Iovance Biotherapeutics, Inc. (IOVA) Earnings Call Transcript & Summary

Thank you for standing by, and welcome to the Iovance Biotherapeutics Update Call. [Operator Instructions] As a reminder, today's call is being recorded. I would now like to turn the conference to your host for today, Ms. Sara Pellegrino. Ma'am, you may begin.

Thank you, operator. Good evening, and thank you for joining us to discuss the positive clinical data for lifileucel to support our upcoming planned BLA submission in metastatic melanoma. During today's call, Dr. Fred Vogt, our Interim President and Chief Executive Officer, will provide a brief introduction; and Dr. Friedrich Finckenstein, our Chief Medical Officer, will further highlight the results from the C-144-01 melanoma study. Following these updates, we will hold a Q&A session. Additional Iovance team members taking part in the Q&A include Jean-Marc Bellemin, our Chief Financial Officer; Dr. Igor Bilinsky, our Chief Operating Officer; Dr. Madan Jagasia, SVP of Medical Affairs; Dr. Raj Puri, our Executive Vice President, Regulatory Strategy and Translational Medicine; and Mr. Jim Ziegler, SVP Commercial, are currently in transit and available for a post-call follow-up. Earlier this afternoon, we issued a press release that can be found on our website at iovance.com, which includes clinical data for lifileucel in melanoma. As a reminder, statements made during this conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans, clinical trials and regulatory plans and results, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance and future updates. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward-looking statements. With that, I will turn the call over to Fred.

Thank you, Sara, and good evening, everyone. I'm excited to share the positive clinical data from the registrational Cohort 4 in our advanced melanoma trial. This trial is also known as the C-144-01 clinical trial. These data represent a major milestone for Iovance, our patients and physicians who participated in the C-144-01 study. It also provides a new sense of hope for thousands of patients and families in the melanoma community who are in urgent need of additional therapeutic options after they progress on anti-PD-1 therapy. In the C-144-01 trial, the primary end point supporting our BLA submission is objective response rate, or ORR, assessed by Independent Review Committee, or IRC, using the response evaluation criteria for solid tumors or RECIST 1.1. Cohort 4 included 87 patients who were all heavily pretreated and had previously progressed after anti-PD-1 therapy. All patients were treated with a single administration of lifileucel. In Cohort 4, we observed an impressive ORR of 29%. Among a total of 25 responders, there were 3 complete responders and 22 partial responders. We believe that the Cohort 4 data may support approval, and we are rapidly moving towards our planned BLA submission. As we previously noted, we received regulatory feedback noting that Cohort 2 may be supportive of registration, and we believe that the Cohort 4 data supported by Cohort 2 data may be the basis for approval. As Friedrich will highlight in a minute, these Cohort 4 data are further supported by the pooled analysis of 153 total patients across Cohorts 2 and 4. With the updated data from the C-144-01 trial, we are confident that we are on track with our prime BLA submission in August. We are also on schedule with our manufacturing and commercial readiness activities to support the launch of lifileucel. We look forward to providing further updates on our progress at Iovance throughout this year. Right now, I will hand the call to Friedrich to highlight some additional data from today's press release.

