Good day. Thank you for standing by. Welcome to the Iovance Biotherapeutics ASCO update call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session, and instructions will follow at that time. If anyone should require assistance during the conference, please press star then zero on your touchtone telephone. As a reminder, this conference call might be recorded. I would now like to turn the conference over to your host, Ms. Sara Pellegrino, Vice President, Investor and Public Relations. Thank you, operator. Good afternoon, thank you for joining our conference call to discuss the clinical data updates at ASCO 2021 for lifileucel and advanced melanoma. For today's agenda, our Incoming Interim President and CEO, Fred Vogt, will do a brief introduction and corporate update. The highlight of today's call will be the clinical data updates presented by Dr. Omid Hamid, Chief of Translational Research and Immuno-Oncology at The Angeles Clinic and Research Institute. Dr. Hamid is recognized nationally and internationally as a key opinion leader in immuno-oncologic drug development and melanoma therapeutics, and we are very fortunate to have him join us today. Our Chief Financial Officer, Jean-Marc Bellemin, will also provide a brief financial summary, and then we will hold a question and answer session. Dr. Friedrich Finckenstein, our Chief Medical Officer, and Dr. Madan Jagasia, our Senior Vice President, Medical Affairs, are also available for the Q&A session. Before we start, I would like to remind everyone that this call will contain forward-looking statements regarding Iovance's clinical results, goals, business focus, business plans, clinical trials, and regulatory plans and results, manufacturing capabilities, regulatory feedback and guidance, collaboration, 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 filings. Our results may differ materially from those projected during today's call, and we undertake no obligation to publicly update any forward-looking statements. With that, I will turn the call over to Fred Vogt. Thank you, Sara. Good afternoon, everyone. We are pleased to host today's call to highlight our very compelling clinical data for lifileucel in advanced melanoma and our first look in early melanoma treatment with lifileucel in combination with pembrolizumab. We're really excited about our pipeline and the potential for TIL therapy in multiple indications as well as earlier lines of therapy, including advanced TIL therapy in non-small cell lung cancer, as well as TIL therapy combined with pembrolizumab and additional indications such as cervical cancer, as well as updates on head and neck cancer. While we aren't providing guidance today, I assure you that we're actively looking at the appropriate means to get more data out across many of our programs soon. We'll provide updates when available. Finally, before we review the data, I would like to address some of our recent updates regarding FDA feedback and potency assays for lifileucel with respect to our BLA filing. We are confident that we can resolve the FDA's questions regarding our potency assays for products for future commercial use. We think we have an understanding of recent FDA feedback, and based on that, we are working on a path forward to complete additional assay work in the near term. We believe we can achieve our new target timelines for our meeting with FDA in the second half of this year and plan BLA submission in the first half of next year. The additional assay work is a top priority, and we look forward to providing more detail and updates when possible. I would like to introduce Dr. Omid Hamid. As the Chief of Translational Research and Immuno-Oncology at The Angeles Clinic and Research Institute, a Cedars-Sinai affiliate, and the Co-Director of Cutaneous Malignancies at Cedars-Sinai Medical Center, Dr. Hamid has been instrumental in bringing novel therapeutics from first-in-human trials to the clinic for patient benefit, including immuno-oncologic therapy such as PD-1 inhibitors, other checkpoint inhibitors, bispecifics, and targeted agents. He has presented the research done at The Angeles Clinic at major national and international meetings and published manuscripts, abstracts, reviews on immunotherapy, targeted therapy, and melanoma care. Dr. Hamid has been a principal investigator in our C-144-01 clinical study and lead author on several of our publications and presentations at medical meetings. We are very pleased he can join us today to review the data for lifileucel. Dr. Hamid, please go ahead. Thank you so much for that lovely introduction. I'd like to thank Iovance and my co-contributors in this trial for allowing me to present this data that was so wonderfully presented by James Larkin earlier this morning at the oral session for melanoma. Lifileucel is a cryopreserved autologous tumor-infiltrating lymphocyte therapy in patients with advanced melanoma, and we are evaluating the evaluation of impact of prior anti-PD-1 therapy in this cohort. In slide three, you'll see the study design of C-144-01. This is a phase II multicenter study to evaluate lifileucel for metastatic melanoma in a patient population that was unresectable and metastatic melanoma treated with greater than one prior systemic therapy, including a PD-1 antibody, and of course, as important, if BRAF V600 mutation positive, a combination targeted