Iovance Biotherapeutics Inc
NASDAQ:IOVA
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Iovance Biotherapeutics Inc
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Welcome to the Iovance Biotherapeutics Fourth Quarter and Full Year 2021 Financial Results. My name is Chery, 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. [Operator Instructions] Please note that this conference is being recorded. I will now turn the call over to Sara Pellegrino, Vice President, Investor and Public Relations at Iovance. Sara, you may begin.
Thank you, operator. Good afternoon, and thank you for joining us. Speaking on today’s call, we have Dr. Fred Vogt, our Interim President and Chief Executive Officer; Dr. Igor Bilinsky, our Chief Operating Officer; Jim Ziegler, our Senior Vice President, Commercial; Dr. Friedrich Finckenstein, our Chief Medical Officer; and Jean-Marc Bellemin, our Chief Financial Officer. Dr. Madan Jagasia, our Senior Vice President, Medical Affairs, is also on the call to participate in the Q&A. This afternoon, we issued a press release that can be found on our website at iovance.com, which includes the financial results for the 3 months and 12 months ended on December 31, 2021, as well as 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 preclinical activities, potential future applications of our technology, manufacturing capabilities, regulatory feedback and guidance, payer interactions, collaboration, cash position, 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.
Thanks, Sara, and good afternoon, everyone. I’m pleased to highlight our fourth quarter and full year 2021 progress at Iovance during today’s conference call. In 2021, we continue to advance toward our first BLA submission and expanded our two platforms into new indications and earlier treatment settings. For our lead TIL therapy, lifileucel, our top priority remains our planned BLA submission in metastatic melanoma. We have continued ongoing work developing and validating our potency assays. We have also engaged discussions with the FDA during the second half of 2021, and we are confident in our current guidance for the anticipated BLA submission during the first half of 2022. Resolution of the potency assay in melanoma is also a key step towards regulatory plans and other indications. 2021 was our busiest year yet in terms of TIL data presentations. Over the past 12 months, we presented data in 118 patients across five indications in sour solid tumor types at multiple medical meetings, including the American Association for Cancer Research or AACR meeting, the American Society of Clinical Oncology or ASCO meeting and the Society for Immunotherapy of Cancer or SITC meeting. We believe that this growing set of clinical data continue to demonstrate the power – the potential power of Iovance TIL therapy to become the next paradigm-shifting treatment regimen for solid tumors. Last year, we also opened the Iovance Cell Therapy Center, or ICTC, in Philadelphia. We have made significant progress in our internal manufacturing capabilities at ICTC, which Igor will highlight further, and we grow our organization to prepare for commercial manufacturing and launch. Today, we have approximately 350 employees at the company who have, on average, more than four years of cell therapy experience. We believe that the breadth and depth of talent within our organization during the support and time of growth is a testament to the potential of our Iovance TIL therapy in solid tumors and our ability to maintain leadership within the field. Looking towards 2022, our milestones include: submitting our BLA for lifileucel in metastatic melanoma in the first half of the year, advancing TIL therapy in non-small cell lung cancer, which Friedrich will highlight; executing an updated registrational strategy in cervical cancer based on FDA dialogue and feedback in reflection of the evolving landscape of care in this indication; defining our strategy for TIL plus pembro combination in early-line solid tumors beginning with melanoma; and finally, initiating the first Iovance clinical study for IOV-4001, a genetically modified TIL product in which PD-1 is inactivated and further advancing our research and next-generation TIL programs to remain at the forefront of TIL therapy in solid tumors. Overall, we are confident in the strength of Iovance’s position to be the global leader in developing, delivering and innovating TIL therapies for patients with cancer. We are well on our way to becoming a fully integrated organization to launch the first onetime cell therapy in solid tumors. Owning our manufacturing capability is the key to our success. So I will hand the call to Igor now to talk more about our progress there.
