Good day, and thank you for standing by. Welcome to the Amtagvi FDA Approval Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there'll be a question-and-answer session. To ask a question during the session, you'll need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Sara Pellegrino, Senior Vice President, Investor Relations and Corporate Communications. Please go ahead. Thank you, operator. Good afternoon, and thank you for joining this conference call and webcast to discuss the U.S. FDA approval of Amtagvi in advanced melanoma. Dr. Fred Vogt, our Interim President and Chief Executive Officer, will provide a brief introduction and key highlights from the label. Jim Ziegler, EVP, Commercial, will discuss next steps for commercial launch, and Fred will conclude the call with further details on value and access. Additional members of the senior leadership team are also on the call and available for the Q&A session. Earlier, we issued a press release that can be found on our corporate website at iovance.com. Before we start, I would like to remind everyone that statements made during this conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans and transactions, revenue, commercial activities, clinical trials and results, regulatory approvals and interactions, plans and strategies, research and preclinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interactions, licenses and collaborations, cash position and expense guidance, and future updates. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filing. Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward-looking statements. With that, I will turn the call over to Fred. Thank you, Sara, and good afternoon, everyone. I'm happy to announce that the U.S. Food and Drug Administration has just approved Amtagvi, the brand name for lifileucel. Amtagvi is the first approved T-cell therapy for a solid tumor and the first treatment option for advanced melanoma after Anti-PD-1 and targeted therapy. Amtagvi deploys patient-specific T-cells that recognize distinctive tumor markers on the cell surface of each person's cancer. Amtagvi is manufactured using our proprietary process to collect the patient's T-cells from a portion of their tumor, multiply them into the billions, and return them back to the patient to fight cancer. Each year, approximately 8,000 people in the United States die from melanoma. Until now, there have been no FDA-approved treatment options for patients with advanced melanoma whose disease progressed following an immune checkpoint inhibitor and, if appropriate, targeted therapy. For these critically ill patients, Amtagvi ushers in a new era for the melanoma treatment landscape as a one-time cell therapy that is made specifically for each patient. The FDA granted accelerated approval for Amtagvi based on the C-144-01 trial. The C-144-01 trial is a global multicenter trial investigating the efficacy and safety of Amtagvi in patients with advanced melanoma who progressed on or after prior anti-PD-1 therapy and targeted therapy where applicable. Efficacy was established based on objective response rate and duration of response. Amtagvi demonstrated deep and durable responses in the C-144-01 trial. We are extremely pleased that cohorts 2 and 4 of the trial, which had the same primary eligibility criteria and treatment protocol, are both represented in the U.S. prescribing information. I'll walk you through a few key highlights. First, the primary efficacy set in the label included 73 patients from cohort 4. I note that this primary efficacy analysis set was determined by the patients who received the recommended Amtagvi dose from an approved manufacturing facility. Among these 73 patients, 31.5% achieved an objective response by RECIST 1.1. The median duration of response was not reached at 18.6 months of follow-up, and 43.5% of responses had a duration of 12 months or greater. In addition, the label includes a supporting cohort efficacy set of 153 patients from cohorts 2 and 4. 31.4% of these patients achieved an objective response by RECIST 1.1. The median duration of response was not reached, and 54.2% of responses had a duration of 12 months or greater at 21.5 months of follow-up. Additional details about Amtagvi are available in the important safety information and prescribing information. Detailed results from our C-144-01 clinical trial were also published in the Journal for Immunotherapy of Cancer in December 2022. We also continue to investigate Amtagvi in frontline advanced melanoma in the phase 3 confirmatory trial, TILVANCE-301, as well as the pipeline in additional solid tumor types, which represent 91% of the cancers in the United States. With the strength of our clinical data, manufacturing capabilities, and commercial readiness efforts, Iovance is well positioned to begin rapidly providing Amtagvi to the U.S. melanoma community. Commercial manufacturing is approved at our internal facility, the Iovance Cell Therapy Center, or ICTC, as