Iovance Biotherapeutics, Inc.

Good day, and 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 the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Sarah Pellegrino, Senior Vice President, Investor Relations and Corporate Communications at Iovance. Please go ahead.

Thank you, operator. Good morning and 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 IOVANS.com. This conference call will include forward-looking statements regarding IOVANS' 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 technology, 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. I will now turn the call over to Dr. Fred Voth, Interim CEO and President of Iovance.

Thank you, Sarah. 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 MTAGV adoption while streamlining costs and optimizing operations. Our operational strength resulted in a robust 30% revenue growth driven by MTAGV 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 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 Ampagni and advanced melanoma. Second, harness the power of our tilt pipeline to expand into new indications and next-generation products. And third, hone our operational excellence as our foundation for success. First and foremost, we're gaining positive uptake commercially with significant potential for Amtagby and Perlucan to reach $1 billion-plus U.S. sales at peak. After a considerable increase in fourth-quarter demand for Amtagby, 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 mTAGV. On top of increasing demand, we are benefiting from operational improvements throughout the entire mTAGV treatment journey, from patient identification through manufacturing to infusion. When the heels of positive momentum in the fourth quarter, we expect remarkable revenue growth in 2026, driven by Amtagme. 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 into 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 Lifolucel is in previously treated non-squamous, non-small cell lung cancer. This blockbuster US market is about seven times larger than our PQS sales opportunity in advanced melanoma. In our registrational patient population, Lifolucel 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 medical need for lepilucel 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 lepilucel announced in the press release alongside positive early data. In previously treated patients with two aggressive difficult to treat advanced soft tissue sarcomas, Leifeluzel demonstrated an unprecedented 50% confirmed response rate. As Brian will highlight, Leifeluzel 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 to 10 months. Together, these sarcomas impact more than 8,000 patients in the U.S. and Europe annually, significantly increasing our market opportunity for Leifeluzel in the U.S. and beyond. We're working expeditiously to initiate and complete a single-arm registrational trial to launch in these sarcomas. Our robust pipeline is the backbone of immuno-oncology in multiple-cell 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 tilt therapies. And 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 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 their 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 Amtagni within our U.S.-based Diaban 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 Coraline Roche, our Chief Financial Officer, who will provide further updates on our fourth quarter and full-year financials.

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 MTAGV. In our first full year of launch, total product revenue of $264 million increased by 61% over the prior year, driven by MTAGV 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 Amtagvy for more patients at an expanding number of treatment centers. The impact of gross to net adjustments remained minimal at less than 2% overall in 2025. Fourth quarter gross margin from cost of sales increased 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.

Thank you, Colleen. Over the course of 2025, we made tremendous progress in three key areas towards our ultimate goal, to establish MTAGV 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 MTAGV, which drove our Q4 revenue. Second, Penetrating the community market will unlock MTagV'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 most from antagonist real-world data resonating with medical oncologists has shown unprecedented efficacy with more than one in two patients responding in the second line setting and one in three patients in patients in later lines of therapy initiatives within academic ATC's are also generating positive results from earlier tissue procurement and earlier treatment for specific patient types for example ATCs are offering antagony 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, antagony has the potential to reach more than towards expansion, including MTAGV approval in Canada, pending approvals in the United Kingdom, Australia, and Switzerland, and additional progress towards resubmitting a marketing authorization application to the European Medicine 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 MTAG-V ATC network of U.S. academic and community practices can leverage their existing TIL infrastructure for rapid adoption and 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.

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 my Felucel 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 of 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.

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 TILVANS 301 trial. We are investigating MTAGV 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 LUN202 Registrational Trial, Life Illusal has demonstrated a best-in-class clinical profile and recently received FAST-TRACK designation from the US 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 uptake 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.

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 de-differentiated liposarcoma. They have no group immunotherapy options. Among six valuable patients, the confirmed objective response rate was an unprecedented 50%. Responses were deep and improved over time, consistent with the durability for liposomal and 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 sterative 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 Tilt 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 Tilt 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 for patients who 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.

As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 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.

Hey, good morning. Thanks for the updates, and thanks for taking my question. Maybe for the Tillvance update that you provided, it sounds like enrollment is picking up nicely. So is it possible that we could get first line melanoma data with mTAGI PD1 combo data later this year. But regardless of timing, what kind of ORR and PFS do we want to see compared to PD1 alone? Thanks.

