Welcome to the Iovance Biotherapeutics Second Quarter and First Half 2022 Financial Results and Corporate Updates Conference Call. My name is Andrew, and I will be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session. During the question and answer session, if you have a question, please press star one one on your telephone. Please note that this conference is being recorded. I will now turn the call over to Sara Pellegrino, Senior Vice President, Investor Relations and Corporate Communications at Iovance. Sara, you may begin. Thank you, operator. Good afternoon, and thank you for joining us. Speaking on today's call, we have Dr. Fred Vogt, our Interim President and Chief Executive Officer, Dr. Igor Bilinsky, our Chief Operating Officer, Jim Ziegler, our Executive Vice President, Commercial, Dr. Friedrich Graf Finckenstein, our Chief Medical Officer, and Jean-Marc Bellemin, our Chief Financial Officer. Dr. Madan Jagasia, our Executive Vice President, Medical Affairs, and Dr. Raj Puri, our Executive Vice President, Regulatory Strategy and Translational Medicine, are also available for the Q&A session. This afternoon, we issued a press release that can be found on our corporate website at iovance.com, which includes the financial results for the three and six months ended on June 30th, 2022, as well as recent corporate updates. 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, pre-commercial activities, clinical trials and results, regulatory 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 filings. 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, Sarah. Good afternoon, everyone. I'm pleased to highlight our significant year-to-date progress at Iovance. I'll begin with our first planned Biologics License Application or BLA for our lead TIL therapy, lifileucel in metastatic melanoma. This is our number one priority on behalf of patients who are eager to see lifileucel approved. We successfully completed a pre-BLA meeting with the FDA in July, and we are on track to begin the BLA submission this month. The FDA provided favorable feedback on the clinical efficacy data from cohorts two and four of the C-144-01 clinical trial, including duration of follow-up and the potency assay matrix. The FDA also agreed that the clinical and safety data set was sufficient for a BLA review and provided valuable feedback and advice regarding various parts of the planned BLA submission. Following the pre-BLA meeting, we will commence a rolling BLA submission this month. The rolling BLA submission is the benefit available under our Regenerative Medicine Advanced Therapy or RMAT designation. A rolling BLA allows us to submit sections of the BLA to the FDA on an ongoing basis. This process enables the FDA to begin review of submission documents as early as possible as they are received, potentially allowing for earlier approval. We expect to complete the rolling BLA submission during the fourth quarter of this year. We are pleased with the outcome of the pre-BLA meeting, which multiple members of FDA senior management team attended. The FDA is engaged and supportive of the BLA for lifileucel, and we look forward to continuing this level of collaboration throughout the submission and review process. In parallel with the BLA-related activities, we're actively preparing to launch lifileucel. Key pre-commercial activities including medical education, treatment center onboarding, payer engagement, commercial manufacturing readiness, and near and long-term capacity planning. We aim to successfully deliver TIL therapy to cancer patients and create value for our shareholders. We are also excited about the advancement of our TIL cell therapy pipeline. We are recruiting patients across five Iovance clinical trials, including the recent, recently initiated trial of our first genetically modified TIL therapy. Six cohorts of non-small cell lung cancer patients are part of three of these active trials, reflecting our focus on that indication. We are also on track to initiate a phase III trial of lifileucel in combination with pembrolizumab in front line melanoma towards the end of the year. As noted in this afternoon's press release, we are expecting our C-145-01. Sorry, C-145-04 study to support a BLA submission for lifileucel in cervical cancer, which Friedrich will highlight further. This updated registration strategy reflects FDA discussions and feedback that address the shift in front-line standard of care in cervical cancer. As we prepare to launch the first one-time cell therapy in solid tumors, we are growing the organization to advance our mission of innovating, developing, and delivering TIL therapies. Today, we have nearly 450 employees that bring deep expertise and successful track records in oncology and cell therapy development and commercialization. The strength within our organization reflects tremendous enthusiasm for Iovance TIL therapies and our global leadership within the field. I look forward to addressing your questions later during this call. I will now ask Igor to discuss manufacturing updates. Thank you, Fred. Our manufacturing network is dedicated to patient needs and operational excellence with a consistent TIL manufacturing success rate of more than 90% in more than 500 patients treated with Iovance TIL therapy to date. The Iovance Cell Therapy Center or iCTC is our 136,000 sq ft internal manufacturing facility in the Philadelphia Navy Yard. We custom designed iCTC and in just 2.5 years, constructed it from dirt on the ground to an operational facility supplying Iovance clinical studies. Manufacturing is critical for any commercial launch, particularly for autologous cell therapies. Our top priority is