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

Good morning, everyone. My name is [ Antoine Natale ], and I'm a member of the JPMorgan health care investment banking team. Thank you all for joining us today. It is my pleasure to introduce Maria Fardis, President and CEO of Iovance. As a reminder, you may submit questions through the ask-a-question feature, which is listed under the presentation on the website. We would advise you to submit your questions live during the session, and they will be answered at the end. Maria, back to you.

Thank you, Antoine. Good morning. I will be speaking about tumor-infiltrating100 lymphocyte cell therapy for treatment of solid tumors. I'm moving to Slide 2, where our forward-looking statements is noted. We are a public company, so I draw your attention to those statements. On Slide 3, we're showing you what is the goal for the company. As I noted, this is a cell therapy company for treatment of solid tumors. We aim to bring TIL therapy into commercial landscape in the near future with a platform that involves treatment of cancers, various cancers with these type of cells. This platform has strong clinical data for melanoma, cervical cancer, head and neck. And we continue working on additional indications, including non-small cell lung cancer. We have a consistent GMP manufacturing process across multiple solid tumors. We have next-generation research that is continuing in -- on focusing on selected TIL as well as genetic modification of TIL. And our pipeline in addition to melanoma programs as well as cervical, we can be focused on non-small cell and head and neck, as well as in late-line patient population and in earlier-line in combination with checkpoint inhibitors. We have a number of academic collaborations through which we look at new mechanism of actions, new potential indications. And once we find something that is of interest, we move those indications into company-sponsored studies. From an asset perspective, we had reported that we had $720 million cash in hand as of end of September 2020 and as well as our Iovance manufacturing facility, which is continuing its build. And I'll show you pictures and give you a status update during today's presentation. Moving to Slide 4. In 2020, we had a number of items that we had accomplished. We had completed enrollment into our Cohort 4 in our melanoma program. This is our pivotal cohort for melanoma. We had a discussion with FDA where they noted that Cohort 2 will be considered supportive and Cohort 4 is pivotal. We continue our work on developing potency assays to support a BLA submission for our product, lifileucel. In melanoma, we also read early data in Cohort 4, and we continued reading study update in Cohort 2 in melanoma as well as the fact that we have shown the median duration of response has not been reached. We have an update at JPMorgan, which I will show you also at the next slide. In cervical cancer, we continued enrollment into Cohort 1, the pivotal cohort. And we closed enrollment into pivotal cohort. In non-small cell, we presented data through our partners at Moffitt Cancer Center with their TIL manufacturing, showing impact of TIL in non-small cell lung cancer. In the head and neck at SITC 2020, we presented data showing combination of TIL plus pembrolizumab data in patients who are PD-1 naive. And we also have continued rolling newer products such as Gen 3 manufacturing into clinic, which is a 16-day manufacturing process, while having maintained an over 90% success rate and having dosed over 400 patients at Iovance to date. In 2021, we will focus on our corporate goals of developing a potency assay in order to reach agreement with FDA and being able to file our BLA in melanoma. We have completed enrollment in our Cohort 2 in cervical cancer, and we believe that FDA may require us to include this particular cohort as part of our original BLA for cervical. In non-small cell lung cancer, we have started a study called IOV-LUN-202, which is registration potential. And depending on the data, we could expand that study. We have added a cohort into our basket study, which allows for TIL plus ipilimumab as well as nivolumab combination to be introduced in second-line patients. In head and neck, we have completed enrollment into our C-145-03 relapsed/refractory head and neck patient population. And instead, we have expanded our Cohort 2A in our basket study, which allows for TIL plus pembro to be administered to patients. In melanoma, we are intending to initiate a cohort of melanoma patients being administered at Gen 3 product into clinic into the basket study. Again, that's a 16-day manufacturing process. And we continue our work in developing our Iovance Cell Therapy Center or ICTC, our manufacturing facility in Navy Yard and the intent to initiate our clinical manufacturing in that facility in 2021. Moving to Slide 5. The update that we are providing in our melanoma program, Cohort 2, is that the median duration of response still has not been reached at a study follow-up of 28.1 months. And we are delighted to see that median dose duration of response continue