Good morning, and welcome to the Sensei Biotherapeutics investor webcast. At this time, all attendees are in a listen-only mode. A question and answer session will follow the formal presentations. If you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player or by emailing your questions to questions@lifesciadvisors.com. As a reminder, this call is being recorded, and a replay will be made available on the Sensei website following the conclusion of the event. I'd now like to turn the call over to Michael Veiga, Senior Director of Investor Relations at Sensei Biotherapeutics. Please go ahead, Mike. Thanks, Tara. Good morning, everyone. Thank you for joining Sensei Bio's webcast. Today, we'll be discussing clinical data, SNS-101, phase I study that was presented over the weekend at ASCO and defining the plans to maximize the value of SNS-101. Joining today from Sensei are John Celebi, President and CEO, Dr. Ron Weitzman, Chief Medical Officer, and Dr. Edward van der Horst, Chief Scientific Officer. We are also pleased to have Dr. Shiraj Sen join us today. Dr. Sen is a Medical Oncologist and Director of Clinical Research at Next Oncology in Dallas, Texas. Dr. Sen received his undergraduate degree from the University of Texas at Austin, and his MD and PhD degrees from the University of Texas at Houston, and MD Anderson Cancer Center Graduate School of Biomedical Sciences. His postgraduate training in internal medicine was performed at the University of Texas Southwestern Medical Center in Dallas prior to completing his Hematology and Medical Oncology fellowship at the University of Texas MD Anderson Cancer Center. Dr. Sen is board-certified in internal medicine and medical oncology and is a recipient of numerous awards for his research, such as the Waun Ki Hong Award for Achievement in Clinical Investigation, the Mary Ann D. Edwards Fellowship in Hepatic Oncology, and the American Society of Clinical Oncology Conquer Cancer Foundation Merit Award. He has also authored more than 30 peer-reviewed publications, presented his research at over 20 international conferences, and has served as a member of the ASCO Scientific Program Committee. He is an investigator on the ongoing phase I/II trial and lead author of the SNS-101 poster that was presented over the weekend. Sen, thank you for taking the time to join us today. Tara, if you can move to the next slide, please. On this call, we will be making certain forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995. With that, I'd now like to hand it over to our President and CEO, John Celebi. John, please go ahead. Thank you, Mike. It's a pleasure to be with everyone this morning and provide an update on the SNS-101 clinical data that was presented at ASCO over the weekend. On today's call, I'd like to provide some important background information about SNS-101 before handing it over to Doctors Weitzman and Sen to take you through the trailblazing dose escalation study that was presented over the weekend at ASCO. They'll also cover the going-forward plan for the dose expansion portion of the clinical study, which is an important catalyst later this year and has the potential to be transformative for Sensei Bio. Dr. van der Horst will also be available for questions. I'd first like to call your attention to some important background information on the target for SNS-101, which is VISTA. That's on slide three. VISTA has been known to be an important immune checkpoint target for well over a decade. It is a B7 family member, like PD-1, PD-L1, and has an immune suppressive function whose expression increases upon immune checkpoint therapy failure. Unlike PD-1, however, VISTA is expressed primarily on cells of myeloid lineage, where it can be found abundantly throughout the periphery and within tumors, and it has pH-dependent activation as an immune checkpoint. It is these two critical features of VISTA, its expression on myeloid cells and pH-sensitive activation, that highlight the impressive commercial opportunity for this drug, as well as the drug development challenges that previous antibodies encountered. And, Tara, if we could stay on slide 3 for a moment. As an example, let's review the data that was presented by J&J in 2016. Sorry, slide 4. J&J was the first anti-VISTA antibody to enter clinical trials, and it's important to note that it was not a conditionally active antibody. However, its development was halted after treating only a dozen patients due to severe CRS at relatively low doses. Another interesting feature of this molecule was its poor PK profile, which was measured in hours rather than days or weeks. As another example, results presented by Pierre Fabre on W0180, another non-conditionally active antibody at AACR in April of this year, confirmed that CRS is a class effect, and poor PK is a defining feature of VISTA inhibition. It was these two important observations, the CRS and poor PK profile, that informed the