Good day and thank you for standing by. Welcome everyone to the Iovance Biotherapeutics First Quarter 2025 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Sara Pellegrino, SVP, IR and Corporate Communications. Please go ahead.

Good afternoon and thank you for joining the Iovance conference call and webcast to discuss our first quarter 2025 financial results, as well as recent corporate updates. Dr. Fred Vogt, our Interim Chief Executive Officer and President will provide an introduction and focus on the U.S. Commercial launch of Amtagvi, including revenue and revenue guidance. Dan Kirby, Chief Commercial Officer, will discuss the Amtagvi commercial launch; Dr. Igor Bilinsky, our Chief Operating Officer, will provide a manufacturing update. Jean-Marc Bellemin, our CFO, will review our financial results, including revenue and revenue guidance, gross margin, and cash burn guidance; and Dr. Friedrich Finckenstein, our Chief Medical Officer, will summarize key pipeline programs. Additional members of our leadership team, including Dr. Raj Puri, our Chief Regulatory Officer; Dr. Brian Gastman, our EVP of Medical Affairs, will be available for the Q&A session. Earlier this afternoon, we issued a press release that can be found on our corporate website at iovance.com. Before we start, I would like to remind everyone that statements made during this conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans and transactions, revenue and revenue guidance, commercial activities, clinical trials and results, regulatory approvals and interactions, plans and strategies, research and preclinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interactions, licenses and collaborations, cash position and expense guidance, and future updates. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time-to-time in our SEC filings. Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward-looking statements. With that, I will turn the call over to Fred.

Thank you, Sarah and welcome to the Iovance first quarter 2025 conference call. We are four quarters into our U.S. launch of Amtagvi, the first FDA-approved TIL cell therapy and the first treatment for patients with advanced melanoma who progress following anti-PD-1 treatment and have appropriate targeted therapy. In the first 12 months of our U.S. launch, we've executed towards our long-term goal -- adoption goals and generated more than $210 million in revenue. This includes infusions from nearly 300 Amtagvi patients in the first launch year, starting with our first infusions in April of 2024. Total first quarter product revenue was $49.3 million, including $43.6 million from more than 80 Amtagvi infusions and $5.7 million from Proleukin sales. Following steady growth throughout 2024, revenue was lower in the first quarter of this year, driven by three key contributors. First, our internal manufacturing facility, the ICTC, completed annual scheduled maintenance in December of last year, as we previously discussed on last quarter's call. As a result of limited production starts for multi-week Amtagvi manufacturing across our network, capacity was reduced by more than half for about one month. In addition, volume was impacted by higher rates of patient drop-off and lower manufacturing success rates, but has since rebounded. Today, we are seeing healthy demand with a record number of production starts in the second quarter. Lower Proleukin sales were the second factor contributing to lower first quarter revenue. We expect two of the three largest U.S. ship wholesalers to start replenishing Proleukin in line with growing Amtagvi demand in the second quarter. We're also growing the other components of our franchise, including sales of Proleukin to third parties for use with manufacturing and clinical research. The third contributor to first quarter revenue was the variable pace at which ATCs began…

Thank you, Fred. Following my first 90 days at Iovance, I'm excited about the potential for Amtagvi to benefit patients around the world. I've identified the strength of our launch as well as opportunities to optimize adoption and accelerate growth. Amtagvi is a game-changer for patients who have failed first-line treatment in melanoma. Amtagvi is also the first cell therapy for patients with solid tumor cancers. I'll begin with my observations of what is going well. First, I'm very impressed by our confident and dedicated commercial organization and cross-functional field teams. These teams have established a solid foundation for Amtagvi by building awareness of the unmet need in advanced melanoma and strong clinical profile of Amtagvi, activating our 70 ATCs within our treatment network and preparing for the next wave of new centers, securing early inclusion in the NCCN guidelines and favorable reimbursement access for more than 95% of U.S. covered lives. As a result of this execution, Amtagvi is a successful cell therapy, the first of its kind in solid tumors. Today, I will discuss status and near-term initiatives to improve our performance across three key areas. First, our ATC network expansion and retention strategy to drive adoption. A second area is to address plans to revamp engagements with medical oncologists to guide earlier consideration for Amtagvi. And the third area is to further establish Amtagvi within the U.S. community oncology networks. I'll start with our ATC strategy. In the first year of launch, we strategically prioritized 70 experienced cell therapy centers in most of the major cancer centers, nearly all currently treated melanoma patients and are within a two-hour drive of these ATCs. Current metrics amongst these 70 centers demonstrate ample growth performance and potential for Amtagvi. 79% or 56 ATCs have completed tumor resections, the starting material…

