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

All right, everyone. Thank you for joining us today at Goldman Sachs Global Healthcare Conference. Really excited to be joined by the team from Iovance Biotherapeutics. Great to be here and let's just get started. All right. So let's start with kind of top of the mind on your lead program, your tumor-infiltrating lymphocyte, or TIL drug, lifileucel, in the upcoming BLA submission in post-PD-1 melanoma. So kind of proximal question, how are things proceeding? And really, what is the cadence of events between now and the BLA submission in August?

So let me take this one. Thank you, Madhu and thanks for the invite. Obviously, it's nice to be in person. So we're on track. I mean let's go short. We are on track to submit the BLA in August after pre-BLA meeting with the FDA in July, as we previously communicated. As you have seen last month, we announced some positive result on our Cohort 4 data, which support expected approval for lifileucel. I mean results have shown that onetime treatment with lifileucel provide -- may provide meaningful benefits and durability for patient treated -- for patient with advanced melanoma who have limited option when they progress of anti-PD-1 therapy. So again, everything is on track. We have now the Cohort 4 data available to go in the BLA.

Okay. So thinking about the July pre-BLA meeting, what should investors be kind of expecting either before that event or kind of around that event? How should we think about what that discussion is going to be like, really practically?

Yes. No. I mean I'm sorry, I'm going to give you a short answer. There is no real milestone between now and the BLA or the pre-BLA meeting in July and nothing specific. Again, the full focus remain on this BLA submission. So a lot is happening in the organization just to get ready towards that, but nothing -- nothing major milestone to highlight.

Okay. So well, obviously, after the Cohort 4 top line data came out, one of the debates that investors had is, what is the importance of Cohort 4 relative to Cohort 2 -- and we're going to like get into Cohort 4 versus Cohort 2 in some detail today because I think it's really informative for investors to think about it in a kind of like level-headed way. And so first question is, what is the importance of those 2 cohorts relative to one another in terms of the BLA submission?

Absolutely, I can take that. So thank you for the invitation, Madhu. So Cohort 4 is the registrational cohort, right? So the FDA, obviously, is going to look at that. But I think it's important to understand that both Cohort 2 and Cohort 4 have the same eligibility criteria, treated with the same product and these were sequentially enrolled: 2017 to 2019 for Cohort 2, 2019 to 2021 for Cohort 4. You have to look at the results of both the cohorts as a pool analysis and that's how the treating physicians are going to look at that. At ASCO, our team met with more than 50 KOLs and we heard it loud and clear from them that they want to look at an aggregate of the 153 patients, which as we've disclosed, had a 31% ORR at 27.6 months median follow-up and the median DOR is not reached. When you look at Cohort 4 by itself, I think everybody got fixated on the mDOR of 10.4 months. But as you know, mDOR is a point estimate on the Kaplan-Meier curve and it is very sensitive to how even a few patients perform. Subsequent to our press release, we updated the data and showed that at the 12-month mark, 44% of patients are still responding. So you can then visualize there's 1 more dot on the Kaplan-Meier plot. And the longest duration of response is 26.3 months. So you can do the math and we can say that many patients are on that tail of the curve and continuing to maintain a response. So you could potentially visualize the Kaplan-Meier plot and say that there is a very stable tail, very similar to what we saw in Cohort 2. Now Cohort 2 obviously had an mDOR that is not reached. So it's possible that numerically, the height of the curve is a little bit better than Cohort 4. But then you have to keep in mind that Cohort 4 enrolled patients that had a slightly more advanced tumor biology and we've measured that through 3 surrogates, right? The proportion of patients with high LDH is higher on Cohort 4. The proportion of patients with more than 3 metastatic lesions is higher in Cohort 4. And the proportion of patients or rather the median prior anti-PD-1 exposure is double in Cohort 4 compared to Cohort 2. So it should not be a surprise that the mDOR has come at a different point estimate, but that doesn't take away from this being a positive study because it met its primary endpoint and rejected the null hypothesis.