well as at a nearby contract manufacturer with capacity as built for up to several thousand patients annually. Both facilities are prepared to begin receiving tumor samples from authorized treatment centers or ATCs and initiate the manufacturing process. We are truly excited about our U.S. commercial launch, and Jim will describe internal efforts and activities. Jim? Thank you, Fred. Our commercial and cross-functional teams are thrilled to launch Amtagvi. I will highlight our ATC onboarding, payer engagement, and commercial operational readiness. First, onboarding is a strong indication of ATC commitment and Amtagvi demand. Today, approximately 30 ATCs have established their TIL service line capabilities. These centers are educated in all aspects of the Amtagvi treatment regimen, with staffing, training, and processes in place to immediately proceed towards treating initial patients. Additional centers are completing final onboarding in the coming weeks, and we remain on track to have more than 50 ATCs within 90 days of the original PDUFA date of February 24, 2024. Many ATCs have patients already identified, and we look forward to supporting them throughout the journey. With the commercial launch of Amtagvi, we also expect strong market access and inpatient reimbursement. Payers have expressed their appreciation for the value proposition for Amtagvi. The payer mix includes a favorable commercially insured population. More than three-quarters of advanced melanoma patients are currently insured through commercial, Medicare Advantage, and Medicare IPPS-exempt segments. Based on our payer interactions, we expect coverage similar to approved CAR-T products requiring prior authorization with coverage consistent to label, medical coverage policies issued within about 90-180 days, and single-case agreements for commercially insured patients. As a reflection of our commitment to access, we developed Iovance Cares as a comprehensive support program which is available for patients with advanced melanoma and ATCs throughout the treatment journey. We are confident in our ability to deliver a successful launch, and I would like to acknowledge the extensive effort of our cross-functional teams in preparing us for today. I will now turn the call back to Fred. Thanks, Jim. Amtagvi is a one-time treatment that has demonstrated significant value to address an unmet medical need for advanced melanoma patients in our C-144-01 clinical trial. Amtagvi also represents a first-in-class approval for an indication with no prior FDA-approved therapies. Based on this value proposition, as well as our analysis of appropriate benchmarks, Amtagvi will have a U.S. wholesale acquisition cost of $515,000 per patient. As a reminder, revenue recognition for Amtagvi occurs upon infusion like other cell therapies, so we expect to begin recognizing and reporting significant revenue in the second quarter of this year. We're committed to the U.S. melanoma community and hope to begin treating patients with Amtagvi as soon as possible. I'll now turn the call over to the Operator to begin the question-and-answer session. Thank you. To ask a question, you'll need to press star one one on your telephone. To withdraw your question, please press star one one again. Please wait for your name to be announced. Please stand by, but we compile the Q&A roster. One moment for our first question. Our first question comes from the line of Michael Yee with Jefferies. Your line is now open. Hey, guys. Thanks. Good afternoon and congrats on the approval, a long-awaited approval, and a great day for you guys. We had maybe two questions. One was thinking about the launch this year and your preparedness. Can you just comment on your expected annual price with the Proleukin, what you're thinking there, and then your visibility on how many patients you think could happen this year? Maybe talk a little bit about that and any bolus. And then the second question was maybe just a little bit more detailed. If I heard you on the label, you said that there was median duration not reached. If I recall, there was some median duration on the cohort 4. So does that sound better than expected? And maybe just comment about your view of the label as it relates to efficacy and safety in that label. Thank you. Yeah, Mike, let me start with the second question first. Yeah, the label was unexpectedly good with respect to median duration of response being not reached. If you recall, at many investor calls, we noted that the full analysis set might change as the FDA reviewed the data. In fact, it did change, and that led to the ORR and MDOR being significantly better than what I think a lot of people in the street may think. So again, it's 31.5% ORR on the label for 73 patients with MDOR not reached, and that's what it says on the label in the efficacy section. You can see that in the press release as well. Back to the launch proposition, preparations, and expected annual price, we can't really