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. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. Please note that this conference call is being recorded. I will now turn the call over to Sarah Pellegrino, Senior Vice President of Investor Relations and Corporate Communications at IOVance. Sarah, 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 Balinski, Chief Operating Officer, and Dr. Frederick Finkenstein, Chief Medical Officer. During the question and answer session, we will also welcome Drs. Raj Puri and Mark Suray from our Regulatory Affairs Executive Leadership Team, and Dr. Brian Gassman, 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 interaction, 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 Sarah. We have no margins, advance our pipeline, reduce expenses and improve operational execution and notably gross margin improved and was 43% following the initial results of our strategic restructuring more improvements are coming including today's announcement of our centralization of manufacturing at our internal manufacturing facility who academic ATC's and multiple community ATC initial patients are being treated in the community or generally earlier in their melanoma treatment journey as we educate community oncologists across our ATC's including the major academic centers we are seeing earlier more frequent patient referrals that drive growth with 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 pill therapy and melanoma to achieve our revenue guidance range of 250 to 300 million dollars for the full year of 2025 with robust current demand we expect a strong alongside increasing proleukin sales, as we saw in late 2020. We continue to project amtagomy peak sales of more than $1 billion in the U.S. in 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, for example, our interim clinical data in previously treated non-cellaneous non-cellular lung cancer showed a best-in-class profile durability compared to standard of care in this population including an objective response and immediate duration of response not reached at more than 25 months of follow-up there's a significant market opportunity in this lung cancer indication which is about seven times greater than our current advanced melanoma indication we expect to quickly complete enrollment in our lung 202 registrational trial in 2026 with approximately 80 patients this This sample size will support an accelerated approval given the unmet need in non-small cell lung cancer, precedent of the antagonist approval in 73 melanoma patients, and recent accelerated approvals based on 70 to 80 patients from the defined non-small cell lung cancer population. The U.S. FDA previously provided positive feedback on our trial design, which aligns with FDA guidance for single-arm trials to support accelerated approvals for single agents in conditions with unmet medical need we look forward to advancing toward a supplemental biologics license application in non-squamous non-small cell lung cancer and a potential launch in the second half of 2027 as we increase revenue and advance our pipeline we are laser focused on expense management profitability we are refining our operating plan to ensure we are appropriately investing in our commercial launch and high value programs Again, cost of sales and gross margin will improve significantly as we transition manufacturing to our internal facility in early 2026. During this call and our future quarterly updates, we will highlight our ongoing efforts toward further expense reductions and resource allocation. 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 includes prioritizing top-line growth, significantly improving margin, and controlling costs with a disciplined approach. In the third quarter our top-line revenue remains strong. Total product revenue increased approximately 13% over the prior quarter to about $68 million. This included the MTGD sales of approximately $58 million and global pro-lucan 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 MTGD sales. 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 five million dollars. We lowered cost of sales by approximately 21% over the prior quarter resulting in improved gross margin of approximately 43% 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 centralized manufacturing at our internal facility cash position of approximately three hundred and seven million dollars as of September 30th was bolstered by expense reductions and is expected to fund operations into the second quarter of

2027. Now I'll turn the call to Dan Kirby our Chief Commercial Officer. Patients deserve a one-time cell therapy with curative intent and caregivers remind us of the commitment to the iAvance mission pioneering a new treatment paradigm for patients with melanoma research foundation to lay the foundation for revenue growth three key areas of new ATC's are driving growth. In the third quarter we added community ATC's alongside new high-volume academic ATC's. These new ATC's contributed to the highest number of patient starts with better capture in the third quarter. Our first community ATC's are beginning to treat patients with entangity in this setting. New ATC's continue to come online, unlocking entangity, increase the frequency, speed, and efficiency of healthcare professional are having a positive impact. The agreement with biologists giving their finance teams has the greatest benefit. New initiatives in academic ATCs will address earlier tissue procurement for patient types, such as BRAF mutations, so they can be treated before their health status. They need to grow through this main revenue channel in addition to the two other revenue channels for clinical and medical. Like other companies, which may help draw. Antegna has the potential to reach more than 30,000 patients with advanced melanoma globally. Canada became the first and approvals are pending in three additional markets. The United Kingdom and Australia in the first in early 2027. In the European Union, scientific advice from the European Medicines Agency and intend to resubmit for regulatory approval of lung cancer with non-squamous at least 50,000 addressable patients in the U.S. alone. The market opportunity is about seven times larger than our current potential U.S. peak sales of 10 billion dollars academic and community practices did to launch and not significant portion of them already treat patients in our LUN 202 trial the ATC footprint essentially that they're eager to leverage their current we have

streamlined our manufacturing organization while reducing costs and improving our manufacturing success rate as reflected in an expansion that the Ivan cell therapy dissipated demand without the need all them tagged in clinical manufacturing will transition to icdc in early 2026 to maximize capacity utilization complete a key step in this pursuit in routine annual maintenance will provide continued access

for this week we reported interim data from our registrational iov lun 202 clinical trial of life elucil the data demonstrated a potentially best-in-class clinical profile and meaningful improvement over current standard of care in previously treated patients with non-schemous, non-small cell lung cancer. Following one-time treatment with lifalutal monotherapy, the objective response rate was an impressive 26%. An objective response was observed in 10 out of 39 patients, which included two 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, the double-digit number of patients are awaiting or have recently received pill 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 lyso-leuthals 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.