to prepare iCTC for BLA submission and commercial supply. Today, the iCTC is operating flex suites for clinical manufacturing and conducting BLA readiness activities in the core suites. In addition, we are on track in preparing the iCTC and our contract manufacturer's facility for FDA pre-approval inspections. The iCTC is expected to supply most of the commercial cell therapies upon approval, with flexibility to use contract manufacturing to optimally manage capacity and fully meet patient demand. As we look to establish TIL as the next paradigm-shifting class of cancer therapy, we are also planning for our future capacity needs. As currently constructed, the iCTC includes 12 core suites and four flex suites with projected capacity to treat more than 2,000 patients per year. Within the existing structure at iCTC, the available shell space allows us to double the number of core suites and increase annual capacity to provide TIL for more than 5,000 patients annually. Longer term, to reach TIL manufacturing capacity for more than 10,000 patients annually, our technology plans include streamlining and automating manufacturing processes while adding new facilities. These new facilities potentially include an adjacent lot in the Philadelphia Navy Yard, where we have an option to build under similar terms as iCTC. To support and protect our proprietary manufacturing processes and know-how and to further solidify our leadership in TIL therapy, we are growing our intellectual property or IP portfolio. We currently own more than 50 granted or allowed U.S. and international patents, including Gen 2 patent rights that are expected to provide exclusivity into 2038. I would now like to hand the call to Jim Ziegler to highlight our commercial launch preparations. Thank you, Igor. Leadership positions and key roles are currently in place for commercial and other important functions supporting the launch of lifileucel for metastatic melanoma patients. Our cross-functional team has built the foundation to scale rapidly and efficiently as we accelerate launch preparations based upon key regulatory milestones. We continue to collaborate with our top targets to become authorized treatment centers or ATCs. We are prioritizing leading cancer centers to treat patients as soon as possible after approval. Our goal is to onboard and train at least 40 ATCs within the first 90 days of launch. From our analysis of CAR T claims data, we anticipate a patient concentration for lifileucel similar to the CAR T market, where approximately 50% of CAR T patients are treated in the top 10 centers, and approximately 80% of CAR T patients are treated in the top 40 centers. Through structured interactions with the ATCs, we are efficiently facilitating the development of new workflows that are unique to TIL cell therapy while leveraging existing workflows within prevalent cell therapy service lines at the ATCs. We designed our customer-centric approach to meet ATC training needs and ensure just-in-time preparation for each center. In addition to onboarding the ATCs, we plan to target high volume community practices to increase awareness and encourage referrals to the ATCs. We foresee a strong collaboration between the ATCs and community medical oncologists because we expect referred patients to receive one-time treatment with lifileucel at the ATCs and then transition back to the community for ongoing monitoring and care. Moving to our reimbursement strategies, we are focused on securing coding, coverage, and payment. Our market access team continues to engage the key national and regional payers to support appropriate and timely access to lifileucel upon approval. As a reminder, lifileucel will be administered on an inpatient basis with reimbursement from payers to hospitals generally falling under a case rate for commercial patients and the DRG or diagnostic-related group for Medicare patients. This means all care, treatment, services, and hospitalization are generally reimbursed under one bundled payment. Our proprietary IovanceCares program is on track to assist healthcare providers and patients through their TIL journey as a best-in-class cell ordering, chain of identity, chain of custody, and patient support program for launch. We prepare for commercialization. I want to acknowledge the strong and sustained effort by our core cross-functional teams who have built the foundation for launch. I will now pass the call to Friedrich Finckenstein, our Chief Medical Officer, to highlight the clinical progress. Thank you, Jim. Today, I would like to share recent clinical and research program updates that reflect the evolution of our pipeline to incorporate additional treatment modalities and next-generation technologies. To address more cancer patients and new tumor types in various stages of disease. First, I will briefly summarize the positive top-line clinical data from 153 patients across cohorts two and four in the C-144-01 trial in metastatic melanoma. We previously reviewed these results in detail in our data press release and conference call in May. Patients in both cohorts two and four met the same primary eligibility criteria, had the same study assessment, and received the same treatment regimen in lifileucel that was produced using the same Gen 2 cryopreserved TIL manufacturing process. Our pivotal cohort four met the pre-specified primary endpoint, which was ORR assessed by IRC. ORR, as well as various measures of durability for cohorts two and four, represent meaningful improvement over available care for our clinical trial population. We look forward to announcing more detailed data from the C-144-01 trial at a medical meeting later this year. We