Iovance Biotherapeutics - Q4 2025

Transcript

Operator (participant)

Good day. Thank you for standing by. Welcome to the Iovance Biotherapeutics fourth quarter and full year 2025 financial results and corporate updates conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you will need to press star one one on your telephone. You will hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. 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, Senior Vice President, Investor Relations and Corporate Communications at Iovance. Please go ahead.

Sara Pellegrino (SVP of Investor Relations and Corporate Communications)

Thank you, operator. Good morning, welcome to the Iovance webcast to discuss our fourth quarter and full year 2025 financial results, business achievements, and corporate updates. This morning, we issued a press release that is available on our corporate website at iovance.com. This conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans and transactions, revenue, 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 filing. Our results may differ materially from those projected during today's call.

We undertake no obligation to publicly update any forward-looking statements. I will now turn the call over to Dr. Frederick Vogt, Interim CEO and President of Iovance.

Frederick Vogt (Interim CEO and President)

Thank you, Sara. In 2025, Iovance delivered substantial revenue growth, achieved groundbreaking data milestones, and strengthened our financial performance. Our fourth quarter and full year 2025 results underscore our focus on value creation for patients and shareholders. We drove AMTAGVI adoption while streamlining costs and optimizing operations. Our operational strength resulted in a robust 30% revenue growth, driven by AMTAGVI and our best-ever 50% margin from cost of sales in the fourth quarter. For the full year, total revenue of about $264 million was well within our annual guidance range. Our cash runway, bolstered by our ongoing cost savings initiatives, now extends into the third quarter of 2027. Following our exceptional performance in 2025, we are well-positioned in 2026 to surge toward a highly profitable and broad business in solid tumor cancer immunotherapy.

We plan to execute across three core pillars. First, continue accelerating our U.S. commercial launch of AMTAGVI in advanced melanoma. Second, harness the power of our TIL pipeline to expand into new indications and next-generation products. Third, hone our operational excellence as our foundation for success. First and foremost, we are gaining positive update commercially, with a significant potential for AMTAGVI and Proleukin to reach $1 billion-plus U.S. sales at peak. After a considerable increase in fourth quarter demand for AMTAGVI, enrollment volumes in 2026 are accelerating within our broad and continuously expanding network of both academic and community Authorized Treatment Centers or ATCs.

These ATCs are further reinforced by excitement surrounding the real-world experience and benefits of early treatment with AMTAGVI. On top of increasing demand, we are benefiting from operational improvements throughout the entire AMTAGVI treatment journey, from patient identification through manufacturing to infusion.

On the heels of positive momentum in the fourth quarter, we expect remarkable revenue growth in 2026, driven by AMTAGVI. In the very near future, we will provide revenue guidance with our growth projections. Our second pillar is the massive expansion potential for our TIL platform to positively impact patients in the new indications. We are harnessing the overlap and scalability of our TIL platform, manufacturing leadership, and commercial capabilities across solid tumors. Our lead indication for lifileucel is in previously treated non-squamous non-small cell lung cancer.

This blockbuster U.S. market is about 7 times larger than our PQS sales opportunity in advanced melanoma. In our registrational patient population, lifileucel has demonstrated best-in-class clinical response rates and durability. This morning, we announced the FDA has granted Fast Track designation that validates our clinical trial data and reaffirms the substantial unmet medical need for lifileucel in this indication.

We are rapidly advancing toward a supplemental Biologics License Application with a potential accelerated approval and launch in the second half of 2027. This morning, I am also excited to introduce entirely new indications for lifileucel, announced in a press release alongside positive early data. In previously treated patients with 2 aggressive, difficult-to-treat advanced soft tissue sarcomas, lifileucel demonstrated an unprecedented 50% confirmed response rate. As Brian will highlight, lifileucel may offer the first durable immunotherapy option in this treatment setting. Current outcomes with standard of care are abysmal, with response rates below 5% and short median overall survival of only 9-10 months. Together, these sarcomas impact more than 8,000 patients in the U.S. and Europe annually, significantly increasing our market opportunity for lifileucel in the U.S. and beyond.

