunotherapy, even in the combination setting. This is the population we're studying in our phase 2 trial. Despite the growing incidence, the treatment options remain limited. For those with advanced disease, the standard of care is currently chemotherapy, sometimes combined with TKIs. Patients who progress often then move to clinical trials or other late-line therapies, with overall survival typically ranging from just six to nine months. Approved immunotherapy agents to date have demonstrated no meaningful efficacy in MSS-CRC, with objective response rates of only 0-3%, even in IO combinations. I'll pause here for a moment and invite Dr. Faqih to please add any additional comments on the challenges of treating patients with MSS-CRC. Yeah, thank you. No, I listen, this is an unmet need. There's no question. I think with metastatic colorectal cancer, we aim for cure with resections. And unfortunately, the majority of patients with metastatic disease have inoperable cancer because the cancer has spread in a pattern that does not allow a curative outcome with surgery. And those still represent probably approximately 90% of the, you know, 80%-90% of the metastatic colorectal cancer patients are not curable surgically. And in that situation, we have two very effective lines of therapy, but even then, the median PFS, progression-free survival in the first line setting, is nine months. In the second line setting, it's about six months. And then you've got third-line therapy where we've made some progress with trifluridine bevacizumab, but even in that setting, the median PFS is four and a half months if the patient had prior bevacizumab, and if they didn't, then it's about six months. So the problem is resistance happens. And I think, you know, the challenges have been that when we look at pembrolizumab, Keytruda as monotherapy, it doesn't work. When we look at randomized phase 3 trials with atezolizumab in the setting of a MEK inhibitor, cobimetinib, with the IMblaze trial, there was no activity, which is actually of relevance to this particular trial because we know atezolizumab has been tested in MSS-CRC, and it has no significant activity. And same applies with nivolumab, ipilimumab. There's no published data that is CTLA4 PD-1 that from the older generation, from the approved CTLA4s, has substantial activity in CRC. And we know that data from tremelimumab, durvalumab, as well, has been negative. So it's important to develop, I think, immunotherapies in this area, but what we really are looking at and hoping to see is that we crack that resistance to immunotherapy and we result in meaningful and durable benefits for our patients because right now, the options of improving survival in third-line setting of by two to four months compared to control is simply not adequate. And we're not saying it's not important. Every month matters, but it's nowhere where we should be. Yeah, totally agree. Thank you, Dr. Faqih. I'll now turn it over to Katarina to walk you through the initial phase 2 data that we will be presenting this week at ASCO GI. Thank you, René. As you've heard from Dr. Faqih, MSS-CRC is an area of very high unmet medical need. Further, this is a tumor type that has not been responsive to treatment with PD-L1 agents alone, and we therefore believe our phase 2 data in this disease setting will enable us to clearly establish the initial proof of concept for vilastobart activity. I'd like to briefly introduce the patient population enrolled in this phase 2 study. As of the data cutoff date, 40 patients with metastatic MSS-CRC had been enrolled at sites in the U.S. only. Patients were treated with a combination of vilastobart at a dose of 100 milligrams once every six weeks and atezolizumab at 1,200 milligrams once every three weeks. Patients in the trial included patients both with and without liver metastases. It is worth noting that patients in phase 2 have been heavily pretreated, with more than 70% of patients having received three or more lines of chemotherapy. 23 patients are still ongoing on treatment, including all of the responding patients. Of the patients who have discontinued treatment, only three patients did so due to adverse events. As a reminder, our goal for the phase 2 POC study was to see at least a 15% response rate in patients without liver metastases. And given the lack of any efficacy for IO agents in patients with liver metastases historically, any evidence of activity in patients with liver metastases would be meaningful. As of the data cutoff date, 18 patients had at least one imaging scan reported and were evaluable for response assessment for RECIST 1.1. Of these response-evaluable patients, 11 patients did not have liver metastases, and seven patients had liver metastases. There were 13 additional patients who were ongoing, but because they enrolled relatively recently, they had not yet had their first imaging scan. In patients without liver metastases, we were pleased to see three partial responses, including two confirmed responses and one response pending confirmation for a preliminary overall response rate of 27%. I will