also continue to develop TIL in combination with pembrolizumab in checkpoint inhibitor naïve patients with various tumor types to expand upon the initial opportunity for lifileucel monotherapy after anti-PD-1 therapy. We are committed to starting a phase III study in frontline melanoma later this year, which is also designed to serve as a confirmatory study. As Fred mentioned, during the second quarter, we also began site activation and patient recruitment for the IOV-GM1-201 first-in-human study of IOV-4001. IOV-4001 is a PD-1 inactivated TIL therapy that incorporates the TALEN gene editing technology licensed from Cellectis. IOV-4001 may leverage the combination of TIL and interruption of PD-1 signaling within a single therapy. In a murine model of melanoma, the antitumor activity of IOV-4001 was superior to non-edited TIL products, whether alone or in combination with an anti-PD-1 antibody. The IOV-GM1-201 study includes two patient cohorts. The first cohort includes advanced melanoma patients who were previously treated with anti-PD-1 therapy, similar to the patient population in our C-144-01 study. The second cohort in IOV-GM1-201 is recruiting metastatic non-small cell lung cancer patients whose disease has progressed after up to three lines of prior therapy, including anti-PD-1 therapy, and will also include patients with tumors with EGFR, ALK, or ROS activating mutations. Data from unmodified TIL clinical trials in comparable patient populations provide appropriate benchmarks for potential differentiation of IOV-4001. We look forward to dosing the first patient in this study in the second half of this year. Continuing on to our non-small cell lung cancer pipeline, we have multiple shots on goal with a total of six cohorts across three Iovance studies now enrolling patients at various stages of disease and using multiple treatment modalities. One cohort, which I just mentioned, will receive our genetically modified TIL therapy, IOV-4001. Three cohorts are being treated with TIL monotherapy LN-145 for metastatic non-small cell lung cancer after progression on chemo and anti-PD-1 in our IOV-LUN-202 clinical study. Two additional cohorts are receiving combination treatment in our basket study, IOV-COM-202. TIL plus pembrolizumab in anti-PD-1 naïve patients and TIL plus ipilimumab, nivolumab in patients who progressed after anti-PD-1 monotherapy. Fred mentioned, we plan to enroll additional cervical cancer patients who have progressed on anti-PD-1 therapy into cohort two of our C-145-04 study. Existing active sites are expected to begin recruitment in the coming weeks. TIL therapy with lifileucel has the potential to offer an entirely new class of treatment to address a significant unmet need for cervical cancer patients who progress after anti-PD-1 therapy. Available care in this setting is chemotherapy, with ORR ranging from 3.4%-15% and median duration of response is 4.4 months. Cohort two is intended to be pivotal to support regulatory submissions for the treatment of cervical cancer after chemotherapy and immune checkpoint inhibitor therapy. The pre-specified primary endpoint for cohort two is Objective Response Rate, or ORR, as assessed by Independent Review Committee, or IRC, using RECIST 1.1. On the CMC side, we plan to leverage our know-how from the potency assay matrix for lifileucel in melanoma. We also have a robust research pipeline advancing towards the clinic. Following the success of IOV-4001, several targets for genetic modification are in preclinical studies using the gene editing TALEN technology licensed from Cellectis, including double genetic knockout programs. Using additional technologies, our research and preclinical studies include approaches to increase TIL potency using CD39/CD69 double negative TILs and gene knock-in targets, as well as IND-enabling studies of our novel interleukin-2 analog. I am available to provide additional details during the question and answer session. For now, I will hand the call over to Jean-Marc to discuss our second quarter and first half 2022 financial results. Thank you, Friedrich. My comments will reflect the high-level financial results of our second quarter and first half 2022. Additional details can be found in this afternoon's press release, as well as in our SEC filings. I will begin with the strength of our cash position. As of June 30, 2022, Iovance held $430.9 million in cash, cash equivalents, investment, and restricted cash compared to $602.1 million on December 31st, 2021. Our cash usage from operations during the second quarter included significant one-time retention-related payments. As a late-stage oncology company approaching potential commercialization, we continue to make prudent investments in commercial launch preparation, internal manufacturing, and pipeline expansion. We maintain prior guidance that our cash position is sufficient to advance these activities and our overall operating plan into 2024. Moving to the income statement. Our net loss for the second quarter ended June 30, 2022 was $99.3 million, or $0.63 per share. This compared to a net loss of $81.4 million or $0.53 per share for the second quarter ended June 30, 2021. Net loss for the six months ended June 30, 2022 was $191 million or $1.21 per share, compared to a net loss of $166.8 million or $1.04 per share for the first half of 2021. Research and development expenses were $73.4 million for the second quarter ended June 30, 2022, an increase of $11.3 million compared to $62.1 million for the second quarter ended June 30, 2021. Research and development expenses were $141.7 million for the six months ended June 30, 2022, an increase of $23.6 million compared to $118.1 million for the first half of 2021. The increase in research and development expenses over the prior three and six months periods was primarily attributable to the growth of the internal research and development team, including stock-based compensation expense to support our ongoing and planned pipeline activities, as well as increased facility related and internal research program costs. These higher costs were partially offset by lower clinical and manufacturing costs in the first half of 2022, driven by completion of enrollment in pivotal clinical trials. General and administrative expenses were $26.3 million for the second quarter ended June 30, 2022, an increase of $7 million compared to $19.3 million for the second quarter ended June 30, 2021. General and administrative expenses were $49.7 million for the six months ended June 30, 2022, an increase of $10.8 million compared to $38.9 million for the first half of 2021. The increase in general and administrative expenses compared to the prior three and six months periods was primarily attributable to the growth of the internal general and administrative and commercial teams, including stock-based compensation expense, as well as costs associated with the build out of the new corporate headquarters and pre-commercial and launch readiness activity, as well as our overall growth. As of June 30, 2022, there were approximately 157.8 million common shares outstanding. With the strength of our balance sheet and by continuing to align our spending with our corporate priorities, we are well positioned to execute our operating plan into commercial launch and beyond. I will now hand the call back to the operator to kick off the Q&A session. Thank you. As a reminder, to ask a question, you will need to press star one one on your telephone. Please stand by while we compile the Q&A roster. Our first question comes from the line of Peter Lawson with Barclays. Great. Thanks for the update. Thanks for taking the questions. I guess during the pre-BLA meeting, was there any discussion around the confirmation trial that's required? And then any commentary around the alignment around the potency assay would be great. Thank you. Yeah, thanks, Peter. Yes, as part of the pre-BLA meeting, confirmatory trials did come up, and we did get some favorable commentary on what we're currently planning. We don't have any updates to the street just yet on that. There is, as you know, we're planning a frontline melanoma study later this year, and the FDA did provide at least some commentary that we read as being favorable towards what we're proposing in that trial. To your second question on the potency assay, matrix situation, that really wasn't a major topic at the meeting, and so we really don't see any change in our prior discussions of that topic coming out of the meeting. Gotcha. I guess a final question around the pre-BLA, or my final question, would just be around the read-through from that meeting and how it could help inform filings for also cervical cancer and lung cancer. Good, interesting question. I think. Look, we learned a lot at that meeting about what it's gonna take right now with FDA to get cell therapies approved. I think in general, it gave us some insight. We're not gonna share all that publicly because I think it's competitively valuable, but we do know quite a bit now having gone to a pre-BLA meeting over this that I think is gonna be helpful. There's nothing specific that I think we've learned there that we didn't already know that would impact cervical or lung right now. There is some general information that we got out of the meeting that we think is helpful as to how you get these drugs approved. We'll certainly take advantage of that. Great. Thanks so much. Thank you. Our next question comes from the line of Michael Yee with Jefferies. Hi, this is Dennis on for Mike. Thanks so much for taking our questions. Two questions from us please. One, can you please talk about what were the issues discussed at the pre-BLA meeting? Was there anything the FDA asked that may have been unexpected? I guess, what were their comments on durability after seeing the cohort four data? Then my second question is, around, you know, what specific gating factors do you, guys need to work through to actually submit the BLA? It's a rolling BLA now too apparently, which wasn't a scenario for most investors I think. Talk about the decision to do that as well. Thank you. Sure. On the first point, FDA commented very favorably about the clinical data, and that includes the durability. They saw all the data. They saw the data that effectively we'll be talking about at medical conference later this year, and there was favorable commentary. We even mentioned that in our press release. We think they're supporters of the product from a clinical perspective, based on what they commented at the meeting. I don't think there was anything specific there and nor would I say there was anything unexpected at the meeting in terms of things that came out of left field that we were not planning for in one way or another. Now, going into the second big part of your question, rolling BLA is something that we are obviously announcing here. The rolling BLA is something that gives us some advantages. It allows FDA to start looking at our filing first and start to potentially get comfortable and work, you know, through some of the modules while we finish up on a few secondary tasks and get those submitted. That's really the story behind the rolling BLA submission. Got it. Thank you. Thank you. Our next question comes from the line of Tyler Van Buren with Cowen. Hey, guys. Good afternoon. Thank you very much for