Study Update

Jun 29, 2021

Thank you for standing by, and welcome to the Iovance Biotherapeutics Update Call. At this time, all participants are in a listen only mode. After the speaker presentation, there will be a question and answer session. Please be advised that today's conference may be recorded. I would now like to hand the conference over to your host, Sara Pellegrino. Please go ahead. Thank you. Good afternoon, and thank you for joining our conference call to discuss the initial clinical data for our Till cell therapy, LN-one hundred and forty five, in metastatic non small cell lung cancer, or NSCLC. For today's agenda, our Interim President and CEO, Fred Vogt, will do a brief introduction Doctor. Frederic Fickenstein, our Chief Medical Officer and Doctor. Mohdan Jogaizia, our Senior Vice President, Medical Affairs, will then highlight the clinical data, and we will hold the question and answer session. Before we start, I would like to remind everyone that statements made during this conference call will include forward looking statements regarding Iovance's clinical results, goals, business focus, business plans, clinical trials, cash position and expense guidance and future updates. Forward looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected during today's call, and we undertake no obligation to publicly update any forward looking statements. With that, I will turn the call over to Fred. Thank you, Sarah, and good afternoon, everyone. I'm pleased to host today's call to review what we believe are very exciting initial clinical data for Till's therapy in non small cell lung cancer, which is the first clinical data for Iovance in this indication and represent the 4th solid tumor indication where our Till platform has demonstrated significant potential to address unmet medical need for cancer patients. We are releasing this data right now because we are excited about the potential for Till in lung cancer and we recently did a data cut gives us confidence in our development strategy for LM-one hundred and forty five in multiple cohorts in the basket study, IOV COM-two zero two as well as in our registration supportive study, IOV LUN-two zero two. With $610,000,000 in cash on the balance sheet as of March 31, this data release is not related to any imminent financing plans and we are well capitalized to develop our pipeline and prepare for commercialization. With that, turning back to the data, I'm pleased to introduce Frederick and Madan. Thank you, Fred. Today, I will review clinical data for our tool therapy, LLM145, in patients with metastatic non small cell lung cancer or MSCLC, who enrolled in Cohort 3b of the ongoing basket study, IOV COM202. Cohort 3b enrolled patients that have progressed on prior immune checkpoint inhibitor or ICI therapy, including patients with oncogene driven tumors who received prior tyrosine kinase inhibitor therapy. While we are saving more detailed baseline for our future medical meeting, it is worth noting that 24 of the 28 patients or 85.7%, including all the responders had received 2 or more prior lines of systemic therapies. If they had an oncogene driver mutation, they had also received at least one targeted therapy. There is a significant unmet need to increase overall response rate or ORR and prolonged survival in this difficult to treat non small cell lung cancer population. So we were very pleased to see an ORR of 21.4%, including 1 confirmed complete response and 5 confirmed partial responses and 64.3% disease control rate. Historically, ORRs of approximately 20% were reported with ICI as second line therapy and ICI naive patients who progressed on frontline chemotherapy. So we are pleased to see a comparable ORR in sicker patients in Cohort 3b who have all received prior anti PD-one therapy. In addition, median duration of response had not been reached at 8.2 months of 1,000,000 study follow-up. In terms of safety, the safety profile was consistent with treatment emergent adverse events that were consistent with underlying disease and non adverse event profiles for non myeloid ablative lymphodepletion chemotherapy and interleukin-two. Turning to the next slide, we show the waterfall plot for all 24 evaluable patients as of a very recent data cut on June 24. Patient 2 had a complete response or CR based on a negative FDG PET scan by investigator. This patient had 2 target lesions going into treatment. One target lesion had 100 percent resolution. Another target lesion was small and remained identifiable on post treatment CT scans, Following multiple negative test scans several months apart with prolonged follow-up and lack of subsequent therapy, this patient has met criteria for a confirmed complete metabolic response and thus also CR in accordance with RECIST-1.1 criteria. The 5 patients in blue showing partial responses had at least a 30% reduction in target tumor burden and at least 2 assessments and thus are confirmed partial responders per RECIST 1.1. Then we have 12 patients with stable disease and 6 with progressive disease as best overall response. Today, we are focused on characterizing the responders as shown on the next slide. The swim lane plot shows time to response for our 6 confirmed responders. As shown on the left, we had 2 responders with PD L1 negative status and 4 responders with PD L1 positive status. This distribution of PD L1 status is reflective of the non small cell lung cancer population in which about a third of patients are PD L1 negative and challenging to address with current standard of care