Thank you, Fred. I am also excited about the clinical results from registrational Cohort 4 and the potential of lifileucel as a new treatment option for patients who progress on anti-PD-1 therapy. To add to Fred's comments on the primary analysis of ORR, the median duration of response, or DOR, was a secondary end point for the trial. In Cohort 4, the median DOR was 10.4 months with a median study follow-up of 23.5 months, further supporting the durability of lifileucel as a onetime treatment for melanoma patients after anti-PD-1 therapy. As a reminder, there are no approved therapies for patients who progress after anti-PD-1 therapy available care for patients with metastatic melanoma in the setting with chemotherapy which has been reported of a 4% to 10% response rate with a short median duration of response. I would also like to describe the data update for Cohort 2 as well as the pooled analysis and patient demographics for Cohort 2 and 4. As many of you know, Cohort 2 is our earlier cohort in the C-144-01 trial that enrolled a similar patient population as Cohort 4. We have presented long-term Cohort 2 data at several important medical meetings over the past 6 years. Most of the Cohort 2 presentations included assessment by investigator. Today's updated data included IRC assessment of Cohort 2 to align with the registrational Cohort 4 data. The IRC assessment of 66 patients in Cohort 2 demonstrated an ORR of 35%. Among the 23 responders, there were 5 complete responders and 18 partial responders. The median DOR in Cohort 2 was not reached at a median study follow-up of 36.6 months. Looking across the full data set for 153 patients within Cohorts 2 and 4, the pooled cohort showed an ORR of 31% as assessed by IRC, and median DOR was not reached at a median study follow-up of 27.6 months. We expect to include the Cohort 2 data as well as the pooled Cohort 2 and 4 data into our BLA submission to support the data from Cohort 4. The safety profile was similar between Cohort 2 and 4 and consistent with the underlying disease and known safety profiles of non-myeloablative lymphodepletion and interleukin-2. As part of our analysis of this important data set, we compared Cohorts 2 and 4 across demographics, disease characteristics and prior therapy to understand any possible differences and similarities. The relevant finding was that patients in Cohort 4 had higher baseline disease burden in comparison to patients in Cohort 2. This finding was supported by a higher proportion of Cohort 4 patients with elevated baseline lactate dehydrogenase or LDH levels, which is a well-known negative prognostic factor in melanoma. Patients in Cohort 4 also had a greater number of IRC-identified tumor lesions than baseline. We also found that in Cohort 2, patients had approximately half the cumulative duration of anti-PD-1 therapy before lifileucel therapy compared to Cohort 4 patients. As we previously reported at ASCO 2021, our analysis of Cohort 2 showed that a reduced duration of prior anti-PD-1 therapy was shown to be associated with an increase of DOR to lifileucel. For anyone who would like to delve into greater detail, this afternoon's press release provides additional information on confidence intervals and other parameters for your reference. We also plan to present detailed clinical data from Cohorts 2 and 4 at an upcoming medical meeting in the second half of this year. I am happy to address your questions during the question-and-answer session that is expected to begin now. Operator?

[Operator Instructions] Our first question comes from Michael Yee of Jefferies.

Maybe a 2-part question. One is maybe talking to the duration of response and obviously a difference from the Cohort 2 data and maybe talk to the clinical meaningfulness of that from both a regulatory standpoint and a clinical standpoint. Maybe you could talk and address that. And I think a related question is the idea that there's a financing overhang, and so maybe you could at least talk to them, how to think about the balance sheet and your financing plans.

Sure. Why don't I take the regulatory part? Friedrich, you could jump on the clinical, and then I could handle the financial -- financing part as well. From a regulatory perspective, we think this data is really, really positive perspective of available care. So as we noted in the press release and as Friedrich noted in his comments, the response rate as well as the durability far exceed what's available to patients. So we don't -- from a regulatory perspective, we think this is very, very good data. And again, Cohort 2, as the FDA told us, can be supportive of the approval, and we'll look to get as much as we can from Cohort 2 when the final negotiation with an update for the label. On the financing overhang, and then I'll switch to Friedrich, we're -- Jean-Marc and I can -- Jean-Marc can chime in here as well. But we're not actively out there looking right now. And we've got -- as you know, we've got over $500 million in cash right now, and we're doing quite well. And we've given guidance in the past, so we've got plenty of runway here. Jean-Marc, do you want to add anything to that? And then, Friedrich, do you want to add anything to the clinical part?

No, I think you said it right. I think with $516 million and enough cash until 2024, we are not considering any financing now. And we, of course, are mindful of our expenses as we ramp up for commercial readiness and manufacturing readiness. But you said it.

Friedrich, do you want to say anything about the durability?

Definitely, yes. Yes, yes, let me comment on the median duration response of 10.4 months in Cohort 4 not reached in Cohort 2. Both of these results are clinically very meaningful. As I mentioned in -- just earlier, the low response rate of 4% to 10%, so that's obviously quite meaningful when you compare it to about 1/3 of the patients responding in our trial. But then also the expected durability of responses with the available therapy, which is monotherapy and chemo, sometimes double the chemo, is as low as 3.5 months. So 10.4 months is definitely meaningful, particularly since we do have an idea around how both of these cohorts together are really best describing the totality of the real-world population, which is some patients with less prior therapy on anti-PD-1, some patients with more, some patients with less tumor burden, some patients with more. So really, the real efficacy, the real benefit is going to be best described by the pool. And I do think that, that will be kept in mind as [ Cohort 4 ] given this data.

