Operator: Good day and thank you for standing by. Welcome everyone to the Iovance Biotherapeutics Fourth Quarter and Full Year 2024 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. [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.
Sara Pellegrino: Thank you, operator. Good afternoon and welcome to the Iovance conference call and webcast to discuss our fourth quarter and full year 2024 financial results, as well as recent corporate and development program updates. Dr. Fred Vogt, our Interim Chief Executive Officer and President will provide an introduction and summarize the latest progress with our U.S. Commercial launch of Amtagvi, including revenue and revenue guidance, and a high level summary of our key pipeline program. Dan Kirby, Chief Commercial Officer, will highlight adoption, market access and demand of authorized treatment center or ATC, community average initiative to drive additional growth for the U.S. Commercial launch, as well as our ex-U.S. launch expansion plans for Amtagvi in advanced melanoma. Dr. Igor Bilinsky, our Chief Operating Officer, will cover our commercial manufacturing experience staff capacity and the status of our ongoing capacity expansion. Jean-Marc Bellemin, our CFO, will review our financial results, including revenue and revenue guidance, gross margin, cash burn guidance, and the strength of our balance sheet. And Dr. Friedrich Graf Finckenstein, our Chief Medical Officer, will summarize key pipeline programs, including our two registrational programs in frontline melanoma and advanced non-small cell lung cancer. Additional members of our leadership team, including Dr. Brian Gastman, our Executive Vice President of Medical Affairs, will be available for the question-and-answer session. Earlier this afternoon we issued a press release that can be found on our corporate website at iovance.com. Before we start, I would like to remind everyone that statements made during 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, 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. With that, I will turn the call over to Fred.
Fred Vogt: Thank you, Sarah. I’m pleased to host this afternoon’s conference call to discuss our financial results for the fourth quarter and full year of 2024 as well as our recent corporate highlights. Earlier this month, we marked the one year anniversary of the historic approval of Amtagvi, the first FDA approved TIL cell therapy and the first treatment for patients with advanced melanoma progress following anti PD-one treatment and if appropriate targeted therapy. In 2024, Iovance fully transformed into a commercial company. We executed a strong start to the Amtagvi U.S. launch, reinvigorated global Proleukin sales growth and gained significant traction in our efforts to launch in the new markets. Meanwhile, we advanced our robust pipeline of current future generation TIL cell therapies across all stages of development to address tens of thousands of patients with solid tumors. Today, I’m pleased to highlight continued growth in total product revenue of both Amtagvi and Proleukin. Total product revenue was $73.7 million in the fourth quarter and $164.1 million in the full year 2024. Importantly, our full year revenue achieved the upper end of our 2024 guidance range of $160 million to $165 million, and we finished above the full year Street consensus. Total revenue consisted of $48.7 million for Amtagvi and $25.0 million for Proleukin in the fourth quarter with $103.6 million for Amtagvi and $60.5 million for Proleukin in the full year period. Our full year product revenue reflects more than 200 patients already treated with Amtagvi in the partial first year of launch. We are pleased with the robust initial uptake and increasing strong demand for Amtagvi as well as continuing momentum in global Proleukin sales. Our team's successful execution as well as the unmet need in advanced melanoma, high awareness, broad patient access, and a motivated expanding network of authorized treatment centers or ATCs continue to drive increasing demand for Amtagvi and Proleukin. Our manufacturing network is well-prepared to supply the current and anticipated demand for Amtagvi. Today, we have staffed capacity to supply more than 1,200 patients per year and continue to scale up for additional U.S. and global launch growth. In the back half of last year, we augmented our investment in focused community referral initiatives. These efforts in the field are targeted at driving additional demand in our ATCs as they scale up to treat more patients. Looking ahead, we are reiterating our full year 2025 guidance of $450 million to $475 million in total product revenue. We expect a significant increase in year-over-year growth in both Amtagvi and Proleukin as ATCs broaden utilization. While new ATCs as well as community referral networks are expected to contribute increasing demand through the year. Our fourth quarter gross margin again improved quarter-over-quarter and is already well over halfway towards our target to surpass 70% over the next several years. And continued increases in revenue and gross margin will also correspond with a significant decrease in our annual cash burn, while maintaining our pipeline of future indications and products. We were judicious in managing our balance sheet in 2024 and expect cash burn, excluding one-time items, to continue to decrease as we execute the launch and drive towards breakeven and profitability. Longer term, we remain confident in significant revenue growth in 2026 and beyond. For the currently approved advanced melanoma indication, the peak sales opportunity is more than $1 billion in the U.S. market alone and more than $2 billion globally. Our ex-U.S. launch expansion plans are on track with the potential to gain three new approvals and provide early access to Amtagvi in several new markets. Iovance has distinct competitive advantages with the first approval launch in large-scale manufacturing of TIL cell therapy combined with strong intellectual property positions and a deep pipeline. Future growth drivers include global label expansions into frontline advanced melanoma, other solid tumor types such as non-small cell lung cancer, and next-generation therapies. As we transition to today's commercial update, I would like to welcome and introduce Dan Kirby on his first quarterly call as a member of the Iovance team. Dan joined us earlier this month in the newly created role of Chief Commercial Officer. As an instrumental leader in cell therapy commercial organizations since the earliest developments in the field, Dan is a perfect fit for Chief Commercial Officer as we grow the Amtagvi launch and expand our Proleukin sales. I'm pleased to hand the call to him to discuss our commercial updates.