to show nice durability. The response rate for that particular cohort has been presented at various other venues, and I will go through some of that data that was presented at ASCO 2020 as part of this presentation today. On Slide 6, we are showing what the technology looks like at a high level. As I noted before, this is a cell therapy for solid tumors. The cells do come from the tumor. From a biological perspective when a tumor develops, our immune system comes to the site of tumor and tries to fight presence of these tumor cells. Typically, in the healthy individuals, these tumors ultimately get cleared, and the patient doesn't develop cancer. In cases where either there is environmental factors or genetic factors or otherwise, the tumor can persist, but that our immune cells still do come to the site of tumor. So the source of our product is, in fact, immune cells that came to the site of tumor called tumor-infiltrating lymphocytes. We get those cells from resection of the tumor. We then expand them ex vivo and rejuvenate those cells. We develop billions of cells. We then bring those cells back to the patient subsequent to lymphodepletion. And then we follow those -- the cell infusion with administration of IL-2 to assure that these cells survive and proliferate. This is, of course, a very personalized therapy. It's an autologous cell therapy. It is a onetime treatment, and it is using patient's own immune system after amplification of rejuvenation. On Slide 7, we show the mechanism of action for TIL therapy. Subsequent to infusion of TIL into the patient, the TIL is in circulation. It detects the tumor from the chemokines that are presented through from the tumor, and it leaves the capillary to come to the site of tumor. At the site of the tumor, it recognizes, The TILs recognize the tumor. Recall they came from the tumor, so they have some degree of recognition of the tumor. And upon recognition of TCR or T cell receptor with the MHC, there is a process by which TIL gets activated and starts the tumor-killing process by production of Interferon-gamma, granzyme B and perforins. And ultimately, the tumor cell is killed and destroyed. Moving to Slide 8. We are showing what the manufacturing process looks like in the bottom of this slide. And on the top of this slide is the patient journey. When the patient comes into particularly in a clinical setting, the patient is consented. They are then undergoing a resection on step 2, where about a centimeter or so cube of the tumor is removed, and it's shipped to our manufacturing facility. The tumor may be removed from various different organs or tissues and maybe from skin, lymph node, liver, lung or otherwise. And once the tumor arrives at our manufacturing facility, it is fragmented. It's placed in media, and the process of expansion is initiated. That process is a 10-day process -- or 22-day process, 2 steps of 11 days each. And at the end of the 22 days, we have billions of cells, which we harvest, we wash, we place an infusion bag, and Iovance is ready for infusion. Going back to where the patient was, once the patient was resected, they went home. They were dismissed and they go home. They come back upon their availability as well as the hospital's availability. And the patient undergoes what is called a nonmyeloablative lymphodepletion procedure of about 7 days, where cyclophosphamide and fludarabine is administered. And this process is expected to remove that hostile microenvironment that is present at the site of tumor and is not allowing for the TIL to do their job. After the 7 days of lymphodepletion is complete, we infuse them with TIL. This is step 4 at the top of the graph. And then we follow with administration of IL-2, which is up to 6 doses. And that's about a 2- to 3-day process subsequent to TIL infusion. And once the adverse events for the patient are resolved, they are discharged from the hospital. The process itself, as I noted before, is a onetime treatment administration. Moving to Slide 9. We currently are using CDMOs for manufacturing our product. However, we also are building our own manufacturing facility, the ICTC. It is located in Navy Yard in Philadelphia, in Pennsylvania. The facility is 136,000 square feet, and Iovance has made rather significant investments to building the facility. We expect rather a significant cost reduction in the commercial landscape having our own facility. First set of clean rooms, in fact, have been completed, and we anticipate to start our clinical manufacturing in 2021 and commercial manufacturing in 2022. We are on schedule for these milestones. On Slide 10, a few pictures of the inside of the facility is shown. The clean rooms are shown. You can see that the equipment are in the room. And as I noted before, they are ready for -- they're getting ready for clinical manufacturing process and submission of the information to the FDA in anticipation for that in 2021. On Slide 11, we show our intellectual property landscape at a high level. We have IP around various aspects of TIL therapy. It includes the tumor source itself where it could be from tumor, it could