disclose much additional details. Proleukin price is out there. Yes, we expect a bolus of patients coming through. As the product launches and we start to see the manufacturing flow, we'll be able to talk more about how we expect the launch curve to go. But as of right now, we're built for a very significant launch, as you know, and we're expecting a lot of patients in each center. We're planning for approximately 30 centers at the time of launch. Good. Very good. Thank you, guys. Thank you. One moment for our next question, please. Our next question comes from the line of Tyler Van Buren with TD Cowen. Your line is now open. Tyler, your line is now open. I'll go to the next question. Our next question comes from the line of Colleen Kusy with Baird. Your line is now open. Hi. Great. Good afternoon. Huge congrats on the approval today. Thanks for taking our questions. If there's any kind of comments you can make, I know you had mentioned there's been patients who have already been identified, but any kind of comments, color, you can provide on the bolus of patients we might expect towards the beginning of the launch. And then can you help us understand the capacity, the patient capacity at these first 30 centers? Yeah. Jim, why don't you take that one? Hi. Thanks for the question. Yes, there is an unmet need, and we are onboarding, as you know, and we'll launch with approximately 30 centers. We're not given specific guidance in terms of how many patients at each center, but I can say that given the unmet need, the strong product differentiation, my team is actively working, as we speak, with these centers to start onboarding and potentially identifying these patients for treatment. Great. And then one follow-up, if I can. I know you had mentioned probably more significant revenue in the second quarter, but help us just understand obviously, there's the manufacturing window in there as well, but just help us understand the timing between kind of patient identification and revenue recognition? Yeah, Jim, do you want to take that one too? I mean, we can both listen to that one, Colleen, if you want. Go ahead, Jim. Sure. Colleen, as we sort of highlighted before, the first step after patient identification is for the centers to work through the prior authorization, and for commercial patients, the single-case agreement. What we do control is the manufacturing process, including the lot release. And then, as you also know from the treatment paradigm, it's followed by seven days of lymphodepletion. As Fred highlighted earlier, revenue recognition is upon lifileucel administration. So that'll give you a sense of how long it'll take from patient being identified to when we recognize revenues. Great. Thanks for taking our questions, and congrats again. Thank you. Thank you. One moment for our next question, please. Our next question comes from the line of Reni Benjamin with Citizens JMP. Your line is now open. Great. Thanks for taking the questions, and congratulations from me as well. Great day for the team and for patients. Fred, can you comment a little bit about the black box label, kind of how you're viewing it? Was this expected? What you think it might what kind of impact it might have on sales? And then maybe from a manufacturing perspective, I think in the label, or at least in the press release, it's talking about 34 days to manufacture. Is that something that is just kind of put out there as kind of like a worst-case scenario? Is that something that you guys can improve upon? Because I don't remember it being that long. Just any comments on the time to manufacture as well. Yeah. So the black box looks pretty good. What we think it's much better than what the CAR-Ts have. It doesn't have a REMS first and foremost like the CAR-Ts do. It's got box warnings essentially for known risks from the lymphodepletion and the IL-2 therapies that we provide. Things include internal organ hemorrhage, cardiac disorder, respiratory acute renal failure, that kind of thing. When the USPI is up, you can see more details about this, or you could glean a lot of it from the press release, but we don't see that having any impact on sales. It's already out there. It's already been reported. You can see it in the studies. And we don't have the things like CRS and HLH and ICANS that you would see with the CAR-T, obviously. On the 34-day thing, that 34 days are a target for the entire process, basically from the arrival at manufacturing to the product leaving the door. And that includes both the 22-day manufacturing process as well as all the QC testing that we have to do, including sterility testing, everything. That's our target. And yes, we think we can improve on it over time, but for now, we have to put a number out there that we think we can hit. So the sites are aware of what we're doing. The ATCs are aware of what we're doing. So that's why we do that. Got it. And maybe just a follow-up for Jim. You mentioned full service line capabilities, that