All right. Great. Good morning, everyone. Tyler Van Buren here, Senior Biotech Analyst at TD Cowen. Thank you very much for joining TD Cowen's 46th Annual Healthcare Conference. For our next session, we have a hybrid presentation followed by Q&A with Iovance. It's my pleasure to introduce Corleen Roche, the Chief Financial Officer, and Igor Bilinsky, the Chief Operating Officer of Iovance. Corleen and Igor, it's a privilege to have you here. Thank you very much for joining me. I'll go ahead and hand it over to you to kick off the presentation.
Thanks, Tyler. As well as the whole team at Cowen for inviting us to present today. Can you hear me? Sorry. I'm not as loud as Tyler.
It's perfect.
I joined Iovance a little more than 6 months ago. Why? Because I'm so excited about the opportunity for TIL cell therapy to meaningfully benefit patients across solid tumor cancers, which by the way, represent more than 90% of all cancers diagnosed each year. Last week, we reported our 4th quarter and full year financial results that underscore our focus on value creation for patients and shareholders. In 2025, Iovance delivered substantial revenue growth, achieved groundbreaking data milestones, and strengthened our financial performance. We drove AMTAGVI adoption while streamlining costs and optimizing operations. Our operational strength resulted in a robust 30% quarterly revenue growth driven by AMTAGVI and our best ever 50% margin from cost of sales in the 4th quarter. Notably, total full year revenue of about $264 million was also well within our annual guidance range.
Following this 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, we will continue accelerating our U.S. commercial launch of AMTAGVI, the first and only approved therapy in previously treated advanced melanoma with a $1 billion-plus market opportunity in the U.S. alone. Second, we will harness the power of our TIL pipeline to expand into new indications and next generation products where we can leverage our existing technology platform, manufacturing, and commercial footprint across multiple blockbuster solid tumor indications. Third, hone our operational excellence as our foundation for success as we increase revenue, optimize spending, and importantly, extend cash runway on our path to profitability.
First and foremost, Iovance is benefiting from positive uptake commercially with a significant potential for AMTAGVI and Proleukin to reach a $1 billion U.S. peak sales. fourth quarter demand for AMTAGVI drove about a 30% increase in quarterly revenue, and like I mentioned, our best everly quarterly gross margin from cost of sales. The current acceleration in enrollment volumes in 2026 are coming from 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 long-term durability data and real-world experience and benefits of early treatment with AMTAGVI. The five-year clinical data, which we presented at ASCO and simultaneously published last June, highlight the powerful durability of a one-time treatment with lifileucel.
The response rate was 31%, median overall survival was near 20% in clinical patients that were heavily pretreated with a median of more than three prior lines of therapy. Complementing this five-year durability data, we recently presented even higher response rates from our very first real-world retrospective study of AMTAGVI. Higher efficacy was observed with earlier AMTAGVI treatment. More than one in two patients responded to AMTAGVI as a true second-line therapy compared to a third of patients in third line or later treatment settings. On top of the 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.
As we mentioned, in the near future, we will provide revenue guidance with our growth projections. Our next slide is a snapshot of our second pillar or the massive potential for our TIL platform to positively impact patients in new indications. Our robust portfolio is the backbone of immuno-oncology in multiple solid tumors today and in the future through next generation approaches. Across our ongoing and planned clinical trials in multiple solid tumor cancers, we are harnessing the overlap and scalability of our TIL platform, manufacturing leadership, and commercial capabilities. I only have a brief time to discuss our programs today, so I'll focus on our lead pipeline indication in non-small cell lung cancer, as well as our newest development program in aggressive soft tissue sarcomas. First, previously treated non-squamous, non-small cell lung cancer is a blockbuster U.S. market.
It's about seven times larger than our peak US sales opportunity in advanced melanoma. In our registrational patient population, lifileucel has demonstrated best-in-class clinical response rates and durability. In addition, the U.S. FDA has granted Fast Track designation that validates our clinical data and reaffirms the substantial unmet medical need for lifileucel in this indication. We are rapidly advancing our registrational trial. We look forward to presenting updated data and completing enrollment this year to support a supplemental Biologics License Application, or BLA, with a potential accelerated approval and launch in the second half of 2027. Notably, we will leverage our existing manufacturing processes and our entire AMTAGVI ATC network of U.S. academic and community practice. They can leverage their current TIL infrastructure for rapid adoption in non-small cell lung cancer upon approval.
