Welcome to the Iovance Biotherapeutics conference call to discuss first quarter 2024 results and recent corporate updates. My name is Olivia, and I'll be your operator for today's call. Please note that this conference is being recorded. I will now hand the conference call over to Sara Pellegrino, Senior Vice President, Investor Relations and Corporate Communications at Iovance. Sara, you may begin.

Thank you, operator. Good afternoon, and thank you for joining this conference call and webcast to discuss our first quarter 2024 results and recent corporate updates. Dr. Fred Vogt, our Interim President and Chief Executive Officer, will provide an introduction and summarize key updates on our U.S. commercial launch of Amtagvi and our pipeline program. Jim Ziegler, EVP Commercial, will highlight our initial success with the U.S. commercial launch of Amtagvi in advanced melanoma. Dr. Igor Bilinsky, COO, will comment on our commercial manufacturing experience and capacity expansion plans. Jean-Marc Bellemin, CFO, will review our financial results; and Dr. Friedrich Finckenstein, Chief Medical Officer, will review key pipeline updates, including upcoming clinical data presentations at ASCO and new next-generation approaches. Dr. Brian Gastman, Executive Vice President, Medical Affairs; and Dr. Raj Puri, Executive Vice President, Regulatory Affairs, are also on the call and available for the Q&A 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, 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 it over to Fred.

Thank you, Sara, and good afternoon, everyone. I am pleased to host our first quarter 2024 results conference call. This has been a decisive year for Iovance following our first FDA approval and a strong start to the U.S. launch of Amtagvi for patients with advanced melanoma. We expect the positive momentum at Iovance will continue to build throughout 2024 as we ramp up U.S. launch and execute across our broad clinical pipeline. To begin, we are very pleased that the high initial demand for Amtagvi continues to accelerate. Demand has increased month-over-month since approval and is expected to grow further throughout the year. As of today, more than 100 patients are already enrolled for Amtagvi therapy, and most are expected to be ready for infusion across the second and early third quarters of 2024. In addition, more than 60 additional patients have been identified at ATCs and are expected to enroll soon. As existing and new ATCs continue to build experience, we expect patient enrollments to steadily increase throughout the year, supporting our expectations for sustained growth. As we anticipated, interest is very high at our ATCs, and they are demonstrating that they have the training, infrastructure and capabilities to treat patients with Amtagvi, which Jim will further highlight. We remain on track to have 50 total ATCs by the end of this month. We also set a new goal of at least 70 ATCs by the end of this year, representing the largest ever number of ATCs for cell therapy launch. We are pleased to see positive reimbursement trends, which is a key indicator for success and adoption. Positive reimbursement decisions are supported by our clinical data and the recent addition of Amtagvi as the preferred second-line or subsequent therapy in the National Comprehensive Cancer Network or NCCN guidelines. The time to treatment will accelerate as ATCs establish a solid foundation for broad market access and reimbursement, which will add to momentum. Jim will describe this in more detail. In terms of commercial manufacturing, we have two FDA-approved manufacturing sites and sufficient capacity to meet near-term demand at launch, setting a new bar for cell therapy launches. Our commercial manufacturing experience is very positive and is consistent with our prior clinical experience. We have successfully manufactured and delivered Amtagvi within our target turnaround time of 34 days. ATCs observe sufficient availability of manufacturing slots and report a positive experience in the scheduling process, which is critical for broader utilization. We expect to have ample capacity to meet the anticipated ramp-up in demand this year. Finally, long-term expansion is already underway to more than double our current built capacity for future growth. In addition to the U.S. launch, we're working on our new markets that can more than double the total addressable advanced melanoma patient population for Amtagvi. Regulatory submissions remain on track this year in the EU, U.K., and Canada, where we have the potential to begin driving significant additional revenue by the end of 2025. We also continue to advance and expand our robust and exciting pipeline, including two registrational programs as well as new next-generation approaches that Friedrich will highlight on this call. As a fully integrated company that's executing a U.S. launch and developing a broad pipeline, Iovance is well positioned to remain the global leader in innovating, developing, and delivering TIL cell therapy for patients with cancer. I'll now hand over to Jim, our Executive Vice President of commercial, who will speak in more detail about our launch metrics.

