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DATE

Tuesday, February 24, 2026 at 8:30 a.m. ET

CALL PARTICIPANTS

  • Interim CEO and President — Frederick G. Vogt
  • Chief Financial Officer — Corleen Roche
  • Chief Commercial Officer — Daniel G. Kirby
  • Chief Operating Officer — Igor P. Bilinsky
  • Chief Medical Officer — Friedrich Graf Finckenstein
  • Executive Vice President, Clinical Development — Brian Gastman
  • Head, Regulatory and Translational Medicine — Raj K. Puri
  • Vice President, Commercial Operations — Ben Burnett

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TAKEAWAYS

  • Product Revenue -- $87,000,000 for the quarter, up approximately 30% sequentially from the third quarter, driven by AMTAGVI demand.
  • Full Year Revenue -- $264,000,000, a 61% increase year over year, with AMTAGVI revenue rising 112% for the same period.
  • Gross Margin -- 50% for the fourth quarter, improving from 43% in the prior quarter, attributed to operational optimization and manufacturing internalization at ICTC.
  • Cash Position -- $303,000,000 at year-end, with extended runway to fund operations into 2027 through cost-saving initiatives.
  • AMTAGVI Peak Sales Potential -- Management projected U.S. peak sales of "$1,000,000,000-plus U.S. sales at peak," with non-small cell lung cancer described as a "seven times larger" market opportunity than melanoma.
  • Proleukin Revenue Proportion -- Represented 17% of full-year product revenue, aligning with previous management projections of 16%-17%.
  • Sarcoma Clinical Update -- Lifileucel showed a 50% confirmed objective response rate among six evaluable patients with undifferentiated pleomorphic sarcoma or dedifferentiated liposarcoma, where standard-of-care response rates are below 5%.
  • Soft Tissue Sarcoma Market Size -- Over 8,000 new cases annually in the U.S. and Europe, with more than 3,500 classified as advanced disease.
  • Fast Track Designation -- The FDA granted Fast Track status to lifileucel for previously treated non-squamous non-small cell lung cancer, supporting plans for a supplemental BLA and potential 2027 launch.
  • Manufacturing Improvements -- All lifileucel production transitioned to the ICTC facility, supporting uninterrupted global supply and enhanced gross margins.
  • Clinical Metrics (IOV-LUN-202) -- Lifileucel showed an objective response rate of 26%, a disease control rate of 72%, and an unreached median duration of response after more than 25 months of follow-up in non-squamous non-small cell lung cancer.
  • Enrollment Trends -- Acceleration noted in the Phase III TILVANCE-301 trial for AMTAGVI, with ongoing expansion in both academic and newly added community ATCs; management reported continued Q1 demand momentum.
  • Gross-to-Net Deductions -- Less than 2% overall impact in 2025, indicating minimal effect from typical pharmaceutical rebates or discounts.
  • Upcoming Revenue Guidance -- Management communicated that updated 2026 revenue guidance will be provided in "the very near future."
  • Proleukin Price Increase -- A 9% price increase was implemented on February 1, 2026, for both Proleukin and AMTAGVI, with wholesalers reordering in advance.

SUMMARY

Iovance Biotherapeutics (IOVA 4.65%) reported quarterly and full-year product revenue growth driven primarily by commercial demand for AMTAGVI in advanced melanoma, with accelerating uptake across both academic and community treatment centers. The company confirmed that lifileucel received FDA Fast Track designation for previously treated non-squamous non-small cell lung cancer and initiated new clinical development in advanced soft tissue sarcoma following a 50% response rate in early data. Operational execution included the complete transition of manufacturing to the ICTC facility, which supported gross margin expansion and secured supply capabilities for anticipated global launches. Management highlighted continued manufacturing efficiency gains, indicated further commercial expansion into additional indications, and reiterated plans to publish updated trial results and global commercialization efforts throughout 2026.