Thank you, Fred. During 2021, we achieved several milestones at the Iovance Cell Therapy Center, or ICTC, which is our 136,000 square foot cell therapy manufacturing facility. We completed commissioning activities and initiated TIL clinical supply from the ICTC in the third quarter of 2021. The first patient with cancer received TIL manufactured at ICTC in September 2021, as part of our ongoing clinical trial. In parallel with clinical manufacturing, we are on track in preparing the ICTC for the BLA submission and commercial manufacturing upon the potential BLA approval. Several important activities are now underway such as validation activities and process, performance qualification or PPQ runs. In addition, we are getting ready for FDA pre-approval inspections at both ICTC and our contract manufacturing partners’ facility, which we expect to occur soon after the BLA filing. Turning to our intellectual property or IP portfolio. We continue to build our robust and growing IP portfolio to support our proprietary manufacturing processes as well as our know-how surrounding TIL therapy. We currently own more than 35 granted or allowed U.S. and international patents. This IP covers TIL 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. Our granted patents as well as our filed patent applications are directed towards Gen 3 manufacturing, selected TIL products, stable and transient genetic TIL modifications, tumor digest and fragment compositions and methods, including cryopreservation and combinations of checkpoint inhibitors and TIL products. I would now like to hand the call to Jim Ziegler to highlight our commercial launch preparations. Jim?
Thank you, Igor. Throughout 2021 and into 2022, the Iovance team has made steady progress in our commercial launch preparations, while maintaining financial discipline. Our launch priorities include the onboarding of our authorized treatment centers or ATCs, payer engagement and related operational readiness activities. Our cross-functional teams continue to partner with leading U.S. cancer centers to build their TIL service line capability. Our training program is designed to ensure cross-disciplinary teams can administer the lifileucel treatment regimen upon FDA approval. Our goal is to onboard at least 40 ATCs per launch. This number is informed by our assessment of the CAR-T market where claims data indicate that the top 10 centers account for about 50% of the CAR-T treated patients, and the top 40 centers account for about 80% of the CAR-T treated patients. We expect a similar concentration across our ATCs for the potential commercialization of lifileucel. Our longer-term goal is to have enough sites so that most patients in the U.S. can be within a few hours drive to an ATC offering lifileucel TIL therapy. The planned timing and execution of key onboarding and training is aligned to BLA-related milestones to ensure just-in-time training and readiness at our ATCs. Although, there is a significant amount of work that will occur between our BLA submission and launch, our core commercial team has built the foundation to scale rapidly and efficiently. Reimbursement is also a critical factor for patient access at launch. In the last year, our market access team engaged commercial and Medicare payers responsible for more than 90% of the covered lives as well as Medicaid states responsible for approximately 50% of the covered lives. Based on these interactions, we believe that payers appreciate the unmet need and the potential clinical value of lifileucel for patients with metastatic melanoma cancer. Our reimbursement strategies are designed to secure coding, coverage and payment. In 2021, Medicare expanded DRG 18 to include CAR-T and other immunotherapies, including lifileucel. This is an important milestone achievement because upon lifileucel approval, hospitals will have more appropriate payment for Medicare beneficiaries. We continue to engage payers and CMS as we plan for BLA submission and prepare for commercialization. We are also pleased with the progress of our Iovance Cares program, which remains on track for launch. Our goal is to deliver a best-in-class cell ordering and patient support system that assist the patients, physicians and ATCs at every step of the process. Iovance Cares includes our proprietary chain of identity and chain of custody system. Our patient management approach and our integrated approach to quality. I will now pass the call to Friedrich Finckenstein, our Chief Medical Officer, to highlight our clinical progress.
Thank you, Jim. I am pleased to share highlights from our TIL clinical programs across the various data presentations from 2021. In melanoma, we presented updated Cohort 2 data at ASCO 2021, we reported 36.4% overall response rate or ORR and a median duration of response, or DOR, that was not reached at 33.1 months of median study follow-up as assessed by investigators. These Cohort 2 data continue to demonstrate the durability of onetime treatment with lifileucel in metastatic melanoma patients after anti-PD-1 therapy. Looking ahead for this year, we plan to report data from the pivotal Cohort 4in our melanoma study, as assessed by an independent review company in connection with the BLA submission. We are also excited about the data for TIL in combination with pembrolizumab in checkpoint inhibitor naïve melanoma patients. The most recent results presented at SITC 2021 demonstrated a 60% ORR and 30% complete response and support the potential for this combination as earlier treatment for melanoma. We look forward to enrolling additional patients to further defining our strategy in frontline melanoma during the coming year. We are also very excited about the proof of concept for TIL plus pembro as an early treatment option in cervical and head and neck cancer patients, which we also highlighted as ITC 2021. Overall response rates for TIL plus pembro were above the published response rates for pembro alone and melanoma, cervical and headed neck patients who are not anti-PD-1 therapies. An additional solid tumor indications, lung cancer patients continue to have an unmet need for new treatment options. Last year, we presented our first clinical data set for Iovance TIL as treatment for non-small cell lung cancer SITC. We were very encouraged by the observed responses in heavily pretreated non-small cell lung cancer patients received one or more prior systemic therapies, including anti-PD-1 therapy. This data set was an important proof of concept for TIL in non-small cell lung cancer and provided valuable learnings to enroll earlier-line patients in our ongoing IOV-LUN-202 study. We are enrolling second-line metastatic non-small cell lung cancer patients in the IOV-LUN-202 study at 30 sites while engaging with the FDA about parameters for further registration. In cervical cancer, as Fred mentioned, we are actively engaged in regulatory discussions. Lastly, I am excited by the growth of our research pipeline as we look to enter the clinic this year with our first genetically modified TIL therapy candidate IOV-4001. IOV-4001 is a TIL product with inactivated PD-1 using the TALEN technology licensed from Cellectis and has the potential to deliver TIL and PD-1 inhibition within a single therapy. I will now hand the call over to Jean-Marc to discuss our fourth quarter 2021 financial results.