these 30 ATCs have already established that. What exactly is that? And is that kind of like the last step in terms of getting on board? So once they have that, they're ready to start treating patients tomorrow if they needed to, or is there something else remaining? No, that's pretty close to it. Let me just describe it in a little bit more detail. So what our team has been doing up to this point is educating on three areas. First, clinical, really making sure that the end-to-end clinical management and the patient journey are well understood by medical oncologist, surgeon, and the cell therapy teams. That's the essence of operationalizing a TIL service line at the ATC. The second component is really important because it's the operational aspects, really around the tumor journey, making sure that we have all systems and processes in place in the OR, chain of identity, chain of custody, product handling, logistics, all of the sort of critical elements of handling the live cells of each and every patient. And then the third aspect is the administrative and reimbursement. So there's different levels of training that we do, and there's a certification process that every center and everyone that's involved has to go through. That's really the last step that we're completing right now. Excellent. Thank you very much. Congrats, and good luck on the launch. Thank you. Thank you. Thank you. One moment for our next question, please. Ladies and gentlemen, we are experiencing technical difficulties. Please stand by for one moment, please. Our next question comes from the line of Andrea Tan with Goldman Sachs. Your line is now open. Good afternoon, everyone. Congratulations on the approval. Jim, maybe one for you. Is there anything you can share on the number of manufacturing slots allocated for Amtagvi at this point? Hi, Andrea. We're not giving guidance on that right now, but we do feel like for launch, we have sufficient capacity as we're onboarding these sites in a controlled, disciplined way. Great. Thanks so much. Thank you. Thank you. One moment for our next question, please. Our next question comes from the line of Asthika Goonewardene with Truist. Your line is now open. Hi. This is Karina for Asthika. Congratulations on the approval. So for the analysis, it looks like 14 patients were excluded from cohort 4. Was this primarily due to the lower dose being administered? You also mentioned manufacturing, or is there anything else that was being noncompliant? I think you're asking why is the cohort 4 dataset 73 patients instead of 87? Yeah. Yeah. It's partly explained in the press release, but the reason for that is FDA tightened up our number, the total viable cell spec. Now, this is something we can deal with pretty easily. We can hit the middle spec where they're tightening us to, but that clipped off some of the patients at the lower end and led us from 87 to 73. That was something that the FDA wanted to do. I alluded to it in my earlier remarks when I said they tightened up the full analysis set. Okay. All right. Thank you. Operator, are you still there? Our next question comes from the line of Yanan Zhu with Wells Fargo. Your line is now open. Great. Great. Thank you for taking the question, and congrats on the approval. I was wondering, perhaps to follow up on the prior point about out-of-spec rate, could you comment on the new criteria and how that compares with the clinical trial rate? And on the capacity, I might have missed this earlier, but in terms of the allowed capacity by the regulator, how does that compare with your expectation, and how much runway do you think that provides in terms of growing the launch? Yeah. And lastly, if I may, how do you think about how you would consider potential BD interests at this point now that you have the approval? Thank you. So yeah, I don't think I fully understood your first question about the rate. What rate are you referring to? Oh, sorry. I thought you mentioned the FDA tightened the out-of-spec criteria for the. Yeah. They tightened the total viable cells criteria, and you can see that in the press release, actually. That's it. So it doesn't really have an effect, really, on anything else except that it kicks out some of the patients, and it resulted in a superior product profile for the pivotal cohort four study. Got it. Right. Okay. Sorry. Yeah. I missed part of the call, so sorry I didn't quite catch that. But it sounds like in terms of the potency because I recall FDA will, in terms of the potency assay and release criteria, I thought the regulator will have a say for what the final criteria might be. Do you think I guess my question is, is that in line with the clinical trial kind of a release criteria? Yes. Yes, it is. If you want to talk in the follow-up call, we can probably get into some more detail here. Why don't I ask Igor to comment on your question about capacity and the scale of capacity, and then I'll come around at the end, and I'll answer the BD