approach. We'll be speaking about cohort two that looks to use the cryopreserved TIL product for 60 patients. As it occurs, 66 patients were accrued in this cohort. Primary endpoint was efficacy per investigator, initiated assessed overall response rate, and the secondary endpoint is safety and additional parameters of efficacy. TIL eligibility here, having one tumor lesion resectable for TIL generation, ECOG performance status 0-1. The patients were enrolled from April 2017 to January 2019. No concomitant cancer therapy was permitted. Image-evaluable disease was required, and all responses required confirmation. This is a data cutoff from April 22nd, 2021. As you can see in slide four, the baseline patient characteristics are indicative of the patients that we see in clinic with a male predominance. As far as prior therapies, all patients had seen a prior anti-PD-1 or an anti-PD-L1. 53 out of 66 patients had a anti-CTLA-4, and of those, 34 patients had concurrent anti-PD-1, anti-CTLA-4. 15 patients had BRAF and MEK inhibitor, and all patients had progressed on anti-PD-1 therapy. You can see here that this is a high-risk population with 41% of patients having elevated LDH, with the sum of target lesions being significant and the 3.3 mean prior therapies and high tumor burden at baseline. When you look at treatment emergence adverse events in slide five, you can see that the adverse event profile was consistent with underlying advanced disease and the safety profile of lymphodepletion and interleukin-2 regimens. You can see most patients received five or six doses of interleukin-2, and six is maximum. A decreasing frequency of adverse events over time is indicative of the potential benefit of this therapy. As you see here, there were no new safety signals after two months. The majority of toxicities are acute and resolve. When you look at the grade toxicities, clearly the initial toxicities are due to the lymphodepleting regimen and then the rest from interleukin-2. A therapy that you give to the patient, and then they resolve the adverse events and move on. Efficacy is shown here on slide six with an objective response rate of 36.4%, complete response rate of 4.5%, and a disease control rate significant at 80.3% with a median duration of response that's not reached. Responses were demonstrated in patients who received prior anti-CTLA-4 and BRAF MEK inhibitors, and response was seen regardless of BRAF mutational status, PD-L1 expression on tumor, or time from stop of anti-PD-L1 therapy to TIL infusion. Various levels of LDH and various visceral metastases patients respond. Here is the efficacy in a waterfall plot on the next slide. 81% of patients had a reduction in tumor burden. 11 patients had further sum of diameter reduction since the last cutoff on April 2020, and you can see here that these were seen in patients, as the asterisk denotes, patients with BRAF V600 mutation. This is again reflected in our swimmers plot. You can see early in our responders, at the first imaging time point at six weeks, response was seen, response was durable, and patients went from initial response in a partial response to complete response, and the responses continued to deepen over time. Slide nine shows the cohort 2 biomarkers. It's important here to show appropriate amount of TIL was manufactured from tumors regardless of location of resection, visceral, lymph node, skin subcutaneous, and other not assigned locations, and the amount of TIL was equivalent in each site. Target lesion sum diameter reductions were seen across the range of TIL total cell dose. Not quite associated with the amount of TIL infused. When you look at univariable analysis for duration of response of lifileucel, although cumulative duration on prior anti-PD-1/anti-PD-L1 was not associated with achieving a response, it was associated with duration of response. When you look here, prior anti-CTLA-4 use, BRAF mutation status, baseline ECOG, baseline LDH, and the location M1C or M1D was not associated with duration of response. Multivariable models look for independent predictors for lifileucel duration of response. Here, variables from the univariable analysis were examined using the best subset approach, and two parameters were identified here. Baseline LDH. Also cumulative duration on prior anti-PD-1 and anti-PD-L1. This cumulative duration was a stronger predictor for duration of response when we looked for each three-month decrease in exposure to prior anti-PD-1 and for each six-month decrease in exposure to prior anti-PD-1/anti-PD-L1. As you can see here, a hazard ratio that is significant and does not cross one, that showed for each six-month decrease in exposure, the duration of response to lifileucel will be nearly doubled. In conclusion, slide 12, in heavily pre-treated metastatic melanoma patients who progressed on multiple prior therapies, including anti-PD-1 and BRAF/MEK inhibitors, lifileucel treatment resulted in a 36.4% overall response rate with a median duration of response not reached at 33.1 months of therapy. Responses deepened over time. We saw 11 patients demonstrating further reductions in sum of diameters since the last cutoff in April 2020. We've seen conversion from a partial response to complete response at 24 months post-infusion on a patient still on trial. What came out of this evaluation, shorter duration of prior