Thank you, Fred. We are excited about the potential for Amtagvi to transform the treatment paradigm in advanced melanoma. My objectives today are to highlight initial U.S. launch metrics, which are supported by robust demand among ATCs and patients as well as progress with payers. ATCs are the key driver of demand and patient enrollments for Amtagvi. Launching with 30 ATCs was a testament to the significant unmet need in advanced melanoma and each center's high level of commitment to offering Amtagvi for their patients. Today, there are more than 40 ATCs, and we remain on track to meet our goal of 50 total ATCs by the end of May. Due to increasing interest by hospitals that offer Amtagvi, we are now targeting at least 70 total ATCs by the end of the year. As Fred mentioned earlier, ATCs have enrolled more than 100 patients for Amtagvi treatment. A patient enrollment is defined as an Amtagvi treatment decision by the provider and patient. The patient enrollment is followed by a commercial payer prior authorization and a scheduled tumor procurement for manufacturing. Based on the patient journey timeline, Amtagvi infusions for currently enrolled patients would likely occur across the second quarter and early third quarter. In addition, existing ATCs are screening an increasing number of patients for treatment eligibility. With more than 60 patients currently in screening today, we expect a high conversion of additional patients to Amtagvi patient enrollment in the near term for potential infusions in the third quarter. We are observing month-over-month growth, and we anticipate sustained growth throughout the year as the number of ATCs expands, and there is broader utilization of Amtagvi. In the short time since approval, favorable reimbursement trends in medical coverage policies have set us up for success and broad access for patients. Early launch data indicates that more than 75% of patients enrolled for Amtagvi are commercially insured, which aligns with our expectations. Thus far, payers responsible for more than 200 million lives have approved at least one patient for Amtagvi treatment. And notably, 13 payers responsible for approximately 90 million covered lives have already published medical coverage policies that are consistent with label, clinical trials, and the recently updated NCCN guidelines. We expect the remaining payers to issue similar favorable medical coverage policies and that timelines for financial clearance will accelerate as more payers issue coverage policies. In summary, we are extremely pleased with the early launch progress, and we expect steady growth as ATCs gain treatment experience, our ATC network expands, and community referrals increase over time. I look forward to providing future updates on these important ATC, reimbursement, and performance metrics. I would like to acknowledge the very talented cross-functional teamwork at Iovance. I'm even more pleased with the deep partnerships our team established with ATCs. Collectively, our goal is to broaden and accelerate patient access to Amtagvi. I will now pass the call to Igor Bilinsky, our Chief Operating Officer, to highlight our manufacturing progress.

