Good morning. Will the meeting please come to order? My name is Ian Jukes, and I'm the Chairman of the Board of Directors of IOVANCE Biotherapeutics. I'm pleased to welcome all of you to this annual meeting of the stockholders of IOVANCE Biotherapeutics. This meeting is being held virtually through a live webcast. Several IOVANCE directors and executive officers are attending today's meeting virtually. Two of our officers, Jean-Marc Bellemin, our Chief Financial Officer, and Fred Vogt, our Interim Chief Executive Officer and President and General Counsel, are in attendance and available to answer questions. Also present is Michael Formalo, a representative of Ernst & Young LLP, the company's independent registered public accounting firm.
Heather Obi of Broadridge has been appointed to serve as the Inspector of Election for the annual meeting and will deliver a report about the results of the stockholders' votes on the matters that will be considered at today's meeting. Ms. Obi has signed an oath to serve as the Inspector of Election, which will be filed with the minutes of this meeting. Ms. Obi, do we have a quorum? Please explain the procedures for voting today.
Good morning. As the Inspector of Election, I hereby confirm that a quorum is present and that this meeting is duly and properly convened. The polls are now open for voting online. If you are a stockholder of record and wish to vote online, please do so by following the instructions in the online meeting portal. As a reminder, you will need your 16-digit control number in order to access the meeting and vote your shares through the online portal. If you require any assistance or experience any technical difficulties, please contact the Broadridge Technical Support Team by following the instructions in the online portal. If you have any questions, you may use the online portal to submit them at any time. At the conclusion of the legal portion of the meeting, Dr. Vogt will give a brief presentation on the company's business.
Following the presentation, approximately 15 minutes have been set aside for a question-and-answer session. If you have already voted by proxy and do not wish to change your vote, you do not need to cast a ballot online today. IOVANCE's proxy statement and notice of meeting were made available on April 30, 2025, to persons holding IOVANCE shares as of record date of April 17, 2025.
We will now discuss and vote upon each of the proposals scheduled to come before the meeting. I'd like to introduce Jean-Marc Bellemin, IOVANCE's Chief Financial Officer, who has been appointed to serve as the Secretary for the annual meeting and will conduct this part of the meeting. Jean-Marc?
Good morning. We will address any questions during the Q&A session following Dr. Vogt's presentation. As a reminder, please refer to our rules of conduct for this meeting, a copy of which has been posted to the online meeting portal. Stockholders are generally limited to one question each, and because our time is limited, we may not be able to answer all of your questions during the Q&A session. The polls are now closed. We will now proceed to a vote of the proposals. Election of Directors. The first matter on which stockholders are voting is the election of a nominated director to serve until the 2026 annual meeting of stockholders. Our nominating committee has recommended, and our Board of Directors has approved the director nominees described in our proxy statement. Approval of Executive Compensation.
The second matter on which stockholders are voting is the approval on a non-binding advisory basis of the compensation of the named executive officers of IOVANCE Biotherapeutics, as disclosed in the proxy statement. Ratification of Ernst & Young LLP. The third matter on which stockholders are voting is the ratification of our appointment of Ernst & Young LLP as the company's independent registered public accounting firm for the fiscal year ending December 31, 2025. As described in our proxy statement, the Board of Directors recommends that stockholders ratify the appointment of Ernst & Young LLP. Approval of Amendment to 2018 Equity Plan. The fourth matter on which stockholders are voting is the approval of an amendment to the company's 2018 Equity Incentive Plan to increase the number of shares of the company's common stock authorized for issuance thereunder by 12,500,000 shares, as disclosed in the proxy statement.
Approval of Amendment to 2020 Employee Stock Purchase Plan. The final matter on which stockholders are voting is for the approval of an amendment to the company's 2020 Employee Stock Purchase Plan to increase the number of shares of the company's common stock authorized for issuance thereunder by 1 million shares, as disclosed in the proxy statement. We will now hear from Mrs. Obi, who will read the preliminary report of the Inspector of Election as to each of the proposals on which the stockholders voted.
Based on the preliminary report, one, each of the nominees have been elected as directors to serve until the 2026 annual meeting of stockholders. Two, the stockholders have approved the compensation of the named executive officers, as disclosed in the proxy statement. Three, the stockholders have ratified the appointment of Ernst & Young LLP as IOVANCE's independent registered public accounting firm for the fiscal year ending December 31, 2025. Four, the stockholders have approved the amendment to the company's 2018 Equity Incentive Plan. Five, the stockholders have approved the amendment to the company's 2020 Employee Stock Purchase Plan. The final results will be disclosed in the company's current report on Form 8K that the company expects to file.
The Inspector's report indicates that all of the proposals before the meeting have passed. I hereby adjourn the legal portion of the meeting. I would like to take this opportunity to thank you for your attendance and continued interest in IOVANCE.