Our next question comes from Tyler Van Buren of Cowen.

So I want to clarify a couple of questions. The first one is just I want to clarify on the filing. You said Cohort 4 data are supported by Cohort 2 data. And I believe that you said you may file the Cohort 2 data. So I guess just to be clear, are you waiting for FDA feedback to figure out if you could file both cohorts together? And what are the important factors to consider in terms of filing with the full population and getting the full data on the label? And then the second question is just, can you give us a sense of where you believe Cohort 2 or the pool data are tracking in terms of median duration of response?

Yes. Sure, I can handle both of those. The discussions with the FDA have already occurred. They basically have said that Cohort 2 may be supportive and, therefore, we are including in our BLA filing. That's not really something that we're discussing with FDA. It's going in. We think that's what they want to see, and it's going to be part of the main body of the BLA filing that it's a clinical study report. So that's done. With respect to where Cohort 2 is trending and the pool is trending, that's in the press release. When you pull the data together, median DOR is not reached and Cohort 2 is not reached. And that's by IRC now as opposed to what we've done previously, which is investigator read. Does that answer your question, Tyler? I could have Friedrich follow up a little bit here if you want.

Yes, I understand it's not reached, so I was just wondering if you could give us any more color than that. But I understand maybe you can't.

Yes. When you cut -- Friedrich, maybe you can jump in here. But we cut the data, it's either reached or not reached based on -- you look at the median from a reverse Kaplan-Meier and you see where it is. I can't tell you that it's going to be reached in 1 month or 10 months or something like that. We have no idea until you cut the data and look at it. But we are not planning to recut the data.

Another thing to keep in mind is -- yes, sorry about that. Another thing to keep in mind is that, that the last patient treated on this cohort was a long time ago. And we've shown the response profile that the vast majority of our initial response occurs early after treatment. So that gives you an idea on how the response durations are distributed, and you can look at the profile that we extended at ASCO '21, granting that's the investigator says. But that kind of gives you an idea. And so wherever the median duration will be turning out, it will be a good number. There's no way that will turn into something short, right? So I think that's what I'm trying to say here.

Our next question comes from Madhu Kumar of Goldman Sachs.

I guess kind of our curiosity on the Cohort 4 patient selection, was there kind of guidance by the FDA for Cohort 4 to be run in these kind of more advanced patients, patients with higher LDH, patients with more lesions, with longer kind of prior PD-1? Like kind of was there a kind of active rationale to recruit those patients? Or is that just kind of like a circumstance of Cohort 4 recruitment?

That was -- we didn't get any active guidance FDA to do that. Friedrich, maybe you can comment here, but that just reflects the patient population that's out there available for these sorts of trials, in my view. Friedrich, do you want to add to that?

Yes, let me add to that. The exclusive criteria were exactly the same. So there was no kind of sort of enrichment of a different population in regards to tumor burden or LDH, prior therapies, duration on prior. What you're looking at is what I think is a fairly expected evolution of how PIs are enrolling to a trial where early on they might be being more conservative. And as then the encouraging efficacy results are coming in, they're getting broader in patients that are being enrolled to the trial. So I'm not surprised that, that changes over time and that we might be seeing from patients who have worse prognostic factors being enrolled. So again, the expectation is that after potential approval, this will be a second line therapy, meaning we will be looking at patients with less prior therapy, we would be looking at patients that are not being recycled and retreated with monotherapy checkpoint inhibitors because now there's additional available therapy with an objective benefit safety profile. So I think in the population that we'll be looking at using it as the standard of care, that will probably be on the better side of the spectrum that we are currently covering Cohorts 2 and 4.

Okay. And then kind of how does this data set in aggregate shape? How you think about a confirmatory trial if one kind of takes the view that you all would file for potentially an accelerated approval in post-PD-1 melanoma? Like how does this data can inform? How you think about a confirmatory trial in that setting?

