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spk17: Welcome to the Iovance Biotherapeutics First Quarter 2022 Financial Results. My name is Andrew, and I'll be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we'll conduct a question-and-answer session. During the question-and-answer session, if you have a question, please press star, then 1 on your touch-tone phone. Please note that this conference is being recorded. I will now turn the call over to Sarah Pellegrino, Vice President, Investor, and Public Relations at Iovance. Sarah, you may begin.
spk12: Thank you, Operator. Good afternoon, and thank you for joining us. Speaking on today's call, we have Dr. Fred Boat, our Interim President and Chief Executive Officer, Dr. Igor Balinski, our Chief Operating Officer, Jim Ziegler, our Senior Vice President Commercial, Dr. Frederick Zinkenstein, our Chief Medical Officer, Dr. Madan Jagazia, our Senior Vice President, Medical Affairs, and John Mark Bellamine, our Chief Financial Officer. Dr. Raj Puri, our Executive Vice President, Regulatory Strategy and Translational Medicine, is also on the call to participate in the question and answer session. This afternoon, we issued a press release that can be found on our website at iovance.com, which includes the financial results for the three months ended on March 31, 2022, as well as recent corporate updates. Before we start, I would like to remind everyone that statements made during this conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans, pre-commercial activities, clinical trials and regulatory plans and results, research and pre-clinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interaction, collaboration, cash position and expense guidance, and future updates. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward-looking statements. With that, I will turn the call over to Fred.
spk18: Thank you, Sarah, and good afternoon, everyone. I am pleased to highlight our positive start to the year at Iovance during today's conference call. First and foremost, we are moving rapidly towards our first-ever BLA submission for our lead pill therapy, lifelucel, and metastatic melanoma. This is our top priority at Iovance. As we announced last month, we received positive feedback from the FDA regarding our potency assays and assay matrix for lifelucel. For next steps, we intend to hold a pre-BLA meeting in July 2022 and submit the BLA in August 2022. In addition, we continue discussions with the FDA about our registrational strategies in cervical cancer and non-small cell lung cancer so that we may offer TIL therapy to patients with significant unmet need in these additional tumor types. As we prepare to launch Leifelucel, we are also making progress in our commercial readiness and internal manufacturing capabilities at the Iovance Cell Therapy Center or ICTC, in Philadelphia. Our organization is growing to further our mission of innovating, developing, and delivering pill therapies. We now have nearly 400 employees at the company who have, on average, more than four years of cell therapy experience. The talent within our organization is a testament to the potential of our Iovance pill therapy and our global leadership within the field. We're excited about the momentum for our glowing pill pipeline. We continue to enroll patients across four Iovance-sponsored clinical trials, and plan to initiate two additional trials this year. The FDA has allowed an IND to proceed for a clinical trial of our PD-1 inactivated gene-edited TIL therapy, IV4001. We also plan to conduct a Phase III trial of TIL in combination with pembrolizumab and frontline melanoma, where clinical data demonstrated the potential to improve patient outcomes compared to pembrolizumab alone in patients who are naive to immune checkpoint inhibitors. As we prepare to launch the first one-time cell therapy in solid tumors, we believe that our TIL platform, clinical data, and people set a strong foundation to establish iAdvanced TIL therapy as the next class of paradigm-shifting therapies for people with cancer. Manufacturing and managing demand for a new cell therapy is key to our success. So I'll ask Igor to talk more about our progress in these areas.
