Earnings Call Transcript
IOVANCE BIOTHERAPEUTICS, INC. (IOVA)
Earnings Call Transcript - IOVA Q2 2022
Operator, Operator
Welcome to the Iovance Biotherapeutics Second Quarter and First Half 2022 Financial Results and Corporate Update Conference Call. My name is Andrew, and I will be your operator for today's call. Currently, all participants are in a listen-only mode. We will have a question-and-answer session later. Please note that this conference is being recorded. I will now turn the call over to Sara Pellegrino, Senior Vice President of Investor and Public Relations and Corporate Communications at Iovance. Sara, you may begin.
Sara Pellegrino, Senior Vice President, Investor and Public Relations and Corporate Communications
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 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 is also on the call to participate in the question-and-answer session. This afternoon, we issued a press release that can be found on our 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 interaction, plans and strategies, research and preclinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interaction, licenses and 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. We undertake no obligation to publicly update any forward-looking statements. With that, I will turn the call over to Fred.
Fred Vogt, Interim President and Chief Executive Officer
Thank you, Sara, good afternoon, everyone. I'm pleased to highlight our significant year-to-date progress at Iovance. I'll begin with our first planned biologic license application or BLA for our lead cell therapy lifileucel and 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 2 and 4 of the IOV-4001 clinical trial, including duration of follow-up and potency assays matrix. The FDA also agreed that the clinical and safety data were 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 the rolling BLA submission this month. The rolling BLA submission is the benefit available under our Regenerative Medicine Advanced Therapy or RMAT designation. The rolling BLA allows us to submit sections of the BLA to the FDA on an ongoing basis. This process enables the FDA to begin a review of submission documents as early as possible as they are received, as they align 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 the FDA senior management team attended. The FDA has engaged in support of the BLA for lifileucel, and we look forward to continuing this level of collaboration throughout the submission and review process. In parallel to BLA-related activities, we're actively preparing to launch lifileucel. Key pre-commercial activities include medical education, treatment center onboarding, payer engagement, commercial manufacturing readiness, and near and long-term capacity planning. We aim to successfully deliver cell 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 5 clinical trials, including the recently initiated trial of our first genetically modified TIL therapy. Six cohorts of non-small cell lung cancer patients are part of 3 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 frontline melanoma towards the end of the year. As noted in this afternoon's press release, we are expecting our C-145-01 study to support the 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 from frontline standard of care in cervical cancer. As we prepare to launch the first one-time cell therapy for solid tumors, we are growing the organization to advance our mission of innovating, developing, and delivering TIL therapies. Today, we have nearly 450 employees who 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 Cell Therapy and our global leadership within the field. I look forward to addressing your questions later during this call. I’ll now ask Igor to discuss manufacturing networks.
Igor Bilinsky, Chief Operating Officer
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 square foot internal manufacturing facility in the Philadelphia area. We custom-designed iCTC and in just 2.5 years, constructed it from the ground up to an operational facility supplying Iovance clinical studies. Manufacturing is critical for any commercial launch, particularly for biological therapies. So our top priority is to prepare iCTC for BLA submission and commercial supply. Today, the iCTC is operating flood 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 manufacturers’ 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 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 shelf space allows us to double the number of core suites and increase annual capacity to provide 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 quality in the Philadelphia area, 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 US 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.
Jim Ziegler, Executive Vice President, Commercial
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 ATC. 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 ATC. We foresee a strong collaboration between the ATCs and community medical oncologists because we expect preferred patients to receive one-time treatment with lifileucel at the ATC 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. Finally, our proprietary Iovance Cares program is on track to assist health care providers and patients through their treatment journey as a best-in-class cell ordering, chain of identity, chain of custody, and patient support program for launch. As 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.
