Earnings Call: Q1 2021

May 6, 2021

Hello, and welcome to the Iovance Biotherapeutics First Quarter 2021 Financial Results Conference. My name is Michelle, and I will be the operator on today's call. At this time, all participants are in a listen only mode. Later, we will conduct a question and answer session. I will now turn the call over to Ms. Sarah Pellegrino. Ma'am, you may begin. Thank you, operator. Good afternoon, and thank you for joining us. Speaking on today's call, we have Maria Fardis, our President and Chief Executive Officer Frederic Finkenstein, our Chief Medical Officer and Jean Marc Bellamy, our Chief Financial Officer. We are also joined by Jim Ziegler, Senior Vice President, Commercial. This afternoon, we issued a press release that can be found on our website at iovance.com, which includes the financial results for the 3 months ended on March 31, 2021, as well as 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 regulatory plans and results, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interactions, 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 intro, I will turn the call over to Maria. Thank you, Sarah, and good afternoon, everyone. I am pleased to highlight our Q1 2021 progress at Iovance during today's conference call. During 2021, we have continued to advance and expand our Iovance Tumor Infiltrating Lymphocyte or Till platform across multiple indications, including metastatic melanoma, cervical, head and neck and non small cell lung cancers. For our lead Till product candidate, lifileucel in metastatic melanoma, we completed the submission of additional information related to our potency assays to FDA in support of a planned biologics license application or BLA submission. Resolution of the potency assay with FDA is our top priority for 2021. We also reported new and updated data from our ongoing C14401 clinical study, demonstrating durable responses in our Cohort 2 for one time treatment with liso leucil. The Cohort 2 data was presented at AACR 2021 and additional data updates will be presented at ASCO 2021. And additional indications, we completed patient dosing in Cohort 2 for lifineustal in advanced cervical cancer. For our registration directed study of LN-one hundred and forty five in non small cell lung cancer, we continue to activate sites for IOV LUN-two zero two and consented multiple patients. We believe that the growing body of Iovance Till clinical data across multiple late stage cancers, coupled with results from combination of our Till and anti PD-one therapy in earlier stages of the disease, validate the significant and broad potential for iovance TIL therapy. We also continue to execute toward all manufacturing and pre commercial activities and furthering our commitment to address the critical need of cancer patients. I am very confident in the quality of our internal team to deliver towards this mission. An impressive 76% of our more than 2 50 employees have at least a year of cell therapy experience. On the call today, I would like to spend a few minutes highlighting our lead indications and manufacturing progress. Then I will let Fredericks review our recent clinical data updates. I will begin with our 1st pivotal program, lifileucel for advanced melanoma. As discussed on our previous calls, metastatic melanoma is a common type of skin cancer. In the U. S. Alone, metastatic melanoma accounts for approximately 100,000 patients diagnosed at 7,000 deaths each year in the United States. We are focused on the growing population of melanoma patients that have exhausted their most commonly used available care options and need alternative therapies in our C1440 1 study. At the American Association For Cancer Research or AACR Annual Meeting, the updated data for Cohort 2 from C14401 clinical study was presented at a clinical trial plenary session. The long term follow-up data shows that median duration of response was not reached at 28.1 months of median study follow-up. Furthermore, overall response rates remained at 36.4% and we saw a continued deepening of response in 17% of the patients. We as well as KOLs, including the physicians who highlighted the at AACR, continue to be very enthusiastic about the durability of response following one time treatment with lifileucel in very difficult to treat metastatic melanoma patients. For the post anti PD-one patient population enrolled in Cohort 2, chemotherapy is the only currently available option and Society of Clinical Oncology or ASCO Annual Meeting in June. Detailed Cohort 2 data has also been accepted for publication in a forthcoming manuscript in a peer reviewed high impact oncology journal. Turning to TIL in earlier lines of therapy, at the upcoming ASCO 2021 meeting, we are excited about sharing clinical data for lifileucel in combination with pembrolizumab and anti PD-one naive metastatic melanoma patients. Combination of Iovance Till with available therapies in anti PD-one naive patients is one of Iovance's main clinical goals toward moving Till into earlier treatment settings. Melanoma is the 2nd clinical setting in which such combination is tested and data are being provided. As previously mentioned, reaching agreement with FDA on the potency assays for Lifileucel is a top priority for IVAN. While the length of time until BLA submission depends on feedback from the