EarningsCall · IOVA Q4 2022

spk32: Welcome to the Iovance Biotherapeutics fourth quarter and full year 2022 financial results and corporate updates conference call. My name is Gigi and I'll be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session. Please note that this conference is being recorded. I will now turn the call over to Sarah Pellegrino, Senior Vice President, Investor Relations, and Corporate Communications 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 Vogt, our Interim President and Chief Executive Officer, Dr. Igor Belinsky, our Chief Operating Officer, Jim Ziegler, our Executive Vice President Commercial, Dr. Frederick Finkenstein, our Chief Medical Officer, and John Mark Belleming, our Chief Financial Officer. Dr. Raj Puri, our Executive Vice President, Regulatory Strategy and Translational Medicine, is also available for the Q&A session. This afternoon, we issued a press release that can be found on our corporate website at iovance.com, which includes the financial results for the three and 12 months ended on December 31st, 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 and transactions, pre-commercial activities, clinical trials and results, regulatory interactions, plans and strategies, research and pre-clinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interactions, licenses and collaborations, cash position and expense guidance, and future updates. Forward looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward looking statements. With that, I will turn the call over to Fred.

spk08: Thank you, Sarah, and good afternoon, everyone. I am pleased to highlight the positive milestones and significant progress that I advanced in 2022 and into the beginning of 2023. We are close to completing our biologics license application, or BLA, for our lead TIL therapy, lifelucel, and advanced melanoma before the end of this quarter. We are also preparing for commercialization, developing our robust immunology pipeline and integrating Prolucan upon the close of our planned acquisition. The BLA for Lefalucil remains our number one priority on behalf of patients with advanced melanoma who progress on or after anti-PD-1 therapy. This represents a significant unmet medical need given that there are currently no FDA-approved treatment options in this setting. I feel very confident going into the BLA review process given the strength of our clinical data and unmet need as well as several positive interactions with and feedback from the FDA during 2022. These included FDA alignment on the potency assay matrix last April and a successful pre-BLA meeting in July where the FDA provided favorable feedback on the clinical efficacy data from cohorts two and four of our C14401 clinical trial, including duration of follow-up and that the clinical and safety data set was sufficient for a BLA review. In the fourth quarter, we also reached agreement with the FDA on our recently started Tilvance 301 phase three trial, frontline advanced melanoma, to serve as a registrational trial on that indication, as well as a confirmatory study supporting full approval of lifelucel in post-anti-PD-1 advanced melanoma. We expect TILVANS 301 to be well underway at the time of potential approval, and Frederick will talk about additional details of the trial on today's call. Overall, the FDA continues to be engaged and supportive. We look forward to continuing this level of collaboration in 2023. We're also preparing to integrate Prolucan upon the close of our planned acquisition of this product. As a reminder, we announced last month that we have entered into a strategic transaction with Clinogen to acquire worldwide rights to Prolucan, an IL-2 product with currently approved indications that is importantly also used to promote T cell activity following TIL infusions. We have a strong strategic fit and rationale for this transaction, which provides immediate and future revenue and full control of the IL-2 supply chain and logistics surrounding TIL therapy. and is expected to lower clinical trial expenses and future cost of goods for Lifolucel. In addition to Lifolucel and melanoma, we are building a deep and diverse till therapy pipeline in multiple solid tumor types that has the potential to create significant value for cancer patients as well as our shareholders. We are conducting six active clinical trials, preparing the randomized patients in the frontline melanoma treatment setting in our first phase three study, and advancing several genetically modified TIL therapies, which Frederick will also highlight on today's call. As we grow our organization to prepare for our first potential launch, we currently have more than 500 iAdvance employees who have expertise in developing and commercializing oncology and cell and gene therapy products. I look forward to addressing your questions later during this call and will now ask Igor to address our manufacturing updates and preparations to supply commercial TIL therapies upon potential approval. Thank you, Fred.

spk04: Manufacturing is critical for any commercial launch, particularly for autologous tail therapies, so our top priority is to prepare for commercial supply to meet patient needs while continuing to scale up our internal capabilities and staffing. We are focused on operational excellence and maintain a consistent tail manufacturing success rate of more than 90% in more than 600 patients We are currently supplying clinical studies from ICTC, which is operating flex suites for clinical manufacturing and core suites for BLA readiness activities in preparation for commercial manufacturing. We have done significant work to ensure that ICTC and our contract manufacturers facility are well prepared for launch with many of our current efforts focused on the FDA pre-approval inspections that we expect to occur during the BLA review process. The ICTC is expected to supply most of the commercial TIL therapies upon approval with contract manufacturers to provide additional flexibility to optimally balance capacity and patient demand. Beyond our initial launch of Lifolucil, we are planning for future capacity needs as we look to establish TIL as the next paradigm shifting class of cancer therapy. The ICDC is currently built as annual capacity to supply TIL products for more than 2,000 patients with available shell space that we can build out to supply products for more than 5,000 patients annually from this facility. Longer term, by adding new facilities as well as streamlining and automating manufacturing processes, our vision is to build capacity for more than 10,000 patients annually. Our intellectual property or IP is also a critical component to support and protect our proprietary manufacturing processes and know-how and to further solidify our global leadership in till therapy. We currently own at least 60 granted or allowed U.S. and international patents, including Gen 2 patent rights that are expected to provide exclusivity into 2038. Extensive detail on ODIP is highlighted on our corporate website and within our annual report on Form 10-K. I would now like to hand the call to Jim Ziegler to highlight our commercial launch preparations.