Thank you, Jim. Today, I want to emphasize our current manufacturing capabilities, our experience with the Amtagvi U.S. launch, and our plans for capacity expansion to support anticipated product growth and demand in the U.S. due to geographic expansion and our promising clinical pipeline. Manufacturing is a key strength for us at Iovance, and we have established our own facility, the Iovance Cell Therapy Center (ICTC), in Philadelphia. ICTC is one of the largest facilities in the world dedicated to cell therapy manufacturing and is uniquely designed for TIL manufacturing. It has received FDA approval for the commercial production of Amtagvi for the U.S. market and continues to support patients in our clinical trials across various regions, including the U.S., Europe, and Australia. To date, ICTC has handled most of the commercial manufacturing volume for Amtagvi. Additionally, the FDA has approved our contract manufacturing site for Amtagvi, offering us extra flexibility and capacity for both commercial and clinical needs. We believe that our manufacturing capabilities are setting a new standard for cell therapy launches, and we are strategically planning for expected future demand. Regarding our initial experiences with the commercial launch, we are executing as planned. The commercial manufacturing process so far aligns with our previous clinical experiences, with turnaround times meeting our initial expectations of about 34 days from the receipt of tumor tissue to the shipment of Amtagvi to the ATC, followed by lymphodepletion and infusion. We are confident in our ability to meet the current and anticipated demand from our U.S. launch and clinical trials, as well as to support Iovance's future growth. Currently, ICTC can provide TIL therapies for more than 2,000 patients annually. Having a skilled manufacturing team is crucial in biotech, especially in cell therapy. We are appropriately staffed for the launch and are continuously hiring to meet the demand for both commercial Amtagvi and our clinical trials. The ICTC Philadelphia location allows us to tap into talent with cell and gene therapy experience from other companies and the next generation of talent from local educational institutions. In anticipation of increasing commercial demand in the U.S. and other regions, as well as for our advancing clinical pipeline, we are expanding capacity at ICTC, which is expected to be completed in a few years. This expansion will enable us to supply TIL therapies for over 5,000 patients annually. Looking ahead, we aim to increase our output to support over 10,000 patients annually from the ICTC campus. We have the option to construct an additional building at the ICTC campus and plan to enhance efficiencies by incorporating more automation into our manufacturing processes. In summary, our team is excited to deliver Amtagvi and our investigational TIL therapies to cancer patients. We are focused on maintaining the highest quality throughout the manufacturing process, ensuring everything is done correctly at each step—from receiving tumor samples, to manufacturing and product release, to shipping Amtagvi to commercial ATCs and investigational TILs to clinical trial sites. I am available for further questions during the Q&A and will now pass the call to Jean-Marc, our Chief Financial Officer.

Thank you, Igor. Today, I will review our current cash position as well as our results for the quarter ended on March 31, 2024. I will also highlight our 2024 outlook. As of March 31, 2024, Iovance had cash, cash equivalents, investments, and restricted cash of approximately $362.6 million. The current cash position and anticipated revenue from Amtagvi and Proleukin are expected to be sufficient to fund current and planned operations well into the second half of 2025. Shifting to our first quarter financial results. Net loss for the first quarter ended March 31, 2024, was $113 million or $0.42 per share compared to a net loss of $107.4 million or $0.50 per share for the first quarter ended March 31, 2023. The net loss for the first quarter of 2024 includes amortization of intangible assets acquired as part of the Proleukin transaction. Revenue for the first quarter ended March 31, 2024, was $715,000 and comprised of sales of Proleukin in licensed markets outside of the U.S. Cost of sales for the first quarter ended March 31, 2024, was $7.3 million, primarily related to inventory costs associated with sales of Proleukin and non-cash amortization expense for the acquired intangible assets for developed technology. There was no revenue or cost of sales in the first quarter ended March 31, 2023. Research and development expenses were $79.8 million for the first quarter ended March 31, 2024, a decrease of $2.9 million compared to $82.7 million for the same period ended March 31, 2023. The decrease was primarily attributable to the transition to commercial Amtagvi manufacturing in the most recent quarter, partially offset by increased costs associated with the purchase of raw materials, and clinical trials driven primarily by the Phase III TILVANCE-301 clinical trial and the planned EU regulatory submissions for lifileucel. Selling, general and administrative expenses were $31.4 million for the first quarter ended March 31, 2024, an increase of $3.3 million compared to $28.1 million for the same period ended March 31, 2023. The increase was primarily attributable to increases in headcount and related costs, including stock-based compensation to support the growth in the overall business and related corporate infrastructure, as well as costs incurred to support the commercialization of Amtagvi and Proleukin, partially offset by a decrease in legal costs. Regarding our outlook for this year, we continue to guide toward full year 2024 cash burn in the range of $320 million to $340 million, excluding one-time expenses, and we'll continue to leverage opportunities to optimize spending. The U.S. launch of Amtagvi, as well as the sales of Proleukin used in conjunction with the Amtagvi treatment regimen, are expected to drive significant revenue in the second half of 2024 and into 2025 and beyond. As a reminder, revenue recognition for Amtagvi occurs upon infusion like other cell therapies, so we expect to begin recognizing and reporting significant revenue in the second quarter of this year. For additional information, please see this afternoon's press release and our Form 10-Q to be filed later today. I will now hand the call to Friedrich, our Chief Medical Officer, to discuss our clinical pipeline.