question that you asked. Great. Iovance, thanks a lot for the capacity question. So there are two parts to that. On the one hand, we are in a strong position to meet U.S. demand for launch and clinical trials between ICTC and our contract manufacturer. The second part is what the FDA allows. So the capacity demonstration submitted to the BLA is higher than the current projections we have for launch. So we actually have a lot of flexibility to increase capacity further by hiring additional staff before we need to go back to the FDA and request approval for additional capacity. The additional expansion at ICTC is actually already underway, which will further significantly increase capacity over the next few years. Got it. All right. And then on your third question, Yinan, about business development, obviously, having an approved product makes Iovance, I think, a very attractive company in this space. However, we are fully built and capable of going on our own here. We would always look at opportunities as they come in, and we're always willing to collaborate with people and work with people on this. Got it. Thanks. And I'll congratulate again. Thank you. If I can, operator, just for one second, there's a little bit of confusion with some of the messages going around here. I just want to clarify for everybody on the call. The price of the product is $515,000, not $550,000. Operator, back to you. Thank you. Our next question. One moment, please. Our next question comes from the line of Tyler Van Buren. Your line is now open. Hey there. Can you guys hear me? Yeah, Tyler. Go ahead. Oh, okay. Wonderful. I'm not sure what happened earlier, but thanks for taking the question. And more importantly, congratulations on the historic approval. Fred, I wanted to follow up on your comment at the end of the prepared remarks regarding the recognition of significant revenue in the second quarter of the year. Can you guys give more granularity on how many patients might be lined up now with the 30 centers waiting for Amtagvi treatment, and also how many patients per month these centers might be able to treat in the early innings of the launch versus where that could go over time? Sure. We've actually commented on this on prior calls. Let me give you a little bit of color here, and then maybe Jim and Jean-Marc can jump in and help here too. At each center, we think there's a backlog of a number of patients right now. We know that from our expanded access program that we ran up until recently. And so we have centers that could have a number of patients. I can't give you exact numbers because it varies from a few patients all the way up to the patients that are in double digits waiting for Amtagvi at the sites. The sites, as you probably know - we spent a lot of time talking about this - can handle anywhere from a few patients a month to several times that. So we can't provide any guidance now on exactly what's happening. And then there's been innumerable calls with the analysts and KOLs about this, but that's basically the Jim and Jean-Marc, is that? Fred, I think you covered it. We are prepared to launch with a significant number of centers among the highest for a cell therapy launch. Each one of these centers have invested a lot of time, energy, and effort because they have patients waiting who right now don't have viable options after progression on a checkpoint inhibitor. We'll all see how this plays out over the next couple of weeks and months. Thank you. One moment for our next question. Our next question comes from the line of Ben Burnett with Stifel. Your line is now open. Thank you very much. And I'll add in my congratulations. It's great news. I want to just kind of go back, Fred, to something you were saying earlier just about the out-of-spec rate. How many patients in cohort 4, I guess, were not included in that analysis because of having out-of-spec products? Roughly, it would be 87- 73, Ben, so 14. Okay. And I mean, is that a good proxy for kind of what to think about in terms of the out-of-spec rate as we go into kind of commercial manufacturing? No. No, because what that represents is total viable cell. And as I mentioned earlier, we have the ability to control that to some extent during our manufacturing within the scope of the BLA, so we can boost that up and make sure we hit specs. Got it. Okay. Okay. Thank you for the clarification. Thank you. Our next question comes from the line of Peter Lawson with Barclays. Your line is now open. Great. Thank you so much. Congratulations on the approval. I apologize with those technical issues. I had some trouble getting them online again, so I'm probably going to ask a question that's already been asked, but just around revenue recognition, kind of what triggers it? I assume it's the TIL infusion. And kind of what's the turnaround time you think you're going to have for identifying a patient to the TIL infusion? Yeah. Jean-Marc, do you want to cover? We did answer that question