agency, continue staying prepared for a BLA submission in 2021. We plan to provide updates when available. Our second pivotal program is investigating LN-one hundred and forty five, now also known as Xipeleucil, in the C14 five zero four study to support a BLA submission in metastatic cervical cancer. During the Q1, Cohort 2 patient dosing was completed in post anti PD-one cervical cancer patients. We believe that a BNA submission that includes both co pivotal cohort 1, which is evaluating lifileucel post chemotherapy, in addition to cohort 2, may strengthen the potential label and reflect the expected upcoming treatment landscape in cervical cancer. As we have mentioned before, the resolution of the potency assay for lifileucel in melanoma and dialogue with FDA around the amount of clinical data follow-up are key steps toward our BNA submission in the cervical cancer indication. As a reminder, the FDA has previously granted both breakthrough therapy and fast track designations for lifileucel in cervical cancer. Turning to our manufacturing facility, Iovance Cell Therapy Center or ICTC, we have completed construction of the exterior core and shell as well as initial clean rooms and we have moved in. Process equipment and necessary utilities are now in place in the available clean room and activities have commenced to support the start of Till clinical manufacturing in late 2021. Commercial manufacturing of Iovance Till remains on track for 2022 with capacity to meet the demand for up to thousands of patients in multiple indications. Iovance has transformed Till manufacturing from a lengthy academic process to a shorter, scalable, centralized GMP process yielding a cryopreserved product. Our GEN-two process is 22 days. To date, more than 4.50 patients have received Iovance Till with a continuing success rate above 90%. We are also looking forward to the potential to further improve the Till manufacturing timelines and efficiencies. A shorter 16 day 3rd generation Iovance Till manufacturing process or GEN-three is being explored in 2 of our clinical studies. The patients receiving GEM3 TIL include a cohort of metastatic melanoma patients in the IOV COM-two zero two clinical study where patient dosing has initiated, as well as a cohort of a non small cell lung cancer patients in the IOV LUN-two zero two study. We have also built and continue to augment our intellectual property, which is covered by more than 25 granted or allowed U. S. And international patents. Granted patents include composition and methods of treatment in a broad range of cancers relating to the GEN-two manufacturing process with expected exclusivity through 2,038. Iovance patent applications and granted patents are also directed towards Gen 3 manufacturing, selected Till products, stable and transient genetic modification of Till, tumor digest and fragment composition and methods including cryopreservation and combination of Till with checkpoint inhibitors. In addition, as noted in this afternoon's press release, we have licensed additional patent rights from National Institutes of Health or NIH for cytokine tethered Till technology, including IL-fifteen and IL-twenty one and similar technology. We also expanded our worldwide field of use to all cancers. We believe that this expanded license and relationship with NIH may further solidify our leadership in the advancement of Till and related intellectual property. Turning to our pre commercial launch preparations, we remain disciplined in our gated approach to commercial readiness. Our core commercial team continues to build the foundation for site training, patient access, payer coverage and other commercialization readiness activities. We are well positioned to rapidly scale and expand efforts across these areas pending alignment with the FDA on our potency assay. Our medical affairs team maintains clinical site engagement in preparation for commercial launch. This team continues to work with key opinion leaders and patient advocacy groups on Till awareness and educational programs and to ensure scientific communication at major conferences and in peer reviewed publications. Commercial team is partnering with the leading U. S. Cancer centers to build their Till service line capabilities. Our training and onboarding program, which we will further expand upon VLA submission, is designed to ensure cross disciplinary teams can administer the lifileucel treatment regimen upon FDA approval. Our market access team continues to engage payers to ensure patients have access to lifileucel. Very recently, the Centers For Medicare and Medicaid Services, or CMS, proposed 2 new international classification of diseases, TENS revision procedure coding system or ICD-ten codes for lifileucel. Additionally, CMS proposed to map lifileucel to existing MS DRG18. CMS also proposed to expand MS DRG18 from CAR T cell immunotherapy to CAR T cell and other immunotherapies including Iovance Till. We believe that CMS' proposal liso leucil in existing MS DRG18 is recognition of the value of Iovance pill and cell therapies for patients and the need to ensure appropriate reimbursement for providers beyond CAR T. The proposal, if finalized, has the potential to strengthen hospital reimbursement for lifileucel therapy at the time of launch. We appreciate CMS' leadership and commitment to access to