Thank you, Jean-Marc. I am pleased to speak today about our key clinical pipeline highlights in solid tumors, which, as you all know, represent more than 90% of all diagnosed cancers in the U.S. One of our key priorities is expanding the label for Amtagvi to address the need of patients with advanced melanoma in the frontline treatment setting. Our registrational Phase III trial, TILVANCE-301 is well underway and on track to support accelerated and full approval of Amtagvi in combination with pembrolizumab in frontline advanced melanoma, as well as regular approval of Amtagvi in post anti-PD-1 melanoma. Global site activation and patient enrollment continue with strong momentum in the U.S., Europe, Australia, Canada, and additional countries. Our frontline advanced melanoma strategy is supported by Cohort 1A in our IOV-COM-202 trial in solid tumors and previously published data on TIL therapy in the pre-immune checkpoint inhibitor era. We look forward to an oral presentation of updated clinical data from Cohort 1A, which continues to strongly support our frontline development plans at the American Society of Clinical Oncology, or ASCO, Annual Meeting on May 31, 2024. Shifting to our program in non-small cell lung cancer. We reported positive updates for our single-arm registrational Phase II trial, IOV-LUN-202, in post anti-PD-1 non-small cell lung cancer. We resumed enrollment for new patients within a very short time after the U.S. FDA lifted our partial clinical trial hold in the first quarter. IOV-LUN-202 includes clinical sites in the U.S., Canada, and Europe, with plans to include additional regions with a strong track record for enrollment in lung cancer studies over the next few months. Enrollment has restarted with high demand, which is driven by encouraging data and further augmented by excitement from the approval of Amtagvi. We expect the registrational cohorts to be fully enrolled in 2025. Current data from IOV-LUN-202 and the FDA interactions regarding our regulatory pathway continue to be positive and support our confidence in the opportunity for TIL cell therapy in lung cancer. The FDA has provided positive regulatory feedback on the proposed potency matrix for lifileucel in non-small cell lung cancer during a recent Type B meeting, and as previously announced, that the design of the single-arm IOV-LUN-202 trial may be acceptable for approval of lifileucel post anti-PD-1 on small cell lung cancer. In other tumor types, we are starting a Phase II trial of lifileucel post anti-PD-1 endometrial cancer, which is a significant opportunity for TIL cell therapy. Our Phase II trial will include patients with advanced endometrial cancer who progressed after platinum-based chemotherapy and anti-PD-1 therapy regardless of mismatch repair status on the tumor. Our rationale is supported by the TIL mechanism of action, which may benefit both patient populations, as well as preclinical and manufacturing success data that we plan to report later this year. There is a significant unmet medical need and no currently approved treatment options for the vast majority of patients with endometrial cancer in the post anti-PD-1 treatment setting. Given this unmet medical need and the enthusiasm we've received from gynecological oncologists, we expect to enroll quickly, and we look forward to seeing the first data soon. As the leader in TIL cell therapy, Iovance is at the forefront of next-generation approaches that have the potential to address unmet needs for patients and solidify our long-term leadership in the space. We reached an important milestone for our genetically modified TIL cell therapy, IOV-4001, in the first-in-human GM1-201 trial in previously treated advanced melanoma or non-small cell lung cancer patients. The Phase I safety portion concluded successfully, and we are progressing into the multi-center Phase II efficacy stage of the trial. IOV-4001 utilizes the TALEN technology licensed from Cellectis to inactivate PD-1 during the TIL manufacturing process. We also have options to continue to develop other investigational gene-edited TIL cell therapies with multiple knockout targets to potentially improve efficacy. We are also making great strides to advance additional next-generation programs towards the clinic. In the third quarter of 2024, we plan to submit an investigational new drug application or IND for a Phase I/II clinical trial of IOV-3001, the modified interleukin-2 or IL-2 fusion protein. At ASCO 2024, a poster will highlight preclinical data that support the potential for improved safety with robust effector T cell expansion with IOV-3001. Lastly, on today's call, we are introducing IOV-5001, a new next-generation program. IOV-5001 is a genetically engineered TIL cell therapy with inducible and tethered IL-12. The addition of IL-12 has augmented TIL antitumor activity in vitro. IOV-5001 also builds on the improved efficacy of a prior generation IL-12 TIL therapy that was observed in a clinical trial at the National Cancer Institute, or NCI. IOV-5001 is currently in IND-enabling studies. We plan to discuss IOV-5001 with the FDA at an INTERACT meeting in the third quarter of 2024 and anticipate an IND submission in early 2025. I'm happy to address questions about these programs and additional trials during the Q&A session. I'll now turn the call over to the operator to begin the question-and-answer session.