Friedrich Finckenstein, Chief Medical Officer
Thank you, Jim. Today, I would like to share a recent clinical and research program update that reflects the evolution of our pipeline to incorporate additional treatment modalities and next-generation technologies to address more cancer patients in new tumor types at various stages of disease. First, I will briefly summarize the positive top line clinical data from 153 patients across Cohorts 2 and 4 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 2 and 4 met the same primary eligibility criteria at the same study assessment and received the same treatment regimen in lifileucel that was produced using the same Gen 2 cryopreserved toll manufacturing process. Our pivotal cohort 4 met the pre-specified primary endpoint, which was ORR assessed by IRC. ORR as well as various measures of durability for Cohorts 2 and 4 represent meaningful improvement over available therapies 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 naive 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 3 study in frontline melanoma later this year, which is also designed to serve as the 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 the Murine model of melanoma, the antitumor activity of IOV-4001 was superior to the non-edited TIL product, 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 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 short-term goals with a total of six cohorts across three IOV studies now enrolling patients in 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 chemotherapy 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, pembrolizumab in anti-PD-1 naive patients and TIL plus ipilimumab/nivolumab in patients who progressed after anti-PD-1 monotherapy. As Fred mentioned, we plan to enroll additional cervical cancer patients who have progressed on anti-PD-1 therapy into cohort 2 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 patients with cancer who progress after anti-PD-1 therapy. Available care in this setting is chemotherapy with ORRs ranging from 3.4% to 15% and median duration of responses of 4.4 months. Cohort 2 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 2 is objective response rate or ORR, as assessed by the independent review committee or IRC using RECIST 1.1. On the CMC side, we plan to leverage our know-how from the potency FA matrix for Lifileucel melanoma. We also have a robust research pipeline and vested interest in taking our work 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 space includes approaches to increase TIL potency using CD39/69 double negative TIL 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.
Jean-Marc Bellemin, Chief Financial Officer
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, investments, and restricted cash compared to $602.1 million on December 31, 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 maintained 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 compares 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 $156.8 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 month 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 activities 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.
Operator, Operator
Thank you. Our first question comes from Peter Lawson with Barclays.
Peter Lawson, Analyst
Thank you for the update and for addressing the questions. During the pre-BLA meeting, was there any discussion about the confirmatory trial that is necessary? Additionally, any insights on the alignment regarding the potency assay would be appreciated. Thank you.
Fred Vogt, Interim President and Chief Executive Officer
Thank you, Peter. During the pre-BLA meeting, confirmatory trials were discussed, and we received some positive feedback on our current plans. We don’t have any updates at the moment. As you know, we're set to conduct a frontline melanoma study later this year, and the FDA offered comments that we interpreted as favorable regarding our proposal for that trial. Regarding your second question about the potency assay matrix, that topic was not a significant focus in the meeting, so we don’t anticipate any changes to our previous discussions about it.
Peter Lawson, Analyst
Got you. And then, I guess, a final question around the pre-BLA. And 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?
Fred Vogt, Interim President and Chief Executive Officer
Interesting question. I think, well, we learned a lot at that meeting about what it's going to take right now with the FDA to get cell therapies approved. So I think in general, it gave us some insight. We're not going to 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 going to 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. But 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. So we'll certainly take advantage of that.
Operator, Operator
Thank you. And our next question comes from the line of Michael Yee with Jefferies.
Dennis Ding, Analyst
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? And I guess, what were their comments on durability after seeing the Cohort 4 data? And then my second question is around what specific gating factors do you guys going work through to actually submit the BLA? It's a rolling BLA now to, apparently, which was in a scenario for most investors, I think. So talk about the decision to do that as well. Thank you.
Fred Vogt, Interim President and Chief Executive Officer
Sure. Regarding the first point, the FDA provided very positive feedback on the clinical data, including its durability. They reviewed all the data, including what we will present at a medical conference later this year, and we also mentioned their favorable comments in our press release. We believe they support the product clinically based on their remarks at the meeting. There wasn't anything particularly surprising discussed, nor did anything arise that we weren't already prepared for. Now, addressing the second part of your question, the rolling BLA is something we are announcing here. This approach offers us certain advantages, as it allows the FDA to begin reviewing our filing and possibly become more comfortable while we finalize some secondary tasks and submit them. That's essentially the rationale behind the rolling BLA submission.
