Iovance Biotherapeutics Q4 2024 Earnings Call Transcript

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Provided by Quartr
February 27, 2025

Key Takeaways

  • Robust 4Q and FY 2024 revenue: Total product revenue reached $73.7 million in the fourth quarter and $164.1 million for the full year, achieving the upper end of guidance and exceeding street consensus.
  • Strong US commercial launch of AMTAGV: Over 200 patients treated through 70 Authorized Treatment Centers across 32 states, driving reiteration of $450–475 million total product revenue guidance for 2025.
  • Manufacturing scale-up: Staffed capacity to supply more than 1,200 patients per year with expansion plans to exceed 5,000 annual patients at ICTC and over 10,000 with further build-out and automation.
  • Pipeline advancement: Two registrational trials in frontline melanoma (TILZAN-301) and post-PD-1 non-small cell lung cancer (IOV LUN202) remain on track for key data in H2 2025, along with new studies in endometrial cancer and next-generation TIL therapies.
  • Financial runway and profitability goals: Net loss improved in 4Q, cash burn within $320–340 million guidance for 2024, $422 million cash on hand as of Feb 2025, and 2025 burn expected < $300 million to drive toward breakeven.
AI Generated. May Contain Errors.
Earnings Conference Call
Iovance Biotherapeutics Q4 2024
00:00 / 00:00

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Operator

Good day, and thank you for standing by. Welcome 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 speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Sara Pellegrino, SVP of Investor Relations and Corporate Communications. Please go ahead.

Sara Pellegrino
Sara Pellegrino
SVP of Investor Relations and Corporate Communications at Iovance Biotherapeutics

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 at authorized treatment centers, or ATCs, community outreach initiatives to drive additional growth for the U.S. commercial launch, as well as our ex-US launch expansion plan for Amtagvi and advanced melanoma. Dr. Igor Bilinsky, our Chief Operating Officer, will cover our commercial manufacturing experience, available staff capacity, and the status of our ongoing capacity expansion.

Sara Pellegrino
Sara Pellegrino
SVP of Investor Relations and Corporate Communications at Iovance Biotherapeutics

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. 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.

Sara Pellegrino
Sara Pellegrino
SVP of Investor Relations and Corporate Communications at Iovance Biotherapeutics

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 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. With that, I will turn the call over to Fred.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

Thank you, Sara. 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 progressed following anti-PD-1 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 a robust pipeline of current and future-generation TIL cell therapies across all stages of development to address tens of thousands of patients with solid tumors.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

Today, I'm pleased to highlight continued growth in total product revenue for both Amtagvi and Proleukin. Total product revenue was $73.7 million in the fourth quarter and $164.1 million in the full year of 2024. Importantly, our full-year revenue achieved the upper end of our 2024 guidance range of $160 million-$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 from global Proleukin sales.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

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 staff 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 and 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-$475 million in total product revenue.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

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. 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, including one-time items, to continue to decrease as we execute the launch and drive towards break-even and profitability. Longer term, we remain confident in significant revenue growth in 2026 and beyond.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

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-US launch expansion plans are on track with the potential to gain three new approvals and provide early access to Amtagvi and several new markets. Iovance has distinct competitive advantages with the first approval, launch, and large-scale manufacturing of TIL cell therapy, combined with strong intellectual property positions and a deep pipeline. Future growth drivers include global legal 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 a newly created role of Chief Commercial Officer.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

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
Dan Kirby
Chief Commercial Officer at Iovance Biotherapeutics

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 are 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.

Dan Kirby
Dan Kirby
Chief Commercial Officer at Iovance Biotherapeutics

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, has also supported patient access. Throughout 2024, we scaled up our ATC network to meet the growing patient demand and fulfilled significant interest among healthcare 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.

Dan Kirby
Dan Kirby
Chief Commercial Officer at Iovance Biotherapeutics

Among 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 planned 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 field 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.

Dan Kirby
Dan Kirby
Chief Commercial Officer at Iovance Biotherapeutics

As more patients embark on their treatment journey, we are making steady progress to speed up the time to Amtagvi 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 a decreased 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 a PD-1 and targeted therapy.