We are working expeditiously to initiate and complete a single-arm registrational trial to launch these sarcomas. Our robust pipeline is the backbone of immuno-oncology and multiple solid tumors today and in the future, as we build upon our established global leadership and define next-generation approaches for TIL cell therapy. Our two clinical stage genetically engineered TIL therapies have the potential to transform the treatment paradigm across a vast number of solid tumor cancers, where patients have few options. Our next-generation IL-2 product may facilitate more accessible TIL therapies. We expect to provide many more updates on our pipeline in 2026. Finally, our third pillar is operational excellence, as we increase revenue, optimize costs, and drive efficiencies toward profitability. In the fourth quarter, we've reported our best-ever gross margin, as Corleen will discuss.

Additionally, our ongoing execution, discipline, and focus on financial excellence will improve current and future gross margin and further extend our cash runway. Within our operational excellence pillar, as Igor will highlight, manufacturing success has improved across the board. By optimizing our processes, we have infused more patients while reducing dropouts to be more efficient ahead of future launches. Importantly, we own and control all manufacturing for AMTAGVI within our U.S.-based Iovance Cell Therapy Center, or ICTC, as well as critical components of our supply chain. We have never been in a stronger position to execute while scaling to new heights. In 2026, we are laser-focused on maximizing shareholder value, ending dilution, and supercharging future profitability. I'll now turn the call over to Corleen Roche, our Chief Financial Officer, who will provide further updates on our fourth quarter and full-year financials.

Corleen Roche (CFO)

Thanks, Fred, and good morning, everyone. Iovance finished 2025 with positive momentum as we reported approximately 30% revenue growth with 50% margin from cost of sales in the fourth quarter. Fourth quarter product revenue of $87 million demonstrated meaningful growth of approximately 30% from the prior quarter, driven by AMTAGVI. In our first full year of launch, total product revenue of $264 million increased by 61% over the prior year, driven by AMTAGVI revenue growth of 112% year-over-year. That was well within our annual guidance range. We drove this impressive revenue growth in 2025 through ongoing market penetration and earlier treatment with AMTAGVI for more patients at an expanding number of treatment centers. The impact of gross to net adjustments remains minimal at less than 2% overall in 2025.

Fourth quarter gross margin from cost of sales increased to 50% from 43% in the third quarter. This margin improvement resulted from ongoing operational optimization and disciplined use of capital. The full internalization of manufacturing operations at ICTC also provides uninterrupted supply with agility for further efficiency. Today, we are capable of scale-up and expansion into new indications globally to bolster revenue without the need for significant capital expenses. Turning to our balance sheet, our cash position was approximately $303 million at year-end. Driven by our commitment to commercial and clinical execution, operational efficiency, and financial discipline, we successfully extended our cash position to fund operations into the third quarter of 2027. In closing, our 2025 financial results reflect our commitment to flawless execution and commercial utilization, improved margin, and extended cash runway that supports our path to profitability.

I will now turn the call to Dan Kirby, our Chief Commercial Officer, to provide additional context.

Dan Kirby (Chief Commercial Officer)

Thank you, Corleen. Over the course of 2025, we made tremendous progress in three key areas towards our ultimate goal to establish AMTAGVI as the preferred treatment option for all eligible patients who deserve a one-time cell therapy with curative intent. First, our ATC network is continuously expanding. In the fourth quarter, new community centers as well as high-volume academic centers contributed to our highest-ever quarterly demand for AMTAGVI, which drove our Q4 revenue. Second, penetrating the community market will unlock AMTAGVI's tremendous potential as we expedite higher-quality referrals to ATCs and begin to treat patients in the community setting.

Recently launched campaigns focused on healthcare professionals and patients are having a positive impact. The community market will expand further and accelerate growth as we build awareness and access. Our third key focus area is to drive treatment and increase penetration earlier when patients benefit most from AMTAGVI.

Real-world data resonating with medical oncologists has shown unprecedented efficacy, with more than 1 in 2 patients responding in the second-line setting and 1 in 3 patients in later lines of therapy. Initiatives within academic ATCs are also generating positive results from earlier tissue procurement and earlier treatment for specific patient types. ATCs are offering AMTAGVI treatment before health status declines in patients with a BRAF mutation, who have no current or pending options beyond targeted therapy. On the heels of our substantial fourth quarter performance, positive trends and increasing demand have persisted into the first quarter and support our confidence in remarkable growth for 2026. Globally, AMTAGVI has the potential to reach more than 30,000 patients annually with previously treated advanced melanoma.

