Iovance Biotherapeutics Inc Stock

Thank you. Thank you, Daniel. Good morning, and welcome to the Iovance webcast to discuss our third quarter 2026 financial results, business achievements, and corporate updates. This morning, we issued a press release that is available on our corporate website at Iovance.com. This conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans and transactions, revenue and revenue guidance, commercial activities, clinical trials and results, regulatory approvals, submissions, feedback and guidance, plans and strategies, research and preclinical activities, potential future applications of our technologies, manufacturing capabilities, payer interactions, licenses and collaborations, cash flow, and more. in 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 Boat, Interim CEO and President.

Thank you, Jen. Good morning, everyone. Our third quarter delivered outstanding record setting results for EyePoint. Our highest ever revenue and margin and strong financial performance across the board. Total revenue of about $122 million surged 80% over the prior year. U.S. Empaveli revenue increased 77% over the prior year and crossed $100 million in a single quarter for the first time. We also passed an important landmark this quarter with more than 1,000 commercial Vyvgart patients now infused in the U.S. since launch. Based on this strong performance, we remain on track to achieve our full-year revenue guidance of $410 to $420 million.

Our authorized treatment center, or ATC network, continues to expand rapidly, and we fully expect to reach 110 or more authorized treatment centers by year end. Third quarter margin of about 60% also set a new all-time high for the second consecutive quarter, and we expect it to expand further over time. Our cash runway is now expected to fund operations well into 2029. The strong performance reflects the financial health of Iovance and the strong platform that we can build upon for upcoming launches. The third quarter and recent updates also reflect major progress across our TIL platform and pipeline programs. In metastatic non-small cell lung cancer, lifileucel continues to demonstrate a potentially best-in-class clinical profile. Earlier this year, the FDA granted fast track designation based on the strength of our data and the high unmet need.

Last week, we reported positive updated results from our registrational Lung 202 trial that included 69 patients with previously treated non-squamous metastatic non-small cell lung cancer. The objective response rate, or ORR, by RECIST 1.1 was 24.6%, consistent with our prior results in 39 patients. Durability, while still maturing, was also consistent with our prior results and has already greatly surpassed the current standard of care, docetaxel, which has a response rate of only 12.8%, short durability of 5.6 months, and median overall survival of just 12.3 months. Safety in Lung 202 is consistent with our lifileucel experience to date across our clinical trials of multiple solid tumors. Encouragingly, the safety profile on Lung 202 improved using the updated reduced dose lymphodepletion regimen. efficacy, including durability, remains comparable and consistent in Lung 202 before and after the change to reduced dose lymphodepletion. We will provide more details on Lung 202 as the study completes with potential presentations at medical meetings in 2027. Looking ahead, we are confident in our plans to submit a supplemental biologics license application, or S-B-L-A, in 2027.

We are completing enrollment in cohorts one and two with a target of approximately 80 patients for the SBLA. In parallel, we are advancing independent review committee assessments, FDA discussions, and other pre-submission activities, including preparation for a confirmatory trial. Alongside our latest Lung 202 update, we launched an innovative precision tilt strategy. We identified a biomarker-enriched subgroup of non-squamous, non-small cell lung cancer patients in Lung 202 that demonstrated a remarkable 59.1% response rate. Nearly six in 10 patients showed a deep, and durable response. These results are the foundation for POSITY, a first in class, prospectively defined, biomarker enriched cohort with registrational intent that we will pursue in addition to our initial sBLA in 2027 in non-squamous, non-small cell lung cancer. Positility is targeting 80 patients and will begin enrollment this month.

Utilizing the existing Lung 202 site footprint to speed enrollment is part of a planned transition. In 2027, we are also planning our OPAL-1 trial to investigate this population in the frontline setting. Together, these biomarkers selected front and second line settings representing U.S. opportunity about 10 times the size of advanced melanoma. At the ESMO Congress in late October, two oral presentations showcased the broader potential for Leifelusel to demonstrate deep, durable responses in soft tissue sarcomas and frontline advanced melanoma. Following one of the oral sessions at ESMO, this morning's press release included our most recent updates in soft tissue sarcoma. The confirmed ORR by RECIST 1.1 for lifileucel in refractory undifferentiated pleomorphic sarcoma, or UPS, and dedifferentiated liposarcoma, or DDLPS, has climbed to 55%. 25.6%, five of nine patients. Multiple durable responses have already been observed, including two ongoing more than a year from infusion.

Safety in the sarcoma trial is consistent with our lete-leucel experience to date across our clinical trials of multiple solid tumors. These powerful results in heavily pretreated patients are the basis for Saratoga, our registrational trial that is actively enrolling to support two more approvals for lete-lucel. After failing chemotherapy, second-line response rates are typically below 5%. Median survival is about 9 to 10 months, and there are no approved immunotherapies. In recognition of this unmet need, as well as our initial results, the FDA granted fast-track designation in both UPS and DDLPS. In addition, we have aligned with the agency on the design and a potential accelerated approval pathway based on the Saratoga trial with 40 patients expected in each cohort and sBLA submissions planned for 2028 or 2029. In our second oral session at ESMO, we focused on frontline advanced melanoma, where about half of patients do not achieve long-term benefit with today's standard combination checkpoint inhibitors.

In our phase two cohort, frontline advanced melanoma, 62.5% of patients responded, including complete responses in 29.2% of patients where tumors disappeared completely and did not Median overall survival was not reached after more than four years of follow-up. Safety was consistent with the known safety profiles of one-time lifileucel and pembrolizumab. These results reinforce Tilvance 301, our Phase III trial enrolling in more than 80 sites and expanding design to support both the frontline approval and serve as the confirmatory trial for full U.S. approval of Amtagvi. In summary, Iovance is focused on growing revenue, expanding into new indications and markets, and broadening TIL therapy into solid tumor indications, including biomarker-selective populations that collectively represent tens of thousands of cancer patients with poor prognosis and limited available options. I'm also thrilled to welcome our new Chief Medical Officer, Dr. Noah Berkowitz, to his first quarterly call at Iovance to discuss additional details about our pipeline. His valuable expertise in global drug development across cancer and blood disorders led to approvals for the CAR T-cell therapies Abecma and Breyanzi while at Bristol-Myers Squibb.

As the first and only company in the world to take TIL Therapy from concept to commercial treatment, we are forging ahead with tremendous momentum toward profitability and long-term value for patients and shareholders alike. Jean-Marc Roche, our Chief Financial Officer, will now highlight our financial results.

Thanks, Fred, and good morning, everyone. The third quarter was another record quarter for Iovance, combining strong revenue, record margin, and disciplined spending.

Revenue is up 80% that's 80 year-over-year. Margin is at an all-time high of 60% 60 and operating expenses reflected discipline, intentional allocation of capital to our highest return priorities and now our cash run way expected to fund operations well into 2029. Total revenue once again achieved a new quarterly record of about $122 million, up 80% year-over-year as I mentioned and 22% sequentially. Amtagvi powered that revenue growth by reaching more patients than ever before. Amtagvi sales of around one hundred and and $2 million represent 77% increase year over year and a 12% increase sequentially, reflecting strong patient demand and broad adoption. Proleukin revenue contributed approximately $20 million in the third quarter, more than double the second quarter level as wholesaler ordering patterns are realigning with Amtagvi demand. As expected, the quality of our revenue remains high, with gross to net deductions around 1% consistent with prior quarters.

That high quality revenue is flowing through to margin, which reached an all time high for the second consecutive quarter of approximately 60%, up sequentially from our previous record of 56%. and that brings our year-to-date margin to 54%. Intacct growth, operational efficiencies, and investment discipline contributed to this margin gain and remain powerful levers for continued expansion as we drive further efficiencies across the company. Turning to operating expenses. Third quarter R&D expenses were down approximately 16% sequentially to about $49 million, marking the fifth consecutive quarter a reduced R&D expense. This trend reflects efficiency of our operations, including clinical and manufacturing, which allows us to advance multiple registrational programs at greater scale and much less cost than any TIL competitor. Total selling general and administrative expenses held flat at about $39 million sequentially, even as revenue grew about 22%. We continue to make targeted investments in revenue generating activities that drive the greatest commercial return. We are reaffirming our recently updated full year revenue guidance range of $410 to $420 million.

At the midpoint, that is nearly 60% growth over last year. Through the first three quarters of 2026, we have already delivered $292 million of revenue, expanded margin, and controlled operating expenses. We end the quarter in a strong financial position with approximately $382 million in cash, cash equivalents, short-term investments, and restricted cash on September 30th. Together with robust revenue and careful capital allocation, this cash position is now expected to fund operations well into 2029, giving us the runway to execute on our growth plan from a position of strength. In closing, we again delivered strong revenue, improved margin, and intentional capital allocation this quarter. With a strong balance sheet supporting us, we are well positioned as we build a valuable, self-sustaining business that delivers lasting value for patients and our shareholders. And behind these record results are the patients we serve.

For more on how we are reaching them, here's Dan Kirby, our Chief Commercial Officer, to review our commercial progress in more detail.

Thank you, Corleen. Third quarter was the strongest quarter of the Amtagvi launch. Amtagvi revenue surpassed $100 million for the first time, and we treated more patients than in any prior quarter. Together with Filspari sales of approximately $20 million, we are confident in achieving our updated full year guidance of $410 to $420 million. We also achieved two milestones this quarter. We have now treated more than 1,000 commercial patients, and we have more than 100 ATCs. Access is expanding and more patients are able to receive a one-time cell therapy that can deliver long-term, durable responses. I'll cover how we got here through our three priorities, physician awareness, growing our ATC network, and clinical data.

First, physician awareness. Our latest market research shows durability of response is the leading reason physicians choose Amtagvi over other treatments. Durability was rated highly by more than 80% of our target physicians and was cited by nearly two-thirds as the key driver for the decision to treat. Durability with mTAGV is measured in years with over three years median duration while other options both on the market and in trials measure durability in weeks and months. Last week, Fox News covered a story about one of our patients, Patty Garcee, who is experiencing a long-term durable response to MTAG-D after a single infusion two years ago. Patient stories like Patty's are increasingly being featured across media outlets and continue to reinforce the promise of our TIL therapy. Also, our expanded sales force returned clear value on investment as they logged more customer interactions than in any quarter since launch, which translated into more patients treated than ever. Second, our ATC network. We now have more than 100 ATCs and are on track to reach at least 110 by the end of Most of the centers we onboarded in Q3 were community based and community ATCs represent over a third of our network.

New centers are also getting started faster as the time between authorization and first patient treatment continues to shorten. Behind these numbers is reliable delivery to patients. For the majority of lots, turnaround time is 30 days or less. only scaled centralized commercial manufacturing process approved by the FDA for TIL therapy. Iovance's manufacturing capabilities are faster and more reliable than any till therapy in development. Third, clinical data. Real-world studies show response rates of 50% or greater in second-line patients, supported by five-year durable responses after a one-time Amtagvi treatment. These results are the standard in second-line plus metastatic melanoma, where patients get better and more durable responses with mTAG-B than any other option. At ESMO, a new indirect comparison suggested that lifileucel may approximately double four-year overall survival compared with standard of care in anti-PD-1 resistant advanced melanoma.

Our teams also met with US and international thought leaders at ESMO who were excited about the data and what it means for their patients. Turning to Proleukin, third quarter sales were about $20 million, driven by Amtagvi demand. We expect that trend to continue in Q4. Now, international, Amtagvi is approved in Canada and Australia for previously treated melanoma, with our first ATCs ready in Canada and onboarding in Australia. We are progressing reimbursement discussions in both countries. These ATCs will initially treat private pay patients while we work towards public reimbursement, which is key to broad access. The UK application is under expedited review and the Swissmedic process is moving smoothly with potential approvals in both markets by the first quarter of 2027.

Also in 2027, we plan to submit an application in Brazil where expedited review is available and to resubmit our application in the European Union. Finally, looking beyond today's indication, in frontline advanced melanoma, the population is more than twice the size of the previously treated population we serve today. in metastatic non-small cell lung cancer with KRAS wild type, the first and second line addressable market is at least 10 times that of Amtagvi's current indication. In soft tissue sarcomas, the U.S. market opportunity in UPS and DDLPS is approximately the same as the current second-line metastatic melanoma opportunity for mTagV. Across indications, these patients are concentrated at centers of excellence that are already ATCs, which we believe positions us well to quickly reach and treat patients upon approval. To close, we had a record third quarter, approximately $122 million in total revenue, including more than $100 million in Amtagvi revenue. reaching more patients than ever. We are on track to reach at least 110 ATCs with community centers and faster onboarding driving growth. Finally, we are on track to achieve all of our commercial goals for 2026.

I'll now hand the call off to Noah, who will cover our pipeline in further detail. Thank you, Dan, and hello everyone. My name is Noah Berkowitz. Having joined the company a month ago, this is my first Iovance earnings call, and I am incredibly happy to be here. I joined Iovance because TIL is the first single administration cell therapy that achieves deep and lasting responses in a significant proportion of patients with advanced melanoma. This success is being replicated across our robust clinical pipeline with translational medicine and early development programs aimed at optimizing outcomes in patient populations that may derive the greatest benefit from TILT therapy. Today, I am pleased to talk more about our exciting pipeline. To begin, we are looking forward to our upcoming sBLA submission for lifileucel in previously treated non-squamous metastatic non-small cell lung cancer.

Our enthusiasm for this submission is driven by the strength of the response rates and the durability of responses in cohorts 1 and 2 in our Lung 202 trials. We believe the data compare quite favorably to docetaxel monotherapy, the disappointing standard of care in this treatment setting, with a published study in the National Institute response rate of under 13%. In our registrational patient population from cohorts 1 and 2, 17 out of 69 patients, or about 25%, experienced a PR or CR as well as durable responses, including many patients treated with reduced dose of lymphodepletion regimen. Impressively, about half of the responders remain ongoing in the study. As you may recall, to manage toxicity, the trial included a reduced lymphodepletion preconditioning dose that became a trial requirement for all patients after mid-2024. We have observed improved safety and are maintaining a similar ORR, including long, durable responses. In parallel, we are aggressively advancing our precision TIL strategy following our identification of a biomarker-enriched subgroup with a response rate of 59.1%, including two ongoing complete responses at 21 and 49 months.

This subgroup includes current or pre-pandemic responses. or former smokers without actionable driver mutations, patients with significant unmet medical need and no targeted therapy options available. This novel biomarker-enriched subgroup will be evaluated prospectively in cohort five for positivity in the LUN202 trial. This is a precision opportunity that we will advance alongside and not far behind our planned sBLA based on cohorts one and two. Our biomarker-enriched frontline strategy in metastatic non-small cell lung cancer is also moving forward. After six out of seven or nearly 86% of patients This subgroup responded. For patients with UPS and DDLPS, poor prognosis variants of soft tissue sarcoma, second-line response rates are typically below 5% after failing chemotherapy. Median survival is about 9 to 10 months, and there are no approved immunotherapies.

In oral session at ESMO Congress highlighted the pilot trial led by Memorial Sloan Kettering Investigator and included a 50% confirmed ORR among the first eight evaluable patients. As Fred mentioned, we included the recent results in today's press release with a 56% five of nine patients is being updated data. Multiple durable responses have already been observed, including two ongoing more than a year from infusion. The data are available in our corporate slide deck in the investor section of iovance.com. We are currently enrolling patients in the Saratoga registration at major US cancer centers. As you may recall, we reported positive initial data in the first quarter of 2026 in the endurance trial. Here we focused on previously treated metastatic serous endometrial cancer using a biomarker strategy based on histology.

Among the first five evaluable patients, we observed a 40% confirmed objective response rate and 100% disease control rate. We are planning discussions with the FDA on an expedited approval pathway and expect to increase enrollment based on this patient population. I'd like Let's shift gears for a moment and highlight our next generation approaches. Let's start with IOV 5001, our IL-12 tethered till therapy. We know that IL-12 engineered tills have previously demonstrated differentiated efficacy with a new mechanism of action. Based on that prior experience, we believe that IOV5001 is designed to remodel the suppressive tumor microenvironment and activate immunologically cold tumors, supporting TIL responses and boosting response rates. POTENTIL, a first in human trial of IOV5001, is currently enrolling patients with metastatic colorectal cancer, triple negative and estrogen receptor low breast cancer, and other solid tumors that represent more than 100,000 U.S. cancer deaths annually.

We're also investigating IOV4001, a PD-1 inactivated TIL therapy engineered to resist inhibitory signals in a first in human trial where we continue to enroll patients with previously treated metastatic non-small cell lung cancer. And finally, we have a phase one safety cohort investigating multiple dose levels of IOV 3001, a second generation modified IL-2 analog designed to selectively expand effector T cells while avoiding activation of regulatory T cells. IOV 3001 is a potential component of future TIL regimens with a lower dose IL-2 regimen and fewer adverse events. I'm energized by the work ahead at Iovance to develop the current and future TIL pipeline. My priority is rigorous execution, close collaboration with regulators, and letting the data speak for itself. I will now hand the call back to the operator to begin the Q&A session.

To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. In the interest of time, we ask that you please limit yourself to one question. Please stand by while we compile the Q&A roster.

Our first question comes from Andrew Tsai with Jefferies. Your line is open. Hi there. Good morning. Great execution. Thanks for the updates. My question is about the commercial franchise right now. So traditionally, you guys have seen some impacts due to maintenance of your facility around the December and January time frame, I think. This time around, is it fair to assume everything will be smooth and good to go because you switched to the modular manufacturing early in the year. And if that's the case, you know the guidance implies maybe a flattish to slightly up quarter-over-quarter growth for Q4.

Is that really going to be the case? Can you maybe then talk about any other potential headwinds we should think about for Q4 as it relates to your guidance? Thank you.

Yes, thanks Andrew for the question. You're correct, the maintenance is no longer an issue. We don't, that will not affect our earnings going forward. That was primarily affecting us in Q1 in the first quarter of each year, and that effect has gone away. We just issued this guidance five weeks ago, and so yes, obviously, We would like to have growth quarter over quarter, and we expect that, and that's something we would aim to do. But just keep in mind that the guidance really just came out five weeks ago. Right now, we're tracking to achieve it.

And of course, of course, of course, if we can beat our guidance, we're very happy to do so. as we just did. Great, thank you.

Thank you. Our next question comes from Edzer Darut with Barclays. Your line is open.

Great, thanks for taking a question. I guess you know with quarterly operating loss of about approximately 24 million I guess, is profitability achievable before launches in lung cancer or sarcoma? And I guess, what remaining revenue scale or gross margin improvements do you think are needed to reach operating cash flow break-even given the momentum we're seeing in second-line melanoma alone?.

Thank you. The answer is yes. So, I mean, if you look at the EPS, it's only 5 cents loss, and that's the best it's ever been. So we are on our way to profitability. I'm not guiding when, but if we continue on this path of revenue growth and disciplined investments, we'll get there.