Thank you, Friedrich. My comments will reflect the high-level financial results from our fourth quarter and full year 2021. Additional details can be found in this afternoon’s press release as well as in our SEC filings. I will begin with our cash position. As of December 31, 2021, Iovance held $602.1 million in cash, cash equivalents, investments and restricted cash compared to $635 million on December 31, 2020. A strong cash position is expected to be sufficient into 2024 to advance our operating plan, including pipeline development, commercial manufacturing readiness and launch preparation. Moving on to the income statement. Our net loss for the fourth quarter ended December 31, 2021, was $99.3 million or $0.63 per share of which approximately $6.3 million or more than $0.04 per share were onetime expenses. This compared to a net loss of $68.4 million or $0.47 per share for the fourth quarter ended December 31, 2020. Net loss for the full year period ended December 31, 2021, was $342.3 million or $2.23 per share compared to a net loss of $259.6 million or $1.88 per share for the full year period ended December 31, 2020. Research and development expenses were $75.6 million for the fourth quarter ended December 31, 2021, an increase of $23.1 million compared to $52.5 million for the fourth quarter ended December 31, 2020. Research and development expenses were $259 million for the full year period ended December 31, 2021, an increase of $57.3 million compared to $201.7 million for the full year ended December 31, 2020. The increase in research and development expenses in the fourth quarter 2021 over the prior year period was primarily attributable to an increase in cost associated with growth of the internal research and development team, including stock-based compensation expenses, and increasing clinical trial costs and facility-related costs associated with iCTC. The increase in research and development expenses in the full year 2021 over the prior full year period was primarily attributable to growth of the internal research and development team and an increase in the clinical trial cost and facility-related costs associated with iCTC. General and administrative expenses were $23.8 million for the fourth quarter ended December 31, 2021, an increase of $7.7 million compared to $16.1 million for the fourth quarter ended December 31, 2020. General and administrative expenses were $83.7 million for the full year period ended December 31, 2021, an increase of $23.5 million compared to $60.2 million for the full year ended December 31, 2020. The increases in general and administrative expenses in the fourth quarter and full year 2021 compared to the period – to the prior year periods were primarily attributable to an increase in costs associated with growth of the internal general and administrative team, including stock-based compensation expenses and an increase in intellectual property filing related costs. As of December 31, 2021, there were approximately 157 million common shares outstanding. We continue to focus on investments in four key areas, as outlined previously, to ensure the growth and strength of our value creation. This includes advancements and expansion of our clinical pipeline, launch readiness, a strong cash position and manufacturing at iCTC, which will provide new cost efficiencies as we are able to shift work currently being done through contract manufacturers to iCTC. I remain confident that by managing our investments across these priorities, we will continue to stay focused and align our spending with our corporate priorities. With late-stage clinical assets in our pipeline as well as our strong balance sheet and focused investment on launch preparation, we are also well positioned to execute our operating plan. I will now hand the call back to the operator to kick off the Q&A session.
Thank you. [Operator Instructions] Our first question will come from Tyler Van Buren with Cowen. Please go ahead.
Hey, guys. Congrats on the progress. Thanks very much for taking the question. Don’t you have to have resolution on the potency assay front in the next month or two in order to be able to run the assay or assays with the Cohort 4 patient samples and generate the data to submit the BLA by the end of the first half? And I guess – my follow-up to that would be, is it possible that you’ve already started testing the Cohort 4 patient samples with the latest iteration of the potency assay or assays in anticipation of the filing?