We have made significant strides towards expansion, including AMTAGVI approval in Canada, pending approvals in the U.K., Australia, and Switzerland, and additional progress towards resubmitting a Marketing Authorization Application to the European Medicines Agency this year. Beyond melanoma, we are preparing for commercial launch in previously treated non-squamous non-small cell lung cancer, the most common form of lung cancer. This blockbuster opportunity is approximately seven times larger than our current melanoma opportunity, with 50,000 addressable patients for peak sales of $10 billion in the U.S. alone. Our entire AMTAGVI ATC network of U.S. academic and community practices can leverage their existing TIL infrastructure for rapid adoption in non-small cell lung cancer upon approval, as well as future pipeline indications such as sarcomas.

After recently celebrating my one-year anniversary at Iovance, I am proud of our accomplishments and inspired by our science and the patient stories that paint a bright future. I will now pass the call to Igor.

Igor Bilinsky (COO)

Thank you, Dan. In the fourth quarter of 2025, we achieved both our largest manufacturing volume and highest commercial manufacturing success to date. Building upon this progress, all lifileucel manufacturing has transitioned to the ICTC, which is a significant milestone to optimize internal capacity utilization, improve operational excellence, reduce cost of sales, and further improve gross margin. I'll also highlight that around year-end, we successfully completed routine annual maintenance at ICTC. During this time, we minimized the impact on manufacturing volume by leveraging our contract manufacturer and increasing internal capacity surrounding the maintenance window. Importantly, ICTC has transformed into a modular facility with capability to provide uninterrupted supply and fully support anticipated global demand today and scale up for the future, even during future annual maintenance periods. I will now pass the call to Friedrich.

Friedrich Finckenstein (Chief Medical Officer)

Thanks, Igor. Today, I'll focus on our two registrational programs. First, enrollment is accelerating across a broad and expanding global footprint on our phase 3 TILVANCE-301 trial. We are investigating AMTAGVI to support a potential U.S. full approval in the current labeled indication and accelerated and full approval in combination with pembrolizumab in frontline advanced melanoma. Shifting to our IOV-LUN-202 registrational trial, lifileucel has demonstrated a best-in-class clinical profile and recently received Fast Track designation from the U.S. FDA. The objective response rate was 26%, disease control rate was 72%, and median duration of response was not yet reached after more than 25 months of follow-up. We plan to present updated data at a medical meeting this year. Key opinion leaders are enthusiastic about these data, which resulted in a meaningful uptick in recent enrollment.

We are excited to be on track to complete enrollment this year in support of a supplemental Biologics License Application. We are also pleased with the progress across the rest of our pipeline, which I am happy to discuss during the Q&A session. I now give the floor to Brian for the sarcoma update.

Brian Gastman (EVP of Transitional Medicine and Research)

Thank you, Friedrich. I'm excited to share positive initial data from a pilot clinical trial in patients with previously treated advanced undifferentiated pleomorphic sarcoma or dedifferentiated liposarcoma. They have no approved immune therapy options. Among six evaluable patients, the confirmed objective response rate was an unprecedented 50%. Responses were deep and improved over time, consistent with the durability for lifileucel in melanoma and non-small cell lung cancer. These high-mortality, aggressive soft tissue sarcomas affect more than 3,000 patients in the United States and more than 5,000 in Europe, including more than 3,500 cases of advanced disease. These patients have poor prognosis and a very high unmet medical need. Grim outcomes with second-line standard of care include response rates below 5% and median overall survival of less than one year.

In summary, these extraordinary results are what I hoped and believed I would see TIL therapy do in solid tumor cancers when I chose to leave academic medicine to join Team Iovance. I am heartened by this major opportunity for patients and the future of TIL therapy. We look forward to commencing and advancing a single-arm registrational trial as soon as possible. As part of this developmental program, we will also explore other subtypes of high-grade soft tissue sarcoma, where patients have no approved effective therapies and urgently await better treatment options. I will now hand the call back to the operator to begin the question and answer session.

