Welcome to the Iovance Biotherapeutics conference call to review updated data from the IOV-LUN-202 trial in non-small cell lung cancer.
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We were live, sir. As we were welcoming everybody to the Iovance Biotherapeutics conference call to review the updated data from the IOV-LUN-202 trial in non-small cell lung cancer. My name is Carmen. I will be your operator for today, and at this time everybody is on 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 Sara Pellegrino, Senior Vice President, Investor Relations and Corporate Communications at Iovance. Sara, you may begin.
Thank you. Welcome to Iovance Biotherapeutics conference call to review updated data from IOV-LUN-202 in non-small cell lung cancer. Welcome to the webcast to review updated registrational trial data in previously treated non-squamous, non-small cell lung cancer and our biomarker-enriched precision TIL strategy. This morning, we issued a press release, and the slides for today's webcast are available in the investor section of our corporate website at ir.iovance.com. Speaking on today's call is Dr. Fred Vogt, Interim CEO and President. During the question and answer session, we will also be joined by Dr. Noah Berkowitz, Dr. Brian Gastman, Dr. Raj Puri, Corleen Roche, and Dan Kirby.
This call will be including forward-looking statements regarding Iovance's goals, business focus, business plans, clinical trials and results, subgroup and biomarker analyses, trial enrollment and initiation, regulatory approvals, submissions, feedback and guidance, timelines, plans and strategies, potential future applications of our technologies, any required companion diagnostics, the size of addressable patient populations, 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 turn the call over to Dr. Fred Vogt.
Thank you, Sara, and good morning, everyone. As the global leader in innovating, developing, and delivering TIL therapy for solid tumors, metastatic non-small cell lung cancer represents the largest opportunity ahead for Iovance. This morning, we announced positive updated data from our registrational Cohorts 1 and two of our IOV-LUN-202 trial in support of our planned supplemental Biologics License Application, or sBLA, in 2027. Detailed results, including waterfall response and swimmer's plots, are available in a slide presentation posted this morning in the investor section of our website. I will first highlight our important results in Cohorts 1 and 2 and our path towards our planned supplemental BLA submission for non-small cell lung cancer in 2027. Then I will turn to a significant novel addition to our precision TIL strategy and the next steps for expanding our non-small cell lung cancer program.
In our registrational cohorts in Lung 202 in non-squamous metastatic non-small cell lung cancer patients, lifileucel shows a potential best-in-class clinical profile with an objective response rate, or ORR, of about 25% by RECIST 1.1, the standard criteria for measuring tumor shrinkage. As of our October 14, 2026 data cutoff, 17 of 69 patients responded with most responses durable. Of these, 15 were confirmed responses, including two complete responses, with two more recent responses awaiting confirmation. These 69 patients, plus several additional patients in the treatment process at the time of the data cut and more patients enrolled in the study, represent the vast majority of the expected 80 patients in our registrational population. These updated results are remarkably consistent with our prior results in 39 patients across ORR, durability, and safety.
Our updated reduced dose lymphodepletion regimen prior to TIL infusion has improved the overall safety profile, which remains consistent with our experience with lifileucel. For patients with metastatic non-small cell lung cancer whose disease progresses after first-line immunotherapy and chemotherapy, time is short and options are few. Recently published response rates with docetaxel, the most commonly used standard of care, were only 12.8%, with no complete responses. The median duration of response was 5.6 months, and median overall survival was 12.3 months. These patients need treatments that deliver better outcomes and, above all, more lasting responses. Our Lung 202 results, including today's updates, are unprecedented in the second-line treatment setting. As I mentioned, waterfall response and swimmer's plots are available in a slide presentation posted this morning in the investor section of our website.
We continue to move forward towards the sBLA submission in 2027, and we will have further updates along the way, including on our confirmatory trial plan. As I mentioned, we expect approximately 80 non-squamous, non-small cell lung cancer patients to be included in the final data set for the sBLA. Today's data update represents nearly all of the patients in the expected data package. Our internal teams are focused on preparing for the sBLA submission. Independent review committee assessments, FDA discussions, and other pre-submission activities, including confirmatory trial preparation, are also ongoing. We look forward to completing enrollment in Cohorts 1 and 2 shortly and are confident in the road ahead in previously treated non-squamous metastatic non-small cell lung cancer, which earned FDA's Fast Track designation on the strength of our clinical data and represents an area of high unmet medical need.