care. The Iovance team is also developing our Iovance Cares program, which remains on track. Our goal is to deliver a best in class chain of custody and chain of identity system, cell ordering platform and patient support capabilities. Iovance Cares is designed to be both customer and patient centric throughout the life in U. S. Treatment journey. I will now pass the call to Fredrick to outline our clinical update. Friedrich? Maria, I am pleased to highlight reasons in upcoming clinical data updates for Iovancerel alone and in combination with pembrolizumab in melanoma as well as the status of our 4 ongoing clinical studies. Our drug development strategy focuses on cancer populations with high unmet need with substantial opportunity for Till to make a meaningful impact. First, as Maria mentioned, we provided an update for Cohort 2 in our C14401 clinical study at AACR at approximately 28.1 months of median study follow-up and longer term updates have been accepted for oral presentation at ASCO. We are also looking forward to an upcoming peer reviewed publication of detailed Cohort 2 data. At the upcoming ASCO meeting, we are also looking forward to the poster presentation of initial clinical data in the IOVCOM202 study from Cohort 1A, which is evaluating lifileucel in combination with pembrolizumab in melanoma. This will represent a second indication with clinical data for Iovance Till in combination with pembrolizumab in earlier treatment settings, following the encouraging data in head and neck cancer presented at last year's Society For the Immunotherapy of Cancer or SITC meeting. While pembrolizumab yields 33% response rate, 6% of which are complete responses in patients with melanoma, 40% to 65% of patients still progress on or after treatment. Therefore, in anti PD-one naive metastatic melanoma, there remains a need to increase the overall response rate and in particular, the complete response rate. We also continue to recruit patients across 4 clinical studies with Iovance Till. Our C-fourteen thousand five hundred and four clinical study in advanced cervical cancer has completed patient dosing in the first two cohorts. We continue to recruit a 3rd cohort of anti PD-one naive patients to receive Iovance pill plus pembrolizumab. We have now activated a total of 10 sites and consented multiple patients for our registration supporting study, IOV, LUN-two zero two in second line non small cell lung cancer. We believe that the patient population in IOV LUN-two zero two as well as the 3 non small cell lung cancer cohorts in the Basket study allow us to broadly address the unmet needs in non small cell lung cancers. Recruitment also continues in our IOVCOM-two 2 study of Iovance Till and Till combinations across melanoma, head and neck and non small cell lung cancers, in addition to the IOV CLL-one study in CLL and SLL. As the impact of the COVID-nineteen pandemic on hospitals results following the rollout of the COVID-nineteen vaccines and as the virus abates, we hope to be able to provide additional data at future medical meetings. I will now hand the call over to Jean Marc to discuss our Q1 one financial results. Thank you, Frederic. My comments will reflect the high level financial results from our Q1 of 2021. Additional details can be found in this afternoon's press release as well as in our SEC filings. I will begin with our cash position. As of March 31, 2021, $610,200,000 in cash, cash equivalents, investments and restricted cash compared to $635,000,000 on December 31, 2020. Our strong cash position is expected to be sufficient into 2023 to deliver on our pipeline programs. Moving on to the income statement. Our net loss for the Q1 ended March 31, 2021, was $75,400,000 or $0.51 per share compared to a net loss of $69,600,000 or $0.55 per share for the Q1 ended March 31, 2020. Research and development expenses were $55,900,000 for the Q1 ended March 31, 2021, a decrease of $1,000,000 compared to $57,000,000 for the Q1 ended March 31, 2020. The year over year decrease in research and development expenses was primarily attributable to a decrease in manufacturing and clinical costs following the completion of enrollment in the pivotal cohorts for melanoma and cervical cancer. General and administrative expenses were $19,600,000 for the Q1 ended March 31, 2021, an increase of $5,800,000 compared to $13,900,000 for the Q1 ended March 31, 2020. The year over year increase in general and administrative expenses was primarily attributable to growth of the internal general and administrative team and higher stock based compensation expenses. As of March 31, 2021, there were approximately 149,300,000 common shares outstanding. Looking ahead, we remain focused on investment in 4 key areas to ensure the growth and strength of our value creation. 