taking the questions. I just had a follow-up on the pre-BLA meeting, of course. Specifically, what feedback did they give you regarding the potential for cohort two data to get into the label? The second question is just a point of clarification for the C-144-01 data being presented at a medical meeting by year-end. Will it include the pooled analysis of cohort two and four? Any additional color there will be helpful. Yeah, let me take them in reverse order. On the second part, yes, we'll definitely be talking about the pooled analysis of cohort two and four. We think that's the most relevant to the medical community, as we said before. I can have other members of the team follow up and tell you more about that. We haven't announced the conference yet, but that is our intention, is to focus on that data because that's really the same patient population with the same unmet medical need, and it means the same thing to the investigators out there. Back to cohort two being supportive, the FDA has reiterated the supportiveness of cohort two. They did mention that, in fact, pooled cohort two and four could be supportive as well. We don't know anything more beyond the fact that they've said that many times now and we think that's what they're thinking. They didn't have anything negative to say about cohort two at the meeting. Great. Thanks. Thank you. Our next question comes from the line of Reni Benjamin with JMP Securities. Hey, good afternoon, guys. Thanks for taking the questions. Maybe just starting off again with the pre-BLA meeting. The total package, Fred, how many patients worth of safety data, you know, will be included? Is it just those from the C-144-01 study or can you pool, you know, others together? When in your discussions with them, were there any review issues or do you think there might be a potential for an ODAC panel? Let me take the second part of that first, Reni, then I'll ask Friedrich to answer the first part, because I actually don't know the exact number of the full size of the safety set, but he can explain that to you. We didn't hear anything at the meeting on an ODAC panel that changes what we said previously. We don't think it's something that is gonna happen here, but we're preparing in case there is an ODAC panel, and you always have to prepare, so we're gonna be well prepared if that does happen. There was nothing at the meeting on that topic that gave us any indication that that would be the case. Friedrich, do you wanna answer Reni's question about the total size of the safety data set? Yeah, I don't think that we've shared the exact number of patients that are going in the safety set. What we have shared is the full analysis set, which is 153 patients from 66 patients from cohort two and 87 patients from cohort four. Those are the patients that will drive the efficacy. There are some additional patients that could be considered as part of the review of the safety data and FDA will certainly do that. Got it. Just as a follow-up, just based on your FDA discussions regarding the cervical study, can you maybe just provide some color as to how you know those discussions went? How many patients actually remain you know on the study? 'Cause now you know you're gonna be re-expanding or reopening cohort two. I'm just wondering if there's a chance for let's say a data update you know for people who had remained on the study versus the you know the new patients that you plan on in enrolling. About how many patients are you planning on enrolling for the new expanded cohort two? Yeah. We haven't disclosed how many patients remain on study. You know, what we have, what we think is a sufficient amount of data. As always, we would put out some data potentially on that. It is a pivotal study, thus we have to be careful about doing that. We're not, at this point, fully finalized on the total patient number here, but you should think of the sample size here as being similar to what we looked at for melanoma. You know, we're taking FDA's feedback into account, so, you know, it could be slightly higher. We'll have to figure that out as we go here. The sample size, I would broadly say it's consistent with what we did with melanoma. Great. Thanks for taking the questions. Thank you. From the line of Mark Breidenbach with Oppenheimer. Hey, good afternoon, guys. Thanks for taking our questions and glad to hear the pre-BLA meeting went relatively smoothly. You know, just one for Fred. I was wondering if you can kind of offer any more granularity around the steps of the rolling BLA submission and kind of like what's giving you the confidence that the process will be completed in the fourth quarter. Then kind of an addendum on the previous question with regard to the cervical cancer cohort that's reopening for enrollment. I know you can't tell me how many patients you're planning to enroll, but does the FDA kind of indicate why they want more patients? Is it more to satisfy a safety database requirement or, you know, where is this request for more patients coming from? Thanks for taking the questions. Sure. I'll take them in reverse order. On cervical, it's not really so much. It's I'm sure safety is part of what they're thinking, but it's just we need a patient size. We need a patient size similar to what's been accepted as statistically meaningful for other cell therapies, including our own. You know, with 20+ patients in that study, that's not gonna do it in the patient population we're interested in. They're just asking us for the efficacy set, first and foremost, to increase the size. Of course, that will inform safety as well, although we've got you know, well more than 500 patients worth of safety data across