On this next slide, I'm very excited to introduce early positive data in our newest indication for lifileucel. In previously treated patients with two aggressive, difficult to treat advanced soft tissue sarcomas, Lifileucel demonstrated an unprecedented 50% confirmed response rate and may offer the very first durable immunotherapy option in this treatment setting, where current outcomes with standard of care are abysmal. More than 8,000 patients annually in the U.S. and Europe are impacted by these soft tissue sarcomas, 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 in these sarcomas. We will also explore expedited pathways for registration as well as additional sarcoma subtypes in the development program.
In addition to our expansion opportunities for lifileucel, we are building upon our established global leadership to define next-generation approaches for TIL cell therapy. Our two clinical stage genetically engineered TIL cell therapies, depicted as IOV-4001 and IOV-5001 on this slide, have the potential to transform the treatment paradigm across a vast number of solid tumor cancers where patients have very few options. Our next generation IL-2 product, IOV-3001, may facilitate more accessible TIL therapies through better safety and less frequent dosing. Finally, our third pillar is to hone our operational excellence in support of the first two pillars as we increase revenue, optimize costs, and drive efficiencies toward profitability. In addition to achieving our best ever margin from cost of sales, we also reported our largest volume and highest manufacturing success rate, optimized spending, and implemented operational efficiencies in the fourth quarter of 2025.
Our cash runway, bolstered by our ongoing cost savings initiative, now extends into the third quarter of 2027. We own and control all of our manufacturing for AMTAGVI within our U.S.-based Iovance Cell Therapy Center, or ICTC as we call it, as well as critical components of our supply chain. We're capable of scale-up and expansion into new indications globally to bolster revenue without the need for significant capital spend. Throughout 2026 and beyond, we are committed to flawless execution and commercial utilization, improved margin, and extended cash runway that supports our path to profitability. Thank you so much.
Wonderful. Is the mic working? There we go. Mic's working. Thank you so much for that presentation, Corleen, and thanks for joining us up here, Igor. Maybe, we'll start with naturally, we'll start with the AMTAGVI launch. You all reported earnings last week, allowing you to meet the revenue guidance. Maybe you could just talk about a little bit more, elaborate on the demand dynamics in the fourth quarter, how you're seeing that continue into early 2026.
Yeah, I think. Is this on? Okay. Can you hear me? All right. I think that that really is representative of the AMTAGVI adoption and how we're driving that across the three pillars I mentioned. First, we're expanding our network of treatment centers. Second, we're going deep into the community. Third, we're utilizing our data, real-world evidence to bolster the education so that patients are getting treated earlier in their treatment journey. You know, as I mentioned, you saw the 30% revenue growth. We are also importantly looking at margins. Margins were 50% from cost of sales in Q4. We have a very sharp focus on that. We have very pointed programs for improving margin. The good news is all the manufacturing is internal.
We do an amazing job, and then, you know, some of these things are just okay, so how can we improve the processes, and how can we become a little bit more efficient as we, as we drive that revenue growth?
It sounds like the ICTC maintenance, this year, was much more seamless relative to last year. Maybe just elaborate on that a bit and if you expect there to be any potential impact to Q1 revenues from the maintenance.
Of course. Darla, good to be here. Is my mic on?
Yep.
Perfect. As Corleen mentioned in her presentation, the fourth quarter saw the highest manufacturing volume to date and the highest success rate to date. At the end of the fourth quarter early this year, we completed scheduled annual maintenance at ICTC successfully, and we learned from the experience the year prior. We put a number of measures in place to minimize any impact on manufacturing volume. We shifted volume to our contract manufacturer, and we increased capacity at ICTC immediately prior and following the maintenance period. Importantly, as a result of the maintenance, ICTC is now a modular facility, so in the future we can conduct maintenance without changing manufacturing volume at the facility.