  • Chief Financial Officer Roche highlighted minimal impact from gross-to-net adjustments, maintaining strong reported revenue integrity through 2025.
  • Chief Commercial Officer Kirby stated, "Recently launched campaigns focused on health care professionals and patients are having a positive impact," resulting in higher-quality referrals and deeper penetration in the community oncology setting.
  • Brian Gastman noted, "Among six evaluable patients, the confirmed objective response rate was an unprecedented 50%," and explained durability of response is consistent with prior lifileucel data in other solid tumors.
  • Friedrich Graf Finckenstein reported that lifileucel achieved a 26% objective response rate and 72% disease control rate in the IOV-LUN-202 registrational study for previously treated non-squamous non-small cell lung cancer, with "median duration of response was not yet reached after more than 25 months of follow-up."
  • Management outlined plans to present expanded clinical trial updates and pipeline progress at major medical meetings in 2026, aiming to support further regulatory submissions and potential new launches.

INDUSTRY GLOSSARY

  • ATC (Authorized Treatment Center): A hospital or clinic certified to administer specialized cell therapy products such as AMTAGVI.
  • TIL (Tumor-Infiltrating Lymphocyte): Patient-derived immune cells used in cell therapy to target solid tumor cancers, the platform for lifileucel.
  • ICTC (Iovance Cell Therapy Center): Iovance's in-house U.S. manufacturing facility for cellular immunotherapy production.
  • Proleukin: Recombinant interleukin-2 (IL-2), administered alongside cell therapy to promote immune cell expansion after infusion.
  • Objective Response Rate (ORR): The proportion of patients with tumor size reduction of a predefined amount, a standard measure of clinical trial response.
  • Disease Control Rate: Percentage of patients in a clinical trial achieving partial response, complete response, or stable disease following therapy.
  • Gross-to-Net Adjustments: Deductions from gross pharmaceutical sales, including discounts, rebates, and chargebacks, to arrive at reported net revenue.
  • BLA (Biologics License Application): Submission to the FDA requesting approval to market a new biological drug product.

Full Conference Call Transcript

Frederick G. Vogt, Interim CEO and President of Iovance Biotherapeutics, Inc.

Frederick G. Vogt: Thank you, Sara. In 2025, Iovance Biotherapeutics, Inc. 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 $264,000,000 was well within our annual guidance range. Our cash runway, bolstered by our ongoing cost savings initiatives, now extends into 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. And third, hone our operational excellence as our foundation for success. First and foremost, we are gaining positive uptake commercially with significant potential for AMTAGVI and Proleukin to reach $1,000,000,000-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 operating 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 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 has been previously treated non-squamous non-small cell lung cancer. This blockbuster U.S. market is about seven times larger than our peak U.S. 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 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 two 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 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 lifileucel in the U.S. and beyond. We are 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 and immune 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, 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 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 of AMTAGVI within our U.S.-based Iovance Cell Therapy Center, or ICTC, as well as the 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 will now turn the call over to Corleen Roche, our Chief Financial Officer, who will provide further updates on our fourth quarter and full year financial results.

Corleen Roche: Thanks, Fred, and good morning, everyone. Iovance Biotherapeutics, Inc. 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 $87,000,000 demonstrated meaningful growth of approximately 30% from the prior quarter, driven by AMTAGVI. In our first full year of launch, total product revenue of $264,000,000 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 $303,000,000 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 2027. In closing, our 2025 financial results reflect our commitment to flawless execution in commercial utilization, improved margin, and extended cash runway that supports our path to profitability. I will now turn the call to Daniel G. Kirby, our Chief Commercial Officer, to provide additional context.

Daniel G. Kirby: 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 while unlocking 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 health care professionals and patients are having a positive impact.

The community market will expand to further 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 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 later lines of therapy. Initiatives within academic ATCs are also generating positive results from earlier tissue procurement and earlier treatment for specific patient types. For example, ATCs are offering the antibody 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 United Kingdom, 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 $10,000,000,000 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 Biotherapeutics, Inc., 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 2025, we achieved both our largest manufacturing volume and highest commercial manufacturing success to date.

Igor P. Bilinsky: 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 will 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 Graf Finckenstein. Thanks, Igor.

Today, I will focus on our two registrational programs.

Friedrich Graf Finckenstein: First, enrollment is accelerating across a broad and expanding global footprint on our Phase III 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: Thank you, Friedrich. I am 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 immunotherapy 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 of 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 we would see TIL therapy do in solid tumor cancers when I chose to leave academic medicine to join Team Iovance Biotherapeutics, Inc. 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. 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: We will now open for questions. To ask a question, please press star 11 on your telephone keypad and wait for your name to be announced. In the interest of time, we ask that you please limit yourself to one question, and you may rejoin the queue. Our first question comes from Andrew Tsai with TD Cowen. Your line is open.