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

Hi, thanks for taking our questions. This is Kuan-Nan for Yonan, and congrats on another strong quarter. For Perlucan, the sales increased from 9 million to 20 million, and you mentioned the ordering patterns are realigning with MTAGV demand. So can you share with us a little bit about the sales growth? How much does that reflect the expected use of mTAC-V? And is there an estimation on the average delay between Perlucan sales and the use for mTAC-V? Thank you.

Thank you, Quan. Great question with it. ProLucan is in line with mTAC-V demand. So we had said before about 16% of the demand was represented by ProLucan. That is what this quarter represented. We're seeing the orders in line. One of the things that the teams are doing to ensure that their supply is a wholesaler is we're communicating planned orders. at the hospitals that pull from that wholesaler. So we are tracking in line with demand in real time with the wholesalers ensuring the hospitals have supply to support the mTAC-V infusions.

Got it. And a quick question on Lung 002. When do you think we may see a mature median DOR data from this study? Thank you.

Well, it's possible that when we complete this study, we may be not reached, so that we may have matured but not reached like we did with some other reports that we've done, so just bear that in mind. But as we mentioned a couple times now, we expect to finish the study imminently at 80 patients. We will report, as I mentioned in the prepared remarks, we'll report data on that at some point next year, and then at that point you should see what you might... I think what you mean by mature, median DOR, but just don't be surprised if it's not reached at that point with a lot of follow-up.

Got it. Thank you for all the color. Thank you. Our next question comes from Nick LaRusso with TD Cowen. Your line is open.

Hey guys, thanks for taking my question. You noted that community ATCs represent about a third of the current network, which is impressive. Can you discuss the current prescribing patterns and maybe the proportion of patients coming from the community versus academic centers and how we should think about this ramping over time?.

Sure, great question Nick. So we are focused, we've been focused for over a year now on opening community hospitals and ATCs to serve What we're seeing is in general we've gotten better at opening accounts, so as I mentioned in the prepared comments, we're seeing a quicker activation of first patient treated, so we are seeing the ramps come up. Our business still is concentrated mostly in the academics, but the community ATCs are growing over time with this. of our ATC world but it's going to represent in the future probably more than half of our infusions right now it's still about two-thirds in the academic world a third in the community world but we do expect that to grow as we continue to open more community Thanks very much for the call.

Thank you. And our final question comes from Joe Pantginis with HC Wainwright. Your line is open.

Hi, this is Josh on for Joe. Thanks for taking our question. So, I just wanted to follow up on LUN202, if there's any additional color you can provide with your, with the discussions you've been having with the FDA about the sBLA submission.

Yes, I'm happy to provide that. We're very focused right now on those discussions with the FDA, and we're having productive discussions right now. And we believe that this data set that we have right now should be registrational and should be approvable. I'll ask Raj Puri here, who's with me, to make some.

comments on this as well. He's our head of Chief Regulatory Officer. Yes, I agree with Fred's comment that the FDA, we are on track to get BLA submission at the end of Q4 and based on our data, we are confident that FDA will consider for that is under prior approvals in this space with about 80 subjects trial.

And just to clarify, we're planning to submit that BLA in 2027. Perfect. Thank you so much.

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 for joining us. This is another record-breaking quarter, and our pipeline is advancing rapidly. We remain deeply grateful to the patients, partners, healthcare professionals, and advocacy communities we serve. Finally, I want to thank our exceptional Iovance team, our dedicated long-term shareholders, and our covering analysts for their continued support. We remain committed to our mission to innovate, develop, and deliver current and next-generation TIL cell therapies for patients with cancer.

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

This live transcript is auto-generated without human intervention or review.

[Call has ended.]

This live transcript is auto-generated without human intervention or review.

Welcome to the Iovance Biotherapeutics conference call to review updated data from the IOV-LUN-202 trial in non-small cell lung cancer. My name is Carmen. I'll be your operator for today.

So as we were welcoming everybody to the Biotherapeutics conference call to review the updated data from the IOV-LUN-202 trial in non-small cell lung cancer. My name is Carmen. I'll be your operator for today. [Operator Instructions] And please note that this conference call is being recorded.

I will now turn the call over to Sara Pellegrino, Senior Vice President, Investor Relations and Corporate Communications at Iovance. Sara, you may begin.

Thank you. Welcome to Iovance Biotherapeutics conference call to review updated data from IOV-LUN-202 in non-small cell lung cancer, and welcome to the webcast to review updated registrational trial data in previously treated non-squamous non-small cell lung cancer and our biomarker-enriched precision TIL strategy. This morning, we issued a press release and the slides for today's webcast are available in the Investors section of our corporate website at ir.iovance.com.

Speaking on today's call is Dr. Fred Vogt, Interim CEO and President. During the question-and-answer session, we will also be joined by Dr. Noah Berkowitz, Dr. Brian Gastman, Dr. Raj Puri, Corleen Roche and Dan Kirby.

This call will be including forward-looking statements regarding Iovance's goals, business focus, business plans, clinical trials and results, subgroup and biomarker analysis, trial enrollment and initiation, regulatory approvals, submissions, feedback and guidance, time lines, plans and strategies, potential future applications of our technologies, any required companion diagnostics, the size of addressable patient populations 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 Vogt.

Thank you, Sara, and good morning, everyone. As the global leader in innovating, developing and delivering TIL therapy for solid tumors, metastatic non-small cell lung cancer represents the largest opportunity ahead for Iovance.

This morning, we announced positive updated data from our registrational Cohorts 1 and 2 of our LUN-202 trial in support of our planned supplemental biologics license application, or sBLA, in 2027. Detailed results, including waterfall of responses and swimmer plots are available in the slide presentation posted this morning in the Investors section of our website. I will first highlight our important results in Cohorts 1 and 2 and our path toward our planned supplemental BLA submission for non-small cell lung cancer in 2027. Then I will turn to a significant novel addition to our precision TIL strategy and the next steps for expanding our non-small cell lung cancer program.

In our registrational cohorts in LUN-202 in non-squamous metastatic non-small cell lung cancer patients, lifileucel shows a potential best-in-class clinical profile with an objective response rate or ORR of about 25% by RECIST 1.1, the standard criteria for measuring tumor shrinkage. As of our October 14, 2026 data cutoff, 17 of 69 patients responded with most responses durable. Of these, 15 were confirmed responses, including 2 complete responses with 2 more recent responses awaiting confirmation. These 69 patients plus several additional patients in the treatment process at the time of the data cut and more patients enrolled in the study represent the vast majority of the expected 80 patients in our registrational population.

These updated results are remarkably consistent with our prior results in 39 patients across ORR, durability and safety. Our updated reduced-dose lymphodepletion regimen prior to TIL infusion has improved the overall safety profile, which remains consistent with our experience with lifileucel.

For patients with metastatic non-small cell lung cancer whose disease progresses after first-line immunotherapy and chemotherapy, time is short and options are few. Recently published response rates with docetaxel, the most commonly used standard of care were only 12.8% with no complete responses. The median duration of response was 5.6 months and median overall survival was 12.3 months. These patients need treatments that deliver better outcomes and above all, more lasting responses.

Our LUN-202 results including today's updates, are unprecedented in the second-line treatment setting. As I mentioned, waterfall of response in swimmers plots are available in the slide presentation posted this morning in the Investors section of our website. We continue to move forward towards the sBLA submission in 2027, and we'll have further updates along the way, including on our confirmatory trial plan.

As I mentioned, we expect approximately 80 non-squamous non-small cell lung cancer patients to be included in the final data set for the sBLA. And so today's data update represents nearly all of the patients in the expected data package. Our internal teams are focused on preparing for the sBLA submission. Independent review committee assessments, FDA discussions and other presubmission activities, including confirmatory trial preparation are also ongoing. We look forward to completing enrollment in Cohorts 1 and 2 shortly and are confident in the road ahead in previously treated non-squamous metastatic non-small cell lung cancer, which earned FDA's Fast Track designation on the strength of our clinical data and represents an area of high unmet medical need.

Next, we have exciting updates on our precision TIL strategy as well as the broader non-small cell lung cancer program and our growing pipeline. For many years, we have been pushing the limits of our biological understanding of TIL therapy, exploring every aspect of our wealth of state-of-the-art genomic and translational data using the best tools available. We are now able to announce the identification of a novel and important biomarker-enriched population in previously treated and frontline metastatic non-small cell lung cancer. This has allowed us to develop a precision TIL strategy to enrich for patients that show the greatest benefit to lifileucel and potentially other pipeline products in non-small cell lung cancer and in other indications.

In the LUN-202 trial, we identified KRAS wild-type status as the lead biomarker. Published preclinical studies in lung cancer models link oncogenic KRAS signaling to impaired antigen presentation and immune suppression. Impaired antigen presentation, in turn, inhibits responses to TIL therapy by limiting the ability of T cells to recognize tumors. In our subgroup analysis, the ORR among KRAS wild-type patients was 43.3% or 13 out of 30 patients, nearly 4x the 11.4% ORR seen in 4 out of 35 patients in the KRAS mutant subgroup. These critical observations provided the rationale for further enrichment within the KRAS wild-type subgroup.

Building on this signal, we further drew on tumor genomic testing and smoking history data to enrich for HER2 and smoking status. Our work has shown that TIL responses need recognizable tumor targets in an environment that can support a sustained antitumor response. Aberrant HER2 signaling can suppress antitumor immunity in preclinical models, while smoking-associated mutations generate additional tumor targets for TIL recognition. Combined with KRAS wild-type population, this subgroup represented less than 1/3 of the broader study population or 22 out of 69 patients, but accounted for more than 3/4 of the observed responses or 13 of 17 with a high ORR of 59.1% or 13 of 22 patients.

In the real world, we estimate that a large population of approximately 45% of non-squamous metastatic non-small cell lung cancer cases diagnosed in the U.S. each year meet the biomarker enriched criteria. This remarkable result with nearly 6 in 10 patients durably responding, including 2 complete responses, along with the biological rationale, drive our plan for prospective evaluation of this combined enrichment strategy for lifileucel in an additional trial that further expands our non-small cell lung cancer program.

Today, I'm excited to introduce POSITILITY, a first-in-class prospective biomarker enriched cohort within the ongoing LUN-202 program designed with registrational intent. Enrollment in POSITILITY is set to begin imminently with the first sites beginning the trial in November 2026 and expanding to over 70 existing LUN-202 sites over the next few months. POSITILITY will enroll patients across both PD-L1 negative and positive populations. We are fortunate to be in a position to enroll POSITILITY quickly with our trial already at full speed and our fully scaled and highly efficient in-house manufacturing capabilities ready to go. We expect momentum to further increase on the back of today's results.

[Technical Difficulty] enrichment strategy into a precision development plan to maximize the benefit from lifileucel therapy and achieve rapid responses -- rapid -- excuse me, rapid approvals in the U.S. and around the world.

We also applied our learnings to frontline metastatic non-small cell lung cancer using our data from Cohort 3A of our COM-202 trial in patients without actionable EGFR, ALK and ROS1 mutations who were not previously treated with checkpoint inhibitors or chemotherapy. Following onetime lifileucel combined with pembrolizumab without adding standard of care chemotherapy, the ORR was 85.7% or 6 out of 7 patients in the subgroup enriched for KRAS and smoking status, including 1 complete response and 5 partial responses, all confirmed and durable. This compares to an ORR of 64.3% or 9 out of 14 patients among all EGFR wild-type patients, again, highlighting the effects of KRAS wild-type biology on clinical responses. This population also represents a population in need of highly efficacious, durable therapies.

Building on these findings in the frontline treatment setting, we also plan to initiate the OPTILISM trial in biomarker-enriched non-squamous metastatic non-small cell lung cancer in 2027. OPTILISM is based on an innovative, highly derisked trial designed to add lifileucel to frontline standard of care, consisting of pembrolizumab and platinum-based chemotherapy regardless of PD-L1 status in non-squamous patients with KRAS and HER2 wild-type tumors and a current or former smoking history. We will share more details on OPTILISM and its unique design in the coming months.

Together, OPTILISM and POSITILITY will evaluate lifileucel across 2 treatment settings and assess the role of biomarker enrichment in our non-small cell lung cancer development program. It is extremely important to note that our biomarkers enriching for higher response rates also represent patients that have no targeted therapeutic options to date.

As a result, we have the potential to treat tens of thousands of patients annually in the U.S. alone that will simply not be eligible for mutant KRAS, HER2 or other inhibitors or antibodies that would often be recycled through multiple lines. Instead, we envision a treatment paradigm where metastatic non-squamous non-small cell lung cancer patients lacking actionable driver mutations and regardless of PD-L1 status, come directly to TIL therapy in the frontline or second-line settings and could benefit from a potentially curative option with deep and durable responses and even complete remissions.

The combined frontline and second-line opportunity represents a significant market opportunity in non-small cell lung cancer that we estimate is at least 10x the size of the current opportunity in second-line melanoma in the U.S. alone.

We are also leveraging these biomarker-driven insights into other indications for lifileucel and our pipeline assets, especially as we are right now entering indications like colorectal cancer with our IOV-5001 program. The biology underlying our findings may translate to other indications of unmet medical need with significant market potential.

The enhanced -- this enriched biomarker strategy provides Iovance with novel and valuable intellectual property. These discoveries create a broad and extensive moat around the field of precision TIL therapies. We look forward to providing further updates on our programs in 2027.

Operator, we're now ready to take questions.

[Operator Instructions] One moment for our first question that comes from Andrew Tsai.

This is Andrew. Thanks so much for the update today. So first question all for us, it's great...

Everyone, if you can hear me apologies for the technical difficulty today. We're just waiting for the operator to queue up the questions.

Operator, I'll let you to help me figure this out.

Andrew, we can hear you.

Okay. Well, it's great to see the ORR being maintained. So as for the durability, it seems like based on the...

Apologies, everyone. We can't hear Andrew, and there seems to be a lot of technical difficulties. Please just give us a minute here to work out what's going on.

Operator, we're unable to hear Andrew's question. Could you just please double check that he's unmuted?

He is unmuted, sir. Everyone can hear Andrew and we can hear you. Sir, can you hear us?

I can hear you, but I can't hear Andrew, unfortunately.

Andrew, go ahead with your question.

Maybe operator, see if another analyst can ask a question and we can come back to Andrew quickly, if that's possible.

Andrew, standby. Our next question is from Yanan Zhu with Wells Fargo.

Thanks for the update. Perhaps 2 questions. One is regarding durability of response. Do you have a median DOR from the data? And secondarily, wondering about the filing strategy, given that you have now identified this more precisely defined subgroup and you are conducting a prospective study, how do we think about the possibility of the previously stated plan? And I think you reiterated that you are talking with the FDA. But what are the -- from your perspective, the likelihood that FDA would accept this as -- the initial broader population as the filing and the basis for approval?

Yes. Yanan, can you hear me before I answer this? Just I want to make sure.

I can hear you. Yes.

Okay. Great. Great. Hopefully, everybody else can hear me too. Thank you for the question. The durability, you can see there's a swimmers plot on our website on Slide 6 of the new deck that we posted. It looks quite good. Right now, if you estimated from that swimmers plot where we would be, we'd be about a year. But I need to stress that it's -- the data is immature and data is still coming in and that we would expect to grow over time, and there are some patients that are coming in right now, obviously, they're responding.

So you really can't assess durability at this stage until the data is finally done, and we're also in the middle of IRC reads and a lot of other things that will affect the outcome. We are confident that the product is durable and will show durability comparable to what we would expect from TIL therapies.

Now on the broader question of whether FDA would accept this filing, we think a 25% response rate durable with a onetime treatment in this population should be approvable, and we think the FDA should accept it and we -- and should go forward. Obviously, we are still in the process of discussions with FDA. It's a little premature to get into a lot of details there. We have reached some alignment with FDA on things like CMC issues and some of the original trial design topics, but we're going to have more to say on that in 2027 as we go through the process. Meanwhile, we're full steam ahead on submitting a supplemental BLA based on Cohorts 1 and 2 of the full data package.

Now the new POSITILITY study, which is -- we call it internally Cohort 5, which is part of the LUN-202 study, is an add-on. It's an additional program that we're adding on to our non-small cell lung portfolio because we've identified a very powerful biomarker signal that we would be fools not to pursue. And if we're going to have a response rate of 60% in certain patients, we're going to need to go after that and try that in a study. That could become very, very meaningful. There's nothing out there in the market that has a response rate in that range in lung patients, and we're talking about lung patients here that don't have access to any targeted therapy. And I hope you could hear me there. So please let me know if any of that kind of cut off. I know there's been a lot of technical issues here.

Thanks, Fred. Yes, I can confirm I heard all the answers.

Operator, can we have the next question? And hopefully, everybody continues to hear each other.

Let me bring Andrew back. So, Andrew your line is open with Jefferies.

Thank you so much for the data update today. So when do you guys think we can get the initial cut once all 80 patients are enrolled? And maybe talk about your level of conviction that should remain unchanged, DOR ultimately unchanged for those remaining 10 patients. In fact, could -- for the remaining 10, are you guys enriching for that remaining 10 by chance? Or is it kind of an all-comer still? Because I wonder could ORR increase from there?

Yes. It's all-comers technically, Andrew, but we've been a little light on KRAS patients -- KRAS wild-type patients. So we do have the sort of the law of averages helping us here, and we think that will come back up a bit. So yes, it could be a little bit higher in the end. We could get a couple of responders with KRAS wild-type patients being in there.

Could you just answer your question again about durability? I didn't understand specifically what you want to discuss there?

That's okay. I didn't -- actually I didn't ask on durability, but maybe I might as well as a second follow-up then because based on the plots, maybe it seems like as of this cut, you need 2 more of your responders to progress in order to calculate the median DOR. But is there a way to maybe tell us what the floor on DOR in number of months could be at this juncture on this existing cut? What would that look like in months? I'm just trying to gauge whether DOR is like above 15 months, for instance, at this juncture.

Yes, you can look at the swimmers plot, which has a very Y-axis that goes out to, I think, 54 months. And you can see that the responders at the top that are going on for years, and then you can come down around the midpoint and kind of estimate a few more patients coming on to that chart at the end that are responders where they might land. And I think it would be fair to say, yes, we could end up with an mDOR of 18 months or beyond with this data set. I think that would be very reasonable based on what we know about TIL therapy right now in the lung population. But again, we won't know until the data is done. And we'll have a final data cut at some point next -- early next year, I think, and then we'll be able to talk a little bit more about that and the FDA process in much more detail.

One moment for our next question please, it comes from Etzer Darout with Barclays.

I guess a question really around maybe a broader biomarker strategy given what you're seeing here in lung. We think about melanoma, sarcoma, endometrial, other tumor types that you're assessing, how are you thinking about maybe broadening out this strategy beyond lung? If you could provide some color there, that would be great.