I don't think it changes our analysis, Madhu. I think that we're prior -- in our previous discussions, we've talked about how we could get a full approval here. Unfortunately, Raj don't play right now, but he'd be happy to follow up with you on this. But it doesn't really change our analysis here. We've got a confirmatory trial prepared, and we're working on that, and we've talked about that publicly. But if we don't need it, we can get a full approval here. There's 153 patients worth of data. It's quite a lot of data for cell therapy that FDA can look at.

Our next question comes from Mara Goldstein of Mizuho.

So I wanted to ask about the significance, if you will, of the differences in the Cohort 4 data to Cohort 2 as it relates how the FDA will -- or what you rather -- sorry, how you may ask for a label to look at and what you think the significance for the medical community assuming, you receive approval and how lifileucel will then be used?

Friedrich and Madan, do you want to try and take this one?

I can speak to the data set and how the FDA might be looking at this data set. And obviously, we can continue having these discussions on lifileucel [indiscernible] and follow-up discussions. The FDA will definitely be interested in seeing as broad of a data set for the safety data if possible, so Cohort 2 will be represented on the label as part of the safety data set for sure. That is then an opportunity -- that's been an opportunity to also represent the efficacy data. So that is the approach that we're going to take. Obviously, this is a question of negotiation and agreement, but I'm fairly confident that there is a good rationale to include the efficacy data in order to provide the full information on the benefit-risk profile of lifileucel. Madan, do you want to comment on how that then would be looked at as part of the medical community as standard of care use after FDA approval?

Absolutely. Thank you, Friedrich. I think that's a really very valid question. So as Friedrich mentioned earlier, what we have seen is the evolution of enrollment of clinical trials. HCPs often enroll patients with less advanced disease as new therapies being tested. As they get more confidence in that, more patients with advanced disease are put on clinical trials. So you clearly see that evolution between Cohort 2 and Cohort 4. I think it's important to keep in mind that in Cohort 2, the median prior lines of therapy as we've declared at ASCO and AACR and the manuscript, was 3 prior lines of therapy. We've not publicly disclosed the median lines of therapy in Cohort 4 at this time. But as you can see, these patients had a high LDH and number of lesions. Once this comes in as an approved product, I would envision that physicians would take patients after the initial progression on anti-PD-1 directly to lifileucel. And we've shown at our ASCO '21 that the cumulative prior anti-PD-1 duration does influence the duration of response. So I think once this gets into the commercial landscape, I do expect that physicians will use this earlier in the disease scores at the time of initial anti-PD-1 progression, and that actually maximizes the patient's benefit from that. But even in the current unmet need, even in the late line setting, currently, the data between Cohort 2 and Cohort 4, as was mentioned by Fred and Friedrich, that the response rate is really robust compared to what is available for these patients today.

Our next question comes from Mark Breidenbach of Oppenheimer.

A couple of questions for me. I guess, first on the topic of cumulative duration of anti-PD-1 exposure, can you give us any specifics on how many months of prior exposure that Cohort 4 had versus Cohort 2? And maybe give us a sense for which of these cohorts is more reflective of a real-world melanoma patient population. And then I have a follow-up.

Sure. Madan, do you want to take that? What we can tell you, Mark, we haven't disclosed it. We're going to go to a medical conference to show more of this, but it had about half of the prior exposure, and we can maybe reference that to what we showed from the investigator read data in Cohort 2. Madan, if you want?

Sure. Absolutely. So in Cohort 2, the investigator led data, again, that should not influence the prior cumulative anti-PD-1 exposure. The median anti-PD-1 exposure was 5.06 months. And as mentioned in the press release, the Cohort 4 patients actually had almost double of that amount, so you can sort of do the math over there. Regarding how this reflects in the real world, I think this reflects that there are no current viable options available after anti-PD-1, and all the HCPs can do is recycle anti-PD-1 therapy with variations, with adding anti-CTLA-4 or adding experimental therapy X, Y or Z. But once this is available in the commercial landscape, I think physicians will switch to lifileucel, and you will actually shorten the prior anti-PD-1 duration appropriately and maximize the benefit to the patient.