Andrew Tsai: Hey, good morning. Thanks for the updates, and thanks for maybe for the TILVANCE 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 AMTAGVI plus PD-1 combo data later this year? And regardless of timing, what kind of ORR and PFS do we want to see compared to PD-1 alone?

Frederick G. Vogt: Thanks. 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 is in the near term that we will be able to do that. We cannot commit to doing that in 2026 right now. It is 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 is a blinded study; we do unblind to do the analysis, and if we announce that, we are basically announcing that we are coming to a supplemental BLA at the same time. That is the whole point of that. Friedrich, do you want to talk about the ORR and PFS considerations on that trial, please?

Friedrich Graf Finckenstein: 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, one of them being ORR, the other one being PFS, 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 percent 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 is what is giving us the confidence around a successful readout for the ORR endpoint.

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

Tyler Van Buren: 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 percentage of sales in subsequent quarters.

Corleen Roche: Hey, Tyler. It is Corleen. First, you talked about Q4 split. We did have all three ordering in Q4, and we also took a—

Ben Burnett: So there is a little bit of buy-in there.

Corleen Roche: Not crazy. We have not guided, so I do not have a split for you going forward. What I can tell you on the margins is, yes, we expect further improvement.

Daniel G. Kirby: And I will just add on to that, Tyler. We did see all three wholesalers, as Corleen mentioned, ordered in Q4. We have already seen reordering happen in Q1. And moving forward, you should see, again, regular orders for AMTAGVI for Proleukin to go with AMTAGVI sales. That is 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 AMTAGVI demand for Proleukin sales.

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

Xiaochuan Dai: Hi. Thanks for taking our question. This is Kwan on for Yanan. You share with us how the manufacturing success rate change over time? And what is the scrap cost for this quarter? Thank you.

Xiaochuan Dai: Could you clarify the last part of the question, which cost?

Andrew Tsai: Scrap cost.

Xiaochuan Dai: Oh, the scrap cost? Scrap cost will be in our 10-K filing that will come out around 9/15. It is consistent with prior quarters. I will—maybe I will make some comments on manufacturing success and then Igor can jump in and help as well. I think we do not release actual percentages and stuff here. We do not think that is helpful to investors. It is improving. We are getting better at it. The margins reflect that. You can see the margins are growing. As Corleen mentioned, margins are being driven not just—really being driven by AMTAGVI performance. Proleukin there comes in and out.

But we have had good margins for two quarters in a row now with Proleukin 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 made with what you said in the earlier part of the call?

Igor P. Bilinsky: Yes. Happy to. Thanks for the question, Yanan. So there are really two avenues for improving success rates. One is internal, where we continue implementing improvements in manufacturing, and those—a lot 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 borne fruit so far, and we continue working on both fronts.

Xiaochuan Dai: Got it. Thank you.

Operator: Our next question comes from Salim Syed with Mizuho. Your line is open.

Salim Syed: Hey, guys. Thanks for the question. Maybe just one on guidance from us. So you provide ’26 guidance—Fred, you mentioned that you plan to provide it shortly. 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 mean or conservative guide? Just help us framework how we should be thinking about that. Thank you.

Frederick G. Vogt: Yeah. Right now, we are seeing remarkable, remarkable growth in the AMTAGVI business. We do need to be sure that our projections are well supported, so we are taking some time to do that. It is very early in the year right now, of course. But as I mentioned during the prepared remarks, we are going to be putting guidance out very, very soon. I think you will see total product guidance; you will see some guidance potentially on quarters, we will 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 Proleukin and the revenue from AMTAGVI have now fallen right in line with what we were saying a year ago, in that Proleukin 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 you have right now to help support that.

Operator: Okay. Thanks very much. Thank you. Our next question comes from Reni John Benjamin with Citizens. Your line is open.

Reni John Benjamin: Congrats—hitting the guidance. Maybe just a couple of questions. One, can you talk a little bit about 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.