Yes, absolutely. There's a number of indications where KRAS wild-type status represents a significant population of the patients that are in the metastatic stage like colorectal, in particular, colorectal cancer. We are looking very closely across the entire landscape of solid tumors for populations like colorectal, where we have a significant population of patients where we could treat them with lifileucel or with one of the other products in our portfolio.

So I think you should stay tuned, and there'll be a lot more to say about that over the next couple of months. Very, very important finding here. And I just want to stress that today, we're announcing both second-line and frontline non-small cell lung updates and that population is -- the KRAS wild-type population, biomarker-enriched population there alone is, we think, more than 10x the size of the current second-line melanoma population. I mentioned that during my prepared remarks, that's extremely important. If you add colorectal on top of that and other indications that are important out there, gastric cancers and beyond, you have a pretty significant market that you're talking about.

One moment for our next question, that comes from Nick Lorusso with TD Cowen.

Thanks for the presentation. What's the minimum follow-up that the FDA wants to see to support the filing based on the LUN-202 data? And could this support a potential approval later in '27 or early 2028? And then second, based on your response on that, do you anticipate releasing more biomarker enriched data ahead of a potential approval to further support the Amtagvi profile, whether from this trial or from your 2 newer trials as well?

Thanks, Nick. And then I assume everybody can hear me still, right? Nick, you can hear. Just want to make sure.

Yes. I can hear you.

Great. Okay. Yes. So the FDA normally requires 6 months of follow-up from the last response, which puts you about 8 months after the last patient comes into the trial. Typically, if you have a response day for day 126 when we do our scans. So hopefully, that answers that question.

And of course, that triggers the filing time lines. We think we can get the supplemental BLA in 2027. And obviously, review would extend into late '27 into 2028, and that's when we would expect an approval.

And on your second question, with announcing additional biomarker data, yes, we definitely want to announce the biomarker data in other indications. We want to delve deeper into this data. We want to present this at medical congresses and talk a lot more about the KRAS, HER2 wild-type population, ever smoker population in the case of lung cancer and then the KRAS wild-type population in the case of colorectal and so on and explain to people why we think TIL therapy is the ultimate therapy in these patient populations. So I think you'll see a lot more from us in the first 6 months or so of 2027 around this topic.

Precision TIL therapy, that's been something that we've been talking about for a while, especially with our sarcoma program as we precisely identify 2 subtypes of sarcomas that respond very well to TIL therapy, greater 50% response rates, even after years of attempting us and others attempting to treat other sarcomas with TIL therapy. So that was sort of the first foray in the precision TIL. Now we're in the second leg where we're using genomics to really get to that additional level and deep insights into large clinical trial data sets that only we have in the field. I hope that answers your question.

Our next question comes from Jack Allen with Baird.

Good [indiscernible] update this morning. Just 2 quick ones from us. I wanted to ask a really interesting work you're doing with the biomarkers around KRAS and HER2, but I'm curious if you looked at other biomarkers in the study and if there was any differential in response around PD-1 status as well? And then I have a quick follow-up as well.

Yes. We looked at -- I couldn't even tell you how many biomarkers. We studied everything. This was a very complex analysis to identify this. There is -- we don't think there's a relationship with PD-L1 status with respect to TIL therapy, and we are -- in most cases. Now if there is a situation where we have a PD-L1 effect, we have a PD-1 knockout TIL therapy that's designed for that situation. So there may be some cases where we talk about that. But at least in lung cancer, we don't see a PD-L1 effect. Go ahead with your second question, though, and hopefully, you heard that.

Yes, I got you. And another one was just very briefly on any comments you can make around the manufacturing success rates seen in the lung cancer study?

Yes, it's consistent with our prior experience. We're getting good response or good total success rates. I don't know the exact number, Jack, off the top of my head, but they can be as high as 90% in some cases. And we're really focused right now on delivering high cell doses and making sure we're delivering quality product. We're -- because of our large in-house manufacturing capacity and our expertise in making Amtagvi commercially, we're getting better and better at making it for trials, too. And we try to leverage that. And that's something we'll use across OPTILISM and POSITILITY as we talked about today as well as additional confirmatory trials for Cohorts 1 and 2 when we announce that.

And this will conclude the Q&A session, and I will turn it back to Fred Vogt for his final comments.

Thank you, operator. Today's findings are reshaping how we develop TIL therapy for non-small cell lung cancer. Before we close, I have 3 takeaways for you. First, in our registrational cohorts, lifileucel again shows a 25% response rate now in 69 patients. Second, in our biomarker enriched analysis, KRAS wild-type and HER2 wild-type tumors in current and former smokers responded best, and we are testing that prospectively in POSITILITY beginning next month. And third, we plan to bring this precision approach to the front line with OPTILISM in 2027. We believe these insights could expand lifileucel's potential as a onetime treatment for non-small cell lung cancer with a best-in-class profile compared to other therapies in development.

Thank you all for joining us this morning, and we look forward to keeping you updated as our non-small cell lung cancer program advances. As always, we're grateful for the patients, caregivers and investigators who participate in the LUN-202 trial and our team, and thank you all on the call, and apologies again for the technical difficulties today.

Thank you all for participating in today's conference, and you may now disconnect.

Thank you. Welcome to the Iovance Biotherapeutics second quarter 2026 conference call. My name is Daniel, and I will be your operator for today's call. [Operator Instructions] Please note that this conference call is being recorded. I will now turn the call over to Sarah Pellegrino, Senior Vice President, Investor Relations and Corporate Communications at Iovance. Sarah, you may begin.

Thank you, operator. Good morning, and welcome to the Iovance webcast to discuss our second quarter of 2026 results, business achievements, and corporate updates. This morning we issued a press release that is available on our corporate website at iovance.com. This conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans and transactions, revenue and revenue guidance, commercial activities, clinical trials and results, regulatory approvals, submissions, feedback and guidance, plans and strategies, reach, prescription-free clinical activities, potential future applications of our technology, manufacturing capabilities, payer interactions, licenses and collaborations, cash position, 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 turn the call over now to Dr. Fred Vogt, Interim CEO and President.

Thank you, Sarah. Iovance is the global leader in innovating, developing, and delivering TIL therapy for solid tumors today and for the next generation. The second quarter of 2026 was our strongest yet. We delivered record revenue and margin, advanced our pipeline, and secured important new regulatory approvals and designations. I'll start by highlighting a few notable achievements. First, our commercial launch reached new heights in the second quarter, while our foundation for growth expanded. More authorized treatment centers, or ATCs, are activating, enrolling, and infusing patients than ever before. We reported $99.3 million in revenue driven by record Amtagvi demand.

We also greatly exceeded both our Amtagvi and total revenue guidance ranges for the second quarter. Second quarter margin also reached an all-time high of 56%. We expect margin to keep expanding as we increase revenue, fine-tune execution, and gain efficiency and scale. Looking ahead, we maintain our peak assumptions for Amtagvi and Proleukin of more than $1 billion in U.S. sales from advanced melanoma alone. The opportunity in other indications is significantly larger. Our third quarter performance to date is very strong. Once we fully assess increasing growth trends, we expect to provide an update to our full year guidance during the third quarter. We are now providing commercially Amtagvi to more than 50 patients a month on top of increasing numbers of clinical patients, which demonstrates both our manufacturing scale and how broadly accessible our cell therapy has become.

We are not choosing between growth and discipline. This quarter we delivered both. Research and development expenses improved for the fourth consecutive quarter, even as every lead program advanced and our pipeline grew. We are closing in on our pursuit of the largest opportunities for cancer patients who have the greatest unmet need. Our technology platform is scaling quickly. Recent regulatory and clinical milestones bring TIL therapy forward for more patients in the U.S., as well as new markets and additional solid tumor indications. Nearly 2,000 patients have received Iovance TIL therapies in commercial and clinical settings across hundreds of centers in the U.S. and in 30 countries. For the coming years, our vision is to reach tens of thousands of patients.

In our registrational trials, enrollment is nearly complete in our LUN-202 trial in the pivotal cohorts in non-squamous, non-small cell lung cancer. This indication represents a blockbuster opportunity that is roughly 7x that of advanced melanoma. We look forward to providing program updates in the fourth quarter as we work towards supplemental Biologics License Application in 2027. We're moving quickly with our registrational [ Saratoga ] trial for [ SAR201 ] in two advanced soft tissue sarcomas. As we announced today, the U.S. FDA granted Fast Track designation in undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma, validating the promise of the initial clinical data for lifileucel, as well as the substantial medical need in both indications. In a pilot study with one-time lifileucel therapy, the objective response rate was an unprecedented 50% in the first 6 evaluable patients, compared with abysmal response rates of less than 5% using current standard of care in these refractory treatment settings.

Our translational data and state-of-the-art technologies are uncovering the next frontier in TIL therapy. We are now able to identify highly responsive patient populations across solid tumor indications that comprise more than 90% of all cancers. For example, a histology-based biomarker strategy produced striking early Phase 2 data in the first 5 evaluable patients with metastatic serous endometrial cancer. In our [ N201 ] trial, we reported a 40% confirmed objective response rate and a 100% disease control rate.

We are submitting a protocol amendment engaging with the FDA on an expedited approval pathway based on patient population. Our leadership in TIL therapy includes continuous investment in next-generation programs. A new trial, known as [ G1-TIL-1 ], is using [ IOB5001 ], our next-generation IL-12 tethered TIL therapy. This Phase 1/2 basket trial will run across prevalent solid tumors representing more than 100,000 U.S. deaths annually, including metastatic colorectal, triple-negative breast, and estrogen receptor-positive breast cancers. We expect to provide more updates this year. Today, profitability is in sight, and with it, lasting value for patients and shareholders alike. Iovance is the first and only company in the world to take TIL therapy from concept to commercial treatment for patients, supported by our scalable manufacturing infrastructure, clinical breadth, commercial experience, and operational discipline. With healthy commercial momentum, broadening pipeline, and solid execution, Iovance has never been better positioned for long-term success. I'll ask Corleen Roche, our Chief Financial Officer, to detail our financial results.

Thanks, Fred, and good morning, everyone. Our highest ever quarterly revenue and margin clearly demonstrate our commitment to top-line growth, operational excellence, and financial discipline as we build a sustainable, self-funded business. Second quarter total revenue was more than $99 million. That is up 66% year-over-year and 39% sequentially from the first quarter, which had included a one-time non-recurring impact from our internal manufacturing upgrades. Amtagvi was the key growth driver, reaching a new high of approximately $91 million in the quarter. We exceeded our second quarter Amtagvi guidance range of $79 to $81 million. Quarter-on-quarter Amtagvi revenue increased roughly 51% over the first quarter of 2026 and 68% year-over-year, reflecting a robust increase in patient demand and adoption.

Proleukin contributed about $9 million in the second quarter, slightly down from $11 million in the prior quarter due to timing of wholesaler inventory stocking. For the full year of 2026, we anticipate that Proleukin as a percentage of total revenue will be in line with 2025. Consistent with the prior quarters, overall gross to net impact remains minimal at [ indiscernible ]. Margin increased to approximately 56%, up from 41% in the first quarter and above our previous all-time high of 50% in the fourth quarter of 2025. With the year-to-date 2026 margin of 50%, the second quarter benefited from higher Amtagvi volume, continued cost optimization, and maturing internal efficiencies during our first full quarter of manufacturing exclusively in-house. We are also deploying and advancing artificial intelligence tools to drive significant future cost efficiencies and new product pipeline insights.

As we expand our business as well as our development pipeline, we are very closely managing operating expenses. Research and development expenses were about $59 million, down from $62 million in the prior quarter, reflecting ongoing efficiency gains as we progress all of our programs. This marks the fourth consecutive quarter of cost savings through R&D optimization. Selling, general, and administrative expenses held essentially flat at about $39 million, even as revenue grew roughly 39%. With clear operating leverage from our commercial infrastructure, we expect to gain further efficiency with targeted investment across the business. I will now cover our outlook for the rest of the year. From second quarter sales, we are reviewing our previously issued full year 2026 total revenue guidance of $350 to $370 million and plan to share more detail in the third quarter.

We are well capitalized to fund both the launch and broader pipeline. As of June 30, 2026, we had approximately $304 million in cash, cash equivalents, and short-term investments. This cash position is now expected to fund operations into the second half of 2028. When I joined Iovance, the priorities were clear. Grow revenue, expand margins, and manage spend to reach profitability as quickly as possible. On my one-year anniversary, I am pleased to highlight that all 3 of these priorities are translating into positive results and lasting value for patients and our shareholders. I will now turn the call to Dan Kirby, our Chief Commercial Officer, to review our commercial progress.

Thank you, Corleen. As mentioned, Amtagvi generated record revenue with more patients treated than in any prior quarter. This commercial momentum is carrying into the third quarter. Adoption isn't just growing. It's broadening into new ATCs and earlier lines of treatment. Today, I will highlight 3 commercial priorities powering that trajectory for Amtagvi growth, which are rising physician awareness, continued expansion of our ATC network, and a deepening body of clinical evidence. The first priority is to continue to increase awareness of Amtagvi. Among both treating and referring physicians, unaided awareness has increased nearly threefold over the past year, driven by two factors.

One, a new marketing campaign unveiled at ASCO, and two, improvement in sales force effectiveness measured by meaningful growth in both number of treaters and referrers. The second priority is increasing our footprint across both academic and community settings. With more than 95 total ATCs today, we are on track to reach at least 110 by year's end. Community ATCs now represent a third of our network and are expected to increase significantly over the next several quarters. Each new ATC is widening our commercial reach to the patients who need it. The third priority is the continued expansion of our already deep industry-leading clinical evidence. Published five-year durability data, and real-world response rates of greater than 50% in patients with 2 or fewer lines of therapy are convincing physicians to adopt Amtagvi earlier. In addition, at ASCO we released a new survival analysis from our clinical trial.

This analysis estimated that the Amtagvi 10-year overall survival for responders would be 46.7% or almost half. Independently, a growing number of our ATCs are publishing their own real-world experience. Across these studies, response rates and patient outcomes consistently meet or exceed what we observed in our clinical trials, which support the emerging practice pattern of treating patients with Amtagvi as soon as possible after checkpoint inhibitor therapy. These aggregated, real-world evidence data are being deployed across our sales force in conversations with ATCs and physicians. This information can be found on the publications page of our website at iovance.com for those interested. Underpinning all 3 priorities is ensuring coverage and access. Amtagvi has strong payer coverage. More than 75% of Amtagvi patients are covered by private payers.

Payers and plans that cover more than 250 million lives have added Amtagvi to their policies. Our U.S. ATCs are strategically located in proximity to most addressable patients. More than 95% of patients live within 200 miles and 80% of patients live within 100 miles of an ATC. With our rapidly expanding ATC network and increased community presence, we expect even broader access to Amtagvi throughout 2026. Importantly, we are also proving we can deliver on our promise to patients with a turnaround time of 31 days or less using the only scaled centralized commercial manufacturing process approved by the FDA for TIL therapy. Demand for Proleukin, our second product, remains strong. All 3 wholesalers have sold through their previous stocking inventory in the second quarter and are currently ordering in line with Amtagvi demand.

For the rest of the year, we expect quarter-on-quarter Proleukin growth tied to Amtagvi growth on a steady basis of approximately 16% of total revenue. Outside of the U.S., with two approvals of Amtagvi in Canada and Australia, we are continuing to expand the new markets for previously treated melanoma patients, a globally addressable population of more than 30,000 patients annually. Our first ATC candidate is ready to support international private pay patients while we work toward public reimbursement. In Australia, I recently visited several of our onboarding ATCs as we collaborated to raise awareness and expand access to Amtagvi. Australia has the highest rate of melanoma in the world. We are opening our first ATCs for private pay patients while we work with the government on pricing. Looking ahead, regulatory approvals are pending in the United Kingdom and Switzerland.

We continue to work closely with health authorities and the European Union towards resubmission. Together, these foundational international markets augment our growing U.S. franchise for Amtagvi. In summary, demand for Amtagvi is strong and continues to grow. Rising physician awareness is accelerating referrals. A growing network of ATCs is broadening access that is converting into more patients treated. And the deepening clinical evidence is expanding the addressable patient population. Iovance is committed to serving patients with a one-time cell therapy that delivers meaningful, validated, systemic clinical benefits. I will now hand the call back to the operator to begin the question-and-answer session.

Our first question comes from Andrew Tsai with Jefferies. [Operator Instructions]

Can you talk about this large upswing in Q2 that even came out well ahead of your guidance? Was it purely due to underlying demand or was there kind of any one-offs in the timing of shipments maybe being more favorable in Q2? Just wanted to check the box on that. And then secondly, on the lung update later in Q4, just wanted to clarify on the cadence of events we can expect here. Is it fair to assume you would first need to complete enrollment in this pivotal cohort first and then generate follow-up data on every enrolled patient before you top-line the data, or can the top-line data be on the majority of patients, not necessarily all patients with follow-up? Thank you.

So I'll take the first part on demand. It's a great question. What we saw on demand was, as I said on the call script, essentially we saw that awareness is increasing among our physician base, both treaters and referrers. We are expanding our ATC network and then the clinical data is evidence of Amtagvi's efficacy. One thing that did happen in the first quarter that helped us in the second quarter was we had the manuscript published on our real-world evidence data that showed over 50% of the patients with 2 or fewer lines of therapy were responding. That data helped propel our sales force and our commercial efforts to raise awareness further and encourage more patients to be treated. We expect this to continue and we are seeing this in the third quarter.

Just to add to Dan, just to be very clear, Andrew, there's not a timing issue or anything. This is organic demand for the product. It's looking very good right now based on all the factors that Dan described and more that we really do expect that demand is going to continue to increase significantly for Amtagvi throughout the coming quarters. On the lung, about the LUN-202 update. Yes, I think it's fair to assume we're going to complete enrollment very soon and we would wanna finish that process before we put any kind of material update out, obviously for FDA purposes we want to do that. But I don't think it's fair to assume that we would wait for every single patient to become evaluable. We really want to make sure the integrity of the trial is clean and we have all patients in before we put some data out.

Some of the patients may still be coming for their first evaluation, that kind of thing. Will we put that out or maybe not? Depends on the timing and how the data looks. So just stay tuned. The lung is looking very positive right now. We feel very good about where we stand with the study and we will have a lot to say about that. I know that's a very key thing for investors and I really urge everybody as we talk about that and maybe even more than what people are expecting in this space.

Thanks so much. Congratulations.

Our next question comes from Yanan Zhu with Wells Fargo. [Operator Instructions]

From Fred's comment, it sounds like for the next two quarters, expect the sales to or the demand to further build upon the current demand level or the second quarter demand level. Just want to see if that's the correct interpretation. And in terms of, you know, given your visibility into the third quarter and perhaps also into the fourth quarter, can you talk about your expectation? And also, the guidance sounds like it's going to come during the third quarter, if that's the case, rather than at the next quarter's earnings call. Perhaps also a question on TILVANCE-301. Can you give an update on where you are? And sounds like you have a presentation. Yes, can you talk about what we can expect the data there? Thanks.