Dan Kirby: Thank you, Fred. I'm very excited to be part of the Iovance team. Like many others in cell and gene, I have been following the Amtagvi launch, and I'm incredibly impressed by the progress the team has made in the first year. Amtagvi has the potential to improve lives of thousands of patients with advanced melanoma and to advance into other solid tumors as well. I came to Iovance because I believe in Amtagvi and the patient-focused mission at Iovance. My objectives today are to highlight the additional details on the commercial progress that Fred summarized. To begin, favorable medical coverage policies and broad reimbursement is critical for success and patient access for Amtagvi. Approximately 75% of Amtagvi patients are covered by private payers and Amtagvi is also covered under the Medicare cell therapy DRG 018. Overall, more than 250 million lives or greater than 95% of the U.S. covered lives currently have access to reimbursement for Amtagvi. Early inclusion in the National Comprehensive Cancer Network, or NCCN guidelines, combined with strong clinical data have also supported patient access. Throughout 2024, we scaled up our ATC network to meet the growing patient demand and fulfill significant interest among health care providers to offer Amtagvi to their patients. After launching with an unprecedented 30 ATCs on day one, we reached our target of approximately 70 ATCs at the end of 2024. Our ATC network now spans 32 states and nearly all treated melanoma patients live within a two-hour drive of the closest center. We treated more than 200 patients with commercial Amtagvi within the first three quarters of launch, and Amtagvi is positioned for significant growth across our ATC network in 2025 and beyond. Amongst the 70 current ATCs, 76% completed tumor resections, 64% infused Amtagvi, 53% infused two or more patients, and 13% infused more than 10 patients. These metrics demonstrate significant growth potential as our ATCs scale up to accommodate growing patient demand. New ATCs are preparing to treat initial patients. Our more experienced ATCs are steadily growing or plan to increase utilization throughout 2025, and we expect new ATCs will follow similar trends as we add steadily throughout 2025. These additional ATCs will be selected for high quality and volume of eligible patients, including large community practices. To further drive adoption, earlier patient identification and higher referral volume into our ATC network, Iovance sales teams are actively engaging top community oncologists and large community practices with a focus on high-volume markets. Additionally, we are aligned with leadership at key community organizations on their preferred ATCs for patient referrals. As more patients embark on their treatment journey, we are making steady progress to speed up the time to impact the infusion. Financial clearance currently averages approximately three weeks and continues to improve. ATCs are saving up to two additional weeks by scheduling in parallel with financial clearance and/or initiating the preconditioning regimen in conjunction with product arrival. And we expect to decrease turnaround time for manufacturing and release testing in 2025. Globally, Amtagvi may address more than 20,000 melanoma patients annually in the U.S. and our targeted international markets. In all future markets, Amtagvi has the potential to be the first and only approved therapy for the treatment of adult patients with advanced melanoma previously treated with the PD-1 and targeted therapy. Three regulatory dossiers are currently under review for potential approvals in 2025, beginning with the United Kingdom in the first half, then Canada in midyear, and the European Union in the second half of the year. We also plan to provide early access for Amtagvi in the U.K., France, Germany, Canada, Switzerland, and Australia. In preparation for our initial ex-U.S. launch, we plan to onboard 15 international treatment centers by year-end. Additional regulatory submissions remain on track, including Australia in the first half and Switzerland in the second half of 2025. In addition to Amtagvi, our commercial organization is dedicated to supporting Proleukin across three key lines of business, which include for use in the Amtagvi treatment regimen, for use in manufacturing clinical trials, and for clinical trial use where appropriate. During the fourth quarter, we activated and provided initial stock for a third and final planned Proleukin distributor. Orders are now being fulfilled at all three major U.S. wholesalers with healthy ordering patterns, including restocking. We expect demand for Proleukin to continue to increase across each of these three key business lines throughout the year. In summary, I am extremely pleased with the U.S. launch performance to-date and the momentum we are building to catalyze and expand Amtagvi adoption while growing Proleukin sales within the U.S. and beyond. I'm fully committed to the opportunity to impact thousands of patients' lives and drive toward $2-plus billion peak sales around the world. I will now pass the call over to Igor Bilinsky, our Chief Operating Officer, to highlight our manufacturing progress.