Yes. Thanks, Tyler. I can answer some of that. The – we haven’t disclosed the detail of how those interactions are going with the FDA and whether we’ve commenced testing or at that level. But in general, yes, we have to get some – we have to be moving towards a BLA filing. I should note that it’s important to understand that we could be holding conversations with the FDA in parallel while we do work. We could be staging it so that we manage the risk really well, and it can come right down relatively late in the game for us to really feel comfortable. But regardless, right now, what we’ve been saying publicly and clearly again here on the earnings call is that we’re comfortable filing a BLA in the first half of this year. So that should give you some indication of where we think we are with the FDA.
That’s great. Thank you very much.
Thank you. Our next question will come from Michael Yee with Jefferies. Please go ahead.
Hi, thank you, and thanks for the update guys. I have one question and a follow-up. My question is – in relation to the filing, is there a scenario where you file and meet your guidance and go ahead and do that and that you have to tell the Street or with the Street that the final agreement or the final sign off or the final validation is obviously an ongoing process. And ultimately, everything gets filed and finalized at the PDUFA date. Can you maybe just talk about that scenario? I think like Wall Street just thinks you have the screen light on a piece of paper and then you just filed. So maybe talk to that a bit in that scenario. One quick follow-up. You did say clearly that you’ll announce the Cohort 4 melanoma data. Can you just – when that gets done, can you just remind me, you had previously had an interim. And can you just tell me where Cohort 4 is and when you do it, it will be an independent review when you present it, and that’s supposed to be similar response rate data as Cohort 2. Just remind us about that status. Thank you. Thank you.
Sure, Michael. Let me take the last one first, actually. Cohort – the Cohort 4 data as part of the BLA submission. It’s IRC red data. And as part of the BLA submission in conjunction with that, we would talk more about that Cohort 4 data because that’s time to go in with the BLA and obviously, it’s important information to put that out. Cohort 2 is already out there, and we’ve been talking about it for a while. You can see that data, we don’t know Cohort 4 yet – something we’re still working on. But the Cohort 2 data is a very similar study in many respects. So I can give some guidance as to what we expect in these populations, although, of course, they can differ. On the assay part, let me try to answer the whole question there, because going all way through to the PDUFA date, which could – would be in early 2023 potentially or very late 2022, depending on when we submit the BLA this year. There can be conversations with the FDA during the entire pendency of the BLA after it gets accepted, as to sort of the specifications and some aspects of your potency assay or assays that you’re proposing for your products. So things can change during that period. I think that’s what you might be asking. Of course, they can comment on validation and you could present additional data, you could provide them with more information about the specifications that you’re proposing. And they get asked questions about any aspect of the validation package during that period and you could go back and forth with them on that. So you’re absolutely right in thinking that you don’t really know for sure until the BLA is approved, that all this is done, and that’s the way it just is in drug development. Earlier in the process, though we submit the BLA when we had the pre-BLA meeting prior to that. We’re trying to get as much clarity as we can from the FDA, so we can make sure we’re successful on the PDUFA date and getting that approval. So we’re not submitting something that has gaps in it that we could have filled we listen to the FDA. So that’s our big goal leading up to the BLA submission itself. And of course, some of that includes successfully completing validations and doing a lot of the work that eventually gets reviewed during the pendency of the BLA. That was a long-winded answer, but I hope I got what you were trying to get there, Michael.
I think, that makes sense. Thank you.
Thank you. Our next question will come from Peter Lawson with Barclays. Please go ahead.
Great. Thanks for taking the questions. Just on cervical cancer, I wonder if you could walk through kind of time lines and what kind of what’s changing around the potential for filing for cervical cancer that we should be thinking about.
Yes, Friedrich, do you want to answer that one? .
Sure, happy to. Good question. So obviously, we are acknowledging that the treatment landscape in cervical cancer has changed quite a bit the approval of checkpoint inhibition as part of first-line standard of care was a paradigm shift, and it’s great to see immunotherapy to enter that field for the patients. So that’s good news. And obviously, now changed the landscape and opportunities after first-line chemo, and we saw that with how this impacted some of the additional checkpoint inhibitors that we’re going after that second line after chemotherapy only spot. TIL therapy is differentiated from checkpoint inhibitors, we know that we see activity in patients that have received checkpoint inhibitor therapy from our melanoma data. And that’s early based on a differentiated mechanism of action. Because we knew that and because we were foreseeing the changes in the first-line landscape and acceptance of checkpoint inhibition as standard of care, we started a post-checkpoint inhibitor cohort early in 2019 already. And we do think that, that is an area of unmet need that we would be able to address the data in that setting. We are planning to execute a registrational strategy, addressing feedback from the FDA and addressing this changed landscape. And we do think that we do have some headway in that post-checkpoint inhibitor setting.