Sure. So there's 2 questions I have following up from that because I think you're dead on the money and there's I mean 2 considerations that will exist beyond that. What are the confidence intervals for Cohort 2 median duration response versus Cohort 4 median duration response? Because you're right, like it could be a case where one is right below 50% and one's right above 50%, but your confidence intervals, if they're sitting on top of each other, mathematically speaking, they're not actually different. Second piece is on that point around the duration of prior PD-1 therapy, I think it's an interesting point and was something that was prospectively raised last ASCO in analyzing the Cohort 2 data. What biologically do you think that means? And what does that biologically mean in terms of the response of certain patients that shows a lack of response of certain patients to TILs who have been on prolonged prior PD-1?

Absolutely. Let me take the first question first. The confidence intervals around the point estimates of the mDOR between Cohort 2 and Cohort 4 are overlapping. In fact, at the ASCO Education session, Allison Betof Warner had a slide that she showed where she's basically showed Cohort 2, Cohort 2 plus 4 and what other options do treating physicians have today, right? And in that, she's been able to show what that confidence interval is in the Cohort 4, right? So it is absolutely overlapping with Cohort 2. So you're absolutely right on that statistically, these are not dissimilar from each other. Going to your second question, what does the prolonged anti-PD-1 duration mean biologically? I think we just need to remind ourselves that the prolonged anti-PD-1 duration does not influence the ORR, but amongst the responders, the duration of anti-PD-1 duration is negatively correlated with the duration of response. So scientifically, why does that happen? It's possible that the surviving tumor after prolonged anti-PD-1 has different mechanisms of resistance. We recently showed in our ASCO publication, the poster, where we looked at the checkpoint naive cohort and in a case match control, found patients from Cohort 2. So 7 from Cohort 1A, 21 from Cohort 2, and did translational analysis and we have a slightly higher number of patients with beta-2-microglobulin deletions. There's 1 patient with the HLA loss of heterozygosity, although that patient actually had a transient response, right? So the biology still needs to be uncovered. I think what's more important is from a treating physician standpoint. The first question we've got to ask ourself is, why did Cohort 4 have a prolonged duration of anti-PD-1 exposure? That's because treating physicians do not have a viable alternative today. So they are basically recycling checkpoint inhibitors. So once lifileucel comes to market in a solid second line indication, I think what we should see is a change in practice where lifileucel is offered to the eligible patients as a second line rather than the alternative of just recycling checkpoint inhibitors.

Well, so on this last point, it kind of runs to this weird almost like paradoxical conclusion that patients who are primarily refractory to PD-1 front line might conceptually do better on lifileucel than patients who responded for a long time to PD-1, because the PD-1 itself is editing the tumor or the T cells in some interesting way. Have you thought about that possibility? How does that influence how you think about kind of the utility of lifileucel after PD-1?

Absolutely. So we've actually thought about it. So in our JCO publication from May 21 in Cohort 2 -- the publication was in the context of 18.7 months of follow-up back then -- we saw patients who were primary refractory to anti-PD-1 actually numerically had a higher ORR compared to even the aggregate of Cohort 2. So it's not again statistically different. But biologically, it's possible that the patients who are primary refractory just have a different biology and are more adept to responding to lifileucel versus patients who respond to anti-PD-1 and then are relapsing. Now that being said, we do not have a large number of patients who receive lifileucel as second line therapy. So once we start seeing that in the commercial landscape, it is possible that we will not see this effect of prolonged anti-PD-1 because the patients will respond, progress and come in with lifileucel.

And the other kind of conceptual point to this is that, yes, there's like maybe a lesser duration of response if you've had a longer term of prior PD-1. It's still like a mountain of duration of response compared to what you'd be taking right now otherwise. So if you pick any alternative, it's still very different anyhow. So kind of moving beyond that, I guess, kind of like how are you thinking about the cadence of the regulatory submissions? So you file in August, kind of you're thinking an acceptance of the filing a couple of months later. How are you thinking about the potential for an AdCom? I mean let's start with those 3. So you file, acceptance of the filing, how do you think about an AdCom after that?