Operator (participant)

As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. In the interest of time, we ask that you please limit yourself to one question, and you may rejoin the queue. Please stand by while we compile the Q&A roster. Our first question comes from Andrew Tsai with Jefferies. Your line is open.

Andrew Tsai (Managing Director)

Hey, good morning. Thanks for the updates, and thanks for taking my question. Maybe for the TILVANCE update that you provided, it sounds like enrollment is picking up nicely. Is it possible that we could get first-line melanoma data with AMTAGVI PD-1 combo data later this year? Regardless of timing, what kind of ORR and PFS do we want to see compared to PD-1 alone? Thanks.

Frederick Vogt (Interim CEO and President)

Yeah, maybe I can take the first part of that, Andrew, and then Friedrich can cover the rest of it. We do have an early interim read in this study, which is a benefit of some of the agreement we have with FDA on this, where we can read ORR as an interim partway through the study. It's in the near term, and we'll be able to do that. We can't really commit to doing that in 2026 right now. It's such a large study, but we are very excited to be able to get that data read. Of course, if we read that data, it's a blinded study. We don't blind to the analysis, and if we announce that, we're basically announcing that we're coming to a supplemental BLA at the same time.

That's the whole point of that. Frederick, do you want to talk about the ORR and PFS considerations on that trial, please? If Frederick is muted, I can. Sounds like Frederick's muted.

Friedrich Finckenstein (Chief Medical Officer)

No, I'm here. I'm sorry about that. I needed to find my window here. Yeah, glad to do so. So I think the best idea around the benchmark for this is the pembrolizumab monotherapy data from the KEYNOTE-006 trial. Remember, the trial design of TILVANCE is a comparison of the combination of pembro plus TIL versus pembro monotherapy. The trial is designed with two dual primary endpoints, with one of them being ORR, the other one being PFS, so ORR giving us an opportunity for an early read.

The benchmark in the KEYNOTE-006 trial for ORR was about in the mid-30s, probably the true real-life ORR with the pembro monotherapy is probably more in the 30 and slightly below % range. Remember, we have very encouraging data on the efficacy of the combination from our C-02 Cohort 1A, which showed response rates up into the 60% range, so that's what's giving us the confidence around a successful readout for the ORR endpoint. Any questions about that? Yep.

Operator (participant)

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

Tyler Van Buren (Managing Director and Senior Biotech Equity Research Analyst)

Hey, guys, good morning. Thanks for taking the question. Can you please elaborate on the big quarter-over-quarter jump in Proleukin revenue and the anticipated split of AMTAGVI to Proleukin revenue moving forward, and if the gross margin can continue to improve quarter-over-quarter, despite Proleukin likely contributing to a smaller % of sales in subsequent quarters?

Corleen Roche (CFO)

Hey, Tyler, it's Corleen. you first, you talked about Q4 split. We did have all three distributors ordering in Q4, and we also took there's a little bit of buy in there. Not crazy. We haven't guided, so I don't have a split for you going forward. What I can tell you on the margins is, yes, we expect further improvement.

Dan Kirby (Chief Commercial Officer)

I'll just add on to that, Tyler. We did see all three wholesalers, as Corleen mentioned, order in Q4. We've already seen reordering happen in Q1. Moving forward, you should see, again, regular orders for Proleukin to go with AMTAGVI sales. That's our major line of business there. Other two channels will come on this year, as they did last year, it mainly is driven by AMTAGVI demand for Proleukin sales.

Operator (participant)

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

Speaker 16

Hi. Thanks for taking our question. This is Xiaochuan for Yanan. Can you share with us, how the manufacturing success rate change over time, and what is the scrap cost for this quarter? Thank you.

Frederick Vogt (Interim CEO and President)

Could you clarify the last part of that question? Which cost?

Corleen Roche (CFO)

Scrap.

Speaker 16

Oh, the scrap cost.

Frederick Vogt (Interim CEO and President)

Scrap cost will be in our 10-K filing that will come out, in, around 9/15. It's consistent with prior quarters. Maybe I'll make some comments on manufacturing success, and any of you can jump in and help as well. I think we don't release actual percentages and stuff here. We don't think that's helpful to investors. It's improving. We're getting better at it. The margins reflect that. You can see the margins are growing. As Corlene mentioned, these margins are being driven, not just, really being driven by AMTAGVI performance. Proleukin is there, it comes in and out, but, you know, we've had good margins for 2 quarters in a row now with Proleukin moving up and down, and we expect that to continue. Manufacturing success is driving that improvement at the end of the day.

