Welcome to the Iovance Biotherapeutics Third Quarter and Year-to-Date 2025 Conference Call. My name is Daniel, and I will be your operator for today's call. [Operator Instructions] Please note that this conference call is being recorded. I will now turn the call over to Sara Pellegrino, Senior Vice President, Investor Relations and Corporate Communications at Iovance. Sara, you may begin.

Thank you, operator. Good morning, and welcome to the Iovance webcast to discuss our business achievements, pipeline milestones and third quarter 2025 results. Members of our executive leadership team speaking on today's call include Dr. Fred Vogt, Interim CEO and President; Corleen Roche, Chief Financial Officer; Dan Kirby, Chief Commercial Officer; Dr. Igor Bilinsky, Chief Operating Officer; and Dr. Friedrich Finckenstein, Chief Medical Officer. During the question-and-answer session, we will also welcome Dr. Raj Puri and Mark Theoret from our Regulatory Affairs executive leadership team; and Dr. Brian Gastman, Executive Vice President of Translational Medicine and Research. This morning, we issued a press release that is available on our corporate website at iovance.com. I would like to remind everyone that this conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans and transactions, revenue and revenue guidance, commercial activities, clinical trials and results, regulatory approvals and interactions, plans and strategies, research and preclinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interactions, restructuring, licenses and collaborations, cash position and expense guidance and future updates. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward-looking statements. I will now like to turn the call over to Fred.

Thank you, Sara. I will start by sharing our continued progress to increase revenue and margins, advance our pipeline, reduce expenses and improve operational execution. Third quarter revenue grew 13% over the prior quarter and notably, gross margin improved and was 43% following the initial results of our strategic restructuring and cost optimization. More improvements are coming, including today's announcement of our centralization of manufacturing at our internal manufacturing facility. Our highest priority is to accelerate revenue growth to increase Amtagvi adoption across our network of academic and community authorized treatment centers or ATCs. We have expanded to include new academic ATCs and multiple community ATCs. Initial patients are being treated in the community and are generally earlier in their melanoma treatment journey. As we educate community oncologists across our ATCs, including the major academic centers, we are seeing earlier and more frequent patient referrals to drive growth. Real-world data showed response rates of 60% in the second-line treatment setting, which has provided a strong foundation to amplify our compelling story to the melanoma community for the power of TIL therapy in melanoma. We are on track to achieve our revenue guidance range of $250 million to $300 million for the full year 2025. With robust current demand, we expect a strong fourth quarter for Amtagvi alongside increasing Proleukin sales as we saw in late 2024. We continue to project Amtagvi peak sales of more than $1 billion in the U.S. and melanoma with larger additional opportunities in international markets and in future indications. For example, our interim clinical data in previously treated non-squamous non-small cell lung cancer showed a best-in-class -- apologies for technical difficulty here for one second. For the -- for example, our interim clinical data in previously treated non-squamous non-small lung cancer showed a best-in-class profile…

Thanks, Fred. Good morning, everyone. During my first quarter as Chief Financial Officer, I want to emphasize our focus on driving the company towards sustained profitability. Our strategy included prioritizing top line growth, significantly improving margin and controlling costs with a disciplined approach. In the third quarter, our top line revenue remained strong. Total product revenue increased approximately 13% over the prior quarter to about $68 million. This included Amtagvi sales of approximately $58 million and global Proleukin revenue of nearly $10 million. As expected and consistent with prior quarters, overall gross to net was less than 2% and is expected to remain minimal. As Fred mentioned, we are on track to achieve our revenue guidance in the first full calendar year of Amtagvi sales. Next, I am pleased to highlight initial improvements in expenses and gross margin from the corporate restructuring and continued cost optimization initiatives implemented in the third quarter. We reduced total costs and expenses by approximately 10% over the prior quarter, excluding restructuring charges of approximately $5 million. We lowered cost of sales by approximately 21% over the prior quarter, resulting in improved gross margin of approximately 43%. Importantly, costs associated with patient drop-off and manufacturing results continue to decline as our revenue continues to grow. Gross margin will improve over time as we accrue benefits from our recent restructuring, implement additional cost savings initiatives and centralize manufacturing at our internal facility. Our cash position of approximately $307 million as of September 30 was bolstered by expense reductions and is expected to fund operations into the second quarter of 2027. I will now turn the call to Dan Kirby, our Chief Commercial Officer.