design of SNS-101 as a conditionally active antibody and the design of our first-in-human dose escalation study. Scientists at Sensei realized that if we could not bypass the abundant VISTA in the periphery and focus the action on the antibody within the tumor, history would repeat itself. So we sought to identify an antibody that could leverage the inherent pH sensitivity of VISTA, and we identified SNS-101. SNS-101 is a potent binder of VISTA, but only at more acidic pH, which, as you recall, is also when VISTA becomes active as an immune checkpoint. It potently inhibits VISTA's interaction with PSGL-1, which we believe is the key ligand and binding partner for VISTA's checkpoint function, but it also inhibits the interaction of VISTA's other putative binding partners. Co-crystallization studies confirmed the unique epitope that SNS-101 binds to on VISTA. It is this antibody epitope interaction that drives the conditional activation of SNS-101. As you can see from this cartoon, SNS-101 does not bind the abundant VISTA in the periphery at neutral pH. Flow data at neutral pH confirm that SNS-101 does not bind to myeloid cells, such as monocytes and neutrophils, in contrast to non-conditionally active antibodies such as J&J or Pierre Fabre. However, in the tumor, SNS-101 binds VISTA and accumulates rapidly in tumors, as you can see from the immunohistochemistry data in the lower right. To summarize, we believe building conditional activation into the design of SNS-101 was a critical feature to avoid the CRS and PK issues experienced with prior VISTA antibodies. Rapidly de-risking these two features clinically became our top priority as we went into clinical development. As you will hear shortly from Doctors Weitzman and Sen, the data, the data we announced at ASCO over the weekend revealed a well-tolerated safety profile and PK measured in weeks, not hours, thus validating the conditionally active approach as it relates to VISTA. Further, we have observed promising initial signs of activity in patients that typically don't respond to single-agent checkpoint inhibition. Ron, I will now turn it over to you. Thank you. So once again, this is Ron Weitzman. I'm a medical oncologist, Chief Medical Officer, with Sensei, and I apologize in advance for the hacking cough. For anyone who's listened to me over the last month or so, don't worry about me. I'm gonna get better. Next slide, please. Great. So I just have a few slides before I hand it over to Dr. Sen. The purpose of this slide that you're looking at here is to provide you a window into our corporate mindset, our corporate objectives as we design this study, prior to, you know, dosing any patient. Beyond the usual and critical objectives of any first-in-human phase I study, which of course include safety, PK tolerability, and of course, any signs of preliminary clinical activity, it was also paramount, paramount for us to confirm what you just heard from John, which is, does this pH-dependent innovation of SNS-101, is it behaving as advertised? Can we achieve high doses without triggering severe CRS and while achieving, robust, a robust PK profile not affected by the, by the target-mediated drug disposition that we saw with both J&J and Pierre Fabre? As a result, and considering the fact that VISTA is a ubiquitously expressed target in both cold and hot tumors... By cold and hot tumor, what I mean here, are tumors that if they're cold, they do not typically respond to single-agent PD-1 with any kind of a robust objective response rate. Hot tumors are tumors such as renal cell, melanoma, non-small cell lung cancer, et cetera, that do have a single-agent, a robust single-agent response rate. So as a result, we, considering our desire to dose escalate rapidly and get to those higher doses, we designed a study that took all comers, so we were agnostic to tumor type. We took solid tumors of all histologies, and of course, if they had a hot tumor, they must have received and failed a prior checkpoint inhibitor. You can go to the next slide. This gave rise to the following trial design, where we had both single-agent or monotherapy dose escalation, which got started off, and trailing behind that, we had a combination dose escalation with Regeneron cemiplimab. This is otherwise known, brand name is Libtayo. This is a PD-1 agent that of course has a label and multiple indications, and we were very happy to collaborate with Regeneron on in this phase I study. The study here that you'll hear more about from Dr. Sen was designed to rapidly confirm the conditionally active mechanism of action. And as you'll see, we were able to demonstrate a lack of severe CRS, an excellent PK profile which permitted a Q3 weekly or was consistent with the Q3 weekly dosing regimen. With that, I'm going to hand it over to Dr. Sen, who can walk you through the data, and I'll come back to you in a few slides. Thanks, Ron. Shiraj Sen here. So I've had the pleasure