Next, we have exciting updates on our precision TIL strategy, as well as the broader non-small cell lung cancer program and our growing pipeline. For many years, we have been pushing the limits of our biological understanding of TIL therapy, exploring every aspect of our wealth of state-of-the-art genomic and translational data using the best tools available. We are now able to announce the identification of a novel and important biomarker-enriched population in previously treated and frontline metastatic non-small cell lung cancer. This has allowed us to develop a precision TIL strategy to enrich for patients that show the greatest benefit to lifileucel and potentially other pipeline products in non-small cell lung cancer and in other indications. In the Lung 202 trial, we identified KRAS wild-type status as the lead biomarker. Published preclinical studies in lung cancer models link oncogenic KRAS signaling to impaired antigen presentation and immune suppression.
Impaired antigen presentation in turn inhibits responses to TIL therapy by limiting the ability of T cells to recognize tumors. In our subgroup analysis, the ORR among KRAS wild-type patients was 43.3%, or 13 out of 30 patients, nearly four times the 11.4% ORR seen in four out of 35 patients in the KRAS mutant subgroup. These critical observations provided the rationale for further enrichment within the KRAS wild-type subgroup. Building on this signal, we further drew on tumor genomic testing and smoking history data to enrich for HER2 and smoking status. Our work has shown that TIL responses need recognizable tumor targets and an environment that can support a sustained anti-tumor response. Excuse me. Aberrant HER2 signaling can suppress anti-tumor immunity in preclinical models, while smoking-associated mutations generate additional tumor targets for TIL recognition.
Combined with KRAS wild-type population, this subgroup represented less than one-third of the broader study population, or 22 out of 69 patients, but accounted for more than three-quarters of the observed responses, or 13 of 17, with a high ORR of 59.1%, or 13 of 22 patients. In the real world, we estimate that a large population of approximately 45% of non-squamous metastatic non-small cell lung cancer cases diagnosed in the U.S. each year meet the biomarker-enriched criteria.
This remarkable result, with nearly six in 10 patients durably responding, including two complete responses, along with the biological rationale, drive our plan for prospective evaluation of this combined enrichment strategy for lifileucel in an additional trial that further expands our non-small cell lung cancer program. Today, I am excited to introduce POSITILITY, a first-in-class prospective biomarker-enriched cohort within the ongoing IOV-LUN-202 program designed with registrational intent.
Enrollment in POSITILITY is set to begin imminently, with the first sites beginning the trial in November 2026 and expanding to over 70 existing IOV-LUN-202 sites over the next few months. POSITILITY will enroll patients across both PD-L1 negative and positive populations. We are fortunate to be in a position to enroll POSITILITY quickly with our trial already at full speed and our fully scaled and highly efficient in-house manufacturing capabilities ready to go. We expect momentum to further increase on the back of today's results. Marker enrichment strategy into a precision development plan to maximize the benefit from lifileucel therapy and achieve rapid responses and rapid, sorry, excuse me, rapid approvals in the U.S. and around the world.
We also applied our learnings to frontline metastatic non-small cell lung cancer using our data from Cohort 3A of our IOV-COM-202 trial in patients without actionable EGFR, ALK, and ROS1 mutations who were not previously treated with checkpoint inhibitors or chemotherapy. Following one-time lifileucel combined with pembrolizumab without adding standard of care chemotherapy, the ORR was 85.7%, or six out of seven patients in the subgroup enriched for KRAS and smoking status, including one complete response and five partial responses, all confirmed and durable. This compares to an ORR of 64.3%, or nine out of 14 patients, among all EGFR wild-type patients, again highlighting the effects of KRAS wild-type biology on clinical responses. This population also represents a population in need of highly efficacious, durable therapies.
Building on these findings in the frontline treatment setting, we also plan to initiate the OPTILISM trial in biomarker-enriched non-squamous metastatic non-small cell lung cancer in 2027. OPTILISM is based on an innovative, highly derisked trial design to add lifileucel to frontline standard of care, consisting of pembrolizumab and platinum-based chemotherapy, regardless of PD-L1 status in non-squamous patients with KRAS and HER2 wild-type tumors and a current or former smoking history. We will share more details on OPTILISM and its unique design in coming months. Together, OPTILISM and POSITILITY will evaluate lifileucel across two treatment settings and assess the role of biomarker enrichment in our non-small cell lung cancer development program. It is extremely important to note that our biomarkers enriching for higher response rates also represent patients that have no targeted therapeutic options to date.