And our first question comes from Michael Yee with Jefferies.

Congrats on all the progress. We have maybe a two-part question. You gave some really great metrics around the indications of interest in the enrollment numbers. Can you maybe just describe sort of the journey of time from enrolling and then getting reimbursed and then I think sort of the 34 days then inbound to get treated? I'm just trying to think about how many of the 100 people who have enrolled are likely to get treated and dosed in this quarter and thinking about the consensus number and then thinking about how many of those would get treated in the third quarter. Maybe just talk a little bit about the journey and how you think about those 100 patients getting treated.

Yes, Michael, I can provide some insight on that. Currently, the patients being enrolled could potentially be treated in the second quarter or early in the third quarter. It takes some time to complete the financial clearance for the patients. After they come in, they undergo resection, and we are currently targeting 34 days from the start of manufacturing through to the completion of quality control testing. Following this process, the patient is lymphodepleted and infused. This process differs from the clinical trial, where we were able to move more quickly since many patients weren't on bridging therapy. Now, however, most of them are receiving bridging therapy, which necessitates this adjusted approach with the commercial product.

Okay. So just to be clear, patients have been treated in April and then some of those patients, as you are going through, would be treated in May and June as part of those 100.

Correct in July and so on.

And our next question coming from the line of Andrea Tan with Goldman Sachs.

Maybe a follow-up there. Just wondering if you're able to provide some numbers around those comments. Just of the 100 plus that have been enrolled, how many specifically have had their tumor resected thus far? And how many have received an infusion?

Yes. We can't give you the detail as we would actually have revenues at that point. But what we can tell you is that right now many of those patients have been resected. We're moving through the process with them. I want to stress the importance of the patients that have enrolled. Some of them will be infused obviously over that large time period that we just mentioned with Mike's question. We also have a few dropouts in OS and stuff like that to account for as well. So it's very difficult for us to predict all that stuff. When we finally report revenues, we'll be able to say a little bit more about how that actually played out the transition from enrolled numbers to revenues.

Got it. And the nature of the dropout, if you're able to share a little bit more there?

Most of the time, the dropouts are due to patient health issues. Unfortunately, some patients pass away while waiting for therapy, and this has happened to us. It's a tragic outcome related to the disease stage these patients are in. Typically, the issue arises when a patient's health deteriorates, leading them to hospice care or resulting in their passing before we can fully manufacture and test Amtagvi for them. This is the main reason behind our dropout rate.

And our next question coming from the line of Peter Lawson with Barclays.

Could you provide more details about the over 100 patients enrolled for TIL therapy? Specifically, what percentage have insurance and how many ATCs have actually resected patients?

Peter, it's Jim Ziegler here. Virtually, all of the 100-plus patients have insurance or have cash, so that's not been an issue right now. And by definition, enrolled patients basically means there's the treatment decision followed soon thereafter by commercial payer prior authorization and the scheduled surgery.

Got you. And then the ATCs that have actually resected, the patient number?

Yes. We can't tell you exactly that, Peter, right now, but it's a substantial number. Let's call it that. It's increasing daily or at least weekly, and it's getting up to the point where hopefully all or almost all of them will resect the patient in the not-too-distant future.