of participating in this trial from the very first patient that was dosed. And this table here shows an overall, you know, disposition of the patients that have been dosed on both the SNS-101 monotherapy portion of the study, as well as the SNS-101 plus cemiplimab portion of the study. As you can see here, you know, 16 patients have been dosed with the monotherapy, and 18 patients with SNS-101 plus cemiplimab. Majority of the patients have discontinued study as of April 30, 2024, the time of the data cutoff. Most patients had discontinued for disease progression in both arms. Of note, in the monotherapy study, you know, there was one individual who unfortunately passed away. This is a patient who passed away from, you know, bleeding related to their actual tumor, in an individual with lung cancer, not related to the study drug. In the combination portion of the study, there was one patient who was noted to have discontinued drug due to an adverse event. This was a patient who discontinued due to an immune-mediated adverse event of a Grade 3 elevation in their liver enzymes, which is an adverse event that is known to occur with PD-1 or PD-L1 inhibition. One patient who withdrew consent and one patient who came off for clinical progression. Next slide. As Ron had highlighted before, the majority of the patients on this study had tumor types that are typically unresponsive to PD-1 inhibitor monotherapy. Again, you know, I think this decision was made to help speed up enrollment, and help understand at the core, well, dosing with this drug as a monotherapy in combination with cemiplimab be safe and potentially effective, and it did allow us to escalate, very rapidly, as Ron had said. The left-hand side gives you just overall basic demographics, which I won't go into, but are presented there, representative of, patients that are largely enrolling onto clinical trials in the United States. On the right-hand side, you can see that in both the SNS-101 monotherapy, as well as the SNS-101 therapy in combination with cemiplimab, that most patients had received about 2 to 2.5 lines of prior therapy in the metastatic setting prior to enrollment on the study. You can see that about half the patients on the SNS-101 monotherapy study, and you know, about one-fifth of them on the combination study had received a prior PD-1 or PD-L1 inhibitor. And to further delineate the tumor types, the patients that enrolled in the study, you can see that the majority of the patients who enrolled on the study, as Ron had mentioned previously, did not have, quote, unquote, “hot tumors” or ones who are known to respond to PD-1 monotherapy. Only three patients in the SNS-101 monotherapy and two in the combination, and most patients again, had what are considered to be, quote, unquote, “cold tumors” or those that are typically unresponsive to PD-1 inhibitor monotherapy in both arms, as detailed below. Next slide. You know, we are, pleased to report this, that SNS-101 was very well tolerated as a monotherapy and in combination with cemiplimab. There were no dose-limiting toxicities observed across either of the 2 arms. Most of the adverse events that were seen were either felt to be a grade 1 or a grade 2. You can see on the left-hand side, the overall summary of adverse events, and you can note that there was 1 individual in the SNS-101 monotherapy that was felt to have, a CRS or CRS-like event, and 1 patient in the SNS-101 plus cemiplimab, combination that was felt to have a CRS or CRS-like event. And these were both fortunately grade 1 events, but did suggest that that CRS is, in fact, a class effect of VISTA targeting antibodies, and so this was again, an on-target effect of the drug. On the right-hand side, you can see what the most frequently occurring adverse events were, regardless of causality. You know, what I'll note is, you know, you can see that most of them fall into one of three categories. Either just general immuno-oncology or immunotherapy-related adverse events that are known to occur with any sort of, you know, checkpoint inhibitor combination or checkpoint inhibitor therapy. A number of adverse events that unfortunately do occur to patients on these phase 1 clinical trials related to their underlying cancer, or adverse events that are infusional in nature, such as infusion-related reactions or these, again, low-grade CRS events. Next slide. We do want to, you know, spend one slide here highlighting that there were, you know, these two mild infusion-related reaction or CRS-like adverse events, which is unlike first-generation VISTA antibodies that were highlighted in the first few slides that had more severe CRS events, which unfortunately then led to discontinuation of development of the drugs. Here you can see a profile of each patient who had any sort of, you know, what I'd say is a cytokine release syndrome or, you know, infusion-related reaction, which, you know, may have had some