Sure, yes. Let me cover the first two, and then Dan can comment, and I'll come back to TILVANCE at the end. Yes, I think you heard correctly. Demand trends are very positive right now for the Amtagvi product, and we expect increasing demand Q3 and Q4. We're obviously seeing quite a bit of Q3 right now. We wanna just evaluate the whole situation because we really focus on long-term guidance here and we wanna make sure we can give good guidance for the full year before we announce it. But you are correct, we are intending to make a separate announcement of guidance. So, you know, one morning, you'll wake up to some hopefully very positive news, I think, from Iovance on the guidance as we get that visibility.

Can't tell you exactly when, but obviously sometime in the third quarter. But yes, that's very strong. Amtagvi is strong, and as we pointed out, Proleukin demand, it's very strong. Dan, do you want to comment and add some detail to that?

Sure. For Q3 right now, as you mentioned, Yanan, and we have pretty good sight into Q3 and what's going on right now, the demand continues to grow, and so we're very confident that Q3 will build upon the success in Q2, and then a Q4, of course, following from that. We've expanded our sales force to continue to evaluate, putting promotional activities in place such as new campaigns, etc., to continue that growth driving not only through 2026 but 2027.

And then I'll come back and answer your question about TILVANCE-301. That study continues to run well. We're very happy with the performance of the study. At ESMO, we're going to, again, in an oral session there, highlight some of the compelling clinical characteristics of Amtagvi plus pembrolizumab in the frontline setting, including the fact that almost a third of patients go into a complete response. A very rapid velocity of response, meaning we can drive patients into a response much faster than other alternative therapies, we think. And we'll show much more insight, I think, from the predecessor Phase 2 study. Obviously, TILVANCE is a randomized trial that we can't look at right now. It's blinded. We'll read that at the interim point, hopefully relatively soon, although these trials take a long time to run, as you know.

But we're going to show the compelling clinical characteristics. And I think it's going to be a very important output for people in the field, especially since some of the excitement around LAG-3 has faded, especially post-ASCO with Regeneron's results. And the LAG-3 is still, in some cases, being questioned whether it's the right combination in the frontline setting and there really is an extremely large need for some alternative to ipi/nivo in the frontline setting for these patients. We think lifileucel's characteristics are perfect for this. It would be one-time therapy combined with what may end up being fairly limited pembrolizumab dosing and the fact that we can drive a large percentage of patients into what's effectively a cure.

Great. Thanks for the update.

Our next question comes from [ Edsir DeRoute ] with Barclays. [Operator Instructions]

One question on margins and then one on lung. You had a meaningful step-up, obviously, in gross margin in the second quarter. Maybe if you could talk about the remaining opportunities to improve margins further, relative to current levels, and where you think mature commercial margins could ultimately trend to over time, that would be great. And then on lung, obviously, the durability exceeds historical benchmarks from what you've previously shown. Is the internal goal there to replicate earlier data from an efficacy and durability standpoint? And also, with enrollment nearly complete, have you continued to enroll patients with similar baseline characteristics from the prior update? Thank you.

Hi, [ Edsir ]. It's Corleen. So I'll answer your question. The driver is a number of things and as you know we've been focusing on this internally and we've been talking about it. Obviously higher volume which you can see. But we have all of our manufacturing in-house and those efficiencies are also helping margin as well as these projects that we have where we're continuing to focus on margin improvement and operational efficiencies within the plant. I would think about that in terms of process, automation, things like that.

And one other point I'll just add to what Corleen said. As Dan and others pointed out here already, with Proleukin now normalizing and then Proleukin sales expected to increase this year and then stabilize at the right percentage going forwards, Proleukin is a very high margin product. So you can expect a little bit of tailwind there as well. On LUN-202, I just want to, you asked two questions there, [ Edsir ]. One was, is our internal goal to replicate the durability, is to actually exceed the durability, because when we reported the durability earlier, we had short follow-up and I think what we're seeing right now, although we're not going to pre-release the results here obviously right now, we're seeing very strong durability, I think very similar in a lot of the cases overall outcome to what we saw in melanoma. It's effectively the same type of product. When we get a response, it's usually pretty durable.

Whether it ends up being two years, three years, whatever it's going to be, we'll find that out when we do the ultimate stats analysis at the end, but it looks pretty good. I think any of those options are going to be successful in the marketplace in terms of a product that will attract a lot of prescribers and patients to a one-time therapy like that. And then you mentioned within the enrollment nearly complete. You asked about the baseline characteristics of the patients. I think we are seeing similar baselines, or we don't have a lot of heterogeneity in our population. We're very comfortable with how we enroll these studies. We've spent a lot of time on our protocols to make sure we get things right.

And yes, I think we're seeing similar patients come through right now than we were throughout the study. Obviously, we changed our lymphodepletion to make it a little less burdensome on patients, and we're seeing really good results with that right now in terms of the safety profile and the overall risk-benefit profile of the product.

Great. Thanks for the color and congrats again.

Our next question comes from Reni Benjamin with Citizens. [Operator Instructions]

One regarding the outlook and the fact that you're reviewing guidance. Can you talk a little bit about what factors go into providing this reviewed outlook and kind of what prevents you from providing that guidance now? And related to that, does Replimune's recent positive FDA advisory committee feedback and maybe even Obsidian going public, does that kind of impact guidance? And if not, what are your thoughts regarding at least Replimune's agent coming into the marketplace? And just as a final question, the endometrial study, Fred, you had mentioned, you know, a histology-based patient selection and that there are protocol amendments going on right now. Can you talk a little bit or provide some color regarding the protocol amendments and, you know, how that study will ultimately reach conclusion? Thanks.

Let me take the last one first, because it's fast. It's a protocol amendment to focus on the serous subtype, and it really links up with the disclosure we had last quarter about the response rate that we're seeing and that precise approach to how we deliver TIL therapy to certain histological subpopulations in our studies. Well, we have a lot more to say that across all the indications soon on the guidance that what we're doing with the guidance internally is we're going to make sure we understand Q3 but really we want to understand full year. We're not looking to give guidance that is just sort of short term. We're really focused on long-term guidance to show the strength of the product overall. We really obviously we cater to long investors, long holders of the stock and we want to make sure they have the information they need to understand the overall trajectory.

So what we're going to do is make sure we have our demand understood fully. Obviously, it's very good. And then we will come back out at some point, which I can't tell you exactly when it's going to be during the third quarter. And we will announce something that I think everybody will find very positive and persuasive. On the competitor front, obviously there's a lot of noise out there. I just want to stress that we stay out of this. This is not our situation. Other people have their drama that's going on with the FDA, obviously. Okay. That product could get approved or not get approved. We don't really know but if it does get approved we view it as primarily competitive with T-VEC which is the product that's on the market today. That's also not an oncolytic virus very similar to that product as well as products like Opdualag that are being recycled in the community right now. It has a lot of barriers like T-VEC did and honestly when a company goes to launch a product, they have to perform.

And we expect Amtagvi is a much more compelling option, I think, for patients with this long-time profile and really fantastic efficacy and tons of real-world experience now. And so we think that'll be good. And with the other company, Obsidian, it's a TIL competitor. I think people should look very hard and carefully at Amtagvi, how far ahead Iovance is in this space and the infrastructure Iovance has and the strength that we have and the experience that we have in this area before they sort of just randomly assume that some other company is going to come out of nowhere and somehow conquer the world here. So just bear that in mind that there's reality all these things. Many investors have visited us and see scale what we do. We can see the power of what we do and how much hard work and experience and intellect went into this whole thing. It's not easy to recruit and there's a giant moat around Iovance. It's I think very, very helpful for investors.

Great. Thanks for taking the questions.

Our next question comes from David Dai with UBS. [Operator Instructions]

So on Amtagvi demand, can you just talk more about the demand across different ATCs? Do you see more demand concentrating on large ATCs, or do you see increasing demand in smaller and newly activated ATCs that have a follow-up?

Thanks for the question. What we saw and what we are seeing right now is the ATCs that we originally opened in 2024 are starting to grow based on patient type and based on the information that we have that's been published recently. The ATCs that we onboarded last year in 2025, those are continuing to accelerate. Some of them are hitting their stride, so to speak, and getting mature and treating their patients. And then in the first half of this year, we've been opening ATCs at a pretty substantial pace. And those are starting to contribute now. So we do see there's a few months between an ATC activation to them starting to treat patients, and then comfort level goes up. So we are seeing growth across the different segments.

In regard to larger ATCs and whether they're contributing to more, I think our larger ATCs are still growing. We still haven't had an ATC that we can say has reached complete peak because they keep looking for new patients and patient types then. So we are seeing across our subset of ATCs, all of them.

Great, thanks for the color. And then on community ATCs, which now represent roughly one-third of the network, how does patient volume, referral behavior, and reimbursement experience differ between community and academic?

Great question. So for patient volume, they have the patients there and it's really not the number of patients, it's what time we're getting these patients. So as we said in the real-world data that got published earlier this year, is that patients that are on 2 or fewer lines of therapy have an over 50% response rate. Those patients reside primarily in the community setting before we refer to the academic. So we see referral barriers go down. The volume of patients are there and they're there earlier. We do see the community ATCs are having learning curves similar to what we saw in the academics. So again, it takes a little while for them to ramp up.

They're doing so now. Most of the community ATCs we started to onboard in the second half of last year joined in the first half and that was one of the things that we said would be in focus. We come through on that focus and now a third of our ATCs, and we do see that they can have a higher ceiling than the academics because again it's organic referral patterns within network which are much easier to maximize than referring to the academic centers.

Our next question comes from Colleen Kusy with Baird. [Operator Instructions]

Just wondering if you could provide any color on how the conversion rate from referrals to treated patients has changed over the last few quarters. And then also just on growth bottlenecks like patient identification or referrals, et cetera, what do you expect to be the biggest constraint on growth going forward? And just wondering if you could talk about how you plan on addressing that. Thank you.

Sure. So as we look at this, the conversion to referrals, what we do see is earlier patients and earlier patients coming in. We're using that data in both non-personal media as well as in face-to-face with our field forces to get that word out. So again, we are seeing the referrals come in earlier, which means we have time to treat the patients. So that is the change in the referral pattern with an earlier patient. And that gets into patient ID as well. We have gone after, I've mentioned in previous calls, the BRAF mutated patients, because that is a very important patient type, 40% of our market that we were having trouble accessing before. We're getting tumor tissue earlier, that is helping us ID these patients earlier to get tissues so we can manufacture for infusion at the right time.

And then as far as constraints with it, the constraints that we're working on is really more penetration into the larger community networks and we see that as an opportunity. We've made a lot of strides over the last 6 to 8 months with other entities, Florida Cancers, et cetera, where we're getting the referral pattern up or we're looking to establish ATCs within their own networks. We've got some up right now in those areas. We're looking to get more up. Fred, did you have anything to add?

No, Dan, I think that's pretty accurate.

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

Thank you for joining us. This was a record quarter for revenue, infusions, and margin. Our pipeline is advancing rapidly with new registrational trials, next-generation clinical programs, and new approvals outside the United States. We are energized by the growing number of patient stories that show the power of our TIL therapies. We remain deeply grateful for the patients, partners, healthcare professionals, and advocacy communities we serve. Finally, I want to thank our exceptional Iovance team, our dedicated shareholders, our covering analysts for their continued support. We remain committed to our mission to innovate, develop, and deliver current and next-generation cell therapies for patients with cancer.

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

Good day, and thank you for standing by. Welcome to the Iovance Biotherapeutics first quarter 2026 financial results conference call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Sara Pellegrino, SVP of Investor Relations and Corporate Communications. Please go ahead.

Thank you, operator. Good morning, welcome to the Iovance webcast to discuss our first quarter 2026 financial results, business achievements, and corporate updates. This morning, we issued a press release that is available on our corporate website at iovance.com.

This conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans and transactions, revenue and revenue guidance, commercial activities, clinical trials and results, regulatory approvals, submissions, feedback and guidance, plans and strategies, research and preclinical activities, potential future applications of our technologies, manufacturing capabilities, payer interactions, licenses and collaboration, 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 statement.

I will now turn the call over to Dr. Fred Vogt, our Interim Chief Executive Officer and President.

Thank you, Sara. Iovance is the global leader in innovating, developing, and delivering current and future generations of TIL cell therapy in solid tumors. We are executing to maximize patient and shareholder value across four pillars: curative platform potential, commercial execution, technology extension, and fully owned manufacturing.

During the first quarter of 2026, we drove Amtagvi adoption, advanced our development pipeline, and streamlined costs and efficiencies. First quarter revenue grew approximately 45% year-over-year. Owning manufacturing is critical for our success. We navigated a temporary capacity reduction to complete maintenance upgrades at our internal manufacturing facility, the iCTC. Since resuming full production, Amtagvi is now exclusively manufactured in-house, and our modular facility can provide uninterrupted supply while supporting global demand and scale. Research and development expenses declined for the third consecutive quarter, helping to extend our cash runway into 2028.

Looking ahead, Amtagvi enrollment and referral trends are at an all-time high in support of our second quarter and full year 2026 guidance issued today. Second quarter total revenue guidance is $86 million to $88 million. Amtagvi revenue is expected to grow to $79 million to $81 million in the second quarter. This is an increase of approximately 23% over our highest quarterly revenue to date in the fourth quarter of last year. For the full year 2026, total revenue guidance for Amtagvi and Proleukin is $350 million to $370 million, predominantly fueled by Amtagvi. Over time, we project we project a $1 billion peak -- $1 billion plus peak sales trajectory for Amtagvi and Proleukin in the U.S. For the rest of 2026 and beyond, we expect gross margins to benefit from our financial discipline, in-house scale, and operational efficiencies.

Shifting to our TIL platform, we're expanding the curative potential across solid tumors. This morning, we announced compelling and clinically differentiated early Phase II data in metastatic serous endometrial cancer. The confirmed Objective Response Rate was 40% with a 100% disease control rate in the first five patients. Metastatic serous endometrial cancer is difficult to treat with an estimated 5,000 annual U.S. deaths. The second-line treatment setting represents a significant unmet medical need with response rates below 15%. We plan to engage with the U.S. FDA to pursue an expedited approval pathway.

I will now highlight additional registrational trials for lifileucel in new indications. To expand the Amtagvi's market potential into advanced frontline melanoma, we continue to execute our global TILVANCE-301 trial. In previously treated non-squamous, non-small cell lung cancer, lifileucel received FDA Fast Track Designation following best-in-class unprecedented response rate and strong durability. This U.S. blockbuster market is about 7x larger than our peak opportunity in advanced melanoma. We plan to complete enrollment and provide a clinical update this year, targeting accelerated approval and U.S. launch in the second half of 2027.

In advanced and difficult to treat soft tissue sarcomas, IOV-SAR-201, our new registrational trial, is underway in refractory patients with advanced undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. The trial is beginning enrollment in the third quarter of 2026.

We are building upon positive early clinical results with a 50% confirmed response rate in comparison to the abysmal response rates of less than 5% with current standard of care. We are actively engaging with FDA soon on path to expedited approval.

As the global leader in TIL cell therapy, we are making significant progress to our next generation programs. IOV-5001 is our IL-12-tethered TIL therapy for highly prevalent solid tumors. A prior generation IL-12 TIL therapy at the National Cancer Institute improved clinical efficacy without IL-2 and informs how we optimize IOV-5001 to enhance efficacy and safety. We recently submitted the investigational new drug or IND application for a Phase I/II clinical trial, which includes indications that represent more than 15% of U.S. cancer deaths annually.

Among these indications are advanced colorectal cancer as well as triple-negative and estrogen receptor-low breast cancers, adding large populations of massive commercial opportunities to our strategy. The trial is expected to begin in the second half of 2026.

Our next generation IL-2 product, IOV-3001, may optimize the TIL treatment regimen. A Phase I safety cohort using IOV-3001 is advancing through multiple dose levels in a Phase I/II trial. We continue to enroll in our clinical trial with our PD-1-inactivated TIL therapy, IOV-4001, which reduces inhibitory signals to enhance the ability of TIL therapies to fight and kill cancer. We are initially exploring melanoma and non-small cell lung cancer. We look forward to reporting data and updates soon.

As we expand our clinical strategy in solid tumor cancers, we now have the opportunity and capability to identify enriched patient populations that are highly responsive to TIL therapy. We are identifying these enriched populations such as the serous endometrial cancer population we highlighted today and our selected populations within soft tissue sarcomas and even within non-small cell lung cancer and other indications, which you will hear more about later this year.

Iovance is well-positioned as the only company to have taken TIL therapy from concept to commercial scale with the manufacturing infrastructure, clinical breadth, commercial experience and operational discipline to back it up. We have momentum, a broadening pipeline and an improving line of sight to profitability. The foundation is built, and as we continue to expand across indications, our ambition is clear. To extend our leadership not just in TIL therapy, but as the backbone of immuno-oncology and solid tumor cancers.

As I conclude this pipeline update, I would like to extend my sincere gratitude to Friedrich Finckenstein, our Chief Medical Officer, as he prepares to retire in June. During nearly 7-years at Iovance, he was instrumental in leading us towards the FDA approval of the first-ever TIL therapy and our leadership position today. Friedrich is available during today's question-and-answer session, and I wish him the best in his retirement. I will now turn the call over to Corleen Roche, our Chief Financial Officer, who will provide further updates on our first quarter financials and full year expectations. Corleen?

Thanks, Fred, and good morning, everyone. Our commitment to operational excellence, commercial growth, and financial discipline drove strong top-line year-over-year growth and meaningful cost containment in the first quarter. We transformed our internal manufacturing facility to meet demand growth and scale for the future without major additional capital investment.

First quarter revenue of $71 million grew roughly 45% year-over-year, driven by strong Amtagvi demand. Amtagvi revenue of $60 million increased by 38% year-over-year on strong demand growth, our second-highest quarterly revenue for Amtagvi. We mitigated the first quarter impact from a temporary capacity reduction as we upgraded our facility.

Moving to Proleukin, $11 million in first quarter revenue nearly doubled from the year ago period on higher Amtagvi adoption. Importantly, gross-to-net impact remains extraordinary and consistent with past quarters at less than 2%. Our first quarter gross margin from cost of sales was about 41%, which absorbed one-time nonrecurring costs related to our facility upgrades. Margin is expected to trend higher for the rest of 2026, excluding one-time items, as we operate our in-house capabilities more efficiently.

We continue to manage our operating expenses carefully, including optimizing research and development while expanding our pipeline. Notably, research and development expense declined for the third consecutive quarter, a reduction of 18% over the prior period and 12% over the prior quarter.