And our next question coming from the line of Tyler Van Buren with TD Cowen.

Congrats on the progress. Shockingly, I have another question regarding the launch. Just regarding the dropouts for enrolled patients that you mentioned, can you discuss what the attrition rate for enrolled patients has looked like so far based upon the dropouts or manufacturing success and then how that attrition rate might differ for patients that are in screening as we think about the 60 patients you mentioned?

Yes. Right now, Tyler, it's in line with our expectations. There's been a few dropouts as well as manufacturing aspects, not many. And based on our experience, we feel like it's playing out the way we had expected. We're only going to get better at this. The patients that are dropping out sometimes were the ones waiting for Amtagvi therapy. And obviously, that will be less of an issue as we go forward with the launch here. So I can't give you any quantitative numbers on that right now. Obviously, it's very early for this, but it's in line with what we anticipated and we're able to handle.

And our next question coming from the line of Yanan Zhu with Wells Fargo Securities.

Congratulations on the progress. I have a question for Fred regarding dropouts. Can you provide insight into whether we might explore historical clinical trial data to determine the percentage of patients who couldn't wait for the manufacturing and insurance approval process? Also, how evenly are the more than 100 enrolled patients distributed across the 40-plus centers? Lastly, I believe Jim mentioned that month-over-month growth in the number of enrolled patients is still expected going forward. I want to confirm that. If that's the case, in addition to the increase driven by more ATCs, could it also be partly due to an increased number of patients from already started ATCs?

The dropout rate comparison between the clinical trial and commercial aspects is quite different. In the clinical trial, financial clearance issues did not exist, and patients were moved quickly to therapy. The trial involved a very advanced patient population who were not receiving any bridging. This means we couldn't provide that support because of the trial constraints. Now, in a clinical setting where we have financial clearance, the process takes slightly longer but we are making progress. Currently, we are bridging many patients, and they are generally not as far along in their treatment journey compared to those in the clinical trial. Therefore, I don't think it's appropriate to compare the dropout rates between the two situations. As for how many patients cannot wait for treatment, I don't have a precise estimate at this time. We'll have to observe how the launch progresses to understand this better, especially as we track the dropout rate. Finally, concerning month-over-month growth, Jim pointed out that it could be influenced by the number of patients. Our centers are currently enrolling at high capacity, and analysts gathering information from these centers are reporting their enrollment numbers. They suggest that we might see increases in enrollment over the coming months. Thus, even without adding ATCs, we anticipate an increase in patient numbers.

Those are great color. Could you, sorry, touch on the second point about how evenly are the currently enrolled distributed across the centers?

We missed that one. Jim, do you want to get that one?

Sure. I can take that. Yanan, it's Jim here. Like other cell therapy launches and, in fact, oncology launches, most launches don't have even distribution of adoption across the centers. And what we will expect over time is all centers will gain experience and increase utilization within each of the centers, but it is not normally distributed for any of the other launches out there.

And our next question coming from the line of Colleen Kusy with Baird.

Can you comment on if there's any anecdotal feedback on the experience with IL-2 so far and how often that would come up as a percentage of reason not to pursue a tumor with Amtagvi? And then can you also comment on the profile of the average patient in process right now? I think you mentioned there have been patient deaths in this waiting period. Are you getting a lot of later line patients? Or are you getting some earlier line patients too?

This is Brian Gastman. I'm happy to answer that. We have not seen really any pushback for the use of IL-2. And in fact, some of the cell therapists who are getting involved in this beyond the medical oncologists who start with the patients have actually commented on how IL-2 is not a rate-limiting issue for them and even mentioned to me personally how it's self-limiting, reversible toxicities. That has absolutely not been an issue. And I would add that one thing that we've noted was our education to these authorized treatment centers has paid off. The patient selection overall has been pretty good, if I have to say for myself, not knowing what we would have expected. The actual drop-off because of progression is rather low. What happens is it's rare enough that it raises an eyebrow, but it's not a very common event at all. It's just something that happened at least once. But it's definitely not more, maybe even less than what we were expecting.