anti-PD-1 therapy maximizes duration of response to lifileucel treatment. All newly diagnosed patients should be closely monitored for progression on anti-PD-1 therapy because early intervention with lifileucel at the time of initial progression on anti-PD-1 agents may maximize benefits. Now, I'd like to present some of the initial data of the safety and efficacy of lifileucel, in combination with pembrolizumab PD-1 inhibitor for immune checkpoint inhibitor-naive patients with advanced melanoma. Again, I'd like to thank the investigators for allowing me to show you and present this information. IOV-COM-202 was a prospective, open-label, multi-cohort, non-randomized, multi-center, Phase II study evaluating TIL therapy in multiple settings and indications. Cohort 1a, which we report here, enrolled patients with immune checkpoint inhibitor-naive, advanced melanoma that's Stage 3 unresectable or Stage 4 metastatic for a combination of lifileucel and pembrolizumab. The key eligibility criteria here, of course, naive to immune checkpoint inhibitor, less than three lines of prior systemic therapy, good ECOG performance status, having a resectable lesion for manufacturing, and then a valuable measurable lesion for response assessment. Efficacy was objective response rate. Safety here will be presented. The data cut off April 29, 2021. The schema, as you can see here, from screening to enrollment, the patients received an initial pembrolizumab administration and then went on to lymphodepletion chemotherapy with Day zero lifileucel infusion and interleukin-2 post-infusion of up to six doses, continuing pembrolizumab on the approved every three or six-week dosing, end of therapy, then an efficacy follow-up. As I showed you on the previous trial, the baseline patient characteristics were similar. The majority of patients here had had no prior therapy. Again, these are seven patients, male preponderance. The prior systemic therapies in these patients, one was chemotherapy, one was targeted BRAF and MEK inhibitor. Sorry. The majority were Stage 4 metastatic. PD-L1 positives were 57% of the patients. Again, similar, a 42% LDH above baseline and a high tumor burden, as you can see here. 85.7% of patients had greater than three lesions and the high tumor burden, as I've noted before. Efficacy is presented here on slide 17. You can see an objective response rate, six out of seven patients, 85.7%. One patient with stable disease for a disease control rate of 100%. The median number of TIL infused was similar to the prior study, and the median follow-up here was 8.2 months. Slide 18 shows best percentage change from baseline and target lesions of all evaluable patients and median number of pembrolizumab doses here in these patients, 10. You can see here there was one unconfirmed complete response and two patients who had partial response that went on to have a confirmed response per PET evaluation. There are four patients with BRAF mutation. As you can see on the spider plot here, early, deep, and durable responses in patients that are going out past month 21. These patients with the asterisks, these are the patients who had CR based on a FDG PET scan. Let me show you these three patients with complete response. As you can see here, these three patients, two had BRAF V600 mutations. Patient three had a non E mutation, and Patient six had a V600E mutation. Patient six had seen dabrafenib and trametinib for 5.2 years with a partial response and discontinued for progressive disease. When you look on the right, you can see here that initial imaging was done by CT scan in all of the patients. In patient three and patient six, after an extensive amount of confirmed response, a PET-CT was done again in patient three at 10.5 months and month 13 that confirmed a complete response by PET negativity, and again in patient six at month six. These are not early PET scans done. These are PET scans done after a significant amount of confirmation of response. Slide 21 shows the swimmer plot here, and you can see that the time to first response on these patients was at initial imaging on the majority. What we've seen is similar to what is seen in the single-agent trial, that patients had initial response and then had deepening responses over time in the complete response patients here. You can see here that the patients are out many months, all out six months, and then some out here past 16 and 21 months. In conclusion, early data here suggests the response rate for lifileucel plus pembrolizumab may be additive in patients with immune checkpoint inhibitor-naive advanced melanoma with an overall response rate of 85.7%, complete response at 42.9%, with responses deepening over time. Most patients had a high disease burden at baseline. We've shown that lifileucel can be safely combined with pembrolizumab. These encouraging data confirm the potential feasibility and activity of the combination in early line treatment of patients with advanced melanoma. With that, I'll conclude and thank you for your time. Thank you, Dr. Hamid. Let me comment very briefly on our current financial and cash position to end this presentation. Which the cash strongly position Iovance to continue to execute towards the BLA submission and prepare for commercial launch while advancing our pipeline. Let me turn to slide 28, please. I will begin with our cash position. As of March 