Igor, do you want to make any comments specifically about what you made, what you said in the earlier part of the call?

Igor Bilinsky (COO)

Yes, happy to. Thanks for the question, Xiao. There are really 2 avenues for improving success rates. One is internal, where we continue implementing improvements in manufacturing, a lot have been implemented and more are coming. The other avenue is commercial and medical affairs teams working with ATCs and the physicians to improve tumor procurement. That also results in better product. Those both of those have bear fruit so far, and we continue working on both fronts.

Speaker 16

Got it.

Operator (participant)

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

Salim Syed (Managing Director and Senior Biotechnology Analyst)

Hey, hey, guys, thanks for the question. Maybe just one on guidance from us. You didn't provide 2026 guidance. Friday, you mentioned that you plan to provide it shortly. Just curious, what was the logic not to provide it now? When we do get it, can you just give us some context, like, is it gonna be total revenue product? Is it more like a mean or a conservative guide? Just help us framework how we should be thinking about that. Thank you.

Frederick Vogt (Interim CEO and President)

Yeah, right now we're seeing remarkable growth in the AMTAGVI business. We do need to be sure that our projections are well supported, so we're taking some time to do that. It's very early in the year right now, of course, but as I mentioned during the prepared remarks, we're going to be putting guidance out very, very soon. I think you'll see total product guidance. You'll see some guidance potentially on quarters. We'll have to see how our, you know, how our data is supported. One thing I do wanna mention is when I know you asked about breaking out the products.

For the full year of 2025, the revenue from Proleukin and the revenue from AMTAGVI have now fallen right in the line with what we were saying a year ago, and that Proleukin generates about 17% of our revenue. If you recall, many calls, we talked about the 16% number based on the ratio of the price. We are seeing that long-term balance come into play. As Dan mentioned, ordering patterns are stabilizing, and we expect normality on that through the year. You may not see us particularly put a number on Proleukin for one quarter over another, but you can be confident in the long-term ratio of these things and use the numbers you have right now to help support that.

Salim Syed (Managing Director and Senior Biotechnology Analyst)

Okay. Thanks very much.

Operator (participant)

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

Reni Benjamin (Managing Director)

Hey, good morning, guys. Thanks for taking the questions, and congrats on hitting the guidance. Maybe just a couple of questions. One, can you talk a little bit about, you know, the fourth quarter kind of acceleration? How much of that came from new community ATCs versus existing academic centers? As we think about going into 2026, do we hope that the new community ATCs, you know, that number will maybe double? Does it triple? Can you give us some sense as to how this is going to grow potentially this year? Then I have a follow-up on the sarcoma data.

Dan Kirby (Chief Commercial Officer)

Sure. Hey, Reni, it's Dan. Thank you very much for the question. For Q4, our base book of business is the academic ATCs, and we saw significant growth in that segment. We did see new community ATCs come online last year. They're coming online as well this year. We expect a learning curve as we saw with the initial academics coming online, so you'll see them slowly increase as the year goes forward. For Q4, what we saw in the academic ATCs, which is carrying over to what we're seeing in Q1, is that there are certain patient types there that were not making it to AMTAGVI treatment that I mentioned during the script.

We have earlier procurement strategies for patients such as BRAF-mutated patients, which make up a significant number of those patients inside of the academic ATCs that we were not previously able to access, that our initiatives now are allowing us to access. We expect growth to continue in the academic segment. The community ATCs are coming online now. They're having their process of testing a few patients out, and they'll be ramping up as the year goes on. We'll see more of them starting in second quarter through the end of the year and into 2027. Right now, our base book of business is strong and growing with the academics.

Reni Benjamin (Managing Director)

Got it. Okay, thanks for that. And then just to follow up, you know, regarding the sarcoma data, you know, it's quite new and unprecedented. Can you, A, give us a sense as to when we might see the full data and at what medical conference? And then also, can you share with us maybe any details on the depth and durability of response, right, that you're seeing here for these patients? And I guess if you can just if I can squeeze one more in regarding the registrational study, how big do you think this study could be given this rare disease?