be from marrow-infiltrating lymphocytes, it could be from PBLs, peripheral blood lymphocytes, it could be a tumor that is frozen or it could be remnant TIL, for example, that is obtained from a digest process. The product itself, the process of manufacturing Gen 2, Gen 3, use of co-stimulants, selection of TILs, stable or genetic -- stable or transient genetic modifications are all part of our intellectual property portfolio. Combination of TIL plus anti-PD-1 as well as various patients of populations have all been claimed in addition to the fact that we have IL-2 variants and regimens that we have considered as part of our IP landscape. In all, as of now, we have 20 granted or allowed U.S. and international patents. Composition of matter for TIL product has been claimed as well as the method of treatment in a broad range of cancers. Moving on Slide 12. Just thinking about sort of the potential market for this therapy, 90% of cancers are in fact solid tumors. On the left-hand side, we are showing that 1.6 cases million cases of solid tumor is developed, unfortunately, a year in just U.S. The indication specifics that we are pursuing, including melanoma, cervical, non-small cells, so lung indications as well as head and neck in terms of the number of new cases and the deaths are highlighted here. And you can see that it is a very large market possibility that is still in need of additional therapeutics to be developed although checkpoint therapy has certainly made a huge impact in treatment of patients with solid tumors. On Slide 13, we show our pipeline. As I had noted before, in melanoma, we have completed our pivotal patient enrollment. In cervical cancer, we have finished our pivotal patient enrollment, and now we are closing enrollment in Cohort 2. Head and neck has completed enrollment as well. Our basket study, which now is expanding, is shown as IOV-COM-202. IOV-LUN-202 is just beginning. It is in non-small cell lung cancer registration directed study. And we have a program in CLL that had been started early part of last year. And the bottom of the pipeline, we're showing our collaborative studies with MD Anderson, for example, as well as one that we have been conducting with Moffitt Cancer Center in TIL plus nivolumab in non-small cell lung cancer. Moving into metastatic melanoma, which is our lead indication. Moving to Slide 15. In terms of the disease facts, there's 309,000 new cases still diagnosed annually, and 62,000 patients unfortunately die. In U.S., about 100,000 patients are diagnosed annually and 7,000 patients die. In terms of available therapies, frontline has been fairly well established as immunotherapy. And if the patient has a BRAF mutation, BRAF/MEK is typically given as a next line of therapy. And by third-line, in patients that have a BRAF mutation or sometimes second-line in patients that have no BRAF mutation, they're BRAF wild type, the patients start running out of therapeutic options. And they may have to be treated with chemotherapy. For these patients, chemotherapy offers an overall response rate of 4% to 10%. OS for these patients typically is around 7 to 8 months. So in the study that we are showing on Slide 16, the C-144-01 study, we enrolled patients that are unresectable metastatic melanoma with one prior systemic therapy, we defined them as patients who had received prior anti-PD-1 and if they had a BRAF mutation, then a BRAF/MEK. Our Cohort 1 was using Generation 1 non-cryo preserved TIL product. Our Cohorts 2 and 4 have enrolled the same patient population noted on the left-hand side of this graph, and they have used the exact same manufacturing product called Gen 2. Our Cohort 2 data is what I will be showing today. The cohort was expected to enroll 60 patients. We had slightly overenrolled at 66 patients, and so I will show you that data. Our Cohort 3 allows for opportunity for retreatment for patients should they choose to do that. From a melanoma perspective, from a regulatory side, we had an RMAT designation, we have an orphan drug designation and a fast track designation from FDA for metastatic melanoma. And we completed an enrollment into pivotal Cohort 4 in early part of 2020 as I have noted previously. On Slide 17, the patient characteristics of Cohort 2 is shown here. 66 patients were dosed and are shown on this slide. I would draw your attention to a few items only on specifically, for example, prior therapies, where we are showing that 100% of these patients had received prior anti-PD-1, 80% had received prior anti-CTLA-4 and 23% had received prior BRAF/MEK. More importantly, not only they had received these therapies, but they had progressed on them. In case of anti-PD-1, 99% of the patients have progressed on anti-PD-1; 80 -- about 80% have progressed on anti-CTLA-4. And then what is also remarkable, maybe on the right-hand side of the table, I'll just highlight a couple of items. Baseline LDH, the median is around 244. About 40% of the patients have elevated LDH when we look at 1 to 2x or over 2x upper limit of normal. Some of the diameters for target lesions only was 106 millimeters. So this is a fairly advanced