Dan Kirby
Dan Kirby
Chief Commercial Officer at Iovance Biotherapeutics

Three regulatory dossiers are currently under review for potential approvals in 2025, beginning with the United Kingdom in the first half, then Canada in mid-year, and the European Union in the second half of the year. We also plan to provide early access for Amtagvi in the UK, France, Germany, Canada, Switzerland, and Australia. In preparation for our initial XUS 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.

Dan Kirby
Dan Kirby
Chief Commercial Officer at Iovance Biotherapeutics

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+ 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
Igor Bilinsky
COO at Iovance Biotherapeutics

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.

Igor Bilinsky
Igor Bilinsky
COO at Iovance Biotherapeutics

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.

Igor Bilinsky
Igor Bilinsky
COO at Iovance Biotherapeutics

We are now establishing logistics and distribution to provide access to commercial product in new markets in the EU, UK, 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 and 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.

Igor Bilinsky
Igor Bilinsky
COO at Iovance Biotherapeutics

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
Jean-Marc Bellemin
CFO at Iovance Biotherapeutics

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 31, 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 and December 31, 2023.

Jean-Marc Bellemin
Jean-Marc Bellemin
CFO at Iovance Biotherapeutics

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-$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.

Jean-Marc Bellemin
Jean-Marc Bellemin
CFO at Iovance Biotherapeutics

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-month period, cost of sales was $4.4 million, primarily related to non-cash amortization for intangible assets.

Jean-Marc Bellemin
Jean-Marc Bellemin
CFO at Iovance Biotherapeutics

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 start-up gross margin for the fourth quarter 2024 was 46%, or $34 million, compared to the total product revenue of $73.7 million.

Jean-Marc Bellemin
Jean-Marc Bellemin
CFO at Iovance Biotherapeutics

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 reflects 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-$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.

Jean-Marc Bellemin
Jean-Marc Bellemin
CFO at Iovance Biotherapeutics

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 an 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.

Jean-Marc Bellemin
Jean-Marc Bellemin
CFO at Iovance Biotherapeutics

The increase in selling and general administrative expenses in the fourth quarter and full year 2024 compared to the prior year periods was primarily attributable to an increase in headcount and related costs, including stock-based compensation to support 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-$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.

Jean-Marc Bellemin
Jean-Marc Bellemin
CFO at Iovance Biotherapeutics

For additional information, please see the company's selected consolidated balance sheets and statement 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 Frederick, our Chief Medical Officer, to discuss our clinical pipeline.

Friedrich Graf Finckenstein
Friedrich Graf Finckenstein
CMO at Iovance Biotherapeutics

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 program, 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, TILVANS-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-PD1 melanoma. Strong momentum with enrollment and high enthusiasm continue among participating and planned clinical sites. As a reminder, TILVANS-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.

Friedrich Graf Finckenstein
Friedrich Graf Finckenstein
CMO at Iovance Biotherapeutics

To explore another potential best-in-class alternative in frontline advanced melanoma for U.S. physicians and patients, cohort 1D in IOV-COM-202 will investigate lifileucel in combination with nivolumab and relatlimab. Our second registration program is investigating lifileucel monotherapy in the single-arm registrational phase 2 IOV-LUN-202 clinical trial to address unmet medical need among patients with advanced non-small cell lung cancer who progress 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.

Friedrich Graf Finckenstein
Friedrich Graf Finckenstein
CMO at Iovance Biotherapeutics

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-PD1 setting.

Friedrich Graf Finckenstein
Friedrich Graf Finckenstein
CMO at Iovance Biotherapeutics

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 two efficacy stage of our IOV-GM1-201 clinical trial.

Friedrich Graf Finckenstein
Friedrich Graf Finckenstein
CMO at Iovance Biotherapeutics

Multiple centers are enrolling at an increasing pace across two 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. A 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.

Friedrich Graf Finckenstein
Friedrich Graf Finckenstein
CMO at Iovance Biotherapeutics

IOV-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'll now turn the call over to the operator to begin the question and answer session. Operator.