Thanks, Corleen. Our ultimate goal is to establish Amtagvi as the preferred option for all eligible patients. Patients deserve a onetime cell therapy with curative intent, and we are steadfast in delivering on that promise. My conversations with patients and caregivers remind us of the commitment to the Iovance mission, pioneering a new treatment paradigm for patients with solid tumor cancers. At the recent Melanoma Research Foundation Gala in Denver, Iovance received the Corporate Leadership Award in recognition of our efforts to advance care for melanoma patients. In my first 8 months at Iovance, we have made notable progress to lay the foundation for revenue growth by driving adoption across our ATCs. I'll highlight 3 key areas of focus. First, new ATCs are driving growth. In the third quarter, we added community ATCs alongside new high-volume academic ATCs. These new ATCs contributed to the highest number of patient starts with better capture in the third quarter. Our first community ATCs are beginning to treat patients with Amtagvi in this setting. New ATCs continue to come online and will drive further growth in the fourth quarter and beyond. Second, penetrating the community market is key to unlocking Amtagvi's tremendous potential as we increase the frequency, speed and efficiency of community referrals to ATCs. Health care professional and patient-focused campaigns are having a positive impact. Under our specialty pharmacy agreement with Biologics by McKesson, patients have broader access to Amtagvi. Hospitals now have flexibility to obtain Amtagvi directly or through a specialty pharmacy, giving their finance teams confidence to place more orders. Our third focus area is to drive earlier treatment with Amtagvi. This will increase penetration in our academic centers. We are educating medical oncologists on the advantages of cell treatment with Amtagvi when it has the greatest benefit. Earlier shifts…

Thank you, Dan. I will provide a brief manufacturing update. We have streamlined our manufacturing organization while reducing costs and improving our manufacturing success rate as reflected in our third quarter gross margin. Importantly, we are finalizing an expansion at our internal facility, the Iovance Cell Therapy Center, or iCTC, that will enable us to support anticipated demand without the need for a contract manufacturer. All Amtagvi and clinical manufacturing will transition to iCTC in early 2026 to maximize capacity utilization, lower cost of sales and drive future gross margin growth. We will complete a key step in this facility expansion during routine annual maintenance around the end of this year. During this time, our contract manufacturer will provide continued access for patients to meet demand before we transition all manufacturing to iCTC. We will also boost capacity immediately prior and following the maintenance period to provide additional manufacturing slots for patients, allowing smooth supply through the next 2 quarters. Bringing all manufacturing internally will be an important milestone for us as a company. In addition to the cost benefits, we will maintain uninterrupted supply during routine maintenance in the future using internal capabilities. We can also scale up within the existing facility to support future markets globally and indications, including lung cancer. I will now pass the call to Friedrich.

Earlier this week, we reported interim data from our registrational IOV-LUN-202 clinical trial of Lifileucel. The data demonstrated a potentially best-in-class clinical profile and meaningful improvement over current standard of care in previously treated patients with non-squamous non-small cell lung cancer. Following onetime treatment with Lifileucel monotherapy, the objective response rate was an impressive 26%. An objective response was observed in 10 out of 39 patients, which included 2 complete responses. The disease control rate was 72%, showing a meaningful benefit for many patients with stable disease. Importantly, median duration of response was not reached at more than 25 months of follow-up, which is unprecedented durability for non-small cell lung cancer therapy in the post-chemo and immune checkpoint inhibitor setting. Standard of care docetaxel monotherapy recently showed an objective response rate of only 13% and a median duration of response of only 5.6 months without any complete responses in the same patient population. We are on track to quickly complete enrollment of approximately 80 patients in 2026. We have seen a strong increase in enrollment this year, driven by the positive reception of the efficacy data among trial investigators. In addition to the 39 patients in the data set, a double-digit number of patients are awaiting or have recently received TIL infusions and more patients have entered the trial as of today. We plan to share more data from LUN-202 at a medical meeting next year, including a meaningful number of additional patients and longer follow-up. We also look forward to advancing towards a supplemental biologic license application for Lifileucel in non-squamous non-small cell lung cancer and a potential launch in the second half of 2027. We also continue to make progress across the rest of our pipeline, which I am happy to discuss during the Q&A session. Thank you.

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

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

Thanks, Andrew. I can start and then maybe Friedrich can chime in here. I don't -- we don't expect any degradation in the efficacy signal. We're getting very good within the LUN-202 trial at making sure our investigators identify the right patients for the trial. And we are obviously going to be cutting the data with longer and longer follow-ups. And with ongoing responders, as you can see in the swimmers plot from that data cut, we would expect to see that durability improve even beyond what we have today. I'll let Friedrich comment a little bit on the details of how we think that study is going to play out, but that's the big picture view.

Yes, I agree with Fred. Not much to add there. I think the study now has reached that phase where folks know what they're doing. They're familiar with the therapy. They know how to identify patients. We are able to communicate best practices. So I think this is all in a very stable place. What is noticeable is that we saw a true uptick in enrollment, which is really driven by the positive data that we were able to share with the investigators lately. That's also fairly typical. It's kind of an inflection point where then things just take off because folks see and believe in the therapy and things are working really well.