findings similar to a CRS event. The first patient listed here was at the, you know, top dose of 15 milligrams per kilogram. The symptoms that the patient had were chills and a fever. And again, you can see that this was about four hours after the infusion had completed of SNS-101. Second patient as well, treated at the dose of 15 milligrams per kilogram of SNS-101, but this patient was given this drug in combination with cemiplimab. Again, this patient had only chills. Again, just a grade one, and again, similar in time course, about five hours after the infusion of SNS-101 had completed. The latter two patients had symptoms that were much more consistent with an infusion-related reaction, both in terms of timing of when it occurred, towards the very tail end of the SNS-101 infusion, but also the symptoms that they had, which were listed here. For CTCAE, these were considered grade two events. But to summarize, I'd say all of these events were low grade, very manageable, and again, demonstrates that SNS-101 does have the potential to overcome a key hurdle that impeded the development of the first generation VISTA monoclonal antibodies, as described in the introductory slides. Next slide. In line with this clinical data, you can see that the pharmacokinetic data did show a very linear elimination kinetics, and did show a long half-life, which, as Ron had mentioned earlier, supported its continued dosing at a Q3-week schedule. You can see that through 5 dose levels of SNS-101 from the 0.3 milligrams per kilogram, all the way up to the 15 milligrams per kilogram dose, that there was dose proportional exposure. This is again consistent with a lack of target-mediated drug disposition and continue to support the Q3-week dosing as I mentioned earlier. There was fortunately no apparent effect on the pharmacokinetic profile when given in combination with cemiplimab, as you can see on the right-hand side. There was some increase with repeat dosing, but no notable accumulation of drug in these patients. And again, no significant immunogenicity detected in the analyses that were done looking at anti-drug antibodies. Next slide. Looking across, like, you know, a group of key inflammatory cytokines listed here, which again, are often ones that we look at when we are worried about events like CRS or other, immune-mediated, you know, events, being worrisome to our patients. There were no significant changes in these key inflammatory cytokines, which was reassuring. And you can see that this was drawn across a variety of time points, before patients received their infusions or after. Next slide. As part of the study, we also looked at a total of 26 different immune cell subsets to understand what the changes in specific T cell populations would be. They did go on to indicate in a dose-dependent manner, as you can see from the 0.3 mgs per kg on the far left side, going over to the 15 mgs per kg on the far right side, the potential for SNS-101-related pharmacologic effect, effects. In the chart on the bottom left, you can kind of see the trend from, you know, the naive cell all the way over to the kind of more mature effector memory cell, how some of these markers are relevant. Next slide. So overall, looking now at efficacy, we saw that, SNS-101 alone and in combination with cemiplimab has begun to show some early signs of clinical activity. In the monotherapy dose escalation, efficacy data, which is shown on top, there was an overall, 16 patients enrolled, and again, 15 patients of whom received both baseline and at least one follow-up scan. Seven patients achieved stable disease as best overall response. There were a few patients of interest in this SNS-101 combination, sorry, SNS-101 monotherapy cohort that are listed here. There was one patient who had, a very, you know, resistant, to prior checkpoint inhibitor therapy, with an HPV-positive head and neck, squamous cell cancer, who had a notable regression of about 17% at a dose level of 15 mg/kg by itself. This patient, however, unfortunately, had to discontinue therapy at week 12 due to disease progression. There was one patient with adenoid cystic carcinoma who continues on treatment with stable disease, now on therapy at the time of data cut off for 42 weeks and counting at a dose of 1 mg per kg. One patient with a leiomyosarcoma of the kidney, who continues on treatment with stable disease at 24 weeks and counting at a dose level of 15 mg per kg. Looking below in the green, the combination dose escalation data. Again, you can see that there have been patients with a more dramatic response to therapy. One patient with, on the far right-hand side of this waterfall plot, an MSS or microsatellite stable endometrial cancer, who continues on study, 30 weeks and counting at a dose of 3 mg per kg of SNS-101, plus cemiplimab, has a confirmed partial response of almost 60%, whose scans we'll show you on the next slide. And an individual with, again, a