Igor Bilinsky: Thank you, Dan. Today, I would like to build on Fred's introductory comments with an update on our commercial and clinical manufacturing network as well as our capacity expansion. Our manufacturing network consists of our internal manufacturing facility, the Iovance Cell Therapy Center, or ICTC, and the contract manufacturer, which helps ensure flexibility and ample capacity for both commercial and clinical production. To support growing commercial demand for Amtagvi, we are steadily ramping up our manufacturing capacity month-over-month, while actively hiring manufacturing quality control and support staff. Within our manufacturing network, the staff capacity is currently at more than 1,200 patients annually. Throughout 2025, we will continue growing staff capacity in alignment with demand, while operating at a high capacity utilization. Each of our facilities is currently required to schedule a brief annual maintenance, which entails a short pause in production. I'm pleased to report that ICTC successfully completed annual maintenance and resumed production promptly at full volume with no issues. We expect the same positive outcome following the upcoming scheduled maintenance at our contract manufacturer. Our commercial manufacturing experience continues to be positive and consistent with prior clinical experience. The medical affairs and commercial teams are effectively sharing best practices among ATCs and contributing to improvements in manufacturing success rates and gross margin over time. The turnaround time is consistently 34 days from receiving cells at the manufacturing facility to Amtagvi being ready for return shipment to the ATC. Our team is planning to shorten the turnaround time in 2025. Our Philadelphia manufacturing network currently serves patients in our clinical trials in Europe, Australia, and other geographies. We are now establishing logistics and distribution to provide access to commercial product in new markets in the EU, U.K., and Canada in anticipation of potential approvals this year. We are also expanding capacity to fulfill our longer term vision. The ICTC is built today has capacity for more than 2,000 patients annually. Once we complete the ongoing build-out of existing shelf space, we expect the ICTC to have total capacity for over 5,000 patients annually within a few years. Additional expansion of our ICTC manufacturing campus, along with process optimization and automation is expected to provide capacity for over 10,000 patients annually. As we grow our manufacturing network, we are focused on improving the cost of goods through economies of scale and operational efficiencies as well as by leveraging our unique competitive advantage as the leader in the TIL cell therapy. Our TIL cell therapy expertise and manufacturing capabilities are protected by a robust intellectual property portfolio, we currently own more than 250 granted or allowed U.S. and international patents and patent rights for Amtagvi and other TIL-related technologies that are expected to provide exclusivity through at least 2042. I'm available to answer additional questions during the Q&A, and I will now hand the call to Jean-Marc, our Chief Financial Officer.