Yes. So again, you're right. So pre-BLA meeting, filing in August, we -- 60 days after BLA acceptance, we are talking about AdCom. We don't know yet, but obviously, this will be more related if you have any kind of safety concern, which we have 153 patients now between Cohort 2 and Cohort 4 worth of data where there is no real safety concern. So we don't think we'll have an AdCom, but again, to be seen. And then after that, yes, we'll go into the approval process and launching the drug early 2023.

So another kind of question that comes up from investors a lot is given to your point about melanoma doctors really want to look at the pool data being Cohort 2 and Cohort 4, the whole 153 patients. How confident are you that given the kind of like requirement for Cohort 4, that they will accept Cohort 2 and Cohort 4 data together as part of both the BLA submission and potentially being part of the label? Like it's basically how confident are you the label will incorporate all 153 patients as compared to only the Cohort 4 population?

Absolutely. So I think the FDA has communicated to us that Cohort 2 is supportive. So for safety analysis, I think they would definitely like to look at the aggregate. Now we will obviously be providing pooled efficacy analysis as well. And I think it's a part of the BLA review process to see if the FDA wants to look at both 2 plus 4 together and how does that influence the table. But obviously, we're going to try our level best to try and at least get the efficacy of Cohort 2 on the label, whether it is a true pool analysis, that that's to be seen.

Okay. And then I guess kind of a last question on the cadence of data from Cohort 4. When can we expect to see -- you mentioned a medical meeting the second half. Is there any more granularity than that? I guess my [indiscernible] question is, should I be flying to Europe this fall or should I be taking a train to Boston?

It's a good question. I would say it's 1 of the 2. So again, we have not provided any public guidance as to which conference we are presenting at, but it's definitely going to be in second half of '22.

Okay, boo. All right. I had to try. So then on this point, so blue skies second quarter, presumably 2023, given the kind of like priority review math people are using. You'd have [indiscernible] a regulatory decision if you file in August. Can you speak to launch readiness with your current manufacturers? Obviously, that's top of mind given some of the things that have happened in the BCMA CAR-T space. And around how many centers and patients practically will you be able to reach at launch? And how many in your [ immediate regions phased ]?

Yes. No, it's a very good question. And after, of course, our priority on the BLA submission, commercial readiness is on top of mind and getting ready for that. So what I can share with you is we have engaged with the top U.S. leading cancer centers just to get ready in terms of the TL delivery capabilities and how to train all the centers. We have disclosed that we will have at least 40 ATCs, what we call authorized treatment centers, at the time of launch. We know that metastatic melanoma patients are very concentrated. So 40 is actually quite a good number. We are training them now. We are training them on what we call COI, COC, so chain of identity, chain of custody, supply chain, quality system, which should definitely help both the patient, the physician and ourself to be successful in the launch. And in parallel to that, on the commercialization readiness, we have all the manufacturing component of it. So we have Iovance cell therapy center now up and running, producing clinical batches for the time being since Q3 last year. But we are ramping it up to be ready for commercialization. And our goal is really to have most of the supply coming from iCTC, although we still have contract manufacturing available, if needed. But yes, definitely ready for commercialization.

And that contract manufacturing, that's across the street at WuXi or...

WuXi is there.

Okay. And then kind of following up to come back to this question. So 40 ATCs at launch. How big does the ATC population get at steady state? We're just really asking the question, how many sites do you think will at steady state be able to give the high-dose IL-2 regimen that's kind of required right after infusion?

Yes. And you're asking the right question about reaching out to the community and going even beyond those authorized treatment center. So I think our goal is clearly to reach every metastatic melanoma patient. That's what we want to accomplish. So I think 40 at the time of launch is already a good number. We know, again, it's a very concentrated patient population. We want to go into reaching 80% of this patient population through maybe 60 authorized treatment centers. Again, to reach the communities to have referral. So the idea will be to drive all those community doctors, to drive those patients into those centers and reaching the total patient population.