microsatellite stable colon cancer, also being dosed at 3 mg per kg plus cemiplimab, who's had a tumor regression of 27%, which is a notable, you know, decrease in their tumor, who was on for about 18 weeks prior to having, you know, evidence of disease progression. And one patient with RCC, renal cell carcinoma, who was on the 10 mg per kg, plus cemiplimab dose, who had a tumor regression of about 18%, but had to discontinue due to that immune-mediated toxicity noted previously. Next slide. And here we you know give details on those two patients with microsatellite stable solid tumors who've had some notable objective tumor regressions. On the left-hand side, the lady who's a 60-year-old woman, who I had the pleasure of taking care of, who's got endometrial carcinoma. You know, she has you know had a prior extensive treatment history listed here, including both a large surgery in addition to adjuvant chemotherapy, which is the standard way to treat these women, followed by hormonal anti-hormonal therapy in the metastatic setting. This lady has had quite a dramatic response to treatment. As you can see from the scans going left to right, this is a rather large metastasis in the lung of this lady, which has, you know, consistently been shrinking with scan after scan. You can see up to the 30-week mark, she's now got about a 60% decrease in her size of her lung metastasis. She is, again, one of the patients that were mentioned earlier in terms of adverse events as well. So she has had a grade 3 diabetic ketoacidosis event, and a few days shortly after her cycle 3 infusions, felt to be potentially related to, you know, either of the two medications. Although I should mention that, you know, we do know that checkpoint inhibitors that are already FDA-approved, that target PD-1 or PD-L1, are known to cause events just like this, although at relatively low rates. This patient has recovered from that event and maintained on insulin therapy and been able to continue on study with, again, this very notable decrease in her cancer. On the right-hand side, there's details of another patient, the patient with an microsatellite stable colon cancer. Again, another cancer type that generally does not respond to any sort of, you know, checkpoint immunotherapies by themselves, such as PD-1, PD-L1 inhibitors, who's gone on the combination of SNS-101 at 3 mg per kg, plus cemiplimab. Was very heavily pretreated with 7 prior lines of therapy in the metastatic setting. Has had some low-grade, largely, dermatologic side effects, but who also was having a notable decrease in the size of their tumor lesions, down to 27%, down from baseline, prior to having disease progression. And I'll just again wrap it up by saying both of these are tumor types that are microsatellite stable and typically do not respond to PD-1, PD-L1 single-agent therapies. Thank you. Thank you, Dr. Sen. This is Ron Weitzman again. So in summary, I think we can conclude that certainly the monotherapy and the combination regimens are both very well tolerated. That said, we're encouraged to see some CRS, which we believe is an indicator of a class effect. Even more encouraged to see that it wasn't severe CRS. Consistent with that, we've observed and demonstrated here, I think, a best-in-class PK profile. Unlike a prior VISTA targeting antibodies that have gone before us, we now have an antibody with a half-life measured in weeks rather than hours, and certainly supportive of a Q3-week dosing regimen. Despite the overwhelming preponderance of cold versus hot tumors, we're also encouraged to see some early signs of clinical activity. And overall, we feel that 101 is well positioned to be the first VISTA-targeted antibody to now test the VISTA IO hypothesis. Next slide. So in terms of next steps, just to elaborate on testing that hypothesis, as you heard, we had more or less sort of laissez-faire type of enrollment in dose escalation, where we took all comers, a preponderance of cold tumors. Now, in dose expansion, we've still enrolled or are enrolling a cold tumor, microsatellite stable colorectal cancer. But the vast majority of up to 50, between 50 and up to 70 patients enrolled and to be enrolled in dose escalation, will be of the hot tumor variety. We focused on a basket of histologies that includes head and neck cancer, squamous cell of the head and neck, non-small cell lung cancer, melanoma. We'll also consider other hot tumors on a patient-by-patient basis. That's ongoing now. Patient enrollment is advancing. We're exploring two dose levels within what we believe are the active, pharmacologically active and relevant dose range of the top dose, 15 mg per kg, and the intermediate dose of 3 mg per kg. I've told you about the tumor types we're focusing on, and we have a cash runway guidance that's unchanged, which takes us to Q3 of 2025. Initial data from these dose expansion cohorts are expected in Q4 later this year. Is that