spk17: Thank you, Igor. Throughout 2022, the commercial team made steady progress towards launch. With the ongoing BLA submission, our launch priorities include onboarding of our authorized treatment centers, or ATCs, securing appropriate access, and achieving operational readiness. Our cross-functional teams continue to partner with and onboard ATCs to develop new workflows that are unique to till therapy while leveraging workflows within existing cell therapy service lines at these centers. Our ATC operations and regional account director teams have structured interactions to support an efficient ATC onboarding process And we have developed a training curriculum to ensure multidisciplinary teams can administer the Lifo-Lucil treatment regimen upon FDA approval. The timing and execution of key onboarding activities and training at each center are aligned to our regulatory timelines. We support each center in developing their TIL service line, and we plan just-in-time training to ensure launch readiness. Our reimbursement strategies are focused on securing coding, coverage, and payment. Our market access team continues to engage the key national and regional payers. As we transition from the clinical trial to commercially approved setting, our goal is to ensure patients have appropriate and timely access to Lipoleucine. Our cross-functional team is also assessing our needs and capabilities and developing our implementation plan for Prolucan. We are also fortunate to have several cross-functional team members with prior Proleukin leadership experience who are leading and developing our end-to-end integration processes. We are preparing for a smooth transfer and operational readiness for Proleukin upon the close of our planned acquisition. We understand that launching an autologous cell therapy requires sustained operational excellence, and I want to acknowledge the critical thinking problem-solving, and tireless efforts of our cross-functional team. Our team has set a high bar for themselves to ensure the highest quality of operational excellence. We are well-positioned to scale our efforts to ensure commercial launch readiness. I will now pass the call to Friedrich Finkenstein, our Chief Medical Officer, to highlight our clinical progress.