Thank you, Dan. Today, I will provide an update on our progress in manufacturing. Our Philadelphia-based manufacturing network consists of 2 FDA-approved facilities, our internal manufacturing facility, the Iovance Cell Therapy Center, or ICTC, and an American-owned contract manufacturer. This network serves commercial patients in the U.S. as well as clinical trial patients across Europe, Australia, and Asia. Our experience in supplying TIL cell therapies to clinical patients around the world provides a strong foundation for delivering commercial product in the EU, U.K. and Canada in the near-term. Today, I'm pleased to report a major step forward in the ongoing review of our marketing authorization application, or MAA, for the European Union approval of Amtagvi. Recently, as part of the MAA process, the European Medicines Agency, or EMA, inspected and confirmed that the ICTC and our contract manufacturers facility are both GMP-compliant. These successful EMA inspections further validate our manufacturing network capabilities to meet regulatory standards from multiple health care authorities as we prepare to serve commercial patients in the European Union. As part of the ongoing launch, we steadily ramped up our staff manufacturing capacity to align with demand while tightly controlling expenses. As a result of our revised revenue guidance and updated demand forecast, as Fred described, we expect to realize additional cost savings by aligning our manufacturing capacity growth plans with demand. Owning our own manufacturing facility provides us with tremendous flexibility to scale up efficiently when needed. As mentioned previously, ICTC conducted and successfully completed annual scheduled maintenance. Given the three-week manufacturing process for Amtagvi, the network capacity was reduced by more than 50% for approximately one month in December 2024, thus lowering available capacity for Q1 Amtagvi infusions. Following maintenance, production resumed successfully with full capacity available for Q2 Amtagvi infusions. I will also comment…

Thank you, Igor. Today, I will review our cash position and results for the first quarter of 2025. I will also highlight our financial outlook, including revenue, expense guidance, and gross margin. As of March 3st1, 2025, our cash position was approximately $366 million. Our current cash position is sufficient to fund current and planned operations, including manufacturing expansion into the second half of 2026. I will now transition to our financial results. Net loss for the first quarter of 2025 was $116.2 million or $0.36 per share compared to a net loss of $113 million or $0.42 per share for the first quarter of 2024. Total product revenue consists of Amtagvi infusion in the U.S. and Proleukin sales. Total product revenue was $49.3 million for the first quarter of 2025, including $43.6 million for Amtagvi and $5.7 million for Proleukin compared to total product revenue of $0.7 million for the first quarter of 2024 for Proleukin. The U.S. commercial launch of Amtagvi and Proleukin sales drove the revenue increase in the first quarter of this year over the prior year period. I will now highlight our cost of sales, which includes cost of inventory, overhead, and related cash and non-cash expenses that are directly associated with sales of Amtagvi and Proleukin as well as manufacturing costs for Proleukin. Cost of sales for the first quarter of 2025 was $49.7 million, including $15 million in period costs associated with patient drop-off and manufacturing success rates, an increase quarter-over-quarter, as Igor previously described. $5.4 million for non-cash expenses, including fair market value step-up and intangible asset amortization and $1.3 million in royalties payable on product sales. During the first quarter of 2024, cost of sales was $7.3 million, primarily related to non-cash amortization for acquired intangible assets. The increase in cost…