Operator, Operator
Thank you. And our next question comes from the line of Tyler Van Buren with Cowen.
Tyler Van Buren, Analyst
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 do they give you regarding the potential for Cohort 2 data to get into the label? And the second question is just a point of clarification for the C144-01 data being presented at a medical meeting by year-end. Will it include the full analysis of Cohort 2 and 4? Any additional color there will be helpful.
Fred Vogt, Interim President and Chief Executive Officer
Yes. Let me take a number in a reverse order. On the second part, yes, we'll definitely be talking about the full analysis of Cohort 2 and 4. 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 that means the same thing to the investigators out there. At Cohort 2 being supportive, the FDA has reiterated the support of Cohort 2. They did mention that, in fact, Cohort 2 and 4 could be supportive as well. So we don't know anything more beyond the fact that they've set that many times now, and we think that's what they're thinking. They didn't have anything negative to say about Cohort 2 at the meeting.
Operator, Operator
Thank you. And our next question comes from the line of Reni Benjamin with JMP Securities.
Reni Benjamin, Analyst
Hi, good afternoon, everyone. Thank you for taking the questions. To start with the pre-BLA meeting, how many patients' safety data will be included in the total package? Is it only from the C-144-01 study, or can you combine data from other studies? During your discussions, were there any review concerns, or do you see a possibility for an ODAC panel?
Fred Vogt, Interim President and Chief Executive Officer
Let me address the second part of your question first, Reni. I'll ask Friedrich to respond to the first part since I'm not aware of the exact size of the safety expansion. We didn’t receive any information during the meeting regarding an ODAC panel that would alter our previous statements; we don't believe it’s likely to occur, but we are preparing in case an ODAC panel does take place. It's always important to be ready for such possibilities. However, there was no indication from the meeting that suggested such a scenario. Friedrich, would you like to answer Reni’s question about the overall size of the safety data?
Friedrich Finckenstein, Chief Medical Officer
Yes. I don't think that we share the exact number of the patients that are going in the safety set. What we have shared is the full analysis that with this 153 patients from 66 patients from Cohort 2 and 87 patients from Cohort 4. So 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 they will certainly do that.
Reni Benjamin, Analyst
Got it. And then 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 those discussions went, how many patients actually remain on the study because you're going to be re-expanding or reopening Cohort 2? I'm just wondering if there's a chance for, let's say, a data update for people who have remained on the study versus the new patients that you plan on enrolling? And about how many patients are you planning on enrolling for the new expanded Cohort 2?
Fred Vogt, Interim President and Chief Executive Officer
Yes, we haven’t disclosed the number of patients remaining in the study. We believe we have a sufficient amount of data, but we need to be cautious about sharing specifics since this is a pivotal study. At this time, we haven’t finalized the total patient count, but you should consider the sample size to be similar to what we used for melanoma. We are taking feedback into account, which may result in a slight increase. We will determine the final size as we progress. Generally speaking, the sample size will be consistent with what we planned for the BLA.
Operator, Operator
Thank you. Your next question comes from the line of Mark Breidenbach with Oppenheimer.
Mark Breidenbach, Analyst
Hey, good afternoon guys. Thanks for taking our questions, and glad to hear the pre-BLA meeting went relatively smoothly. 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? And 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 indicate why they want more patients? Is it more to satisfy, safety database requirement or where is this request for more patients coming from? Thanks for taking the questions.