Our next question comes from Yanan Zhu with Wells Fargo.

Congrats on the quarter. Just a quick one on the lung cancer. Can you talk about when did you touch base with FDA regarding the path and the regulatory path? And you did mention 80 patients. I wanted to hear your confidence that 80 patients is enough for the lung cancer filing. Then on Amtagvi in melanoma, can you talk about infusion growth into fourth quarter and into 2026, your confidence for inflection point in the patient infused? And lastly, sorry, if I may, on the improved gross margin, great to see that result. Can you comment on how much of it is coming from patient dropout and manufacturing success rate improvements versus how much is coming from cost reduction measures?

Thanks, Yanan. Why don't I start on the FDA point and then Raj Puri will jump in, and I'll ask Dan and Corleen to help out with the Amtagvi, the inflection point as well as the gross margin questions here. We've engaged heavily with FDA on the LUN-202 trial and gotten guidance from them, feedback on the trial design, patient population, CMC, things like the potency assay. We feel very comfortable that we're on the right track here. Obviously, engagement with FDA is a continuous process during the trial. As I'm sure investors know, we have to engage frequently and we do engage frequently. A lot of it doesn't get talked about. So we'll continue to do that on this trial, but we're very comfortable with where we stand right now in the trial design and what we need to do to get a supplemental BLA submitted on time. On the sample size for the patient -- for the 80 patients, we pointed out during a lot of our calls earlier this week as well as during our prepared remarks here that we think 80 patients will be sufficient based on the precedent of Amtagvi with 73 patients which led to the approvals on label in melanoma as well as a lot of recent FDA meeting the last couple of months, FDA approvals in non-small cell lung. So I'll let Raj and maybe Mark comment on that on what they've seen with the FDA and why they think that's reasonable.

In addition to what Fred said that we in continuous interaction with the FDA, we plan to apply for many different priority designations such as Fast Track designation, RMAT designation, et cetera. And as Fred mentioned that 80 patients also based on the 73 melanoma patients that we got Amtagvi approval on. And recently, Mark will elaborate further that the FDA has approved about 4 non-small cell lung cancer trials based on accelerated approval of patients list to 70 to 80 patients.

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

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

Thank you. And thanks, Fred, and thanks, Yanan, for the question. First, the answer is yes, we expect continued growth in the fourth quarter and beyond into 2026. The reasons behind that are -- I'm going to separate this from academic and community. In the academic setting, we've launched field efforts, including a disease awareness campaign in Q3 to educate medical oncologists for earlier referral into those centers. We're seeing some results from that right now that will continue moving forward. We also are launching in the academic setting initiatives to increase penetration, which would have to do with addressing certain patient types that we haven't been able to capture such as BRAF mutations I mentioned, where we have opportunities to get tissue earlier. So we do see growth in the academic setting. Moving to community. I mentioned that we're onboarding now and we've started to treat at the first community sites. We have several large ones that are coming on in this quarter that will drive significant growth in Q4 and beyond in 2026, and that also sets the table for...

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

Our next question comes from Salim Syed with Mizuho.

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

Yes, Salim, we reiterated our guidance range of $250 million to $300 million, which is a pretty narrow range to begin with. It's our first full calendar year on the market, as you know, and we're on track right now towards that guidance. Fourth quarter, as Dan was just mentioning a minute ago, we have a large influx of new ATCs. We've got Proleukin sales to contend with, which we think will be very strong in the quarter, especially based on fourth quarter last year. You can go back and look at those numbers. And we have got this ATC growth both in the community and in the academic setting. So I think at this point, we're just comfortable with the guide that we put out, $250 million to $300 million, and we'll be in that range, and that's what we're comfortable saying right now.

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

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

Yes. Nick, we're not going to -- we're not talking about infusions anymore. We're just going to use revenue going forward, as you can see from our press release. We think that's the ultimate story here, and we hope investors appreciate that we're focusing on the dollars, and that's what matters at the end of the day. On the iCTC maintenance, I'll pass it to Igor for that question. I think he had covered it in his prepared remarks, maybe you can highlight it again, Igor.

Yes, of course. Thanks for the question, Nick. So as I mentioned, as part of the routine maintenance this year, we'll complete the expansion part of the facility that's important for centralizing manufacturing at iCTC and also kind of continue providing uninterrupted capacity from iCTC during future maintenance periods. And this year, we've learned from our experience in Q1 2025. So we made several improvements. We will boost manufacturing capacity immediately and prior to the iCTC maintenance that will provide additional manufacturing slots for patients, and that will allow essentially smooth supply through the next 2 quarters.

Our next question comes from David Dai with UBS.