Okay. That's helpful. And this actually might be kind of a naive question, but I know the last patient in Cohort 4 was dosed way back in January 2020, at least that's when you announced it. That was over 2 years ago. And I'm just trying to reconcile how the median follow-up time is only 23.5 months for Cohort 4. Were more patients enrolled after that January 2020 announcement? Or just what was going on there?

So median described the midpoint of the distribution, which includes patients who were coming off a follow-up because they have a progression, for example. So I think that is -- or they have events that make them come off the follow-up for the study. So don't -- you can't count every single patient from the beginning or from the time of that treatment. That's not [ some thesis ], it's the duration of them being on follow-up. And when patients come off follow-up early, then they basically feed the left side of the distribution curve.

Okay. Yes, makes perfect sense. I just want to make sure something else wasn't going on there.

No, nothing else is going on, just statistic.

Our next question comes from Colleen Kusy of Baird.

So the background on the difference in patient demographics is really helpful. Was there any notable difference in the drug product you were able to produce? And can you remind us if the manufacturing approaches were the same for Cohort 2 and Cohort 4?

Sure. Igor, do you want to handle that one?

Of course. Thanks for the question. The drug product is the same. We're using our Gen 2 manufacturing process. And so there were no differences between the product provided to patients in Cohort 2 or Cohort 4.

Okay. And then just as a follow-up, with -- I assume that this data reflects the new potency assay that you agreed to with the FDA. Can you speak to whether that impacted the results of this readout versus the potency assay that you used for Cohort 2?

Colleen, it really didn't. It's -- that's subject to further discussion with FDA during the BLA review process. But at the end of the day, this is the data set that we think FDA is going to want to see from a potency matrix angle as well. So this is where -- the 87 patients is what we're submitting. But you don't have to think of the potency assay as having any kind of major effect on this.

Our next question comes from Ren Benjamin of JPM Securities (sic) [ JMP Securities ].

I'd like to talk about the wide confidence intervals that you're seeing both from ORR perspective and a median duration of response perspective. Have you done the analysis to show that those patients with a lower LDH level or lower tumor lesion, baseline levels or what are driving those higher responses and higher durations of response?

Friedrich, do you want to take this one?

Sure. So let's talk about the confidence in them both. First, I think the confidence in both are also important as you're looking at the totality of the data and, for example, also comparing Cohort 2 and 4, you see that these are very overlapping, indicating that the activity in regards to response is very, very comparable. As you are then looking for factors that might be associated with ORR or duration of response, you're doing subgroup analysis and you're dividing patients into, for example, subpopulation based on distribution versus the medium. Or in case of the LDH, you're just looking -- you're comparing the population with LDH levels within normal range versus LDH that was elevated. And you're looking for statistical differences there. LDH was clearly statistically different, but it wasn't a black and white kind of association that would now tell us that from a certain LDH level on patients should not receive lifileucel. There was still benefit in that group. It was a big difference, and that's what we are picking up here. Does that answer your question?

Yes. No, that helps quite a bit. And then when we start thinking about PFS, is it fair to assume that, okay, if the duration of response is 10.4 months and the median PFS is likely to be significantly shorter than that. And when we're looking at these patients in Cohort 4 in particular, are they progressing because of new lesions? Or are there old responding lesions suddenly growing?

Good question. I think one thing to keep in mind is duration of response is a very different parameter and describes a different population than when you're looking at the PFS, right? PFS is looking at the entirety of all patients that basically looks the duration from time of treatment to an event, right? That's the same for all time-driven endpoints. Durability of response is looking at the durability in the -- of the response in the responding patients. So that's a subgroup of the total group. That is a much more meaningful parameter in the context of a single-arm trial like this. And that is going to be an endpoint that is much more important to the FDA than the time period and end point, for example. So I would really focus on the DOR here. PFS, again, is something that we haven't disclosed at this point but probably in the context of reviewing this data will play less of a role than DOR.

And just in terms of the progressions that are taking place, is there any sort of difference in Cohort 2 and Cohort 4?

Not really. We haven't really seen kind of clear patterns where we are seeing many more mixed responses or mixed progression than you would be seeing with other modalities or other agents for all immunotherapy agents. Seeing mixed responses and mixed progression is not atypical, but we haven't really seen any specific pattern that we would be comparing now between Cohort 2 and 4. There's nothing unusual there.