Thank you, Jean-Marc. Building on the team's comments about Amtagvi, the durability of responses following one-time treatment is a key differentiator from other available and emerging therapies. We will present five-year results from our C-144-01 trial at the American Society of Clinical Oncology or ASCO Annual Meeting on June 2nd. Compared to prior data updates, these results show consistent trends for overall survival and durability over a five-year period. Our clinical programs and next-generation approaches are the next frontier for TIL cell therapy in solid tumors, which represent more than 90% of all diagnosed cancers in the U.S. Future growth drivers include global label expansion for Lifileucel into frontline advanced melanoma, other solid tumor types such as non-small cell lung cancer, and next-generation therapies. Today, I will summarize our latest pipeline updates. First, we are making progress towards the broader commercial opportunity for Amtagvi in frontline advanced melanoma. Our global registrational Phase 3 trial, TILVANCE-301, remains on track to support accelerated and full approvals of Amtagvi in combination with pembrolizumab in frontline advanced melanoma as well as regular approval of Amtagvi in our initial indication in post anti-PD-1 melanoma. A proof-of-concept cohort is also investigating Lifileucel in combination with nivolumab and relatimab in the U.S. Our registrational program in advanced non-small cell lung cancer, the single-arm Phase 2 IOV-LUN-202 clinical study is designed to show efficacy and safety of Lifileucel monotherapy in patients progressing after anti-PD-1 therapy. There is a significant unmet medical need as most patients progress and chemotherapy, the current standard-of-care in this treatment setting provides limited rate and duration of responses. We remain on track as planned to share additional data from IOV-LUN-202 in the second half of 2025. The trial is designed with the potential to support a potential regulatory decision on U.S. accelerated approval in…

[Operator Instructions] Our first question comes from Andrew Tsai with Jefferies. Your line is open.

Hey. Thanks. Good afternoon. Thanks for taking my question. Appreciate the update. My question is around the line of sight you're having amidst the revised guidance. Presumably, you do have some direct line of sight, maybe at least a month in advance into the number of patients who are waiting to get dosed in the Q. Can you confirm whether you're seeing or have seen a spike or an inflection in patient uptake as of today to give you the confidence around your guidance of 110 patients for Q2? Thank you.

So Andrew, this is Dan. Thank you very much. Yes, we're confident in that number, and we are seeing demand, as we stated in the script, in quarter two be strong.

Thank you. Our next question comes from Tyler Van Buren with TD Cowen. your line is open.

Hey guys. Thanks very much for all the information. So, for the 11 ATCs that have infused more than 10 patients, were most of them involved in the clinical program? And it's just a matter of getting the other ones that weren't up to speed? Maybe you could discuss the barriers of the other 37 ATCs that have infused more than one patient but haven't infused 10 plus and what tactics you're employing to get them to increase their utilization?

Yes, Tyler, I'll start, and I'll pass it over to Dan to give you a little bit more on the second part of that question. On the trial, only a few of those ATCs were actually involved in the trial. It's not necessarily a correlation between the clinical trial unit at the site and their experience and what the site does with commercial Amtagvi. A lot of times it's different people, and we have to work closely with that unit at each ATC to get them up to speed. So, there is some learning there, but we're able to overcome it. And obviously, we're learning quite a bit ourselves about how to do that, and we're getting better and better all the time. And that's why we have confidence that many of those other ATCs are going to come along quickly. And in fact, we're seeing that today. But Dan, do you want to take the second part of the question?

Sure. And looking at just with cell therapy in general, there's actually patients coming into treat and there's a cell therapy experience level at these centers. So, what we'll say is that the larger centers that got off to a quicker start, those are the ones with the infrastructure from various cell therapy launches that were ready for Amtagvi to enter in. The other ones are ramping up to speed. They're doing this with other cell therapies as well. But infrastructure such as billing, mechanism, cell therapy lab, et cetera, are coming online with that. So we are seeing them increase their ramp a lot quicker once they get that infrastructure in place. Does that answer your question?

Yes. Thank you.

Thank you.

Thank you. Our next question comes from Salim Syed with Mizuho. Your line is open.

Great. Thanks for the question guys and there color there. I guess on your guidance kind of going forward here for 2025, if I'm doing my math correctly here and assuming something like 20% Proleukin, sort of backing into that the balance of the year, you're going to have something like 250 or 325 infusions. So, roughly like, call it, 100, 110, something like 100 per quarter roughly. Is that a correct way to sort of think about this, which essentially apply no growth versus like the 2Q number?