on my...? I think we can turn it over, back to you, Tara, for questions. Great. Thanks, Mike. So at this time, we'll be conducting a question-and-answer session with our speakers. If you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player. Please hold for a brief moment while we pull for questions. So our first question comes from Samantha Semenkow at Citi. Please go ahead, Samantha. Hi, good morning, everyone, and thank you for taking the question. I have two. Just the first one, kind of a big picture question: As you look forward to the dose expansion data that you're expecting later this year, what would you consider the bar for efficacy, based on the early responses or response and activity data that you've seen thus far? Just trying to get a feel for how you're thinking as you move and collect that data. Sure, uh- I'll follow. Yeah. This is Ron Weitzman here. I'll take that. I think if the, if the population were a single tumor type for which there would be irrelevant or relevant historical controls. We could talk about a sort of bar focusing on, let's just say, an objective response rate, above which we'd say we want declared victory. But because the expansion core, while we've reduced the tumor type heterogeneity, we're only focusing on a handful of tumor types and not, you know, all comers. It's still too heterogeneous to rely on a single historical control, primarily because there's no, there's no historical study that will have enrolled this portion, exact sort of mix of tumor types. As a result, you know, I would still say that we need to see a totality of evidence that is comprised of tumor responses, tumor shrinkages, a durability component, and an acceptable safety continuation of an acceptable safety profile. So, you know, I can't yet quote or cite a specific response rate above which we need to be because of the heterogeneity, and I would still be falling back on a totality of evidence. I don't know. We could also ask Dr. Sen to comment, you know, from his perspective. Shiraj, what do you think? Yeah, great question. Shiraj Sen here. You know, I fully agree with Ron. You know, I think each tumor type is a little different. Even within each tumor type, you know, in a phase I dose escalation and expansion study, you know, in—like in this one, we're gonna be typically treating very refractory patients. And in each case, there'd be a different bar, right? So if someone has, let's say, a squamous head and neck cancer, you know, there are gonna be some who may have initially responded to, you know, a Keytruda-based therapy, some who may not have. And again, I think expectations for how they may or may not do, within a novel combination after that might be different. But again, I think too early to say, but that's why, where I do think it could, there could be different benchmark you would have, depending on which patient population you're looking at. Got it. That's very helpful. And then just one clarifying question. Either the MSS patients that you highlighted, have either of them been previously treated with a PD-1 or PD-L1, or was that not part of their prior treatment plan? And then, secondly, you know, as you're enrolling more, a much higher proportion of what you would consider those hot tumors into the dose expansion, do you feel that you have a good handle on the activity in the "cold" tumors like MSS, CRC? Or I guess I'm trying to get a feel for which types of tumors you're expecting to see the most activity as we look into that dose expansion data. Yeah, thank you very much. Sure. So your first question, neither of the two microsatellite stable patients were treated with IO therapy. You wouldn't... unless they were on a clinical trial, the colon patient, let me start with that patient. The colon patient wouldn't be expected to receive a checkpoint inhibitor, since the anticipated rate of response with an IO type agent in that setting would be, if not 0%, close to 0%. The endometrial patient's a little different. In that disease, I think many gyne oncologists or general medical oncologists will use a checkpoint inhibitor, but in combination with active therapy, such as chemotherapy or a tyrosine kinase inhibitor. Although that patient did not receive a prior checkpoint inhibitor, I believe the historical rate of response with just IO therapy, leaving out chemo or TKI combination, ranges anywhere between 0% to around 10%. It's just sort of IO-only therapy. So that's the answer to question number 1. Question number 2, we don't yet have a handle on the response rate in either cold or hot tumors, certainly not in hot tumors, since we have enrolled so few. But that's gonna change over the remainder of this year. As far as the cold tumor setting, specifically colorectal cancer, we're just enrolling those patients now and following them up, so I don't have I can't tell you what we have yet, and what our read is on that. Ask us all about dose escalation. Where