patient population with bulky disease at baseline. And about 80% of the patients had over 3 lesions, so highly metastatic setting for these patients of [indiscernible]. Moving on Slide 18. Adverse events over time is shown on the left-hand side of this slide. And on the right-hand side, we are seeing treatment-emergent adverse events. On the left-hand side, as one would expect, adverse event over time is signature of a onetime treatment. You can see that the patients are having adverse events on the left-hand side up to around maybe day 10 or day 14. And once they are released and adverse events are released -- are resolved, there's very little that's happening all the way out to month 20. On the right-hand side, treatment-emergent adverse events that are over 30% are shown here. Bulk of adverse events are associated with lymphodepletion as well as IL-2 and sort of considered expected, so to speak. The median number of IL-2 doses that were administered for patients was in fact 6, and this is very much sort of indication that most of the patients are tolerating up to 6 doses of IL-2 just fine. On Slide 19, we are showing the efficacy data. As you can see, among the 66 patients, there were 24 responders, 2 of these patients were complete response and 22 were partial response. What is noteworthy here is also disease control rate of 80%. And the reason this is important is recall the patients were all in progression. So disease control, which includes stable disease perhaps could be a meaningful clinical response as well. I had noted previously, and I'll just highlight again that median duration of response has not been reached at 28.1 months of study follow-up, and this is as of a mid-December data cutoff. Mean number of doses of TIL that was administered for this patient population was 27 billion cells. On Slide 20, we are showing a swim lane of the response on the right-hand side, which you can see is time to response is fairly quick. At around first assessment, you can see a response. And the response may deepen over time. A stable disease can turn into a PR, and a PR can turn into a CR over time. On the left-hand side, we are showing the best response on prior anti-PD-1 or anti-CTLA-4 and the PD-L1 status of the patients. And what is noteworthy is that many of the patients, in fact, have had a PD as the best response in prior anti-PD-1 and certainly have seen prior anti-CTLA-4 and may or may not have responded to that therapy as well. On Slide 21, we're showing the waterfall data from this cohort. What is noteworthy is, again, that the responses are deep. The patients with a star on the bars are patients who had a BRAF mutation, and it does not appear that there is a particular correlation with BRAF mutation in response. To summarize, in metastatic melanoma, in our Cohort 2, we saw a 36.4% overall response rate and 80.3% disease control rate. Median duration of response has not been reached at 28 months of study follow-up. This is as of December of 2020. Responses do seem to be deepening over time, and we are certainly encouraged by the data we see in terms of potential therapeutic option for lifileucel in late-line metastatic melanoma patients. Moving to Slide 23. I will be turning our attention to head and neck and non-small cell. Slide 24 shows a graph of the basket study so-called, that we are conducting. It's called IOV-COM-202. The first 3 cohorts are metastatic melanoma, fourth cohort is in head and neck, and the last 3 cohorts are non-small cell lung cancer. We had shown data for head and neck, which is Cohort 2A at SITC, and we will review some of that data here today. There is a few new cohorts, Cohort 1C, which will administer Gen 3 in the patients that were in the same patient population as we have administered Gen 2 before is added as, well as Cohort 3C, which is patients with one prior systemic therapy in non-small cell lung cancer, and we will be administering TIL plus ipi/nivo. Moving to Slide 26. In head and neck, just to remind ourselves, this still remains quite an unmet medical need. 890,000 cases are diagnosed annually, and 507,000 patients unfortunately die annually, globally. In U.S., we see 66,000 new cases and with 15,000 patients dying annually as well. In frontline, per NCCN, a number of therapies are available. A single-agent checkpoint would offer a 16% response rate; a chemoimmunotherapy combination will allow for a 36% response rate; and a chemotherapy -- in the front line, specifically EXTREME, the regimen called EXTREME offers 36% response rate with 5.6 months of median duration of response. In second line, the patients may receive anti-PD-1 antibody with an expected response rate of 16% with an 8 months of median duration of response. So that's similar to patients that we would -- we are enrolling in our Cohort 2A. On Slide 27, I'm showing the response data that we had showed at SITC 2020. On the left-hand side, we are showing the waterfall, on the right-hand side is the swim lane. The overall response rate was 44%. Among 9 patients that were administered TIL, 8 patients were evaluable for response. 