Event for the 2024 ASCO annual meeting. As a reminder, we're going to be making forward-looking statements at this presentation, so that is included here for reference. For the agenda today, we are going to have Dr. Thomas from Orlando Health present Cohort 1A data from his recent oral presentation during the ASCO conference. Then we will have a KOL panel to hear some perspectives on the launch of Amtagvi. We have Dr. Daniel Olson from University of Chicago, Dr. Donald Lawrence from Mass General, and Dr. Bruce Brockstein from Endeavor Health North Shore, who is a referring physician. We look forward to the session today. Do I have a mic? Oh, hey, can you guys hear me pretty well? Yeah. All right, perfect. Again, my name is AJ Thomas, Medical Oncology at the Orlando Health Center. I primarily just practice melanoma sarcoma. I've been a lead investigator for a lot of the cellular therapy trials, so I'm told I can give the abbreviated version of the talk, right? So I hope most of you guys heard it. Again, the efficacy and safety of lifileucel TIL therapy combined with pembrolizumab in patients with anti-checkpoint inhibitor naive unresectable metastatic melanoma. And again, the updated results of the IOV-COM-202 data. This is a phase 2 study showing that the combination of lifileucel and pembrolizumab had deep and durable responses, and these are immune checkpoint naive metastatic melanoma patients. 2/3 of these patients had a confirmed response. A third of these patients had a complete response, and all evaluated patients had regression of their target tumors, and the vast majority of the responses were ongoing. The safety profile was consistent with the one-time dose of lifileucel and the pembrolizumab treatment, and these results support the ongoing phase 3 TILVANCE-301 trial. Again, for a lot of us who deal with melanoma, we know that more than half our patients are not going to respond with dual checkpoint therapy. It's like 67% of these patients will have recurrence and progressive disease. How do we get that tail to curve up and get a little higher? Lifileucel is approved as a second-line option based on the C-144-01 study that showed the response rate of 31.4%. That was a response in patients who had, you know, multiple lines of therapy, median line of 3 lines of treatment. The longest duration response, independent response, was 55 months, and I have patients who are now 6 years out. You know, and patients who would have opted for hospice care 6 years ago, right? Now in remission, long term, doing really well. I think we all have patients like that. Lifileucel has the potential to improve the outcomes over the mono and the dual checkpoint therapy. This was based on the National Cancer Institute data, where they had 190 patients that were immune checkpoint, treated with a single TIL monotherapy, and the response rate was 56% in their hands, 25% complete response. What's more interesting, their CR patients had a 96% 10-year melanoma-specific survival. The IOV-COM-202, cohort 1A, was assessing the efficacy and safety of lifileucel and pembrolizumab in this immune checkpoint-naive population. These patients could have had prior BRAF/MEK therapy. And then again, eligible patients had 1 resectable tumor and another measurable tumor for a response assessment. These patients are screened in, had a harvest, followed by an early dose of pembrolizumab, and then lymph depletion, lifileucel, IL-2, up to 6 doses, and then they can continue their pembro every 3-6 weeks thereafter. 23 patients that were treated, the median age was 51. Most of these patients were cutaneous subtypes. There were a few acral, mucosal, and there were 4 unknown primaries. 50% of these patients were visceral-involved disease, and 56% of these patients had PD-1 positivity, one or more. A third of these patients, liver mets, nobody had brain mets, and 8 of these patients are BRAF mutated. Only 3 of these folks had prior BRAF/MEK therapy. If you look at the safety, and again, this is something unique and different from what we've seen with prior therapy, all of it's due to IL-2 and lymphodepletion. Most, if not all, are due to IL-2 and lymphodepletion. 30% of the non-hematologic issues were specifically chills and pyrexia, nausea, vomiting, fatigue, febrile neutropenia, right? And that's something that we've, I think we've all seen. These patients become neutropenic during that second week. They're getting TIL, they're getting IL-2, and the IL-2 is typically the cause of the fever in the majority of these patients. So most of those folks typically don't have any culture positivity, but yet we've all escalated treatment to a neutropenic protocol in those patients. 100% of these cytopenias are due to lymphodepletion. The good news is that by day 30, grade 3, grade 4 resolve to less than a grade 2 in a majority of these cytopenias, with the exception of maybe lymphopenia, that took a little bit longer, and then we give PCP prophylaxis. So AEs consistent with lifileucel, anything more than 30 days in terms of AE issues are typically, you know, consistent with what we expect with PD-L1 monotherapy. The response rate, 65%. You know, complete response, 30%, probably the highest complete response rate we've seen. And partial response of 34.8%, so a total of 15 patients having a nice response. And 4 of these patients who were stable had an initial regression of target tumors, but then there's a repeat confirmatory scan that's required for this. And with the repeat scan, they had some evidence of progression, so they were reclassified as stable disease. And one patient over here that was progressive had regression, 80% regression of target tumors, had a progressive lesion in the brain that was treated but had to come off a protocol. All response-evaluated patients demonstrated regression in their target tumors. And again, 2 of the unconfirmed response were now confirmed response. Majority of these patients had ongoing, durable, deepening responses. Again, pointing out that 2 of these patients had 100% regression at the very first week assessment, and then the other folks, you got 4 or 5 of these folks evolved into a CR over time, typically a year and a half, and one patient is now 3 or 4 years out with a CR rate. The interesting thing about TIL, and we've seen this before with TIL therapy in the refractory setting, if they're going to respond, typically you kind of know it within the first, you know, 6th week or 12-week assessment, right? Majority of the partial response is early, and then a few of these folks evolve to a partial response over time, complete response. Then you have 3 of these folks that had ongoing response, but they withdrew for other reasons. I always love to talk about that one patient right there, 'cause that's my patient, right? That patient right there had a nice response, 2 years, had an oligomet progression, and that was dealt with surgically, and has now another 2 years, still ongoing without any evidence of progression for a total of 4 years since the initial PD-1 TIL. Duration response not reached, and 53% of these patients had responses that are beyond 12 months. Median time to response was 2.6. Again, 10 out of 15 ongoing, with three that withdrew from the study for other reasons, and they had ongoing response. And I will add in that one patient who continues to do well, even though he's considered a progressor. This is, again, looking at unique T cell receptors that we can find in the TIL product, the lifileucel, and how does it match to what we see in the tumor, right? That's overlapping TCR clonotypes. The responders had a higher rate of that overlapping shared TCR TCR clonotype compared to the non-responders. The persistence of seeing that shared clonotype to 12 months, which is above, the levels were a bit, above higher than the pre-infusion levels of 13%. So again, higher overlapping shared clonotypes may be predictive of TIL response. Number two, that durability, right? The persistence of shared clonotypes suggesting ongoing immunity, ongoing immune surveillance for these patients. Supporting the TILVANCE-301, phase 3 study, global study, right? combination... 