spk19: Thank you, Fred. Across our manufacturing network, we continue to focus on patient needs and operational excellence, maintaining a till manufacturing success rate of more than 90% in more than 500 patients treated with IVAN still therapy. Today, I will summarize key activities at the IVAN Cell Therapy Center, or ICTC, which is our 136,000 square foot cell therapy manufacturing facility. Recently, our event was honored by the International Society for Pharmaceutical Engineering with a 2022 Facility of the Year Category Award for ICDC, a remarkable reflection of what we have accomplished since the initial groundbreaking of this facility only three years ago. At ICDC, the main priority remains preparation for the BLA and commercial launches. We designed ICTC to have the capacity to provide commercial and clinical till supply for thousands of patients per year. We expect ICTC to handle most of our commercial demand at launch with the added flexibility to use contract manufacturing to optimally manage capacity and address patient demand. We are performing numerous activities to support the BLA submission at ICTC in parallel with clinical manufacturing, which began at ICTC last year. In addition, we are on track in preparing the ICDC and our contract manufacturer's facility for BLA for FDA pre-approval inspections, which we expect to occur as part of the BLA review process. In addition to manufacturing, we have established a strong quality control, or QC, group at ICDC. The QC team performs release testing of TIL products, which will include commercial release testing of lyphosyl upon potential approval. In collaboration with our analytical development group, our QC team has been completing BLA-related activities needed for our TIL potency assays and assay matrix, including our new potency co-culture assay. Turning to our intellectual property, or IP, we continue to build our robust and growing IP portfolio to support our proprietary manufacturing processes, as well as our know-how surrounding TIL therapies. We currently own more than 40 granted or allowed U.S. and international patents. This IP covers till compositions and methods of treatment and manufacturing in a broad range of cancers, including Gen 2 patent rights that are expected to provide exclusivity into 2038. I would now like to hand the call to Jim Ziegler to highlight our commercial launch preparations. Over to you, Jim.
spk04: Thank you, Igor. Our cross-functional team has built a foundation to scale rapidly and efficiently from BLA submission into launch and commercialization. We are partnering with the leading U.S. cancer centers to develop their TIL service line capabilities, and we aim to have at least 40 authorized treatment centers, or ATCs, for launch. The key onboarding and training activities are also aligned with the BLA-related milestones to ensure just-in-time training and readiness at our ATCs. Our market access team continues to engage commercial, state, and federal payers, such as the Centers for Medicare and Medicaid Services, or CMS, to ensure patients have appropriate and timely access to life elusal. CMS released the fiscal year 2023 inpatient prospective payment, or IPPS, proposed rules as part of their annual process in April. In this draft rule, CMS proposes to continue policies that were finalized in the fiscal year 2022 rulemaking cycle, which expanded DRG 18 for CAR-Ts and other immunotherapies, including lifelucid. This means hospitals will have more appropriate payment for Medicare beneficiaries upon lifelucid approval. In the rule, CMS also summarizes the new technology add-on payment, or NTAP applications, including lifeloosal. With the anticipated BLA timelines, we plan to submit our NTAP application in the next fiscal cycle. We appreciate the positive steps CMS has taken to improving Medicare patient access to cell therapies, and we look forward to working with CMS and other key stakeholders to ensure access for the emerging class of cell therapies. In addition to supporting access, we are also developing our proprietary Iovance CARES program to assist healthcare providers and patients through every step of their TIL journey. Our goal is to deliver a best-in-class self-ordering, chain of identity, chain of custody, and patient support program for launch. I will now pass the call to Friedrich Finckenstein, our Chief Medical Officer, to highlight our clinical progress.
spk07: Thank you, Jim. Today, I would like to share recent updates for our TIL clinical programs. We have made great strides in evolving our TIL technology platform to incorporate additional therapies and technologies to address more cancer patients and new tumor types and indications. The important proof of concept for TIL in combination with pembrolizumab in multiple solid tumors, as well as our IND-enabling work to proceed to a clinical trial with IOV4001, are two prime examples of our platform expansion and commitment to TIL innovation. Our strategy for TILT in combination with pembrolizumab in checkpoint inhibitor-naive patients expands upon the initial opportunity for life-reducible monotherapy after checkpoint inhibitor therapy. In an April 2022 press release, we announced updated clinical data for life-reducible in combination with pembrolizumab from cohort 1A in our IOV COM202 trial. In melanoma patients who were naive to immune checkpoint inhibitor therapy, the overall response rate was 67%. Eight out of 12 patients had a confirmed objective response, including three complete responses and five partial responses. Overall and complete response rates for this combination were above published response rates for PEMBRO alone in frontline melanoma. Based on the promising clinical data and to offer possible benefits from TIL therapy to more melanoma patients, we are working with our internal teams and key opinion leaders to finalize the design for a phase three trial. We currently expect this trial to begin at the end of this year and look forward to providing updates as available. In addition, we are advancing our first genetically modified till therapy candidate, IOV4001, into the clinic. During the first quarter, the FDA allowed our IND to proceed for IOV4001 for previously treated advanced melanoma or metastatic non-small cell lung cancer. IOV4001 is a PD-1 inactivated TIL therapy that incorporates the talent gene editing technology licensed from Selective. Preclinical results for IOV4001 were recently presented in a poster at the American Association for Cancer Research annual meeting, or AACR. In the murine model of melanoma, The anti-tumor activity of IOV4001 was superior to non-edited TIL product, whether alone or in combination with an anti-PD-1 antibody. We're excited about the potential for IOV4001 to deliver TIL and PD-1 inhibition within a single therapy and look forward to starting a first-in-human study with IOV4001 later this year. Turning to our strategy for TIL in non-small cell lung cancers, We are currently enrolling second-line non-small cell lung cancer patients in the IOV Lung 202 trial at 30 sites. We recently amended the trial protocol to broaden the patient population in reflection of real-world practice and the unmet need in non-small cell lung cancer. This amended protocol also provides flexibility around the timing of tumor harvest as well as around therapy prior to tumor infusion, which may inform new practices for patients across all the tumors. To elaborate on our medical education and outreach efforts, I will hand the call to Madan to discuss.