4 responders were among the 9 patients, one of which was a CR. And on the right-hand side, we can see that the same signature, that stable disease can turn into a PR, the PR can turn into a CR over time can be seen. In the middle of the graph, we are also showing PD-L1 status of the patients, 3 of which were PD-L1 with CPS score of over 20 and one of them was less than 20, although it was more than one. We certainly are highly encouraged with what we're seeing in head and neck. And this is why we expanded the Cohort 2A in our basket study to include additional patients to see what the ultimate final response rate and median duration of response may be. Moving to Slide 30. I will be turning my attention to non-small cell lung cancer. This is an indication that is quite large, globally as well as in U.S. I'll just stay focused on U.S. here. 229,000 cases are diagnosed annually in U.S., and 136,000 patients still die a year, quite an unmet medical need despite the fact that we have developed excellent therapies; anti-PD-1s have been really revolutionary in treatment of these patients. In frontline, of course, chemoimmunotherapy is fairly commonly used as well as immunotherapy and maybe even chemotherapy can be administered. Ultimately, the patients become unmet medical need by second or third line, and their available therapy becomes docetaxel in second line typically, with an expected overall response rate of around 9%. And so that's our benchmark in terms of what is available for patients we are enrolling in LUN-202. The data that we are looking at on Slide 30 was presented through Moffitt Cancer Center. This is a collaboration we had with Moffitt Cancer Center, where they had enrolled patients that were PD-1 naive. They were resected for their tumor. They were then administered nivolumab, and upon progression, TIL was administered to those patients and nivo continued until progression or, I think, some defined time afterwards. On the left-hand side, you're looking at the waterfall where 2 CRs -- there's 2 CRs on the right-hand side. You can see they are continuing at 12 months. There was one PR, which the patient progressed at 18 months, with an overall response rate of 25% in this patient population. And again, it was highly encouraging for us. Once we saw this proof of concept, we have initiated a broader lung cancer program at Iovance. This specific study that is noted on Slide 31 is IOV-LUN-202. This study allows for patients that have a TPS score of less than 1 or over 1 to be enrolled in Cohorts 1 or 2. The patient population is shown on the left-hand side. There are metastatic patients who have progressed on a prior chemoimmunotherapy as prior therapy. Cohort 3 is more of an exploratory cohort with core biopsy and Gen 3 manufacturing, and Cohort 4 allows for retreatment. This study is just in process of activation, and we have 2 sites active, but we have not started patient dosing in this study. Slide 32 is showing our research focus on next generation of TIL products. We continue our focus on the sort of package of what goes with TIL therapy, including analogs of IL-2. We have a product IOV-3001, which is an IL-2 analog, which was licensed from Novartis. And we expect to be an IND-enabling studies in 2021. We are looking to select more potent TILs through a selection process, which is proprietary work that Iovance has been undertaking. We also have a collaboration on that front. We continue looking at TIL for genetic modification through a talent technology. We have a collaboration with Cellectis and focusing on this type of genetic modification. And we continue with our process optimization through use of, for example, core biopsy or Gen 3 manufacturing process. I will now turn the microphone to Jean-Marc to talk about our corporate infrastructure. Jean-Marc?

Thank you, Maria, and good morning, everyone. My name is Jean-Marc Bellemin. I'm the Chief Financial Officer of Iovance. So first, let me briefly present to you Iovance's footprint, and let's go to Slide 33. We have currently roughly 250 employees, who are located in 3 different sites in the U.S. First, we have our headquarter located in the Bay Area in San Carlos, California. Then on the East Coast, we have a manufacturing commercial facility called ICTC, Iovance Cell Therapy Center, previously described to you by Maria, which is located in Navy Yard, Philadelphia. We have also a research facility in Tampa, Florida. Finally, we have established a business office in Zrich, Switzerland as our first European footprint. I also would like to point out to you on this slide, the high level of skilled employee we have at Iovance. As you can see, we are mentioning that over 76% of our employees have at least 1 year of cell therapy experience. Next slide, Slide 34, is about our financials. Iovance has a strong balance sheet position with close to $720 million of cash or cash equivalent at the end of September 2020, and we have no debt. We also have publicly disclosed that we anticipate to close the year with a cash position above $630 million. This concludes our presentation, and Maria and I will be happy to answer any questions. Thank you.