That's interesting. Because as I'm sure you're aware, there are kind of 2 schools of thought on this question. So the school that you kind of highlighted is refer patients from the community into the authorized treatment center. The other alternative that exists is figure out a means of delivering TILs without IL-2, such that it becomes more available to the community treatment center. How are you guys thinking about that question and kind of approaches that could be taken to that?

Yes. Absolutely. So I'm sure there is. Clearly IL-2 can be perceived as a barrier, but as we interact with all the ATCs, when you utter the word IL-2, what comes to mind is single-agent IL-2, 18 to 20 doses. That's not the IL-2 we are using. We are using a short course, high-dose IL-2 with a total of 6 planned doses. And across the various cohorts that we have presented, the median IL-2 dose is 5 to 5.5. So we're trying to educate the ATCs that this is getting the patient through 5 to 5.5 doses of IL-2. And once they get that awareness, they're actually fairly comfortable delivering that. That does not take away from the idea whether we should have an aldesleukin-free regimen. And that's where IOV-3001 is an asset that we are developing right now and we hope to get that to the clinic, which will have an enhanced safety profile and will allow us to kind of move away from aldesleukin.

Okay. Great. So moving beyond post-PD-1 melanoma, why don't we sort of walking through some of the earlier line melanoma data you guys have and then we can start to dig in a little bit into like what that plan is for the kind of front line trial? So...

Absolutely. So we've disclosed our early line melanoma in the checkpoint naive setting and in 2 different conferences -- sorry, at SITC '21 and in a press release. So the most updated data is we've treated 12 patients. We're seeing an overall response rate of around 66%, with a 25% CR rate. Many of these patients are now beyond the 1-year mark and continuing to do really well without any progression. We obviously need to increase the N, to increase the confidence that this is the ORR and the CR rates that continue to hold up. But as you've seen in the public domain, our plan is to take the TIL plus pembro combination in checkpoint naive melanoma into a Phase III study to try and get into the front line setting.

So on that point, how many more patients do you need in a kind of Phase II trial versus just rolling them into the Phase III?

Yes, it's a good question. So we are continuing to enroll as fast as we can on the Cohort 1A to try and get to that higher number, where we have more confidence, the confidence intervals start coming together. But I think our initial results, that ORR of 60% and more interestingly, that the CR rate is 25% and these patients are not progressing, is really very enthusiastic for us.

Okay. So on that point, so then as we think about this Phase III trial, I mean it's been asked before by other people, the notion of like what is the template? Certainly there's a notion that like RELATIVITY is the template for this trial. So first, could you briefly explain how the RELATIVITY trial was designed and then explain how much that influences how you think about a lifileucel trial?

Yes, absolutely. So I can say that we've not publicly disclosed what the control arm is going to be. RELATIVITY trial had a very different sort of focus, right? The target population was patients that are ideal for single-agent anti-PD-1 and you're giving them nivo plus rela to try and sort of enhance the response rate without compromising the safety profiles. It's a very different group of patients that they were enrolling versus patients who need to be sort of TIL eligible. So again, study design to be disclosed. We've not disclosed that, but we are very mindful of the changing landscape in melanoma and we are watching that very closely.

I mean I guess to that point, do you think there is a need to go against like a physician's choice PD-1 or PD-1 combo, to practically compete in that early line population?

Again, a very valid question. I think when you design a study, the goals are: Is it scientifically valid? Is it accruable very easily? And will the patients sign up for the study? So that's how we have to look at all of those attributes. So if you go against investigators' choice, obviously, it cannot be anything that they can offer, right, because we've got to keep the control fairly homogenous as well.