Perfect. Thank you. And just with the addition of Dr. Perry, does that change the process in any way for filing? Is there any chance you’d file at risk?
No, I don’t – no, that’s not really the plan here, Peter. He’s essentially a great addition to our team. That’s not really – it’s not really tied to the BLA or how we would handle the BLA. Of course, having them join us is going to be very helpful and do an anything from a regulatory perspective, but that’s not really something we’re thinking about. .
Got you. Okay. Thank you so much. Thanks for taking the questions.
Thank you. Our next question will come from Nick Abbott with Wells Fargo. Please go ahead.
Good afternoon. Thanks for taking my questions and I appreciate your clarity for it as always. First one, so just going back, following up on Mike’s question from earlier. So have you closed a Cohort 4 database is being cleaned, ready for analysis?
We haven’t announced that yet, Nick. We are without getting the details there, obviously, we’re very late in the game. So that’s something we would need to do in a relatively short time period here, but we haven’t spoken directly about that yet.
Okay. And then maybe thinking forward, the potential approval of nivo and relatlimab, do you think you need to show benefit in these patients that’s a similar magnitude to what you’ve shown currently from Cohort 2 and presumably what you’re showing Cohort 4?
It could be important in the future landscape, of course, because there will be patients coming off that line of therapy that would potentially be candidates for lifileucel, but don’t assume that we haven’t seen some of those patients already because those patients are out there right now in the clinical trial is getting. So that’s something we’re looking at closely. I can tell you that’s something we’ve considered closely, and we’ll try to provide updates at medical meetings on how we might address those patients.
Thank you.
Can I chime in here? So I think 1 thing to keep in mind is that the deal that we have presented are clearly indicating benefit that’s comparable between patients who have failed PD-1 monotherapy and patients were failed PD-1 and CTLA-4 blockage combination. So I think that might be indicative of what we might be seeing in patients who got failed other combinations as well. Obviously, we don’t have data on that yet in a controlled fashion, but I think that’s something to keep in mind for that setting.
Yes. It’s a good point, Friedrich.
Thank you. Our next question will come from Mara Goldstein with Mizuho. Please go ahead.
Thanks for taking the question. Just on the initiation of the trial for IOV-4001 in this year that you’ve indicated. Can you talk about the clinical plan for that and what indications you might look at? And then I just wanted to ask about the sequential R&D spend and what that run rate looks like going forward, given the different – the delta in the fourth quarter versus the prior quarters?
Yes. Maybe I can take the first one and have Jean-Marc follow up on the second one. So we haven’t disclosed that yet, Mara, but that’s something we’ll obviously talk about the clinical plan for that asset as soon as we can because that’s tied once we get the regulatory following through, I think we’ll – you’ll hear a lot more from us on that. We’re obviously indicating – interested indications that we know and can benchmark against as well as potentially new indications that might benefit from the – having to combine effects of a checkpoint inhibition like mechanism built into the TIL cell itself, which can theoretically infiltrate better into the tumor than the antibody as well as our polyclonal T cell platform combined in the same asset. So we’re looking for indications that would benefit from that approach. And hopefully, we’ll be able to talk about that pretty soon. Jean-Marc, do you want to talk a little bit about the R&D spend?
Yes, sure. Thanks for the question. Look, honestly, of course, we are focusing spending on building our pipeline and the research will be part of it. So IOV-4001 is only one aspect of the program that we are building. But from a spending perspective, I mean, we are definitely looking at reallocation of expenses in a way that if you think about what we spent for building iCTC, for example, in 2021 will be reallocated to research for 2022. So we have an increase in research and development spending in Q4. I’ve mentioned during the script that we have this onetime $6.3 million. So that’s why you have a bit more of expense there. But honestly, there is no real concern we will keep steady on the research and development spending for 2022.
Okay. And if I could just also ask a question around the CEO permanency and what that looks like from this – at this point in time from a timing perspective?
Basically, our Board is conducting a search, and we’re still looking for candidates. It continues to be ongoing top priority for our Board, and we’ll announce the outcome as soon as we can. I don’t really have anything else.
Okay. Thank you.