our total programs. Onto the rolling BLA and a little bit more granularity. You know, we're primarily gonna be submitting supportive information during the rolling period, such as manufacturing capacity demonstration, information and things like that. These things are not super complicated. They're things that we think we can get done fairly quickly, which is why we've got confidence in that fourth quarter, and then hopefully as early as possible, completion of the rolling BLA. All right. That's helpful. Thanks. Thanks for taking the questions and congrats. Thank you. Our next question comes from the line of Mara Goldstein with Mizuho. Great. Thanks for taking the question. I have a question on manufacturing. At the time of launch, I know you'll have annualized capacity of about 2,000 patients. But what should we think about for sort of steady state, if you will, for those initial few months of launch? How much capacity do you need to leave back to fulfill clinical trial requirements? I'm just curious about the possibility of improvement on a margin basis from where you will be at launch to where you will be when you get to steady state. Thanks, Mara. Igor, would you be able to answer that one? Happy to. Mara, thanks for your question. I guess it's a twofold question. At launch, we have very detailed plans. We're not disclosing the exact numbers, but we're planning obviously for meeting the commercial demand that we anticipate. In parallel, of course, we continue clinical trials. All of that's included in the capacity that we're planning to have at iCTC, at the Iovance Cell Therapy Center in the Navy Yard, and also supplemented by additional capacity as needed at our contract manufacturer. The cost of goods, there's a lot of focus on the margins, obviously, and that's the team's working on that. Yes, we anticipate as we scale up, the cost of goods, we have more control over that by having our own facility, and we expect that to improve over time. Okay. Just on the rolling BLA, sort of what's the statutory, if you will, timeframe for FDA decision time, from completion of that rolling BLA? Like, how should we think about that? From the completion of the rolling BLA, they calculate eight months to the PDUFA date. However, because you're submitting a rolling BLA, the benefit is they get to look at it early, you have a, you know, higher chance of early approval. At the outset, it's eight months is what you're thinking? Yes, that's the way they calculate it. Again, the benefit of rolling BLA is to get in front of the, you know, to get them. Right. Early so that they can beat that date. Okay. Thanks so much. I appreciate it. Thank you. Our next question comes from the line of James Shin with Wells Fargo. Hey, guys. Thanks for taking the question. For the frontline melanoma study in PD-1 naïve patients, can you disclose if you will take into account the number of baseline tumor lesions and LDH levels, like, what matched cohort four? It's a different patient population we're talking about there. Friedrich, do you wanna maybe talk about how we're thinking about that patient population from that perspective? Yeah, a good question. No, I don't think that we would try to match cohort four because again, as Fred just said, it's a different patient population. It's a much earlier treatment setting. Remember, median number of prior lines of therapy on cohort two and cohort four was three. Many patients had more lines of therapy. These are checkpoint inhibitor-naïve patients, so frontline therapy-naïve patients. So the distribution of numbers, other prognostic factors is very likely to be different and we will certainly not try to match the late line population. There are though some steps that you need to take when you run a randomized trial, and that means you need to stratify for known prognostic factors. We're certainly going to do all the standard measures that you'll usually do in a study design like that. Appreciate it. Thanks, guys. Thank you. Our next question comes from the line of Asthika Goonewardene with Truist. Hi, this is Bill on for Asthika. We had a couple questions for you guys. We were wondering how much would it cost for you to increase your capacity from 2,000 to 5,000? How much more additional to increase to 10,000 patients per year. It's a complicated question, but let me give you some yardsticks and then Igor feel free to chime in. The total capital investment we had in Philadelphia to get us to where we are right now is about $85 million of tenant improvement, and that built shell space. Now, that includes a lot of support services as well, and the building is built so we can just expand the shell space for manufacturing. It would not be anywhere near $85 million to expand that space, and that would get us up to approximately 5,000 patients a year. To go to higher than 5,000 a year, to go to the next level, we're talking about another building, and that's something, you know, you could again, you can do a comparison to what we've done in Philadelphia, but it depends on where you do that. You know, we do have a very favorable, financially favorable option on land here in Philadelphia to expand onto, but we could also do it elsewhere. You know, it would be something like the investment that we made in this facility in terms of the lease plus the $85 million, just adjusted for inflation and, you know, the things that have changed in the real estate market. Igor, do you wanna add anything to that? Fred, I think you covered it again. It's important to understand that the first expansion would be within the existing buildings. It's within the existing shell. We can add 12 core suites to double the core suite