spk08: Thank you, Friedrich. Our medical affairs team has a depth of experience in oncology with longstanding relationships with many of our key opinion leaders. Over the past three years, our medical affairs team has been active in engaging centers and physicians about IOAN still therapy. These interactions include scientific exchange at individual and small group meetings or during medical conferences. In total, the team has interacted with approximately 500 healthcare providers or HCPs. Among these HCPs, 70% are dedicated to hematology oncology, 20% are cell therapy specialists, and the remaining 10% are surgeons. Our medical affairs team also leads the publication and scientific communication strategy and execution at IOVAN. Our goal is to present and publish clinical data and engage with physicians so that we can attract top centers to participate in our clinical trials, increase scientific awareness, drive patient recruitment, and increase share of voice for IOVAN still therapy within the oncology and cell therapy communities. In 2021 alone, our clinical trial data presentations represented 136 patients across four tumor types. The venues included three major medical meetings, AACR, ASCO, and CITC, and one manuscript, which was Melanoma Cohort to Data in the Journal of Clinical Oncology. In addition, our Iowans Medical Affairs team has interacted with with more than 100 centers as we work cross-functionally to facilitate onboarding activities at the authorized treatment centers. Among these centers, 60% are designated cancer centers by the National Cancer Institute and or member institutions of the National Comprehensive Cancer Center Network. The remaining 40% are a mix of academic and large community networks. I will now hand the call over to Jean-Marc to discuss our first quarter 2022 financial results.
spk01: Thank you, Madame. My comments will reflect the high-level financial results from our first quarter of 2022. Additional details can be found in this afternoon's press release as well as in our SEC filings. I will begin with the strengths of our cash position. As of March 31st, 2022, Iovans held $516 million in cash, cash equivalent investment and restricted cash, compared to $602.1 million on December 31st, 2021. Cash usage from operations included certain annual payments, totally $16 million. We maintain prior guidance that our cash position is sufficient to advance our operating plan into 2024, including pipeline development and expansion, commercial manufacturing readiness, and launch preparation. Moving to the income statement, our net loss for the first quarter ended March 31, 2022, was $91.6 million, or 58 cents per share. is compared to a net loss of $75.4 million, or 51 cents per share, for the first quarter ended March 31, 2021. Research and development expenses were $68.3 million for the first quarter ended March 31, 2022, an increase of $12.4 million compared to $55.9 million for the first quarter ended March 31, 2021. The increase in research and development expenses over the prior year period was primarily attributable to the growth of the internal research and development team, including stock-based compensation expense, to support our ongoing and planned pipeline activities, as well as increased facility-related costs. General and administrative expenses were $23.4 million for the first quarter, ended March 31, 2022. an increase of $3.8 million compared to $19.6 million for the first quarter ended March 31, 2021. The increase in general and administrative expenses compared to the prior year period was primarily attributable to the growth of the internal general and administrative team, including stock-based compensation expense, an increase in marketing, intellectual property, and legal expenses, as well as the build-out of our new corporate headquarter office and information technology infrastructure to support pre-commercialization, launch readiness, and overall growth. As of March 31st, 2022, there were approximately 157.2 million common shares outstanding. With the strength of our balance sheet, and by managing our focused investments across the pipeline, launch readiness, and internal manufacturing, we are well positioned to execute our operating plan while continuing to align our spending with our corporate priorities. I will now hand the call back to the operator to kick off the Q&A session.
spk17: Thank you. As a reminder, to ask a question, you will need to press star 1 on your telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. And our first question comes from the line of Madhu Kumar with Goldman Sachs.