Fred Vogt, Interim President and Chief Executive Officer
Sure, I'll address them in reverse order. Regarding cervical cancer, it's not entirely about safety considerations; the main issue is the need for a substantial number of patients. When we have a sample size comparable to what has been accepted, it becomes statistically meaningful for other cell therapies, including ours. The FDA is primarily requesting the efficacy data first to increase the sample size, which will also contribute to safety assessments. We already have well over 500 patients for safety data across various programs. Moving on to the rolling BLA, we plan to submit supportive information during this period, such as demonstrating manufacturing capacity. These tasks are not particularly complex, and we believe we can complete them quickly, which is why we are confident in finishing this during the fourth quarter, or even as early as possible within the rolling BLA timeline.
Operator, Operator
Thank you. And our next question comes from the line of Mara Goldstein with Mizuho.
Mara Goldstein, Analyst
Great. Thanks for taking the question. I have a question on manufacturing. And at the time of launch, I know you have annualized capacity of about 2,000 patients. But what should we think about for steady state, if you will, for those initial few months of launch? And how much capacity do you need to lead back to fulfill trial requirements? And 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 a steady state?
Igor Bilinsky, Chief Operating Officer
Happy to. Mara, thanks for your question. So, I guess it’s a two-fold question. So at launch, we have very detailed plans. We're not disclosing the exact numbers, but we're planning, obviously, to meet the commercial demand that we anticipate, and in parallel, of course, we continue clinical trials. And all of that is included in the capacity that we're planning to have at iCTC, 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 is working on that. And, yes, we're in discipline 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.
Mara Goldstein, Analyst
Okay. And just on the rolling BLA, sort of, what's the statutory, if you will, time frame for FDA decision time from completion of that rolling BLA? Like how should we think about that?
Fred Vogt, Interim President and Chief Executive Officer
So 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 so you can have a higher chance of early approval…
Mara Goldstein, Analyst
Okay. But at the outset, it's eight months. Is that what you're thinking?
Fred Vogt, Interim President and Chief Executive Officer
Yes, that's how they calculate it. However, the advantage of submitting rolling BLAs is to address it sooner, allowing us to potentially achieve approval before that date.
Mara Goldstein, Analyst
Right. Thanks so much. I appreciate it.
Operator, Operator
Thank you. And our next question comes from the line of James Gin with Wells Fargo.
Unidentified Analyst, Analyst
Hey, guys. Thanks for taking the question. For the frontline melanoma study in PD-1 naive patients, can you disclose if you will take into account the number of baseline tumor lesions and LDH levels that match Cohort 4?
Fred Vogt, Interim President and Chief Executive Officer
It's a different patient population we're talking about there. Friedrich, do you want to maybe talk about how to think about the patient population from that perspective?
Friedrich Finckenstein, Chief Medical Officer
Yes, that's a good question. I don't believe we will attempt to match Cohort 4 because, as Fred mentioned, it represents a different patient population. This is an earlier treatment setting. Recall that the median number of prior treatment lines in Cohort 2 and Cohort 4 was three, with many patients having undergone more treatments. These are checkpoint inhibitors, so they involve patients who have not received frontline therapy. Therefore, the distribution of numbers and other prognostic factors will likely differ, and we certainly will not attempt to match the late-line population. However, there are steps to consider when stratifying for non-prognostic factors. We will definitely implement all the standard measures typically used in a study design like this.
Unidentified Analyst, Analyst
Appreciate it. Thanks, guys.
Operator, Operator
Thank you. And our next question comes from the line of Asthika Goonewardene with Truist.
Unidentified Analyst, Analyst
Hi. This is Bill on for Asthika. We had a couple of questions for you guys. We're wondering how much would it cost for you to increase your capacity from 2,000 to 5,000? And then how much more additional to increase to 10,000 patients per year?
