Welcome again, everyone, to the first day of TD Cowen's 44th annual health care conference. My name is Tyler Van Buren, and for this next session we have a fireside chat with Iovance. It's my pleasure to introduce Fred Vogt, CEO, Jean-Marc Bellemin, CFO, and Peter Prieto, Senior Vice President of Medical Affairs. Fred, Jean-Marc, Peter, thank you very much for being here. Yeah, thank you for having us. Before I get started, if you guys have questions in the audience, feel free to raise your hand or speak up. But let's go ahead and start with Amtagvi in melanoma. Less than a month ago, you guys received approval in second line plus melanoma with a very favorable label and a $515,000 price tag. During earnings, just very recently, you announced that 20 patients are in process and 10 are scheduled or pending manufacturing slots. So can you? Are you willing to provide an update of patients today? Well, it changes literally hourly, so it's kind of hard to provide an update. It's gone up significantly since then, I can tell you that. It's really going well. The launch is going well. People are very excited about this drug. You can see that all over social media. Anybody that any of the investors that follow social media can see just how much is going on there. So we're very, very bullish about this right now. We're just trying to make sure we get everybody scheduled as fast as we can. There was an article, I think, over the weekend from Precision Oncology that talked about the bolus, the backlog at one center, Orlando Health, and the investigator mentioned what was it, 12 or 13, I think, patients. Only very few of those are actually scheduled right now. So that's the bolus that's coming that we've been talking about. Just one site's example of that. With 30, it gets big really fast, and then we're going to be going to 50 within 3 months. Sounds great. Are you guys in terms of ATCs, are you guys above that 30 number, and you plan on giving an update? It's obviously a fluid number that's changing every day, right? It's a fluid number. Yeah. We'll probably give an update at the first quarter earnings call along with an update on where we are in terms of number of patients that have been resected or in manufacturing and what we expect ultimately the second quarter to look like. Although we're not going to be able to guide the results, at least we can give some picture of what the patient flow looks like. Okay. Sounds good. On the approval and the earnings call, you talked about the process of the patient flow, starting with the tumor board and then moving to resection and manufacturing and then infusion, which leads to obviously you guys recognizing revenue. Maybe for those who are less familiar with it, you could give a brief overview of that. Of revenue recognition? Yeah, just the process once a patient comes in of treatment all the way to when revenue is recognized. Yeah. So when the patient comes in, I mean, you will have surgery, then the sample will be sent to our manufacturing site, iCTC. It's a 22-day process. And we are sending back Amtagvi to the hospital, which will be infused, and the revenue will happen at the time of infusion. So that's why we've said we just had the first patient at the end of February, so don't expect revenue in Q1. Most of the revenues will be for sure in Q2. Okay. You mentioned that iCTC has started manufacturing commercial product. Obviously, tumors have been resected. In process for those 20 patients, what exactly does in process mean? I can take that. So what that meant when we said 20 patients are somewhere in the flow, in the process of coming into our therapy, right? So they've been identified to us as a patient. The site's going to schedule them pretty soon. Some of them were scheduled. 10 of them, like we said at the call, were scheduled. But that just means the sites have identified the patients. We know about them. They're coming. They're working on financial clearance and stuff like that before they come in. That number's gone up significantly, too, since the announcement. We're not at 3 weeks yet. We'll be 3 weeks this Friday from the approval. So still early days, but really looking very promising. Yeah, gone up significantly sounds awesome. I guess on the call, when I asked you about the 20 patients, whether that was a majority of the bolus or a tiny fraction or a fraction, you said it was a tiny fraction. And are you referring to a tiny fraction, just to clarify, of the bolus at these ATCs or of the addressable patient population? Of the bolus. Yeah. Okay. Awesome. All right. And then I guess payers. You guys have said you have engagement with payers covering 90% of lives. When do you expect coverage to catch up, potentially to 80%-90% levels? Yeah. No, we do anticipate, actually, very strong coverage and reimbursement for Amtagvi. We have seen from the early days that the experience that the ATCs benefit from their CAR-T experience to get the process running in parallel. So the