immunotherapy. So we are happy to see responses with Till regardless of PD L1 status, which is consistent with what we have seen in other solid tumor indications as well. Overall, we are very pleased to see that these data confirm what we saw as promising results from the H. Lee Moffett Center at AACR last year and gives us further confidence in advancing Iovance Till in non small cell lung cancer. A lot of people are asking for the context of our results in the basket study to the MOSFET data. So we'll ask Madan to present a brief summary of the MOSFET study. Madan? Thank you, Friedrich. I would like to highlight the proof of concept for Till therapy in non small cell lung cancer patients were naive to anti PD-one and which gave us confidence in moving ahead with our own Iovance Till Lung Cancer Program. This study was a single center academic study with a very different patient population and study design. So it's not a real comparison, but a proof of concept. Moffitt enrolled patients much earlier in the disease course as compared to Cohort 3B as they had received only 0 to 1 prior systemic therapy and all patients were naive to anti PD-one or anti PD L1 therapy. The tumor samples were resected and harvested using a tumor banking model, which has many disadvantages, including lack of commercial viability and the Till repertoire in the tumor microenvironment at harvest may differ from the Till repertoire in the patient at the time of progression. All patients began with nivolumab treatment and patients who subsequently progressed on nivolumab received a combination regimen of Till followed by IL-two and then subsequent continuous treatment with single agent nivolumab. Among the 12 evaluable patients, the ORR was 25%, including 2 complete responses and one partial response for RECIST-1.1. Again, this is a good proof of concept study in the anti PD-one naive patient with a combination regimen and we are exploring combination regimens in our Basket study in 2 additional cohorts. Cohort 3A is investigating Till in combination with Sembrolizumab. In addition, our Cohort 3C, which we recently opened at the beginning of 2021, is evaluating TIL plus ipinivo. The next slide, our registration supporting study, IOV LUN-two zero two, which shows the first patient recently, we are investigating LN-one hundred and forty five in recurrent or metastatic non small cell lung cancer patients without driver mutation who previously received a single line of approved systemic therapy with a checkpoint inhibitor and chemotherapy. Within this patient population with significant unmet need, we will look at 4 different cohorts. Cohort 1 will include patients whose tumors at baseline at the time of diagnosis did not express PD L1 with a TPS score of less than 1%. Cohort 2 will have tumors that express PD L1 with a TPS score greater than 1%. Cohort 3 patients also will have TPS scores less than 1%, in which we will grow Till from core biopsies to infuse back to the patient. And finally, Cohort 4 will offer retreatment for patients who progress in cohorts 1 to 3. The cohorts in LUN-two zero two study are distinct from the 2 cohorts in our ongoing IOV COM202 basket study in patient populations that they enroll. The primary efficacy endpoints will be objective response rate or ORR assessed by independent review committee or IRC. With that, I will hand it over to Fred to discuss the milestones. Thank you, Mittal, and thank you, Frederick, for your updates. I'll just briefly touch on some of our milestones in non small cell lung quickly and then we'll move to questions. 2 milestones that we've achieved recently, obviously cohort 3b, which we reported on today, is a big milestone for us and we fully enrolled that cohort. We've also just announced today that the first patient has been dosed in the registration supporting study, IOV LUN202. Two upcoming milestones of importance in NSCLC for us are additional Cohort 3b data at a medical meeting, hopefully in the second half of this year and activation of additional sites and enrollment in IV LUN202 as well as the other cohorts that we've got open. As you heard, we have 7 total cohorts open of lung studies counting the retreatment cohort. Now you went to it too. I'd now like to hand it over to the operator to begin the Q and A session. Thank you. Our first question comes from the line of Michael Yee of Jefferies. Your line is open. Hey, guys. Congrats on this data and thanks for hosting the call. Two questions. One was your thoughts about the LUN-two zero two study in the context of comments around the potential pivotal nature of that or registrational nature. Can you just comment on how you think about what the bar is or why you think that could be pivotal as other companies I think generally are trying to run randomized studies? So maybe just comment on the context of LUN-two zero two in the context of this data presented today. And then one detailed comment about that. Thank you. Michael, thanks. I want to Frederic, would you be able to take those questions? Sure. Happy to. Thank you for the question. So as Madan described, the LUN-two 2 study is a study that will generate response rate data that our IRC reviewed in 2 cohorts separated by PD-one status, PD L1 negative or PD L1 positive, which gives us some flexibility in exploring and determining the activity and the benefit risk separately, but also these are similar to pool the data and look at this together in the larger sample set. The bar that we are looking at really is the currently available therapy for