review each of these patients in detail momentarily. Additionally, I do want to highlight a fourth patient without liver metastases but with a peritoneal lesion. This patient had a 24% decrease in their target lesions assessed as their first on-treatment scan at nine weeks. Similar to the patients with partial responses you will hear about, the tumor reduction for this patient was accompanied by a decrease of the serum tumor marker CEA, or carcinoembryonic antigen, to normal values. This patient is ongoing on treatment, and we look forward to further follow-up. Moving to the waterfall plot, here, patients with liver metastases are shown in orange, and the patients without liver metastases are shown in yellow. The patients noted by a green dot remain on treatment, including all of the patients with meaningful tumor reductions. We are very encouraged by the depth of these three partial responses, as well as the fourth patient that you can see here with a 24% tumor reduction. As you can see on the spider plot, observed partial responses have continued to deepen over time, including the patient with a partial response that deepened to 57% reduction at 18 weeks. Generally, tumor reductions have been rapid and observed at the time of first response assessment at nine weeks. I'd also like to briefly touch on some patients with liver metastases and stable disease or mixed response. Here you see one patient marked with an asterisk and stable disease through 13 weeks. I will review circulating tumor DNA, or ctDNA data, for all patients shortly, but what was interesting is this patient's ctDNA increased initially and now appears to be decreasing. In addition, a separate patient with multiple liver metastases has shown decreasing levels of the serum tumor markers, including CEA. We look forward to continuing to evaluate these patients as ctDNA and serum tumor markers' decreases have been generally heralding tumor regressions for patients in this study. Now, I'd like to share additional details on the three patients who experienced partial responses, all of whom are currently continuing on treatment. Patient A is a 50-year-old male with four prior lines of therapy. He experienced a partial response, now confirmed, with a 47% decrease in target lesions at 13 weeks, which was accompanied by a meaningful decrease in CEA, a multi-log fold decrease in levels of ctDNA, and improvement of symptoms such as cough. Patient B is a 69-year-old female with two prior lines of therapy. As you can see in these images, the reduction in the tumor lesions was obvious even at nine weeks, where the initial 37% reduction was observed. The response has continued to deepen to 57% at 18 weeks. Not only was this patient's partial response accompanied by a 100% reduction in ctDNA to non-detectable levels, but as you can see in the table, the CEA levels were significantly elevated at screening and rapidly decreased and now remain low at normal levels. Patient C is Dr. Faqih's patient, so I would let him speak more about this patient in a minute. Notably, this patient with six prior lines of therapy had a preliminary 35% tumor reduction, which is pending confirmation, as well as decreases in ctDNA and CEA levels. Dr. Faqih, I'll now hand it over to you to describe this patient. Yes, thank you. This is a 67-year-old female, and she has RAS wild type, BRAF wild type metastatic colorectal cancer, and as you can see, had received multiple lines of therapy. Her disease is refractory to combination chemotherapy, had progressed following 5-FU, oxaliplatin, irinotecan, bevacizumab, and an anti-EGFR agent, namely panitumumab. When she presented to us, she was somewhat symptomatic with cough and shortness of breath on exertion. I think what's interesting about this particular case is that the patient had a relatively high burden of disease, you know, which speaks to the fact that immunotherapy, particularly with the combination discussed here with XTX-101 and atezolizumab, can be associated with benefits even in patients with bulky disease. This patient had, you know, well over 20 lesions in the lungs, you know, some pleural effusion on the right chest, on the right lung, and presented for this particular trial. And I think what is also notable is that with immunotherapy, sometimes you can see an early immune activation that can sometimes lead to a tumor flare. And indeed, in this patient, at approximately three weeks after we started therapy, she had an increase in cough and some slight increase in her shortness of breath, which led to earlier imaging. And what we had seen at almost three weeks of therapy is that increased haziness around the tumors and notably some increase as well, you know, suggesting that, you know, that there is some immune infiltration in the tumors. Now, of course, you can never be able to tell at that point, is it 100% a pseudoprogression with infiltration with immune cells versus progression, but, you know, that was our impression, and we continued with therapy, and sure enough, by the two-month marker, symptoms resolved. She was no longer short of breath. Her cough reduced