patient can get in and get the prior authorization, single case agreement. But we do expect to have the coverage policy done at most of the payer between 90-180 days. That's what we said. So strong coverage. I want also to highlight that 75% of our patients will be either commercial or will be IPPS exempt at the hospital. So the cost will be charged will be at full cost, or they will also be insured through Medicare Advantage plan. Again, same thing, billed at almost full cost. Yeah. I get a lot of questions or have gotten a fair number from clients on the DRG code. I guess they don't necessarily appreciate that that's actually quite a small fraction of the total patients you plan to treat. Yeah, 27%. So it's really a small portion of the patients that will go with the DRG 18 coding. Okay. And when you mentioned on the approval call that you would expect significant revenue in Q2, got some questions from clients asking what significant means. So, curious if you have anything to add to that. Yeah. That'll be the first real revenue for Amtagvi, and there'll probably be some Proleukin revenue in there, too. So I would say the first time you're going to see real numbers from the launch for Amtagvi. If your launch curve is doing this, it's going to be right at the start of the launch curve. Still significant numbers, though, because this is at that point, the rate we're going, we could have a very good number of patients at that time. You can see the rate right now is quite high, and it's only accelerating. Wonderful. And when you talk about the launch curve, how do you expect that to progress over the course of the year? A normal launch curve, this is going to have a little bit of a bolus, I think, but then we're going to have a second launch curve superimposed on it as the additional 20 ATCs come up a couple of months in. So you'll see kind of a curve that does this, if you will, and then ultimately steadies out at some kind of rate. That's what I anticipate, at least. Great. And how big of an opportunity do you believe second-line melanoma is for Amtagvi over the long run? So I mean, I'm joining what Fred just said. If you think about the curve, we have 8,000 deaths in melanoma every year in the U.S. There is 6,700 patients being treated in second line melanoma. So we have a huge opportunity there. It's a high unmet need, of course, so patients are waiting. Amtagvi will be the only approved drug in this setting for quite some time. So we should see a nice curve there. And remember, this, I mean, TIL. Patients have waited decades for TIL. Proleukin, obviously a complementary product. How big do you think that could be over time? So what we like to comment on Proleukin, first of all, is, of course, it's part of the Amtagvi treatment regimen, so it will be given to the patient. The patient will receive six doses of Proleukin, which is 18 vials at the WAC price of $5,551 exactly. So roughly $100,000 per patient. So it's quite nice, significant revenue we could get from Proleukin. We are just careful about how much inventory is still in the channel. So we'll see how much Proleukin will contribute to the revenue second, third, fourth quarter this year. We want to see that. But definitely, $100,000 per patient is a nice number. Sorry, inventory in the channel, so. Yeah. So before we acquired the asset from Clinigen, obviously, there was inventory buildup in the U.S., and we don't have control over that, so we don't know how much is out there. There's a benefit to sell as much as possible before we acquire it. Yeah. Good for them. So it's going to take maybe a few months to get through that. It's already coming. Yeah. They couldn't sell anywhere near what they wanted to. Got it. Interesting. So you're preparing for MAA and additional ex-US submissions. And you said on the call in response to the question that you're not planning on partnering now. I believe you said it could potentially dilute the value of the asset. So curious to hear you just follow up on that. I mean, obviously, it could be maintaining optionality for potential acquisition, but if you're filing now, you don't have to do anything now, right? You could do something a little bit closer to launch. But you guys aren't actually curious to get your thoughts on that comment and then also the potential for you guys to actually launch ex-US. Yeah. So right now, in the geographies we're targeting, we feel like we can do these ourselves. We're very conscious of equity dilution, of course, but worse to us is asset dilution. So if we go and we partner with somebody in Europe or something like that, you're potentially giving up a significant portion of the value, and you're effectively putting a ceiling on the value of the asset, which is not appealing to a potential acquirer at some point. It's a general rule. So we're very much focused on owning our asset. We have the scale to do it. We have the manufacturing scale. It's not like we need somebody. Putting a commercial