Great. And one follow-up, if I can. You mentioned that about 60 patients are in screening right now. What are some common reasons a patient might fail that screening and not pursue treatment?

Patients must go through financial clearance, and they may not qualify for various reasons. This could be due to not meeting label requirements or not having melanoma. Additionally, there are a number of factors that could disqualify patients based on medical screenings required for a prescription.

Yes. Just like the enrolled patients that we currently have, we expect a high conversion because these treating physicians understand the unmet need and are choosing, in as much as possible, the right patients balancing the unmet need.

Congrats on the progress.

And our next question coming from the line of Asthika Goonewardene from Truist.

I want to congratulate you on the quarter and the update. I know this question has been asked in different ways, but let me phrase it like this. Of the 100 patients who have been enrolled, can you tell us how many have been resected so far?

Not yet, Asthika, but there is a very large number that have been resected. I can tell you that.

Got it. Okay. And then, Fred, when talking about getting financial clearance, can you give us some sort of an idea from enrollment, how many days does it take on average to get financial clearance? I understand it's very early in the launch, but so far, what are you seeing?

It is very early in the launch, and it's very consistent with what we've seen with other cell therapy launches. Prior authorizations take about three days, and single-case agreements vary. It ranges anywhere between two to six weeks, with an average of three to four.

Got it. Okay. And then lastly, about how many, on average, vials of IL-2 do you anticipate being used per patient? I know it could be up to 18. But what are you seeing so far in the patients that have been dosed?

I don't have anything new to add there except that I can say, in the trial, the average was, for the medium vial, I think, whatever it was, was 16, and I would expect something similar in real practice. But I don't think I would want to quote a stat to you right now. It's close to 18, thought, per patient, and that's the way it should be.

Our next question coming from the line of Joe Catanzaro with Piper Sandler.

Appreciate you taking my questions here. Maybe similarly, a sort of same question in a different vein as we think about the cadence and rate of the 100 patients ultimately being infused. At the end of February, you said there were about 20 patients in progress. We're now about 2 months past that, I guess. So can you say or give any sort of additional comments on how many of those 20 patients were ultimately infused? And then my second question is on the early sort of experience or feedback you're seeing on the use of bridging therapy or physicians using that and then stopping once they receive Amtagvi and ready to go. Are they sort of receiving the cell shipment and sort of continuing bridging therapy for a prolonged period of time if the patient is benefiting and tolerating that?

Yes, Joe, I can address the first part, and then Brian will handle the second part. From the initial 20 patients, the current number has now increased to over 160. I'm not certain about the exact count of patients who progressed through the treatment, but I believe that the majority likely did move forward in the process. However, I cannot confirm whether all of them have been infused, as we do not have that information yet. Importantly, what we reported on February 28—that we had 10 and 20 patients—has now risen to over 100 and more than 160, showing a significant increase. Brian, can you provide some insights into the bridging therapy?

Yes. I think it's important to note that we don't have clear line of sight on every patient. The way they get entered into our system, there's a certain level of assumption that the physician has a background in treating a patient. Where we get the information is when a peer to peer or a response and when that happens, we get really good engagement with the sites, the physicians treating the patients. We offer them obviously scientific exchange when needed. And that's where we found out about maybe bridging patients. Interestingly, sometimes the bridging therapy is literally done not because the patient is progressing or can't make it to the therapy. But sometimes the patients themselves want to sort of dictate when the therapy is being given. So bridging therapy really affords a lot of latitude for these physicians. But how often it's actually being used, we probably won't know until some real-world evidence comes out.

And our next question coming from the line of Reni Benjamin with JMP Securities.

