Iovance Biotherapeutics, Inc. (IOVA) Earnings Call Transcript & Summary

Thanks 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. And then we will have a KOL panel to hear some perspectives on the launch of Amtagvi. We have Dr. Daniel Olson from the University of Chicago, Dr. Donald Lawrence from Mass General, and Dr. Bruce Brockstein from Endeavor Health NorthShore, who is a referral physician. So we look forward to the session today.

You guys hear me pretty well? All right. Perfect. Again, my name is Sajeve Thomas, medical oncology at the Orlando Health Center. I primarily just practice in 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 autologous TIL therapy combined with pembrolizumab in patients with a checkpoint inhibitor-naive unresectable metastatic melanoma. And again, the updated results of the IOV-COM-202 data. This is a Phase II 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. 1/3 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 a onetime dose of lifileucel and the pembrolizumab treatment. And these results support the ongoing Phase III TILVANCE-301 trial. Again, for a lot of us who deal -- treat melanoma, we know that more than half our patients are not going to respond with dual checkpoint therapy. It's like 60%, 70% of these patients will have recurrence of progressive disease. How do we get that tail, the curve up and get it a little higher? Lifileucel is approved as a second-line option based on the C-144 study that showed the response rate of 31.4%. And that was a response in patients who had multiple lines of therapy, median line of 3 lines of the treatment. The longest duration response, independent response was 55 months, and I have patients who are now 6 years out, 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. And this is 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 was more interesting, their CR patients had a 96% 10-year melanoma-specific survival. And so the 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 one resectable tumor and another measurable tumor for a response assessment. These patients are screened in, had a harvest, followed by early dose of pembrolizumab and then lymphodepletion, lifileucel, IL-2 up to 6 doses, and then they can continue the pembro every 3 to 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 are 4 unknown primaries. 60% of these patients were [ viscera ] involved disease and 56% of these patients have PD-1 -- a positivity of 1 or more. 1/3 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-heme issues were specifically chills and pyrexia, nausea, vomiting, fatigue, febrile neutropenia, right? And that's something that I think we've all seen. These patients become neutropenic during the second week. They're getting TIL. They're getting IL-2. And the IL-2 is typically the cause of the fever in 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 resolved to less than a grade 2 in the majority of cytopenias. And with the exception of maybe lymphopenia that took a little bit longer, and then we get PCP prophylaxis. So AEs, consistent with lifileucel. Anything more than 30 days in terms of AE issues are typically consistent with what we expect with PD-1 monotherapy. The response rate, 65%. Complete response, 30%, probably the highest complete response rate we've seen. And partial response of 34.8%, so a total 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 up for 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 in the other folks, you got 4 or 5 of these folks evolving to a CR over time, typically 1.5 years. 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 6 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, you got 3 of these folks that had ongoing response, but they withdrew for other reasons. And I always like to talk about that one patient right there because 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 though. Duration of response not reached in 53% of these patients had responses that are beyond 12 months. Immediate time to response was 2.6. Again, 10 out of 15 ongoing, with 3 that withdrew from the study for other reasons and they had ongoing response. And we'll 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 that match to what we see in the tumor, right? That's overlapping TCR clonotypes. And the responders had a higher rate of that overlapping shared TCR clonotype compared to the nonresponders. And the persistence of seeing that shared clonotype to 12 months, which is above -- the levels were 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. So supporting the TILVANCE-301 Phase III study, global study, right? 370 patients being randomized to the combination versus pembro monotherapy. These folks will be locked and loaded and have surgery. If they randomize the combination, they'll have surgery and move on to TIL PD-1. In those who get pembro, the surgery will be canceled. Surgeons are okay with that. They were happy to -- they'll have a backup. And they do pembro monotherapy. And if they progress on pembro monotherapy, they have the option to get lifileucel monotherapy at the time that's independently progressed, the tumor, with a primary endpoint of response and progression-free survival 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 durability of response in that immune checkpoint-naive, 65% response rate, a complete response of 30%, all evaluated patients had regression of their target tumors. In the median duration response not reached, rates and depths of response were again compare favorably to what we've seen with mono and dual checkpoint therapy. I think that's all I got. Any questions?