As a result, we have the potential to treat tens of thousands of patients annually in the U.S. alone that will simply not be eligible for mutant KRAS, HER2, or other inhibitors or antibodies that would often be recycled through multiple lines. Instead, we envision a treatment paradigm where metastatic non-squamous, non-small cell lung cancer patients lacking actionable driver mutations, and regardless of PD-L1 status, come directly to TIL therapy in the frontline or second-line settings and could benefit from a potentially curative option with deep and durable responses and even complete remissions. The combined frontline and second-line opportunity represents a significant market opportunity in non-small cell lung cancer that we estimate is at least 10 times the size of the current opportunity, second-line melanoma in the U.S. alone.
We are also leveraging these biomarker-driven insights into other indications for lifileucel in our pipeline assets, especially as we are right now entering indications like colorectal cancer with our IOV-5001 program. The biology underlying our findings may translate to other indications of unmet medical need with significant market potential. This enriched biomarker strategy provides Iovance with novel and valuable intellectual property. These discoveries create a broad and extensive moat around the field of precision TIL therapies. We look forward to providing further updates on our programs in 2027. Operator, we are now ready to take questions.
Thank you. As a reminder, to ask a question, simply press star one-one to get in the queue and wait for your name to be announced. To remove yourself, press star one-one again. One moment for our first question. That comes from Andrew Tsai.
Operator, we are now ready to take questions.
Hi. Good morning. This is Andrew. Thanks so much for the data update today. First question. Well, first, it is great to hear the ORR.
If everyone can hear me, apologies for the technical difficulties today. We are just waiting for the operator to queue up the questions.
Operator, I will let you help me figure this out.
Andrew, we can hear you.
Okay. Well, team.
Andrew, go ahead.
It's great to see the ORR being maintained. As for the durability, it seems like based on the.
Apologies, everyone. We cannot hear Andrew, and there seems to be a lot of technical difficulties today. Please just give us a minute here to work out what is going on.
Please stand by, ladies and gentlemen. Please stand by, Andrew. We appreciate your patience.
Thanks.
Operator, we are unable to hear Andrew's question. Could you just please double-check that he is unmuted?
He is unmuted, sir. Everyone can hear Andrew, and we can hear you, sir. Can you hear us?
I can hear you, but I can't hear Andrew, unfortunately.
Andrew, go ahead with your question.
Okay. Team, can you hear me?
Operator, see if another analyst can ask a question, and we can come back to Andrew quickly.
Sure.
If that's possible.
One moment, please. Andrew, stand by. Please queue back up. One moment, please. Our next question is from Yanan Zhu with Wells Fargo.
Oh, great. Thanks for taking our question. Fred, can you hear me?
Yes, I can hear you, Yanan.
Oh, okay. Great. Thanks for taking our questions—
Thank you.
—and for the update. Perhaps two questions. One is regarding durability of response. Do you have a mDOR from the data? Secondarily, wondering about the filing strategy, given that you have now identified this more precisely defined subgroup, and you are conducting a prospective study, how do we think about the possibility of the previously stated plan? I think you reiterated that you are talking with FDA, but what are the, from your perspective, the likelihood that FDA would accept the initial broader population as the filing and the basis for approval? Thank you.
Yanan, can you hear me before I answer this? I want to make sure.
I can hear you, yeah.
Okay, good. Great. Hopefully, everybody else can hear me, too. Thank you for the question. The durability, you can see there's a swimmer's plot on our website on slide six of the new deck that we posted. It looks quite good. Right now, if you estimated from that swimmer's plot where we'd be, we'd be at about a year, but I need to stress that the data is immature and data is still coming in and that we would expect to grow over time, and there's some patients that are coming in right now, obviously, that are responding. You really can't assess durability at this stage until the data's finally done. We're also in the middle of IRC reads and a lot of other things that will affect the outcome.
We are confident that the product is durable, and we'll show durability comparable to what we would expect from TIL therapies. On the broader question of whether FDA would accept this filing, we think a 25% response rate durable with a one-time treatment in this population should be approvable, and we think the FDA should accept it and should go forward. Obviously we are still in the process of discussions with FDA. It's a little premature to get into a lot of details there. We have reached some alignment with FDA on things like CMC issues and some of the original trial design topics, but we're going to have more to say on that in 2027 as we go through the process. Meanwhile, we're full steam ahead on submitting a supplemental BLA based on Cohorts 1 and 2 of the full data package.