31st, 2021, Iovance held $610.2 million in cash equivalent, investment, and restricted cash, inclusive of $42.9 million proceed raised through our ATM offering. As a reminder, the total ATM offering is for up to $350 million. This strong cash position is expected to be sufficient into 2023 to deliver on our pipeline programs with no immediate need to access capital at or near the current stock price. We will continue to focus on investment in four key areas to ensure the growth and strength of our value creation. First, advancing our current clinical programs and indications. Second, scaling up our manufacturing capacity to support our clinical manufacturing while preparing for expected commercial supply in 2022. Third, ensuring the launch readiness. Fourth, maintaining a strong balance sheet and cash position. I will now hand the call back to the operator to kick off the Q&A session. Thank you. As a reminder, if you have a question at this time, please press the star and then the number one key on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. Please limit yourself to ask one question. Our first question is from the line of Benjamin Burnett from Stifel. Your line is now open. Hey, thank you very much. I appreciate the update. Actually, I have a question about the disclosure of the pivotal cohort for melanoma data. I think in the past, disclosing this was gated by the BLA filing. I guess, is that still the case? Is there any chance that we could get the results of cohort 4 earlier than that? Hi, Ben. This is Fred. Yeah, that's correct. We had gated the BLA filing. Given all the recent events, we'll take a look at that, of course. I don't have any updates for you today, but that's something that we're thinking about. Next question is from the line of Michael Yee from Jefferies. Your line is now open. Hi, good afternoon. Maybe two quick ones, one for the doctor and one for the company. Maybe, Dr. Omid Hamid, you could talk about maybe how this data stacks up with other combination regimens, obviously, Phase III data here at the conference and your analysis of two years only. Is that why you should expect a long duration of therapy early in first line? What do you think the implication is of that analysis? Then maybe for the company, I know that you just talked about potentially unblinding cohort 4. Does that have to do with trying to get agreement on the ASCO and not wanting to have all of that information out before they ask this? You just need to ask the FDA if that would be okay. Maybe just clarify that comment. Thank you. Why don't I go first, Michael, and I'll hand it over to Dr. Hamid. On the assay related to the cohort four data, it's one of many factors we're considering as we consider what to do with that data. The BLA timing was our primary driver for that because of the need to cut the data and do all the work prior to the BLA. I'll give the second question to Dr. Hamid. Just note that this call is really about Iovance's TIL therapy and not so much about some of the other things that he's involved with. Dr. Hamid, would you be able to answer that? Thank you so much for that. Let me just tell you that, number one, I'm not only a physician researcher, but I run a very robust clinical practice where I see a significant proportion of patients four and a half days in clinic. I would say when you look back at this first-line data, what you notice is that these are the patients that came to lifileucel. These are the patients that have progressed on these therapies. When you look at LAG-3, the data presented by Paolo Ascierto post-PD-1, way back when, three years ago, the response rate was 11%. When you look at the data in KEYNOTE-006 post-pembrolizumab, the response rate to anti-CTLA-4 therapy was 15%. When you look at the response rate to ipi/nivo post-PD-1, it's somewhere between 20%-30%. This population of patients that you're looking at have progressed on those therapies, and you're not expecting them to respond in as robust way as they have done to lifileucel with a 36.4% response rate. Something that wasn't presented here has been presented before, and that's the checkpoint refractory population, the patients that don't respond initially. These were about 80% of the responders to this therapy. Now you're looking at trying to find answers to patients who would never respond to an immune checkpoint inhibitor. What you're seeing here is an early indication of a different paradigm when you're looking at patients who really have shown you that they are not going to respond or benefit. We know that 25% of patients that respond to anti-PD-1 therapy then subsequently progress. What I'm saying here is there's enough patients looking for this, and if this was available, the patients would want it. The combination first-line data is interesting here, where you look at these patients who come in with the best performance status and an ability to move forward. It may be that you're looking here on a way to synergize these therapies at a time where the patient has less tumor burden, a lower LDH, and is more able to tolerate the therapy, therefore expanding what has been an exclusion for some patients, age, comorbidities, and getting this therapy to a wider range of patients. What that means for other combinations is unimportant in relation to reviewing this data and understanding its importance and role