these patients, which is as it was in the initial approvals of checkpoint inhibitors in second line monotherapy, chemotherapy. So docetaxel is probably the best bar here with response rate below 10% short durability of responses. We believe that single arm data may be a potential route for a registration strategy, given the fact that this is a novel therapy. The Till regimen is a one time therapy. So we are, as you all know, administering this only one time with no maintenance therapy. And obviously, depending on the degree of benefit and difference in response rates over docetaxel. The question about the prognostic factors, really what we are planning on doing and since this involves kind of a summary of the larger context here is this data and detail that we would be presenting at a future upcoming medical conference. Got it. Thank you, guys and congrats on the data. Thank you. Thank you. Our next question comes from Mark Breidenbach of Oppenheimer. Your line is open. This is Matt on for Mark. Just wanted to touch on the topic of biopsy banking. I think as you mentioned, the Moffett trial was banking the biopsies before PD-one exposure, whereas you're biopsying right before killinfusion, so post PD-one. Do you think we have enough data now to really determine that banking biopsies is not the optimal way to go? Why don't I I can answer that initially, Mark, but then I'll ask Madan and Frederic to chime in if they have any additional thoughts on this. Right now, there's preclinical information preclinical data out there that suggests that we are the tumor microenvironment and the total repertoire changes when you administer checkpoints, right? So that's the key aspect of that. The banking model is also, you have to remember is not really commercially viable from our perspective, at least today, because of the fact that you have to find a way to somehow reimburse and pay for banking treatment ahead of some other line of therapy long before you ever had Till therapy. So again, I'd like to just reemphasize those two points as being pretty critical. While it's great in an IST type setting and investigator sponsored trial setting or in academia, MD Anderson does this as well. It's difficult to see that in a commercial landscape. Don and Frederic, do you want to add anything to add from the scientific side? Yes. This is Madan. Yes, I echo Fred's comments over there. I think this is not feasible in the commercial setting. And also if you look at the other tumor types where Iovance has experienced, we have successfully harvested a tumor specimen grown till after prior PD-one exposure. And also biologically, it is possible that the Till repertoire that the patient has at initial therapy and at subsequent progression is significantly different. So, we feel that harvesting the Till at the time most proximal to the administration till biologically makes more sense. That makes sense. Thanks. And I had a follow-up on LUN-two zero two, if you don't mind. Can you just jog our memory if you're going to be excluding patients with oncogenic drivers, so mutations like EGFR, RET, MET? And maybe given the strong data that we've seen today, maybe just explain what would be the rationale behind excluding those patients? Thanks. From I assume you mean from IOV LUN202, right? Correct. Yes. Frederic, do you want to explain the enrollment criteria? Yes, absolutely. So what we're going for here really is patients who have received a single line of biosystemic therapy for non small cell lung cancer with chemo and ICI combination. That is usually standard of care that is not used in patients with TAVAL mutations because there's an understanding that the addition of checkpoint inhibitor in that population does not necessarily generate benefit in these patients. So in order to number 1, keep the cohort homogeneous, which is important if you're making a statement around or if you're trying to generate the data that's supporting potential registrational efforts, but also in order to reflect standard of care, we are excluding these in alignment with label for the use of checkpoint inhibitors in first line non small cell lung cancer. Got it. Thanks for the update guys. Congrats. Sure. Thanks. Thank you. Our next question comes from Mara Goldstein, Mizuho. Your line is open. Great. Thanks so much for taking the question. Just a clarification on the data set and then a question on the overall study. The patients in the data that you released had at least two lines of therapy. How many had more than two lines of therapy, if you don't mind me asking, if you know the answer to that? And then the second question I just had is that the, 1202 study, right, will include individuals who've had disease progression on prior checkpoint plus chemo. Is that described as checkpoint plus chemo or checkpoint follow like a sequential treatment as opposed to combination? And do you think that will matter? Yes. Why don't I take the first one and Frederic, you can take the second one. So on the first one, Meyer, we're trying to save some of this stuff for a scientific conference later and that's our intention is to present more detail on the prior lines of therapy at that conference. We've disclosed what we have and what you've seen already today is that 2428 including all the responders that have received at least 2, if not more prior lines of therapy, all the dates that are prior to PD-one, PD L1 and all responders prior to chemo. Other than that, we still analyze and we still have to look at that for future medical conference. Frederick, do