After completion of the maintenance, we shifted 100% of the volume in-house into ICTC, so we fully control all manufacturing right now, which gives us a lot of levers to improve operational excellence, take advantage of better economies of scale to improve cost of goods, continue improving cost of goods and margins over time.
That's great. On gross margins, the 50% in Q4, I think the best gross margin since launch, so it's really encouraging to see. Can you just elaborate on what drove that improvement? You know, I think also like the big Proleukin quarter helped, should we expect to see that 50% and potentially grow over the next few quarters? How do we think about Q1 and beyond?
On the quarters, I mean, look, it might not be exactly linear. We did have a little bit of maintenance in Q1. That margin is really an effect of, you know, our cost containment. We did reorg when we saw what we needed to do. We also have these continuous improvement exercises. Those are impacting. Our shift to internalization will help going forward. The goal is to continue to improve the margin.
Okay. It's still ultimate 70% gross margin over the long term, how do you guys get there?
Yeah, look, I mean, we get there with our continued programs. We just brought all the manufacturing in-house in January. Our CDMO has concluded production. That will give us economy of scale. We're continuing as we grow revenue to control the costs and work on efficiency. That is a very big focus for us.
Okay. Proleukin had a nice fourth quarter, so can you talk about the cadence of Proleukin sales moving forward and kinda what you might expect the split between AMTAGVI and Proleukin to look like?
Absolutely. One thing I just wanna mention, there's been a lot of noise around Proleukin because it has been lumpy with the distributors. All three of them ordered in the fourth quarter. We're hoping that we'll have a smoother projection. What I wanna emphasize is it's really an AMTAGVI story. The vast majority of Proleukin is used in the treatment program post-AMTAGVI. If we could focus on AMTAGVI, I think that'll drive. There was a little bit of disconnect on the timing in the past, and we might see a small amount of that going forward, but hopefully it smooths out, and you're always gonna see a little bit of uptake before a price increase.
Are you able to put a finer point on the vast, what vast majority means with respect to Proleukin use related to AMTAGVI as opposed to other uses?
Yeah. I mean, look, first of all, what I can do is I can help you with the split. Full year last year, we saw 17% of revenue coming from Proleukin. I think that's probably where you need to look. It's a good proxy. As far as... Look, the vast majority of Proleukin is used with AMTAGVI. There's a little bit, for commercial use, and there's a little bit to other manufacturers. I wouldn't focus on that.
Okay. you know, I guess a question following the quarter that I'm sure you guys got a lot was, why not give guidance? You know, when can we expect guidance? What are you guys waiting for other than the obvious of seeing more commercial performance this year?
Absolutely. We have said. First of all, I wanna just go a little bit more into the remarkable comment. We are definitely seeing the momentum out of Q4 continue into 2026. I would just like a little bit more data points before giving everyone some more specific guidance. Look, as soon as we're ready, and that might even be before the Q1 call, we will guide.
Got it. All right. you know, what factors in the near term, like could the Replimune approval be a factor that, you guys take into account when thinking about guidance?
We are not actually assuming that as we think about our guidance. why? It's different patient populations. It's a different product. I don't know if they're gonna get approved. If they do, we think that that's completely separate and not impacting what we're trying to do with our patient population.
Got it. Again, the remarkable comment, that's related to the year, not necessarily Q1, you know, a huge spike in revenues in Q1 or so.
Agree. Yes, it is.
Okay.
Look, we're seeing good momentum, like I said. The leading indicators going into the year are good. As that continues, look, we're very encouraged, obviously, or we wouldn't have said remarkable growth.
Got it. In terms of growth in 2026, year-over-year growth, achieving that, is it more ATCs? Is it a deeper penetration and utilization within the ATCs? 'Cause you guys are already in a fair amount of ATCs. Can you help us understand that?
That it's definitely both, right? Growth within the current ATCs as well as expanding the network, so it's twofold. Importantly, not just expanding the network, but expanding into the community. That initiative was kicked off last year, and I think we're starting to see that pull through.