substantially, and her two-month mark imaging studies showed a, you know, dramatic response compared to the three-week CT scan and compared to baseline. What you're seeing is the baseline on her slides, and so there was no question there was not just a radiographic benefit in this case, but a very early clinical response in this patient with amelioration of symptoms related to metastatic disease. Her tumor burden is low, and so this is, you know, there's no particular biomarker here that we can say that, you know, predisposed this patient to response, with the exception that maybe, you know, we know that non-liver mets are a little bit more responsive than liver mets, but that's the story behind this patient. And she continues on treatment, doing remarkably well, no significant side effects whatsoever. Thank you, Dr. Faqih. We appreciate having your insights on this patient. I'll now turn it back to Katarina to review some of the biomarker data and safety data for the trial. Thank you, René. Here you can see the ctDNA that we highlighted for each of the patients' vignettes. In particular, each of the patients with partial responses is noted by the orange circle, and you see all of these patients experience a rapid and significant decreases in ctDNA of at least 50% or even to undetectable levels. You may recall I mentioned a patient with liver lesions who had stable disease. This is the patient in black whose ctDNA initially increased and then is seen decreasing. We believe it is possible that responses in patients with liver metastases may take longer, and we will certainly continue to watch this closely. Consistent with the phase 1 safety data we reported previously, and in line with the tumor selective design, we continue to see a differentiated safety and tolerability profile for the combination. Notably, only six patients experienced grade three or four treatment-related adverse events. Of these, only two patients experienced grade four treatment-related AEs, both of which were lab abnormalities, with one instance of thrombocytopenia and one instance of neutropenia. There were no grade five treatment-related AEs. Importantly, no patients needed a dose reduction for vilastobart, and only three patients discontinued treatment due to treatment-related AEs. In addition, the combination continued to demonstrate a meaningfully differentiated profile with respect to immune-related adverse events, or IRAEs, most of which were low-grade. Specifically, as of the data cutoff date, minimal endocrine IRAEs were reported with only two patients, or 5%, and limited skin IRAEs with only five patients, or 13%. To help put this in context, the observed incidence of endocrine and skin IRAEs was consistent with what was reported for atezolizumab alone. In addition, only two patients, or 5%, experienced grade three colitis, which is considerably lower incidence compared to what was reported with systemically active anti-CTLA-4. We believe this differentiated safety profile continues to highlight the potential for vilastobart as a next-generation anti-CTLA-4, particularly in light of the initial clinical activity data observed to date on this study. I'll now turn the call over to Dr. Faqih to provide his clinical perspective on these data and his experience to date as an investigator in the phase 2 study. Thank you, Katarina. I think what you see here is a proof of principle of the activity of CTLA-4 targeting, especially with, you know, masked CTLA-4, Fc fragment-enhanced CTLA-4 inhibition, and I think, you know, the field here is moving, and it's thankfully moving quickly, and thankfully for our patients. We have seen now, you know, multiple presentations recently about activity with the more novel CTLA-4s. And what we understand and see is that the more active our CTLA-4s are in depleting Tregs and activating T cells, the more likelihood it is that we are going to be able to turn cold tumors into, you know, responding tumors. I think we're understanding the field better in that, yes, you know, it is time to start thinking about classifying metastatic colorectal cancer based on site of metastatic disease, not just based on molecular characteristics and the location of the primary tumor. I think there's still what we're seeing today is that, yes, non-liver metastases patients can respond extremely well, and what we hope to see is that those responses are durable. I mean, what we've seen with other combination therapies, such as botensolimab, balstilimab, with more mature data published in Nature Medicine, is that some of these responses can be extremely durable for patients, which is really what our patients deserve and are looking for. I think what would be interesting as we move the field forward is to combine, you know, that ability to activate these immune cells in the tumors, lead to responses, and be able to, you know, afford these patients as much as possible minimal toxicities. I think that's where, you know, some of the research that you have seen today is really trying to focus. Can we make these CTLA-4 antibodies more active within the tumor, limit systemic exposure, and