No, Salim, that's not how you want to think about it. We're actually -- right now, as you know, we did $164 million in revenue last year, including quite a bit of Proleukin. And what we're projecting is $250 million to $300 million this year, which is some growth there, obviously. That's fiscal year aligned. If you want to think of it as just infusions, though, you can look at the four quarters. We infused our first two patients back in April of 2024. And through to the end of March, we were about 280-some patients infused. Our guidance implies that in this year, we'll probably get over 500 patients infused and that's in the four quarters of the fiscal year. And of course, there'll be another quarter into 2026 that will grow more. So, you are looking at like a 50% or more growth rate there as you go through this time period year-over-year, and there's a lot of upside there as well. And Dan, do you want to add to that?

Sure. So, what I would say is the way you can look at this is that we expect continued growth throughout this year. So it will not be flattening, it will continue to grow. That's driven by two factors. One, as we talked about the increase of adoption in our centers, both the ones that started in the very beginning and the ones that ramped up through 2024 and the addition of new ATCs that have enhanced referral networks within the community to get patients not only in quantity, but also quality, meaning they're getting earlier referrals.

Okay. Thank you so much.

Thank you. Our next question comes from Andrea Newkirk with Goldman Sachs. Your line is open.

Good afternoon. Thanks for taking the question. Maybe a follow-up there, Fred, on what your guidance is implying per infusion. I just want to make sure I understood this. But are you suggesting that 500 infusions should be on top for 2025? And if that's the case, then what are you assuming for Proleukin through the remainder of this year even after the uptick expected in 2Q?

So, if you just take the guidance we gave, subtract off the number like what Salim just gave you for Proleukin and divide that through by 550 or so, you're going to get something in the high 400s, close to 500 depending. And if you think there's some upside here, there could be some upside on top of that. Does that answer the question?

Okay. Thank you. And then just really quickly, Igor, could you just speak to what drove the higher patient drops or lower manufacturing success in the quarter? And what gives you the confidence that this will reverse on the forward?

So, some of this -- thanks for the question, Andrea. Some of this or much of this is related to patient selection and the tumor procurement technique. And as I mentioned, we already saw the return to normal rebound in the Q2 so far. What gives us confidence is the success rate trends that we see among ATCs who have been up and running for a long time and the experience curve that they've been able to achieve. So, that gives us confidence that it's teachable and can be translated to other ATCs across the network.

Thank you. Our next question comes from Yanan Zhu with Wells Fargo. Your line is open.

Thanks for taking our questions. First, a clarifying question. I must be missing something. So, assuming each Amtagvi product is roughly north of $500,000, that's $0.5 million. And then if there's 500 patients infused this year, that alone will be $250 million, which is the lower bound of the guidance. So, if that's the case, then adding IL-2 on top of that, the lower bound of guidance should really be above $250 million. So, I'm trying to see is my assumption for per patient price off? And -- thank you for clarifying. My actual question is on COGS. And can you talk about the -- it seems like COGS -- as a ratio of revenue has increased over the last quarter. Just wanted to understand what proportion of the COGS is due to patient attrition, i.e., patient passing away cannot get the product or manufacturing failure. If you can give us some color there. Thank you.

Yes. Yanan, on the first part, our guidance, we consider this guidance to be fairly conservative. So, as you go and do your math there, there's going to be some upside on what we're giving here. If we get to 500 infusions, it might be above 300 on the upper end. And that's something that we really want to -- with this new guidance, we really want to show that we can actually exceed guidance here and do well here with this launch. So, it's not going to work out exactly to where you might think maybe it's 450 patients if you want to be more conservative. However, it's still growth. It's still growth over the first three quarters of the launch. If you want to look at it on a fiscal year basis or four quarters, you want to look at it on a launch year basis. But again, the first four quarters of our launch, we treated about 280-some patients. Now, for the COGS question, let me ask -- and that's the ratio of scrap and Jean-Marc and maybe Igor might need to help out with that one.

Can I just say one thing -- so one of the things -- I mean, first, the quarter, the $250 million is a 50% growth over 2024 sales, revenue, I should say. So, that is definitely a growth in the lower end for it. And yes, the -- we would love to have upside to that. The second part, when you talk about patient health, I just want to clarify that statement. Those are patients who went to hospice or died prior to the manufacturing process starting. They went there before we had tumor procurement. So, therefore, they would not be affecting COGS. And Igor, do you want to take the COGS question? You and Jean-Marc?