Fred Vogt, Interim President and Chief Executive Officer
That's a complex question, but let me provide some information and then Igor can add to it. The total capital investment we made in Philadelphia to reach our current position is around $85 million for the improvements and shelf space. This figure includes various support services as well. We've built in the capability to easily expand the shelf space for manufacturing, so the cost to increase that space will be much less than $85 million, and this will allow us to accommodate approximately 5,000 patients a year. To exceed 5,000 patients a year and move to the next level, we would need another building. We can compare this to our Philadelphia operations, but the location will determine the specifics. We have a financially advantageous option for expansion in Philadelphia, but we could also consider other locations. The investment required for the lease of that facility was around $85 million, adjusted for inflation and changes in the real estate market. Igor, do you want to add anything?
Igor Bilinsky, Chief Operating Officer
Fred, you covered it well. It's crucial to note that the initial expansion will occur within the existing buildings, allowing us to add more core suites to double our capacity. As Fred mentioned, our expansion options are still being considered, and while greenfield opportunities seem likely, there are various locations we could explore. We will discuss this further at the appropriate time, but it's too early to provide more details today.
Unidentified Analyst, Analyst
Great. When do you think you will receive approval for LUN-202 as a registrational study? We noticed that you had distinct populations in that study, specifically PD-L1 and PD-L1 0%. Are you confident that one of these subpopulations would have a lower benchmark for viability?
Fred Vogt, Interim President and Chief Executive Officer
Let me address the first part and then turn it over to Friedrich to discuss the PD-L1 status. We are still seeking feedback on LUN-202 as a registrational study, and we don't have any updates at this point. We consistently mention that we are exploring studies to evaluate how the earlier lines of treatment perform for cell therapy in those patients. Friedrich, would you like to share your insights on the PD-L1 status in the two cohorts and what the expectations are?
Friedrich Finckenstein, Chief Medical Officer
Yes. Happy to. I think that deserves discussion. So remember, the PD-L1 status that we're defining for the scores is the PD-L1 status prior to first-line therapy. So 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 therapy might be different. And 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 outcome. So that is obviously something that we will have to explore and demonstrate. If we are not seeing differences, there is 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.
Unidentified Analyst, Analyst
Clear. Thank you so much.
Operator, Operator
Thank you. And our next question comes from the line of Ben Burnett with Stifel.
Ben Burnett, Analyst
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?
Fred Vogt, Interim President and Chief Executive Officer
This is something that can be clarified during the review. While we are cautious about sharing our product specifications, it is an important topic for discussion. We believe we have a good understanding of our position in this area right now. However, we will likely keep our explanations limited until we reach an agreement on those specifications.
Ben Burnett, Analyst
Okay, understood. If I could ask one other question. Previously, you mentioned that the melanoma cohorts two and four, when combined, have a median duration of response that hasn't yet been reached. Can you comment on whether that is still the case today?
Fred Vogt, Interim President and Chief Executive Officer
All I can say is to stay tuned for our presentation and another conference later on this year.
Operator, Operator
Thank you. And our next question comes from the line of Colleen Kusy with Baird.
Colleen Kusy, Analyst
Hi, good afternoon. Thanks for taking my 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? And then, within those 40 centers, what do you expect the average capacity will be? Do you think about that as patients per month, their beds at a time or just understanding how many patient plants fit into that 40 launch?
Jim Ziegler, Executive Vice President, Commercial
Hi Colleen, it's Jim here. Thanks for that. So 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. And 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%. So 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.
Colleen Kusy, Analyst
And anything kind of capacity within those?
Jim Ziegler, Executive Vice President, Commercial
Yeah. So I think the way we think about capacity with them is what is their bed capacity where they are conducting the cell therapy treatment and follow-up. And so it's going to vary site-by-site. But we have an idea of how many beds they are in the ICU, how many beds they are on the general oncology ward. And we'll be working with each site specifically to ensure that we really understand their capacity, our capacity, and make sure that we're able to treat patients appropriately.
Colleen Kusy, Analyst
Got it. Thank you. And then, 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?
Jim Ziegler, Executive Vice President, Commercial
Not right now because lung is really important to us. That's something that we will 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.