team, medical affairs team, and so on in Europe is not that difficult to do. Putting one in Australia, Canada, all these places is not that difficult. We can do it. We can manufacture from the United States for now. So we're very comfortable with going ourselves for now. Yes, years from now. We're always open to ideas. Years from now, things could change, but right now, we're sticking to our normal philosophy. Okay. And with the existing cash on hand, do you think that is enough to get you guys through profitability, or how do you think about the runway? Yeah. I think it's a little bit premature to talk about profitability or break even. I want to have a few quarters in hand of revenue to be able to talk about that, and we'll talk about that. Now, having said that, from a cash perspective, we just raise additional dollar. We have enough cash until well into second half of 2025. So we are well capitalized at the moment, strong balance sheet. We don't need to do anything. If we have to do something to bridge with the break even or profitability, then we'll do certainly, but opportunistically at the right price for the shareholders. Okay. I want to ask about the TILVANCE-301 trial. So the phase 3 confirmatory trial, frontline melanoma. When can we expect enrollment completion and a potential top line readout? What's the rough timeline for that? And then also, what do they need to show on the response rate or PFS endpoint for approval, or what do you need to show? Yeah. So TILVANCE remains accruing. Remember, this was designed to support full approval based on dual primary endpoint of ORR and PFS, with the possibility of accelerated approval on ORR and conversion to full approval with PFS. It's a global, multi-center randomized trial, so it's a little premature to comment on enrollment completion or data timelines. But that being said, we anticipate interim analysis of ORR and the possibility we feel that this would probably be quite favorable to, again, facilitate accelerated approval. Based on enrollment, we can expect maybe to see some of that in 2026, but we may have more to comment on in 2025. In terms of benchmark, if you look at Pembro, at about 33%, Ipi/Nivo 50, Rela/Nivo 43. Again, when we presented at our SITC about two years ago in our COM202 trial, patients with metastatic melanoma that were immune checkpoint naive response rates of north of 60%. So we feel we're very competitive in that space. Okay. And as we think about the front line, I mean, obviously, in the second line, these patients are largely out of options, and the options that they have are lacking, which is why you guys are seeing strong early uptake. But this is a process that patients have to undergo, and it's a different value proposition than the front line, or there's different considerations. So I'm assuming you guys don't expect to treat the entire front line with the combination. So what would your ideal patient population in the front line be? The ideal patient population will be those that have tumors that, again, can be resectable, that really have the opportunity to use this therapy, which is a one-time treatment. It's a living treatment that has, unlike other treatments, a real potential chance for long-term durability. Remember, in our deck, we have a drug-treated population slide in there. In the front line, it's about 10,000 patients a year in the United States. That market is moving to consolidate around ipi/nivo and Opdualag. Right now, there's some single agent use still in the United States, and there's still BRAF/MEK, which is all moving late. So we could capture, potentially, in a bullish scenario, a third of that market, which would be 3,000-plus patients a year, just added on front line and maybe even more. Yeah. That'd be great. Any questions on melanoma before we move to lung cancer from the audience? Do you guys have a target gross margin that you're looking for? Because that's one of the concerns, right, the high cost and. I'll repeat it. So yeah. So you asked if we have a target gross margin. Internally, we do, and it looks a lot like what Big Pharma would appreciate. So that's probably the best I can tell you right now. All right. We'll move to lung cancer. So this morning, you announced that the partial clinical hold for LUN202 has been lifted by the FDA. Great timing. Maybe you could explain any protocol changes or next steps. Yeah. So the FDA lifted the clinical hold. We're very pleased. They were very collaborative, working with us to get to spec the patients quickly. There's lung patients waiting right now for this. Primarily, like we said, there was a focus around one single case that they were interested in in particular, and it's been largely focused around the lymphodepletion that we use and some of the risks that come with the lymphodepletion. So the solution to this is going to be to soften that a bit. We've already allowed that as an option in that study and other studies. We'll focus on that and some