The new POSITILITY study, which we call it internally Cohort 5, which is part of the IOV-LUN-202 study, is an add-on. It's an additional program that we're adding on to our non-small cell lung portfolio because we've identified a very powerful biomarker signal that we would be fools not to pursue. If we're going to have a response rate of 60% in certain patients, we're going to need to go after that and try that in a study. That could become very, very meaningful. There's nothing out there on the market that has a response rate in that range in lung patients, and we're talking about lung patients here that don't have access to any targeted therapy. I hope you could hear me there, so please let me know if any of that got cut off. I know there's been a lot of technical issues here.
Thanks, Fred. Yes. I can confirm I heard all the answers. Thanks for all the color.
Thank you, Yanan. Operator, can we have the next question? Hopefully everybody continues to hear each other.
Thank you so much. Let me bring Andrew back. One moment, please. Andrew, your line is open with Jefferies. Please go ahead.
Great. Good morning. Thank you so much for the data update today. When do you guys think we can get the initial cut once all 80 patients are enrolled? Maybe talk about your level of conviction that should remain unchanged, DOR ultimately unchanged, for those remaining 10 patients. In fact, for the remaining 10, are you guys enriching for that remaining 10 by chance, or is it kind of an all-comer still? I wonder, could ORR increase from there? Thank you.
Yeah. It's all-comers technically, Andrew, but we've been a little light on KRAS wild-type patients, so we do have the law of averages helping us here, and we think that will come back up a bit. Yes, it could be a little bit higher in the end. We could get a couple of sure responders with KRAS wild-type patients being in there. Can you just ask your question again about durability? I didn't understand specifically what you want to discuss there.
It's okay. I actually didn't ask on durability, but maybe I might as well as a second follow-up then. B ased on the plots, maybe it seems like as of this cut, you need two more of your responders to progress in order to calculate the mDOR. I s there a way to maybe tell us what the floor on DOR in number of months could be at this juncture on this existing cut? What would that look like in months? I'm just trying to gauge whether DOR is above 15 months, for instance, at this juncture.
You can look at the swimmer's plot, which has a y-axis that goes out to, I think, 54 months. You can see that the responders at the top that are going on for years, and then you can come down around the midpoint and kind of estimate a few more patients coming on to that chart at the end that are responders, where they might land. I think it would be fair to say, yes, we could end up with an mDOR of 18 months or beyond with this data set. I think that would be very reasonable based on what we know about TIL therapy right now in the lung population. A gain, we won't know until the data's done.
We'll have a final data cut at some point early next year, I think, and then we'll be able to talk a little bit more about that and the FDA process in much more detail.
Thank you so much.
Thank you.
Thank you. One moment for our next question, please. It comes from Etzer Darout with Barclays. Please proceed.
Great. Thanks for taking the question. Can you guys hear me?
Yes. Etzer, can you hear me okay?
Yes, I can. Thank you.
Great.
I guess question really around maybe a broader biomarker strategy, given what you are seeing here in lung. We think about melanoma, sarcoma, endometrial, other tumor types that you are assessing. How are you thinking about maybe broadening out this strategy beyond lung? If you could provide some color there, that would be great. Thank you.
Yeah, Etzer. Absolutely. There is a number of indications where KRAS wild-type status represents a significant population of the patients that are in the metastatic stage, like colorectal, in particular colorectal cancer. We are looking very closely across the entire landscape of solid tumors for populations like colorectal, where we have a significant population of patients where we could treat them with lifileucel or with one of the other products in our portfolio. I think you should stay tuned, and there will be a lot more to say about that over the next couple of months. Very, very important finding here. I just want to stress that today we are announcing both second-line and frontline non-small cell lung updates, and that population is the KRAS wild-type population, biomarker-enriched population. There alone is, we think, more than 10 times the size of the current second-line melanoma population.
I mentioned that during my prepared remarks. That is extremely important. If you add colorectal on top of that and other indications that are important out there, gastric cancers and beyond, you have a pretty significant market that you are talking about.
Great. Thank you.
One moment for our next question. That comes from Nick Lorusso with TD Cowen. Please proceed.
Thanks, guys. Thanks for taking my question, and thanks for the presentation. What is the minimum follow-up that the FDA wants to see to support the filing based on the LUN-202 data? Could this support a potential approval later in 2027 or early 2028? Second, based on your response on that, do you anticipate releasing more biomarker-enriched data ahead of a potential approval to further support the AMTAGVI profile, whether from this trial or from your two newer trials as well? Thanks very much.