spk16: Yeah, everyone, thanks for taking our questions. I guess our first one is, again, kind of a simple one of looking at the calendar. How should we think about the cadence of events in terms of the release of cohort four toppling data vis-a-vis this July pre-BLA meeting and the August BLA submission?
spk18: It's going to be part of that process. We can't really give any more guidance to that, but effectively it's part of that process. We're trying to get the BLA in and we're trying to talk more about COVID-4 and complete the process of filing the BLA at the same time. I wouldn't think about it as any particular cadence. It should come as soon as we're able to do it.
spk16: On non-small cell and cervical cancer You mentioned you would plan to have regulatory interactions to discuss kind of making registrational cohorts. In both indications, what do you see as the effective population for unmet need where either TIL monotherapy or TIL plus PB1 blockade kind of makes sense as a line of therapy for whom you could have a registrational cohort?
spk18: Well, in both indications, you have the post-checkpoint population available where there's significant unmet medical need today. So that's sort of the short answer to your question. There's obviously much finer points, and we can talk more about the details of each study. And hopefully after getting our strategy together and regulatory input and sorting out our plans here, we can talk more about this. But that's the general approach. And then, of course, we've got frontline studies running in combination with PEMBRO and both as well to look at earlier lines of therapy as you normally do in oncology drug development.
spk16: Okay, one last question, kind of maybe scientific-slash-philosophical one. How do you think about PD-1 knockout TILs as compared to TILs plus PD-1 in terms of therapeutic evidence? Where would the PD-1 monoclonal antibody combination make more sense? Where would a PD-1 knockout TIL population make more sense? And I guess kind of which raises the question, how much of TIL efficacy is from the initial TIL product versus kind of epitope spread?
spk18: Well, all right, let me take the first part of your question, and we can talk a little more about till efficacy as we go here, and Medina and Frederick can jump in as well as needed. It's untested as of today, but we do believe that knocking down the gene within the T cell may lead to a more efficacious till and a more efficacious MOA for PD-L1 blockade. There's a number of reasons for this. and there's a number of advantages to knocking down the gene as opposed to giving the patient an antibody. For example, better penetration of the TILs into a tumor, stromal layers in the microenvironment as opposed to an antibody, and separately, that's an efficacy side argument, but on a toxicity side argument, you could argue that less off-target effects from the TIL having a knockout versus the antibody being systemically delivered. On the question of where the TIL efficacy comes from, Steve Rosenberg's lab has published a lot on this, and it's generally believed that the efficacy of TIL therapies occur in the early period after administration, although obviously we see, from a clinical perspective, we see responses that can originate later, after some time. You can have an SD convert to a PR and that kind of thing. But Rosenberg's imaging studies from back, you know, 20-plus years ago now, show TIL trafficking rapidly to the lungs and then to the tumor, and then generally show signs of tumor clearance early in the process. Medana, Frederick, do you want to add anything to that?
spk09: Yeah, this is Timer. This is Medana. Just a comment. I think even in the post-TIL infusion TCR persistence, right, in a non-genetically edited TIL, the TCR, the clonotypes that are persisting have the potential of getting exhausted with repeated antigenic stimulation. But once you knock out the PD-1, the immune surveillance capability of these genetically edited TILs may hypothetically be much more superior to the current TILs that we have. Again, as Fred said, it's untested, and we have to get into the clinic to test all these hypotheses.
spk18: All right, great. Thanks, everyone. As you probably saw me do, we're about to get into the clinical net, so that's something that's imminent. Our clinicaltrials.gov posting went up yesterday.
spk17: Cool, thanks. Thank you. And our next question comes from the line of Michael Yee with Jefferies.
spk05: Hi, this is Dennis staying on for Mike. Thanks for taking the questions. Two for me. One on the BLA, can you discuss any other gating factors we should be thinking about, like assay validation or perhaps even CMC? What else needs to happen between now and when you submit in August? And then my second question is on second-line lung cancer. You talked about using the LUN202 study as a registrational. Do you need to include a docetaxel arm, or can you get approval on just ORR, or do you think you need PFS? Thank you very much.