1st, advancing our current clinical programs and indication second, scaling up our manufacturing capacity support our clinical manufacturing while preparing for expected commercial supply in 2022 3rd, ensuring launch readiness and 4th, maintaining a strong balance sheet and cash position. I remain confident that by managing our investments across these four priorities, we will continue to stay focused and align our spending with our corporate priorities. I will now hand the call back to the operator to kick off the Q and A session. Thank you. We will now begin the question and answer The first question in the queue comes from Peter Lawson. We'll go to the next question, Michael Yee. Can you hear me okay, Maria? Yes, we can. Hi, Michael. Hey, guys. Thanks and appreciate the update. In the interest of, I guess, one question, our question was regarding the commentary around the progress in submitting additional data for assays. And the question was around your confidence level that things are absolutely moving on a pace to get an agreement. And if there was an agreement, you would just be able to come out and say that. And if that was not going along the right path, there are mechanisms to be able to either engage with the broader ODAC team or do other things to just be able to go ahead and push a little harder? Sorry for the different questions here, but it's all kind of related to the confidence level and the time lines. Thank you. Understood. Thank you so much, Michael. We have submitted, as we noted, we have submitted our prior responses to agency to the questions that were issued as part of the Type B meeting. We also have now provided the validation data that we had committed to provide to FDA as part of our responses in Q1 of 2021. We have not heard back from the agency, and I think a degree of confidence would depend on feedback from them. We really do need to hear from them. In terms of mechanism of escalation, there are So yes, there are venues and we certainly have considered them. So yes, there are venues and we certainly have considered them. Thank you very much. Thank you. Okay. And Peter Lawson, your line is open. Please proceed. Great. Thank you so much. Sorry, I joined late, so I apologize if you drowned through this. But when in lung cancer, when you think about the subsets kind of post TKI and PD-one high and low and failed, where do you think Till therapy could potentially fit in? Where do you think you've got the best shot at generating efficacy over both existing and emerging therapies coming through? Hi, Peter. Thank you for the question. The study that was conducted by Moffett and was published at AACR 2020 was incredibly helpful in showing that there really didn't seem to be a particular subpopulation that was responding to Till or not responding to Till. What you might have seen is patients who had a PD L1 low expression level were still among the responders or patients that were post TKI if they had an oncogene driver mutation. So that's highly encouraging. It's quite consistent with the signature of Till where there's not a specific subpopulation that may not respond to Till. Now our study design, such as the specific IOV COM202 or LUN202 is more designed with a registration program in mind. So LUN202 specifically is potentially supportive of registration. And so the subpopulation that we selected there is trying to identify a patient population that is both on a net medical need and yet early enough in lines of therapy that the patients have an opportunity to benefit from Till. It's not selected based on where we think Till may be active or not active. It's really what we see is Till seems to be active regardless of the subpopulations to the degree we have data in non small cell. Got you. Thank you. And then this may be addressed, but when was the last time you spoke to the FDA? I know the FDA is kind of not on a time clock with you, But when was the last time you spoke about the BLA? And when do you anticipate speaking again? And do you think things are moving forward or have they paused or just your sense around that dialogue? Sure. So FDA is a pretty large body. The review team or formal meetings is one venue for communication. There certainly are informal other ways of talking to FDA through either regulatory project managers or other venues. So the dialogue with the agency is very much ongoing. It doesn't necessarily mean this is a standard sort of a new type of a meeting, like a Type B meeting. But there definitely is dialogue between our regulatory team and FDA to make sure that they have received the package, that they satisfied time to review it and they will respond to us in a timely manner. Great. Thank you. The next question in the queue comes from Mark Breidenbach. Your line is open. Please proceed. Hey, good afternoon and thank you for taking our question. Just switching over to the upcoming data from lifileucel combined with pembrolizumab in frontline melanoma. I'm curious how many patients we're likely to see in that presentation, maybe ballpark how much follow-up we can expect? And Maria, I'm also curious to get your thoughts on what you see as likely next steps for development in an early line setting. Would this, basket trial cohort potentially balloon into a randomized study versus single agent pembro? Or what do you have in mind, assuming these initial data look good? Sounds good. Thank you, Mark. The number of patients has not quite been disclosed once the abstracts come out, away from embargo, we can certainly discuss how many patients are in there. What I can say is that the cohort itself was designed for 12 patients and the cohort is still open. So it's still continuing to enroll into the cohort. In terms of what the next steps would be, it is important for us to understand with larger number of patients and longer follow-up what the real data is. These early looks are