capacity. Beyond that, as Fred mentioned, it depends on the options. We're considering several where to expand. Likely to be Greenfield, but there are several location options that could be on the table, and we'll talk about that in due time. It's premature to comment on that today. Great. I guess when is the soonest you think you'd get a green light for LUN-202 as a registrational study? We noted that you had distinct populations within that study, mainly PD-L1 1%-49% and PD-L1 0%. Do you feel confident that one of those subpopulations would have a lower benchmark for filability in terms of? Let me take the first part and then ask Friedrich to speak to the PD-L1 status. We're still in this, you know. We've been seeking FDA feedback on LUN-202 as a registrational study. We don't have anything to update you on right now. All we can say is we're continuing to enroll as best as we can in that study to see how the earlier line of treatment works for, you know, with cell therapy for those patients. Friedrich, do you wanna comment on the PD-L1 status in those two cohorts and what the expectations might be? Yeah, happy to. I think that deserves discussion. Remember, the PD-L1 status that we're defining for these cohorts is the PD-L1 status prior to first-line therapy. That is the PD-L1 status before they start the chemo checkpoint inhibitor therapy. We have separated these cohorts like that because we thought that there is a chance that the treatment course under first-line, on first-line therapy might be different. Because of that, these patients might go into cell therapy slightly differently. Not because we think that the PD-L1 status at start of cell therapy necessarily would be driving treatment outcomes. That is obviously something that we will have to explore and demonstrate. If we are not seeing differences, there's a very good chance that we would simply collapse and be able to look at this as a single population. I hope that makes sense. Clear. Thank you so much. Thank you. Our next question comes from the line of Ben Burnett with Stifel. Hi, thank you very much. I have a question around the release criteria for lifileucel. Understanding that the assays themselves have been established and agreed upon, I guess, can you talk about the release margins or release criteria? To what extent are the release margins established and agreed upon with the FDA? Or is this something that could potentially get ironed out during the review? This is something that can get ironed out during the review. That's pretty sensitive stuff for us to release our product specifications, but it's basically a big topic during the review. We think we have a pretty good idea where we stand in that area right now, but I think, you know, publicly, we're gonna say very little even after we get it agreed as to what those are, unless we have to. Okay. Understood. If I could ask one other question. I think previously you'd mentioned that the melanoma cohorts, two and four, when they were combined, have a median DOR that hasn't yet been reached. I guess, can you comment? Is that still the case today? All I can say there is, stay tuned for our presentation at, you know, a medical conference later on this year. Okay. Understood. Thank you very much. Thank you. Our next question comes from the line of Colleen Kusy with Baird. Hi, good afternoon. Thanks for taking our questions. I know you said previously you're targeting 40 centers at launch. Can you remind us roughly how that compares to what the CAR Ts had at launch? Within those 40 centers, what do you expect the average capacity will be? Do you think about that as patients per month or beds at a time, or just understanding how many patients might fit into that 40 launch? Hi, Colleen. It's Jim here. Thanks for that. We've done a lot of benchmarking of the CAR T market, and we look specifically at claims data over about a four-year period. What we found is the top 10 centers drive about 50% of all the CAR T treated patients, and the top 40 centers account for 80%. Based upon those insights and the centers of excellence that have been established in the CAR T market, that's how we are targeting the 40 centers, the top 40 centers within the first 90 days after approval. Anything on kind of capacity within those numbers? I think the way we think about capacity with them is, you know, what is their bed capacity? Where are they conducting the cell therapy treatment and follow-up? It's gonna vary site by site, but we have an idea of how many beds there are in the ICU, how many beds there are on the general oncology ward, and we'll be working with each site specifically to ensure that, you know, we really understand their capacity, our capacity, and make sure that we're able to treat patients appropriately. Got it. Thank you. Just wondering if there's any guidance that we could expect any updates for the lung programs, either PD-1 combo or additional to monotherapy data this year? Not right now, but that's something. It's as I mentioned earlier during the early earnings report there, you know, lung is really important to us, so that's something that we'll be looking to do as soon as we can. With that many cohorts open, we hope to be able to get some more data out soon. Great. Thank you. Thank you. Our next question comes from the line of Joe Catanzaro with Piper Sandler. Hey, guys. Thanks for the update. Thanks for taking my questions. Wondering first if you could clarify whether the decision to move to a rolling BLA submission was driven by any of the feedback you received during the pre-BLA meeting, or was that decision wholly independent of that? Second question, maybe perhaps a bit speculative, but