spk18: Sure, why don't I take the first one, and Frederick, could you take the second one? On the validation, on activities like validation and anything else we do in the CMC sphere to get ready for the BLA, we're not talking about the details of this publicly, but you can assume that a lot of that's happening or has already happened, and we're making great progress or we've already completed most of those tasks. There is a tremendous amount of work to be done here, but nothing that rises to the level of the potency assay situation that we were in before where there was more or less a gating item type of thing there that we had to resolve. So the teams at I-Advance, the employees at I-Advance, and all our partners are working really hard to get all these things done. Yes, there's tons of validations. There's tons of PPQs and comparability and all the stuff that needs to be run and succeed, but that's stuff that we think we can handle. Frederick, do you want to talk a little bit more about WN202 and then those attacks as a comparator and making that study registrational?
spk07: Yes, sure. Good question. So one thing to keep in mind here is that the FDA is happy to review single-arm data. It looks at single arm clinical trial data in a somewhat different way than randomized studies and will have preferences for where they would prefer which type of data but they are looking at single arm data they are looking at those data in the context of risk benefit assessed by the totality of the data which does include available therapy at that time But they are generally happy to look at that data. Keep in mind, docetaxel itself is not a great drug. It's not popular with non-cancer doctors. It has low response rates, short durability, a lot of toxicity. So there certainly is an unmet medical need, and that would certainly support bringing single-on data forward. The FDA generally will look at that. Got it. Thank you. Let me just add one more time. The other point to add is this is not combination therapy, right? In a combination therapy, that then gets a little more complicated because the SDA usually likes to look at data that will identify and pinpoint the contribution of components. Power therapy is a monotherapy. that you can compare with historical data from available therapy.
spk17: Thank you. And our next question comes from the line of Peter Lawson with Barclays.
spk15: Great. Thank you so much. I'm just kind of curious on just going back to the kind of sequence of events for the BLA submission. When would we get the first feedback from the FDA regarding that when we can see that?
spk18: Peter, probably the first real feedback comes at the time of acceptance of the BLA, which is 60 days after submission.
spk15: Would there be any commentary around the alignment around the potency assay?
spk18: I can't say for sure what FDA is going to say at that stage, but typically at that stage, they're going to tell you that the BLA has been accepted, and then later during the During the review process, they typically make requests where they could ask for more details about all sorts of things, including assay information. Now, we think we've addressed all that up front, and our goal is to address all that up front with the idea that any requests that come in are simple and easily dealt with.
spk15: Gotcha. And then as that communication kind of unfolds, you'll – you'll keep us in the loop of, like, how that communication is evolving, whether you need additional questions, et cetera. Is that the plan?
spk18: I think we'll probably get a lot of questions about it during that period, Peter, as you can imagine, but we'll do our best to keep everybody informed. You know, I don't think companies typically do a blow-by-blow as everything comes in from the FDA, but I'm sure you'll hear us talk about this as people check in. Let's say it's, you know, November, on the earnings call, people are checking in on how things are going, and we'll hopefully be able to give some updates then as to how we see the BLA review progressing at that stage.
spk15: Gotcha. And then just the final question just around when the BLA is submitted, will we get kind of more information around the potency assay, and will we see, I guess, IP filings as well around the potency assay?
spk18: Ultimately, you will see IP filings. I can't tell you exactly when because it's a little sensitive right now. But, you know, as you probably know, patent filings eventually become public, you know, typically around 18 months or greater after the first priority date. So there's some, you know, there could be information out there of some level. I don't think that I've tried to caution analysts to think that we're going to put details out on some of this stuff. It is, you know, competitively sensitive, and I think we'll probably continue to talk about it in the local culture.
spk15: Perfect. Okay. Thank you so much. Thanks for taking the questions.
spk17: Thank you. And our next question comes from the line of Colleen Cousy with Baird.
spk14: Hi. Good afternoon, and thanks for taking our questions. Have you received confirmation of the scheduling of the July meeting, or what is the likelihood that that might slip and could further delay your BLA filing?
spk18: Colleen, we don't, you know, a pre-BLA meeting is a Type B meeting, so they're requested 60 days in advance. We're not putting out details exactly on what's going on there, but right now the July timing is, you know, we just reannounced it, so we're very comfortable with that timing.
spk14: Okay, that's helpful. Thank you. And what is your latest understanding on whether the BLA submission and late-line melanoma would support accelerated or a full approval?
spk18: We don't know for sure. We think that with the size of the data set we're coming in with, with cohort four and cohort two, that there's a good chance of full approval. We've spoken about that a few times on calls recently. We do have the option of the phase three study that we've been talking about also serving as a confirmatory trial should the need be there. So we're planning for every scenario.