Operator

As a reminder, 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, and you may rejoin the queue if you have any additional questions. Please stand by while we compile the Q&A roster. Our first question comes from Andrea Newkirk with Goldman Sachs. Your line is open.

Andrea Newkirk
Andrea Newkirk
VP and Biotechnology Equity Research Analyst at Goldman Sachs

Good afternoon. Thanks for taking our 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 were only one quarter into the launch, is still intact. Thanks so much.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

Yeah, sure, Andrea. We're not, from in the press release and in 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 over-interpretation. We provide 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% have infused more than 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.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

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
Andrea Newkirk
VP and Biotechnology Equity Research Analyst at Goldman Sachs

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
Peter Lawson
Managing Director and Senior Equity Analyst at Barclays

Great. Thank you so much for taking the question. As we think about the IL-2 revenues, kind of they had a nice spike this quarter. Should we view that as a signal for future TIL demand, or is that kind of a stock in from distributors? And kind of how should we think about the IL-2 sales going forwards? What component of 2025 revenues could that be? Thank you.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

Yeah. 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 a 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-$475 guidance that we have out there. It could be as close as $80-$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
Peter Lawson
Managing Director and Senior Equity Analyst at Barclays

Gotcha.

Operator

Thank you. Our next question comes from Ben Burnett with Stifel. Your line is open.

Ben Burnett
Ben Burnett
Managing Director and Equity Research Analyst at Stifel

Hey, great. Thanks so much. I guess 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
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

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've also seen 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 have 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 of metastatic melanoma. So we don't really see it as being any kind of significant impact on our launch.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

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 getting other indications as soon as we can.

Ben Burnett
Ben Burnett
Managing Director and Equity Research Analyst at Stifel

Okay. Appreciate that color. Thank you.

Operator

Thank you. Our next question comes from Colleen Kusy with Baird. Your line is open.

Colleen Kusy
Colleen Kusy
Director and Senior Research Analyst at Baird

Great. Thanks for taking our questions. Understand you're not giving interquarter updates going forward, but since you did provide them for Q, can you speak? Was there a slowdown in infusions in the back half of the quarter, and did you see any seasonality in 4Q?

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

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 Breyanzi, Yescarta, and Carvykti, you'll see there's little peaks and dips and valleys in those as things like that happen. But nothing in terms of a holiday seasonality, if that's what you're asking.

Colleen Kusy
Colleen Kusy
Director and Senior Research Analyst at Baird

Great. Thanks for taking our question.

Operator

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

Operator

Great. Thanks very 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-US expansion having a potential impact on guidance? Thanks.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

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-US.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

Thank you.

Operator

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

Yanan Zhu
Yanan Zhu
Senior Analyst in Biotechnology Equity Research at Wells Fargo

Oh, great. Thanks for taking our questions. I was wondering how many infusions were performed in Q4, and did 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 Q1 over Q4? Thanks.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

Yeah. 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 for Proleukin sales, for example. But 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, there were quarters where they grew 10%. There were quarters where they were flat. There were quarters where they grew 30%. Our intention is to drive growth, and we have tremendous opportunity at the ATCs that we have right now to do that as well as we get in the community.

Yanan Zhu
Yanan Zhu
Senior Analyst in Biotechnology Equity Research at Wells Fargo

Great. Thanks for the call.

Operator

Thank you. Our next question comes from Asthika Goonewardene with Truist. Your line is open.

Asthika Goonewardene
Asthika Goonewardene
Managing Director and Senior Biotech Analyst at Truist

Hey, guys. Thanks for taking my question. Fred, if I can ask, to the new data that you provided, the interquarter 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
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

I think it's a very low number. I can't tell you exactly, but it's probably 10% or less have 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 he's seen so far on the potential upside of those ATCs. Sure, Fred. I think one of the things is 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 from the community into those. They're the ones that have developed expertise with Amtagvi. And we have other ones that are inching towards that 10-plus infusion number with it.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

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
Managing Director at JMP

Hey, guys. Thanks for taking the questions and congratulations on the quarter. Maybe just one from me from the pipeline for Frederick. 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.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

Yeah. To start with the lung, too, 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 one and two, 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.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

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
Managing Director at JMP

Thank you.