additional monitoring of the patients as well for cardiopulmonary function. That's pretty much what's going on. So we do have to push a protocol amendment through, as you normally do in a trial. The United States can take a few weeks. Outside the United States, it can take two months. We'll push that through as quick as we can. Be back up and running very quickly, and I think the study will and then we'll be able to say more at some point about the target completion. Right now, we said 2025 for now. We'll refine that. Softening the lymphodepletion regimen, that means bringing the doses down or doing one less dose or extending the interval between doses? No. We talked about this before, actually, but I'll recap it for everybody. We're basically cutting the dose of cyclophosphamide and fludarabine from 60 mg per kg twice to 30 mg per kg twice. We've already done this. A lot of people have done this. This is all out in the literature. We don't do this in melanoma. We give them the full dose. That's more historical, but this reduced dose cuts down a lot of the toxicities and makes it a little bit easier for the lung patients who are really, really ill with very poor lung function. The fludarabine dose stays the same. Do you expect that to have any potential impact on efficacy? No. No. All right. Is it possible that maybe when you go into earlier patients and earlier lines, that you go back to the melanoma dose? Yeah. Yeah. The FDA's clinical hold was focused solely on LUN202, not on Cohort 3A, for example, in front line and COM202. Got it. Okay. LUN202, there's Cohort 1 and 2. Maybe for everyone, you could briefly describe those cohorts and what you think the probability of success is in each one, if one is more likely to succeed than the other. Yeah. We think they're equally likely to succeed. We did that in the beginning because we were looking at the market. So we have one cohort that's PD-L1 negative, TPS score less than 1, and we have one cohort that's PD-L1 positive, TPS score greater than or equal to 1%. And that includes the one with 49% and 50% and greater that you see stratified in a lot of other studies. In the beginning, we weren't sure how we were going to do it, so we're just going to effectively combine those cohorts. We did discuss that with the FDA. They understand that if we could go back in time and run the study again, we would probably just run one cohort, but that's how we did it. But it's okay to have those separately. We don't anticipate any balance issues between them. Okay. I know you touched on this briefly, but you said that you expect the trial to wrap up next year, so we'll get data at some point next year from both cohorts. Well, so we originally expected to do this year. We pushed it. We just said in the quarter, the fiscal year 2023 call, we said 2025. We'll refine that at some point. I think the ultimate delay here is going to end up being something like 4-5 months, but I'm not sure yet. We have to do a little bit of work to see if that's the case. If that's the case, it will push us into the earlier part of 2025, but I can't say that for sure yet. Understood. What would you need to show in each of those cohorts for approval? I think if we have an ORR in the mid-20s and our durability remains very strong, and we reported durability recently on this study when the hold actually came out, we let everybody know that we had 71% of the patients still responding greater than six months. If you look at that compared to REVEL, it looks pretty good. REVEL had a median PFS that was very short in the four-month range, and they literally never published the DOR. FDA knows the DOR, but literally never published it, and it's not that great, we think. So we think with some good durability, mid-20s, one-time dosing, it's going to be a very competitive product, and it should meet the threshold for approval. Mid-20s regardless of TPS status in both cohorts? I think I don't see TPS status playing a big role in this. TILs respond in both areas. We've seen that across many different indications, so I don't view that as part of the approval at this point. Okay. Maybe you could just briefly describe the type of patients that you're enrolling in this trial, how many prior lines, how heavily pretreated they are? They have had prior chemo and prior PD-1, and they've progressed on those. So they're basically past where they're at the point now where there's no options. Okay. For the front line registrational trial in lung that aims to treat more as a maintenance and combo with IO following chemotherapy induction, can you give us a little bit of background on why you decided to do that trial and when the FDA discussions will conclude and when you could initiate it? Yeah. That study is built on the idea that we could combine chemo and checkpoint in the front line with TIL maintenance therapy, which means we would combine it's a way of combining TIL therapy with what's becoming standard of care in a front line setting. You