spk14: Okay, great. Thank you. And one more follow-up, if I can. The comments on the call around potentially using a CMO if needed upon launch, would you expect that that would be driven more by limited capacity at the ICTC early on or more due to any sort of indication you're seeing of high demand at launch?
spk18: It's probably a demand at launch issue first. We're trying to learn as much as we can from the launches of the two BCMA parties right now and just make sure we've got a really, really flexible footing when we go to launch. So the ICDC obviously bears the brunt of the capacity, but having the CMO available to help is going to just allow us to potentially do better than what happened with some of the 2-BTMA products, certainly with the Beckman.
spk14: Okay, great. Thanks for taking our questions.
spk17: Thank you. Our next question comes from the line of Tyler Van Buren with Cowan.
spk10: Good afternoon. Thanks for taking the questions. The first one, Dr. Puri, great to have you on board and congratulations on the new role. I'd love to hear why you decided to join Iovance at this stage in your career and the confidence you have in LifeLusil receiving approval. And then the second question is related to LN145 and lung cancer. When should we expect to get the next data update with earlier stage second-line patients? Could we get an update later in the year?
spk18: Sure. Why don't you take the second one first? Go ahead, Raj. Go ahead. Why don't you take the first one? I'll come back around. You went through it, too.
spk03: Go ahead. Yeah, I just want to say after a significant number of years at the FDA, 19 as division director, I was interested in other career goals, and I see that T-cells, TILs, have a great potential for solid cancer compared to other modalities such as checkpoint inhibitors or CAR T cells, which only works in the hematological malignancies, and checkpoint inhibitors have limited effect to 15 to 20% of the cases. So vast majority of the patients with solid cancer has no other option. And TIL cells, the broad reactive T cells, CD4, CD8 cells, have a great potential in the solid cancer. So I think that was one of the main goals to join a company, and IRAN is an important part of this therapy. So that's the reason I joined IRAN.
spk18: And then with respect to LUN2 and data possibly later this year, we haven't said specifically. Obviously, we're trying to optimize enrollment in that trial and get more data there to – to bolster what we think is a clean efficacy signal in tilt therapy and non-small cell lung. And if we get some data that we think is worth putting out, I think we would try to put that out as soon as we can. We tried to do that specifically with lung last year. So all I can say there is just hang tight and let us continue to enroll and generate data.
spk10: Thanks very much.
spk17: Thank you. And our next question comes from the line of Mark Bradenbach with Oppenheimer.
spk11: Hey, good afternoon. Thanks for taking the question. Just a quick one for me with respect to the new trial of IOV-4001. Can you just remind us why the protocol is focused on melanoma and non-small cell lung cancer only and is not inclusive of some of the other tumor types you've investigated TIL therapy? And also, will this trial kind of be competing at all with the LUN202 trial in terms of trying to enroll the same types of lung cancer patients, or are they more or less distinct populations? Thanks.
spk18: Frederick, do you want to take this one?
spk07: Yeah, sure. Good, good question. Thanks. So there's really two strategies here in the same trial. Number one, the cohort that enrolls melanoma patients is an opportunity to enroll and generate clinical data fast because we know there is demand for access to TIL therapy. This is an attractive opportunity. new approach, really promising based on the preclinical data and the rationale that Fred and Madan spoke about earlier. So we'll be able to generate data in a population that we know very well based on our own data and the academic data, which then allows us to compare and draw some conclusions as soon as possible. So that's really the strategy for melanoma here. Non-small cell lung cancer is a really important indication and prototype for us. We have generated data in COVA3B that indicate activity of TIL therapy in non-small cell lung cancer. We hope that with the technological approach of PD-1 knockout, we are improving on both response rates and durations, and in addition, If you look at the populations, we are going to a broader patient population than the population we're targeting in LUN202, both in regards to allowed numbers of prior therapy as well as a drive of mutations in the patient's tumor. So there's really an opportunity to go and take another shot at those late-line patients and start exploring activity and drive a mutation positive station. So that all speaks to your question about overlap with existing studies. For melanoma, we do think that because we are going to enroll rather quickly, that there's little risk of overlap with other efforts in melanoma that we are currently taking.
spk11: Understood. All right. Thanks for the detailed answer.
spk17: Thank you. And our next question comes from the line of Mara Goldstein with Mizuho Securities.