really helpful for us to understand what the potential may be. But at the same time, we recognize that we want to make sure we have large enough sample size that we understand what the product is or is not doing. In terms of next step, I think once the data is visible, it's a little bit easier to speak to it. In general, I'll speak to I'll answer your question in a general sense. Typically, when you have a combination in early line, the next step typically is a randomized study that would show the contribution of elements. I do not rule out single arms in general. If the contribution of elements is extremely high in that single arm, there may be possibilities of talking to the agency and defining a registration path with a single arm. It's not very common though. So typically, a randomized Phase 3 type would be a next step to take. Got it. Thanks for taking the question. Thank you. And the next question in the queue comes from Boris Peaker. Your line is open. Please proceed. Great. I just wanted to ask in terms of the lung cancer cohorts, when should we be expecting updates from those? And what are some of the factors that go into kind of deciding the timing of those updates? Hi, Boris. Good afternoon. Yes, absolutely. So we have really 2 cohorts that have lung cancer patients. 1 is in our basket study, the COM202 study has 2 cohorts, Cohorts 3a and 3b. Cohort 3a, which is early line patients, the treatment naive or actually PD-one naive patients, has been a little bit slower to enroll during COVID and this may very well be the impact of hospitals having been impacted by COVID as well as the fact that these patients obviously have available therapies to receive at their local institutions. In Cohort 3b, we do have some patients. We have not committed to a specific data flow timeline. We drew the conclusion that patients that are second line are certainly much better in terms of non small cell. The accretion from first line to second line in non sponsored lung cancer is quite large. Unfortunately, many patients around 70% of the patients don't make it to second line. So we are trying to limit our subsequent upcoming cohorts to second line non small cell, but we do have some patients in that Cohort 3b, which once we have long enough follow-up, we could disclose the data. We haven't committed to a specific venue or a timeframe yet. Great. Thank you very much for taking my question. Thank you, Boris. And the next question in the queue comes from Mara Goldstein. Please proceed. Great. Thanks so much for taking the questions. Just a couple of things. First, I just wanted to circle back to make sure that I understood correctly on the submission that was made to the FDA around the assay, that the FDA is not obligated to respond to you within a specific timeframe for that submission. And on the cervical program, can you give us a bit more background on how the decision was made to combine the 2 cohorts? And was that made based on discussions with FDA? And where does that leave a potential filing timeline? And then the last thing I was just a curiosity more than anything. On the reimbursement front and the determinations that have been made around codes and whatnot, is there a specific time limit, in which those must be made active such that you don't have to reapply back to the agencies? Mara, I understood your first two questions. Let me answer them, but I didn't catch quite your third question. Let me try and answer the first few and then I'll ask you to repeat number 3. In terms of the assay, you're correct. The agency is not on a PDUFA clock to answer in a given time line. However, when a CMC IND amendment is submitted to the agency, there's guidelines that typically limit the duration of time they review. It's usually 1 to 2 months. And so that guideline is what we are sort of referring to and waiting for the agency to respond within that window of opportunity. In terms of cervical, we have been quite committed to combining the cohorts. I just want to be sure that we are clear. We gave the visibility to investors that we have the possibility of combining Cohorts 1 and 2. It's certainly subject to discussion with FDA. Cohort 1 were patients that were post chemotherapy in metastatic setting and cohort 2 were patients that also could have received anti PD-one in a metastatic setting. Now the reason we went down that path is we wanted to make sure that the investors are aware that there's a possibility, given the potential change in the landscape of cervical cancer, there's a possibility that the agency may request for 2 and or Iovance may want to include that data. So it's very much subject to discussion with FDA. If that addresses your questions 12, do you mind repeating your question 3? Sure, Nalitam. But on question 2, if you do if the determination is that those cohorts will be combined from a potential filing perspective, is that what does that do to sort of the internal time line that you have or the one that you shared? Understood. Understood. From a timing perspective, just to kind of lay out what is required to reach a cervical BLA, let me just sort of lay out the steps that are needed. 