Moving to our revenue outlook. After thorough analysis of demand trends and internal forecasts, we expect total revenue between $86 million and $88 million for the second quarter, driven by strong Amtagvi demand. This momentum carries through into our full year 2026 guidance of $350 million to $370 million for the full year. As of March 31, we had approximately $319 million in cash and equivalents. Thanks to careful cost management and financial discipline, we expect to fund our operations into 2028.

In closing, we are building momentum and focusing on operational excellence to grow revenue, manage expenses, and improve margins. We are on a clear path to profitability and remain committed to creating lasting value for our shareholders. I will now turn the call to Dan Kirby, our Chief Commercial Officer, to review our strong commercial progress.

Thank you, Corleen. Building on Corleen's comments, strong demand in the first quarter culminated in our second-highest quarter of Amtagvi revenue. This performance was achieved with reduced capacity and yielded much better results compared to the first quarter of 2025. Demand continued to increase throughout the quarter. March was our largest month ever for reported Amtagvi revenue. Second quarter is off to a very strong start with projections supporting our guidance that this will be our best Amtagvi quarter to-date.

In addition to generating demand, our three commercial priorities are further solidifying Amtagvi as the choice for patients. First, our expanding ATC network of academic ATCs together with new community ATCs are creating more patients, establishing both a reliable base of business as well as driving additional growth in 2026. Second, patients are increasingly referred for Amtagvi earlier in the treatment cycle. The recently published real world evidence combined with published 5-year durability data has been very impactful in educating physicians on the value of earlier referrals and optimal treatment with Amtagvi. Our field teams are committed to educating our physicians while advocating for our patients. Third, Amtagvi awareness continues to build among our key target physicians. Our latest market research shows physician awareness increased to 70%, up from 50% over the last 6-months. Earlier this year, we further expanded our field sales force with plans for additional increases in field staff as more ATCs onboard and demand continues to strengthen.

Proleukin is seeing robust demand, driven primarily by its use alongside Amtagvi. Proleukin sales were $11 million in the first quarter, down from the prior quarter due to wholesale buying patterns, but a substantial increase from the prior year as all 3 wholesalers ordered. We expect Proleukin to stabilize and grow throughout the year with increasing Amtagvi demand. Globally, we are making meaningful progress on [ ex-U.S. expansion ]. Amtagvi has the potential to reach more than 30,000 patients annually with previously treated advanced melanoma.

Following Amtagvi approval in Canada, the first ex-U.S. treatment center is officially authorized to support international [ private-pay ] patients. At the same time, we are advancing reimbursement discussions with the Canadian government. Regulatory decisions are anticipated in Australia in the first half of this year and in Switzerland next year. We continue making progress with regulatory submissions in other markets as well.

Finally, May is Melanoma Awareness Month. We are collaborating with advocacy groups to celebrate the patient experience while spreading awareness of Amtagvi. Yesterday, the Today Show posted an inspiring story highlighting Jennifer, a mother of 3, who is back to enjoying her family after receiving Amtagvi more than a year ago. Her story is one of many that represents the hope of Amtagvi. Jennifer is now also featured on our website, amtagvi.com. A growing network of patients are sharing how this one-time cell therapy has helped their own immune system, fight cancer.

I will now hand the call back to the operator to begin question and answer session.

[Operator Instructions] Our first question comes from Andrew Tsai with Jefferies.

Hey, guys. This is John on for Andrew. Congrats on all the progress. For Q2, if your Amtagvi sales guidance of $79 million to $81 million, how much can that improve gross margins quarter-over-quarter as well? And then can we assume that the Q2 gross margins will be better than the Q4 gross margins at 50%?

Yeah. Thanks, John. Well obviously, the margins we showed in Q4 of 2025 were really where we aspire to be or above that. We can't say just yet where our margins are going to be exactly. But I would expect generally that they will trend upwards throughout the year. We're working very hard on that. It depends a lot on the product mix and a lot of other factors. So we really do want margins to be better throughout the year and then of course, in 2027 and beyond, we're driving towards higher and higher margins all the time.

Yeah. Just to emphasize, John, the margin was impacted, like I mentioned, from one-time nonrecurring costs. That should not happen again. It will be nonrecurring. Our margins should be continuing to grow. As i keep mentioning, we have a lot of efforts. We brought everything in-house, right? So we use the capacity of our own facility. We'll have economies of scale there. We also have targeted projects focused on operational excellence in the plan specifically. And as you see, as revenue grows, that also helps. Does that help you?

Yes, definitely. And then also maybe just a quick follow-up, if I can. Is it fair to assume that the lung data would come at a major medical meeting in the second half of 2026 versus something like Q2 at ASCO? And then would you be inclined to press release the data before? Any timing granularity would be helpful. And maybe also just remind us your expectations on ORR and potentially even DOR?

Yes. As you can see, we released data in lung only about 6 months ago that had excellent durability, which is typical of immuno-oncology approaches that work really well. So you can go back and look at our November press release, that's basically what we're looking at for this product and what we think is something that we get approved for non-squamous non-small cell lung. I can't really say much more about conference stuff except that we've guided, obviously, to 2026 disclosure at a medical meeting, and we continue to plan to do that.

Our next question comes from Reni Benjamin with Citizens.

Congrats on the progress. Maybe two questions. One, as we think about the ATC network and now bringing to the 90, I think you're targeting 110 by the year-end. Can you maybe talk to us a little bit about what the split will be between these academic ATCs and community ATCs? And what do you think will be the max capacity across these ATCs?

And I think, Fred, you mentioned that the sales force is going to be growing throughout this year. Can you give us an idea as to what the optimal number of that may be? That's the commercial question. One for Friedrich because this will be the last time that we're speaking to him. Congratulations, Friedrich, on retirement. Kind of wanted to just get a sense as to the 40% confirmed ORR in endometrial, kind of your thoughts and any kind of details you can provide us in terms of depth of response or durability and how it compares to what's already out there?

So Remi, thank you very much for the question. I'll start first and hand to Friedrich. In regard to the ATC network, we see ATCs now on-boarding and starting to treat faster than they were last year. So the ones that on-boarded in the second half of the year are treating faster. Our academic and community mix is starting to get more balanced, whereas at the beginning, we were mostly academic. Now we're going more into the community hospitals, and getting closer to the patients, where the opportunity is greater for us. So we do see that, that is going to, over the year, mix more into a greater percentage of community entering-in because we do have the key academics already onboard and treating.

In regard to sales force, we did increase our sales force going into this year based on the second half ATCs entering into Amtagvi authorization. We did see and have seen and are seeing increased demand from those ATCs. The new reps are being very impactful in the field with it, and we have a plan now to expand in Q2 as well as looking at later this year based on the timing and pace of both demand in our current ATCs and on-boarding new ATCs. Hopefully, that answers your question. I'll hand over to Friedrich for the second half.

Yes. Thank you. Thanks for the question, Remi. Yes, so this is a really, really exciting result that we're seeing there. As you know, in endometrial cancer, the checkpoint inhibitors are -- have moved into frontline therapy. So standard of care or really available therapy, if you want, in second line is dire. Usually, these patients are being treated with monotherapy, chemotherapy and response rates are usually below 10%, 15% highest when you look at control arms of randomized trials. So that's not good enough. These patients have highly unmet medical need and seeing another immunotherapy come through with these response rates and typically durability that is differentiated from chemotherapy, that's really important. That's why we're planning on jumping on this and taking this further.

Our next question comes from Etzer Darout with Barclays.

Congrats on the quarter. Just looking again at your 2Q guide, just wondered how much of this rebound with the step-up from the first quarter is maintenance disruption versus maybe underlying demand trends, and what the key assumptions are behind the outlook there?

And then maybe secondly, on the pipeline, just as you think about the endometrial regulatory path, should we think about a potentially similar framework for -- as you're employing for sarcoma in terms of the regulatory path to accelerated approval?

Yes. So let me take the second question first actually because, yes, that's correct. We are looking at a similar regulatory path for serous endometrial versus UPS and [ DDPS ], and we'll come back soon after we have some interactions with FDA. We're going to try to optimize as much as we possibly can to supplemental BLA filings and if possibly, we combine stuff and work together to make sure that we can get these things approved as quickly as possible with the FDA. So stay tuned for a lot more detail on that. We're very excited, obviously, about all 3 indications. We think they all significantly to Amtagvi's potential, and we're currently built to launch all these indications quite quickly on the back of our commercial expertise and manufacturing.

On the Q2 guide, you were asking about maintenance versus demand. Demand trends are extremely strong, as Dan highlighted earlier. I really don't think about it as a maintenance issue. I think about it as something that we had to address. We fixed it, it's done. We won't talk about maintenance ever again. It's now built in our system so we can do it without any kind of -- any kind of impact whatsoever. Demand is very, very, very strong for the product right now. So Dan, do you want to emphasize again some of the points you made during the prepared remarks on demand trends?

We continue to see demand increase. This has happened through fourth quarter and the first quarter and carried into the second quarter. I mentioned before that March was our largest reported month to date. We continue to see a strong start to Q2, which is why we have the guidance set.

Our next question comes from Colleen Kusy with Baird.

It's Nick on for Colleen. Congrats on the progress. Just -- so with the new guidance, expecting $209 million in product sales in the back half of the year, can you just speak to your confidence in hitting that goal? And what else needs to be done to get there?

Yes. So right now, Nick, we're highly confident we can achieve that. We've obviously already done a lot of it. We have visibility right now in Q2 into essentially the entire quarter. That's why we're giving such strong guidance for Q2 Amtagvi revenues as well as Proleukin. And then the back end of the year, we can see very clearly, too. And when you look at the guidance that we gave today, it's easily achievable with some growth as we go from Q2 to Q3, Q4 that we have line of sight and visibility to.

We have a much better understanding of our ATDCS and how they perform, how we can produce the product and every step of the process of getting Amtagvi to the patient. And I think it's extremely responsible guidance that we've given -- its guidance that we will do everything in our power to beat, of course, but it's guidance that we can stand by and live with and it's quite strong compared to where we were last year.

And I would just add on to that, Nick, that this is our second full year on the market. We're over 2 years since launch. So variables such as seasonality, et cetera, we have a much better handle on. And we can project based on new ATCs coming and growth in the current ATCs where demand is picking up and where demand continues to increase. And that's why we look at the second half of the year as being extremely strong. It starts right now in the fourth quarter. We're seeing it right now in the demand and what's lining up for the centers.

[Operator Instructions] Our next question comes from Tyler Van Buren with TD Cowen.

Can you talk about the progress you made with the TILVANCE-301 enrollment, where you are in terms of percent enrollment? And what's been working to enroll patients? And what are some of the hurdles that you've had to overcome like sites in the U.S. using Nivo Ipi in the front line?

Yes, I can get that and then maybe Friedrich can add a little bit to it, too. We're seeing good enrollment in TILVANCE-301. Obviously, we do a lot of it outside the United States because it's easier outside the United States with standard of care. But it's a study that we think is well designed. We have very good FDA feedback on the design of the study. We're very focused on getting to the interim read where we can read ORR and have an early discussion with FDA about confirming Amtagvi's approval as well as getting additional approval. You can go on clinicaltrials.gov and see the vast scope of sites that we're running right now. It's all over the place.

There's -- obviously, with any trial, there's things that you have to do to pound through it and succeed. Every company has to deal with this, and we're encountering and overcoming, I think, a lot of those right now, with this trial. So we expect good things for TILVANCE, and we think that TIL therapy in the frontline setting, especially combined with pembrolizumab can vastly improve the chances of a good overall survival outcome for patients. Our COM-202-1A data shows that. You've seen that publicly. We'll talk about that more this year, but that's really what's driving the study right now. Friedrich, do you want to add anything?

No, I think you've said it. I think it's important to remind folks that pembrolizumab is standard of care, and there are some geographic differences around this and not everyone believes that everyone should be getting -- frontline combination therapy. And then, Fred, you already highlighted the data from Cohort 1A from COM-202 that is proof for the potential for durable meaningful benefit for patients in that treatment setting from TIL therapy when used as early. So I totally agree.

Our next question comes from Salim Syed with Mizuho.

Would love to ask more than two questions here, but I'll limit myself. Corleen, Fred, maybe just one -- I'll limit myself to two here. On the ATM usage, this is now the fifth quarter you guys have access to ATM in a row, 4 of the 5 quarters, it's been pretty heavy usage. What -- could you just outline for us just your financing plans here? I mean this seems to be egregious at this point beyond any biotech company that I'm aware of how much you've access to your ATM. Why don't you just do a more traditional sort of financing path here? Or what are your financing plans going forward, should we expect this continued sort of practice?

And then just second, on guidance, could you just outline for us, please, how do you come up with your guidance now? Like is it -- you have your sort of internal forecast and it's a plus/minus when you get to that? Or is it just downside? Just how conservative is this guidance?

Yes, we don't think the ATM usage is egregious at all. We dipped on the ATM occasionally, and we use it as needed to sort of top up where we are, and we've been really, really disciplined in how we use it. We're really driving the cash runway extension and now we pushed the cash runway out 2 quarters, more than 2 quarters in this most recent. By the way, every single quarter, we're pushing it out a quarter. So we're now all the way well into 2026, as you can see in the press release today. That's largely on the back of cost discipline. And we're getting -- internally, we're getting better and better at saving money when we run our trials, and we're obviously boosting margins and we're making more revenue to the top line. Everything is coming together to really extend our runway. And we are very, very focused on breakeven and any dilution for the shareholders.

So yes, we do have to make use of the ATM. We still explore non-dilutive options. We're still working on them right now, but we think the lowest cost of capital right now for the company is to do a little bit of equity here and there, to make sure that we are getting closer and closer to that breakeven every quarter.

On the guidance, we think this guidance is responsible. We are in possession, of course, as a company of detailed information about each ATC, the performance of each ATC, performance of our manufacturing, every aspect of what we do with Amtagvi, much more detailed than we were when we launched the product in the beginning. Now we have all the information we need. Dan's team is doing a great job identifying all the trends. As we onboard new ATCs, we have a much better understanding of what they're going to add to the picture. We know which ATCs to focus our sales teams on and which ATCs can produce for us reliably -- product that is the highest quality that we can make very reliably for them.

And so we have internally, I would call them extremely sophisticated forecasts that we are watching every day to make sure that they are accurate in the launches. So for example, for Q2, practically every resection that we have for Q2 has already been performed. So we already have a very good understanding right now of what's going to happen for Q2. That's why we can give that guidance so tightly. And we're really, really comfortable in that guidance. That's why we're giving it. We know investors want it. And like I said earlier, we're going to do our absolute best to beat it.

I'll just add on to that, Fred. Looking at that, and I agree that the guidance that we said, I've been here over a year and really, we've learned a lot about this market and how to forecast and understanding it. So that's responsible, as Fred said.

But I would also say that my teams are focused on beating that. That is our mission. That's what we're going to do and our expectations are higher than that. But again, the guidance is responsible, what we believe we're going to do based on the current information we have, but we will seek to onboard more ATCs than our goal. We'll seek to treat more patients than our goal. So I hope that gives you an idea of the mindset from my teams on that, but also to what we issued publicly is what we believe is responsible and what we are going to do based on the information we have today.

I'm showing no further questions at this time. I would now like to turn it back to Fred Vogt for closing remarks.

Thank you again for joining the Iovance Biotherapeutics First Quarter 2026 Conference Call on the heels of record high demand for Amtagvi as well as significant progress across our pipeline. As we continue to work on therapies with curative potential in solid tumors, we are energized by the growing number of patient stories reflecting the impact of our TIL therapies, some benefiting upwards of 6 years and counting. We remain deeply grateful to the patients, partners, health care professionals and advocacy communities we serve.

Finally, I want to thank our exceptional Iovance team, our dedicated shareholders and covering analysts for their continued support and commitment to our mission to innovate, develop and deliver current and next-generation TIL cell therapies for patients with cancer. Thank you.

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

Hello, everyone. My name is Etzer Darout, the senior biotech analyst at Barclays. It's my pleasure to have Iovance Therapeutics for our next fireside chat. With me today, I have Brian Gastman, Executive Vice President of Translational Medicine and Research; and Sara Pellegrino, Head of IR. Thank you so much for joining us this morning. Maybe just Brian -- just Sara, just maybe give us an overview of Iovance for those less familiar with the story.

Great. So that's a great place to start. At Iovance, we have 3 key pillars of strength that we are focusing on in 2026 and into the future. Our first pillar of strength is our U.S. commercial business, driven by our commercial product, Amtagvi, which is approved in previously treated advanced melanoma in the United States and has at least a $1 billion U.S. peak sales potential. The next pillar of strength is our pipeline, which we are building as the backbone of immuno-oncology in solid tumors.

And our lead program there is a registrational program in advanced non-small cell lung cancer, where we have potential best-in-class profile that Brian can talk more about today. And third, we are honing our operational excellence as we grow revenue, reduce expenses and realize efficiencies on our path to profitability.

So we'll talk in more detail about these pillars of strength today. But on the heels of a strong 2025, we are confident in remarkable revenue growth, financial discipline and important pipeline catalysts in 2026.

So I guess, maybe take a step back just in terms of what Iovance was able to accomplish in 2025, around sort of commercial traction for Amtagvi and improving margins. Maybe you can just start with what gives you confidence in the business and your ability to execute on that in 2026?

Well, for me personally, I can just say that we're seeing growth. I think the second half of 2025 is quite strong. The fact that we're penetrating into the community, which we really didn't do prior to that, I give our new CCO, he's not so new anymore, a lot of credit for those initiatives, a number of ATCs have stepped up that were slow to start and now have really not only showing good volume, but also good quality in that volume and the strong commitment to getting these patients early. I think that's the main thing we're seeing across the board.

It helps with our manufacturing. It helps with us getting the drug manufactured to the patients. And then ultimately, we'll talk about this for real-world evidence, the results have been dramatically better when we do so. So I think all those give us a lot of confidence. And I think -- and finally, I would just say just the sentiment enthusiasm in the community. I came 18 years in practice with those same people. You can feel probably the change.

Yes. When a new ATC in the community setting comes online, what tends to be the hardest part of the learning curve for that facility?

Yes. So each one has its own challenges potentially depending on their strengths, depending on whether or not they participate in clinical trials. But ultimately, what ends up happening is a trifecta of the medical oncologists who are identifying and referring these patients, the cell therapists who control the floor that the patients can be treated on and the -- all the reimbursement specialists and case management and the surgeons.

And when we see them come together and work as a team, not as just technicians as part of something needs to get done, that's when we see the excellence from the centers. Some centers, of course, are built in with gigantic volumes the usual players, so to speak. And when we do so, these really drive our business. And I think each center has its own version of that. So I can't say specifically. I don't want to call it specific means. But you can imagine you can -- we know how to tailor those issues to the center.