spk06: Hi, guys. This is Jerry on for Mara Goldstein. Thanks for taking our questions. So first is also on IOV4001. How do you anticipate prioritizing the two melanoma NSCOC cohorts?
spk18: How do we anticipate prioritizing? They're both going to be open at the same time, and they're different. patient populations, and different investigators. So I kind of view them as equal priority, but Frederick just mentioned a little bit earlier that we do expect melanoma to enroll rapidly because of the demand in that area right now. So I can't tell you for sure exactly how enrollment will go in one versus the other, but melanoma should enroll faster, I would think. That doesn't mean we're prioritizing it.
spk07: These two cohorts are open simultaneously. They're expecting different enrollment rates, But there's really no overlap or competition. We're certainly not held back by having limited manufacturing slots or anything like that. So we don't have to decide which patient is next because of any sort of concerns around having slots for these patients. So there's no need to prioritize based on that.
spk06: Gotcha. Thanks for that, Calder. Next one is on LN145. With the slight trial protocol change, do you expect a similar strategy to be applicable for other tumor types as well?
spk18: Are you talking about LUN202? Yes. Yes, there is going to be potential for that, yes.
spk06: Gotcha. Okay. Well, thank you for taking our questions.
spk18: Thank you.
spk17: Thank you. And our next question comes from the line of Ben Burnett with Stifel.
spk20: Hey, thank you very much. Just a couple commercial questions. I guess, first, is there any color you can provide just at this point in terms of securing IL-2? Just commercially, will this be procured kind of on an as-needed basis in real time or otherwise? And I guess, how confident are you that your IL-2 supplier can handle the initial commercial demand?
spk04: Hi, this is Jim Ziegler. We've met with the folks from Clinigen that supply IL-2 in the past. As you know, they're going through a transition right now. We'll be working with them as we approach our BLA and coordinating forecast needs with them to ensure that we have adequate supply across the board. We have looked at all of the potential ATCs that we're working with, And all of them basically have the ability to order IL-2 with their current wholesalers.
spk20: Okay. So they would order IL-2 on their own. You wouldn't be ordering IL-2 and then supplying it yourselves.
spk04: Correct.
spk20: Okay. Okay. And then if I could, just another question. Really, I guess just on the sort of the patient journey that you're expecting if Lifeloosil is approved. Like specifically, are you expecting cardiac and pulmonary functions to need to be verified? And if so, does that happen after the biopsy is taken?
spk09: This is Mehran Jagesh. It's a very valid question. So the conduct of the clinical trial, patients have to obviously meet eligibility criteria prior to the tumor harvest. I suspect that will be the same pattern of practice once we are in the commercial landscape. HCPs will need to ensure that the patients have adequate cardiopulmonary reserve before they go in for a tumor harvest, which then subsequently leads to the TIL cell therapy. So that's a pretty standard practice in the world of stem cell therapy, in the world of CAR T cell therapy as well today.
spk20: Got it. Okay. And would they, I guess, would they go through those tests again after the manufacturing process when it's ready, when TIL infusion is ready? Okay.
spk09: Not necessarily. Obviously, if they have had any further cytotoxic therapy, which may influence their cardiac or pulmonary reserve, which is highly unlikely given the agents that are in use for metastatic melanoma. So typically it is done once, and unless the clinical situation changes, it's typically not repeated.
spk20: Okay. Super helpful. Thank you very much.
spk17: Thank you. And our next question comes from the line of Estika Gulwardeen with Truist.
spk13: Hello. This is Anand Shah on for Ostica Today. Just one question on lung and then one on cervical. So on the 202 study protocol amendment, if you gather resections for a patient and they haven't yet progressed, how do you determine when to manufacture a TIL product? And will you guys have TILs manufactured and stored somewhere until needed?
spk09: Yes, this is Medan. Good question. So I think what you're referring to is what we allude to as a pre-progression resection. So, yes, the patients will have their tumor resected and the tools manufactured. We expect most of these patients to eventually progress because the chance that a patient is going to, quote, unquote, respond for perpetuity in a non-small cell lung cancer is very small. So we do expect most of these patients to progress on their frontline therapy and does the probability of using the TILs that have been manufactured approaches at a very, very high number.
spk13: And would that be a gating factor from presenting data from the study? And any other gating factors that you could mention in terms of just presenting the data would be very helpful as well?