Yeah, maybe I can take the first part of that, Andrew, and then Frederick 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 that 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. And then, of course, if we read that data, it's a blinded study. We don't blind to do 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... It sounds like Frederick's muted, so... 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 06 trial. Remember, the trial design of TIL-LANS is comparison of the combination of PEMBRO plus TIL versus PEMBRO monotherapy. The trial is designed with two dual primary endpoints, one of them being OR or the other one being PSS. So OR giving us an opportunity for an early read. The benchmark in the Keynote 06 trial for ORR was about in the mid-30s. Probably the true real-life ORR with temporal monotherapy is probably more in the 30 and slightly below percent range. Remember, we have very encouraging data on the efficacy of the combination from our COM2 to 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. Questions about ?

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

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

Hey, Tyler. It's Coraline. So first you talked about Q4 split. We did have all three distributors ordering in Q4, and we also took a break. So 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 improvements.

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

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

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

Could you clarify the last part of the question? What cost? Scrap.

Oh, the scrap costs?

Scrap costs will be in our 10-K filing that will come out around 9-15, but it's consistent with prior quarters. Maybe I'll make some comments on manufacturing success, and then 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 Corley mentioned, these margins are being driven, not just really being driven by antagony performance. Prolucan's there. It comes in and out. But, you know, we've had good margins for two quarters in a row now with Prolucan moving up and down. And we expect that to continue. And manufacturing success is driving that improvement at the end of the day. Igor, do you want to make any comments specifically about what you said in the... Earlier part of the call?

Yes, happy to. Thanks for the question, Jan. So there are really two avenues for improving success rates. One is internal, where we continue implementing improvements in manufacturing, and those have been implemented and more are coming. And 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. So both of those have their route so far, and we continue working on both fronts. Got it.

Thank you. Our next question comes from Sawim Saeed with Mizuho. Your line is open.

Hey, guys. Thanks for the question. Maybe just one on guidance from us. So you didn't provide 26 guidance. Fred, you mentioned that you plan to provide it shortly. I'm just curious, what was the logic not to provide it now? And when we do get it, can you just give us some context? Like, is it going to be total revenue product? Is it more like a meat or conservative guy? Just help us framework how we should be thinking about that. Thank you.

Yeah, right now we're seeing remarkable growth in the MTAGNY 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 data is supported. One thing I do want to mention is when – I know you asked about breaking out the products. For the full year of 2025, the revenue from ProLucan and the revenue from Amtagby have now fallen right in the line with what we were saying a year ago, in that ProLucan generates about 17% of our revenue. If you recall, many, many calls, we talked about the 16% number based on the ratio of the price. So we are seeing that long-term balance come into play, and as Dan mentioned, ordering patterns are stabilizing, and we expect normality on that through the year. So you may not see us particularly put a number of proleukin for one quarter over another, but you can be confident in the long-term ratio of these things and use the numbers that you have right now to help support that.

Okay. Thanks very much.

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

Good morning, guys. Thanks for taking the questions and congrats on hitting the guidance. Maybe just a couple 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 and 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 a sense as to how this is going to grow potentially this year? And then I have a follow-up on the sarcoma data.

Hey, Randy, it's Dan. Thank you very much for the question. So for Q4, our base book of business is the academic ATCs, and we saw a 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. But for Q4, what we saw in the academic ATCs, which is carrying over to what we're seeing in Q1, that we're not making it to MTAGI 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. So we expect growth to continue in the academic segment. And then 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. So we'll see more of them starting in second quarter through the end of the year and into 27. Right now, our Facebook business is strong and growing again.

Got it. Okay. Thanks for that. And then just to follow up, you know, regarding the sarcoma data, you know, this is quite new, and as you mentioned, unprecedented. Can you, it's in six available patients. 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?

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

Yeah. So in terms of depth and durability, I think it's important to note that, obviously, the trial has been running for years. Like all of our trials, our durability tends to be measured in very long time frames. So I think it will be a while before we'll be able to tell you because of the power of having 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 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, and so we still have patients that, you know, if it was on a swimmer's plot, we would see them swimming, and on a spider plot, they'd still be dropping, and so we don't even know how good these patients will get, but I think for all of us, it was really remarkable when we saw how many respirers we got and how they were deepening, so I I think more to come there, but I think it gave us a lot of encouragement.