would give the course 12 weeks of chemo, start checkpoint therapy, and then at the end of the chemo, you provide the TIL dose. Obviously, the chemo would be detrimental to the TILs, so we would not do that during that period. So you would effectively debulk, start them on the immuno-oncology agent, and then jump in with TILs and hopefully drive something like a major PFS benefit. I don't have any updates for you on the meeting on that right now. We'll come back later. We'll talk more. We were really focused on getting LUN202 back on track. Now that that's happening, we'll come back and talk more about our confirmatory strategy at some point. Okay. And that front line confirmatory trial, I mean, obviously, that could take longer than something like LUN202. So that's going to be potentially PFS and OS endpoints with maybe an accelerated look on PFS with OS confirmatory? Could be. Yeah. It could be. We'd have to talk to the FDA. We haven't done that yet. Okay. The first patient was treated with IOV-4001, the PD-1 inactivated TIL therapy, in the third quarter of 2022, I believe. So what's the latest there, and when might we get some of that data? So that study's running right now. FDA, with most of the at least probably all the gene-edited TIL products, as far as I know, is forcing us to do a safety run-in. That means we have to do each patient sequentially, wait for one patient to clear at one center before we can do anything else in parallel like a normal study. We think it should be off and running pretty soon, but we're just finishing that safety clearing right now. And that took a long time to get that done. Unfortunately, that's going to be a problem, I think, for everybody in the business. But hopefully, we'll have some data soon on that. That's a very promising product to have a PD-1 knockout in the TIL itself. Any other questions on lung cancer? All right. Can you talk about the other tumor types, cervical cancer? Obviously, there was a change of standard of care there, and you guys had to deal with that. Where are you in the process of developing in cervical cancer? Yeah. Cervical cancer, we have a trial running right now, C-145-04, but we are prioritizing endometrial at this point for our gynecological oncology program. The market is literally probably 12 x, 13 x the size. The cervical market has shrunk. It's become very competitive. So even though we know there's efficacy of TILs in this indication, we're really focused on endometrial at this point. Makes sense. Is there any preclinical or initial clinical data that makes you believe that it'll be more effective in endometrial versus cervical? I don't know if we'd say more effective, but we have preclinical data that we should talk about at some point this year. Okay. Any other tumor types or TILs that you guys are evaluating? Yeah. We're still interested in head and neck, and a TIL maintenance strategy like what we showed for non-small cell lung could work there. Again, it's chemo and checkpoint in the front line, so you could do a maintenance strategy there. We did have some good data in head and neck. The overall picture for TILs in the carcinomas is very strong. Anywhere you see a checkpoint response, TILs could potentially do better. So the sky is the limit for this. We just have to we just got approved, so we have to kind of industrialize this at massive scale now. The first time it's ever been done. And I think we could start to take on a lot of different solid tumors. You guys are obviously pioneers in the TIL space, and there's been other TIL companies that have kind of come and gone, and there's new ones popping up. But curious to just get your overall thoughts on the TIL space, the competitive landscape. I know you guys are way ahead, but are there any technologies emerging that you find particularly interesting or potentially competitive? Well, we're very interested right now in the gene knockouts in TILs, and we're very interested in tethering cytokines to TILs, so adding a cytokine booster like you see in the CAR-Ts. Particularly interested in IL-12, IL-15. We talk about that. I think you'll see more from us on that soon. We're trying to get those things into the clinic. Our competitors are all doing the same thing. The advantage of Iovance is we have the scale to do it and know how to do it. We've been through with the FDA. We know how to get these things approved now. We can manufacture on the scale of potentially in the future tens of thousands of patients right now. We've already spent the capital on that. We've built that. We've got a pretty to me at least, when I see a small company coming in, I kind of wish them well because they have a huge mountain to climb, whereas we're at the top of the mountain and can choose as much as different ski slopes to go down at this point. It's been quite a climb too over the years. Yeah. It's been quite a climb. Since you mentioned the manufacturing, I know you guys are past 2,000-patient capacity on