might this drug be active? Well, preclinically, you know, if we were gonna, you know, before we ever dose the patient, I think if we were gonna rank sort of where, where VISTA might play a role, you know, that's hard to say, because it's absent clinical data. The best data we have comes from our preclinical results, which suggest a role in both the cold and hot tumor setting. All right. Great. Thanks for the question, Sam. So our next question comes from Sudan Loganathan at Stephens. Please go ahead, Sudan. Hi, everyone. Thank you, Sensei team, for having me on the call, and Dr. Sen for joining. It was great seeing everyone over the weekend at ASCO, and congratulations on achieving this important milestone for the company. My first question is regarding the hot versus cold characteristics of the patient tumors enrolled in the trial. Correct me if I'm wrong, but I remember, you know, you noted the reason to include all comers for the dose escalation was to test, among other hypotheses, the scientific question, if SNS-101 could make cold tumors hot. Would you say at this point, looking at the data at hand, you would have a conclusive result for that question, or still pending on that theory? And then secondly, keeping on the same theme on cold versus hot tumors, has there been any studies looking at the pH levels of cold versus hot tumor microenvironment? A hypothesis is that cold tumors have less hypoxia, potentially keeping the pH higher, more and more alkaline, versus a hot tumor with more hypoxia having a lower pH and acidic tumor microenvironment. Could this play a role in the conditional binding of SNS-101? However, the tumor regression seen in the cold tumor patients goes against this hypothesis and ties, which also ties back to my first question. In this case, for cold tumors treated with combination, seeing a tumor regression, could it be attributed primarily to the effect of Libtayo? And then lastly, when looking at the safety and tolerability of SNS-101, it's great to see the CRS class effect being a low-grade event at higher doses as a signal of on-target activity. However, the two patients that experienced CRS were at the highest dose range, 15 milligrams per kg for SNS-101 for the six weeks, you know, before discontinuing due to PD, which would be the focus of the upcoming expansion trial. So based on the CRS effect with prior VISTA targeting agents, was the onset as early as within the first six weeks? And how do you predict that to progress, you know, at that higher dose range going forward in the expansion cohort? Thank you for that question. A lot of questions in there, so I wanna make sure- Yeah. Okay, you can refresh me if I get any of the questions wrong. But let me just start with the last one. It's true, the two sort of bona fide CRS events, at least as recorded in our clinical database, did occur at the top dose level, one in the monotherapy setting, and I think one in the combo setting. Those were first dose or first infusion events, which is totally consistent with CRS in general, which tends to be a first or maybe second dose effect. It tends to be, I'll use the term tachyphylaxis, or some tachyphylaxis or waning in terms of that event over time. Neither of these patients had any-- there was no seriousness to these events. They were very easily treated. They didn't require tocilizumab. I might also note that none of the patients at baseline coming into the study, per the protocol, received any prophylaxis because we wanted to see what we had. So these are non-concerning, but actually reaffirming events that we believe are consistent with the VISTA class effect. I say it's a class effect because this has now been seen with two different, at least two different prior VISTA-targeting, non-conditionally active antibodies. And so this is, you know, to some extent, comforting to see, especially comforting that it's not severe. Can you remind me of your first and second question, just in short. Yeah. because you asked a bunch of questions, so I apologize. I- No, no, no worries. I kind of, you know, rapid fired. Yeah, I guess for the first question was kind of in regards to the, you know, testing the hypothesis if SNS-101 can transform a cold tumor into a hot tumor- Yes. Okay. Yeah, let- Yeah. Let's just pause it there before you go to the second one again. Mm-hmm. I don't think we can say that yet. Why do I say this? First of all, the number of patients is small, relatively, for a dose-escalation study, number one. Number two, it's highly heterogeneous. If you look at the baseline characteristics that Dr. Sen reviewed, there is not one predominant cold tumor type in here. And so owing to that heterogeneity, owing to the fact that some of the doses in dose escalation may very well be subtherapeutic, I won't use the term homeopathic, but below sort of the threshold of efficacy, based on preclinical models, it is not yet possible to confirm or not or disprove