Jean-Marc Bellemin: Thank you, Igor. Today, I will review our current cash position as well as our results for the fourth quarter and full year 2024. I will also highlight our financial outlook, including revenue, expense guidance, and gross margin. As of December 31st, 2024, our cash position was $330.1 million. As of February 26, 2025, our unaudited cash position was approximately $422 million. Our current cash position is sufficient to fund current and planned operations, including manufacturing expansion into the second half of 2026. I will now transition to our financial results. Net loss for the fourth quarter of 2024 was $78.6 million or $0.26 per share compared to a net loss of $116.4 million or $0.45 per share for the fourth quarter ended December 31st, 2023. Net loss for the full year 2024 was $372.2 million or $1.28 per share compared to a net loss of $444 million or $1.89 per share for the full year 2023. Total product revenue consists of Amtagvi infusion in the U.S. and global sales of Proleukin within three different lines of business, as Dan described. Total product revenue was $73.7 million for the fourth quarter of 2024, including $48.7 million for Amtagvi and $25.0 million for Proleukin. For the full year 2024, we achieved the higher end of our product revenue guidance range of $160 million to $165 million. Total product revenue for the full year 2024 was $164.1 million and consisted of $103.6 million for Amtagvi and $60.5 million for Proleukin. Revenue increases in the fourth quarter and full year 2024 over the prior year periods were primarily driven by the U.S. commercial launch of Amtagvi and strong demand from global Proleukin sales. I will now highlight our cost of sales, which includes cost of inventory, overhead, and related cash and non-cash expenses that are directly associated with sales of Amtagvi and Proleukin as well as manufacturing costs for Amtagvi. Cost of sales for the fourth quarter was $45.5 million, including $9.1 million in period costs associated with patient drop-off and manufacturing success rates, which decreased quarter-over-quarter as a percentage of total revenue, $5.9 million for non-cash expenses, including fair market value step-up and intangible asset amortization and $6 million in royalty payable on product sales. In the prior year three months period, cost of sales was $4.4 million, primarily related to non-cash amortization for intangible assets. Cost of sales for the full year 2024 was $124 million, including $26.3 million in certain costs associated with patient drop-off and manufacturing success rates, $26.2 million in non-cash expenses, including fair market value step-up and intangible asset amortization, and $14.2 million in royalties payable on product sales. In the prior full year, cost of sales was $10.8 million, primarily related to non-cash amortization for intangible assets. The increase in cost of sales in the fourth quarter and full year 2024 over the prior year's periods were primarily attributable to the U.S. commercialization and sales of Amtagvi as well as Proleukin sales growth following the initiation of product sales in the U.S., commercial manufacturing and related cash and non-cash expenses tied to Amtagvi and Proleukin. Our standard gross margin for the fourth quarter 2024 was 46% or $34 million compared to the total product revenue of $73.7 million. Cost of sales has improved over time as we increased volume and capacity utilization throughout the launch ramp-up. The higher gross margin over the previous quarters reflect our ongoing focus on profitability and is well over halfway towards our target for gross margin to surpass 70% in the coming years. Our ongoing manufacturing expansion, strong coordination with our ATCs, and efficiencies in manufacturing and release testing are expected to further optimize our cost of sales with a correspondingly higher gross margin. I will now shift to our operating expenses. For the full year 2024, our total cash burn, excluding one-time expenses, was within our guidance range of $320 million to $340 million. Research and development expenses were $72.2 million for the fourth quarter of 2024, a decrease of $15.3 million compared to $87.5 million for the same period prior year period. Research and development expenses were $282.3 million for the full year 2024, a decrease of $61.8 million compared to $344.1 million for the full year 2023. The decrease in research and development expenses in the fourth quarter and full year 2024 over the prior year period was primarily attributable to the transition of Amtagvi from clinical to commercial manufacturing. This decrease was partially offset by increase in headcount and related costs, including stock-based compensation and clinical trial costs. Selling, general, and administrative expenses were $42.5 million for the fourth quarter of 2024, an increase of $12.6 million compared to $29.9 million for the prior year period. Selling, general, and administrative expenses were $153 million for the full year 2024, an increase of $46.1 million compared to $106.9 million for the full year 2023. The increase in selling and general and administrative expenses in the fourth quarter and full year 2024 compared to the prior year periods was primarily attributable to increase in headcount and related costs, including stock-based compensation to support our overall growth as well as legal and commercial-related costs. Looking ahead, we continue to reiterate our prior total product revenue guidance within the range of $450 million to $475 million for the full year 2025. In addition, we anticipate our cash burn for the full year 2025 to be less than $300 million, including investment in our ICTC facility expansion. Over time, we expect cash burn to decrease as we continue to grow revenue and as gross margin improves. We also plan to keep leveraging additional opportunities to further optimize spending this year. For additional information, please see the company's selected consolidated balance sheets and statements of operations in this afternoon's press release and our Form 10-K to be filed later today. I will now hand the call to Friedrich, our Chief Medical Officer, to discuss our clinical pipeline.