in melanoma care and therapy. We have our next question from Mark Breidenbach from Oppenheimer. Your line is now open. Hey, guys. Thanks for the update, and thanks for taking my question. I find it really striking that you're still seeing tumor shrinking this long after a one-time therapy. It looks like maybe even a couple of patients are on the cusp of achieving partial responses in cohort 2. I'm wondering if this is a general trend with TIL therapy. Have you seen this, not just in melanoma, but in other indications as well? Maybe, Fred Vogt, you can give us updated guidance on plans for readouts from additional cohorts in the Basket study and/or the cervical cancer trial later this year. Thank you. If you'd allow me to go first, Fred, I would just say that this is not an amazing or not interesting, because if you look back on Michael Atkins' data on the approval of interleukin-2 for melanoma, even though the response rates to that were much less, these are patients who are durable and have responses, even Mike's discussed running into a patient 30 years later having a response and benefit. This is the whole idea of immunotherapy. These are similar in patients who received only four doses of anti-CTLA-4 therapy and are still benefiting with a partial response that's durable and a complete response that's durable a decade later, plus on trials. We've also seen this in prior TIL trials. For us that have been giving these types of therapies, it's not surprising. It's interesting and welcome that we're seeing a higher rate of patients responding. These patients are some of our most heavily pretreated patients who've had prior PD-1, prior BRAF inhibitors, prior anti-CTLA-4. That's the majority of patients that come to my clinic. That's what's going to happen now based on what's been presented at ASCO. These patients will receive standard therapies in clinics and community will be seeking a therapy that can show high response rates, durable responses, and deep response. Totally agree, Dr. Hamid. Why don't I go back and just answer the first part of Mark's question there about the other indications in our Basket study. Yes, we have obviously a lot of ongoing cohorts in the Basket study. We've just put one of them into this ASCO conference that we just had, and Dr. Hamid just talked about there on Friday. There's other cohorts running there. We haven't committed to data flow yet on those, but we're working as hard as we can to get those ready. Just note that those cohorts started a little bit later than the frontline melanoma cohort that we were talking about here. Stay tuned on that, and we'll come back as soon as we possibly can to talk about additional data. There was another aspect of the question as to whether we had seen this across other indications. Can I ask Friedrich on our side to step in and talk about that a little bit? Sure. I don't have a lot to offer to Dr. Hamid's really powerful and also true statements and descriptions there. I think what I can contribute is to point to our data in the CPI-naïve head and neck cancer cohort that we presented last year at SITC. There is an example that looks very similar to what you're seeing here of a patient who had a response initially observed after on his second assessment and then converted to a CR late at month nine after TIL therapy. I do think that this is a general feature of immunotherapy, but our data are suggesting that is true for TIL as well, and that might be true across tumor types. Next question is from the line of Asthika Goonewardene from Truist Securities. Your line is now open. Hi, guys. Thanks for taking my questions. One to Dr. Hamid, if I may. Dr. Hamid, the data that was presented today was quite interesting, and just to summarize, for each six months decrease in exposure to prior PD-1, the duration of response to the TIL is doubled. I'm wondering what do you think is happening here? I was hoping you could maybe speculate in terms of the quality of T cells you might be getting as starting material and speculate on the type of tumor that you'd be treating here. In the likely event that, well, relatlimab, the LAG-3+ nivolumab becomes a standard frontline therapy. I know there isn't much data, could you maybe tell us what you think how that changes the tumor and the TILs? Yeah, that's a great question, and I can really see that you've spent the time to try and suss this out. I would say to you that it's too early to really speculate. I would more than likely say that what we've seen is an interaction with patients who've received PD-1 an extended time, and there's some evidence of T cell exhaustion there that we could look to recover. What this points to is further work that will need to be done evaluating the biomarkers on these patients who are on therapy. It does point to a plan that Iovance and others have had that's visible here, that they're not just waiting on the data to be evaluated by FDA for single agent. They're moving further into first line prior to ICI. When that data matures, I think we'll have a better answer to give to you. Next question is from the line of Peter Lawson from Barclays. Yeah. Thanks for taking my questions. For Dr. Hamid, just as we think about the use of TIL therapy in a broader melanoma group of patients, what's the biggest restriction there? Is it the ability to generate TILs or use of IL-2? Just your