Thank you. To ask a question, please press star 11 on your telephone and wait for your your name to be announced. To withdraw your question, please press star 11 again. In the interest of time, we ask that you please lend yourself to one question. Please stand by while we compile the Q&A roster. Our first question comes from Andrew Tsai with Jeffries. Your line

is open. Hey, good morning. 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 Frederick can chime in here. We don't expect any degradation in the efficacy signal. We're getting very good within the Lone 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 in the details of how we think that study is going to play out.

Yeah, 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 infection point where then things just take off because folks see and believe in the therapy and things are working really well.

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

Great. Thanks for taking our questions, and 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 regular 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 MTAGV in melanoma, can you talk about infusion growth into fourth quarter and into 2026, you know, your confidence for inflection points 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.

Thank you. All right. Thanks, Jan. Why don't I start on the FDA point, and then Raj, before you'll jump in, and I'll ask Dan and Corleen to help out with the impact of inflection point as well with the gross margin questions here. We've engaged heavily with FDA on the Lung 202 trial, gotten guidance from them, feedback on the trial design, patient population, CMC, things like the potency assay, and 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 will continue to do that on this trial but we're very comfortable where we stand right now in the trial design and all what we need to do to get us up on the other supplemental BLA submitted on time on the on the sample size for the patient you know for the 80 patients we pointed out during a lot of our call 80 patients will be onoma as well as a lot of recent FDA meeting the last couple months FDA approvals and non-small-cell lung so I'll let Raj and maybe Mark comment on that if you see the FDA why they think that's reasonable in addition to John

and Fred said that we in our continuous interaction with the FDA we plan to apply for many different priority designations such as fast track designations. And Fred mentioned that 80 patients based on the 73 million our patients that we got MTAG the approval on. And recently remark will elaborate further that the FDA has approved about four non-small cell lung cancer trials based on accelerated approval of patients.

Some patients in patients who are on cancer are in very high unmet medical needs with their response rate and particularly this...

On the fourth quarter growth, obviously we feel very confident having a strong fourth quarter, but I'll let Dan talk about that.

Thanks, Fred. Thanks, Janet, for the question. First, the answer is yes. We expect continued growth. The reasons behind that are 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. 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 B-RAP 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 site. 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 months.

Let me just focus you on one, which is patient drop-off and manufacturing. If you think about the dollars that are driving...

Thanks for the update and congrats on all the progress.

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

Thanks so much, guys. Congrats on the progress. I guess one for me on the guidance here. I know you're reiterating the guidance, Coraline. I guess, is there any scenario here in your mind where you're going to actually hit the closer to the top end here? I'm just curious why at this point, two months left in the year, why we haven't narrowed it down the top end of the range to a

number that seems more reasonable thank you yes we reiterate our guidance range of 250 to 300 which is a pretty narrow range to begin with it's our first full calendar year on the market as you know 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 pro lucan 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 you know we have got this CTC 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 to 300, and we'll be in that range, and that's what we're comfortable saying right now. Okay. Thank you very much.

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

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

Thanks very much.

Yeah, 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 on the ICTC maintenance. I'll pay it to Igor for that question. I think he had covered it in his preparatory. So, as I mentioned, as part of the routine maintenance this year, we'll complete the extension of ICDC and continue providing. So, we'll boost manufacturing capacity immediately and prior to the ICDC maintenance. That will provide additional manufacturing slots for patients, and that will allow essentially smooth two quarters.

Thank you very much. Thank you. Our next question comes from David Dye with UBS. Your line is open.

Great. Thanks for taking my questions. A couple of questions from me. So, just on the ATC REM, 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 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, you know what is like the the of the margin we should be expecting over the next quarters you know essentially one should be expecting you know the the the plateauing of the 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 we'll 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 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

David on the gross margin yes we mentioned 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 Corlea and others discussed, we expect this to have additional margin improvements on the back of that. That's not something that's reflected in the 43.

Thank you so much for the color.

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

Thanks for taking our questions, and 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?

So, thank you very much, Colleen, for the question. The capacity of the 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.

100%. That's helpful. Thank you. Thank you. And our final question comes from Rennie Benjamin with Citizens. Your line is open. Hey, guys. Thanks for taking the questions. 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 that you highlighted. You know, how do you how do you envision this programs or, you know, the expansion without a partner? 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 was 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.

So first on the global expansion, we're not thinking right now really about partnership tool technology and the science of delivering tools 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 that. Those are going to be extremely powerful in the future, and we would like to. That said, we may work with distributors in certain markets. We may work with people that can help tend to stay up 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 since Dan heads those teams, I'll let him give us some color and maybe just highlight the markets and we're going to go back into it.

Our global expansion 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, and 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 our first ATC. We have pending approvals in the U.K. We're in discussion right now in the U.K. about getting NHS support. So we're getting the process within Switzerland and then refile energy with it, And something that we will see if you look at Kite, who did a great job with several years from the approvals to get revenue in there. So we followed that model, knowing it would take 2027, saying we won't get any next year.

And I'll focus on lung too, Renny, because Tobin, we really haven't said anything publicly about the enrollment therapy right now, but hopefully Lee. Just really quick, Renny, since I don't know when you joined, I described that before earlier in the call.

So 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 group.

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 know, you might be following the DLA? Have you provided any of that guidance before?

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 this study, and that's not too far off. We have not guided anything publicly, and there's obviously, for a 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.

Excellent. Thanks very much for taking the questions.

Thank you. 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 IVAN biotherapeutics third quarter 2025 conference call. We look forward to providing future updates on our commercial launching 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 IVAN's till cell therapies. I'm confident that IVAN will remain the global leader in innovating, developing, and delivering current and future generations of pill cell therapies for patients with cancer. Partners and our exceptional IVANCE team.

This concludes today's conference call. Thank you for participating.

You may now disconnect.