Thank you. Our next question will come from Mark Breidenbach with Oppenheimer. Please go ahead.
Hey, guys. Good afternoon. Thanks for taking our question. Just one for me, maybe directed at Friedrich. I was hoping you could provide a little more color on the nature of these parameter changes to the LUN-202 trial that you’ve been discussing with the FDA. Maybe a little bit more detail on that would be appreciated.
So I don’t think that we have spoken about the exact details of our discussions with the FDA in regards to LUN-202. So I’m not sure I can really comment on that. Just as a reminder, what we’re doing with LUN-202 is we are enrolling specifically patients that have sales the single line of checkpoint inhibitor plus standard of care chemotherapy. So this is a earlier line population than – the population that was enrolled to those proof-of-concept Cohort 3B from our basket study. So that’s the parameter changes that you’re referring to. So that’s really the main point is focused on an earlier line population with this prior therapy.
Okay. That wasn’t already part of the protocol as it was originally designed.
No, that was the design of the study as we opened, and we have not changed the design since then.
Okay, thank you.
Thank you. Our next question will come from Colleen Kusy with Baird. Please go ahead.
Great. Thank you so much for taking the questions. So are there any characterizations you’re able to provide as to how the latest conversations with the FDA have progressed regarding the potency assay?
Yes. Sure, Colleen. They’ve given us a lot of good advice, lot detailed advice, and we feel like we really understand what they’re looking for, and we think we’re going to be able to address that. At the technical level, the details of that are still confidential, and that’s not something we’re quite ready to talk about. But as a general matter, it’s at the level where really productive discussions can be had, and we can respond to what the – what we think their concerns are and we can provide them with data and assays and sets of assays that we think address our concerns and detail. So it’s advanced quite a bit over the past nine months in that respect.
Understood. That’s helpful. And then any comments on how the PD-1 combo in lung cancer is advancing and when we might see data from that combination?
Sure. That study is Cohort 3A in our COM-202 study. That study has been enrolling for a while now. We haven’t guided to specific conferences or anything where we would present, but it is one of those studies where, obviously, we’d like to present some data at some point soon. So we presented as much data as we possibly could last year, and I look forward to 2022, we’ll try to keep that up. I just can’t say exactly when we’ll be able to do that.
Great. Thanks for taking my questions.
Thank you. Our next question will come from Ben Burnett with Stifel. Please go ahead.
Hey, thank you very much. I had a question regarding the melanoma BLA in the new manufacturing center ICTC. I guess how much patient experienced have you accrued from product manufactured here for late-line melanoma specifically? And I guess can you provide – just a little more color just regarding your expectations for what’s likely needed in terms of validation data, numbers of samples or anything like that?
Igor, do you want to talk about at least the first part of that? And I can maybe cover on the last part.
Happy to. So thanks for the question. So we – the facility is focused on two things right now. One is clinical manufacturing for ongoing clinical trials. And that’s primarily the Gen 2 process that’s part of the Cohort 4, but we intend to file BLA and then the other part is preparation for commercialization and BLA filing, including – all including the filing and the subsequent inspection that we expect to take place soon after the filing and then following that, getting the capacity ready to meet the commercial demand after the potential BLA approval. So that’s we’re well on track along all of those activities. And then Fred will…
I think we – go ahead, Igor. If you want to get the part about the retains. I think that’s what you were asking about then, right?
Yes, there’s anything you can say about just the number of samples kind of ballpark in terms of validation data that’s needed.
I mean it’s a good number of samples. Igor, go ahead, if you want to answer it.
Actually, Fred, go ahead. I’m not sure I understood the question fully, so.
I think what you’re saying, Ben, is the number of samples needed to perform validation exercises both for the assays and for anything we need to do with the facility. Is that right?
Yes. Sorry, I’ll be more clear. I think to validate that the product that’s manufactured at the new site is similar to what’s been manufactured here, yes.
So that’s what we call comparability and part of comparability in what we call PPQs or process performance qualification. It’s we have – it’s a good number of samples. I don’t have the exact numbers, Igor provide doesn’t either. But there’s obviously a lot of work done to make sure it statistically well justified with the FDA, and that’s what really drives the number of samples. And we’re well – we’re set in that area, we think.
Okay. Thank you very much.
Thank you. Our next question will come from Asthika Goonewardene with Truist Securities. Please go ahead.