1st and foremost, we absolutely want to make sure that our potency assay issue is resolved with the melanoma team, which is right now the dialogue that is ongoing. As a next step, we still do need to meet with the cervical review team to discuss the amount of follow-up they're going to request and whether cohort 1 plus cohort 2 is something they want or they want to stay just with cohort 1. And subsequent to that, we can think about sort of the BLA timeline. A scenario during which this submission can happen later part of this year is still in the picture from my perspective. It really depends on when we get the potency assay resolved. Okay. That's great. And then I was just curious, as you were discussing in the top of the call around having determinations from CMS and whatnot around potential codes such that you could get reimbursed. I know typically those need to be in the books, I believe by August. And so I'm just curious, do you have to have a commercialized product within a certain amount of time, if those are still valid? So would you have to go through this exercise again next year? Sure. Let me ask Jim to actually address that question. He's in the room with me. Thanks, Maria. Hi, Mara. With respect to DRG, if it's approved, it will be approved upon product approval. I think your real question is around MTEM. So for products or technologies that are approved by 1 July, they would be implemented in the next fiscal year, beginning 1 October, so in this case, 2022. For products that don't meet that 1 July approval date, would have to resubmit with the NTAP. There are 2 separate processes, right? So one is the DRG, the other one is Okay. I appreciate the clarification on that. Thank you. Thank you. And the next question in the queue comes from Asthika Goonewarden. Your line is open. Please proceed. Hi, this is Avi on for Asthika. Can you hear me? Yes, we can. Hi, good afternoon. So one quick question about this license agreement with the NIH. Can you just give a little color on so these are exclusive agreements and every time there's a BLA approval, you're subject to paying out a low single digit $1,000,000 payment, right? That's correct. Okay. Got it. And one last thing, just circling back with the FDA, a lot of clarity today. Thank you. But one so you mentioned that it was a 1 to 2 month general guidelines, but it's not required by the typical PDUFA date. So your last can you give a little more clarity on like the day or the week you guys submitted the most recent data back to them? Thank you, Avi, for the question. So we didn't disclose the exact date, but we did say that we have submitted the validation package to the agency in Q1. We had committed to investigate that and that was completed on time. All right. Thanks. Thanks for our questions. Sure. Thank you so much. The next question in the queue comes from Madhu Kumar. Your line is open. Please proceed. Hey, everyone. Can you guys hear me okay? Hi, Madhu. Yes, we can. Okay, great. So, kind of thinking about the frontline melanoma trial a little bit, I guess kind of a very simple question. Where do you think are the gaps in frontline melanoma on PD-one blockade where TILs can provide specific benefit like duration of response, complete response? Where do you think there's a kind of window for TILs plus PD-one to give edge? That's a great question, Madhu. So, melanoma is a disease that is fairly well addressed with checkpoint inhibitors. However, I think that it really depends on the data itself. And I think we can comment a little bit more once the data for Till plus pembro shows up at ASCO. There's always room for improvement if the patients are not reaching a complete response or that their duration of response could be improved. So from my perspective, a patient that experiences a deep durable response in frontline really offers a lot of benefit to the patients. The clear second unmet need is exactly what we have been doing, which is a post PD-one patient population. I'm going to ask Frederic to comment if he has anything to add. Did you want to add to this? I agree, Maria. What we shouldn't forget, although a lot of progress has been made with the checkpoint inhibitors in various indications, the majority of patients still will progress either primarily or secondarily because of resistance mechanisms. You will make that less likely and you will increase benefit by pushing down the responses even deeper and complete responses are a real good goal here. So I think I totally agree with Maria that that is really where there's room for improvement. Okay, great. And kind of to follow-up on some of the questions around the cell potency assay issues. I mean, I guess kind of ultimately to what extent is this whole situation about kind of educating the FDA about the differences between TILs and kind of earlier generation cancer cell technologies like CAR T? And to what extent is this about kind of you mentioned having a panel of cytokines type factors that demonstrate kind of T cell potency beyond just a single type of factor assay to demonstrate T cell potency? It's a great question, Madhu. I don't know if I can comment on educating the agency. I mean, the agency, certainly on our review team, there are members who have been at NCI before. Now how much internal communication there is, it's a little hard for me to sort of comment on that. I can tell you that the requests that they have made so far have been reasonable in the sense that they're not asking, for example, for go find yourself an antigen specific assay. That