Thank you, Jean-Marc. I do see a few questions, so I can read them and start addressing them. And if you have additional questions, please send them through. I have a question that says, when can we expect data from Cohort 4 in metastatic melanoma? Is there a potential for this to be at ASCO 2021? Thank you for the question. Typically, when we have agreement with FDA that a program is supportive of registration, we have put processes in place where we do not read the data either internally or disclose it publicly. So when we have agreement with FDA that the cohorts are ready for submission, we can certainly go ahead and read the data, and we will disclose it publicly. As of now, I cannot commit that, that could be done by ASCO. I don't know when the time frame would be. We continue our discussions with FDA, with -- as it pertains to potency assays. So that would be the driver as to when we might be able to read Cohort 4. There was one opportunity to read Cohort 4 in May of 2020, and that was in response to an FDA request to read the data. At the time, we had around 68 patients with 2 assessments, so we presented that data publicly, and we provided it back then. But since then, we have not continued to look at the data in any way. And the primary endpoint of this study is by IRC. And so that endpoint has not been read out yet. I have a second question that is asking, could you be more specific about when in 2021 do you expect to file with the FDA on metastatic melanoma? Yes, I wish we could be more specific. The discussion with FDA continues. We have been providing information to the agency. We don't have specific guidelines from them as to when they would be ready to receive the BLA. So the timing of submission cannot be further clarified until the agency gets around reviewing what we have submitted to them, as well as at that same point in time, we can read our Cohort 4 as well. So the 2 are very much related. I have another question that says, do you expect that TIL therapy will always be followed by IL-2? Or is there a potential to develop TIL without IL-2? That's a great question, actually. The reason IL-2 is administered is fairly historical, it's based on Steve Rosenberg's data. Steve Rosenberg, who, by the way, is the innovator around TIL therapy, and we licensed the technology from him, did do an early study where he did not administer IL-2. And he saw a diminishing response when IL-2 was not on board. Now the patient population that he was investigating was early-line patients as well as patients that -- it's not today's patient population. The sample size that he had used was fairly small as well. So it appears that IL-2 is important in survival and thriving of the T cells that are infused into the patient. I think, maybe I can answer the question a little bit differently, that I probably would not want to completely remove IL-2 from the regimen. But there are other analogs of IL-2, including one that we ourselves have licensed, as I noted, from Novartis, IOV-3001 is what we call that product. And these products are expected to have a different safety profile and different PK profile. And certainly, their CMC attributes are quite different. So perhaps a better approach would be to try alternative IL-2 analogs, to still stimulate IL-2 receptor but not have the same safety profile that is associated with aldesleukin, the IL-2 analog that is being used today. So that probably would be my approach to how to administer IL-2. I have -- yes, thank you. There's a last question that I see. It's can you comment on commercial readiness for TIL? Absolutely, we continue working very actively in preparing the market, for bringing TIL to market. There really is 2, maybe 3 sort of large work streams that we continue working on from our commercial side. Work stream number 1 is hospital preparation. These cell therapies are generally high touch, they're autologous. There's quite a bit that needs to happen at the hospitals. And so we continue engaging the various hospitals that we intend to commercialize our TIL therapy at those hospitals. We train those sites. We want to make sure that they understand how the product is going to come, how it's going to get administered. And we also want to understand the hospital infrastructure and how they're going to receive the product and assure that the right patient gets the product itself. So a significant amount of time is being spent in hospital preparation, understanding of the hospital's infrastructure and our working -- inner workings in terms of the cell orchestration. We have a platform called Iovance Cares, which is a platform where the hospital has visibility to what is happening to the patient's product, the manufacturing facility does, Iovance does and our payer system sort of connects through to that Iovance Cares infrastructure. So a lot is happening on that front as a matter of fact. In terms of the second work stream that we work on is the payers, the payers involved, the commercial payers. We, of course, are educating them in terms of TIL therapy, what the product means and what the patient population is that it could address, how it could impact the outcome of the patients that is being -- that are being treated. We also work very closely with -- we have been talking to CMS, the Medicare and Medicaid supporting body for well over a year. And we have presented before Medicare multiple times at this point. So this is very much something that we continue working with and want to make sure that the payers are aware of TIL coming into the market. And then the third avenue, which is something we still continue working on is working with various trade groups and government affairs to assure that there's an understanding of the patient population, again, on the use of this type of cell therapy specifically, and the positioning of the product. So there's quite a bit that is happening in the commercial readiness landscape for the TIL to come to market. There actually is additional questions. So if you don't mind, we have a few more