Frederick Vogt (Interim CEO and President)

All right, I'll take the first part of that, then I'll ask Brian and Raj to answer the other part of it. We're excited to present this to the medical congress this year. We haven't identified that congress yet, obviously, we really like the big ones, like ASCO and ESMO. We'll have to see how the timing goes, the data is available right now. I do expect we'll be able to put it together pretty quickly for presentation. Stay tuned for that. It should be pretty exciting. Brian, do you wanna take the second part?

Brian Gastman (EVP of Transitional Medicine and Research)

Yeah. In terms of depth and durability, I think it's important to note that obviously, the trial hasn't been running for years. You know, like all of our trials, our durability tends to be measured in very long time frames. I think it'll be a while before we're able to tell you because of the power of having a living therapy on board. In terms of, though, the depth, what's really exciting to see is these responses, similar to what we saw in lung and in melanoma cancers.

We can actually see them get stronger over time. Of course, sometimes it happens right away, but we've actually watched, really excitingly, these scans get better and better and better. We, we saw patients that, you know, if it was on a swimmer plot, we would see them swimming, and on a spider plot, they'd still be dropping. We don't even know how good these patients will get. I think for all of us, it was really remarkable when we saw how many responders we got and how they were deepening. I think more to come there, but it, I think, gave us a lot of encouragement.

Speaker 17

Mark.

Reni Benjamin (Managing Director)

Thanks a lot.

Speaker 17

Mark, would provide any sample size for.

Brian Gastman (EVP of Transitional Medicine and Research)

Yeah. Yeah, thank you for the question. you know, based upon the prior approvals in very soft tissue sarcoma subtypes recently by FDA, approval size for the various subtypes has ranged between 30 patients and 60 patients, but predominantly in the 40-patient range. Based on the characteristics of these two subtypes that we are discussing today, we really expect very similar patient numbers for our registration strategy.

Reni Benjamin (Managing Director)

Perfect. Thanks for taking the questions.

Operator (participant)

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

Speaker 15

Hey, this is Nick on for Colleen. Thanks for taking our question. Just for a commentary on the recent enrollment trends for the non-small cell lung cancer study. Could you talk about just latest thoughts on path to full approval in non-small cell lung cancer? I had a follow-up question as well. Thanks.

Frederick Vogt (Interim CEO and President)

We, the Fast Track designation that we announced today, Nick, was obviously very helpful because that provides us with a lot of benefits in working with FDA. We already, as I mentioned in the prepared remarks today, we are planning on the same timings we mentioned before with this potentially launching in 2027. This is pretty exciting to us. We're finishing the trial right now, and we're very confident that this product provides great benefit for non-small cell lung patients.

Speaker 15

Thanks. Just a quick one on sarcoma. Just wondering if you're considering expanding into other subtypes of sarcoma outside of these initial two?

Frederick Vogt (Interim CEO and President)

Yes, we mentioned that in both the press release and in the prepared remarks. We are looking at additional subtypes, maybe on one of the private calls, Brian can tell you more about it. We are looking at additional. Besides UPS and DDLPS, there's a number of other sarcoma subtypes that are of interest. Now that we see strong activity for TIL in the space, and a lack of approved options, including approved checkpoint options for these patients, nor are there anybody interested in apparently in getting their checkpoints approved here, or they, or they lack the efficacy to do so. We're really going to look across the entire space and really try to tap into this area of unmet medical need.

Speaker 15

Great, thank you.

Operator (participant)

Thank you. Our next question comes from David Dai with UBS. Your line is open.

David Dai (Director)

Hey, great. Thank you for taking my questions, and congrats on the progress. I just, you know, first on the Proleukin sales, we see a little uptick in fourth quarter. I'm just curious, how much is coming from restocking and how much is coming from real AMTAGVI demand? Then moving forward with Proleukin, is it fair to assume that it will stabilize around that level with the maturity of that contributing to real demand from AMTAGVI demand? I have a follow-up question.