370 patients being randomized to the combination versus pembro monotherapy. These folks will be locked and loaded to have surgery. If they randomize the combination of surgery, move on to TIL PD-1, and those who get pembro, the surgery will be canceled. The surgeons are okay with that. They were happy to... they'll have a backup. And they do pembro monotherapy, and then if they progress on pembro monotherapy, they have the option to get lifileucel monotherapy at the time that it's independently progressed the tumor, with the primary point of response and progression-free survival and key and, key, secondary point of overall survival. So in conclusion, the combination is manageable, safe. Again, unique profile. Most of the side effects are just that first 30 days, reversible, expected, treatable. The efficacy and durable response in that immune checkpoint naive, 65% response rate, a complete response of 30%. All evaluated patients had regression of target tumors, and the median duration response not reached. Rates and depths of response were, again, comparable to what we've seen with mono and dual checkpoint therapy. I think that's all I got. Any questions? At the end. At the end. Mm-hmm. Hi, everyone. My name is Sarah Pellegrino, and I am the Head of Investor Relations and Corporate Communications at Iovance. I'm going to moderate the KOL panel discussion with my colleague, Dr. Peter Prieto, the Senior Vice President of Medical Affairs at Iovance. Our goal today is to engage our key experts from authorized treatment centers, as well as a referring physician, about the AMTAGVI launch. I will begin by inviting each of our panelists to provide a quick one to two-minute overview of your practice, your institution, how many advanced melanoma patients you see a year, and the, you know, greatest impact of AMTAGVI on your patients since launch. Would you like me to go first? Sure. Okay. I'm Don Lawrence. I'm the Clinical Director of the Melanoma Program at Mass General and have been responsible for standing up our lifileucel program, and it's killing me. We're so busy, right? But it's also a lot of fun and, you know, we've seen patients who have had dramatic benefits on these trials. We have a lot of trials, and we treat a lot of patients and, you know, research is our focus and we try to learn, but, you know, this is our number one option for our progressors on checkpoint blockade. And, you know, we really have just scratched the surface of what we can do with this. So, you know, I'm just very optimistic about the future with this treatment. It's been a long time coming since we had something that could help the people who are refractory to immune checkpoint inhibitors. Thank you. My name is Dan Olson. I'm a medical oncologist here in town at University of Chicago Medicine, and I've been in practice now for just over a few years. But I did a lot of my training in melanoma, and I also take care of patients with sarcomas. And I've had some clinical trials and worked in the post-PD-1 space, so I've been really attuned to what treatment options we have for these patients and also helped to run immunotherapy-based trials in patients who progress through PD-1 inhibitors, and that's mostly the referrals I get, are people in the community who are looking for trials and other options. And so I see, you know, just over 100 patients, probably, that I'm taking care of in a general year. But a lot of those referrals are for later lines of treatment. So as soon as some of the data started to come out about lifileucel working really well for those patients, we were incredibly excited and we've had some experience institutionally working with TILs and patients with cervical cancer. But our first experience in melanoma is with the commercial product. We're really excited to start this, and so we've begun the process of sort of restructuring our program so that we can get patients to surgery and then get them treated. And we've had lots of referrals. We've had some of our patients go through it so far, and we're really excited to have this as an option. So, I want to echo that same sentiment that we know what's out there, we know what we can get with the standard therapies, and it doesn't really seem to be anything close to this, so we're really excited to be able to use it. Thanks. My name is Bruce Brockstein. I'm a medical oncologist. I've been in practice for almost 30 years. I'm the medical director for the Kellogg Cancer Centers at Endeavor Health, which is in the north suburbs of Chicago. Endeavor Health used to be called NorthShore University HealthSystem, and Evanston Northwestern Healthcare before that, if you're familiar with the landscape. Clinically, I treat patients with melanoma and sarcoma and head and neck cancer. I'd say interestingly, melanoma used to be my least, least busy clinical practice, and that changed about 10 years ago with checkpoint inhibitors. It's now my busiest practice because of availability of referrals and patients living to continue on in clinic. I say that, 'cause I think it's an important point in terms of proof of principle of the fact that there can really be, you know, changes, you know, almost on an order of magnitude. I've been doing this long enough, 30 years, to see that in a few different diseases. I think cell therapy is kind of on the cusp of being kind of that next one, you know, where there's actually something new, and we'll probably be talking about some patients in a bit. As a busy referring physician, I see about 60 or 80 new melanoma patients a year. There are these patients who were kind of at the end of the line in these last, you know, 3-12 months, who you- You're dropping out. Oh, I'm sorry. Okay. I'm so sorry. I don't want anyone in the room. What you saying? Oh, my God, sorry. Okay. Thank you. Just put that in there. Okay. Okay. I'll start over. No, I'm kidding. But no, you know, these last three to 12 months, I've had a number of patients who were kind of really at the end of the line of standard therapies, really trying to kinda help them, you know, in a sense, limp along until there was a availability of lifileucel to Amtagvi TIL therapy. So it's been a wonderful thing for, for me and my patients, so... So thank you. Thank you, Doctors Lawrence, Olson, and Brockstein, for joining us this evening. It's a very exciting time for Iovance. When we talk about your advanced melanoma patients, can you talk and speak about when they're receiving their first line of therapy, when they begin to progress, when they begin to have, relapse on that first line of therapy? When do you begin discussions about the next line of therapy for those patients? When does that discussion begin for your patients? Pretty much right away. It's probably even before they start to progress. I mean, most people want to know what the plan would be if they're not responding to first-line therapy. And it was really incredibly frustrating for the last several years because we've known that TIL... I mean, we've known for decades that TIL works, and I've been waiting my whole career to give it, but patients knew as well. And it was, you know, the clinical trials were limited, and it was really hard to have to tell some people that they weren't eligible or that, you know, and they developed brain mets, other things that excluded them. So it was always part of the conversation, but it was only a reality for a small minority. Now, it has become a possibility for a larger percentage. So second line, even front line, we prioritize clinical trials, and that would be usually checkpoint inhibitors plus something else. But we are already thinking second and third line at the time we start. You mentioned brain mets too. So when we start to think about patients that are now, potentially, eligible for Amtagvi, what characteristics within those patients do you consider when you are thinking about this therapy? The presence or absence of brain mets, the true second line indication, third line, the rate of progression, how do these factor into, to your decision making? Do you want me to keep going or...? So yeah, I can talk about that. So we think about this, you know, from the very beginning, we're wondering, we, we know we have a set of therapies. If you have a BRAF mutation, we have a target therapy we can use. Otherwise, we have a series