Congratulations on the progress. I guess I'm kind of curious about whether there's the potential for a backlog at the manufacturing side and how you might handle that. With the number of patients and the surgeries that are happening, how these samples kind of wait, I guess, before they're getting processed, how many samples can you handle in a month? That would be my first question. And then second, just switching gears to the Type B meeting you had for non-small cell lung cancer. It looks like you got positive feedback on the proposed potency matrix. And I thought we were kind of all done with discussions regarding potency matrix. So I'd love to get some idea as to what's happening there.

Are you able to comment on the manufacturing question?

I can address that. Currently, we have enough capacity at our manufacturing facility and with our contract manufacturer for the launch. The capacity is adequate to meet the demand from commercial Amtagvi patients as well as the clinical trial, and we are continuing to hire additional staff because we expect demand to grow throughout the remainder of 2024 and beyond. I hope that answers your question. The capacity we have is certainly sufficient for the demand we're experiencing.

On the Type B question, is Raj available? Raj, can you take that question? We may have a breakdown here in the audio. I'll handle it. We need to have regulatory meetings with the FDA for each indication regarding potency assays at this time. Ultimately, we might adopt a platform approach. I'm sure you've noticed Peter Marks discussing platforms recently. However, currently, we are presenting each of our indications to the FDA and discussing the specifics of the potency assay for that indication. We recently achieved this successfully for non-small cell lung, which is a crucial step towards a BLA submission for lifileucel targeting non-small cell lung cancer.

As we consider the timing, Fred, can we at least assume that since it took a considerable amount of time to reach an agreement and ensure everyone is aligned, we can say we are about 80% or 90% there with non-small cell lung cancer? Should we expect the process to move more quickly now, or are we starting from scratch with each indication?

No, we're definitely not starting over. What we're doing now is following what we believe is the correct approach. We're engaging with the FDA at an appropriate stage in our clinical development program for non-small cell lung cancer. We are still enrolling participants for that study. We now have sufficient data from enough patients to present what we consider a viable potency matrix proposal based on data from the pivotal patients, which is crucial, especially since we are early enough in the study to make adjustments if they have questions or suggestions for changes. This is different from our previous experience with melanoma, where most of that discussion happened after the study was already concluded. We believe that our current strategy for developing polyclonal T cell therapies is the right approach, and it should accelerate our process so that once we complete the non-small cell lung study, we can directly move to a pre-BLA meeting and then to submission.

And our last question are coming from the line Ben Burnett with Stifel.

Could you discuss the patient flow within the hospital? Are you experiencing any bottlenecks? Have there been any lessons learned regarding coordinating efficiently with the surgeon or similar matters?

Yes. Actually, I would say the opposite. We've really seen tremendous enthusiasm from the surgeon all the way through to the cell therapists and the nurses that treat these patients. We've seen hospitals bend over backwards to find operating room time, space in the hospital. We really haven't experienced any of the potential bottlenecking even as we increase. Most of the things that we encounter are really just sort of small questions on details but not the big issues like having a time or place to treat a patient.

Okay. That's excellent. And if you could also just comment on just the quality of tumor sample coming in for manufacturing, how is like kind of the specifications around those tumor samples compared to like what you saw in clinical trials?

I can take that or, Igor, if you would like.

Happy to. Good question. So far, the experience has been very consistent with our clinical experience, including the size and quality of the tumor samples for manufacturing.

And ladies and gentlemen, that's all the time we have for our Q&A session. I will now turn the call back over to Dr. Fred Vogt for any closing remarks.

Thank you again for joining Iovance Biotherapeutics' First Quarter 2024 Financial Results and Corporate Updates Conference Call. As we've shared on this call, we are very pleased with the strength of the Amtagvi launch and excited to see accelerated growth throughout the rest of 2024. Thank you to those in the patient health care and advocacy communities, our partners, and our exceptional Iovance team. I would also like to thank our shareholders and covering analysts for their support. We look forward to presenting data at ASCO on lifileucel in frontline melanoma, and we'll host an analyst and investor event on May 31. Please feel free to reach out to our Investor Relations team for follow-up. Thank you.

Ladies and gentlemen, that does conclude our conference call for today. Thank you for your participation. You may now disconnect.