Dan Kirby (Chief Commercial Officer)

Sure, David. This is Dan, I'll take the question on Proleukin. We saw in Proleukin, as you recall, all throughout last year, we had one first wholesaler came on in Q2, two were reordering in Q3, all three were reordered in Q4. We started to see regular demand come in. We did do a price increase back to February first, so there was a little bit of buy-in, but not much going into the end of the year with it. The primary driver for Proleukin in Q4 was AMTAGVI demand. As we look at Q1, we already have the wholesalers reordering. Two have already placed orders. We're expecting the third to order soon, then they will continue to move forward with Proleukin orders based on AMTAGVI demand. That is our number one source of revenue.

You are going to see this level out. As we look at having Q1 price increases in the future, this will even out as you look at yearly forecasts into time.

David Dai (Director)

Got it. Thanks for that color. Just, a follow-up on Fred's earlier comment around AMTAGVI being a $1 billion peak sales opportunity. Maybe just, you know, help us understand how you get there, especially how should we think about contribution of melanoma, and non-squamous non-small cell lung cancer, and also the soft tissue sarcoma?

Frederick Vogt (Interim CEO and President)

Yeah, I think when I talk about that, David, I'm talking about continued growth in the AMTAGVI melanoma U.S. franchise, and we're seeing that growth. We're only in our first year of launch here, and we're at $264 million in revenue. Again, I know this is all this discussion about Proleukin versus AMTAGVI, but AMTAGVI is driving the whole thing. Yes, we do sell a small amount of Proleukin for other things, but the vast majority of these numbers are coming from Amtag. That's the point we're trying to make. We talk about $1 billion, we think that's the ultimate potential for this product in the U.S. and melanoma. On top of that, you've got non-small cell lung at 7x. On top of that, you've got sarcoma. On top of that, you've got frontline melanoma.

Just bear that all in mind. Do you want to follow up, Dan?

Dan Kirby (Chief Commercial Officer)

Sure. Sure. $1 billion in melanoma alone is completely achievable. If you look at where we are right now, we're a quarter way through that journey, and we are just loading up the community ATCs right now. If you look at cell therapy launches in the liquid tumor space, they did have the advantage of following an allotransplant treatment modality with hematology oncology pathway. We're creating a pathway with the solid tumor medical oncologist. We're standing that up now, and in the initial phase, we're doing over a quarter billion dollars with both products, and we see that escalating in the U.S. alone to over $1 billion. When we talk about layering lung in, I mentioned in the script, that is a $10 billion opportunity, a much larger market to go into.

Sarcoma we do see as being equivalent to melanoma, so we do see tremendous potential to be well over $10 billion-$12 billion in the U.S. with AMTAGVI.

David Dai (Director)

Scott, thank you so much.

Dan Kirby (Chief Commercial Officer)

Good.

Operator (participant)

Thank you. Our next question comes from Etzer Darout with Barclays. Your line is open.

Etzer Darout (Managing Director and Senior Biotechnology Analyst)

Great, thanks for taking the question. Congrats on the quarter. Just, on gross margins, wondered if you could comment at all on, what may be the near term impact on the ex-U.S., commercial launches, Canada and others, could have on gross margins, given the improvement that you've seen, to date? Thank you.

Corleen Roche (CFO)

Okay, Etzer. Well, I think I just wanna make sure I'm understanding. You're asking, what will the ex-U.S. launches, what impact will they have on margins? All of our manufacturing operations today are in-house, so we're gonna have economies of scale. I think that can only help margins, right? As we grow and add in additional volume from those launches.

Dan Kirby (Chief Commercial Officer)

Can I add on to that quickly?

Corleen Roche (CFO)

Yeah.

Dan Kirby (Chief Commercial Officer)

As we look at it, manufacturing for our ex-U.S. launches will be out of our Philadelphia facility. We do not plan on adding additional manufacturing facilities worldwide. We're already servicing those regions in our clinical trials, and we can service them commercially, so there's no added expense there. Also, too, if you look at what's going on in the landscape, most-favored nation, et cetera, we do not have an ex-U.S. price negotiated yet. We're in the process of that as our approvals come. We do not have a lower price outside the U.S. We are going to see how this situation evolves, but we are in a good position not to have that as we're going into our negotiations with the U.K., Canada, et cetera.

Etzer Darout (Managing Director and Senior Biotechnology Analyst)

Great, thanks for that color.