Daniel G. Kirby: Sure. Hey, Reni, it is Dan. Thank you very much for the question. So 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 are coming online as well this year. We expect a learning curve as we saw with the initial academics coming online, so you will 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 are seeing in Q1, is that there are certain patient types there that were not making it to AMTAGVI treatment.

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 ATC we were not previously able to access, that our initiatives now are allowing us access. So we expect growth to continue in the academic segment, and then the community ATCs are coming online now. They are having their process of testing a few patients out, will be ramping up as the year goes on. So we will see more of them starting in the second quarter through the end of the year and into 2027. Right now, our base book of business is strong and growing with the academic—

Reni John Benjamin: Got it. Okay. Thanks for that. And then just a follow-up, you know, regarding the sarcoma data. You know, this is quite new and, as you mentioned, unprecedented. Can you—it is in six evaluable 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 are seeing here for these patients? 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 G. Vogt: I will take the first part of that, and then I will let Brian and Raj answer the other part of it. We are excited to present this to a medical congress this year. We have not identified that congress yet, but obviously we really like the big ones like ASCO and ESMO. We will have to see how the timing goes, but the data is available right now. I do expect to be able to put together pretty quickly for presentation. So stay tuned for that. It should be pretty exciting. Brian, do you want to take the second part?

Brian Gastman: Yeah. So in terms of depth and durability, I think it is 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. Think it will be a while before we will be able to tell you because of the power of having a living therapy on board. In terms of, though, the depth, what is 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 have actually watched, really excitingly, scans get better and better and better.

And so we saw patients that—if it was on a swimmer's plot, we would see them swimming, and on a spider plot they would still be dropping, and so we do not even know how good these patients will get. But I think for all of us, what was really remarkable, we saw how many responders we got and how they were deepening. So I think more to come there, but it gave us a lot of encouragement.

Raj K. Puri: Will provide any sample size for the—

Brian Gastman: Yeah. Thank you for the question. So based upon the prior approvals in various soft tissue sarcoma subtypes recently by FDA, approval size for the various subtypes did range 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 registration strategy.

Operator: Perfect. Thanks for taking the questions. Thank you. Our next question comes from Colleen Margaret Kusy with Baird. Your line is open.

Nicholas Lorusso: 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, and could you talk about just latest thoughts on path to full approval in non-small cell lung cancer? And then I have a follow-up question as well. Thanks.

Frederick G. Vogt: Yeah. 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, are planning on the same timing we mentioned before, with this potentially launching in 2027. This is pretty exciting to us. We are finishing the trial right now. And we are very confident that this product provides great benefit for non-small cell lung patients.

Nicholas Lorusso: Thanks. And then just a quick one on sarcoma. Just wondering if you are considering expanding into other subtypes of sarcoma outside of these initial two?

Frederick G. Vogt: 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 are a number of other sarcoma subtypes that are of interest, and 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 is there anybody interested in apparently getting their checkpoints approved here where they lack the efficacy to do so—we are really going to look across the entire space, really try to tap into this area of unmet medical need.

Nicholas Lorusso: Great. Thank you.

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

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

Daniel G. Kirby: Sure, David. So this is Dan. I will take the question on Proleukin. You saw in Proleukin, as you recall, all throughout last year, we had—when first wholesaler came on in Q2, two were reordering in Q3, all three ordered in Q4. Started to see regular demand come in. We did do a price increase effective February 1, so there was a little bit of buy-in, but not much, going into 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 are expecting the third to order soon.

And 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, and as we look at having Q1 pricing increases in the future, this will even out as you look at yearly forecast in the past.

Operator: Got it. Fantastic color. And then just a follow-up on Fred's earlier comment around AMTAGVI being one billion-plus sales opportunity. Maybe just, you know, help us understand how you get there, especially—should we think about contribution of melanoma and non-squamous non-small cell lung cancer, also soft tissue sarcoma.

Frederick G. Vogt: Yeah, I think when I talk about that, David, I am talking about continued growth in the AMTAGVI melanoma U.S. franchise. And we are seeing that growth. So we are only in our first year—launch year. And we are at $264,000,000 in revenue. And, 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 AMTAGVI. That is the point we are trying to make. We talk about $1,000,000,000. We think that is the ultimate potential for this product in the U.S. melanoma.