I would now ask Dr. Vogt to give a presentation about IOVANCE's business and operations, and there will be an opportunity for questions from stockholders after his presentation. At the outset, I would just like to note that during the course of Dr. Vogt's presentation and the Q&A session, Dr. Vogt or other representatives of the company may make forward-looking statements regarding future events or the future financial performance of the company. Such statements are prediction only, and actual events or results could differ materially from those made in any forward-looking statement due to a number of risks and uncertainties, including assumptions about future events based on current expectations, planned business development efforts, near and long-term objectives, potential new business strategies, organization change, changing markets, marketing efforts, future business performance, and outlook. I refer you to the company's most recent filings with the U.S.
Securities and Exchange Commission, which contain and identify additional information covering factors that could cause the result to differ materially from those contained in our projection or forward-looking statements. Except as required by law, the company does not assume any responsibility for updating any forward-looking statements, and the company claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995.
Thank you, Jean-Marc. IOVANCE is the global leader in innovating, developing, and delivering TIL therapy for cancer patients. We have two approved products, Amtagvi and Proleukin. We've treated more than 1,000 commercial and clinical patients with our TIL products. We have a commercial launch right now that has been able to address patients with more than 250 million covered lives, more than 80 treatment centers onboarded or about to be onboarded as of May 8th. We have a global advanced melanoma patient treatment opportunity of about 70,000 patients. In our pipeline, which is also summarized here, we have three ex-U.S. regulatory filings currently in review, 11 ongoing clinical trials, and a large number of priority designations from the FDA. We had $366 million of cash as of March 31st, 2025, greater than $210 million of total product revenue, and more than 1,000 employees. Next slide, please.
This slide summarizes our solid tumor portfolio in our pipeline. At the top, you see our two commercial products, Amtagvi and Proleukin, which represent our melanoma franchise. Amtagvi right now is approved in the United States and is submitted in the European Union, the U.K., and Canada. Proleukin is a component of the Amtagvi treatment regimen and is approved in many countries for other indications, including advanced melanoma and renal cell carcinoma. In the middle portion of the slide, we see our pipeline of expansion and new indications using Amtagvi, lifileucel, and other combinations with pembrolizumab and other agents. At the top, we have our non-small cell lung program and our TOVANS-301 program in frontline melanoma. In the middle, we have our endometrial program, which I'll cover in a little bit. Towards the bottom, we have our combination regimens, including lifileucel combined with immune checkpoint inhibitors and chemotherapy.
At the bottom, we have our next-generation products, including our PD-1 inactivated TIL product, IV-4001, our PD-1 inactivated TIL, or sorry, our IL-2 analog, IV-3001, and our IL-12 tethered TIL product, IV-5001, all of which are early stage and are entering the clinic or are in the clinic in the case of 4001. Next slide, please. TIL therapy is a unique platform for cancer care. It's individualized, it's a one-time therapy, and it deploys the patient's own T cells to fight cancer. We start with the tumor tissue collection. We grow from that tumor tissue patient-specific T cells into the billions of cells, and we provide a treatment regimen back to the patient that can potentially lead to a durable, deep response. Next slide, please.
There's a significant market potential for solid tumors, with 91% of all cancer cases being solid tumor cancers, 1.8 million new cases every year in the United States. On the right-hand side of this slide, we show the U.S. deaths and the global deaths from our top three indications: melanoma, lung, non-small cell lung, and endometrial. You can see how significant the burden is right now and the potential opportunity for TIL therapies to provide a meaningful therapy for these patients. Next slide, please. Last year, Amtagvi became the first to ever approve TIL therapy. It's the preferred second-line therapy right now in the NCCN guidelines and is currently in the fourth quarter of its launch right now. Next slide, please. Amtagvi delivered deep and durable responses, and we just recently recapped this at the ASCO conference with our five-year follow-up data.
This slide summarizes a combination of data from the label and from the ASCO conference. We have an objective response rate of 31.4%. Median DOI was now reached at 36.5 months, representing a very long, durable response for our patients. Five-year overall survival was 19.7%, meaning one out of five patients are still alive at five years, which is significant given the high likelihood of death for patients at this stage of their cancer. Next slide, please. Now I'll summarize our expansion plans in advanced melanoma. Next slide. We have a significant opportunity to expand Amtagvi into other markets around the world for melanoma. The annual U.S. and ex-U.S. addressable opportunity is about 30,000 patients in our current target markets and our future target markets. The overall opportunity is greater than 70,000 patients. On the right-hand side of this slide, you can see the annual deaths in the U.S.