Sure. All right. So looking outside of melanoma, let's walk through the non-small cell lung cancer program. I guess more practically, how to think about the 202 study and really in terms of what are the key patient populations you guys are pursuing in non-small cell?

Absolutely. So let's kind of back up a little bit. So we disclosed the Cohort 3B data at SITC '21 where the goals of Cohort 3B was to show that TIL regimen is feasible in the lung cancer population. The answer is yes. Can lung cancer patients get a thoracic surgery resection of the tumor? The answer is yes. Can a lung cancer patient tolerate aldesleukin? The answer is yes. So we saw a signal. Yes, the duration of response was not optimal. So we've got different strategies around lung cancer. First with LUN-202, and we're asking the question, moving TIL therapy to a solid second line rather than late line, does that change the outcome? And within that, we recently had an amendment that we've publicly disclosed. The concept is called pre-progression resection. Currently, in our TIL regimen, we wait for the patient to progress, then we resect the tumor. They're not getting any interim therapy. They're just waiting until the product is manufactured. So what pre-progression resection allows us to do is to imagine a lung cancer patient on first-line chemo IO. And after X number of cycles, they have stable diseases, the best response. Most of these patients we know are going to progress. So at the time of that suboptimal response, they get the tumor resected. We manufacture the TILs. They continue on their first line. When they progress, TILs are ready on the shelf. So the downtime for the patient is eliminated. Plus we are asking scientific questions. When the tumor is resected with minimal exposure to cytotoxic anti-PD-1, is the quality of the TIL product any different versus harvesting the tumor at the time of progression in non-small cell lung cancer? So this pre-progression resection will give us an opportunity to answer that scientifically as well. So that's LUN-202. It's enrolling and we'll disclose data once we have a meaningful subset of patients over there. Cohort 3A in the basket study is in non-small cell lung cancer checkpoint naive, where we are combining TIL plus pembro. That study is continuing to accrue as well. And then we have the PD-1 inactivated TIL program or IOV-4001, which also has a non-small cell lung cancer cohort that are checkpoint -- post-checkpoint patients. So we've got multiple shots at goal with lung cancer, with LUN-202 checkpoint naive with Cohort 3 and then the new asset, IOV-4001 and the post checkpoint.

So on that kind of like in-progress resection to isolate TILs, this is very reminiscent of the Creelan academic trial out of Moffitt. And we've always had 2 schools of thought of that trial. Because for sure, you're right, there is a banking advantage of being able to get the TILs and have them ready to go such that when progression happens, you could immediately react. But there's always for us kind of like maybe it's an intellectual concern that the TILs that are resident at the point of progression might be biologically different from the TILs that are just resident before the progression event happens. How do you kind of think about that? And how do you kind of reconcile that there might be a kind of efficacy disconnect for those TILs from, say, many cycles of PD-1 chemo ago versus the ones that are resident at the point of progression?

It's a very valid question. I think if we were to, at the risk of cross comparing Creelan's data set with Cohort 3B, very different -- the ORR is in a very sort of a similar range, right? Also it's known from a biological standpoint that the subclones that recur at the time of progression after PD-1 should be carrying some sort of a clonal neoantigen along with cell, right? So hopefully, the TILs that you have harvested at the pre-progression resection has enough of a TCR repertoire to take care of the metastatic lesions. And then the bigger question is that is there a phenomenon of epitope spreading that we could rely on that could allow us to sort of counter those new subclones that have come up.

Okay. So I want to then also come to the gene inactivated TILs, the PD-1 inactivated TILs. I mean certainly, conceptually, we understand the idea of inactivating PD-1 in the TILs. Kind of it gives you the PD-1 blockade with a massively larger therapeutic window. But the other school of thought is when we'd only look at the Caribou data from EHA last weekend, where there was a great response rate that was not durable. And obviously, there are many issues with that. I mean an allogeneic CAR-T therapy has those kind of separate concerns, but there's also been this debate, based on the old Carl June data, that PD-1 knockouts might cause exhaustion. So like how do you guys think about that? And how do you get comfortable with kind of like, again, that cost-benefit of getting cell intrinsic PD-1 blockade, but risking early exhaustion of your T cells?