Okay. And then from a safety perspective, these appear to be higher disease burden patients, right, elevated LDH levels and they are like, harder-to-treat patients potentially. Was there any differences seen from the 2 cohorts in terms of safety?

No differences that would be clearly sticking out as being related to the higher tumor burden, for example, that's for sure. But even overall, the safety profiles are fairly consistent between Cohort 4 and 2 even when we look and compare it across patients with other tumor types. Safety really is driven by the lympho-depleting chemotherapy and the IL-2. And so it's not surprising that we wouldn't be seeing any differences between the cohorts.

Got it. And I guess just my final question, why announce the data now? Is there anything in particular that was driving this? Would -- instead of announcing it in August, was there some sort of requirement? Or what drove the decision?

Well, we're trying to get it out as fast as we could after getting it. So that's Part 1. We're in the middle of FDA discussions with the pre-BLA in July. So we were trying to get -- we're essentially trying to get it out as fast as we could, as we've always said we would.

Our next question comes from Ben Burnett of Stifel.

I wanted to just follow up on the last question. I think the DOR or the median DOR is a helpful metric for understanding kind of durability. But just curious if you've seen kind of the broader sort of Kaplan-Meier curve. And is there a plateauing below the median, but do you see a plateauing in Cohort 4? If you do, can you maybe talk about it?

Friedrich, do you want to comment on that beyond what we...

Yes, I think -- so I don't think that I can talk about the plateau on the time period than Kaplan-Meiers without us having disclosed the data or being able to show you Kaplan-Meier plot. What I can talk to you about is, is that if you look at both of these cohorts, you are seeing impressively long responses. Obviously, follow-up is longer in Cohort 2 there, but I think Cohort 2, this is good feel for where things might be moving, where we're seeing very long responses, including in the complete responders, where now I think I can share this much now we're getting with this data cut to a duration of 4 years of complete response in a patient number. 5 years response in any cancer patients is getting close to cure. So that's very encouraging. And we do think that with the observation of deepening responses and conversions from PR to CR and also long PRs, we are looking at a subgroup of patients which will [indiscernible] clearly a long-term benefit. And that's been described in the NCI data in myeloma patients.

Okay. Okay. That's great. This also -- this notion of some of these patients or these patients on average in Cohort 4 having a longer duration of anti-PD-1 treatment relative to Cohort 2. Just curious, is there any hypothesis as to how that could impact TIL efficacy? Like could that maybe impact the ability to harvest TILs? Or I guess, how does that sort of fit into this picture?

Yes, I can speculate. We don't have a good understanding of what is actually the mechanism of [indiscernible], but in broad strokes, this could be -- effect long-term checkpoint blockade might have on the tumor microenvironment. And that might be the tumor microenvironment at the time of the tumor harvest or the tumor microenvironment that the TILs are encountering as they are being infused back into the body or on the tumor filtrating lymphocytes themselves at the time of harvest. We don't have a good understanding of that yet. Obviously, [ it's subset of ] a lot of research and translational work, but there might be several mechanisms in play at the same time. What we do see is this association with durability of responses. And that also fits differences that we're seeing in patients who are checkpoint that are pretreated versus checkpoints that are naive. And that's well described. So there is something and say what it is that we do not know.

Our next question comes from Asthika Goonewardene of Truist Securities.

Wonder if maybe ask was there any differences in the baseline in terms of the patients receiving prior CTLA-4 between Cohort 2 and Cohort 4.

No, they were quite similar.

Okay. And then do you have any biopsy data -- as this is a pretty fresher, but do you happen to have the biopsy data on patients on Cohort 4 that might give you any other clues as to what's happening in the tumor microenvironment on progression?

We have a significant translational program at the company. And yes, we do have the ability to look at both the products. It sounds like we have separate biopsies, but we have the ability to do that. That may be something that we can present in the future at the conferences in the second half of this year.

Got it. Okay. And then just maybe reflecting on Cohort 4 having a higher proportion of patients with -- or rather a higher number of baseline lesions, want to reflect back on Ren's question and maybe ask it in a different way. So given that you had a high number of baseline lesions, was progression that you're seeing due to nontarget lesions growing or were they previously controlled target lesions growing or were they new target lesions emerging -- or new regions emerging?