considerations there around the potential expansion of TIL use in patients. I would say, good question. I'm grateful for Iovance to be able to bring this to many different centers and hospitals throughout. A major issue in the past, as I've worked with Dr. Mark Faries, who's the co-director of our program here and a surgical oncologist, is for most people, was finding a GCP facility a way to generate TILs. They've overcome that. The second thing would be the ability for centers that are interested in doing this to be able to bring forth a team and mobilize a team to be able to present this and be able to give this to patients. This adoptive T cell therapy, for us, would have never been accessible if we didn't have this pathway. It took us some time initially to get the hospital involved and the clinical pathways put together. I think Iovance is working to help novel centers do that. If you go back to the understanding and the use of IL-2 for patients with metastatic melanoma that was pioneered and worked on with Chiron and others, it's the ability to clearly relate the benefit, clearly relate the therapy, and then clearly translate that into action at many different sites We have our next question from the line of Joseph Catanzaro from Piper Sandler. Your line is now open. Great. Thanks for the update. Thanks for taking my questions here. Dr. Omid Hamid, you had noted earlier that melanoma patients refractory to PD-1 still represents a sizable proportion of patients. With that as context, I was wondering if for the liposomal pembrolizumab combination, if any of those patients were experiencing increases in their target lesions during the pembrolizumab run-in ahead of TIL infusion that markedly reversed after TIL infusion. Maybe one quick one on the potency discussion. Company, you've previously spoken about a front-runner assay and a secondary assay that you've provided data around. Can you say whether both of those assays are still in play following the most recent feedback? Thanks. Yeah. Why don't I start here, Dr. Hamid, and then I can loop you back in here. To answer the second question first, all things are on the table with the FDA. Obviously, we've been talking about additional potency assays that we've developed and getting them in front of FDA, but that doesn't mean that we would not use those in combination with prior assays or alone. We just haven't had that. We haven't got to that level of discussion yet with the regulator, and we'll update the Street as soon as we can. Regarding the first question, maybe, Dr. Hamid, I don't know if you want to take that one or maybe Friedrich can jump in on that one. Well, let me take it to the best of my ability. As you can see here, the patients that were screened and placed on study and received one dose of anti-PD-1 therapy then went on to lymphodepletion chemotherapy. There was no imaging done in the interim, then there were seven patients. I would say that there's really not anything to mention, there wouldn't have been any type of progression from starting therapy and receiving the first dose. Next question is from the line of Madhu Kumar from Goldman Sachs. Your line is now open. Hey, everyone. Thanks for taking our question. Our first one is to Dr. Hamid. In your experience, have patients who've been on PD-1 blockade who discontinue therapy maintain responses? How do you think about that aspect of the PD-1 naive trial, people can come off therapy and maintain response? Right. Good question. I would put it this way to you, that the majority of clinical protocols that are written at this time in melanoma have a finite limit of therapy at two years. When you look at the KEYNOTE-006 trial, they allowed patients to come off early if they had shown a complete response that was maintained for, I believe, six weeks. When you look at the data from CheckMate -067, which was just presented, they have interestingly shown patients who have come off for toxicity initially and never been retreated, continuing to have a benefit and a response. This is something that's very familiar to us who take care of patients with melanoma. I think it's possible in the same fashion for the patients who are on the combination first-line trial. Okay, one other question we've gotten from people is the notion, have you seen any studies combining IL-2, either long course or short course IL-2 with PD-1 blockade and melanoma? To what extent do you envision that some of the effects may be contributed by just the very short period of IL-2 given after TIL infusion, and how you think about that aspect of the combination of the PD-1 naive trial? Look, I'm going to be straightforward here. I can't talk to the PD-1 naive trial. It's an early trial of seven patients. I will say that if you're looking for data about IL-2 combinatorial therapies, look no further than the amazing work done by the Cytokine Working Group, which we're a part of. That's aside from what we're talking about today. Clearly, the IL-2 experience has shown responses that are somewhere under 12%-15%. Really, the data that was presented in the past was prior to the checkpoint era. Additionally, you'd want to compare it and see that the response rate here is greater by more than a factor of two. You can't just say this is IL-2. No one would say that. Hi, Madhu. This is Madan Jagasia, senior vice president for Medical Affairs. I would