Great. And with the real world data that you recently disclosed, obviously, higher responses with earlier use and that was interesting to us. How are you seeing that data sort of update influencing, again, uptake of Amtagvi or just any conversations that you're having based on that data set?

Sure. So let me just remind the audience. What we're talking about here is that our pivotal trial showed a 31% response rate with really -- and I think we may talk about this also incredible durability not seen prior and not seen since. But the question has always been what will happen in the real world. We've seen in immune check inhibitors is actually worse real-world evidence than actually we saw on some of those top line trials that was even Nobel Prizes, for example. So we were pleasantly surprised that, first of all, we saw at least as good, if not better, in all lines of therapy. And ultimately, what we found was a 44% response rate, which was definitely higher than 31%.

However, when we broke it down by lines of therapy, the early patients actually drove that to be higher. It was over 50% response rates. And you can see our responses tend to be so durable, sometimes immeasurably durable. So we're very excited that if we can get every patient and almost every melanoma patient in this class is a TIL-worthy patient, if we can get them at the right time, everybody should be able to achieve those kind of responses.

And so I think your question then is, what has that data done? Well, first of all, for some centers, it's validated what they already knew, but they didn't have it objectify. Two, it allows centers to question why are they doing so much better than we are to now understand what the gap was. And three, they now can communicate to the non-authorized treatment centers why they need to and should absolutely ethically refer these patients as early as possible because ultimately, we want the best for our patients.

And then quite frankly with you, a lot of referring physicians, they may not be giving you the therapy, but they actually get the benefit both the personal satisfaction, but also even the business satisfaction of being able to treat these patients and follow them for many years to come. So there's a lot of win-win for everybody, but ultimately for the patients.

Right. And the deepening of response dynamic, I think you presented some data at ASCO, I think, is another sort of access this. Are you hearing anything around sort of adoption or anything around sort of driving more adoption based on that deepening of responses? Are physicians aware of the data in your conversations with different communities?

Well, for those who are absolutely aware, it is very impactful. First of all, to have a onetime therapy that can work even years later is incredible. And I think that not only goes to the living therapy side of it, but also it's polyclonality. So for example, if the tumor immuno edits one of the targets that our therapy goes after, we have other targets that all of a sudden as that tumor changes, our therapy actually can actually go after.

We saw patients go from a partial response to complete response almost 3 years later, but no therapy. They're just sitting at home and the therapy is just working, which is incredible. What it does though, it goes back to my point earlier, many -- especially in the oncology world, a lot of their business -- I mean, sadly, there's palliative care, there's current treatment, but a lot of it's follow-up on these patients.

That's what they do. They order scans, they get blood work. Well, when they see that if I can send someone to a center and my patient can come back to me for years on end, always with smiles on each other's faces, and I get to actually run my business by just following them for years, it's very impactful. I think the challenges on our centers and us to get down to the people who need to know this information, ASCO is great, but people go to ASCO for many things, not just the melanoma sessions. But for those who've heard it, it's been very impactful.

Right. For U.K. and Australia, given potential approvals in the first half of '26, do you expect to start generating initial revenues in '26 in those regions?

Great topic. So we're really excited about the opportunity to expand -- to expand Amtagvi beyond the U.S. And there's approximately 30,000 patients globally that could potentially benefit from Amtagvi around the world. We really think that the ex U.S. markets are upside beyond 2026. We're approved in Canada. We're pending in the U.K. and Australia this year, and the reimbursement and pricing discussions are happening in parallel, but they also do continue after the approvals. So the process is a little bit longer than outside of the U.S., and that would be -- something that would be factored in more after 2026.

Great. Maybe we can switch over to lung cancer for cell. So lung cancer, different market than melanoma, it's larger, more heterogeneous, also more competitive. I guess when physicians look at this data later this year, what do you think will matter most for them when they take a look at that data set?

Sure. So let me remind the audience that if you look at the best-in-class frontline therapy for non-small cell lung cancer, essentially the 5-year data shows that everybody is basically progressing. Less than 20% of those patients are alive, let alone not progressing in 5 years. So I think to many in the field, there's really not a cure out there, whereas in melanoma, if you do well in front line, you could do well. So there's less of this. Let's just keep trying these therapies in more what else is next.

To have a drug with this potential durability and as you've seen some of the data that we've put out there where in swimmers plots, these patients are swimming for years on and it's reminiscent of melanoma, and there's a deep need for this type of therapy. There's just nothing else out there. It's competitive but most of the competition is just get responses, not for durability. And again, I think that's our strength. And I think that's what's really going to be energizing the community moving forward. So ultimately, bigger unmet need, a lot more patients and then the fact that we hit the unmet need with an incredible amount of durability. I think that's what I would be looking for when we show this data.

Right. And maybe just remind audience around sort of the second-line nonsmall cell lung cancer setting in terms of responses, the duration of responses we've seen historically? And what you sort of view as sort of a benchmark that you would view as a positive update when we get that lung cancer data?

Generally speaking, docetaxel or docetaxel plus something else, which causes lots of toxicity are the benchmarks. But you'll see docetaxel used mostly as your standard. And I think the main thing is whether you see a 10% or more response rate, the median progression-free survival, somewhere between 4 and 6 months. It's very -- it really is a palliative drug. So where we went out on this is less on the responses and more of the fact that if you get a response, it could be immeasurable.

And so I think the bar is extremely low. And ultimately, you see that because as I told you in the frontline patients, most of them don't -- aren't really surviving, A lot of them actually got that docetaxel. And then they got some clinical trial and a fourth line. And now they're in that 5-year status where most of them are not live. So whatever it is out there, benchmarked or not, there's a major dissatisfaction in the current options.

Right. And when you think about the ATC network currently in place for melanoma lung cancer significantly bigger opportunity. Is there going to be teaching involved? How are you thinking about expanding sort of the ATC network to be able to meet the demand of a much larger population in lung versus melanoma?

Well, first of all, there's a huge overlap here. I mean, basically, it's the exact same centers. It's the exact same cell therapists, same case management, reimbursement team, cell therapy force, all that's the same. Even surgery, I know centers -- personally, I'm a surgeon, so I could talk to a lot of surgeons who they love if they're going to go for a visceral starting material for Amtagvi to go to the lung.

So they're using already the same surgeons. And then finally, there's a growing number of medical oncologists who are like basically saying, yes, I started out melanoma doing TIL, but I really wanted to do TIL and cell therapy in general in solid tumors. And so I'm starting with melanoma, Oh, I can't wait to start with 1, 2. So there's -- I don't want to call it just derisking, but just lack of -- there's a higher floor.

So -- and then finally, the manufacturing is literally the same place. In fact, where we do our manufacturing for clinical trials literally will then simply flip a switch and it's the same place and you're doing it commercially. We don't have to now go somewhere else to show it works commercially. It's literally the same place. So there's so much. It's so ready to go, unlike what we had done before. And I don't think there is a single other company that has such a ready-to-go model as we do in solid tumor cell therapy.

Maybe we can just switch to lifileucel and cell tissue on sarcoma. You obviously presented some pretty encouraging data during your last call, particularly given how refractory those patients were. When you think about a registrational study for sarcomas, which I think starts in the second quarter. What does success look like? And what type of population can we expect you to explore in a pivotal study?

Sure. So let me just tell the audience a little background on that. One of the things I get to do is run these ISTs. And in fact, this was not meant to be as fast as it was, and it was a relationship I had with my own CEO, and we did it, and it's been a special relationship with MSK. And we have looked at other soft tissue sarcoma. Sarcoma in general is sort of like this grab bag of all kinds of tumors, they don't want us to call them, right? So although they're called sarcomas, they're not -- they can be very disparate diseases.

And there were some reasons why these 2 in particular, which we had not really studied before, despite studying others, look interesting. So we decided to do it. And first thing we know is right away we're able to manufacture, which is terrific. Second thing was our first patient, which was almost a response, patients start telling the doctors, I feel really well. I mean, I'm like really, this is crazy. These patients I've treated them before, they are really sick. And they have very little to treat them with other than things that don't work and make them sick, and they're getting it constantly.

Second patient response. And then before you know it, 6 patients -- 3 out of 6 responded. Now let me explain to you, even if one of those was by fluke, that will be 2/6, 1/3. The benchmark in the second line is less than 5% responses. And talk about progression-free survival, it's even worse than long. It's 2 to 3 months. It's basically -- it's -- I'm not sure it's much better than placebo. That's how bad it is. In fact, I would argue that there -- because there are 8,000 frontline patients like this in Europe and the United States, there's about 3,500 of which get second-line therapy. Many of the reasons why it's not 8,000 is because doctors like, look, there's -- you fail your front line, which almost all of them do, you can take the second line or you could just go to hospice.

I -- in my mind, that means likely the real number is 8,000 and by the way, it's growing. And these patients are desperate. I mean they wait they succumb to this disease, it should not happen to anybody. So my point is it was exciting to see this level of response. Those are patients that are continuing to respond. Ultimately, patients' quality of life is improving. And remember, it's a onetime therapy. They are just at home with nothing else being treated to them. They're not coming back to infusion chairs every 3 weeks. They're living their lives. And we know patients have gone back to work. I mean it's an early trial, but the benchmarks are exceedingly low. And what we do with our ISTs, I think to answer your other question, is we design them is if they -- because if they're successful, we want them to be used to derisk the experimental arm of a clinical trial.

We know that about 40-plus patients is all we need per indication in sarcoma as has been previously approved. Single arm trial is a style that we would do. And that's what we're going to plan on doing in a registrational trial. And it's going to be reminiscent already of what we've done, our IST with some tightening of the restrictions that make it a more homogeneous population to make it easier for an approval pathway. But we're extremely excited because these responses are unprecedented, and it's a huge opportunity for patient, doctors and trial events.

And I would also point out that our current registrational program in non-small cell lung cancer we decided to move that forward because of some early data that we had seen out of the academic setting, and it's now a registrational program. So it's a good model for us.

Yes. In fact, I didn't know when it was going to come up. But we know that our current trial for lung, which is designed to be about 70 or 80 patients, matches very well with 5 recent FDA approvals in lung cancer. So we've really -- we get these questions asked a lot, as I say, why people sweeten up their models, they are -- this is what is getting approved and how it's being approved. And so we're following a similar model here, too. And ultimately, Amtagvi got approved through a 73-patient single-arm trial.

Right. And as far as where sort of TIL can go next, obviously, right now, you can show activity now across 3 tumor types. And there's more to come. And when you think about sort of how you sort of triage the opportunities for TIL, maybe you can talk about sort of what you view as potentially the next opportunities for lifileucel in various solid tumors.

So there's 2 ways of looking at it. The first is our current manufacturing style of making lifileucel. There, we're using certain aspects of tumor such as they get immune checkpoint inhibitors in the front line. There's really no good second-line therapy. And of course, the solid tumors. That's where we tend to focus. And for those kind of metrics, with those kind of qualities, we are using ISTs to help like we did with sarcoma and I can tell you, we have another one that's opened now. You can look at clinicaltrials.gov looking at continuos squamous cell and Merkel cell, as an example.

So these are -- that's how we do it. These are sort of like feelers. And if we get responses, you see how fast we turn those responses into an investment. And also, we realize when it doesn't work. We have a large amount of data on where that TIL does not work in. That leads me to the other side of what we're doing, and that is our genetically modified next-generation cell. There is no company that is as advanced in that as we are. We have the first genetically modified 4001 program, which I could say -- I can't give you public data now, but we're very excited about the responses that we're seeing and we're trying to figure out where to apply that to. We want to make sure it's the right setting for the right indication.

I think what makes me even more excited is our 5001 program, running research and knowing this came from the research area in Iovance is really exciting. And basically, this is a TIL that is tissue sensing. It actually notices where it is and it only then armors itself with a tethered IL-12. One of the advantage of Iovance over almost anybody else, including [ anemia ] is that we get to work in something that has already worked in humans and then work backwards. So this is based on a trial that was published that had over 60% response rate, very few cells, even as much as 1,000 full cells can give complete responses than our current TIL. The problem was toxicity. And the issue was the TIL that was used secreted IL-12.

So we're trying to capture lightning in the bottle by -- instead of secreting it, tethering it. So it only travels with that cell to the tumor. And what's exciting about that is that if we can not only have low safety signal, have incredible efficacy, we can start then going into tumors that don't have a lot of T cells to begin with because we don't need a lot of T cells to end with. And that allows us to go into all kinds of indications that we've tested and not done well with or you haven't even tested, and you will see that happening this year.

And can you remind folks for 4001, 5001 programs, what you're communicating about sort of data disclosures?

Yes. So for 4001, we haven't announced when we're going to present it. I know there's a commitment to do that, but we have to go through phases with the FDA. There's a Phase I., there's a safety run in, there's analyses, and there are reasons to or not to present that data. So I can't give you public timing of that right now. For 5001, I can tell you, I'm presenting it at -- this is SITC spring in a couple of weeks in Tucson, we'll be discussing again the preclinical background of this, including showing that the tumor doesn't -- excuse me, the T cells don't shed the IL-12 and what kind of effects it can do, and they actually head to head against our Gen 2 product. So if anybody is interested, please look out for that presentation. And that's the kind of data we'll have until we'll actually get into patients.

Great. Maybe a last question around margins and the margins improvements that we've seen with Amtagvi, maybe can you speak to sort of maybe where you see sort of further operating leverage coming from? Is it just really is volume increases, other dynamics that we should be thinking about for margins?

Sure. So margin expansion is a top priority at Iovance and there are a lot of key positive drivers. In the fourth quarter, we reported our best ever margin from cost of sales at 50%. That was driven primarily by optimization, disciplined use of capital and high manufacturing volume as well as high manufacturing success, the highest that we have had to date.

Now more recently, in the first quarter, we transitioned all Amtagvi into our internal facility. So the in-house manufacturing is going to drive even more improvements on an ongoing basis and over time. And the ongoing execution and more discipline and focus on excellence will also be impacting gross margin on top of that. So stay tuned.

Great. Thank you. Brian, Sara, thank you for your participation. Thank you for our listeners for listening in, and we'll be back soon with our next session. Thank you.

Thank you.

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.

[Operator Instructions]

Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Sara Pellegrino - Senior Vice President of Investor Relations & Corporate Communications at Iovance.

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 iovance.com. This conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans and transactions, revenue, commercial activities, clinical trials and results, regulatory approvals and interactions, plans and strategies, research and preclinical activities, potential future applications of our technology, manufacturing capabilities, regulatory feedback and guidance, payer interactions, licenses and collaboration 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. Frederick G. Vogt - Interim CEO and President of Iovance.

Thank you, Sara. In 2025, Iovance delivered substantial revenue growth, achieved groundbreaking data milestones and strengthen our financial performance. Our Fourth Quarter and Full Year 2025 results underscore our focus on value creation for patients and shareholders. We drove an Amtagvi adoption while streamlining costs and opting operations. Our operational strength resulted in a robust 30% revenue growth, driven by Amtagvi and our best ever 50% margin from cost of sales in the fourth quarter.

For the full year, total revenue of about $264 million was well within our annual guidance range. Our cash runway bolstered by our ongoing cost savings initiatives now extends into the third quarter of 2027. Following our exceptional performance in 2025, we are well positioned in 2026 to surge toward a highly profitable and broad business in solid tumor cancer immunotherapy. We plan to execute across 3 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, how our operational excellence as our foundation for success.

First and foremost, we are gaining positive uptake commercially with a significant potential for Amtagvi and Proleukin to reach $1 billion plus U.S. sales at peak. After a considerable increase in fourth quarter demand for Amtagvi enrollment volumes in 2026 are accelerating within our broad and continuous expanding network of both academic and community authorized treatment centers or ATCs. These ATCs are further reinforced by excitement surrounding the real-world experience and benefits of early treatment with Amtagvi.

On top of increasing demand, we are benefiting from operational improvements throughout the entire Amtagvi treatment journey. From patient identification through manufacturing to infusion. When 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 color is the massive expansion potential for our to 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 lifileucel previously treated nonsquamous non-small cell lung cancer. This blockbuster U.S. market is about 7x larger than our PQS sales opportunity in advanced melanoma. In our registrational patient population, lifileucel has demonstrated best-in-class clinical response rates and durability. This morning, we announced the FDA has granted fast track designation that validates our clinical trial data and reaffirms the substantial unmet medical need for lifileucel in this indication. We are rapidly advancing towards a supplemental biologics license application with a potential accelerated approval and launch in the second half of 2027.

This morning, I am also excited to introduce entirely new indications for lifileucel announced in a press release alongside positive early data. In previously treated patients with 2 aggressive difficult-to-treat advanced soft tissue sarcomas, lifileucel demonstrated an unprecedented 50% confirmed response rate. As Brian will highlight, lifileucel may offer the first durable immunotherapy option in this treatment setting. Current outcomes with standard of care arm abysmal with response rates below 5% and short median overall survival of only 9 to 10 months.

Together, these sarcomas impact 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 the sarcomas. Our robust pipeline is the backbone of immuno-oncology and multiple cell tumors today to the future as we build upon our established global leadership and define next-generation approaches for to cell therapy. Our 2 clinical-stage genetically engineered TiL therapies have the potential to transform the treatment paradigm across a vast number of sawtimber 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, discipline and focus on financial excellence will improve current and future gross margin and further extend our cash runway.

Within our operational excellence pillar, as Igor will highlight, manufacturing success has improved across the board. By optimizing our processes, we have infused more patients while reducing dropouts to be more efficient ahead of future launches. Importantly, we own and control all manufacturing for Amtagvi within our U.S.-based Iovance Cell-Therapy Center, or ICTC, as well as critical components of our supply chain. We have never been in a stronger position to execute while scaling to new heights. In 2026, we are laser-focused on maximizing shareholder value, ending dilution and supercharging future profitability.

I'll now turn the call over to Corleen Roche, our Chief Financial Officer, who will provide further updates on our fourth quarter and full year financials.

Thanks, Fred, and good morning, everyone. Iovance finished 2025 with positive momentum as we reported approximately 30% revenue growth with 50% margin from cost of sales in the fourth quarter. Fourth quarter product revenue of $87 million demonstrated meaningful growth of approximately 30% from the prior quarter driven by Amtagvi. Our first full year launch total product revenue of $264 million increased by 61% over the prior year, driven by Amtagvi revenue growth of 112% year-over-year. That was well within our annual guidance range. We drove this impressive revenue growth in 2025 through ongoing market penetration and earlier treatment with Amtagvi for more patients and 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 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, Corleen. Over the course of 2025, we made tremendous progress in 3 key areas towards our ultimate goal to establish Amtagvi and the preferred treatment option for all eligible patients who deserve a onetime cell therapy with curative intent. First, our ATC network is continuously expanding. In the fourth quarter, new community centers as well as high-volume academic centers contributed to our highest ever quarterly demand for Amtagvi, which drove our Q4 revenue.