Hi, everyone. My name is Sara 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. And our goal today is to engage in our experts from authorized treatment centers as well as our referring physician about the Amtagvi launch. So I will begin by inviting each of our panelists to provide a quick 1 to 2-minute overview of your practice, your institution, how many melanoma -- advanced melanoma patients you see a year and the 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, but it's also a lot of fun. And 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 research is our focus, and we try to learn. But this has now provided -- this is our #1 option for our progressors on checkpoint blockade. And we really have just scratched the surface of what we can do with this. So 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 Hospital. 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. Some clinical trials and works in the post-PD-1 space, so I've been really tuned to what treatment options we have for these patients and also help to run immunotherapy-based trials in patients who progressed 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 just over 100 patients probably then, 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're incredibly excited. And we have some experience institutionally working with TILs in 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 it as an option because 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, have 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 Health System 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. It's interesting. Melanoma used to be my 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. And I say that because I think it's an important point in terms of proof of principle of the fact that there can really be changes almost at an order of magnitude. And I've been doing this long enough, 30 years, to see that in a few different diseases. And I think TIL therapy is kind of on the cusp of being kind of that next one, where there's actually something new. And we'll probably be talking about some patients in a bit. And 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 3 to 12 months who you...

You're jumping out ahead. I'm so sorry. I don't want anyone on this too excited.

I'll start over. No, I'm kidding. Okay. But no, these last 3 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 kind of help them, in a sense, limp along until there was availability of lifileucel to Amtagvi TIL therapy. So it's been a wonderful thing for me and my patients.

So thank you. Thank you, Drs. 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's 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 -- clinical trials were limited, and it was really hard to have to tell some people that they weren't eligible or 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 in into your decision-making?

Do you want me to keep going?

See, I can talk about that. So we think about this from the very beginning, we're wondering, 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 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 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 risk change, we'll think about other things later based on how they do. But yes, so I think if you don't have a BRAF mutation and you're not responding to initial anti-PD-1-based therapy, we're really thinking about how do we safely get you to TIL. And so we're -- it really depends on their sites of disease, how well they're doing, their age, their fitness because 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 you're -- 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 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 has taken off and we're sort of against the clock and things can get out of our control. So that's the way I think about it. But we're being careful with the patients with brain mets, making sure they're treated. And then age and fitness and things like that, we can consider to make sure if TIL therapy is appropriate.

Yes. So in terms of when do I think about 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, 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 going to come to that next treatment, I mean, this is a dynamic thing, right? We're only 3 or 4 months into actually having this clinically available. So in the past, it was -- am I ready to launch the 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 the complexity of actually getting the patient on to therapy, I think the key thing is early referral. 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 going to get to that point, I would rather have him to see the patient. Maybe it's going to become unnecessary. Maybe the patient won't need TIL therapy. But if they do, then that conversation has already happened already in the system. And with the complexity of getting the patient from progression to treatment and time being really, really important, I think that's actually a really key step. It's the early referral.

And along those lines, Dr. Brockstein, let's take a deeper dive into your particular practice as you're not currently at an ATC. Can you give some more specifics about how that process has kind of streamlined or how you get patients to it, authorized ATC, and maybe how that's changed 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 going to need that, I either give a call or send a text or an e-mail to Dan and say, here's the next patient. I've sent them I think about 5 so far for potential therapy. And so really, from my e-mail to him to his coordinators, back to the patient, has been a number of -- a matter of a few days. And the consultation, over a week or 2. They may not be needing therapy at that point. Some of them started seeing Dr. Olson 9 or 12 months ago as we were close to launch. And we've kind of bridged and things like that. But I think that's the key thing, it's getting that working relationship. At least for people who have a melanoma practice, it's kind of easy to know who's doing it. You 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 we're maybe kind of developing that process. For me, it's fairly straightforward.

So maybe I can just address that also. So we talk a lot about delayed responses or pseudo-progression with checkpoint inhibitors, but we talk about it more than we actually see it. We pretty much know after 2 cycles if somebody is going to respond or not. There are exceptions to that. And so we really do want to see these patients early. And yes, I think I promised you guys I would get you a 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, 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 medical problems? And then before we even see the patient, I'm talking with the surgeon, either a thoracic surgeon or surgical oncologists, whatever it may be, so that we're ready when that patient hits the door because it's a tight time frame 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 the -- how receptive patients are and open to the opportunity for Amtagvi?

They're open. They're seeking us out. I mean, we've had people from -- a patient from Poland, I had a patient from France, Canada, Brazil, who sought us out for this stuff. People know that it's out there. So we try to get people in within a matter of days to -- 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, so what can we harvest. My nurse practitioner plays a key role, so we -- it happens. It's almost like instantaneous. Is this patient a good candidate or not? And if they are, we'll get them in within a few days.

Yes. And I can add to that and say that there are patients who come in where it's not always crystal clear. I think there's a group of patients who are being referred who have been kind of waiting 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, the optimal spot to move on to treatment. And so I've had a couple of 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 going to be able to go through things and get control of their disease, then we know we can extend them through and get them to TIL therapy. And so I 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 people thinking about it, and we want to 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 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?

Yes. It's -- there's a small amount that's my own patients. It's -- actually, most of it is coming from outside, so it's grown our center. I think it's actually -- it's been good in terms of our program and seeing more patients. But yes, it's been a lot of people referred from places that I've never got referrals from before. And I think that's really because we're one of -- 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 yes, 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 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 previously.