you want to talk a little bit more about sequential versus the same time for CPI plus chemo? Is that how you went to it too? Sure. Absolutely. Everybody go on for me please, Pierre. Thanks, Rod. So we are requiring the tick fun of the chemotherapy to have been given as a combination therapy as part of a single line of biotherapy. The rationale for doing that is number 1, that's really how the majority of patients is receiving this therapy. Now. And second, what we are trying to accomplish is to keep the number of prior therapies at the time on systemic therapies for metastatic disease somewhat shorter because we believe that patients in earlier settings with less pretreatment, less time on pretreatment may fare better on 12 therapies. Okay, thanks. Sure. Thank you. Our next question comes from Peter Lawson of Barclays. Your question please. Hi, thanks for taking the questions. Thanks for the update today. Just as we think about the next update, kind of will we get further data, more data, or just more detail around the existing patients that we've seen? Hi, Peter. You mean the medical conference where we would potentially present the additional data on GOAT 3B or more generally? On the 3b. Yes. We don't know for sure, but if that conference, the timing permits, it's possible we could put more data in there. It depends on when we cut the data and timing for the conference and everything else. So that one all I can say there is stay tuned and we'll see what happens. So that's where we get lines of therapy and spider plots, etcetera? Yes. Well, our intention is to submit additional to have a full package for a medical conference later this year. And typically, we'd have that kind of thing in that sort of presentation. Okay. Thank you. And then you had for the patient that was a CR, would that have been a CR under resist? And I guess why wasn't that 100% reduction when you look at the waterfall chart? Frederic, do you want to take on the pet question there? Yes, Yes, happy to. So why you're not seeing a reduction to 100% on the waterfall is because there was a remaining mass on the CT scan. So that stayed remaining for a while, which triggered the PI to look at whether that mask actually representing tumor or potentially scar or fibrous tissue, which is sometimes what you see with immunotherapy. The way you do that is to do an FGP PET scan. So you're looking at whether that is actually high metabolic activity, but high glucose uptake that would indicate presence of tumor cells in this. This particular mask did not enrich, did not uptake labeled glucose indicating that that it's likely not tumor. And in a situation like that, RESIST-1.1 criteria, that data and that information to support a CR assessment as part of that, because really it's an assessment as non tumor. But you still have something you still measure something on the CT scan and that's what you're seeing on the waterfall plot. Got you. Thank you. And then I guess on the other side of things, you had a couple of patients with pretty PRs. What kind of kept them away from being called CRs? Yes. So for what you're seeing on the labels on the waterfall chart are really confirmed response assessments. So all the PRs and all the CRs that you're seeing now are confirmed assessments, which requires confirmation in at least 2 subsequent assessments for CT scans or FTTP PET scans in the case of the CR patients. These are patients where an initial response was not confirmed by subsequent CT scans. So you're seeing the best single time points and then the color code giving information on the BOL assessment, which requires confirmation. Got you. And were these on like PET scans showing activity, so there was residual tumor there? In a situation like that, there's really no good clinical reason to do a PET scan. The PET scan is really something that is done by a PI in the right clinical context, which oftentimes is when you have a tumor that over a number of assessments doesn't change in size. Great. Thank you so much. Thanks for the detail. Sure, sure. Thank you. Our next question comes from Asthika Goonewardene of Chorus Securities. Your question please. Hi guys. Thanks for taking my questions. Maybe one to Frederic. I'm going to ask you a baseline question, but I'll ask it qualitatively, so hopefully you can give us some indication, Frederic. Did you have any patients with primary progressive disease or best response of progressive disease to prior PD-one? And if so, did any of them have a PR? And I have a follow-up. Thanks, Asthika. This is a good example for the type of data that we want to that we really want to show as part of the description of the entire population as part of a future medical conference. Okay. And then maybe, Frederic, could you tell us anything about the patient that had the initial response and then progressed? Was that maybe a new lesion or was that the actual target lesion grow? So I believe this was a new reason. Got it. Excellent. Thanks guys for taking my questions. Sure. Thank you. Our next question comes from Boris Peaker of Cowen. Please go ahead. Boris, your line is open. Please make sure your line is mute. Yes, we'll go to the next question that comes from Madhu Kumar of Goldman Sachs. Your line is open. Hey, guys. This is Rob on for Madhu. I was just going to ask a question. Do you envision using LN-one hundred and forty five as a monotherapy immediately after PD-one or PD-one plus platinum chemo regimens or after these regimens plus taxane chemo? No, we're focused right now on monotherapies and