just like to reemphasize that it's highly unlikely that a median of five doses of IL-2 can affect any sort of a major response just by itself, even if you were to say that. Remember, in the cohort 1A study, right? Patients have had one dose of pembro. Two weeks later, they get lymph depletion, and then they get up to around five to six doses of IL-2. It's highly unlikely that one dose of pembro plus five doses of or six doses of IL-2 is giving you a response that we are seeing of 86% ORR with a 43% CR without the TILs doing anything. It's just scientifically very improbable. This is Frederich. Maybe I can just add to that as well. Friedrich Graf Finckenstein, Chief Medical Officer at Iovance Biotherapeutics. Remember, therapeutic IL-2 is dosed in repeated cycles of many more doses over a longer time than the 6 doses that we are administering over a maximum of three or four days duration. I totally agree with what was said here. This is not therapeutic IL-2. This IL-2 is administered in order to continue the TIL expansion after administration in vivo in the patient. That's its purpose. Next question is from the line of Mara Goldstein from Mizuho. Your line is now open. Great. Thanks so much. Appreciate your time. Just first on the results, looking at those converted CRs and particularly that late CR, I'm curious if you have any information about what is going on for those patients biologically and how that might translate into practice. Hello? It's very difficult to hear you. Sorry. Is this better? Yeah. Could you restate that question? It got partially cut off in the first part. Sure. Thank you. I'm just curious around the complete responders in the trial and what might be going on biologically for those individuals and how that might translate into clinical practice. Secondarily, I did want to ask on the question of assays, and new data, whether or not, as you say, everything's on the table, whether de novo data will be required to complete this assay process with the agency. Yeah. Let me start with the potency assay question first. By the way, are you talking about cohort 2 when you say the trial? Yes. Thank you. CRs. Okay. All right, regarding the potency assay and de novo data, yes, some additional data is required. We've been talking with the street about that. We're going to have to generate data packages as part of our interactions with the FDA in the second half of this year. However, we've already done a lot of that work, and we have retained samples that we can use to facilitate that process. For the first part of your question, Friedrich, would you be able to speak a little bit more about the CRs? Yes. I think what I heard was the question, what is going on biologically in patients who have CRs or respond to the combination. Was that your question? I think so, Friedrich. Go ahead. I think one thing to keep in mind when we are looking at TIL therapy, these are autologous, non-modified T cells. It would make sense that they are subject to the checkpoints that are controlling their activity. Combining with checkpoint inhibitors is perfectly rational, and it makes a lot of sense that you would be seeing at least added response as we are watching these data, potentially even synergistic data. These cells are subject to PD-1 mechanisms, and blocking them makes a lot of sense. Obviously, what lies closest is to use a validated mechanism and approved agents that do exactly that. Does that answer your question? I guess so. Thank you. Next question is from the line of Nick Abbott from Wells Fargo. Your line is now open. Hello, congratulations on two terrific sets of data here. My question is on the checkpoint inhibitor-naive cohort with focus on the two patients that progressed. Are you able to characterize the nature of progression? I think we're calling the advanced setting that progression at a single site can be addressed by resection or local regional therapy, those patients remain treatment free. If that's not the case here, are these patients eligible for resection and retreatment with a new TIL product? Thank you. Friedrich, can you answer that one, please? Yes, I can definitely address the second question. Progression that we see in patients after TIL therapy is often related to the development of new lesions, but not always. All of our protocols allow, if the PI and the patient agree, and this is thought to be of benefit for the patient, for retreatment after rebiopsy and manufacturing of a new product. Was that undertaken? I was just going to ask if that was undertaken in these two cases. This is early. This is really hot-off-the-press data. We're very early in this stage. Next question is from the line of Colleen Kusy from Baird. Yeah. Good afternoon. Thank you so much for taking our questions. In the pembro combo, it looks like based on the somers plot, we're seeing some variability in the amount of pembro given. Can you just talk about how that's determined in this early trial and how you expect, in the future, pembro will be dosed? Friedrich, can you answer that one for Colleen? Can you repeat the question, please? I'm having a bad connection here. I apologize. Sorry about that. Just looking at the somers plot, it looks like the amount of pembro and the frequency of pembro infusion is variable between patients. How do you expect that to be dosed going forward in the trial? How would you expect