of immune checkpoint inhibitors, and you can use them in sequence, use them all together. Roughly 50% of patients will get some long-term control. So from the beginning, though, we're saying, you know, we've got this sequence of therapies. We know what our overall outcome can be, so we want to think about how to use those best. And the idea is we don't have any idea ahead of time who's going to respond to these or not. And so, we sort of use those clinical parameters of, you know, how much tumor is there? How sick are the patients? What do we think they're going to be able to tolerate? And ultimately, how do we get them to take as many shots on goal as possible? Because we don't know if they're going to respond to that first therapy. So, we might sequence which types of therapy we use in the beginning to make sure we don't expose them to too many side effects, and then if the risks change, we'll think about other things later, based on how they do. But, yeah, so I think if you don't have a BRAF mutation and, you know, you're not responding to the initial anti-PD-1 based therapy, we're really thinking about how do we safely get you to TIL. So, you know, really depends on their sites of disease, how well they're doing, their age, their fitness, 'cause it's not for everyone ultimately. If you're older, if you have untreated brain mets, you're going to need to have those treated first with radiation. So there's other things that we have to do to make sure they're eligible, and ultimately, not everyone will be. But especially if we think you're going to be able to tolerate the conditioning chemo and the IL-2, we're going to very quickly have you see the surgeon, get things in a row so that we can set them up for treatment. If they have the BRAF mutation, we'll use BRAF MEK inhibitors to try and, you know, control their disease. We know that ultimately, almost every patient will progress through that, and sometimes it can be really dramatic, and so we don't want to wait until the patient has a dramatic progression event and then be unable to rescue them and get them back to TIL therapy. So we're timing things really to- ... get the benefit with that therapy, but then say: Where are we? How are we doing? Let's think about doing this. And again, it's really trying to make sure we have control over the process as much as possible, rather than trying to regroup when the melanoma is taking off, and we're sort of against the clock, and things, you know, can get out of our control. So that's the way I think about it, but we're being careful with patients with brain mets, making sure they're treated. And then age and fitness, and things like that, we consider to make sure if TIL therapy is appropriate. Oh, I was just gonna- Yeah. Yeah. So, in terms of when do I think about the, you know, the next therapy, as Dr. Lawrence pointed out... I mean, I think at the point of consultation, you have the discussion about what are your treatment options. So at that point, you've generally had the discussion of what's my first recommendation, but here's the things that might come on the heels of that. That's the discussion with the patient. Hopefully, you never get to that second-line thing, but you often do. For myself, I organize myself even in the context of my own notes, you know, patient on this treatment, here's what I'm doing next. That way, I've got that ready to go, ready to launch. And if I have a patient who I think is really gonna come to that, next treatment, I mean, this is a dynamic thing, right? We're only three or four months into actually having this clinically available. So in the past, it was, am I ready to launch that patient either to the next treatment or to check into clinical trials that we might have or somebody else might have? Now, at this point, I think because there's a complexity of actually getting the patient onto therapy, I think the key thing is early, early referral. And Dan and I have a good working relationship. We have for a number of years, so it's very easy. If I have a patient, I think they're gonna get to that point, I would rather have him see the patient. Maybe it's gonna become unnecessary, maybe the patient won't need TIL therapy. But if they do, then that conversation's already happened, already in the system. With the complexity of, you know, getting the patient from progression to treatment and time being really, really important, I think that's actually a really key step, is the early referral. So- Along those lines, Dr. Brockstein, let's take a deeper dive into your particular practice, as you're not currently at an ATC. Right. Can you give some more specifics about how that process has kind of streamlined or how you get patients to an authorized ATC and maybe how that's changed? Yeah ... through launch in the early days? It's kind of a simple answer, to be honest. Like, if I have a patient, I know they're gonna need that, I either give a call or send a text or an email to Dan and say, "Here's the next patient." I've sent him, I think, about five so far for potential therapy. And so really, from my email to him, to his coordinators, back to the patient, has been a number of, you know, a matter of a few days, and then consultation over a week or two. They may not be needing therapy at that point. Some of them started seeing, yeah, Dr. Olson nine or 12 months ago as we were close to launch. Yeah, it was, You know, we've kind of bridged and things like that. But I think that's the key thing, is getting that working relationship, at least for people who have a melanoma practice. It's kind of easy. You know who's doing they already have that relationship you probably have for a while. Probably the harder thing is for people in community practices that still treat melanoma patients, and it may be a rare patient that they need to refer. So that's where maybe kind of developing that process. For me, it's fairly straightforward. So maybe I can just address that also. So, yeah, we talk a lot about delayed responses or pseudoprogression with checkpoint inhibitors, but we talk about it more than we actually see it. We pretty much know after two cycles if somebody is gonna respond or not. There are exceptions to that, and so we really do want to see these patients early. And yeah, I think I promised you guys I would get you our sort of checklist of what we look at and how we evaluate these patients, but that's all in my head right now. And when I hear about a patient, you know, I reach out to the referring oncologist. I say, "I need to look at the scans. Have they had a recent brain MRI? Are they BRAF mutated or wild type? Any other major, major medical problems?" And then, before we even see the patient, I'm talking with the surgeon, either a thoracic surgeon or a surgical oncologist, whatever it may be, so that we're ready when that patient hits the door, because it's a tight timeframe to move ahead with these people, so earlier is always better. So, key launch metrics for the initial launch of Amtagvi, we have talked about the number of patients who enroll for treatment, which means that they are treatment eligible and have decided to move forward. And in addition to that, we have talked about patients who are in screening, who represent that next wave of enrollment. So once you identify a potential patient who could be a treatment candidate, how quickly can you get them screened to determine treatment eligibility? And how is that process working so far? And how would you characterize how receptive patients are and open to the opportunity for Amtagvi? Oh, they're open. They're seeking us out. Mm-hmm. I mean, we've had people from... I have a patient from Poland, I have a patient from France, Canada, Brazil, who've sought us out for, for this stuff. People know that it's out there. So we try to get people in within a matter of days to... You know, we, as I said, we go through this thought process. I have one surgeon who's my main go-to person. She doesn't do all of the surgeries by any means, but she's the one who will help me look at this and say: What can we harvest? My nurse practitioner plays a key role. So we, you know, it happens, it's almost, like, instantaneous. Is this a patient, a patient, a good candidate or not? And