wondering if the impact of duration of prior PD-1 that you've observed in melanoma is something you expect to extrapolate into other settings. I guess I'm asking that in the context of post-PD-1 cervical now being the emphasis in that indication. Thanks. Let me take the first one, and Friedrich, maybe you can take the second question. During the pre-BLA meeting, I think provided us with some context for our submission as a whole, and I think as a result of that, we just basically came to the conclusion that a rolling BLA submission was the best approach here. Really, I don't wanna say any more that you know about how that went down, but it's basically a full picture of what happened led us to the conclusion that the rolling BLA was the best approach for the success of the product, and we think FDA is very supportive and understandable of that. Friedrich, do you wanna answer the second part of the question? Yeah, sure. Good question. I don't think that we have sufficient information at this point yet, either based on clinical data that we generated nor on really fully understanding. What the mechanism of action is that prior PD-1 therapy might drive that explains some of the differences that have been observed mainly in melanoma really, between patients that were previously treated with checkpoint inhibitors such as the patients in cohort two and four in our C-144-01 study, versus patients that are checkpoint inhibitor naïve. There are a couple of hypotheses out there, and there are some recent publications coming out of the Rosenberg group that are elucidating some of that. Whether that translates into other indications or tumor types, I think that needs to be shown clinically. We have presented initial data on combinations of lifileucel with pembrolizumab in checkpoint inhibitor naïve patients, namely in patients with head and neck cancer, with cervical cancer. We are seeing encouragingly high response rates that are clearly higher than what you would be expecting with pembrolizumab. We might be seeing that difference as well, but I think we need to generate more data. For cervical cancer, however, the unmet medical need certainly is in the post PD-1 setting. There's really nothing good out there for this patient. This is an underserved population of patients. Chemotherapy is terribly inefficient after failure of frontline doublet chemo. TIL therapy is a real opportunity for these patients, and that's what we are focusing on currently. Okay, great. Thanks for taking my question. Thank you. Our next question comes from the line of Madhu Kumar with Goldman Sachs. Hi, this is Omari in for Madhu. We have two questions. First, how should we think about the Objective Response Rate that will be necessary for accelerated approval of lifileucel in post-PD-1 cervical cancer? Two, on post-PD-1 melanoma, beyond cohort four, can we expect any additional data disclosures from the pipeline in 2022? Your second question, I missed. What, from which study? The second question beyond cohort four from post. Beyond cohort four. Okay, I'm sorry. Yeah, beyond cohort four, can we expect any additional data disclosures from the pipeline? Got it. Okay. This year? On the first question, right now, there's no approved therapy in post-PD-1 cervical patients. There's available care out there that the FDA would look at that's chemotherapy with very poor results. Maybe Friedrich, if you wanna add a little bit to that. You know, these are things that we don't view as huge barriers to a successful study. Friedrich, do you wanna add anything about the available care for post-PD-1 cervical patients? Yeah. There is limited data on late line outcomes of cervical cancer patients with chemotherapy, which is really the main therapeutic options these patients have, ORRs ranging somewhere between 3%-15% with chemo. That includes additional doublets, so it's quite toxic. That's the duration of responses, last time I looked, in these historical cohorts, between four and five months. That bar is relatively low. There is no experience with chemo after failure of PD-1 checkpoint inhibitors. The FDA usually, when you're looking at what would be required for an approval, says that they are going to look at the totality of the data at the time of approval in the context of available care. There is not much activity in that field, so maybe these initial numbers give you a rough idea. To answer the second part of your question, you wanna think about data flow beyond the melanoma cohort two, cohort four data flow that we already talked about. The way we're thinking about it at least is, you know, non-small cell lung is one of our priority areas. That's the one we would like to get some data out on soon. We haven't been given any specific guidance on that, but it's high on our list. Then after that, the other indications. All right. Thank you. Thank you. I'm showing no further questions. With that, I'll hand the call back over to Interim President and CEO, Fred Vogt, for any closing remarks. Thank you, operator. Thank you again for joining the Iovance Biotherapeutics second quarter and first half financial results conference call. It's an exciting time to be part of Iovance. I would like to recognize the patients, physicians, and regulators who have collaborated with us throughout the journey to develop TIL therapy, as well as our employees and cross-functional teams for their hard work in arriving at this point. I would also like to thank our shareholders and covering analysts for their support. Please feel free to reach out to the relations team if you wish to follow up. Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for participating, and you may now disconnect.