Operator

Thank you. Our next question comes from Salim Syed with Mizuho. Your line is open.

Operator

Hi. This is Bennett for Salim. Thanks so much for taking our question, and congratulations in the quarter and all the progress. So also on the registrational phase two trial in post-anti-PD1 non-small cell lung cancer, so could you remind us what the bogey there? I mean, we believe Taxane plus anti-EGFR response rate is 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
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

Yeah. I can start. Maybe Frederick can get the rest of that. So first of all, FDA has told us we can run a single-arm trial here. We're not running randomized against docetaxel. What we would 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.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

They've told us quite a bit about this. Frederick, if you're online, you're welcome to add to that.

Friedrich Graf Finckenstein
Friedrich Graf Finckenstein
CMO at Iovance Biotherapeutics

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 ramucirumab, although, again, as Fred mentioned, it's about 20% response rate. PFS is about four 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 IOV-LUN-202 to indicate 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.

Friedrich Graf Finckenstein
Friedrich Graf Finckenstein
CMO at Iovance Biotherapeutics

Thank you.

Operator

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

David Dai
David Dai
Research Analyst at UBS

Hey, Greg. Thanks for taking my question. Fred, I know you mentioned that you didn't see any seasonality for the holiday break, but I'm just wondering, do you see any kind of spillover impact from holidays on start forms or resections?

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

Could you repeat that, David? On resections, seasonality on resections?

David Dai
David Dai
Research Analyst at UBS

No, no. Just, yeah, wondering if there's any kind of spillover impact from holidays on any kind of start forms or any kind of tumor resections, if that makes sense?

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

Yeah. I'm not following you. 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 other 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. And actually, just carrying 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
David Dai
Research Analyst at UBS

All right. Thank you so much.

Operator

Thank you. Our next question comes from Andrew Tsai with Jefferies. Your line is open.

Andrew Tsai
Andrew Tsai
Research Analyst at Jefferies

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
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

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. And Dan, go ahead. Sure.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

And Andrew, I think one of the things 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 on 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, excuse me, really is to pull the referrals and drive more patients in there. And that's where we're working in the community, not only at the clinic level, but also the leadership level in the community to make sure those centers are getting to see the most patients.

Andrew Tsai
Andrew Tsai
Research Analyst at Jefferies

Makes sense. Thanks.

Operator

Thank you. I'm showing no further questions at this time. Oh, now I'd like to turn it back to Fred Vogt, Interim President and CEO, for closing remarks.

Fred Vogt
Fred Vogt
Interim CEO and President at Iovance Biotherapeutics

Thank you again for joining the Iovance Biotherapeutics fourth quarter and full year 2024 financial results and corporate updates 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, healthcare, 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.

Executives
    • Jean-Marc Bellemin
      Jean-Marc Bellemin
      CFO
    • Friedrich Graf Finckenstein
      Friedrich Graf Finckenstein
      CMO
    • Sara Pellegrino
      Sara Pellegrino
      SVP of Investor Relations and Corporate Communications
    • Igor Bilinsky
      Igor Bilinsky
      COO
    • Fred Vogt
      Fred Vogt
      Interim CEO and President
    • Dan Kirby
      Dan Kirby
      Chief Commercial Officer
Analysts
    • David Dai
      Research Analyst at UBS
    • Reni Benjamin
      Managing Director at JMP
    • Asthika Goonewardene
      Managing Director and Senior Biotech Analyst at Truist
    • Yanan Zhu
      Senior Analyst in Biotechnology Equity Research at Wells Fargo
    • Analyst at Mizuho
    • Peter Lawson
      Managing Director and Senior Equity Analyst at Barclays
    • Andrew Tsai
      Research Analyst at Jefferies
    • Analyst at TD Cowen
    • Andrea Newkirk
      VP and Biotechnology Equity Research Analyst at Goldman Sachs
    • Colleen Kusy
      Director and Senior Research Analyst at Baird
    • Ben Burnett
      Managing Director and Equity Research Analyst at Stifel
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