Hi guys, thanks for taking my questions. Just maybe a logistical one here. If I understand your answer to Tyler’s question and you might be doing some of these potential potency assay work to include in the filing prior to you getting your official okay from the FDA. Is there a scenario that the FDA comes back to you and says what we want to do a couple more things and you run out of samples? And then I have a follow-up question about lung cancer after that.
All right. Let me – yes, let me take the first one. They could always come back and ask and ask and ask for stuff and you could always just run it retains at some point, but we don’t expect that to be the case. We think we’ve got the retains we need to answer their questions right now. And we’re comfortable performing the assays that we’ve developed and that we think are responsive to what the FDA wants. I think maybe sort of the core of your question is the timing of the whole thing because you mentioned the concept of the FDA giving us to go. What I was saying earlier to both Michael and the Tyler and their questions was – you don’t really know it’s done until the PDUFA date and they approved your BLA. That’s when they truly say go. But what you’re trying to do is your response to their feedback during the process and of course, preserve your retains and preserve your – provide them with information as they ask for it and not burn stuff up unnecessarily during the process. So that’s something we’re doing very carefully here.
Got it. Okay. Thanks. And then a question for Friedrich, if I may. I mean given what we’ve seen with the non-small cell lung data that you presented earlier, I wanted to just get your thoughts on the confidence that you have that LUN-202 by going at a maybe potentially earlier stage than the previous data that was presented that you could have better durability of the responses that you have there? And then related to that, is there a – do you think that it could be an option for you to consider giving – and maybe adding another arm to LUN-202 where you’re combining the TIL with PD-1 with the goal help at a PD-1 to give the TIL to a little bit more kick to continue then persisting.
Yes. So those are two good questions. So obviously, about the durability and our confidence that going into an earlier line will improve the durability is the number one. That is, to some extent, just clinical experience and [Technical Difficulty] knowing how sick late-line non-small cell lung cancer patients often are in regards to organ function and performance status. So going into an earlier line will somewhat gets you into a little better starting point. Really, the confidence comes from the data that were presented by [indiscernible] from the Moffitt was obviously a slightly different design. And a single institution experience there in what was overall an earlier line population with patients that had either received a single prior line over even treatment naïve. Long-term and long durability responses were so that was informing the step to long to it at least partially. We obviously have to now run this clinical experiment and generate the data supporting that, but that’s the rationale. About your question of adding PD-1 blockade to TIL for better durability, that’s something that we are actively exploring in Cohort 3A of the basket study and as checkpoint under that naïve population, albeit but we are generating data on non-small cell lung cancer with that combination. So we are interested in that whether that is something that one would want to translate into a checkpoint that are pretreated population is a question that we can have once we understand what we’re seeing and let’s see one of the naïve population. Keep in mind, lung cancer docs do not tend to reuse checkpoint inhibitors after failure of checkpoint inhibitors is slightly different from melanoma. There usually – there is not a lot of confidence in checkpoint inhibitors, at least not by themselves and reusing them after failure. So that’s no different to the situation in melanoma.
Got it. Thanks, guys.
Well, thank you.
Thank you. Our next question will come from Reni Benjamin with JMP Securities. Please go ahead.
Hey, good afternoon, guys. Thanks for taking the questions. And I apologize, I jumped on the call a little late, so I apologize if you guys have already answered this. Can you just tell us what – how are you thinking about ex-U.S. or specifically a European filing, especially if this BLA, you were able to pull up this BLA submission on time here in the U.S. what are the kind of gating steps going forward? And then also just to clarify, we typically see clinical data more as a review issue. Is there any reason to think or ever consider that the potency assay or any part of the CMC could be part of a review issue, if there is one? Thanks.
Sure. I can take those. Our European strategy really is hinges on the FDA outcome. So really, we’re focused on the FDA right now. And then since we have European patients in the trial, as we’ve talked about before. If things go well with the FDA, we think we can turn around the EMA and hopefully move pretty quickly there. We haven’t announced any details on that yet. So you just kind of stay tuned on some of this, but yes, we did prepare for that eventuality, and we do think we can do something there fairly quickly after we resolve the issues with the FDA. Your second question, yes, I mean, look, there can be review issues on everything with FDA can always say that they sometimes use that language in every single question that you ask them a Type B or Type C meeting. But our goal is to try and get it to whatever is left is a review issue is so minor that we feel very comfortable that we’ll get a successful approval when the PDUFA day hits. That’s really the way we look at it. The fact is they could say that. They could say that for the clinical side, they can say it from the CMC side, what you can say for non-clinical side. But we try to close that window as tightly or as close to completely close as we can with pre-BLA filing interactions to make sure that we’re not caught in a situation where during the review, something becomes a real problem.