spk18: No, that should not be a gating factor for data from this study. We view that as actually something that we think will lead to improved involvement in and more flexibility, and it could be something that we explore, like I said earlier, on other indications too.
spk13: Okay, great. And then on cervical cancer, when can we expect an update just on the regulatory discussions that you've been having with the FDA? It seems like it's based on the cadence of these earnings releases that you've been talking to them for somewhere between like two to five months. And, yeah, just when can we get an update on that?
spk18: Bear in mind that the announcement with Pembrolizumab's approval came at the very end of last year. So, yes, it's been a few months, but it does take some time to get in front of the regulator and then also build a strategy. So we haven't guided to a specific date yet because we don't have one yet, but we are working hard on cervical, and hopefully we'll be back with more information soon.
spk13: Final one, would you expect a similar sort of timeline with longer? Is there anything different there versus your conversations on cervical?
spk18: They're separate conversations, and so I can't say the timelines would be the same, but it's similar in a sense that we're having those discussions separately with the FDA and setting the strategy for those things. Other than that, I can't really link them.
spk17: Okay, thank you so much. Thank you. And our next question comes from the line of Ren Benjamin with JMP Securities.
spk02: Hey, good afternoon, guys. Thanks for taking the questions. Fred, I think I heard this right. I'm not sure. In the prepared remarks, I believe you said that there would be data at ASCO and CITSE. If I did hear that right, can you give us an idea as to what are the most likely trials that might be updated at those conferences?
spk09: This is Madan. So I think what we mentioned in the prepared statement is our data that we had presented in 2021. at ASCO, CITC, and AACR on the 136 patients across four tumor indications.
spk18: And we do have a title up for ASCO coming this year, which you can see, but we can't really say much more about that right now.
spk02: Okay. And then with the potency assays, I'm just kind of curious, are those assays already integrated into the new ISTC facility, or is that something that's done you know, sort of outside the facility.
spk18: Now, that's something that we do at our facility, and we can do it elsewhere as well, but that's something that, you know, the facility, Rennie, I can't remember if you joined us for any of our open houses, but if you have come and seen it, you'll see it's fully integrated in terms of QC, and that includes the ability to do the potency matrix that we talk about a lot.
spk02: Yep, got it. Okay, that makes sense. And then just a couple of other ones. I don't know if you've mentioned this in the past, but how are you thinking about a potential sales force, and how big could it or small could it possibly be?
spk04: I think you can think of it on a comparison basis to the existing cell therapy field forces for the other CAR-Ts. You know, the way that we'll be operating is through the potential authorized treatment centers. there's a pretty high concentration of care, and then the community referrals will come in through the ATCs. So I would say if you benchmark the current CAR T field forces, you're right in the ballpark.
spk02: Okay. And I guess one final one for me. In your discussions with the regulatory agencies, have they brought up anything in particular that could be a review issue Or do you think that since this is the first time that a TIL is going through, that it's most definite that you'll have an ODAC now?
spk18: We don't know that for sure. It's possible because it is the first therapy in this class that we could get in a committee, advisory committee. But TIL therapy is also very well known. And it's well known from NIH and NCI experience, as well as plenty of other academic centers' experience in We've got tons of data at IVANCE, too, so that doesn't mean we have to get an advisory committee. We may not get one. To the bigger part of your question, basically, are there any other things? No. Right now, we feel pretty comfortable with our timings and all the things we're doing. We have to, obviously, for biotech, it's a big thing to file its first BLA, so we have to execute on that. But other than that, we think we're in good shape.
spk02: Terrific. Thanks for taking the questions.
spk17: Thank you. And I'm showing no further questions. So with that, I'll turn the call back over to Interim President and CEO, Fred Vogt, for any closing remarks.
spk18: Thank you again for joining the Iovance Biotherapeutics First Quarter 2022 Financial Results Conference Call. It's an exciting time to be part of Iovance as we move towards our first BLA submission. Continue our ongoing clinical trials and expand our growing pill pipeline into new clinical trials, including the clinical trial of IV4001 that just posted to clinicaltrials.gov yesterday. I would like to recognize the patients and physicians who are participating in our clinical studies, as well as our employees and cross-functional teams for their hard work in moving pill therapy forwards. I would also like to thank our shareholders and covering analysts for their support. Please feel free to reach out to our investor relations teams if you wish to follow up.
spk17: Ladies and gentlemen, this concludes today's conference call. Thank you for participating, and you may now disconnect.
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