Friedrich Graf Finckenstein: Thank you, Jean-Marc. We continue to be excited about the potential of TIL cell therapy in solid tumors, which represent more than 90% of all diagnosed cancers in the U.S. Today, I will summarize key updates for our clinical programs as well as our exciting next-generation pipeline. Expanding the commercial opportunity for Amtagvi into frontline advanced melanoma is a top priority at Iovance. Our global registrational Phase 3 trial, TILVANCE-301, remains on track to support accelerated and full approvals of Amtagvi in combination with pembrolizumab in frontline advanced melanoma as well as regular approval of Amtagvi in our initial indication in post anti-PD-1 melanoma. Strong momentum with enrollment and high enthusiasm continue among participating in planned clinical sites. As a reminder, TILVANCE-301 is supported by positive results for Lifileucel plus pembrolizumab from IOV-COM-202 Cohort 1A in patients with advanced melanoma naive to immune checkpoint inhibitors. To explore another potential best-in-class alternative in frontline advanced melanoma for U.S. physicians and patients, Cohort 1D in IOV-COMMERCIAL-202 will investigate Lifileucel in combination with nivolumab and relatimab. Our second registrational program is investigating Lifileucel monotherapy in the single-arm registrational Phase 3 IOV-LUN-202 clinical trial to address unmet medical need among patients with advanced non-small cell lung cancer who progressed after anti-PD-1 therapy. Single-agent chemotherapy, the current standard-of-care in this setting provides limited rate and duration of responses. We expect to share additional data from IOV-LUN-202 in the second half of 2025. Enrollment continues with high demand at clinical sites in multiple countries to support a potential accelerated approval of Lifileucel in post anti-PD-1 non-small cell lung cancer in the U.S. with an anticipated regulatory decision in 2027. We also continue to pursue earlier treatment settings in non-small cell lung cancer. In frontline advanced non-small cell lung cancer, our strategy is to establish a new frontline regimen of Lifileucel plus pembrolizumab following standard-of-care chemo pembrolizumab for patients with EGFR wild-type non-small cell lung cancer who represent the majority of patients with an unmet medical need in this setting. We will investigate this regimen in Cohort 3D in the IOV-COM-202 clinical trial to inform a registrational and confirmatory trial design in frontline advanced non-small cell lung cancer. Our goal is to further augment the strong efficacy seen in Cohort 3A with Lifileucel in combination with pembrolizumab in patients who were not previously treated with immune checkpoint inhibitor therapy. Moving along the pipeline, we are excited about our first clinical trial in advanced endometrial cancer, a significant new opportunity for TIL cell therapy in an additional post anti-PD-1 setting. Our IOV-END-201 clinical trial is investigating Lifileucel after frontline standard of care of chemotherapy and anti-PD-1 therapy in patients with endometrial cancer, regardless of mismatch repair or MMR status. Recent approvals of immune checkpoint inhibitors in combination with chemotherapy for frontline endometrial cancer have created an unmet need. There are no currently approved therapies for patients who progress. We look forward to sharing initial data from END-201 in the second half of this year. As the leader in TIL cell therapy, Iovance is also at the forefront of next-generation approaches to optimize TIL and TIL treatment regimens. I'll briefly summarize our three main programs in this area. Our next-generation PD-1 inactivated TIL cell therapy IOV-4001 is investigated in the Phase 2 efficacy stage of our IOV-GM1-201 clinical trial. Multiple centers are enrolling at an increasing pace across 2 Phase 2 cohorts of patients with previously treated advanced melanoma or non-small cell lung cancer. Building on our successful Proleukin franchise, we recently initiated a Phase 1/2 clinical trial of IOV-3001, a second-generation modified IL-2 analog for use with the TIL cell therapy treatment regimen. IOV-3001 may result in a better safety profile and support less frequent dosing compared to Proleukin. Lastly, we plan to submit an IND to FDA this year for IOV-5001, a genetically engineered inducible and tethered IL-12 TIL cell therapy. The clinical trial of a prior generation IL-12 TIL therapy at the National Cancer Institute showed improved efficacy with low cell doses without the use of IL-2 and provides the rationale for the modifications in IOV-5001 to enhance TIL efficacy, while optimizing safety. IV-5001 could facilitate expansion into a wide range of common solid tumor cancers beyond our current pipeline with significant market opportunity. I'm happy to address questions about these programs and additional trials during the Q&A session. I look forward to sharing additional updates this year as we continue to work to deliver TIL cell therapy to cancer patients in additional therapeutic settings and with additional tumor types. Thank you to the talented multidisciplinary team and research partners who make this possible. I will now turn the call over to the operator to begin the question-and-answer session. Operator?
Operator: [Operator Instructions] Our first question comes from Andrea Newkirk with Goldman Sachs.
Andrea Newkirk: Good afternoon. Thanks for taking my questions. Fred, on prior calls, you've provided an update on the number of patients infused thus far in the quarter. Just wondering if you'd be willing to share where you stand as of today? And then just remind us or help us understand what gives you the confidence that the range for full year 2025, which was set when you're only one quarter into the launch is still intact? Thanks so much.