Got it. Okay. And just as a quick follow-up regarding the European filing. Is that something you do kind of like right after submitting the BLA because you’ve worked everything out or waiting for the BLA to be accepted? Or is it something that you do after an approval here in the U.S.? How should we think about that?
I’d probably be more like the latter, but we haven’t determined that fully yet. So we want to – again, our focus is on the U.S. market for melanoma first and foremost because that’s the market we want to be in. But we would look at the European opportunity as much as we possibly could with the resources that we have.
Perfect. Thanks. Thanks for taking the questions.
Thank you. Our next question will come from Madhu Kumar with Goldman Sachs. Please go ahead.
Hey everyone, thanks for taking our questions. So I apologize that I’m going to beat this dead horse. How should we think about news flow through June 30 with regards to lifileucel and post-PD-1 melanoma, – like we will have the BLA submission they’ll have Cohort 4 data analyzed. Like how should we think about kind of like what information is going to come between now and June 30?
Yes, it’s a good question, Madhu. All that information comes out in that period basically or should come out in that period we expect will come out in that period. So how it comes out in the order comes out and it’s still something that needs to be determined, but those are the critical elements which you mentioned there, basically the Cohort 4 data, so the clinical data that will be or at least a top line Cohort 4 data, the clinical data will be in the BLA package where we stand with respect to the CMC issues as much as we know, the actual occurrence of a pre-BLA meeting and the actual occurrence of filing, all that stuff has to happen. We’ll try a time – we don’t know the details yet. We can’t predict exactly where this is going to happen, but we’ll try to time the news flow and keep the news flow coming as that process continues.
Okay. And then following up on the last question, kind of a bigger picture question about accelerated approval in this context. What does the confirmatory trial look like to you in with lifileucel as monotherapy in kind of advanced solid cancers?
In melanoma or just in general?
Well, I mean, as a confirmatory trial for the melanoma BLA, I mean, previously, it has been discussed idea that a confirmatory trial doesn’t necessarily need to be in the same indication. But like is that the current view? Or is there a notion there needs to be a confirmatory trial specifically in post PD-1 melanoma like actually to think about that what a confirmatory trial looks like?
So a couple of things there. FDA generally discouraged you for having a confirmatory trial in the same indication you just got approval for. They’re more interested in different like going to an earlier line of therapy. Another thing I need to point out is that with the RMAT designation, we don’t know for sure where we’re required to have a confirmatory trial. That’s very important to make clear. And we will be submitting, as we said many times, Cohort 2 data IRC red data for Cohort 2 to the FDA as part of this as well, which FDA said can be supporting. So all that kind of goes in the same blender. And from that, you will find out whether you need a confirmatory trial in the first place. And if you do, it’s not likely to be in the same indication that you just got – you just ran your pivotal data. Does that help?
[Indiscernible] Is there kind of like a natural data set you guys have in hand that serves that function? I mean kind of when would logically think something like the cervical cancer data set that you have developed over the last few years. Is that kind of like a natural kind of confirmatory population to submit as a confirmatory group?
No. That would be for a separate label on cervical. So that’s – would they be looking for a confirmatory trial should they require one in melanoma would be in melanoma. And so maybe the natural one that you could think of would be in an earlier line of therapy in melanoma like our Cohort 1A account to a 2 or something similar to that. And FDA’s current thinking on this matter, as they talk about publicly is that the sponsor should have that trial up and running at the time of approval or earlier.
Okay. Thank you.
Ladies and gentlemen, thank you for participating in today’s question-and-answer session. I would now like to turn the call back over to Dr. Fred Vogt for any closing remarks.
Thank you, operator, and thank you again for joining the Iovance Biotherapeutics fourth quarter and full year 2021 financial results conference call. We are really grateful for the patients and physicians who are participating in our clinical studies and moving the field of cancer forward. I want to acknowledge our employees and cross-functional teams who are working tirelessly to prepare for our BLA filing to bring lifileucel to patients. I would also like to thank our shareholders and the covering analysts for their collaboration and support of Iovance. All of you are key contributors in advancing our mission to be the global leader in developing, delivering and innovating TIL therapy. Please feel free to reach out to our Investor Relations team if you wish to follow-up. Thank you.
Ladies and gentlemen, this concludes today’s conference call. Thank you for your participation. You may now disconnect.