if they are, we'll get them in within a, within a few days. Yeah, and I can add to that and say that, there are patients who come in where it's not always crystal clear. You know, I think there's a group of patients who are being referred, who have been kind of waiting for- ... TIL, you know, for TIL therapy to come along, and so they've been hanging on, and their disease has grown, and they're not always in the best spot, you know, the optimal spot to move on to treatment. And so I've had a couple patients where we've had conversations about that and think about doing bridging therapy with something that generally doesn't work that well in melanoma, like chemotherapy. But then, if that allows us to sort of test to make sure they're gonna be able to go through things and get control of the disease, then we know we can extend them through and get them to TIL therapy. So I've started doing that, and that's, I think, reflects the patient population right now. But obviously, as things smooth out, as we get more familiar with taking the referrals and getting people to think about it earlier, we're hopefully not trying to pull things together in later lines, but that's definitely something that happens at the beginning, is that we get a lot of referrals and there's people thinking about it, and we wanna make sure it's the right thing for them. And so sometimes it's a little borderline, and we do some things to get them in good shape beforehand. And how would you characterize the growth that you're seeing in enrollments and screenings? Is it coming from, you know, your center reaching out to say it's available and getting using that as a source of referrals? Do you have a lot of patients coming to you directly or both? Yeah, it's, there's a small amount that's my own patients. You know, it's actually most of it's coming from outside, so it's grown our center. I think it's actually, it's been good in terms of, you know, our program and seeing more patients. But yeah, it's been a lot of people who've been referred from places that I never got referrals from before, and I think that's really because we're the only site in town doing it at the moment, and so people are coming from surrounding states. I'm getting people from out of state. I'm getting international patients. And, so yeah, it's really busy. It's coordinating a lot of people and getting them to fly back in and see a surgeon on a date and then, you know, get ready, so it's a lot of back and forth. But ultimately, we're excited to do it because we can help people in a way we couldn't from, you know, previously. Mm-hmm. Dr. Lawrence, did you wanna add anything? No. I think I don't have anything. It's a lot of work. All right. Well- It's a lot of work. Yeah. But it's great. Thank you for discussing- Yeah. Mm-hmm ... patient selection, including referrals, as well as the growing interest among patients to undergo screening and enrollment. I'll ask Peter to lead, next on the patient journey once they are enrolled. Thanks, Sarah. So, again, Doctors Lawrence and Olson, thank you so much for your enthusiasm, and you really are exemplary programs. Your ATCs really have streamlined the processes, the workflows, and understanding how to get these patients quickly to treatment. Understanding that there is some timelines that will be changing in terms of financial clearance, single-payer agreements, can you speak to how that process has evolved or changed, or the velocity of that has changed since day one of launch? Well, we had to work out our procedures, our workflows, and that included not only me and the surgeon, it included the whole cell therapy team. I mean, we benefited from the fact that we have a very well-oiled machine for CAR T, and we piggybacked on that. So all of the administrative stuff of, you know, chain of custody with the product, all. They knew how to do that. Our nurses, our coordinators, and our insurance people also were very proactive. You know, some of the payers had never heard of this stuff, and they didn't have any way to even, you know, pre-authorize or evaluate it, and so we had to teach them. Also, the hospital was helpful with that, and I think you guys were helpful with that also, and just helping to navigate some of those insurance issues which, you know, with any new complicated treatment like this, it's gonna be a challenge. So I think... Well, I shouldn't say we've got the problem solved. There's always things that you cannot imagine that will happen, but those logistical challenges, we've made enormous headway in just, you know, it's been, you know, three months now. So, I think we were one of the first centers to start offering this, and so we had this huge rush. I think it's gonna even out now among the other centers that are offering it, and so we may not see quite as many patients as we've been seeing, which is frankly okay with me, as long as the patients get treated. Yeah, but it is. I think there's an opportunity as these centers come on board to do some teaching and share experience and get them up and running, you know, smoothly. Yeah, and I can also say that, you know, we similar process where we had a good CAR T cell program. The way to organize payers was really similar, and so institutionally, there was people in place to make that happen pretty quickly. There were some bumps at the beginning, again, where different payers had no idea what we were talking about, and we had to let them know, but then that worked out, and it's not really a problem at the moment. I think the bigger piece is just the sort of cultural change in the institution to bring the surgeons back into care for patients with stage four disease that weren't doing this before. And so they're fine. They're obviously really happy to, you know, know that they can offer patients something where we can increase, increase the overall benefit for patients and, and do better. But then when it gets down to the brass tacks of making it happen on a timeline, that's always... There's a little rub there because we're asking them to schedule their OR times as quick as possible, whereas usually they might be pushing things out for a couple of weeks or three weeks, but even those extra weeks that get added on matter. So, that's a shift, and that's something we're working on. And ultimately, we have you know, a cohort of people who are really invested and involved, and then we'll get a tumor in a weird place where we have to go get a thoracic surgeon or someone who doesn't know what we're talking about. And then, you know, we've got to do the whole thing over again. But then now we have them on our side to make it happen. So there's this whole shift, but that'll get worked out, and it becomes more common. I think we'll get, make sure the OR times happen quickly, and then we can get people to treatment sooner. Yeah. I think. Well, our surgeons are very invested in this because, you know, they're immunologists and PhDs, and they like to take little pieces to the lab and play with them. So, I mean, they are extremely enthusiastic. But I think through, like, the SSO and other organizations, this is the, the news is being disseminated, and it really is a, you know, multidisciplinary approach, and it absolutely requires having surgeons who understand what's going on. So that's another, you know... To stand up a program, that's really essential. Thank you. And what about your experience with manufacturing slots and aligning that with surgical resections? What is your experience there, with coordinating, as you mentioned, the surgical resection with the identification of the patient? How are you, how are you managing that? It's getting harder, honestly. So you know, again, I think as more centers are coming online and, you know, it's so it can be challenging to, you know, make the stars align. The surgical date has to be there, our cell therapy lab has to be available, and you guys have to be available. So, you know, it takes some coordination. We always make it happen, but it sometimes takes a little arm twisting on our end with our... I shouldn't say that. Our surgeons are very willing. They've bent over backwards to do this, but it just takes a lot of coordination. Once Amtagvi is manufactured and release