I think Jean-Marc may need to take that.

Yes. I'm happy to take the COGS question. So, yes, you're correct. We had an increase -- and the overall cost of sales together, as Igor mentioned during the script is that we see a spike in the out of spec on the first quarter that we know will improve over time, but you have to think also relative to the overall revenue. So, yes, the cost of goods and the cost of sales has increased in Q1, particularly related to revenue, but we know this will definitely improve in Q2. And our standard gross margin remained positive in Q1, as you heard me saying.

Got it. Thanks for the color.

Thank you. Our next question comes from Colleen Kusy with Baird. Your line is open.

Good afternoon. Thanks for taking our question. So, you reported patient dropout and out-of-spec rate together, but can we assume that, that out-of-spec rate went up? And if so, what drove that? Was it anything to do with the annual maintenance? And then would we expect that same one-month interruption going forward every year? Thank you.

So, Colleen, thanks for the question. So, again, regarding the patient drop-offs and manufacturing success rate, these closely relate to each ATC's track record in patient selection and tumor tissue procurement. And again, the increase we saw in Q1, we believe it to be transient. It's already normalized in Q2 to-date. So, that's what we believe is driving it. We have new ATCs, new surgeons and some of that needs to be optimized over time, which our teams are working on. What was the second part of the question?

Just the annual maintenance, whether that will be a similar one month, 50% reduction in capacity?

Annual maintenance, so we are now completing build-out of the shelf space at ICTC. Once that shelf space is operational, which will not be this year, but should be later on. Once that shelf space is operational, then we don't need to -- the maintenance will only affect part of the ICTC facility, not all. So, does that--

It will have less impact.

It will have less impact.

But yes, Colleen, this is -- it is an annual event that you have to do it.

But for now, this year, we'll still need to do it. But in the subsequent years, again, once the ICTC is fully built out and fully up and running, we will not see that effect.

Helpful. Thank you.

Thank you. Our next question comes from Peter Lawson with Barclays. Your line is open.

Great. Thank you so much. Just going back to kind of manufacturing success, has that returned back to normal levels? And was that also related to the -- I thought you had a problem in 4Q as well associated with the same thing. Is the same thing kind of spread into 1Q or a separate issue?

I'm not really sure, Peter, what you're asking out there. The important point is we didn't talk about that in the last quarter at all. What we did mention back then is there was going to be a shutdown, and we were in the process of, at that point, actually hitting the shutdown. But no, we don't--

That doesn't -- there was no issue with manufacturing success rate in Q4. No, Q4 was actually a good quarter.

The important thing to remember here, Peter, is rebounded already. Again, we think it has to do with individual activities in some of the ATCs and how they procure tumor as well as some things that we can learn from throughout the entire process and how we can improve those things. And it looks like it's already rebounded pretty well, and we're back in the zone where we think we were during the first part of the launch.

Got you. Thank you. And is there any way of breaking out sort of the revenue weakness you had and lower guidance, kind of how much of that's due to demand uncertainty or and/or manufacturing uncertainty?

No, I don't really think there's a way of doing that. No, that would be very complicated to analyze that. I can't Dan or Friedrich.

I mean we see demand being consistent and growing, especially with the new centers coming on with it and now the ones ramping up. So, demand is not an issue for that part of it with it. And I think Igor address the manufacturing.

Sure. And the manufacturing success rate, the trend over time from the beginning of launch, the success rates are improving, and we expect that to continue this year.

Again, the guidance, Peter, is really driven by ATC launch dynamics more than anything. It's not really about uncertainty in those areas.

Got you. Okay. Thanks so much.

Thank you. Our next question comes from Reni Benjamin with Citizens. Your line is open.

Hey guys. Thanks for taking the questions. Igor, you had mentioned that these different ATCs are doing things slightly different. I'm kind of curious, what are the strategies, the different strategies that you guys are employing right now to kind of get all these ATCs rolling in the same direction to improve all these -- improve the various manufacturing things to help improve kind of the overall processes there? And then just as a second question, it's a revised guidance. I guess we were all kind of surprised to begin with when last year, you provided guidance for this year. I'm kind of curious as to -- I get being conservative now, why provide guidance for 2025 way back in 2024 to begin with?