can this result in durable responses, and can this also be associated with favorable toxicities? I think the data that we've seen today is extremely intriguing and extremely exciting, and we hope to continue to see those responses deepen and be maintained. In general, what we see with immunotherapy is that if you do have a response, even in MSS patients, that those patients who do respond have a very high chance of having a durable response. And I think the ability to maintain the immune activation in this setting and maintaining, you know, the CTLA-4 inhibition will be hopefully helpful and a key in driving deeper responses. So I'm looking forward to continue to work with this combination, and I'm looking also forward to see the data mature, but there's no question there is a very strong signal here, and I think it's time to say that, yes, immunotherapy can work very well for MSS, CRC, and have these options for our patients. Thank you, Dr. Faqih, for sharing your clinical perspectives on the data overall to date, so to summarize, as Katarina mentioned earlier, our goal going into this phase 2 POC trial was to achieve a minimum of a 15% response rate in patients without liver metastases, along with that differentiated safety profile, particularly with regard to immune-related AEs like colitis that are challenging for systemically active anti-CTLA-4s historically. We're very pleased with the initial results reported for vilastobart and atezolizumab today, which really surpassed our expectations, including a preliminary ORR of 27% and a clearly differentiated safety profile. We believe these data highlight the potential for vilastobart as a combination therapy, not only in MSS, CRC, but also a range of other tumor types, including other cold tumors that have been historically resistant to immunotherapies. We look forward to reporting additional data in the middle of 2025, including longer-term follow-up from this ongoing trial. We believe these data really set the foundation for a compelling opportunity for business development, and we plan to explore partnering opportunities to pursue further clinical development beyond this initial Phase 2 POC trial and into additional indications. With that, we'll now open the line for questions for members of the management team and to Dr. Faqih. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. And one moment for our first question. Our first question will be coming from Michael Ulz of Morgan Stanley. Your line is open. Good morning, and thanks for taking the question. Maybe just one on the subset of patients with liver mets. You know, it looks like you didn't see any responses there, but I believe in the past you had seen a response in those types of patients with a combo. So just curious your thoughts around that, and is this a situation where longer-term treatment maybe starts to translate into some responses, or do you think you really maybe have to go up on a dose here? Thanks. Yeah. Yeah, thanks, Mike, for the question. It's clear, right, that the patients with liver metastases are more challenging and also where there's tremendous unmet need. So we're going to continue to watch these data closely. As you point out, we have seen activity in liver mets in the past, both in the monotherapy setting in a non-small cell lung cancer patient that had innumerable liver mets, which were resolved. There was a PD-L1 negative patient, and in the 1c combination dose escalation with atezolizumab in an MSS, CRC patient with liver met that did resolve. So we do think the potential is there. As you also point out, both of those cases were at the 150 milligram dose of XTX-101 or vilastobart, where our phase 2 initial phase 2 dose for this trial has been 100 milligrams q6 weeks for vilastobart. It could be that a higher dose is needed. We also see some signals that it may take longer, where we're looking at things like ctDNA and CEA coming down in some of the liver met patients, but later. I think we're going to watch those patients where the biomarkers are changing closely, and in some cases, there's sort of a mixed response. I think we just need to continue to see the data. We have seven patients, as you know, with a scan, so it's small numbers, but we'll be looking at, you know, duration of therapy and also dose potentially for these patients. Yeah, makes sense. Maybe just a quick follow-up. Obviously, we've seen some data in the CRC today, but it looks promising. You know, how do you think about expanding into other indications? You know, what could that look like? What is the trigger? What are the timeframes? Thanks. Yeah. Yeah, we agree. So in our mind, you know, MSS, CRC is kind of one of the highest bars, right, for immunotherapy. So we believe if you show activity here and you can maintain a tolerability profile like we're seeing, that that really opens up many opportunities for additional indications and also different combinations given the safety profile. One in particular that we have been thinking a lot about is non-small cell lung cancer, given our activity in the phase 1 monotherapy, but we think there's also