Got it. There's plenty of patients out there clearly, right? There's no shortage of patients. As you guys think about the launch to date, what has been the most significant learnings from the launch that you guys feel that you can improve upon to really increase those revenues meaningfully in the coming years?
I think we've already pivoted from the learnings from the early launch with these new initiatives into the community, making sure that we can get the product to the patient, because there is no shortage of patients.
Got it. When you talk about the community, I imagine you're referring to these larger community centers that are still relatively close to the academic, what the academic groups are like, right? They need to have the surgeon to do the coordination. They need all those groups within the community, right? It's not there's a defined set of community centers that you guys are focusing on, right?
Yes, that's correct. As you look at the patient journey, if they're being treated, I guess, first line in the community, it's much easier for the doctor to just switch them over, right, for them. They can always be referred, but that's the goal, right? Just make it easier. Make the patient journey easier.
Okay. Since you mentioned, first line, maybe that's a good segue into, ongoing first-line program, TILVANCE-301. Can you talk about how that's progressing and when we should expect data?
The TILVANCE is progressing very well. It's an important trial for us. As you know, it's intended to provide convert the current approval into full approval in the current label and provide accelerated and then full approval in front line in combination with pembrolizumab. The trial has dual primary endpoints, and it was designed very closely in interaction with the FDA. It has dual primary endpoints, ORR and PFS. ORR can be read out first to provide accelerated approval in front line melanoma. That's The trial itself, of course, it's a large multinational trial. It takes years to complete, but we don't need to enroll all patients to read out the ORR.
What would you guys have to show on ORR for an accelerated approval or to have confidence to file?
The control arm pembrolizumab has reported re-response rates about 30-33%. In the previous cut of the phase 2 data in front line, we reported over 60% response rate. Anything close to that range would be sufficient.
Great. Over the longer term PFS expectations, what is the you need to show on PFS?
We'll need to beat what pembrolizumab demonstrated, which based on the published data, we are very optimistic about.
Got it. All right. lung. follow-up data from IOV-LUN-202 trial later this year. What should we expect from that data, and when will the final data cut be for potential approval in the second half of next year?
Lung, we're very excited about that program. It's the market opportunity that about seven times greater than melanoma. There are a lot of patients out there who need the therapy. The preliminary data that we presented demonstrated best-in-class response rate and durability. What we plan for this year is complete enrollment and then present data update at a major medical meeting this year. All of that in anticipation of submitting an sBLA and potentially launching before the end of 2027. Those are the major milestones.
Okay. The data later this year will be, I guess, more response rate focused with early durability, and you're going to have to wait for more mature durability before filing next year. Is that fair to say?
Correct. The data this year, we expect more patients, longer follow-up, but then again, full data set, we expect to be ready with the appropriate follow-up to support launch by the end of 2027.
Got it. Again, related to the frontline melanoma question from TILVANCE, what do you guys think you need to show on response rate and durability to be able to file for approval?
We believe that basically seeing response rates in the current range in more patients confirming durability should be sufficient for approval and importantly for uptake based on the KOL feedback. Response rates in the 20s% should be sufficient for both approval and penetration in that high, high unmet medical need indication.
When you say confirming durability, can you just elaborate on that? You guys have come a long ways from your very first presentation in lung in terms of durability.
I mean, the Again, we'll present more data this year. Stay tuned. There are patients with responses who've been in response for more than two years as of the previous update. That is remarkable in that setting.
Yep. Don't get that with docetaxel.
No.
Yep. All right. Latest thoughts on a confirmatory trial in lung cancer patients?
Very similar how we designed TILVANCE confirmatory trial in melanoma in very close consultation with the FDA. There were multiple options at the time that we picked from. We plan to work closely with the agency to design a confirmatory trial in lung. Again, we'll consider various options as part of that discussion.
Great.
By the way, of course, we received Fast Track designation from the FDA just a couple of weeks ago for that indication, so there's a lot of positive tailwinds that we see there.