Second, penetrating the community market will unlock Amtagvi's tremendous potential as we expedite higher quality referrals to ATCs and begin to treat patients in the community setting. Recently launched campaigns focused on health care professionals and patients are having a positive impact. The community market will expand further and accelerate growth as we build awareness and access.

Our third key focus area is to drive treatment and increase penetration earlier when patients being benefit most from Amtagvi. Real-world data resonating with medical oncologists has shown unprecedented efficacy with more than 1 in 2 patients responding in the second-line setting and 1 in 3 patients in later lines of therapy. Initiatives within academic ATCs are also generating positive results from earlier tissue procurement and earlier treatment for specific patient types. For example, ATCs are offering Amtagvi treatment before health status declines in patients with a BRAF mutation who have no current or pending options beyond targeted therapy.

On the heels of our substantial fourth quarter performance, positive trends are an 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 the marketing authorization application to the European Medicines Agency this year.

Beyond melanoma, we are preparing for commercial launch in previously treated nonsquamous non-small cell lung cancer, the most common form of lung cancer. This blockbuster opportunity is approximately 7x larger than our current melanoma opportunity, with 50,000 addressable patients for peak sales of $10 billion in the U.S. alone. Our entire Amtagvi ATC network of U.S. academic and community practices can leverage their existing TIL infrastructure for rapid adoption in non-small cell lung cancer upon approval as well as future pipeline indications such as sarcomas. After recently celebrating my 1-year anniversary at Iovance, I am proud of our accomplishments and inspired by our science and the patient stories that paint a bright nature. 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 like follows manufacturing has transitioned to the ICTC, which is a significant milestone to optimize internal capacity utilization, improve operational excellence, reduced 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 2 registrational programs. 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 AMF approval in combination with pembrolizumab in frontline advanced melanoma. We Shifting to our IOV-MEL-202 registrational trial, lifileucel has demonstrated a best-in-class clinical profile and recently received Fast Track designation from the U.S. FDA. We -- 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.

Thank you, Friedrich. I'm excited to share positive initial data from a pilot clinical trial in patients with previously treated advanced undifferentiated pleomorphic sarcoma or dedifferentiated liposarcoma. They have no group immunotherapy options. Among 6 evaluable patients, the confirmed objective response rate was an unprecedented 50% and Responses were deep and improved over time, consistent with the durability for lifileucel in melanoma and non-small cell lung cancer. These high mortality aggressive soft tissue sarcomas effect 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, [indiscernible] outcomes with second-line standard of care include response rates below 5% and median overall survival of less than 1 year.

In summary, these extraordinary results are why I hope and believe, I would see TIL the redo in solid tumor cancers when I chose to leave academic medicine to join team Iovance. I'm heartened by this major opportunity for patients and the future of TIL therapy. We look forward to commencing and advancing a single-arm registrational trial as soon as possible. As part of this developmental program, we will also explore other subtypes of high-grade soft tissue sarcoma where patients have no approved effective therapies and urgently await better treatment options.

I will now hand the call back to the operator to begin the question-and-answer session.

[Operator Instructions]

Our first question comes from Andrew Tsai with Jefferies.

Thanks for the update -- maybe for the Telvance 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 PD-1 combo data later this year? And -- but regardless of timing, what kind of ORR and PFS do we want to see compared to PD-1 alone?

Yes. 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 the benefit of some of the agreement we have with FDA illness, where we can read ORR as an interim partyway 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 bind 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 what we'll point out. Friedrich, do you want to talk about the ORR and PFS considerations on that trial, please? Friedrich is muted.

I'm sorry about that. I needed to find my window here. Yes, 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 Telvance comparison of the combination of pembro plus TIL versus pembro monotherapy. The trial is designed with 2 dual primary end points with one of them being ORR and the other 1 being the PFSO giving us an opportunity for early read.

The benchmark in the KEYNOTE-006 trial for ORR was about in the mid-30s probably the true real life or with the pembro monotherapy is probably more in the third slightly below percent range. Remember, we have very encouraging data on the efficacy of the combination from our 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.

Our next question comes from Tyler Van Buren with TD Cowen.

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.

Tyler, it's Corleen. So first, you talked about Q4 split. We did have all 3 distributors ordering in Q4 and we also took -- 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 improvement.

And I'll just add on to that, Tyler. We did see all 3 wholesalers, as are mentioned, order in Q4. We've already seen reordering happen in Q1. And moving forward, you should see again regular orders for Proleukin to go with Amtagvi sales. That's our major line of business there. Other 2 channels will come on this year as they did last year, but it mainly is driven by Amtagvi demand or Proleukin sales.

Our next question comes from Yanan Zhu with Wells Fargo.

Can you share with us how the manufacturing success rate change over time? And what is the great cost for this quarter?

Can you clarify the last part of that question, what cost?

The scrap cost.

Scrap costs will be in our 10-K filing that will come out around $915, but it's consistent with prior quarters. I'll maybe give some comments on manufacturing success and the year 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 Corleen mentioned, these margins are being driven not just really being driven by Amtagvi performance, Proleukin comes in and out. But we've had good margins for 2 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 comment specifically about what you made what you said in the earlier part of the call.

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

Our next question comes from Salim Syed with Mizuho.

Maybe just 1 on guidance from us. So you didn't 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 a conservative guide? Just help us framework how we should be thinking about that?

Yes. Right now, we're seeing remarkable growth in the Amtagvi business. We do need to be sure that our projections are well supported. So we're taking some time to do that. It's very early in the year right now, of course. But as I mentioned during the prepared remarks, we're going to be putting guidance out very, very soon. I think you'll see total product guidance. You'll see some guidance potentially on quarters. We'll have to see how our 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, the revenue from Amtagvi

have now fallen right in the line with what we were saying a year ago. And that Proleukin generates about 17% of our revenue. If you recall, many, 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 1 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.

Our next question comes from Reni Benjamin with Citizens.

Congrats on 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, that number 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.

Reni, it's Dan. Thank you very much for the question. So for Q4, our base book of business is the academic ATC, and we saw significant growth in that segment. We did see new community agencies come on the line, 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 is that there are certain patient types there that we're not making into Amtagvi treatment that I mentioned during the script, we have earlier procurement strategies for patients such as BRAF mutated patients, which make up a significant number of those patients inside of the academic ATC 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 will be ramping up as the year goes on. So we'll see more of them starting in the second quarter through the end of the year into '27. Right now, our base book of business is strong and growing with the academics.

Got it. Okay. And then just a follow-up regarding the sarcoma data, is quite new and as you mentioned, unprecedented. Can you -- it's in 6 evaluable patients, can you 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 I guess if you can just -- if I can squeeze 1 more in regarding the registrational study. How big do you think this study could be given this rare disease?

Reni, 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 at a 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 get it very quickly for a presentation. So stay tuned for that. It should be pretty exciting. Brian, do you want to take the second part?

Yes. 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 a very long time frame. So I think it will be a while before will 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 -- if it was on a some 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 respires we got and how they were deepening. So I think more to come there, but I think it gives us a lot of encouragement.

Marc will provide any sample size of the...

Yes. Thank you for the question. So based upon the prior approvals in very soft tissue sarcoma, sometimes recently by approval size for the various subtypes range between 30 patients and 60 patients, but predominantly in the 40-patient range and based on the characteristics of this these 2 cell types that we are discussing today, and we really expect very similar patient numbers for registration strategy.

Our next question comes from Colleen Kusy with Baird.

This is Nick on for Colleen. 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.

Yes. The Fast Track designation that we announced today, Nick was obviously very helpful 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 timing 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 a great benefit for a non-small-cell lung patients.

And then just a quick 1 on sarcoma. Just wondering if you're considering expanding any -- into other subtypes of sarcoma outside of these initial too.

Yes. And we mentioned that in both the press release and in the prepared remarks. We are looking at additional subtypes maybe on 1 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 we see strong activity for TIL in the space. and a lot of approved options, including approved checkpoint options for these patients nor are there anybody interested apparently getting their checkpoints approved here? Are 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.

Our next question comes from David Dai with UBS.

Congrats on the progress. Just first on the prelude 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 antagonic demand. And then moving forward with Proleukin fair to assume that it will stabilize around that level with maturity of contributing to real demand from Amtagvi demand? And then I have a follow-up question.

Sure, David. So this is Dan. I'll take the question on Proleukin. We sell on Proleukin, as you recall, all throughout last year, we had when first wholesaler came on in Q2, 2 were reordering in Q3, all 3 were ordered in Q4. We started to see regular demand come in. We did do a price increase effective February 1. So there was a little bit of volume, but not much going into the end of the year with it. The primary driver for Proleukin in Q4 was Amtagvi demand. As we look at Q1, we already have the wholesale is reordering. 2 have already placed orders. We're expecting the third to order soon. And then they will continue to move forward with Proleukin orders based on Amtagvi demand. That is our #1 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 forecast.

Got it. And then just a follow-up on Fred's earlier comment around Amtagvi being a $1 billion peak sales opportunity. Maybe just help us understand how you get there, especially, how should we think about contribution of melanoma and non-small cell lung cancer also sub-tissue sarcoma?

Yes. I think when I talk about that, David, I'm talking about continued growth in the Amtagvi melanoma in the 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 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 numbers are coming from Amtagvi. That's the point we're trying to make. We talk about $1 billion, we think that's the ultimate potential for this product in the U.S. and melanoma.

On top of that, you've got non-small cell lung at 7x. On top of that, you've got sarcoma, on top of that frontline melanoma. So just bear that online. Do you want to follow up, Dan?

Sure. So $1 million in on is completely achievable. If you look at where we are right now, a quarter away 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're creating a pathway with the solid tumor medical oncologists. So we are standing that up now. And in the initial phase, we're doing over $0.25 billion with both products. And we see that escalating in the U.S. alone to over $1 billion. We talk about layering lung in, I mentioned in the script, that is a $10 billion opportunity, a much larger market to go into.

In sarcoma, we do see as being equivalent to melanoma. So we do see tremendous potential to be well over $10 billion to $12 billion in the U.S. with Amtagvi

Our next question comes from Etzer Darout with Barclays.

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

So well, I think -- I just want to make sure I'm understanding you're asking what will the ex U.S. 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 right, as we grow and add an additional volume from those launches.

And I can add on to that correctly. As we look at manufacturing for ex U.S. 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 no added expense there. Also, too, if you look at what's going on in the landscape, most favoration, 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 through our negotiations with the U.K., Canada, et cetera..

And our final question comes from Asthika Goonewardene with Truist.

So let me start thinking about you painted into the community in the U.S. and say you have agencies there. Is there going to be a material difference in the timing, it place 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 one who already have some sort of a cell therapy program versus those who don't?

And then I have 2 follow-up questions. I'll ask on 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 1 regarding the community uptake. One of the things that we do see with the community will be similar to what we saw in the academics and that is just the relationship with the surgeon, the medical oncologist and the cell therapy lab to get up and running for it. That should be a similar learning curve. We did have some academic sites in the clinical trial. So that was the initial wave with the Amtagvi launch. But we are seeing them come online. This is also balanced with the fact that they are closer to where these patients are being treated with frontline melanoma and subsequent therapy.

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 1 or 2 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 2 go through, they start to accelerate patients and treatment.

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. Brian?

Yes. Thank you, Dan. Well, first of all, we presented nationally or internationally, at the Tandem meeting in Salt Lake City a couple of weeks ago. It got a lot of attention I've heard personally people very excited but not just because the detail was out, but also it validated what many PIs, KOLs physicians have been seeing in the clinic, and they need this data and 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.

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 after the February 1 price increase?

So they typically over before the price increase. wholesalers operate on very low margins. So we did a 9% price increase on both products effective February 1 of this year. 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're post price increase right now. So they were aware of the price increase pending and would buy accordingly.

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 Iovance Biotherapeutics Fourth Quarter and Full Year 2025 Conference Call. We plan to provide more detail on U.S. launch for our community [indiscernible] when we introduce our full year revenue guidance in the near future. Please stay tuned to updates to 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 for more and more patients who are benefiting from our TIL cell therapies. As always, we're thankful to our patients, health care professionals and advocacy communities as well as our partners. I would also like to thank our exceptional Iovance team in addition to our dedicated shareholders in covering analyst for their commitment to the mission to remain the global leader in innovating, developing and delivering current future generations of TIL cell therapy. Thank you.

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

Welcome to the Iovance Biotherapeutics Third Quarter and Year-to-Date 2025 Conference Call. My name is Daniel, and I will be your operator for today's call. [Operator Instructions] Please note that this conference call is being recorded.

I will now turn the call over to Sara Pellegrino, Senior Vice President, Investor Relations and Corporate Communications at Iovance. Sara, you may begin.

Thank you, operator. Good morning, and welcome to the Iovance webcast to discuss our business achievements, pipeline milestones and third quarter 2025 results.

Members of our executive leadership team speaking on today's call include Dr. Fred Vogt, Interim CEO and President; Corleen Roche, Chief Financial Officer; Dan Kirby, Chief Commercial Officer; Dr. Igor Bilinsky, Chief Operating Officer; and Dr. Friedrich Finckenstein, Chief Medical Officer.

During the question-and-answer session, we will also welcome Dr. Raj Puri and Mark Theoret from our Regulatory Affairs executive leadership team; and Dr. Brian Gastman, Executive Vice President of Translational Medicine and Research.

This morning, we issued a press release that is available on our corporate website at iovance.com. I would like to remind everyone that this conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans and transactions, revenue and revenue guidance, commercial activities, clinical trials and results, regulatory approvals and interactions, plans and strategies, research and preclinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interactions, restructuring, 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 like to turn the call over to Fred.

Thank you, Sara. I will start by sharing our continued progress to increase revenue and margins, advance our pipeline, reduce expenses and improve operational execution.

Third quarter revenue grew 13% over the prior quarter and notably, gross margin improved and was 43% following the initial results of our strategic restructuring and cost optimization. More improvements are coming, including today's announcement of our centralization of manufacturing at our internal manufacturing facility.

Our highest priority is to accelerate revenue growth to increase Amtagvi adoption across our network of academic and community authorized treatment centers or ATCs. We have expanded to include new academic ATCs and multiple community ATCs. Initial patients are being treated in the community and are generally earlier in their melanoma treatment journey.

As we educate community oncologists across our ATCs, including the major academic centers, we are seeing earlier and more frequent patient referrals to drive growth. Real-world data showed response rates of 60% in the second-line treatment setting, which has provided a strong foundation to amplify our compelling story to the melanoma community for the power of TIL therapy in melanoma.

We are on track to achieve our revenue guidance range of $250 million to $300 million for the full year 2025. With robust current demand, we expect a strong fourth quarter for Amtagvi alongside increasing Proleukin sales as we saw in late 2024. We continue to project Amtagvi peak sales of more than $1 billion in the U.S. and melanoma with larger additional opportunities in international markets and in future indications. For example, our interim clinical data in previously treated non-squamous non-small cell lung cancer showed a best-in-class -- apologies for technical difficulty here for one second.

For the -- for example, our interim clinical data in previously treated non-squamous non-small lung cancer showed a best-in-class profile and unprecedented durability compared to standard of care in this population, including an objective response rate of 26% and a median duration of response not reached at more than 25 months of follow-up. There is a significant market opportunity in this lung cancer indication, which is about 7x greater than our current advanced melanoma indication.

We expect to quickly complete enrollment in our LUN-202 registrational trial in 2026 with approximately 80 patients. This sample size will support an accelerated approval given the unmet need in non-small cell lung cancer, precedent of the Amtagvi approval in 73 melanoma patients and recent accelerated approvals based on 70 to 80 patients from defined non-small cell lung cancer population.

The U.S. FDA previously provided positive feedback on our trial design, which aligns with FDA guidance for single-arm trials to support accelerated approvals for single agents in conditions with unmet medical need. We look forward to advancing toward a supplemental biologics license application in non-squamous non-small cell lung cancer and a potential launch in the second half of 2027.

As we increase revenue and advance our pipeline, we are laser-focused on expense management and profitability. Following our third quarter reorganization, we are refining our operating plan to ensure we are appropriately investing in our commercial launch and high-value programs. Again, cost of sales and gross margin will improve significantly as we transition manufacturing to our internal facility in early 2026. During this call and our future quarterly updates, we will highlight our ongoing efforts toward further expense reductions and resource allocation.

Corleen will now highlight our third quarter financials in further detail.

Thanks, Fred. Good morning, everyone. During my first quarter as Chief Financial Officer, I want to emphasize our focus on driving the company towards sustained profitability. Our strategy included prioritizing top line growth, significantly improving margin and controlling costs with a disciplined approach.

In the third quarter, our top line revenue remained strong. Total product revenue increased approximately 13% over the prior quarter to about $68 million. This included Amtagvi sales of approximately $58 million and global Proleukin revenue of nearly $10 million. As expected and consistent with prior quarters, overall gross to net was less than 2% and is expected to remain minimal. As Fred mentioned, we are on track to achieve our revenue guidance in the first full calendar year of Amtagvi sales.

Next, I am pleased to highlight initial improvements in expenses and gross margin from the corporate restructuring and continued cost optimization initiatives implemented in the third quarter. We reduced total costs and expenses by approximately 10% over the prior quarter, excluding restructuring charges of approximately $5 million. We lowered cost of sales by approximately 21% over the prior quarter, resulting in improved gross margin of approximately 43%. Importantly, costs associated with patient drop-off and manufacturing results continue to decline as our revenue continues to grow.

Gross margin will improve over time as we accrue benefits from our recent restructuring, implement additional cost savings initiatives and centralize manufacturing at our internal facility. Our cash position of approximately $307 million as of September 30 was bolstered by expense reductions and is expected to fund operations into the second quarter of 2027.

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

Thanks, Corleen. Our ultimate goal is to establish Amtagvi as the preferred option for all eligible patients. Patients deserve a onetime cell therapy with curative intent, and we are steadfast in delivering on that promise. My conversations with patients and caregivers remind us of the commitment to the Iovance mission, pioneering a new treatment paradigm for patients with solid tumor cancers.

At the recent Melanoma Research Foundation Gala in Denver, Iovance received the Corporate Leadership Award in recognition of our efforts to advance care for melanoma patients. In my first 8 months at Iovance, we have made notable progress to lay the foundation for revenue growth by driving adoption across our ATCs.

I'll highlight 3 key areas of focus. First, new ATCs are driving growth. In the third quarter, we added community ATCs alongside new high-volume academic ATCs. These new ATCs contributed to the highest number of patient starts with better capture in the third quarter. Our first community ATCs are beginning to treat patients with Amtagvi in this setting. New ATCs continue to come online and will drive further growth in the fourth quarter and beyond.