Operator, Operator
Thank you. And our next question comes from the line of Joe Catanzaro with Piper Sandler.
Joe Catanzaro, Analyst
Hey guys. Thanks for the update and thanks for taking my questions. I was 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? And then 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. And I guess I'm asking that in the context of post PD-1 cervical now being the emphasis in that indication. Thanks.
Jim Ziegler, Executive Vice President, Commercial
Let me take the first one and Friedrich, maybe you can take the second question. During the pre-BLA meeting, I think it 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 rolling submission was the best approach here. And really, I don't want to say any more about how that went down, but it's basically a full picture of what happened that led us to the conclusion of Iovance was the best approach to the success of the product, and we think. Friedrich, you answer the second part of the question.
Friedrich Finckenstein, Chief Medical Officer
Yes, 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 PD 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 check inhibitors such as subpatients in cohort 2 and 4 in our C-144-01 study versus patients that are checkpoint inhibitor naive. 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 naive patients, namely in patients with head and neck cancer or cervical cancer. And we are seeing encouragingly high response rates that are clearly higher than what you would be expecting with temporal loss. So 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 is really nothing good out there for these patients. This is an underserved population of patients. Chemotherapy is terribly inefficient after failure of frontline doublet chemo, and TIL therapy is a real opportunity for these patients, and that's what we are focusing on currently.
Unidentified Analyst, Analyst
Okay. Great. Thanks for taking my question.
Operator, Operator
Thank you. And our next question comes from the line of Madhu Kumar with Goldman Sachs.
Unidentified Analyst, Analyst
Hi, this is Omar in for Madhu. So we have two questions. First, how should we think about the objective response rate that will be necessary for expedited approval of lifileucel post-PD-1 cervical cancer? And then two, on post PD-1 melanoma beyond cohort - 4, can we expect any additional data disclosure from the pipeline in 2022?
Fred Vogt, Interim President and Chief Executive Officer
What is – on your second question, I missed for which study?
Unidentified Analyst, Analyst
And the second question, beyond cohort 4, can we expect any additional data disclosure from the pipeline this year?
Fred Vogt, Interim President and Chief Executive Officer
Got it. Okay. Well, the first question, there is currently no approved therapy for post-PD-1 cervical patients. There is available care that the FDA will consider, which is chemotherapy with significantly improved results. Friedrich, would you like to add anything regarding available care for post-PD-1 cervical patients?
Friedrich Finckenstein, Chief Medical Officer
There is limited data on the outcomes of cervical cancer patients receiving chemotherapy, which is the primary treatment option for these patients, with response rates ranging from 3% to 15%. Chemotherapy that includes additional combinations can be quite toxic. The duration of responses has historically been around four to five months, indicating a low benchmark. There is no established experience with chemotherapy following the failure of PD-1 checkpoint inhibitors. The FDA typically evaluates the overall data at the time of approval in relation to the available treatment options, and there isn't much activity in this area. These initial figures may provide a rough estimate.
Fred Vogt, Interim President and Chief Executive Officer
To address the second part of your question, it's important to consider the data flow beyond the melanoma Cohort 2 and Cohort 4 discussions we've had. Our focus includes lung cancer, particularly non-small cell lung, which is a priority for us. We aim to provide some data soon, although we haven't offered specific timelines yet. This remains a top priority, followed by updates on other indications.
Operator, Operator
I'm showing no further questions. So with that, I'll hand the call back over to Interim President and CEO, Fred Vogt for any closing remarks.
Fred Vogt, Interim President and Chief Executive Officer
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 with TIL therapy as well as our employees and cross-functional teams for their hard work and arriving at this point. I'd also like to thank our shareholders and covering analysts for their support. Please feel free to reach out to our relations team if you wish to follow up. Thank you.
Operator, Operator
Ladies and gentlemen, this concludes today's conference call. Thank you for participating, and you may now disconnect.