that's what we're looking at in the ILUM-two study, for example, cohorts 1, 2 and 3. And that's what we're talking about today with respect to cohort 3 days. Not in combination with that, responses among the remaining 28 patients? The data set here is fully resist. So it's everything's confirmed. I think that's the correct response. Yes. We don't we're only reporting confirmed PRs, so. Okay. Thanks. And then one last one. Do you think between the Moffett EGFR responder plus your data, you could support the use of LN-one hundred and forty five monotherapy in the post TKI setting in RTK mutant, in small cell lung cancer? Certainly, it's promising. It's an example of the power Till therapy. I think it needs to be further explored. It's something that we're certainly very interested in. You can see the focus value on 2,002 right now is on patients without actual driver mutations. Richard or Madan, do you want to add anything to that? No, I would agree with that, Greg. Go ahead, Cedric. Yes. And I think I can share that we have studies that are enrolling patients who have failed TKI therapy and then go into Till containing regimens as part of our ongoing of small cell lung cancer studies. So we are interested in exploring and generating data in that setting. Right, in COMTOS still? That's correct. It's ARM 3A. Okay. Thanks for taking my questions. Thank you. Our next question comes from Ben Burnett of Stifel. Please go ahead. Hi, thank you very much. I just wanted to ask a clarifying question about, I think this is something that's come up, but on the waterfall plot, 2 patients, looks like they had a reduction in tumor size beyond that 30% threshold needed to codify a PR. Is the reason they're not codified as a PR and codified as stable disease because they were unconfirmed and they only have one scan? Roger, do you want to take that one? Yes, that's correct. It's the RECIST is reporting patients with an initial response at a single assessment that is not confirmed in follow-up assessments as stable disease. And what they're using at the convention where you're following. Okay. So the subsequent follow-up scan showed not a response and that's why they're deemed stable disease, not because there just hasn't yet been a follow-up scan? That's correct. Yes. Got it. Okay. And then I just want to ask the other question is, so how did the number of IL-two doses used here compare Why don't you take it, but just bear in mind that some of this might be on our future medical announcements presentation? Exactly. That's what has been my answer. But if you want to ask the paradigm that helped you at all versus IL-two 600000 IU, same approach. Okay. And then maybe just the last question. Are you still enrolling patients in this cohort? In 3B? And 3B. Yes, one of the I mentioned on one of the milestones, 3B is fully enrolled. Got it. Okay. All right. Thank you very much. Thank you. Our next question comes from Reni Benjamin of JMP Securities. Your question please. Hey, good afternoon guys. Congrats on the data and thanks for taking the questions. As I think about PR to CR conversions or even SD to PR conversions from prior studies like melanoma and cervical, is there any reason a non small cell lung cancer indication might not behave in a similar way? Or should we be anticipating or thinking about the potential for other conversions to take place, given the follow-up? Frederic or Madan, maybe it's worth just reviewing some of the other the experience we've had in other therapy, other indications and then try to provide some color on that. Sure. I think the question is about previous data that we reported where you saw conversions from stable disease to PR or from initial PR to then a later CR. I think you see examples for that happening in this study as well. So on Slide 5, which is the same main plot, patient 17 developed a PR at an assessment about 5 to 6 months in. That patient would have been stable disease at the assessments prior to that. So there you have an example for stable disease to PR conversion and then patient 2 had an initial PR and then converted to a CR. So I think you see some more things happening here, obviously. More follow-up will give us a better idea of what's happening in the patients that are currently ongoing with the PR. Got it. And then from the safety profile, I know that it's supposed to be similar to other studies, but the background here is different, right, different chemo regimens and the like. Is there anything different at all from the safety perspective that's worth noting? Or did it pretty much all the typical grade 1, 2, 3s that we've seen before occur here as well? Well, let me preface it by saying, obviously, this is a lot of this will be in the future medical conference presentation. So just bear that in mind. But, Frederic, please feel free to comment. Yes. I mean, at a high level, again, keep in mind, the Till regimen consists of the non myelopatibil depleting chemotherapy, the Till administration and the post Till Interleukin 2, how we are usually looking at the safety profile and what we would be presenting similar to how we presented this in the previous presentations is look at the common treatment emergent adverse events and then cuts into the more common group. So I think that's the type of data that we would be presenting. And that is the basis for what we've said in other settings as well. And this one is really the consistency of those adverse events with either the chemotherapy or IL-two therapy. Got it. And just one, I guess, two real quick ones for