your way to 5,000. Can you just talk about where you are in that process and when you guys could get to 5,000, and then beyond that, how you think about toggling that up further? Have you been to our facility for TILs? Yes. You have? Yeah. Okay. So within our facility, we can actually—it's called a butterfly design. You can actually flip mirror the design, and you may have seen it. Maybe some of your clients saw it too. But it's a big open-shell space, and we can build in that space. That is already underway. We've already started doing that, so we can double the size of that facility very quickly internally. And from there, it's basically hiring and qualifying the facility, which is straightforward stuff. At the end, we do have to make some filings with the FDA, but we've become pretty good at that, so we think we'll be comfortable with it. And then we're at 5,000. But that's, again, hiring, expanding, qualifying, and getting things ready there. Okay. In business development, we touched upon maintaining, obviously, the rights to Amtagvi, at least in the near term. What other sort of business development activity do you guys anticipate? What's your focus moving forward, at least for the year? So we'll have to see how the market goes this year, but M&A is always a possibility with Iovance. Obviously, in a company in this position, it is relatively attractive to big pharma. Sort of the more general BD that we do, we're always looking to license in new ideas, new technology. We did licenses repeatedly with NCI. We work very closely with Steve Rosenberg's group. Peter actually came from Steve's group many years ago. So we've got an in-house team that knows him very well. We want to continue to collaborate. He's at the cutting edge of getting TILs into all the common epithelial cancers, the carcinomas, basically, and we go beyond that. We're even in the sarcomas and stuff too. So we're always looking for opportunities to bring stuff in that could help with that. I think you'll see more in-licensing from us at some point on the lower end BD. At the big level, there's always that possibility of the buyout. Yeah. Yeah. Yeah. The tip of the iceberg, really. I think that 90% of patients that die of cancer in this country are solid tumor. So you're going to see, as I like to say, rapid expansion of our indication, so. Yeah. I mean, when you think about larger groups that'd be interested in you guys, clearly, this is a unique manufacturing process, right, that you guys have invented, pioneered, built out. So it's not like someone who's in CAR-T for liquid tumors. There wouldn't really be synergy there, right? Obviously, anyone in oncology could potentially be interested. I guess, obviously, there's synergy with IO that you guys are exploring. Any comments on what type of company you think this platform would fit best with? I'll give you one example. It was in the news last week. So Pfizer came out and said they're going to increase their percentage of biologics in their oncology pipeline from some low numbers, some high. I can't remember the numbers. Apparently, they're very reliant on small molecules, which I love, by the way, but I used to do that. But biologics have more IP protection around them, more favorability legally to protect the exclusivity. And in the space of Iovance, with our type of product, we don't have the IRA cliff either. So you got a very complex biologic. You got patent protection. It could potentially be out in 2042. You've got 12 years of regulatory exclusivity right out of the gate. Huge moat around the company to do this kind of stuff, manufacturing. That can be very attractive for big pharma when you've got billions of dollars of revenue coming. I mean, will anyone ever be able to biosimilarize Amtagvi? I mean, unless you guys give away your secrets, right? I don't know if for me, I don't think there's a true regulatory pathway right now for that. I think that's going to have to be determined. Obviously, there'll be pressure to do that at some point because people want to come in, but at least for now, the answer is probably no. I don't think it's possible. Any questions before we wrap up? All right. I'm going to go ahead and close with a question that I'd like to close with, which is, what aspect of the Iovance story do you guys believe is underappreciated by investors at the moment? Probably the one that Peter and I were mentioning, which is the potential applicability. As long as we can industrialize this at scale, and we've already done it to some extent, you could cover a vast number of cancers with this, just like checkpoint. Just like PD-L1 is done. So I think that future is extremely bright for TIL therapy. I think over time, you'll see the technology barriers break down. The scale will get up into the hundreds of thousands of patients, and you'll be treating cancers across the board with this. That's what I think the underappreciation is here. Sounds great to me. Thank you very much. Thank you.