already, Peter, but you asked it in a way. I think maybe Jean-Marc should take that one. Yeah. Thank you, Peter, for the question. I think we did answer. I mean, we do expect to have revenue recognition for Amtagvi at the time of infusion like all other cell therapies. So that's why during the call, Fred mentioned that we are actually expecting to report significant revenue more in the second quarter of this year. There is a time between, of course, the time the patient is getting the surgery until the manufacturing process and the TIL is being infused. So stay tuned on more detail around that. We will get you more information as we have the patients coming through. Gotcha. What's the basic assumption around that turnaround time from identifying a patient or the collection of TILs to the actual TIL infusion? You can see, Peter, if you look at the press release we talked about earlier, in order to go from resection through to basically the shipping points, from arrival of the resection at the site all the way through to shipment back, we're targeting 34 days right now. Perfect. Thank you. And then where do you think the successful kind of manufacturing rate is going to lie based upon your ability to kind of boost the out-of-spec sales? We can't give exact numbers, but I'll let Igor Igor, do you want to give Peter a little bit of color on that? Well, Peter, yeah. We're not going to give you exact numbers. I mean, what we have in the packaging insert is probably representative of what we'd expect. But initially, there'll be some kinetics to that. So initially, when we see some sicker patients, and then the patient profile will change to those with fewer lines of therapy, so that will change over time. And then, as Fred mentioned, we're also working with several initiatives in place to improve the TVC of the final product and that way to reduce the OOS rate. And some of those initiatives are actually already in place. Some will take a couple of months. So you'll see an improvement in the OOS in the coming weeks and months. Gotcha. Thank you. Then just a final question around the IL-2 regimen. Is that separate from the TIL therapy regimen? Yes. Yes. Yes. Yes. I was jumping in. Yes, Peter, it's completely separate. Of course, Proleukin is related as part of the regimen of TIL, but the revenue itself will be recognized separately, including also reimbursement, etc. Great. Thank you so much. Thank you. One moment for our next question. Our next question comes from the line of Kelsey Goodwin with Guggenheim. Your line is now open. Oh, hey. Yeah. Congrats on the approval. It's great news, and happy Friday. Thanks for taking my questions. A lot of good questions have been asked already, so I'll shift gears a bit. Maybe just big, big picture, could you provide some color on how we could or should think about the margins here, maybe differences versus CAR-T cells? And then even bigger picture, I guess, could you just remind us potential data we'll see in 2024 and the status of the current hold on the 202 trials? Thanks so much. Jean-Marc, do you want to talk a little bit about the margins in comparison to CAR-Ts? Yeah. Sure. Definitely. As we have commented, and now you have even a price reference that we just disclosed. So margin, of course, which will not be negative, I expect it to improve over time because, of course, it's a function of us getting experience, adding efficiency and improvement. Also, it's related to higher commercial volume and capacity usage at a facility. But again, you should expect a good margin from the get-go that will improve over time. And then on the data flow this year, yes, there'll be some data flow from some of the trials. We haven't committed to anything just yet. Obviously, we have some trials running that we really want to report out, and we still have some data coming out from the COM202 study as well as LUN-202, LU-202. And while on topics of LU-202, we're working to get off hold as quickly as possible, and hopefully, we'll have some updates for you in a few weeks. Great. Thanks. And congrats again. Thank you. Thank you. I'm currently showing no further questions at this time. I'd like to hand the conference back over to Dr. Vogt for closing comments. Thank you again for joining the Iovance Biotherapeutics U.S. FDA approval conference call. I want to express my heartfelt appreciation to the patients and their families who have advocated for treatment options and participated in the clinical trials of Amtagvi and the Melanoma Community of Physicians and Treatment Centers that made this U.S. approval possible. I am also grateful to our employees and cross-functional teams in advancing our mission to be the global leader in TIL therapy. I would also like to thank our shareholders and covering analysts for their support. Please feel free to reach out to our investor relations team for follow-up. Thank you, everyone. This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone, have a wonderful day.