testing is completed, and the product is now sent to you, what is your plan in terms of lymphodepletion for those patients? How are you coordinating that? Do you want to take that or- Sure. Yeah. Yeah. So we, You know, once we know the cells are coming, at that point, it's time to start the patient in. So we sort of have a tentative plan date. We can predict that and schedule their admission. Right now, there's some complexity around how you give lymphodepleting chemotherapy. I mean, if someone's coming from way out of state, they're going to want to just stay in the hospital, so we do that, and it gets covered. Obviously, it's more expensive overall, but it's just more practically feasible for the patient. If someone's local, then we have an option to give it outpatient, which, you know, has its own payer implications. It's cheaper to do that. It's also nicer, probably for those patients, if they live locally, to sleep at home, rather than spend, you know, up to potentially weeks in the hospital. So, yeah, we set them up. Once we have the cells here, we say it's... We really feel comfortable. So at this point, we've started lymphodepleting once we really have confirmation the cells are ready in there. You know, have the patient go through that. It's relatively straightforward. At that point, I kind of take a step back, and I hand it over to my cell therapy colleagues or the people who do CAR T cells and transplants. They handle a lot of the, you know, hematologic toxicity, and they know how to do IL-2, so, they actually do probably the heavy lifting. But then they get the patients through it. Obviously, the patient could be inpatient or outpatient, get the IL-2. We usually have a discussion about that. I join their meetings, and we talk about how to handle it. Then we see the patients outpatient, you know, initially, pretty quickly in clinic, a couple of times a week, but a lot of the toxicities are getting much better within weeks, and so we can scale it back and eventually, you know, scan the patient. We want to see how things are going, and then send them back and see their oncologist. Send them back to, you know, our referring team. Yeah, we heard from Dr. Thomas that this disease is certainly very manageable. But, Dr. Lawrence, any insight or comments there on how you manage the components of the therapy from infusion, lymphodepletion infusion, and supportive IL-2? Yeah, I mean, I look at this as kind of like CAR T without the cytokine release or neurologic toxicity. Mm-hmm. But, you know, but our cell therapists were kind of terrified by interleukin-2. I actually now round on that service and, you know, so I've had to learn how to treat cytokine release and so on. But, you know, we just don't see that. So they, they're like febrile neutropenic patients after they're done, and, you know, most of them actually go through IL-2 very easily. I think it's, it's easier to give IL-2 to somebody who's lympho-depleted than it, than it was in the old, old day. You guys probably don't remember. You do. High-dose IL-2, the, you know... I have PTSD- Yeah. -from that. But, yeah, we at least so far have gotten in five or six doses in all our patients without too much of a hitch. And then they're febrile, neutropenic, and they get treated like any other cell therapy patient, and then they go home, and then we see them again, and we scan them. I mean, we keep them pretty tightly in our grasp rather than sending them back to the community, probably because we don't have folks like you who have the same expertise. At least that's what we've done so far. We've also done all the lymphodepletion inpatient so far, but it's certainly on the agenda to move it outpatient when it's feasible for the patient. Great. I think it's been great to hear your insights on the initial adoption, but it would also be helpful to see how you're thinking about broader utilization of Amtagvi and managing that growth, not just of Amtagvi, but having more cell therapies available at your center and planning ahead for that. Would you say, do you plan to begin treating a certain number of patients initially? And then how does that number move up? And ultimately, how many patients a month do you think you could see, and what needs to happen to get you there? Yeah, I think for us, there was this initial deluge because we were one of the first centers. So, I don't have any, like, monopoly. You know, if patient can get treated elsewhere or at Mass, you know, we're gonna have our patients, and it'll settle down, it'll even out. But in terms of where this is going, again, we're a research institution, as you guys are, and we'd like to take this platform and move it ahead. And, you know, so we are really doing a very deep dive into the tumors, why they respond, why they don't respond, mechanisms of resistance, things that we can do to manipulate the tumor microenvironment that will make this work better. And it's almost like there are too many ideas and options even. We really have to focus in on what we think will be best, and that's gonna come out of our laboratories, and that's where the hypotheses will be generated. I'm sure this is the same in Chicago. This is really... I know you guys have been working like hell for years on this. This is really just the beginning. I mean, and then it's gonna, you know, other tumors, you know. So I think it's just... You know, it's so exciting now, but it's gonna get better. Yeah. And on a personal level, it's been really nice because I came in treating patients with melanoma and, as you know, there were starting to be cell therapy trials, and it was all being run by our cell therapy doctors who were all treating leukemia and lymphoma, and so... But they weren't familiar with these different indications, whereas I was just out of training, and I was like: Yeah, I would definitely do this. And I was interested in immunotherapy, so it was fortuitous that I was in that right place to sort of be the solid tumor cell therapy person, and I also happened to do a lot of melanoma. So this has been great. But I think the reason I'm so excited about that is that we do have all these trials going on, which I also participate in and help run. But then in this- we're seeing this sort of culture shift to actually using some cell therapies for solid tumors, which for now will be something we run in big centers that are willing to do that. But it's... You can see the data, that there are many exciting things come out, and you know, there might be an approval for sarcomas, which we treat too, and, that would also be a great option. And so I think we're excited institutionally to be set up like that, to be offering these really exciting therapies, and then to also have the ability to study those patients. You know, we're hoping to expand this treatment, you know, anywhere between five up to five patients a month, more if we could handle it. But I think right now that's probably our capacity. Then, you know, we study those patients, we biobank them. The patients who are older, who are probably less fit, we actually plug them into this program that we call the optimization clinic for people who are undergoing transplant, where they've generated lots of data about different performance characteristics in patients and who does well and what things can you modify to make their transplants go better. But a lot of this is analogous in some ways to TIL, and so we're pulling those people in. It's part of their experience. We're studying those patients. It's gonna be really exciting to be able to answer those questions, which are important in practice, but then actually have this be a new part of oncology, that we're doing cell therapy and solid tumors. That's great. I have to talk to you. Yeah. About the optimization clinic. Yeah. So. That's great. Thank you. How are your centers investing in expanding your cell therapy unit, you know, new facilities or more staffing or both? Yeah. So, so far, we've had enough bandwidth to do this, and like, I can see more patients with melanoma, take the referrals. I'm sort of handling a lot of it, and at some point, it'll be, when we have more, I'll try and get some help with it. But, I have another doctor who can see my patients with