versus other markets, ex-U.S. markets, 22,000 deaths in the ex-U.S. markets. You can also see the frontline opportunity, which is the opportunity as we shift into the frontline, which I'll cover shortly here, and use Amtagvi in earlier lines of therapy is even greater with 14,000 deaths in the U.S., 14,000 addressable patients in the U.S., 27,000 outside the United States. Right now, we've got five regulatory approvals planned or underway. This year and 2025, we've got the United Kingdom, European Union, and Canada, and next year we're planning Australia and Switzerland. Next slide, please. In the frontline setting, Amtagvi or lifileucel delivers unprecedented rate, depth, and durability of responses, 65% ORR, objective response rate, and a 30.4% complete response rate in the frontline setting, meaning 30.4% of the patients saw no evidence of disease after treatment. This is in combination, this is lifileucel in combination with pembrolizumab.
On the right-hand side, you can see the waterfall of response plot and the swimmers plot showing deep durable responses for many of these patients. This data was presented at ASCO last year. Next slide, please. This data was the basis for us to initiate and conduct the TOVANS-301 global phase 3 trial, which also serves as the confirmatory trial for the C144-01 trial that led to our approval in the United States and is being used outside the United States for the initial approvals. This is a study design. This was done with FDA agreement. We use dual primary endpoints of objective response rate, which we can read relatively early, and progression-free survival, or PFS.
We can perform an interim analysis on objective response rate and use that for an accelerated approval, as well as the confirmation of the benefit of the prior approval, and then use the same trial to generate a final analysis on PFS for full approval of this indication as well, the frontline indication. We get two for the price of one with this study. It's extremely valuable to the field, and we'll demonstrate that TIL therapy can be used in earlier line settings more effectively, just like we saw on slide 12. Next slide, please. Now I'll cover some of our TIL therapy pipeline. Next slide, please. We have a huge market opportunity in non-small cell lung cancer with 50,000 patients a year in the United States and 50,000 in the target European Union markets. Globally, it's even larger.
We have 210,000 addressable patients in the frontline setting in non-small cell lung in the United States. Lung cancer, of course, is the leading cause of all cancer deaths in the United States, with one in five cancer-related deaths coming from lung cancer. The real-world overall survival for these patients is less than six months, and there's a 9% five-year survival rate, highlighting the significant unmet medical need and the importance of therapies that can deliver deep durable responses for non-small cell lung patients. Next slide, please. On this slide, we show our Lung TUA-2 trial. This is a registrational trial that we're currently running in second line non-small cell lung. The patient population is shown on the left here. There's two cohorts at the top that we consider to be registrational after discussions with the FDA, cohort one and cohort two.
The endpoints for this trial are objective response rate by independent review committee, and we anticipate having interim data for these cohorts at some point in 2025. Next slide, please. We previously showed data from this study. Next slide, please. Thank you. We previously showed data from this study, which delivered a 26.1% objective response rate. Regardless of PD-L1 status, the duration of response was greater than six months for 71% of the confirmed responders. The waterfall plot and the swimmers plot are shown here. This shows the potential of TIL therapy in non-small cell lung cancer, and this is supported by two earlier studies, cohort 3B, which we ran as part of the COMTO-2 study and published. The publications can be found on our website, as well as the investigator-sponsored trial that we ran with Moffitt, also showed durable responses with TIL therapies in this setting.
Next slide, please. Now I'll switch to endometrial cancer, which also has a tremendous potential market opportunity. 90% plus of uterine cancers are endometrial cancers. It causes 13,000 plus annual deaths in the United States alone, almost 100,000 globally. There's no standard of care in the second-line post-anti-PD-1 or post-anti-PD-1 and chemotherapy setting, and that's the setting that we're operating in with the N201 trial. Next slide, please. The N201 trial is a proof of concept study. We've divided the patients into MMR proficient and deficient subgroups. The endpoints here are ORR again, and this study could potentially be registrational should we have proof of concept in the study. Next slide, please. IOAVANCE is also a leader in the next-generation TIL programs. As I showed back on the pipeline slide, we've got multiple assets with genetic modification engineering.
We've got next-generation processes, and we've got new treatment regimens that we're developing. Next slide, please. Now I'll go to the corporate summary. Next slide, please. IOVANCE is in a strong financial position for commercial success and pipeline growth with a cash position of $366 million. This slide details some of the other particulars. Our cash runway is sufficient into the second half of 2026. Our full year burn for 2025 is anticipated to be under $300 million, and our gross margins are expected to increase to greater than 70% over the next several years. With that, I'll conclude the presentation, and we'll open the floor for questions. Operator, can you confirm there's no questions?
Confirm there's no questions.
Thank you. Ladies and gentlemen, that concludes our meeting. Thank you for your continued support of IOVANCE.
Ladies and gentlemen, that does conclude today's presentation. We do thank you for joining. You may now disconnect your lines.