that hypothesis. And this is gonna require more patients treated at therapeutically relevant doses. So, we're still patient, and we eagerly await the results of the expansion and, of course, phase two, which we shed more light on this. And the second question again? Apologies for not remembering. Should've- Yeah, no worries. And it was, you know, in regards to the hot versus cold tumor thing. So the, you know, hypothesis, potentially, that cold tumors will have a more alkaline, you know- Oh, yeah ... microenvironment versus a hot, you know, is that, could that play a role in SNS-101 binding and, you know, conditional active binding? And then, obviously, we did see some effect in cold tumors, efficacy-wise. So just wanted to see how that all kind of- Yeah comes together, uniquely. I might ask, Edward, our Chief Scientific Officer, to comment on that. But, and I could be wrong about this, but I don't... You know, my review and understanding of Warburg metabolism, and data generated well before the era of hot versus cold tumor designation, is that, tumor microenvironment acidity is a pretty ubiquitously found or existing phenomenon across all solid tumors. And I'm unaware, personally unaware, of a distinction in that, based on hot versus cold. But, Edward, you might know more about this than I do. No, I think, I can't add anything. You precisely described it. Cool. No, thank you guys so much for answering all my questions. You know, once again, congratulations on achieving this milestone here at ASCO. Thank you so much. Thank you, Sudan. Thanks for the question, Sudan. This concludes the verbal portion of our Q&A session. I'll now turn it back over to Mike for any questions that came over the webcast. Thanks. Maybe, the first one to start with, would be, maybe to you, Ron. Are the two low-grade CRS events expected, given this the targeting? And then moving forward, what are your thoughts about CRS management? Is a prophylactic treatment possible to manage CRS? Okay, well, you know, I can't definitively state that the presence of CRS confirms VISTA targeting, although I'm highly, highly, highly suspicious that it reflects that. Since we know that, CRS, and when I say CRS, this is a clinical diagnosis. It's a syndrome. You know, one of the patients certainly had very high levels of IL-6, and other classic cytokine bumps. They had symptoms consistent with CRS. The timing of the onset was late versus early, which would be more akin or consistent with infusion-related events. By the way, those are just a spectrum of findings. But, I'm quite sure that that is reflective of VISTA targeting. Now, there are presumably multiple acidic compartments in the body, and so I you know I can't definitively state that the VISTA targeting is coming from the tumor microenvironment. Although I highly suspect it, given the fact that these patients have advanced cancer, have known existing metastatic sites of disease. When you factor in Warburg metabolism and the presence of VISTA as a ubiquitously expressed target in that setting, we believe that this reflects a VISTA engagement in the tumor microenvironment. Thanks, Ron. Oh, I know. We don't see a need for prophylaxis, given the low-grade nature and ease of management of these events really. No one needed steroids, no one needed tocilizumab. But again, we've enrolled 34 patients, and we'll have to broaden out our experience before I can be definitive in stating that. Great. I think we only have time for a few more questions. Maybe one more for you, Ron. Why are you testing lower doses of SNS-101, since your top dose seems to have been well tolerated? Yeah, that's a good question. So it's been well tolerated in 18 patients. 18 patients have, you know, error bars, confidence intervals, and so we're very happy with the tolerability profile at 15 mg per kg. But it's still early days, and we'd like to be sure in a broader patient population, or in an expanded patient population, that the safety profile we've observed at that top dose is indeed the safety profile that continues to show itself in more patient numbers. To that end, FDA would expect lower doses being explored consistent with Project Optimus, and we'd like to be sure that early on, we've spent some time and resources in optimizing our future phase 2 dose. To do that, you need to look at more than one dose. Thanks. And maybe one for you, John, that came in. It was mentioned cash would last until Q3 2025, but previous guidance was Q4. Can you please clarify that? And anything else you wanna add? Yeah. Thank you, Mike. That's an important clarification. Don't know if there's somebody misspoke or maybe the line broke up. Cash runway guidance has not changed, so cash runway guidance was and still is Q4 2025. Thank you. It looks like that's the end of our questions. So at this point, I'd just like to thank the audience for your time and participation. Hope everybody has a great week. Thank you.