opportunity in additional tumor types and cold tumors. So our approach here, based on these data, is to seek a partner because we think the path forward can be pretty broad in terms of indications and combinations, and with the right partner, we can do that in an accelerated way. Great. Thank you. One moment for our next question. Our next question will be coming from Mark Frahm of TD Cowen. Your line is open, Mark. Hi, thanks for taking my questions and congrats on the data. I think if I'm doing my math correctly, there's nine patients who discontinued without a scan and therefore were unavailable. One, if you can confirm that, but then also, can you give the breakdown of those patients who had liver mets versus who did not, just trying to track patients for more of like a housekeeping perspective? And then maybe following on the last, I'll have a question after that. You, if you guys want to answer that one first. Okay. Okay. Yeah. So I would just sort of preview by saying the data are evolving in real time. And so there are eight patients that discontinued without a scan, but we're going to continue to follow up to try to get those scans. So hopefully this changes over time and we have more information. Of those eight patients, five are in the non-liver mets category and three are in the liver mets category. So if you put all five in the non-liver mets into the denominator in the most conservative assessment and assume there were failures, that still gives us a 19% response rate, which is, you know, above our target of 15%. So regardless, I think we're in a good place, but we'll continue to look to get follow-up scans on those patients. Okay. That's very helpful. And yes, and it's still impressive data. As I said, even if you kind of kitchen sink it. Maybe just following on that last question, though, just correct, it sounds like you're interested pretty broadly, but you're going to kind of leave it to a partner, you know, to your partnership discussions to help guide exactly which indications to pursue next, or do you plan on getting that ball rolling yourself kind of in advance of a partner? Yeah, I think our plan in the near term is really to allow the full 40 patients in this dataset to evolve and to have ideally two scans on everyone that's available, which we plan to report around mid-year. And I think with that dataset, that's going to tell us a lot more about the directions to go in. But I think in all scenarios here, because we see such potential, such broad indication applications for this molecule and combinations, that we will seek that partner with that strongest data package in hand, you know, that's really fully matured around mid-year. So we look forward to seeing how this data matures. But yeah, I would say generally the partnership, we are open to how to bring this molecule forward into which indications first and which combinations, depending on the partner. Okay. Thank you. Congrats again. Yeah. And one moment for our next question. And our next question will be coming from Laura Prendergast of Raymond James. Your line is open, Laura. Hey, guys. Thanks for taking the questions. You know, just curious regarding path forward, you know, in light of this early data cut, how do you guys think about the potential for an accelerated approval, you know, especially given Genentech not having given the path there? You know, do you guys have any sense of what the FDA's bar might be on ORR? Yeah, thanks, Laura. I think it's, you know, premature for us to comment on that because we have not yet engaged the FDA with this dataset. But I would certainly say we're thinking hard about that. If we continue to see a response rate like we're seeing here, we, you know, certainly expect to have conversations with the FDA with this full dataset in hand and to do everything we can to pursue accelerated approval if it's an option, particularly given the unmet need in these patients and the tolerability profile. Looks like the risk-benefit may be there for this molecule. That said, I think we also recognize that historically the FDA has not given accelerated approval for this indication. So in our mind, you know, we're always planning for, you know, a randomized controlled phase 3 trial with OS as the endpoint, and that's kind of our baseline assumption. But certainly we're thinking hard about that as we look at these data, and we expect to talk to the FDA once we have this complete data package more mature through full scans, second scans on all available patients. Thanks. And then one quick follow-up. I noticed on the swim plot that there were a couple of patients with progressive disease who were still ongoing on therapy. Can you comment on those patients? Yeah, so this, it's interesting. This happens often, I think, in our trials when patients are clinically doing well and the molecule's well tolerated and they may be having some clinical benefit that often we will have investigators request to keep patients on therapy despite either progressive disease or mixed response. We're also keeping in mind what you heard from Dr. Faqih, that there may be incidents