sarcoma and sort of doing... prioritizing this right now. And, you know, that allows us to expand to a certain extent. But as we get more, and certainly if more, cell therapies become the norm in solid tumors, it would be a new inpatient service that handles that, and we would just adapt to it. So I think it's in the interest of the institution, certainly to be known as a cell therapy program, whether that's in blood cancer and solid tumors. So I think a lot of those interests overlap, and certainly the research interests overlap for the people who want to study this. And so, they all point in the right direction, and the, you know, the hospital and the university have been really supportive. And so far, we've just had enough people to absorb it, but as it grows, they'll hire more people. Dr. Brockstein, how do you feel, or how are you seeing your referrals patterns changing now that AMTAGVI has been available and it's growing? There's multiple centers now in the Chicago area. How do you see your role evolving? Hopefully in two ways. In the short term, I think, making sure that, you know, as I mentioned, that the referrals happen early, that they're timely. So that is close to 100% of the patients who might be eligible end up actually getting to therapy, and not, you know, hitting a bump in the road where they progress before they can actually get onto treatment. Ultimately, I'd like to become an ATC, an authorized treatment center. You know, I think there'll come a point, as we heard, where the current number of ATCs, you know, exhaust their capacity or, you know, have difficulty. And assuming that the indications, you know, continue to grow, I think there'll be that need. I'm not trying to make my pitch to become an ATC here, but answer your question, that's what I would hope. You know, my role will be dual, both referring patients, and then at some point, maybe becoming an ATC. So this is a very interesting political moment in Boston. In that Dana-Farber and the Brigham are getting divorced. They have been, you know, basically married for many years, and that moves Mass General and the Brigham closer together as a unified cancer center. Just local politics, but so there's a process now of setting the agenda for the future for this big entity, the MGB Cancer Center, and cell therapy is at the pinnacle of that. I mean, I'm amazed. My cell therapy colleagues, it seems like they get whatever they ask for. You know, so we are hiring a new faculty member who's gonna be, as, joint appointment in cell therapy and melanoma. But again, the people recognize that this is the future in melanoma and other cancers, solid tumors, you know, so they're really prioritizing that in terms of the agenda of the larger cancer center. Wonderful. Thank you. So those are all of the questions that we had prepared for you, but we have other people in the room who would also like to ask some questions to you. So we will let our covering analysts start. Do you want to start off first? Thank you so much. Pete Lawson, Barclays. Just continuing off of the question or your pitch, Dr. Brockstein, just around what would you need to do to become an ATC? In terms of infrastructure, you know, we do hematological cell therapy, we do CAR T, modest-sized program. It's relatively small, but we have the infrastructure for the financial part, for the inpatient care, the expertise from the heme colleagues and then, you know, myself on the melanoma side. So obviously, we'd have to, you know, I would have to learn, our team would have to learn. But for us, I don't think it would be a big, big step up just because we have some of that infrastructure. That sounds like both of the other centers grew off of bigger infrastructures, but we have at least some of that. Obviously, the other part is actually getting the authorization. I think it's, you know, showing that you have the infrastructure to get the authorization and then get the authorization. Then just a question for Dr. Lawrence and Dr. Olson. Just how they think demand's gonna shape out for the second half of the year? Oh. If there are any constraining factors there around hospital beds, et cetera. No, I think demand is it, the pent-up demand was there, and I think as the word gets out, it's gonna... there are gonna be more and more referrals. But as I said, it may not be to me, it may be to other centers that are closer to home for people. So, I mean, we have the same constraints. I mean, at most, we can treat four or five patients a month because, you know, just the hospital beds, everything else. But, you know, I don't see the demand going down. I see us probably treating similar or maybe even fewer patients, but it's just gonna be distributed to other centers. I agree. Mm-hmm. Reni Benjamin, Citizens JMP. Thanks for, you know, all the answers. I'm still kind of curious about frontline usage and how ultimately, you know, how many are coming to the community setting versus the academic? I would think the large majority are coming to the community setting. And then how that ultimately, you know, will get... Yeah, how you use pembro until in that setting. It seems to me that everyone would be using CPIs, right, checkpoint blockade, and then once you failed from that, would ultimately move to, you know, the TIL therapy. It seems like that's the standard. So, I'm kind of curious how you see this shaping up. Could it ever get to that real frontline setting? And then specific to the trial, I think you mentioned that there was a DLT in the question and answer session. I'm kind of curious what the grade 5 event was, you know, the specifics around that, and the two unconfirmed CRs, when did they ultimately become confirmed? The grade 5 question I can probably answer quicker. So I think that patient had liposuction and then a lymphodepletion, and then had a septic event, probably 3 or 4 days after the liposuction infusion. And that's sometimes one of the risk factors, right? These patients are gonna be neutropenic and certainly at risk for infection. You're giving them prophylactic antibiotics, antivirals, antifungals, but if they develop an infection, you treat through it. My understanding with that patient, that patient also had aggressive biology, maybe high elevated LDH. I think there's some factor we're seeing, and I've mentioned this, like 20% of these patients where we harvest, and then you're waiting 4 weeks to get that product back, and probably 70% of these patients will be ready to get that product and good to go, but we have these, this 20% of folks, I think, that have this aggressive biology, and they decline, right? The disease is progressing more rapidly. They're not eating as much. Natural history of the disease is to lose weight, not eating, more chair bound, more bed bound, and that's the worst time to give lymph depletion to that patient. And certainly, you have a patient who's waiting for this product too, and you almost feel guilty not to even try at that point. Sometimes you have those patients that are sitting right there at the fence, should you, should not, and, I've gone both ways. I can imagine a young patient who's got aggressive biology, maybe reasonable up front, and then you give therapy and then having septic issue because they're probably not in the best of condition at that point in time. That was the one patient. What was the other question? Frontline setting? Well, so the frontline for sure, how you ultimately, you know, would be able to do this, especially since I think the majority are being treated in the community? ... Yeah, but right now it's still a phase 2 study, right? So it's not prime time for the first line. We need to prove that these outcomes are probably gonna be better. I do hope that that CR rate of 30%, which is probably the best CR rate we've seen. You know, if you look at ipi-nivo, initial CR rate of 11% with the initial publication, that evolved to 22%. And PD-1 response CR rates were around 10%. You know, rela-nivo was probably 16%, but if we're seeing 25%-30% response rate in the upfront setting and the NCI showed this, right? 