Absolutely. Very valid question. So I think we can look at it from multiple lens, right? So we've got our data with TIL plus pembro, where at least numerically, the ORR is higher than pembro alone, right? So that gives us some confidence that TIL plus blocking an anti-PD-1 pathway may have benefit. So we are coming in with a cell therapy solution, sort of both are packaged into one. That's 1 way to look at it. You raise a very good point, right? So if you knock out PD-1, does it create a different set of problems? Now we are using TALEN technology. And as we've shown in our poster at ASGCT earlier this year, that our knockout efficiency ranges between 50% to 70%. So fortunately, that may work in our favor because essentially, we are giving a hybrid product. Part of the product is not PD-1 edited at all, while a subset of the product is PD-1 edited. So you may get the best of both worlds, where the PD-1 knockout product gives you that sort of good tumor kill and it is not as exhausted versus the product that did not get -- had the PD-1 inactivation maybe more susceptible to exhaustion. So I think -- and the challenge is there is no good animal model to do this. So completely aware about the Caribou data. Again, very tough to extrapolate. It's a CD19 CAR. It's an allogeneic product. It's a PD-1 knockout. And I don't think, to the best of my knowledge, I've seen what the mechanisms of resistance are. So we haven't seen that. I mean it still could be a CD19 antigen escape, which is so fundamental in CAR-T cell biology.

Sure. So I guess that's a fair and interesting point. I guess kind of ultimately, when can we expect non-small cell lung cancer data from any of these cohorts that kind of serve to really shine a light as to what the strategy is in non-small cell lung cancer for TILs?

Very valid question. Again, what we want to do is showcase the data when there is a clinically meaningful number with not just an ORR but with some mature DOR data, right? It's no point showing an ORR of X percent with a follow-up of 3 months. It really doesn't serve any purpose. So these patients have to accrue. We need a reasonable follow-up before we disclose the data.

Okay. I guess kind of beyond that, I guess how do you think about the edited TIL product versus a combination with like PD-1 blockade TIL product in terms of utility of one versus another?

That's a valid question. So I think TIL plus pembro, we still have to give pembro post until infusion. I think the advantage -- the theoretical advantage of a PD-1 knockout product is that you don't have to continue to give pembro. Hopefully, the PD-1 knockout cells persist in the peripheral circulation. They provide more active tumor surveillance and you don't need ongoing therapy. And I think if that is a true phenomenon, then it realizes the dream of a one-and-done therapy even in the checkpoint naive setting.

Okay. We had not spoken about potency assay so far. Why don't we have a brief discussion of them, because obviously, they're still top of mind for a lot of people. You mentioned a few months ago that kind of you had positive feedback. I will say certainly investors, it's hard for some of them to interpret what positive feedback means. I guess kind of coming down to brass tacks, like do you believe the potency assay issue has been resolved such that you do not believe it will be an overhang in the early stages of the filing process for lifileucel in post-PD-1?

Yes. We believe that, as we've messaged, that the structure of the potency matrix, we have alignment with the FDA. We obviously are doing or have done all the historical lot testing. Some of the potency assays are qualitative, some are quantitative. The quantitative numbers, the specs have to be set, that is going to be obviously part of the BLA process, right? So that part, we obviously need FDA alignment, but we are confident that our manufacturing success rate, which has been north of 90%, will not be affected by the new potency assay.

Okay. Great. So kind of briefly, can we kind of walk through some of the other programs in like cervical cancer, head and neck cancer? For cervical cancer, we'll start. It has been noted for a while that there's -- you have a post PD-1 dataset of some form in cervical cancer. Is there any expectations to present that data at some point? For a long time, I think the potency assay and BLA clarity was a gate. Based on the last answer, that would seem to be resolved. When can we expect to see cervical cancer data, look at that for that post-PD-1 cohort?