A couple of questions from me. So just on the ATC ramp, you're seeing early community initiatives in there. I'm just curious in terms of what are the timeline for the community activation to actually see patients treated. That's the first question. And the second question is just around the margin improvement. You said you're planning to have more margin improvement over the next few quarters. So I'm just curious what is sort of like the margin we should be expecting over the next quarters, essentially, one should be expecting the plateauing of the margin over time?

So I'll take the ATC one first and look at the ramp for that. So you mentioned specifically community. Our first community centers are starting to treat now. Typically, with centers, they treat a few patients, they make sure the insurance goes through, they get comfortable with it and they start ramping patients after that. That is expected to continue with our community ones that are just starting to treat now. The newer ones coming on with the volume will start slow in -- with a few patients in there for it, but then will start to ramp up. The key with the community is that the referral patterns are already there to get those patients in earlier. So as we discuss with those larger entities opening them, we also have robust discussions regarding referral patterns and patients lining up. So we will see a ramp there a little faster than you'll see with the academics, but it should be coming over in the next quarter and 2, and then we'll get to full peak probably by mid next year.

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

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

Our next question comes from Colleen Kusy with Baird.

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

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

And our final question comes from Reni Benjamin with Citizens.

I'm sorry, I jumped on the call a little late. So you may have answered this already, so just indulge me. I'd like to understand a little bit more about the global expansion that you highlighted. How do you envision these programs or the expansion without a partner? Should we really be -- should we be thinking about any sort of a meaningful contribution in terms of revenues going forward or at least in 2026? Or is this something that goes out much further? And just a follow-up question regarding both TILVANCE and the LUN-202 study. It seems like enrollment will slow at least from the 202 study. Can you just give us a better sense as to how enrollment is progressing in each of those studies? That would be great.

Yes, Ren. So first, on the global expansion, we're not thinking right now really about partnership. TIL technology and the science of delivering TILs to patients, the medicine behind it is complicated. We're not really sure there's a partner out there that would give us any kind of advantage. And we're always really cautious about asset dilution and giving anybody rights to anything that we do because we think that TILs are going to be extremely powerful in the future, and we would like to own all of that. That said, we may work with distributors in certain markets. We may work with people that can help enter markets for us. We tend to staff very light and lean in those markets while we wait for revenue to appear. In 2026, I don't expect a significant amount of revenue from those markets. However, we'll start to see that business grow. And then over time, I think it will become a major component of our business in the future. And since Dan heads those teams, I'll let him give some color and maybe just highlight the markets that we're going to go back into, include the U.K. and we're going to be entering for the first time in the U.K. and Australia and other places where there's a significant number of melanoma patients in need.

Sure. And so Reni, one of the things we've always said about our global expansion, if you look at the history of cell therapies globally, this has been more of a long-term strategy to produce revenue in 2027 and beyond, but you needed to get the filing and approvals in place because reimbursement does take a while in those regions, you want to make sure you do it in the proper sequence. So where we are right now with it, we are ramping up in Canada with our first ATC. We have pending approvals in the U.K. as well as Australia. We're in discussion right now in the U.K. about getting an NHS support on which ATCs will go up and running there. So we're getting the process in place as well as within Switzerland and then refiling in the EU. So this has been a long-term strategy with it and something that we will see, if you look at Kite, who did a great job with Yescarta globally, it took them several years from the approvals to get revenue in there. So we follow that model, knowing it would take 2027 would be our first year to have any appreciable revenues. Not saying we won't get any next year, but really appreciable revenues in 2027 from ex U.S.

And then on the enrollment question, I'll focus on LUN-202, Reni, because TILVANCE, we really haven't said anything publicly about the enrollment there beyond that it's going well, and we think that's on track right now. But on LUN-202, enrollment has really picked up lately. And if you heard on the calls earlier this week, we have double-digit patients right now waiting for infusions, and we have a lot of activity there. I'll let Friedrich comment in a second here, but we think we can easily hit the time line that we gave for the launch of Lifileucel in non-small cell lung in the second half of 2027 based on our current enrollment timings in the LUN-202 trial. Friedrich, do you want to add to that?

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

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

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

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

Thank you again for joining the Iovance Biotherapeutics Third Quarter 2025 Conference Call. We look forward to providing future updates on our commercial launch and pipeline as well as our cost optimization initiatives to drive towards profitability. We are motivated by the stories we continue to hear about the patients who benefit from Iovance TIL cell therapies. I'm confident that Iovance will remain the global leader in innovating, developing and delivering current and future generations of TIL cell therapies for patients with cancer. As always, we are thankful to our patients, the health care and advocacy communities, our partners and our exceptional Iovance team. I would also like to thank our dedicated shareholders and covering analysts for their support. Thank you.

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