On top of that, you have got non-small cell lung at 7x. On top of that, you have got sarcoma. On top of that, you have got frontline lung. From frontline lung—so just bear that all in mind.

Daniel G. Kirby: Do you want to follow up, Dan? Sure. So $1,000,000,000 in melanoma is completely achievable. If you look at where we are right now, we are 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 allo-transplant treatment modality with hematology-oncology pathway. We are creating a pathway with the solid tumor medical oncologist. So we are standing that up now. And in the initial phase, we are 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, and I mentioned in the script, that is a $10,000,000,000 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 $10,000,000,000 to $12,000,000,000 in the U.S. with AMTAGVI. Scott, thank you so much.

Operator: Our next question comes from Asthika Goonewardene with Barclays. Your line is open.

Asthika Goonewardene: Great. Thanks for taking the question, and congrats on the quarter. Just on gross margins, wondered if you could comment at all on what maybe the near-term impact on the ex-U.S. commercial launches, Canada and others, could have on gross margins given the improvement that you have seen to date? Thank you.

Corleen Roche: Okay, Asthika. So, well, I think I just want to make sure I am understanding. You are asking what will the ex-U.S. launches—what impact will they have on margin? So all of our manufacturing operations today are in-house. So we are going to have economies of scale. I think that can only help margin, right, as we grow and add additional volume from those launches.

Daniel G. Kirby: So I can add on to that, Corleen. Yeah. As we look at it, manufacture for ex-U.S. launches will be out of our Philadelphia facility. So we do not plan on adding additional manufacturing facilities worldwide. We are already servicing those regions in our clinical trials, and we can service them commercially. So there is no added expense there. Also, too, if you look at what is going on in the landscape—most-favored nation, etcetera—we do not have an ex-U.S. price negotiated. We are 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 are going into our negotiation with the U.K., Canada, etcetera.

Asthika Goonewardene: Great. Thanks for that color.

Operator: And our final question comes from Asthika Goonewardene with Truist. Your line is open.

Asthika Goonewardene: Hey, guys. So when we start thinking about the new—penetrating into the community in the U.S., and say you have ATCs there, is there going to be a material difference in the timing if in case you get a community site up and running versus, let us 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 that already have some sort of a cell therapy program versus those who do not? And then I have two more follow-up questions.

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

Daniel G. Kirby: So great questions. I will 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 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—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 AMTAGVI and Proleukin throughout all the payers. So once they see the first go through, they start to accelerate patients and treat. 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 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 do not know if Brian—anything to add on to the real-world data. It is tremendous news about the earlier line treatments.

Brian Gastman: Yeah, thank you, Dan. Well, first of all, we presented it nationally or internationally at the Tandem meeting in Salt Lake City a couple weeks ago. It got a lot of attention. I have 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 are better than we saw in our trial.

They are the best in class, and this is the kind of results that we have been looking for.

Asthika Goonewardene: Great. Thanks, guys. And then lastly, just on the Proleukin reordering that happened in Q1, just curious—you mentioned you had a February 1 price increase. Did any of the reordering happen before the February 1 price increase?

Daniel G. Kirby: So they typically order before the price increase. Wholesalers operate on very low margins. So we did 9% price increase on both products effective February 1. So 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 are post price increase right now. So they were aware of the price increase pending and would buy accordingly.

Asthika Goonewardene: Got it. Thanks for taking my questions, guys.

Operator: Thank you. This concludes the question-and-answer session. I would now like to turn it back to Frederick G. Vogt for closing remarks.

Frederick G. Vogt: Thank you again for joining the Iovance Biotherapeutics, Inc. fourth quarter and full year 2025 conference call. We plan to provide more detail on the U.S. launch 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 profitability. We are motivated by the frequent stories from more and more patients who are benefiting from our TIL cell therapies. As always, we are thankful to our patients, healthcare professionals, and advocacy communities as well as our partners.

I would also like to thank our exceptional Iovance Biotherapeutics, Inc. team, in addition to our shareholders and covering analysts, for their commitment to the mission for maintaining a global leader in innovating, developing, and delivering current and future generations of TIL cell therapies for patients with cancer.

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