Iovance Biotherapeutics, Inc. (IOVA) Earnings Call Transcript & Summary

Welcome to the Iovance Biotherapeutics conference call to review updated data from the IOV-LUN-202 trial in non-small cell lung cancer. My name is Carmen. I'll be your operator for today. So as we were welcoming everybody to the 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'll be your operator for today. [Operator Instructions] And 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, and 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 Investors 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 analysis, trial enrollment and initiation, regulatory approvals, submissions, feedback and guidance, time lines, 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 2 of our LUN-202 trial in support of our planned supplemental biologics license application, or sBLA, in 2027. Detailed results, including waterfall of responses and swimmer plots are available in the slide presentation posted this morning in the Investors section of our website. I will first highlight our important results in Cohorts 1 and 2 and our path toward 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 LUN-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 2 complete responses with 2 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 LUN-202 results including today's updates, are unprecedented in the second-line treatment setting. As I mentioned, waterfall of response in swimmers plots are available in the slide presentation posted this morning in the Investors section of our website. We continue to move forward towards the sBLA submission in 2027, and we'll 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. And so 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 presubmission 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 LUN-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 4x the 11.4% ORR seen in 4 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 in an environment that can support a sustained antitumor response. Aberrant HER2 signaling can suppress antitumor 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 1/3 of the broader study population or 22 out of 69 patients, but accounted for more than 3/4 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 6 in 10 patients durably responding, including 2 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'm excited to introduce POSITILITY, a first-in-class prospective biomarker enriched cohort within the ongoing 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 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. [Technical Difficulty] enrichment strategy into a precision development plan to maximize the benefit from lifileucel therapy and achieve rapid responses -- rapid -- 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 COM-202 trial in patients without actionable EGFR, ALK and ROS1 mutations who were not previously treated with checkpoint inhibitors or chemotherapy. Following onetime lifileucel combined with pembrolizumab without adding standard of care chemotherapy, the ORR was 85.7% or 6 out of 7 patients in the subgroup enriched for KRAS and smoking status, including 1 complete response and 5 partial responses, all confirmed and durable. This compares to an ORR of 64.3% or 9 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 designed 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 the coming months. Together, OPTILISM and POSITILITY will evaluate lifileucel across 2 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 10x the size of the current opportunity in second-line melanoma in the U.S. alone. We are also leveraging these biomarker-driven insights into other indications for lifileucel and 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. The enhanced -- 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're now ready to take questions.

[Operator Instructions] One moment for our first question that comes from Andrew Tsai.

This is Andrew. Thanks so much for the update today. So first question all for us, it's great...

Everyone, if you can hear me apologies for the technical difficulty today. We're just waiting for the operator to queue up the questions.

Operator, I'll let you to help me figure this out.

Andrew, we can hear you.

Okay. Well, it's great to see the ORR being maintained. So as for the durability, it seems like based on the...

Apologies, everyone. We can't hear Andrew, and there seems to be a lot of technical difficulties. Please just give us a minute here to work out what's going on. Operator, we're unable to hear Andrew's question. Could you just please double check that he's 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.

Maybe operator, see if another analyst can ask a question and we can come back to Andrew quickly, if that's possible.

Andrew, standby. Our next question is from Yanan Zhu with Wells Fargo.

Thanks for the update. Perhaps 2 questions. One is regarding durability of response. Do you have a median DOR from the data? And 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? And I think you reiterated that you are talking with the FDA. But what are the -- from your perspective, the likelihood that FDA would accept this as -- the initial broader population as the filing and the basis for approval?

Yes. Yanan, can you hear me before I answer this? Just I want to make sure.

I can hear you. Yes.

Okay. Great. Great. Hopefully, everybody else can hear me too. Thank you for the question. The durability, you can see there's a swimmers plot on our website on Slide 6 of the new deck that we posted. It looks quite good. Right now, if you estimated from that swimmers plot where we would be, we'd be about a year. But I need to stress that it's -- the data is immature and data is still coming in and that we would expect to grow over time, and there are some patients that are coming in right now, obviously, they're responding. So you really can't assess durability at this stage until the data is finally done, and 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 will show durability comparable to what we would expect from TIL therapies. Now on the broader question of whether FDA would accept this filing, we think a 25% response rate durable with a onetime treatment in this population should be approvable, and we think the FDA should accept it and we -- 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. Now the new POSITILITY study, which is -- we call it internally Cohort 5, which is part of the 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. And 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 in 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. And I hope you could hear me there. So please let me know if any of that kind of cut off. I know there's been a lot of technical issues here.

Thanks, Fred. Yes, I can confirm I heard all the answers.

Operator, can we have the next question? And hopefully, everybody continues to hear each other.