Fred Vogt: Yes, sure, Andrea. We're not -- from -- in the press release and on the call, we're not going to be providing the infusions right now. We're not sure how useful that metric was to long investors. And as some of you know, it was prone to overinterpretation. We provided some different metrics this time around, including the potential for growth at the ATCs. And that actually is a part of the answer to your second question, if you look at our press release and heard Dan's commentary, within the 70 ATCs that we have right now, only 13% of infused in 10 patients, which gives you a very good idea of the upside that we're expecting, the acceleration we're expecting in the second half and second quarter of 2025 here as we go through. So, we still have confidence in those numbers because the growth curve for this type of product can accelerate quite a bit, and we see that happening across our ATC network right now. We see the potential for that in those ATCs.
Andrea Newkirk: Okay. Thank you.
Operator: Thank you. Our next question comes from Peter Lawson with Barclays. Your line is open. Peter, your line is open, please check your mute button.
Peter Lawson: Great. Thank you so much for taking the question. As we think about the IL-2 revenues, kind of had a nice spike this quarter. Is that -- should we view that as a signal for future TL demand? Or is that kind of a stock in from distributors? And kind of how should we think about the IL-2 sales going forward? What component of 2025 revenues could that be? Thank you.
Fred Vogt: Yes. So, we continue to believe and continue to talk about IL-2 revenue as being a leading indicator for Amtagvi sales, like we've been saying for quite some time now. And I think what you're seeing there is you're seeing the uptake by all the SDs now in the United States. As Dan pointed out, we restocked two of them and sold block to a third. And I think you'll see in 2025, we'll be restocking again, and it will represent a significant portion of the $450 million to $475 million guidance that we have out there. It could be as $80 million to $100 million or more. We think it's a fantastic business. That's why we acquired it. It's performing very well right now. So, we're very happy with that number.
Peter Lawson: Got you. Thank you.
Operator: Thank you. Our next question comes from Ben Burnett with Stifel. Your line is open.
Ben Burnett: Hey, great. Thanks for much. I guess a question for us is what are physicians saying about sort of the evolving landscape and just the potential for a new entrant later this year?
Fred Vogt: I think many of your colleagues have written notes about this lately, and there's been a lot of discussion about this. We view the potential entrant as basically being very similar to a currently marketed product known as T-VEC. We're not really sure what the differentiation is between that. We also have a lot of information on how that product launched. We view the clinical data as not being comparable to ours. Their patient population is much, much earlier. 65% of their patients had one to two prior lines. They had about a quarter of patients with adjuvant PD-1 only in the study, and we're looking at 65% of our patients with three or more prior lines, a much more real-world population in metastatic melanoma. So, we don't really see it as being any kind of significant impact on our launch. We're out there with what we think is the premier product, and we're looking to grow our market, launching outside the U.S. and get other indications as soon as we can.
Ben Burnett: Okay, appreciate that color. Thank you.
Operator: Thank you. Our next question comes from Colleen Kusy with Baird. Your line is open.
Colleen Kusy: Great. Thanks for taking our questions. I understand you're not giving intra-quarter updates going forward, but you did provide in 4Q. Can you speak -- was there a slowdown in fusions in the back half of the quarter? And did you see any seasonality in 4Q?
Fred Vogt: Colleen, no, we don't see any seasonality. As Igor mentioned, we did have a manufacturing maintenance period there. So we have those kind of things in cell therapy. If you look at the launch curves for ABECMA, YESCARTA, and CARVYKTI, you'll see there's little peaks and dips and valleys in those as things like that happen. So, -- but nothing in terms of a holiday seasonality. That's what you're asking.
Colleen Kusy: Great. Thanks for taking our question.
Operator: Thank you. Our next question comes from Tyler Van Buren with TD Cowen. Your line is open.
Unidentified Analyst: Great. Thanks so much for taking our question. This is Nick on for Tyler. Thinking about guidance, 2025 guidance, is the potential price increase currently included in that guidance? And also, how should we think about the global ex-U.S. expansion having a potential impact on guidance? Thanks.
Fred Vogt: Yes. The price increase that's coming in April has been factored into that guidance for both Proleukin and Amtagvi. And right now, the guidance doesn't include any contribution from ex-U.S.
Unidentified Analyst: Thank you.
Operator: Thank you. Our next question comes from Yanan Zhu with Wells Fargo Securities. Your line is open.
Yanan Zhu: Great. Thanks for taking our questions. I was wondering how many infusions were performed in 4Q? And the quarter-over-quarter growth over the prior quarter, which was 82 infusions, how does that compare with your expectation? And do you think that growth will either be the same or be different for 1Q over 4Q? Thanks.