of pseudo progression, so you get that initial inflammation of tumor early on with an early scan that then, if they continue to dose through, may actually prove to be immune infiltration leading to a response later on, so we tend to allow patients to stay on trial at the investigator request, especially if they're having, you know, a good tolerability profile with the molecule, so we'll be watching those closely as well. Great. Thank you. Thank you. One moment for our next question. And our next question will be coming from Daina Graybosch of Leerink Partners. Your line is open. Hi, guys. Thanks for the question. I'd say we posit that in this setting, in this combination, you have about a 15%-25% response rate if you were to add more patients. For me, that's sort of right on the border of potentially being able to translate into overall survival benefit versus the standard of care, of course, the durability being important. But I wonder how you've thought about optimizing this and the path forward to optimizing sort of increase your probability of success. I'm interested in the company and in your KOL's opinion both on is there a potential to move to earlier lines and different combinations? And if you could talk more about what you can do in terms of getting more dose on board, whether it's ramp up dosing or any practical steps you're going to take there in your term. Thank you. Yeah. Thank you, Daina. Appreciate the questions. So I think you hit the nail on the head, right? We are treating very late-line patients here, particularly Dr. Faqih's patient where this is a seventh-line therapy. So what we're excited about is the tolerability profile. Look, it's early, but we think it may support earlier line use, right, and the risk-benefit again being there. And certainly we think in earlier lines of therapy, you're going to be able to improve response rate and OS. And I think that is certainly where our head is at, but of course it's early. So I think we agree with you on that. And let me just open that up to Dr. Faqih to weigh in as well. Yeah. I think we shouldn't be looking at these as medians in general, but as a hazard ratio improvement. And to me, as a clinician who sees patients with advanced disease, with metastatic disease every day, who have failed therapy, a 20% chance or a 15% chance or 25% chance of being without progression at a year and a half, two years down the road is extremely, extremely meaningful. And that's really what we are striving to look for in combination immunotherapy now. And so the key is going to be in later lines of therapy, treating the right population and patient selection. So I'm sure as the data matures from this combination that we will be, we should be interrogating, you know, additional biomarkers, whether they're clinical biomarkers or additional tumor biomarkers. But I do agree 100% that, you know, there may be a role for immunotherapy in earlier lines of treatment, and there may be a role for immunotherapy in MSS, CRC, even in earlier stages of disease. So, you know, and there it's important to start thinking about, hey, if we're going to be using a strategy that reduces recurrence by 5%-10%, you know, what are the risk-benefits of such strategy, right? So if you're looking at adjuvant strategies in the future, you know, what combination you want to use and what are the side effects, how long you're going to use it. And obviously you want to see earlier signs of improvement in metastatic disease. Combining such agents with systemic therapy will be extremely important in the development because arguably you may enhance the response better and arguably you may actually drive a higher, you know, likelihood of potentially having a CR in some patients and stopping therapy altogether. But, you know, again, all of these are important research questions, and I think we need to wait for the data to mature to guide us further. Yeah. Thank you, Dr. Faqih. And Daina, to your second question about ramp up dosing and how we think about that, I'll just mention we are continuing to assess the 150 milligram vilastobart dose in combination with the atezolizumab in the phase 1c. If we clear that dose, it's certainly an option to bring that then into the phase 2. We know historically, primarily from data from tremelimumab, that CTLA-4 tends to be a CMAX-driven, right, mechanism. And so getting potentially that highest dose you can, at least at the initial dose, might be important and might have an impact here. So I think dosing and pushing the dose higher, particularly in the liver met setting, I think is also something we'll be looking closely at. Great. Thank you. Again, as a reminder to ask a question, please press star 11 and wait for your name to be announced. I'm showing no further questions. I would now like to turn the call back to René for closing remarks. Thank you very much, and thank you all again for joining our call today. We look forward to formally presenting these data at ASCO GI later this week. Thank you, Dr. Faqih. Thank you. This concludes today's conference. Thank you for participating. You may now disconnect.