So the first part, perhaps Dan can answer.

Sure. I can also throw over to Brian for that. One of the things we're seeing for the tumor tissue procurement that's happening at the centers and replicating the successes that we're seeing with the surgeons that are doing it better than others. We actually have our field teams out there now to really focus and actually on the medical affairs side. So, I'll hand to Brian. But Brian, can you talk about how your field teams are addressing that at the centers to replicate success?

Yes, I think one of the things that's happening is we recognize that these centers continue to grow internally and keep adding new members. And what we've been doing really, we call it a white glove service where we're getting in there and actually certainly for the newer surgeons to actually go from -- we call it the start program, start to finish program where we actually go in and we'll walk through the surgery and beyond with them to try to make sure that every case is as successful as possible. We've had very good feedback. They're enjoying it, especially the new centers and the new surgeons, and we're hoping to try to really speed up those learning curves for our newest ATCs so that they can learn from the successes of our best ATCs that have been around a long time.

I guess I can get the second part of your question, Reni. Back in August, we were trying to give investors our best line of sight to what we thought was going to happen. At that point, we were very well aware of the high demand for the product, and we were ramping up our manufacturing as fast as we could. So, we built our model on the back of how many manufacturing slots we would make available maximum ramp. Now, as we've gone, we've learned a lot about the launch, especially recently as we watch some of the dynamics with the ATCs, we looked at our experience with growth trajectories there. We look at the time lines it takes for new ATCs to come on board and begin treating their first patients and how they work through their processes. We're onboarding these large community practices, which takes some time, and we're doing the community referral process, which takes a lot of time, too. And as we looked at that, we just decided that it was better and more accurate for us to forecast guidance that we gave today to show you that we can still make this product grow very, very substantially. But now what we're going to do is we're just going to limit some of our manufacturing slots. It ends up being essentially almost a neutral with respect to how we use our cash, and we'll roll forward and we'll continue to succeed on the launch. But we think we'll do it on terms that are, I think, a little bit more in line with what we actually see at the ATCs.

Thank you. Our next question comes from Asthika Goonewardene with Truist. Your line is open.

Hi, this is Corrina for Asthika. Thanks for taking the questions. What percentage of the product is currently being manufactured at the ICTC versus contract manufacturer? And then also, again, on lower manufacturing success rate, some of the clinicians they noted that there's a need for a larger amount of tissue to improve success rate. Can you comment on that? Thanks.

So I'll take the first part. ICTC, our internal manufacturing facility is responsible for most of the manufacturing volume and has significantly higher capacity than our contract manufacturer. And then the second part, perhaps I'll turn it over to Brian.

Yes. I mean we've made a lot of guidance changes in terms of best surgical practices. It goes from volume of tumor to handling of tumor in general and preparing it before it's being sent. To be honest with you, do we need all the tumor that we get sent? Not always, but we generally guide towards what I would call the average ATC, the average surgeon because the best surgeons probably don't need any guidance and probably the below average need a lot of guidance. And so in general, we do try to ask them for as much tumor that reasonably fits into our -- into the vial that we give them.

All right. Thank you.

Thank you. I'm showing no further questions at this time. I would now like to turn it back to Fred Vogt, Interim President and CEO, for closing remarks.

Thank you again for joining the Iovance Biotherapeutics first quarter 2025 financial results and corporate update conference call. We look forward to providing future updates on our growing commercial and clinical portfolio, including our data presentation and investor event at the upcoming ASCO Annual Meeting in Chicago. We are motivated by the stories we continue to hear about the patients who benefit from Iovance TIL cell therapies in our clinical trials in the commercial setting. I'm confident that Iovance will remain the global leader in innovating, developing and delivering current and future generations of TIL cell therapies for patients with cancer. As always, we are thankful to the patients, health care, and advocacy communities, our partners, and our exceptional Iovance team. I would also like to thank our shareholders and covering analysts for their support. Thank you.

This concludes today's conference call. Thank you for participating. You may now disconnect.