Thanks, Nick. I assume everybody can hear me still. Right, Nick? I just want to make sure.
Yeah. We can still hear you.
Yeah. Okay, great.
Thanks very much.
Yeah. The FDA normally requires six months of follow-up from the last response, which puts you to about eigt months after the last patient comes into the trial. Typically, if you have a response, day 84, day 126, when we do our scans. Hopefully that answers that question. Of course, that triggers the filing timelines. We think we can get the supplemental BLA in in 2027, and obviously, review would extend into late 2027 into 2028, and that's when we would expect an approval. On your second question, with announcing additional biomarker data, yes, we definitely want to announce the biomarker data and other indications. We'll want to delve deeper into this data.
We'll want to present this at medical congresses and talk a lot more about the KRAS, HER2 wild-type population, ever smoker population, in the case of lung cancer, and the KRAS wild-type population in the case of colorectal and so on, and explain to people why we think TIL therapy is the ultimate therapy in these patient populations. I think you'll see a lot more from us in the first six months or so of 2027 around this topic. Precision TIL therapy has been something that we've been talking about for a while, especially with our sarcoma program. As we precisely identified two subtypes of sarcomas that respond very well with TIL therapy, greater than 50% response rates, even after years of us and others attempting to treat other sarcomas with TIL therapy. That was sort of the first foray in the precision TIL.
Now we're in the second leg, where we're using genomics to really get to that additional level and deep insights into large clinical trial data sets that only we have in the field. Hope that answers your question.
Yes, it does. Thank you very much for the color.
Thank you.
Thank you. Our next question comes from Jack Allen with Baird. Please proceed.
Hey, thanks for taking the questions, and congrats on the update this morning. Hopefully, you can hear me.
Yes. Hopefully, you can hear me, too.
Great. Yeah, I got you, Fred. Just two quick ones from us. I wanted to ask a really interesting work you're doing with the biomarkers around KRAS and HER2, but I'm curious if you looked at other biomarkers in the study and if there was any differential in response around PD-L1 status as well. I have a quick follow-up as well.
Yes, we looked at, I couldn't even tell you how many biomarkers. We studied everything. This was a very complex analysis to identify this. We don't think there's a relationship with PD-L1 status with respect to TIL therapy, and we are in most cases. If there is a situation where we have a PD-L1 effect, we have a PD-L1 knockout TIL therapy that's designed for that situation. T here may be some cases where we talk about that, but at least in lung cancer, we don't see a PD-L1 effect. Go ahead with your second question, though, and hopefully you heard that.
Yeah, I got you, Fred. Thanks for the color there. Another one was just very briefly on any comments you can make surrounding the manufacturing success rates seen in the lung cancer study.
Yeah. It's consistent with our prior experience. We're getting good total success rates. I don't know the exact number, Jack, off the top of my head, but they can be as high as 90% in some cases. We're really focused right now on delivering high cell doses and making sure we're delivering quality product. Because of our large in-house manufacturing capacity and our expertise in making AMTAGVI commercially, we're getting better and better at making it for trials, too, and we try to leverage that, and that's something we'll use across the OPTILISM and POSITILITY as we talked about today, as well as additional confirmatory trials for cohorts one and two when we announce that.
Great. Thanks so much for taking the questions.
Thank you.
Thank you so much, and this will conclude the Q&A session, and I will turn it back to Fred Vogt for his final comments.
Thank you, operator. Today's findings are reshaping how we develop TIL therapy for non-small cell lung cancer. Before we close, I have three takeaways for you. First, in our registrational cohorts, lifileucel again shows a 25% response rate, now in 69 patients. Second, in our biomarker-enriched analysis, KRAS wild type and HER2 wild type tumors in current and former smokers responded best, and we are testing that prospectively in POSITILITY beginning next month. Third, we plan to bring this precision approach to the frontline with OPTILISM in 2027. We believe these insights could expand lifileucel's potential as a one-time treatment for non-small cell lung cancer with a best-in-class profile compared to other therapies in development. Thank you all for joining us this morning, and we look forward to keeping you updated as our non-small cell lung cancer program advances.
As always, we are grateful for the patients, caregivers, and investigators who participate in the Lung 202 Trial and to our team. Thank you all on the call, and apologies again for the technical difficulties today.
Thank you all for participating in today's conference, and you may now disconnect.