Perfect. On the earnings last week, you guys mentioned the soft tissue sarcoma early data and opportunity. You know, sarcoma obviously is a horrible disease, very difficult to treat, not great standard of care. People generally think of it as a low or a small market, right? I don't know, maybe you could elaborate on the overall market that you guys could potentially go after in sarcoma and why you're so excited about the early data.
As far as the market as Corleen presented, there are about 8,000 patients with these sarcoma types in the U.S. and Europe, and about 3,500, late stage, refractory patients. In the refractory setting, response rates are truly abysmal, 5% or less, or our survival's typically, less than a year or less in the real world setting. Showing a 50% response rate with responses deepening over time, that is very encouraging. The other aspect of this that. It's an indication that's not really sensitive to checkpoints. If you think about it, demonstrating that TIL can show this type of response rates in a solid tumor indication that is not sensitive to checkpoints, that can be huge. We're still at the early stages of that, but it's very, very exciting for that reason.
Great. I guess 600,000 times a few thousand patients is not necessarily a tiny opportunity for you all, right? Could definitely be incremental.
Correct. Again, the initial data are in the undifferentiated pleomorphic sarcoma, UPS, and dedifferentiated liposarcoma, DDLPS. We plan to expand as part of this program, expand to potentially other soft tissue sarcoma types. That's also coming as part of this market opportunity.
At what point do you.
Well-
Can you talk about your plans to discuss with the FDA the potential for an expedited approval? Do you have any early thoughts on what it might be like? Could it be a single-arm registrational trial? Could there be a rapid path?
Yes and yes. So yes, we plan to discuss with the FDA, and we do expect it to be a single-arm registrational trial that we expect to initiate very shortly and potentially complete very rapidly based on the enrollment rates we've seen so far and the unmet need in that population. As far as the size of the trial, again, we expect it to be very modestly sized based on the unmet need and the complete absence of responses basically in the current standard of care, which doesn't really exist as such.
That's great. You all highlighted the earlier programs, 3001, 4001, 5001. I think it's unlikely investors are gonna be able to focus intently on all three of them. If there was one of them that you would push investors to, which program would it be? Are there any, you know, upcoming catalysts for one or more of these that people should be paying attention to?
Well, all three are important in different ways. I'll just digress for a moment. At the IO360 conference just a couple of weeks across the street, I was on a panel. There was a keynote plenary with Ira Mellman speaking. He was head of IO at Genentech for a long time. At the end of his keynote, he was asked the question, "What do you think is next in IO 2.0?" His answer was, "First, TILS." I subscribe to that. I mean, the programs we have in development are intended to progress TILS to the next level. IOV-4001 is a PD-1 inactivated TIL that's actively enrolling patients with melanoma in lung. IOV-5001, we plan to file an IND very shortly this year.
It's an IL-12 genetically engineered TIL, where IL-12 is inducible and tethered. We expect it to potentially address many other tumor types, many of which are not IO or checkpoint sensitive. That's the future we see coming very soon.
Great. We're approaching the end of the session here, so maybe we'll wrap up by asking you both what you believe is the most underappreciated aspect of the Iovance story by investors right now.
It's twofold for me. I think that the help for patients. When I met, and I've been meeting patients since I joined, that have no evidence of disease and to hear their story, I just think we need to focus on the patients, and that's what we're doing. Also, we mentioned it on the earnings call, I'll mention it here, and Igor can talk about it because he runs this area, but, we own our own manufacturing. We do it well. We're working on doing it in an even more efficient manner. That's really important, I think, in our industry.
I mean, I'll echo that. TIL is here. It's approved in one indication. It's scalable. It can scale to both many more patients in terms of manufacturing. It can scale to many more indications, both with the current Gen 2 manufacturing process that we use for AMTAGVI, but also we intend to remain the leader in this field and scale it to next generations, genetically engineered TIL for the years to come. It's like where antibodies were 30 years ago, this is where TIL is right now, and we are the leader in the field, and we intend to remain the leader in the field.
Per Dr. Mellman, it should be TIL first.
TIL first.
TIL first.
Great. Wonderful. Corleen, Igor, thank you so much for your time.
Thanks, Tyler.
Thank you.