Fred Vogt: Yes, Yanan, it's about 95 revenue infusions. There's other infusions that occur with single patient INDs and that kind of thing that still generate revenue Proleukin sales, for example. It's about 95 revenue infusions is what we're reporting for the fourth quarter. I think the quarter-over-quarter growth is quite strong. We're seeing the growth that we need to see. It's going to go up and down as we go. Just like I said, with the CAR-T products, if you look back at their growth -- they were -- there were quarters where they grew 10%. There's quarters where they were flat. There's quarters where they grew 30%. Our intention is to drive growth, and we have tremendous opportunity in the ATCs that we have right now to do that as well as we get to the community.
Yanan Zhu: Great. Thanks for the color.
Operator: Thank you. Our next question comes from Asthika Goonewardene with Truist. Your line is open.
Asthika Goonewardene: Hey guys. Thanks for taking my question. Fred, may I ask for the new data that you provided in the quarter data that you provided, of the 70 ATCs that are online, what proportion have reached a steady state? I'm wondering, does that align with the 13% of ATCs that have already treated more than 10 patients? Thanks.
Fred Vogt: So, I think it's a very low number. I can't tell you exactly, but it's probably 10% or less of reached steady state at this point. We know that the vast majority of those 70 ATCs have tremendous upside. Maybe I'll ask Dan to comment a little bit on what we've seen so far on the potential upside of those ATCs.
Dan Kirby: Sure, Fred. And I think one of the things as you look at the ATCs, you look at the ones that are doing 10-plus, I don't really think they're saturated with it because our strategy is, again, to increase referrals in the community into those. They're the ones that have developed expertise within Amtagvi, and we have other ones that are inching towards that 10-plus infusion number with it. Those are really our centers of excellence that are leading the way for not only the other centers, but also for our activities in driving referrals to those centers.
Operator: Thank you. Our next question comes from Reni Benjamin with Citizens JMP. Your line is open.
Reni Benjamin: Hey guys. Thanks for taking the questions and congratulations on the quarter. Maybe just one for me from the pipeline for Friedrich. We have data coming out in the second half of this year. Can you talk a little bit about or set expectations for both non-small cell and endometrial? How many patients worth of data? And I guess with this data, is this the registrational set? Do we need to enroll even more patients before filing for accelerated approval in both non-small cell and endometrial? Or do we need to start another cohort that ultimately becomes the registrational data set? Any color would be great.
Friedrich Graf Finckenstein: Yes. So, to start with LUN-202, thanks for the question. Obviously, we're going to time our data disclosure with an appropriate venue, and we'll time our cut with that. Where we are in regards to enrollment will really depend on the timing, and I can't really comment on this at this point. This will be an update on what is obviously of the priority interest, which is the data from Cohorts 1 and 2, which are the registrational cohorts. There's not going to be additional cohorts or anything that we would be reporting out because we think that, that is probably not that relevant. About timing of the registrational plan, I said in my script, timing will be that we're expecting a registrational decision by the end of 2027. We are enrolling currently. We're seeing good momentum, and we are on track with that. I hope that answers your question. Around endometrial, similarly, I can't really commit to a specific patient number here, but it's going to be a meaningful number that at least gives you an initial idea around the signals that we're seeing in this trial. We find this important enough to share an early data set this year still.
Reni Benjamin: Thank you.
Operator: Thank you. Our next question comes from Salim Syed with Mizuho. Your line is open.
Unidentified Analyst: Hi. This is Bennett for Salim. Thanks so much for taking our question and congratulations on the quarter and all the progress. So, also on the registrational Phase 2 trial in post anti-PD-1 non-small cell lung cancer. So, could you remind us what's the bogey there? I mean we believe taxane plus anti-VGFR2 response rate around 30%, but I'm not sure if that's the best comparator here or if you can just talk a little bit about the bogey and the bar here? Thank you.
Fred Vogt: Yes, I can start and maybe Friedrich can get the rest of that. So we -- first of all, we can run -- FDA has told us we can run a single-arm trial here. We're not running randomized against docetaxel. What we will look at is with that BLA submission, the FDA would look at available care for those patients, and that includes the REVEL study, which is ramucirumab plus docetaxel or docetaxel monotherapy. And there, you're looking at response rates in the low 20s, but very short durability. And with TIL therapy, we have much longer durability. So we're thinking if we come in with response rates in the mid-20s like we showed before with the durability like we've been seeing, we should be fine in terms of getting approval on this product based on what FDA has told us today, and they've told us quite a bit about this. And Friedrich, if you're online, you can -- you're welcome to add to that.