minutes. I'll just take a few as much as we have as time. I see that there is -- last question is what is the difference between Gen 2 and Gen 3? Gen 2 is a 22-day manufacturing process; Gen 3 is a 16-day manufacturing process. We haven't disclosed the details of what exactly did we do to go from Gen 2 to Gen 3. Maybe I'll just help with Gen 2. The initial goal was to stay very close to Steve Rosenberg's process. The goal was not to change the process in any way. We were not sure if the process has tolerability for being modified and whether clinical responses may be affected. For Gen 3, however, that wasn't the goal. The goal was how short can we make it, how robust can we make the process? And so we were able to shorten the process to 16-day fairly comfortably. So that's sort of the big-picture difference between them. The expectation around COGS is that COGS for Gen 3 is, of course, lower than Gen 2. Let me see additional questions are -- right, very good question. There's a question about IOV-3001, the product that we have licensed from Novartis. The question is asking, is the end goal for IOV-3001 to replace Proleukin in metastatic melanoma? Would you have to run another trial for metastatic melanoma to switch out to IOV-3001? So this is a preclinical program as I had noted. We hope to be in IND-enabling activities in 2021. The hope over time is the IOV-3001 may be a better IL-2 analog. Exactly what is the clinical program, we have not disclosed. And I think some of that has to do with our own understanding of the behavior of IOV-3001. It is an early-stage compound. We certainly have not engaged FDA to have a discussion with their vision. We're also -- from a precedent perspective, we're in somewhat of an unknown territory in the fact that you're switching a component of the regimen. So exactly what is going to be required to bring that type of a compound or that type of a regimen with IOV-3001 into the market, we have not laid that out quite yet. It will be dependent on some of the data we are generating in 2021 and a potential -- some type of a pre-IND discussion with FDA. So once we have that information, we can share publicly. Could you please comment -- the next question I have is, could you please comment on the competitive landscape? And how do you differentiate? In -- sorry, I had to shorten our corporate deck for this presentation, given we had limited amount of time. In our full corporate deck that is on our website, we have a competitive landscape slide for melanoma and cervical. If I can ask the person who's asking the question to take a look at that slide, and again, we only have so much space. So not every single competitor is listed, but the ones that are closest and furthest in development are listed in those slides. Please take a look, and we're happy to answer any further questions if you might have any. The timing of data from lung update, we have not disclosed or committed to specific data flow for lung. I do highlight that we have 2 cohorts that are ongoing in our basket study. Cohort 3A is PD-1, PD-L1 naive patients. And that's a little harder to enroll. Cohort 3B is relapsed/refractory patient population. And those patients are particularly difficult to treat because they have very short life expectancy of maybe 3 to 6 months at most. So we have found that they're not particularly easy to keep alive, unfortunately, and be able for them to receive TIL and then yield the data points. But as soon as we have any information that is worth presenting, we certainly would be happy to provide lung update on data. I don't see any additional questions. If Jean-Marc or [ Chris ] see additional questions, please let me know. Otherwise, I know we only have about a minute left. I see one more question. As soon as I see it, I'll read it. So here's the question. CAR-T hematology launch has been disappointing. How confident are you about long-term market opportunities for solid tumor? Gosh, that may not be a 1-minute response. I'll do my best. I do think -- I just want to make sure that we put various variables in perspective. CAR-T products that have come to market are, from a response perspective, have been outstanding. These are really life-changing therapies for patients who would have been out of options. So it's not the clinical response that has been the issue. There's been other issues around their launches. And I agree with the person who's asking the question that there has been challenges. Some of the challenges have been logistics, some of it has been -- to do with how well the hospitals are prepared to receive the products, how well the payers have been ready to reimburse for the products. And a previous person asked the question, how are we preparing the market? We actually did learn a thing or 2 from the CAR-T product launches, and this is why we are targeting well over 40 sites for our initial launch. We are preparing these hospitals very closely. We work with our payers as well as CMS to ensure that the payer landscape is much more favorable than when CAR-Ts came to market. So I think there are things that are addressable, certainly. And I think that we have learned from the frontrunner CAR-T therapies, how to make sure that we address the market a bit more proactively before the products come to market. And just to defend, as a last sort of piece of my opinion, the CAR-T products is a story of success. They came to market very quickly, and so there was not a lot of time for the payers to get ready, for the hospitals to get ready. We now have had a few years under our belts in terms of the hospitals' understanding of how to address cell therapies and how the payers would reimburse for these products. So we're very optimistic. We think that solid tumor is a very broad landscape. There's a large unmet medical need, and I'm very encouraged with the data we see in metastatic melanoma in terms of duration of response for a onetime treatment. With that, I thank you for your time, and I know we are out of time and out of questions. So have a great day.

Thank you.