Right. We've not publicly guided to as to when we are releasing the post-PD-1 cohort. All we can say is that we've disclosed this previously that we've met with the agency and we are going to be guiding to what that strategy would look like regarding expanding the cohort or what the next steps are. So that -- so stay tuned on that.

Well, I guess kind of like what would it take to reach resolution on that front?

I think it's a matter of just getting perfect alignment with the FDA on what is the sample size and whether we can -- the way we are looking at it is we want the BLA out of the door with the FDA before we start messaging on any other of the other [indiscernible].

Okay. And then on head and neck, just kind of steady as she goes, kind of says it is.

Yes, absolutely.

All right. So I guess from that point, kind of beyond Cohort 4, which I failed but tried to press on earlier with -- about timing for data, when do we expect any other data from your various clinical TIL programs this year? Like is I mean historically, you've been an ASCO SITC company. Is SITC a natural venue, not for Cohort 4 per se, but for kind of like the TIL products that you all tend to develop? Would that be a natural venue to see some new updated data from various TIL clinical trials you have?

Right, we've not provided any public guidance. As I said before, right, once we have clinically meaningful data with mature follow-up, that's when we will be messaging that.

Okay. So stepping back to a very high level, maybe, Jean-Marc, you can speak to the cash runway. And I guess kind of at a more specific operational level, a lot of interesting things going on, but I mean like this is also a time when [indiscernible] choices need to be made. Commercialization of a bespoke cell therapy, you will have -- that have required specific treatment centers, you will have a potentially substantial Phase III trial in front line melanoma. What else do you believe you can practically do with your cash runway in terms of other programs to pursue? And what are the decision factors of like choosing to not pursue or deprioritize some programs in that context?

Yes. I think let's step back a second. So we have $516 million at the end of Q1 guidance through 2024, which include everything you were talking about. What I mean by that is there is a time for the proper allocation of expenses. We have finalized the build-out of a manufacturing facility last year, $40 million was spent there. Now we're spending to get ready for commercialization and ramping up. That will be done also this year. Then next year, we can start to reallocate some of those spending towards the Phase III and all the clinical programs we are talking about. So everything is already scheduled and prioritized in a way that we can afford for it with our cash runway until 2024. It's really reallocation of expenses.

So that's cash runway to 2024. But realistically, that will not cover the completion of the Phase III trial of melanoma?

Definitely not. You're right, we will just ramp up starting 2023. So at some point, having a need of more capital, yes, then we'll have to raise cash.

Okay. So I guess kind of the final question we're asking every company and no surprise for you all, I think, a straightforward case here. What is the reason to own Iovance stock in the next 12 months?

Yes, let me take this one because it's a super exciting time for us. If you look ahead the next few months, 12 months, if you want to take this period, we are going to have the BLA submitted. We are going to have a BLA approved. We're going to launch the first TIL therapy. We are going to launch, therefore, the first cell therapy treatment in solid tumor. So a lot of positive momentum on top of our clinical pipeline, again, 6 active clinical trial for solid tumor. We have released data and we will release data when they will become available. So super exciting. We just talked about the balance sheet strength. So exciting time definitely to invest at Iovance now.

So I'll also -- let me actually take a little time to ask a follow-up question on the balance sheet question. Given kind of the opportunities that are available for commercializing this kind of drug and -- but also the challenges that could exist, have you -- like how are you considering business development or other financing opportunities, things like royalty financing, geographic distributional partnerships as ways to kind of cover that balance sheet concern without having to go to straight equity financing or debt financing?

Fair question. I think it's the job of a CFO to bring every option on the table to the Board and the Board will consider what's the best option. It's a question of stock price, time, cash need and all those things are being looked at.

Okay. Excellent. Well, thank you so much, team from Iovance, for joining us today and we're glad you could join us and thank you for coming today.

Thank you, Madhu.

Thanks, guys.