Second, penetrating the community market is key to unlocking Amtagvi's tremendous potential as we increase the frequency, speed and efficiency of community referrals to ATCs. Health care professional and patient-focused campaigns are having a positive impact. Under our specialty pharmacy agreement with Biologics by McKesson, patients have broader access to Amtagvi. Hospitals now have flexibility to obtain Amtagvi directly or through a specialty pharmacy, giving their finance teams confidence to place more orders.

Our third focus area is to drive earlier treatment with Amtagvi. This will increase penetration in our academic centers. We are educating medical oncologists on the advantages of cell treatment with Amtagvi when it has the greatest benefit. Earlier shifts in referral patterns are supported by our first real-world data that shows 60% of patients respond in the second-line setting. In addition, new initiatives in academic ATCs will address earlier tissue procurement for patient types, such as BRAF mutations, so they can be treated before their health status declines.

Proleukin revenue also grew in the third quarter. Our main revenue channel for Proleukin is use with Amtagvi. Two U.S. wholesalers ordered in the third quarter, and all 3 wholesalers are expected to order significant volume in the fourth quarter. Proleukin will continue to grow through this main revenue channel in addition to the 2 other revenue channels for clinical and manufacturing use. Like other companies, we are evaluating our Proleukin pricing strategy outside of the United States based on the current environment, which may help drive future revenue growth.

Amtagvi has the potential to reach more than 30,000 patients with advanced melanoma globally. Canada became the first new market to approve Amtagvi and approvals are pending in 3 additional markets. The United Kingdom and Australia in the first half of 2026 and Switzerland in early 2027. In the European Union, we are confident in our planned strategy. We are seeking scientific advice from the European Medicines Agency and intend to resubmit for regulatory approval shortly thereafter.

Looking at the broader potential of lung cancer, our interim data demonstrates that onetime treatment with Lifileucel represents a true game changer and potential cure for patients with non-squamous advanced non-small cell lung cancer. With approximately 50,000 addressable patients in the U.S. alone, the market opportunity is about 7x larger than our current melanoma opportunity and represents potential U.S. peak sales of $10 billion.

U.S. academic and community practices are enthusiastic about our lung cancer program. All of our current and future ATCs are expected to launch in non-small cell lung cancer. A significant portion of them already treat patients in our LUN-202 trial. The ATC footprint for lung cancer is essentially the same as our melanoma treatment network. ATCs are eager to leverage their current TIL infrastructure to quickly adopt Lifileucel in lung cancer upon approval.

I will now pass the call to Igor.

Thank you, Dan. I will provide a brief manufacturing update. We have streamlined our manufacturing organization while reducing costs and improving our manufacturing success rate as reflected in our third quarter gross margin.

Importantly, we are finalizing an expansion at our internal facility, the Iovance Cell Therapy Center, or iCTC, that will enable us to support anticipated demand without the need for a contract manufacturer. All Amtagvi and clinical manufacturing will transition to iCTC in early 2026 to maximize capacity utilization, lower cost of sales and drive future gross margin growth.

We will complete a key step in this facility expansion during routine annual maintenance around the end of this year. During this time, our contract manufacturer will provide continued access for patients to meet demand before we transition all manufacturing to iCTC. We will also boost capacity immediately prior and following the maintenance period to provide additional manufacturing slots for patients, allowing smooth supply through the next 2 quarters.

Bringing all manufacturing internally will be an important milestone for us as a company. In addition to the cost benefits, we will maintain uninterrupted supply during routine maintenance in the future using internal capabilities. We can also scale up within the existing facility to support future markets globally and indications, including lung cancer.

I will now pass the call to Friedrich.

Earlier this week, we reported interim data from our registrational IOV-LUN-202 clinical trial of Lifileucel. The data demonstrated a potentially best-in-class clinical profile and meaningful improvement over current standard of care in previously treated patients with non-squamous non-small cell lung cancer.

Following onetime treatment with Lifileucel monotherapy, the objective response rate was an impressive 26%. An objective response was observed in 10 out of 39 patients, which included 2 complete responses. The disease control rate was 72%, showing a meaningful benefit for many patients with stable disease. Importantly, median duration of response was not reached at more than 25 months of follow-up, which is unprecedented durability for non-small cell lung cancer therapy in the post-chemo and immune checkpoint inhibitor setting.

Standard of care docetaxel monotherapy recently showed an objective response rate of only 13% and a median duration of response of only 5.6 months without any complete responses in the same patient population. We are on track to quickly complete enrollment of approximately 80 patients in 2026. We have seen a strong increase in enrollment this year, driven by the positive reception of the efficacy data among trial investigators. In addition to the 39 patients in the data set, a double-digit number of patients are awaiting or have recently received TIL infusions and more patients have entered the trial as of today.

We plan to share more data from LUN-202 at a medical meeting next year, including a meaningful number of additional patients and longer follow-up. We also look forward to advancing towards a supplemental biologic license application for Lifileucel in non-squamous non-small cell lung cancer and a potential launch in the second half of 2027. We also continue to make progress across the rest of our pipeline, which I am happy to discuss during the Q&A session. Thank you.

[Operator Instructions] Our first question comes from Andrew Tsai with Jefferies.

Nice execution this quarter. Great to see various dynamics improving. Good job. So my question this quarter is on the lung cancer data update that you had. It's interesting that the signal did not necessarily degrade compared to the prior data cut. In fact, maybe the efficacy on DOR seemed to get better. So for the remaining batch of patients, would you expect the third data cut to be also similar or even better than what we're seeing in this interim that you just had? Or would you expect some kind of efficacy degradation on a larger sample size?

Thanks, Andrew. I can start and then maybe Friedrich can chime in here. I don't -- we don't expect any degradation in the efficacy signal. We're getting very good within the LUN-202 trial at making sure our investigators identify the right patients for the trial. And we are obviously going to be cutting the data with longer and longer follow-ups. And with ongoing responders, as you can see in the swimmers plot from that data cut, we would expect to see that durability improve even beyond what we have today.

I'll let Friedrich comment a little bit on the details of how we think that study is going to play out, but that's the big picture view.

Yes, I agree with Fred. Not much to add there. I think the study now has reached that phase where folks know what they're doing. They're familiar with the therapy. They know how to identify patients. We are able to communicate best practices. So I think this is all in a very stable place.

What is noticeable is that we saw a true uptick in enrollment, which is really driven by the positive data that we were able to share with the investigators lately. That's also fairly typical. It's kind of an inflection point where then things just take off because folks see and believe in the therapy and things are working really well.

Our next question comes from Yanan Zhu with Wells Fargo.

Congrats on the quarter. Just a quick one on the lung cancer. Can you talk about when did you touch base with FDA regarding the path and the regulatory path? And you did mention 80 patients. I wanted to hear your confidence that 80 patients is enough for the lung cancer filing.

Then on Amtagvi in melanoma, can you talk about infusion growth into fourth quarter and into 2026, your confidence for inflection point in the patient infused?

And lastly, sorry, if I may, on the improved gross margin, great to see that result. Can you comment on how much of it is coming from patient dropout and manufacturing success rate improvements versus how much is coming from cost reduction measures?

Thanks, Yanan. Why don't I start on the FDA point and then Raj Puri will jump in, and I'll ask Dan and Corleen to help out with the Amtagvi, the inflection point as well as the gross margin questions here.

We've engaged heavily with FDA on the LUN-202 trial and gotten guidance from them, feedback on the trial design, patient population, CMC, things like the potency assay. We feel very comfortable that we're on the right track here. Obviously, engagement with FDA is a continuous process during the trial. As I'm sure investors know, we have to engage frequently and we do engage frequently. A lot of it doesn't get talked about. So we'll continue to do that on this trial, but we're very comfortable with where we stand right now in the trial design and what we need to do to get a supplemental BLA submitted on time.

On the sample size for the patient -- for the 80 patients, we pointed out during a lot of our calls earlier this week as well as during our prepared remarks here that we think 80 patients will be sufficient based on the precedent of Amtagvi with 73 patients which led to the approvals on label in melanoma as well as a lot of recent FDA meeting the last couple of months, FDA approvals in non-small cell lung.

So I'll let Raj and maybe Mark comment on that on what they've seen with the FDA and why they think that's reasonable.

In addition to what Fred said that we in continuous interaction with the FDA, we plan to apply for many different priority designations such as Fast Track designation, RMAT designation, et cetera. And as Fred mentioned that 80 patients also based on the 73 melanoma patients that we got Amtagvi approval on.

And recently, Mark will elaborate further that the FDA has approved about 4 non-small cell lung cancer trials based on accelerated approval of patients list to 70 to 80 patients.

I agree with what you had said, Raj. I think there's recent precedent for this number of patients in patients with non-small cell lung cancer and very high unmet medical needs with the response rate and particularly this unprecedented duration of response, we feel based on the precedent and the data thus far, patient data set would be sufficient and compelling.

All right. So on the inflection question and fourth quarter growth, obviously, we feel very confident having a strong fourth quarter, but I'll let Dan talk about some of the details there.

Thank you. And thanks, Fred, and thanks, Yanan, for the question. First, the answer is yes, we expect continued growth in the fourth quarter and beyond into 2026. The reasons behind that are -- I'm going to separate this from academic and community.

In the academic setting, we've launched field efforts, including a disease awareness campaign in Q3 to educate medical oncologists for earlier referral into those centers. We're seeing some results from that right now that will continue moving forward. We also are launching in the academic setting initiatives to increase penetration, which would have to do with addressing certain patient types that we haven't been able to capture such as BRAF mutations I mentioned, where we have opportunities to get tissue earlier. So we do see growth in the academic setting.

Moving to community. I mentioned that we're onboarding now and we've started to treat at the first community sites. We have several large ones that are coming on in this quarter that will drive significant growth in Q4 and beyond in 2026, and that also sets the table for...

Gross margin, let me just focus you on 2 areas, and I think you mentioned them, one, which is patient drop-off and manufacturing results. So if you think about the dollars that are written off from out specs since the beginning of the year, they have decreased by 40%. They're about $9 million this quarter. And we are now seeing the initial benefit of the restructuring that we announced in Q3. So those are 2 key areas that are driving revenue improvement or margin improvement.

Our next question comes from Salim Syed with Mizuho.

Congrats on the progress. I guess one for me on the guidance here. I know you're reiterating the guidance quarterly. And I guess, is there any scenario here in your mind where you're going to actually hit closer to the top end here? I'm just curious why at this point, 2 months left in the year, why we haven't narrowed it down the top end of the range to a lower number that seems more reasonable.

Yes, Salim, we reiterated our guidance range of $250 million to $300 million, which is a pretty narrow range to begin with. It's our first full calendar year on the market, as you know, and we're on track right now towards that guidance.

Fourth quarter, as Dan was just mentioning a minute ago, we have a large influx of new ATCs. We've got Proleukin sales to contend with, which we think will be very strong in the quarter, especially based on fourth quarter last year. You can go back and look at those numbers. And we have got this ATC growth both in the community and in the academic setting.

So I think at this point, we're just comfortable with the guide that we put out, $250 million to $300 million, and we'll be in that range, and that's what we're comfortable saying right now.

Our next question comes from Tyler Van Buren with TD Cowen.

This is Nick on for Tyler. Just one for me. Can you let us know how many Amtagvi patients were treated this quarter? And then also, how will the CTC maintenance this quarter impact Amtagvi infusions and sales?

Yes. Nick, we're not going to -- we're not talking about infusions anymore. We're just going to use revenue going forward, as you can see from our press release. We think that's the ultimate story here, and we hope investors appreciate that we're focusing on the dollars, and that's what matters at the end of the day.

On the iCTC maintenance, I'll pass it to Igor for that question. I think he had covered it in his prepared remarks, maybe you can highlight it again, Igor.

Yes, of course. Thanks for the question, Nick. So as I mentioned, as part of the routine maintenance this year, we'll complete the expansion part of the facility that's important for centralizing manufacturing at iCTC and also kind of continue providing uninterrupted capacity from iCTC during future maintenance periods.

And this year, we've learned from our experience in Q1 2025. So we made several improvements. We will boost manufacturing capacity immediately and prior to the iCTC maintenance that will provide additional manufacturing slots for patients, and that will allow essentially smooth supply through the next 2 quarters.

Our next question comes from David Dai with UBS.

A couple of questions from me. So just on the ATC ramp, you're seeing early community initiatives in there. I'm just curious in terms of what are the timeline for the community activation to actually see patients treated. That's the first question.

And the second question is just around the margin improvement. You said you're planning to have more margin improvement over the next few quarters. So I'm just curious what is sort of like the margin we should be expecting over the next quarters, essentially, one should be expecting the plateauing of the margin over time?

So I'll take the ATC one first and look at the ramp for that. So you mentioned specifically community. Our first community centers are starting to treat now. Typically, with centers, they treat a few patients, they make sure the insurance goes through, they get comfortable with it and they start ramping patients after that. That is expected to continue with our community ones that are just starting to treat now.

The newer ones coming on with the volume will start slow in -- with a few patients in there for it, but then will start to ramp up. The key with the community is that the referral patterns are already there to get those patients in earlier. So as we discuss with those larger entities opening them, we also have robust discussions regarding referral patterns and patients lining up. So we will see a ramp there a little faster than you'll see with the academics, but it should be coming over in the next quarter and 2, and then we'll get to full peak probably by mid next year.

David, on the gross margin, yes, we mentioned that it will continue to improve. So that will be further benefit from the restructuring, but also a number of initiatives across operational efficiency in the manufacturing plant as well as cost savings initiatives to run the organization as efficiently as possible.

And just to finish off, we did announce one of those things today, David, by transitioning all manufacturing to internal as Igor and Corleen and others have discussed, we expect this to have additional margin improvements on the back of that. That's not something that's reflected in the 43% that we reported today.

Our next question comes from Colleen Kusy with Baird.

Congrats on the progress. On the community ATCs that you're seeing come online, can you just speak to the capacity that you see at those centers versus what the capacity is that you're seeing at the academic centers?

Sure. So thank you very much, Colleen, for the question. The capacity with community centers, they are hospitals. They do have the bed space comparable to the academics. What we do see with them, though, is less of a clinical trial allocation and other competing priorities for those beds and more of a priority in the solid tumor space than we see in the academics for it because they do split beds in the academics with the hematology space, where the CAR-Ts are, et cetera. So we do see an opportunity to have a larger percent of their capacity in the community setting.

And our final question comes from Reni Benjamin with Citizens.

I'm sorry, I jumped on the call a little late. So you may have answered this already, so just indulge me. I'd like to understand a little bit more about the global expansion that you highlighted. How do you envision these programs or the expansion without a partner? Should we really be -- should we be thinking about any sort of a meaningful contribution in terms of revenues going forward or at least in 2026? Or is this something that goes out much further?

And just a follow-up question regarding both TILVANCE and the LUN-202 study. It seems like enrollment will slow at least from the 202 study. Can you just give us a better sense as to how enrollment is progressing in each of those studies? That would be great.

Yes, Ren. So first, on the global expansion, we're not thinking right now really about partnership. TIL technology and the science of delivering TILs to patients, the medicine behind it is complicated. We're not really sure there's a partner out there that would give us any kind of advantage. And we're always really cautious about asset dilution and giving anybody rights to anything that we do because we think that TILs are going to be extremely powerful in the future, and we would like to own all of that.

That said, we may work with distributors in certain markets. We may work with people that can help enter markets for us. We tend to staff very light and lean in those markets while we wait for revenue to appear. In 2026, I don't expect a significant amount of revenue from those markets. However, we'll start to see that business grow. And then over time, I think it will become a major component of our business in the future.

And since Dan heads those teams, I'll let him give some color and maybe just highlight the markets that we're going to go back into, include the U.K. and we're going to be entering for the first time in the U.K. and Australia and other places where there's a significant number of melanoma patients in need.

Sure. And so Reni, one of the things we've always said about our global expansion, if you look at the history of cell therapies globally, this has been more of a long-term strategy to produce revenue in 2027 and beyond, but you needed to get the filing and approvals in place because reimbursement does take a while in those regions, you want to make sure you do it in the proper sequence.

So where we are right now with it, we are ramping up in Canada with our first ATC. We have pending approvals in the U.K. as well as Australia. We're in discussion right now in the U.K. about getting an NHS support on which ATCs will go up and running there. So we're getting the process in place as well as within Switzerland and then refiling in the EU.

So this has been a long-term strategy with it and something that we will see, if you look at Kite, who did a great job with Yescarta globally, it took them several years from the approvals to get revenue in there. So we follow that model, knowing it would take 2027 would be our first year to have any appreciable revenues. Not saying we won't get any next year, but really appreciable revenues in 2027 from ex U.S.

And then on the enrollment question, I'll focus on LUN-202, Reni, because TILVANCE, we really haven't said anything publicly about the enrollment there beyond that it's going well, and we think that's on track right now. But on LUN-202, enrollment has really picked up lately. And if you heard on the calls earlier this week, we have double-digit patients right now waiting for infusions, and we have a lot of activity there.

I'll let Friedrich comment in a second here, but we think we can easily hit the time line that we gave for the launch of Lifileucel in non-small cell lung in the second half of 2027 based on our current enrollment timings in the LUN-202 trial.

Friedrich, do you want to add to that?

Yes. Just really quick, Reni. Since I don't know when you joined, I described that before earlier in the call. I think in the lung study, we've now reached this point where, number one, we have stability and familiarity of the investigators and the sites with the therapy. They know how to pick patients. And important, we have a data set that has the size and the quality and the data that are driving investigator engagement. They see the potential for this therapy, they see the benefit in the patients, and they now are enrolling at the speed of what is typical for a trial that has shown data like this. So I share Fred's confidence in us being on track here with our goals.

Got it. And just as a quick follow-up, maybe, Fred, to your comments about TILVANCE that enrollment is going well and things are on schedule. Can you just remind me when do you think ultimately enrollment would be complete or when you might be filing the BLA? Have you provided any of that guidance before?

Not yet. We're still pretty early in this trial here. This is a longer-term study. We do have the ability to read at an interim time point for ORR and seek an accelerated approval in first-line melanoma in the study. And that's not too far off. We have not guided anything publicly, and there's obviously a first 670-patient trial, at least 600 patients on the main population. That's tough to predict accurately right now. But we should be in touch pretty soon with some more updates on that as that starts to crystallize for us.

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 Iovance Biotherapeutics Third Quarter 2025 Conference Call. We look forward to providing future updates on our commercial launch and pipeline as well as our cost optimization initiatives to drive towards profitability.

We are motivated by the stories we continue to hear about the patients who benefit from Iovance TIL cell therapies. I'm confident that Iovance will remain the global leader in innovating, developing and delivering current and future generations of TIL cell therapies for patients with cancer.

As always, we are thankful to our patients, the health care and advocacy communities, our partners and our exceptional Iovance team. I would also like to thank our dedicated shareholders and covering analysts for their support. Thank you.

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