96% ten-year melanoma specific survival in a young patient, where we wanna try to get complete remission off therapy, right? The best patient to see is the one we're seeing every six months, doing well, and I just get to say hi to them, right? And so if we can show that those patients are, you know, we're getting a better percentage of those patients upfront, I think it's gonna be easier, easier to take that combination. And knowing that the, the side effect issues you have to deal with are gonna be more reversible, short-term related issues, and then you're just dealing with the, the PD-1 monotherapy, which is relatively safe on the back end if you're going two months and beyond. I think you had another question about the confirmation of the unconfirmed CRs that you see on the slide. They actually already confirmed. Oh. So they confirmed post-data cut. So we have a little asterisk on there saying that they confirmed. So all of the CRs that are being reported there are confirmed by repeat assessment. Hi, it's Michael Yee from Jefferies. In the commercial setting now, where it's approved, maybe just talk a little bit about how fast and how smooth enrollment, excuse me, reimbursement is going. I know there's been differing messages about how long that is, and perhaps that's the gating steps. So maybe just talk about that journey and the speed as to how long it takes to get people from enrollment to actually getting the drug. Uh, sorry. And then in first line, following on that question, can you just talk a little bit about who the right patient is to be using this in first line, and the relevance of pembro as a control arm and how people should think about the design of that study? Thank you. So I'll answer the first question, 'cause it's easier. That it's entirely payer dependent. And again, it's getting smoother. That's not the rate limiting factor for us right now. There are occasional cases that, you know, we have to go to wrestle and go to the mat, but, you know, it's, it's the indication is there, and the payers need to be educated. So... But you need a team, you know, prior auth and hospital, who is, who's behind you, and we, we have that. I imagine you guys do as well. Yeah. So I can speak to that and say that we've not had a big problem with reimbursement. We did in the initial phase when there were payers from small out-of-state, HMOs and things like that, that didn't know what it was, and so we just had to go through, peer to peers and talk to them about it, but we didn't have any issue. Yeah. I had a patient who had to go to his senator's office to call his insurance carrier, so that worked. But yeah. Your second question around what, how do you use it in frontline? And so, you know, and it's not gonna be like everyone's gonna get TIL plus pembro, if that, you know, tends to be pembro on its own, which, you know, based on the data we've seen so far, we're optimistic about. But, you know, we wanna think about our tool set and what we can do to get patients that long-term immunotherapy response. You can get that with checkpoint inhibitors. You can get that with TIL. That's what we want for everyone, and we wanna do that and get them there without being, you know, having long-term side effects. So, you know, if it does turn out that TIL plus pembro looks significantly better, then you're gonna offer that probably to the patient who wants to swing for the fence from the get-go, and that's gonna be the younger, fitter patient, someone who's not gonna have a big issue getting through the treatment. But then I think we'll be really interested to learn about, like, what the long-term safety data looks like. So, you know, TIL therapy is gonna be short and intense therapy, whereas checkpoint inhibitor can be intense and short, but also long-term side effects. And so getting the comparison of what that looks like five years down the road, I think there's... That's a little bit unknown, but actually could favor, you know, TIL therapy, since you, you get through it, a lot of the toxicities are reversible. So it's still to be determined, but I think it would be a great option if it is successful and, you know, being able to offer that to the motivated patients who wanna go through that upfront. And also the patients who you would predict are not going to do well with checkpoint inhibitors, the mucosal patients- Yeah. acral patients, patients with a low tumor mutational burden. There may be other, you know, markers of poor... There are a lot of other indicators, predictors of poor responsiveness. Those are the patients I actually put on the frontline trial, selectively, you know, mucosal patients primarily. And then- Sorry, but once you cover the clinical aspects, maybe I can comment on some of the rationale for PD-1 and for pembro- Session. For pembro and the control arm, but I wanna let the clinical discussion to complete first, but I'm happy to comment on that. Go for it. That's what I was gonna talk about, but I think you know about. Yeah. So let me... Because it's really more of a drug development and regulatory strategy, right? So primarily, the combination with pembro is a rational combination, right? Remember, these are unmodified T cells. They are subject to control mechanisms, and that includes the PD-1 axis. Interrupting the PD-1 axis that inhibits our T cells makes a lot of sense. Do you necessarily need to add IP to that? No, probably not, because-... again, we're still discussing what Ipi actually does. Part of what Ipi does is acting on the T-regs, which are depleted at the time we are administering this, right? So it's probably PD-1 is much more important to add to TIL than adding Ipi to that. So doing a triple combination is not only more potentially not the most obvious first thing to do when you go into the combinations, might also not be as rational of a combination. So now that we are set with TIL plus Pembro, the question of the control arm becomes a regulatory question around what do the reviewers now need to see when we present a randomized comparative data set? And they will not—they would not accept a data set where we are doing TIL plus Pembo versus Nivo/Ipi. They cannot isolate and identify the contribution of components, and they're going to send it right back to you and say, "No, that doesn't work for us." We've had discussions with the regulators, and we presented this design to them. They agreed to it wholeheartedly, and they said that's the right study. Is that now addressing some of the questions that were asked, which is now how does it compare to Nivo/Ipi in the combinations? Well, you're gonna do cross trial comparisons, which you saw in this session. Everyone is very happy to do. And then we can maybe, as a next step, think about running some additional trials that address that. But the first thing is we need to get this through and in front of regulators, and that's really the rationale for it. It's not unethical. It is a very straightforward drug development strategy that makes a lot of sense, and that's been aligned on with the health authorities, who are ultimately the first reviewers of what we're presenting there. Does that make sense? Yeah. You know, I would just add that in practice, you know, PD-1 monotherapy, especially in PD-L1 positive patients, many different subgroup analyses have shown that survival is very similar, when compared to combined checkpoint inhibitors. And so there's a lot of enthusiasm in the field to use combined, immune checkpoint inhibitors because the response rates in cross-trial comparisons are better, but the direct comparisons are not there. But then multiple subgroup analyses suggest, especially in those PD-1 positive patients, Pembro monotherapy, PD-1 monotherapy is absolutely a standard of care. So, you know, if you're concerned about that, you think about that selection for your patients, but I think in practice, I think that's fine. Yeah. All the benefit of adding Ipi to Nivo is in the BRAF mutant patients. So that's another consideration. But it's-- I can't say it's not problematic. Many people are convinced that frontline therapy should be combination checkpoint inhibitors. I mean, if I had to bet, I would say this is gonna be a resoundingly positive trial, and it's gonna be a more rigorous comparison. You know, it's just, it's hard for many people to get away from Ipi and Nivo and Nivo and Rela as first-line therapy. I