that to impact the response? Yeah. You're looking at the somers plot, and you're seeing the dose indicating the pembro infusion. Again, if you see a patient discontinuing pembro, then that is due to toxicity, which is to a certain extent expected in patients treated with checkpoint inhibitors. What I find remarkable is that there are patients that are actually, although they are discontinuing pembro, are deepening responses or maintaining that response. I think that is for a long time. That is a really important observation. As currently, I think this is too little data to inform on what we should be doing with this combination. I think we need to generate more data with it. For now, this study will continue to explore continued maintenance with pembrolizumab, and then we will learn from it. Great. Thank you. Next question is from the line of Boris Peaker from Cowen. Your line is now open. Great. Thanks for squeezing me in. Maybe for Dr. Omid Hamid. I'm curious, are there any mechanisms to assess the expansion or persistence of these TIL cells? I know they don't have conserved antigen like CAR T-cell do. If there is such a mechanism, has anybody looked at to see if that persistence or expansion is improved by checkpoint inhibitors or full dose of IL-2 versus people that require reduction of IL-2 or any other correlation to performance? Thank you. I just want to reiterate what was said before, that the amount of IL-2 here is not dosed in a similar fashion in the past as to toxicity, and this is just to expand the T-cells only. We would not be expecting or would not have anyone be doing full dose IL-2 in multiple doses up to 12 or 14 in the past. As far as the other assays, I'll leave it to Iovance to speak in relation to what they have done in relation to this product. Boris Peaker, I can talk a little bit about this. Checkpoint, if you're talking about expansion of TILs, the impact of checkpoint doesn't seem to be significant from what we know. If you're talking about ex vivo, for example. I'm not sure if that fully answers your question, but that's what we know as of today. Well, my general question is there any way to monitor these cells once they're injected back into the patient? Can you assess if they are actually persistent for a long period of time or not? Oh, yes. Yeah. All right. Got you. Great. If you look back at some of our posters, you'll see some of our data that we've done with iRepertoire, which is a company that offers TCR profiling services. We do have ways of assessing that, although I don't have any information for you right now on how that affects this particular trial. You can look back and see what we were able to do with some techniques if you look at our posters. Fred, I can just confirm that we are collecting samples for similar analyses as we have presented previously for melanoma, so we could trial and those data are on our website. Great. Thank you. Again, if you have a question at this time, please press the star and then the number one key on your touchtone telephone. Next question is from the line of Reni Benjamin from JMP Securities. Your line is now open. Hey, guys. Thanks for squeezing me in and congratulations on the data. Maybe just starting off with the checkpoint inhibitor naive trial. The patient number two who didn't respond, is there anything that you can glean from that patient as to why they might not have responded? Is that person still on study with an SP? Have you ever seen SVs across any of the studies converting to PRs? Friedrich, why don't you take this one? Sure. I think a single patient out of a total of seven patients is much too early to try to learn any sort of predictive characteristics, but obviously, that's something that we're going to continue to explore. This patient stays on trial. We are following patients with stable disease. Yes, in other trials, we have seen later conversions to partial responses. Got it. Just as a follow-up for the relapsed refractory study, IOV-COM-202, you talked about 11 patients who had further reductions, and at least when I was looking at the slides, it looked like, for example, patient 39 improved to a CR. Should we be thinking about this data now that instead of three patients with CR, it could be that we actually have four patients with CR? How do we incorporate the new patient's data that occurred past the April 2021 cut? Fred, do you want me to take this question? Yeah. Why don't you take that one about patient 39? So far, follow-ups are showing partial response regardless of timing. As you've seen, and that's been previously presented, and that was an AChR. The additional patient of the 3 CRs converted late, and now we are counting this patient as additional CR patient. The patient number 39, although that patient shows a total reduction of target lesion to minus 100%, may not have resolved non-target disease, and because of that is not formally considered a CR patient. Got it. Great. Thank you for the clarification. We are on top of the hour, and at this time I would like to turn it back to Mr. Fred Vogt. Sorry, I was on mute. Apologies. Thank you again for joining the Iovance ASCO update call. Special thanks to Dr. Hamid for joining us to present the data. Feel free to reach out to our investor relations team if you wish to follow up. Thanks, everyone. This concludes today's conference. You may all disconnect.