Dr. Lawrence, did you want to add anything?

No. I think it's a lot of work. It's a lot of work. But it's great.

Thank you for discussing 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, Sara. So again, Drs. Lawrence and Olson, thank you so much for your enthusiasm, and you really are exemplary programs. Your ATCs really have streamlined the processes, workflows and understanding how to get these patients quickly to treatment. Understanding that there is some time lines 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 chain of custody with the product, they knew how to do that. Our nurses, our coordinators and our insurance people also were very proactive. Some of the payers have never heard of this stuff, and they didn't have any way to even preauthorize or evaluate it. And so we had to teach them. Also, the hospital was helpful with that. And you guys were hopeful with that also in just helping to navigate some of those insurance issues, which with any new complicated treatment like this, it's going to 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 3 months now. So I think we were one of the first centers to start offering this. And so we had this huge rush. It's -- I think it's going to 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. But it is -- I think there is an opportunity as these centers come on board to do some teaching and share experience and get them up and running smoothly.

Yes. And I can also say that we've a similar process where we have a good CAR T-cell program, the way to organize payers is really similar. And so institutionally, there is people in place to make that happen pretty quickly. There are 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 4 disease that weren't doing this before. And so they're fine -- they're obviously really happy to know that they can offer patients something where we can increase the overall benefit for patients and do better. But then when it gets down to the brass tacks of making it happen on the time line, it'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 3 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 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 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 will 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.

I think those -- well, our surgeons are very invested in this because they're immunologists and PhDs, and they like to take little pieces to the lab and play with them. So they are extremely enthusiastic. But I think through like the SSO and other organizations, this -- the news is being disseminated and it really is a multi-disciplinary approach, and it absolutely requires having surgeons who are -- who understand what's going on. So that's another -- 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 managing that?

It's getting harder, honestly. So again, I think as more centers are coming online, and it's -- so it can be challenging to 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 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 does 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?

Sure. Yes. So we -- once we know the cells are coming, at that point, it's time to start the patient. And 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 has its own payer implications. Cheaper to do that. It's also nicer probably for those patients because they live locally. They can sleep at home rather than spend up to potentially weeks in the hospital. So yes, we set them up. We get -- once we have the cells here, we say, we really feel comfortable. So at this point, we've started lymphodepleting once we really have confirmation of the cells already in there. 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 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, a 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. And then we see the patients outpatient, 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, scan the patient. We want to see how things are going, and then send them back and see their oncologist, so send them back to our referring team.

Yes. We heard from Dr. Thomas that the disease, it's 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 support of IL-2?

Yes. I mean, I look at this as kind of like CAR T without the cytokine release or neurologic toxicity. So -- but our cell therapists were kind of terrified by interleukin-2. I actually now round on that service. So I've had to learn how to treat cytokine release and so on. But we just don't see that. So they're like febrile neutropenic patients after they're done. And most of them actually go through IL-2 very easily. And it's easier to give IL-2 to somebody who's lymphodepleted than it was in the old days. You guys probably don't remember. You do. High-dose IL-2, I have PTSD from that. But yes, we, at least so far, have gotten in 5 or 6 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. And 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 on Amtagvi, but having more cell therapies available at your center and planning ahead for that. So 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?

Yes. I think for us, there was this initial deluge because we were one of the first centers. So -- and I don't have any like -- patients can get treated elsewhere or any -- we're going to have our patients. And it will settle out down, it will 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 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's a -- there are too many ideas and options even. We really have to focus in on what we think will be best, and that's going to come out of our laboratories. And that's where the hypothesis 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. It's really just the beginning. I mean -- and then it's going to other tumors, so I think it's just -- it's so exciting now, but it's going to get better.

Yes. And on a personal level, it's been really nice because I came in treating patients with melanoma, and there are starting to be cell therapy trials. And it was all being run by our cell therapy doctors who are all treating leukemia and lymphoma and so -- but they didn't -- more familiar with these different indications. Whereas I was just out of training, I was like, yes, I would definitely do this, and I was interested in immunotherapy. So it was fortuitous that this -- I was in that right place to sort of be the solid tumor cell therapy person, and I also happen 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 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. And so we're hoping to expand this treat anywhere between 5 -- up to 5 patients a month, more if we could handle it. But I think right now, that's probably our capacity. And then we study those patients, we bio bank 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. They've generated lots of data about different performance characteristics in patients on 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 for studying those patients. So it's going to be really exciting to be able to answer those questions, which are important practice, but then actually have this be a new part of oncology that we're doing cell therapy in solid tumors.

That's great. I have to talk to you on about optimization.