Thank you for the question. So you're based upon the prior approvals in various 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. And based on the characteristics of these two subtypes that we are discussing today, we really expect very similar patient numbers for a registration strategy.

Perfect. Thanks for taking the questions.

Thank you. Our next question comes from Colleen Cousy with Bayard. Your line is open.

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

Yeah, 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-fossil lung patients.

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

Yes. And 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. But we are looking at additional, besides UPS and DDLPS, there's a number of other sarcoma subtypes that are of interest. And now that we see strong activity for tilt in this space and a lack of approved options, including approved checkpoint options for these patients, nor are there anybody interested in apparently getting their checkpoints approved here where 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.

Great. Thank you.

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

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

Sure, David. So this is Dan. I'll take the question on ProLucan. We saw in ProLucan, as you recall all throughout last year, we had one first wholesaler came on in Q2, two were reordering in Q3, all three were reordering in Q4. We started to see regular demand come in. We did do a price increase back to February 1st, 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 ProLucan in Q4 was was Antagni 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. And then they will continue to move forward with Prolucan orders based on Antagni Demand. That is our number one source of revenue. You are going to see this level out. And as we look at having Q1 price increases in the future, this will even out as you look at yearly forecasts in the

Got it. Thanks for that color. And then just to follow up on Fred's earlier comment around antacid being a women's BLM 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-spleen and non-small cell lung cancer and also sub-tissue sarcoma?

Yeah, I think when I talk about that, David, I'm talking about continued growth in the antacid melanoma U.S. franchise. And we're seeing that growth. So we're only in our first year launch here, and we're at $264 million in revenue. And again, I know this is all this discussion about Prolucan versus Antagni, but Antagni is driving the whole thing. Yes, we do sell a small amount of Prolucan for other things, but the vast majority of these numbers are coming from Antagni. 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. in melanoma. On top of that, you've got non-small cell lung and 7X. On top of that, you've got sarcoma. On top of that, you've got frontline melanoma. So just bear that all in mind. Do you want to follow up, Dan?

Sure. So $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 outlet transplant treatment modality with hematology oncology pathway. We're creating a pathway with the solid tumor medical oncologist. So 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 a billion dollars. We talk about layering lung in. I mentioned in the script that is a $10 billion opportunity, a much larger market to go into. And sarcoma we do see as being equivalent to melanoma. So we do see tremendous potential to be well over $10 to $12 billion. in the U.S. with MTAGI.

Scott, thank you so much.

Thank you. Our next question comes from Edser Daru with Barclays. Your line is open.

Great. Thanks for taking the question, and 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 XUS commercial launches Canada and others could have on gross margins given the improvement that you've seen to date? Thank you.

Okay, sir. So I think I just want to make sure I'm understanding. You're asking what will the XUS launches, what impact will they have on margins? So all of our manufacturing operations today are in-house. So we're going to have economies of scale. I think that can only help more than, right, as we grow and add in additional volume from those launches.

So I can add on to that, Courtney. As we look at it, manufacturing for XUS launches will be out of our Philadelphia facility. So 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. So 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.

Great. Thanks for that, Culler.

Thank you. And our final question comes from Asika Goonwarden with Truist. Your line is open.

Hey, guys. Morning, and thanks for taking my question today. So, when we start thinking about the community in the U.S., and so you have agencies there, is there going to 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. And 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? And then I have two 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?

So 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 trials, so that was the initial wave with the mTAGD 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. So 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 MTagV and ProLucan throughout all the payers. So once they see the first two go through, they start to accelerate patients and So 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 the website right now. In regard 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 treatments.

Right. Yeah, thank you, Dan. Well, first of all, we presented it nationally or internationally at the TANF meeting in Salt Lake City a couple 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. And 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.

Great. Thanks, guys. And then lastly, just on the pro-looking 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?

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

Got it. Thanks for taking my questions, guys.

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

Thank you again for joining the IVANCE 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 tilt-self 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 I-VANCE 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 tilt-self therapies for patients with cancer. Thank you.

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