Operator (participant)

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

Asthika Goonewardene (Managing Director and Senior Biotechnology Analyst)

Hey, guys, morning, thanks for taking my question today. When we start thinking about the, you penetrating into the community, in the U.S. and setting up ATCs there, is there gonna be a material difference in the timing it takes to get a community site up and running versus, let's say, what on average it takes you to get an academic center up and running? How should we think about that? Is there a lot of diversity in the different community settings, maybe ones who already have some sort of a cell therapy program versus those who don't? I have 2 more follow-up questions. I'll ask one of them now.

Can you comment on the Tandem data, and the better ORR that was seen early this year when that was presented? Can you use this real-world data when your MSLs are talking to physicians?

Dan Kirby (Chief Commercial Officer)

Great questions. I'll start with the first one regarding the community uptake. One of the things that we do see with the community will be similar to what we saw in the academics, and that is just the relationship with the surgeon, the medical oncologist, and the cell therapy lab to get up and running for it. That should be a similar learning curve. We did have some academic sites in the clinical trial, so that was the initial wave with the AMTAGVI launch, but we are seeing them come online. This is also balanced with the fact that they are closer to where these patients are being treated with frontline melanoma and subsequent therapies, so we can get them to treatment quicker. The learning curve will go up.

As you see with most ATCs, it is a financial reimbursement where they want to run one or two patients first, make sure the financial reimbursement is there with the payers. We have that established and tremendous coverage with AMTAGVI and Proleukin throughout all the payers. Once they see the first two go through, they start to accelerate patients in treatment. It should be similar to the academics when we look at getting them up and running. You can see the first couple are even on our website right now. In regards to the real-world evidence that was presented at the cell therapy meeting earlier this month, I will say that the MSLs already have that information reactively, and we are submitting that for publication as well to allow it to be more broadly distributed.

I don't know if Brian has anything to add on to the real-world data. It is tremendous news about the earlier line treatment. Brian?

Brian Gastman (EVP of Transitional Medicine and Research)

Yeah, thank you, Dan. Well, first of all, we presented it nationally or internationally at the Tandem meeting in Salt Lake City couple a weeks ago. It got a lot of attention. I've heard personally people very excited, but not just because the data was out, but also it validated what many PIs, KOLs, physicians have been seeing in the clinic. They need this data to actually help get their message out to their local physicians, because the right time to treat the patient is as soon as possible, and you can see what happens, how great the responses are. They're better than we saw in our trial. They're the best in class, and this is the kind of results that we've been looking for.

Asthika Goonewardene (Managing Director and Senior Biotechnology Analyst)

Great. Thanks, guys. Then lastly, to sum up, Proleukin reordering that happened in Q1. Just curious, you mentioned you had a February 1st price increase. Did any of the reordering happen after the February 1st price increase?

Dan Kirby (Chief Commercial Officer)

They typically order before the price increase. Wholesalers operate on very low margins, we did a 9% price increase on both products, affected February 1st of this year. They would do the buy-in for Proleukin in advance of that price increase. We did announce it to allow for payer case rates to adjust, which have happened, because we're a post-price increase right now. They were aware of the price increase coming and would buy accordingly.

Asthika Goonewardene (Managing Director and Senior Biotechnology Analyst)

Got it. Thanks for taking my questions, guys.

Operator (participant)

Thank you. This concludes the question and answer session. I would now like to turn it back to Fred Vogt for closing remarks.

Frederick Vogt (Interim CEO and President)

Thank you again for joining the Iovance Biotherapeutics fourth quarter and full year 2025 conference call. We plan to provide more detail on U.S. launch growth when we introduce our full-year revenue guidance in the near future. Please stay tuned to updates through 2026 on our commercial launch and pipeline, as well as our cost optimization initiatives to drive towards profitability. We are motivated by the frequent stories from more and more patients who are benefiting from our cell therapies. As always, we're thankful to our patients, healthcare professionals, and advocacy communities, as well as our partners. I would also like to thank our exceptional Iovance team, in addition to our dedicated shareholders and covering analysts for their commitment to the mission to remain the global leader in innovating, developing, and delivering current and future generations of cell therapies for patients with cancer. Thank you.

Operator (participant)

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