would have told me that well, for Till, it's going to be very difficult to do. But that type of a request hasn't come through, so which tells me that they do understand the power of Till, the fact that it ultimately addresses multiple neoantigens and it is highly, highly polyclonal. So I think that maybe education is not the right word. Maybe the way is to better define a 1st in class product with this sponsor. There definitely is some time that needs to be spent between both the agency and the sponsor in trying to define how do we define such a complex product. I think that's probably the true statement. Okay, great. Thanks guys. Thank you. Thank you. And the next question in the queue comes from Nick Abbott. Your Abbott. Maria in co, so in the current JCO, Jason Luke and colleagues report encouraging data for a combination of PD-one and CTLA in patients who really considered primary PD-one failures and acknowledging these are largely second line CTLA-four naive patients and so clearly not apples to apples with the colucels, so the patient cohort. Do you think these data changed the use of that doublet in the sort of second line setting? And does it create a barrier for nifolucine use? Thanks. Hi, Nick. Thank you for the question. I'll do my best to give you preliminary answers. I'm going to invite Frederic to also comment. I do we have seen the manuscript. I'm glad you're it's getting noticed. I highlight a few differences between the manuscript in terms of the patient population, the endpoints with what Iovance is doing. The endpoint that is reported at the manuscript is IR resist, not resist 1.1. Resist 1.1 is a regulatory endpoint that has been very well understood and requested by FDA. IR resist is an immune mediated type of endpoint and has not been really accepted by the agency as an appropriate endpoint. Terms of the patient population, this is strictly speaking second line and in some cases front line metastatic patients because they could have had adjuvant therapy and subsequent to that they would have entered the study. I highlight a couple of other points. The amount of time on prior anti PD-one as a median was reported at 4.8 months. That's a pretty short duration of time. It probably looks like a primary refractory patient population. What was also remarkable from my perspective was the time from prior ANG PD-one, which was quite short. And that may yield to the previous products still being on board given the long half life of prior ANGPD-one. The median duration of response had been reduced and was reported. And some of the patients, as I noted, were coming from an adjuvant setting. So I think that there's meaningful differences both between the endpoints as well as the patient population making it very difficult to compare. Frederic, did you want to add any comments to this? I think maybe a couple of comments comparing from Chastor. So this is an academic paper. This was generated in 7 U. S. Sites. The data that we are presenting for our program is a global multicenter study. I think that is relevant in this context as well. And maybe one just one quick comment on the nature of the therapy. The treatment that was explored in this manuscript still requires continuation of pembrolizumab for up to 2 years, which is a big contrast to a onetime treatment with the lifeluto regimen. And that is meaningful as well. And other than that, I think Maria summarized the differences very well. Yes. Just maybe one more point, Nick, that I was reminded. Again, strictly speaking, there's 2nd line at the latest. Many of the patients, the percent of the patients were first line, sort of systemic therapy and then the some of them were second line. The patients had not received prior anti CTLA-four or other therapeutics, which is pretty much a reality of life for these patients nowadays and outpatients never see them. Okay. Thank you. Thank you. And we have one more question in the queue, and that question comes from Ben Burnett. Your line is open, Mr. Burnett. Hi, good afternoon. This is Carolina Ivanoventos on for Ben Burnett. My call dropped earlier, so my apologies if you already touched on this. We were wondering if you could talk a bit more on the Cohort 3 arm of the cervical cancer study and if you expect this would be needed for approval. Carolina, if I understand let me make sure I understand the question. Were you asking about Cohort 3 of cervical? Yes, correct. So Cohort 3 is patients that are PD-one naive and they get 2 placenta in PD-one. Is that the cohort you're asking? Or are you asking about cohort 2? No, I'm asking about cohort 3 and if you find that this will be needed for approval. Great questions. I don't believe so. That was really an exploratory cohort that we started trying to understand what a combination of Till plus pembro in PD-one naive patients would yield. So this has not been subject to any regulatory discussion. The patient population is an earlier line patient compared to cohorts 12. Cohort 1 was discussed with FDA. Cohort 2 is a patient population, which is post PD-one as well as post chemotherapy. And we think this is the landscape of patients that is coming. So we have added that support into the program and we think it might be also important in submission of the BLA. Okay, perfect. Thank you. Thank you. We have no further questions at this time.