guess I would add in again, as someone who's—I mean, we're at a kinda hybrid community academic center, but still a community center. For me, first line is not always combination therapy, and I think it's on us as oncologists to parse the data. Right? So we have two markers that I think have been pretty well established, PD-1 and BRAF. I think the BRAF data is actually really compelling from the CheckMate-067 study, with you know, only the BRAF positive patients benefiting from combination therapy in a big magnitude. So even for my younger, healthy patients, at least until Opdualag came along, if they're BRAF wild type, I did not necessarily subject them to Ipilimumab. Of course, there's the whole population of patients who are older. You know, not everybody's going to be eligible for this therapy because we treat a lot of patients who are 75, 80, 90, you know, with PD-1 inhibitors. It's actually not that hard. So there, there's that population of patients. But I think the data is gonna shake out and tell us, right? Thank God, these studies are being done. The way that study design is being done, and in my mind, it may take a little longer because the survival data will take second line, Ipi and second line, TIL therapy to actually see if there's an overall survival benefit. So maybe it takes a little bit longer than if it was the combination up front. So you know, it's on us to look at the data, but from the standpoint of actually giving the treatment, I mean, we all know, like, if you're giving even Ipi/Nivo, IO therapy, TIL therapy, a lot harder. So in the community setting, it's gonna take people seeing that the data shows that there's a benefit to their patients to give up those patients. But if it's... If that's what the data says, they will. Okay. Just... Please. Go ahead. Go ahead. Well, we're getting short on time here, and everybody's hungry. Do we have - do we wanna just maybe one more question? Okay, one more quick question. We got a lot of... Yeah, Yanan's got one, too. Just keep it to, like, a really quick one. We'll find that out. Hi, guys. Asthika from Truist. So Dr. Lawrence, you talked about identifying patients early on. Dr. Olson, you also spoke about patients—some patients are hanging around that you—and you're thinking you want to put them on this, but they're waiting for the TIL therapy. So maybe you can help us in figure out this launch, how it's going. Can you maybe say give us some sense of, given your current run rate in which you're treating patients, how soon you will be able to get to and address those patients who are, quote, unquote, "hanging around" and waiting for for this versus purely just going to a run rate of where you're just treating the patients who you've identified and have recently had TIL had frontline failure? Yeah. If, if we have a patient who's a candidate, we're gonna get them in and get started. No one is hanging around at this point. There's no... I mean, there's some bottlenecks, but they are openable. Is that right? So- ...Yeah, the patients that are waiting is more that I have concerns about their fitness and that they, even in the most optimal conditions to get them to therapy for TIL therapy, that I thought they were going to go through it. I wouldn't think it would work, so I'm giving them chemo to try and control things. But there's not really any bottlenecks to get them there. It's just more that I don't want their disease to progress so fast, so I'm giving some time to work it out. Yeah. So, hi. A quick question from, I'm Yanan from Wells Fargo. So, there was a comment made today at the presentation by the discussant about the overall age of the frontline study is a little younger than other IO studies. So I was wondering if that a result of because, you know, patient selection, and these kind of patients are more appropriate for the TIL pembro. And if that's the case, then when you look at a higher response rate, and then how do you explain the potential contribution from the younger age, when you have the ultimate data? What kind of delta are you looking for between the two arms, you know, at this time point, that you would think you can declare, you know, this is the therapy that you think is worth approval and adoption? Thanks. So I'm in the state of Florida, so I think, you know, there's a third of patients are not going to be eligible for a trial, just because of brain mets and, and poor biology or, you know, they're declining perform status. I have another third of patients who run for the hills if I say clinical trials or, you know, mRNA, that kind of thing. The younger, more educated patient, you know, they're gonna come in, and they're very in tune to the trials and doing something. Now, because they're pretty aware of their dis-- you know, their situation, and they want to take the best chance for the long-term response and long-term remission. So those are the patients, typically, they're more likely to be in a clinical trial and participate in a study. And hence, why I think, in my opinion, at least in, in my situation, those patients tend to enroll in clinical studies. I don't think the age sort of influenced the response. I think we've seen responses to IO therapy, whether they're elderly or young in the checkpoints. But I think in terms of the clinical trial enrollment and the population we're seeing, it's that patients who are educated and want to make sure they, optimize their best chances for long term. Yeah, ultimately, that's why we're running a randomized trial, right? So in order to really control for the composition of the population, ultimately you have to run a randomized trial. This was the initial trial to present the proof of concept for, number one, safety of the combination. Number two, the efficacy. I think we clearly saw that it's worth taking it to the next step, and that's what we do with TILVANCE, right? The delta, as you know, the primary endpoints for that study is ORR, as well as PFS. And it's designed like any randomized comparative phase 3 study with underlying statistics that make assumptions around the delta that that's meaningful to what you expect the control arm to have. Again, we have data on the control arm, pembro monotherapy from KEYNOTE-006, right? So now look at the data that we presented, that were presented at NCI, and I think that will be pretty clear what we're shooting for. PFS, similarly, it's driven by time to event and your usual statistics that are not different from any other comparative trial with the PFS endpoint. Okay. Ben Burnett from Stifel. Just one quick question on just coming back to the logistics for Dr. Lawrence and Dr. Olson. How long did it take you to get, I think you both mentioned something in the neighborhood of sort of 4-5 patients per month, kinda, flow rate. How long did it take for you to get to that point? Instantly. Really. I mean, we had-- there's a pent-up demand and... Well, at least for us, it's actually coming down a little bit, but that's because other centers are opening. Yeah, it took us maybe a little bit longer, just because we had a couple payer issues in the very beginning, that's gone away. So, like, we're treating a couple patients a month or a few patients a month right now. And then we had to change some of our processes with the surgeons. You know, one or two who are super involved, some of the other ones who had tumors in places where we had to get a subspecialist surgeon who was not familiar with the process, and it, you know, delayed some OR scheduling, but that's mostly been taken care of. So, it took a couple of months. Yeah. All right, I think we have to get on to dinner here. Everybody's starving, and we have a lot of additional stuff to do tonight. I wanna thank Dr. Thomas for the great presentation at ASCO today. That was fantastic on the frontline data. We really appreciate it. And I wanna thank Dr. Lawrence, Dr. Olson, and Dr. Brockstein for coming here and giving their perspectives to the audience here on how the Amtagvi process goes, how launch is going. If you have any questions, feel free to follow up, either right here, you can probably grab some more time a little bit here, or with our IR team for questions, and we'll still have some time to speak. Thanks, everyone.