Friedrich Graf Finckenstein: No, that's exactly right. The one thing to add here is it's really the durability that is the limitation here for the standard-of-care. For docetaxel plus ramu, although, again, as Fred mentioned, it's about 20% response rate. PFS is about 4 months and duration of response data has never been shared. So, I think that is indicating the limitations and the challenges that we are planning on addressing with Lifileucel therapy. Just as a reminder, the data that we had previously shared from LUN-202 indicated a response rate in the mid-20%, 26%. And then in a follow-up communication around it, we saw that 71% of the confirmed responders had DOR of more than six months, which in this population is very meaningful.
Unidentified Analyst: Thank you.
Operator: Thank you. Our next question comes from David Dai with UBS. Your line is open.
David Dai: Hey great. Thanks for taking my questions. Fred, I know you mentioned that you didn't see any seasonality for the holiday break. But I'm just wondering if you see any kind of spillover impact from holidays on start forms or resections?
Fred Vogt: Could you repeat that, David, on resection seasonality on resections?
David Dai: No, no. Just -- yes, wondering if there's any spillover impact from holidays on any kind of start forms or any kind of tumor resections, if that makes sense?
Fred Vogt: Yes, I'm not following you. We haven't -- maybe I can try to just answer more generally. We didn't really see any slowdown in terms of the ATCs just for the holidays, if that's what you're asking for any of their operations because they are generally running through the Christmas holidays without any interruption for cancer patients. Yes, of course, there could be one or two patients here or there.
Dan Kirby: And actually, just paring on top of that, Fred, I think for seasonality, we didn't notice it from my understanding in the clinical trials. But as we go commercially, we're just finishing our first year. So, we're going to look at those trends and patterns as we go forward to see if there is seasonality. Right now, we're not seeing it in the data. Hopefully, that helps you, David, but that is something we're looking at.
David Dai: All right. Thanks so much.
Operator: Thank you. Our next question comes from Andrew Tsai with Jefferies. Your line is open.
Andrew Tsai: Hey thanks. Good afternoon. Appreciate the updates. Look forward to 2025. So a quick one is, in terms of the launch uptake, what exactly would you say is the bottleneck at this juncture? If it's not patient demand nor supply chain nor even beds at sites, what is the gating factor to seeing an acceleration in sales for 2025 like you guided? Thanks.
Fred Vogt: So, I think above all, the ATCs that are starting up now have to get their feet under them and get running. We've got some ATCs that are performing very, very well right now. And we've got a lot more that are working their way up. I think in each ATC, there's a difference. Each individual ATC has its own little bottlenecks or whatever it might be. Some of them have staffing issues. Some of them have financial clearance challenges that we're helping out with. But all these things are pretty easily resolvable, and we've been able to show that a good portion of our ATCs can really fly right now, and we think we can get a lot more there pretty soon. Dan, go ahead.
Dan Kirby: Sure. And Andrew, I think one thing to add on top of what Fred said regarding not really a bottleneck, but there's a process they go through. They have to make sure they operationally can do it again. We're the first TIL in the market. So there's a learning curve there. As you see, we said 13% have hit 10% or more. That number continues to grow. So, once they hit that wave where they understand how to use the product with it, then the lever really is to pull the referrals and drive more patients in there. And that's where we're working with the community, not only at the clinic level, but also the leadership level and the community to make sure that those centers are getting to see the most patients.
Andrew Tsai: Make sense. Thanks.
Operator: Thank you. I'm showing no further questions at this time. I would now like to turn it back to Fred Vogt, Interim President and CEO, for closing remarks.
Fred Vogt: Thank you again for joining the Iovance Biotherapeutics fourth quarter and full year 2024 financial results and corporate update conference call. As we close the first calendar year of our first commercial TIL cell therapy launch, we look forward to providing future updates on our growing commercial and clinical portfolio. We continue to be motivated as we hear frequent feedback from ATCs about advanced melanoma patients benefiting and finding hope with Amtagvi in the commercial setting. I'm confident that Iovance is poised to maintain our global leadership in innovating, developing and delivering current and future generations of TIL cell therapies for patients with cancer. As always, we are thankful to the patients, health care and advocacy communities, our partners, and our exceptional Iovance team. I'd also like to thank our shareholders and analysts for their support. Thank you.
Operator: This concludes today's conference call. Thank you for participating. You may now disconnect.
Read More