me. Fred, can you remind us, I think you mentioned this in the prepared remarks, but what triggered the reporting of the data now versus, let's say, closer to an abstract being accepted at a medical conference? And then also the reporting of the cadence of data, you said an update for IIIB, right? This is fully enrolled. What's happening with IIIA? Sure. So remember, we are going to our intention is to present us at a medical conference. What we try to do here in the spirit of communicating with the investment community is get data out when we could. We've been on a lot of the calls we've held recently and hosted. We've heard the feedback and we want to make sure we're getting data out as soon as we possibly can. So what we did here was recognizing the fact that it's a long time until some of the major medical conferences, we tried to get some data out as quick as we could and we wanted to be meaningful data. So we tried to provide some extra data here, which is hopefully useful to everyone. That doesn't stop us from having meetings, having presentations at meetings and we intend to do that. With respect to 3a, 3a is one of the cohorts that's active in COM202 obviously and we've been we mentioned it several times today, I can't commit any dates on that except to say that stay tuned on that and we will try to get data out as soon as we can just like we did with 3P. Great. Thank you, guys. Thank you. Our next question comes from Nick Abbott of Wells Fargo. Please go ahead. Good afternoon. Thanks for taking my questions. So other than the 6 patients in the swimmers plot, are there any other patients still being followed on the protocol? And if so, how many? And why were 4 patients efficacy ineligible? And I have a follow-up. Thanks. Frederic, why don't you answer those, please? Sure. So on the patients in follow-up, again, that's a question related to the entire larger population. So we'll give updates and summarize that at the upcoming medical conference. Typical reasons for patients being non evaluable is if they are not on study long enough in order to make the first tumor assessment. Okay. And then I guess, if I think back to the head and neck data, there was a 38% response rate, but duration was considered suboptimal. So why do you consider these data in lung encouraging given such a limited follow-up? And what additional response duration should we expect at the time of data presentation? Thank you. Frederic, are you able to answer that one? Yes. So I think really, what interests me in this data set and why we think it's worth showing and why we also think there's value in sharing this with the scientific community as additional driver for enrollment in our programs is the response rate. Seeing a response rate above 20% in this population, which is similar to what we've seen with the first checkpoint inhibitor studies post platinum doublet chemotherapy when pembro and nivo were approved in second or second, third line setting. That's encouraging, particularly since these patients are more heavily pretreated than those patients because they have also seen prior checkpoint inhibitors. So I think just the response rate is worth updating the community on. Obviously, following the durability of these responses will be important, but the response rate itself merits attention and sharing. Great. Thank you. Thank you. Our next question comes from Joe Catanzaro of Piper Sandler. Please go ahead. Hi, this is Sam on for Joe. Could you talk to us about, what's the intent to treat number of patients and the data cut for this analysis? Redroof, could you take that one, please? So the data cut for this let's start with that one for this presentation is very recent. That's 24th June, just last week. We are considering sharing information around the entire population as part of our upcoming presentation. But just this context, I think we've shared in the past that the success rate across indications in our entire portfolio being above 90% in regards to manufacturing. Okay, great. And then could you also just talk to us one more about the decision to close enrollment? Just, Perjic, do you want to handle that? I mean, it wasn't it was reached a predefined size, but, Craig, go ahead, please comment on that if you want. Yes. No, I think exactly it. You predefined, you've predefined, you accept some over enrollment, obviously, in these types of signal generating studies like this one, you have some flexibility there. And you get it to a point of where something is decision enabling and gets you the confidence that you need to then build on that. In this case, for non small cell lung cancer, we've described the LUNG-two zero two study that really is the study that is the next step. Building on the data from this study as well as on the data from our collaborators at the Moffitt, which Megan described. So really, we have taken it to the next step in now bringing this therapy to a more homogeneously and better defined population with less prior therapy and better comparability with benchmarks. Great. Thank you. Sure. Thank you. At this time, I'd like to turn the call back over to Fred Voitfa for any closing remarks. Thank you, operator. With that, we'll close today's call. I'd just like to thank all the teams at Iovance, all the patients and their families, everybody who participate in the study, all the investigators for their help with Cohort 3b. Thank all of you for your attention. Have a nice afternoon. And this concludes today's conference call. Thank you for participating. You may now disconnect.