Friedrich?

I can take that, Fred. Yes, it's really -- the answer to that question is yes. So it could be any of these. We are -- as I told you, we do not see specific patterns of progression dominate here. We have a mixture of progression because of new lesions occurring. We have target lesions progressing or we have nontarget lesions that are testing or overlapping. So it's a mixture, no patterns and no differences in the cohorts that we were able to detect at this time.

Got it. And then just one final quick one, and maybe just more for me to understand this a little bit better. Was progression on Cohort 2 determined by investigator or by IRC?

In both of these cohorts, the data that we just disclosed, the data that we presented are assessed by IRC.

Got it. Okay. I think I just want to confirm.

Sure. Thanks.

Our next question comes from Joe Catanzaro of Piper Sandler.

This is Sam on for Joe. I guess just a couple. Would you be able to tell us how many of these -- or what proportion of these responses lasted longer than 6 months? And then, I guess, secondly, in terms of the label, I just wanted to confirm that I did hear that the potential future label would detail potentially Cohort 2 safety and efficacy as well.

Confirmed on the second question. On the first question, we'll save that for a medical conference that detail that we will present later.

Our next question comes from Nick Abbott of Wells Fargo.

Congratulations on the data. I personally think it's really quite impressive. But can you say whether there was a difference where the PD-1 was the last line of therapy versus used in an earlier line, primary refractory versus relapsed? And then a follow-up as well, please.

Friedrich?

Sure. Good question. We didn't have requirements around this. So patients could have had prior therapy -- prior anti-PD-1 therapy directly before entering the trial or within the current other therapies. They could have had more than one line of therapy with checkpoint inhibitor monotherapy or combination, and we didn't have any requirements around certain sequences. So it's really a mixture. . As Madan said, this is a late-line population. These patients have received multiple lines of prior therapy. And also, as Madan said, oftentimes, you're now seeing recycling of checkpoint inhibitors either as monotherapy or combination. This is a population that has received -- where the majority of patients has received anti-CTLA-4 either monotherapy sequentially with PD-1 or in combination. So it's really a true mixture. No requirements. There was, for example, no requirement for immediate start of lifileucel just after PD-1 failure. It's really wide open and late-line population.

But have you looked at those sort of fairly discrete buckets of patients to see if there are differences based on when they received and also whether it was immediately prior to lifileucel?

Yes. So we're exploring all characteristics. We're exploring baseline disease characteristics, patient characteristics, prior therapy. We are exploring this for that, right now, there is no patterns that are worth reporting here. We may be kind of focusing this in future publications. We've spoken about some of the subgroup analysis in the context of the Cohort 2 investigators of this data, where we also spoke about patients with primary refractory disease, meaning patients who have best response of PD on prior anti-PD-1. And even there, we're not necessarily seeing that those patients, for example, would be worse. It might even be more an indicator of or associated with shorter prior anti-PD-1 therapy, which is good in the context of lifileucel therapy. So stay posted on us reporting on those details in the future.

Okay. And then last one, you mentioned safety, but were there any Grade 5-related events or treatment-related events in this cohort?

So we will present on the details of the adverse event profile as we are bringing forward the data and more details, so stay posted on that. As I told you, the safety profile is very much consistent with what you are seeing with non-myeloablative lymphodepletion chemotherapy or IL-2.

Thank you. I'm showing no further questions at this time. I'd like to turn the call back over to Fred Vogt for any closing remarks.

Thank you again for joining us this evening. Iovance today is well positioned to complete our BLA submission and executing our strategy towards becoming a fully integrated commercial company to deliver TIL therapy to patients while pursuing substantial opportunities within our pipeline. I would especially like to acknowledge and thank our patients, their families and our investigators, employees, shareholders and advocates for their support. We look forward to keeping you updated on our progress throughout the rest of the year. If you would like to follow up, please reach out to our Investor Relations team. Thanks, everyone, and good evening.

Thank you. Ladies and gentlemen, this does conclude today's conference. Thank you all for participating. You may now disconnect. Have a great day.