spk16: Thank you, Jim. Today, I would like to summarize our TIL therapy pipeline and next-generation technology. I'll begin with our multi-pronged strategy in advanced melanoma. Our ongoing rolling BLA submission for lifelucid and post-anti-PD-1 advanced melanoma is based on the results from our C14401 trial, the largest single clinical study ever conducted for TIL therapy in post-ICI melanoma. In the fourth quarter, we presented positive data from C14401 cohorts 2 and 4 to the medical community for the first time at the Society for Immunotherapy of Cancer, or FITC, annual meeting last November, and published results from the study in the Journal of Immunotherapy of Cancer, or JITC, in December. We are confident that the strength of the clinical data from 153 patients in the C14401 trial, including our Pivotal Cohort 4 and Supportive Cohort 2 support approval. Following the recent posting of our Phase III TIL-VANCE 301 trial and frontline advanced melanoma on clinicaltrials.gov, I would like to highlight additional detail on this trial today. We reached agreement with the FDA for TIL-VANCE 301 to serve as our registrational trial for accelerated and full approvals of Lifolucel in combination with Pembrolizumab in frontline advanced melanoma, as well as a confirmatory trial to support full approval of Lifolucel in post anti-PD-1 advanced melanoma. Notably, we were very pleased that the FDA agreed to dual primary endpoints of Blinded Independent Review Committee or BIRC-Assessed Objective Response Rate, or ORR, and progression-free survival, or PFS. CLIL-LANS 3.1 also includes several secondary endpoints, such as overall survival and duration of response. In terms of trial design, we plan to randomize 670 patients who are naive to therapy in the advanced setting, equally to either life-elucidant combination of pembrolizumab in the experimental arm or pembrolizumab monotherapy in the control arm. We are including an appropriate number of global sites such as many large U.S. and European cancer centers and numerous other countries where we expect strong involvement. In the control arm, patients will have the option to receive TIL monotherapy upon confirmed disease progression verified by BIRC. Additional information on trial design, outcome measures, and eligibility criteria are available on clinicaltrials.gov. Our confidence in the success of TIL-VAMP3A1 is based on results from cohort 1A in our IOV COM202 trial of lifelucidin combination with pembrolizumab in ICI-naive advanced melanoma, in addition to prior data at the NCI for TIL monotherapy in anti-PD-1-naive melanoma generated in the pre-ICI era. We look forward to advancing our frontline melanoma strategy through our 2023 including site activation and patient randomization in TIL-VANs 301. As Fred mentioned, TIL-VANs 301 is expected to be well underway at the time of potential BLA approval for lysoleucine-posed anti-PD-1 advanced melanoma. We continue to execute on our non-small cell lung cancer, or NSCLC, pipeline at IOVAN, with six cohorts across three IOVAN studies to investigate multiple treatment regimens in various populations at various stages of disease. We recently shared top-line initial data from cohort 3A of the IOV COM202 trial, which we highlighted in a press release and investor conference call last month. Based on initial cohort 3A positive results in patients with advanced NSDLC who are naive to ICI treatment, particularly within the treatment naive and post-chemotherapy subset, We plan to meet with FDA in 2023 to discuss data and the potential registration path for Liferleucine frontline advanced and SELC patients. Enrollment to Cohort 3A is ongoing, and we plan to present details and updated results at a medical meeting this year. Our IOV LUN202 trial is investigating LN145 monotherapy in patients who have received prior anti-PD-1 and chemotherapy in combination or sequentially and includes an option for pre-progression tumor harvest. We enroll patients for 2022 and expect to continue enrollment this year. Moving to cervical cancer, enrollment is underway in our expanded cohort 2 in the ongoing C14504 trial in patients who have progressed after chemotherapy and anti-PD-1 therapy. As a reminder, cohort 2 is intended to be pivotal to support regulatory submissions following dialogue and feedback from the FDA, and we look forward to continuing cohort 2 enrollment during the year. We are excited about our next-generation TIL therapies. We are developing several genetically modified TIL therapies that utilize the gene editing talent technology licensed from Selectis to optimize TIL therapy by inactivating immune checkpoint proteins that inhibit anti-tumor response. IOV4001 is our first genetically modified PD-1 inactivated TIL therapy candidate. In the third quarter of last year, we treated the first patient with IOV4001 in our first in-human IOV GM1-201 trial in patients with previously treated advanced melanoma, or NSCLC. Additional programs using the TALENT technology are expected to enter clinical development in 2024, including genetically modified TIL therapy with multiple inactivated immune checkpoint targets. Earlier stage research in preclinical studies include additional approaches to increase tilt potency, including the selection of CD39-69 double negative tilts and enhancements such as tethered cytokines. As part of our strategy to optimize the tilt treatment regimen, we also continue IND-enabling studies of our novel interleukin analog IOB3001. I am available during the question and answer session. For now, I will hand the call over to Jean-Marc to discuss our fourth quarter and full year 2022 financial results.

spk14: Thank you, Frédéric. My comments will summarize our planned acquisition of Proloquin, as well as the high-level financial results from our fourth quarter and full year ended on December 31st, 2022. More details can be found in this afternoon's press release, as well as in our SEC findings. Last month, we announced that we have entered into an agreement to require polluting from Clinigen. Terms of the agreement include an upfront payment of £167.7 million British Pounds, the £41.7 million British Pounds milestone payment upon first approval of lipolucel in advanced melanoma, and double-digit polluting global sales royalties from AirAvance to Clinigen. The transaction will be financed with existing cash and is expected to close after all conditions are met, including regulatory approvals and clearance and other customary closing conditions. As a late stage oncology company approaching potential commercialization this year, we are also investing in launch preparations, internal manufacturing, and pipeline activities. As of December 31st, 2022, We held $478.3 million in cash, cash equivalents, investments, and restricted cash, compared to $602.1 million at December 31, 2021. Taking into account proceeds raised in 2023 from our at-the-market or ATM facility, our unaudited cash position is approximately $670 million as of February 24, 2023, which includes approximately $450 million in net proceeds raised through the ATM during the fourth quarter of 22 and into the first quarter of 23. This current and transcend cash position is expected to fund our operating plan into the second half of 2024, including the product acquisition, manufacturing activities, launch readiness and execution, plan clinical trial, and pipeline advancements. Transitioning to the financial results for the fourth quarter and full year on December 31st, 2022. Our net loss for the fourth quarter of 2022 was $105.3 million, or $0.64 per share, compared to a net loss of $99.3 million, or $0.63 per share, for the fourth quarter of 2021. Net loss for the full year of 2022 was $395.9 million, or $2.49 per share, compared to net loss of $342.3 million or $2.23 per share for the full year of 2021. Research and development expenses were $80.6 million for the fourth quarter of 2022, an increase of $5 million compared to $75.6 million for the fourth quarter of 2021. Research and development expenses were $294.8 million for the full year 2022, an increase of $35.8 million compared to $259.0 million for the full year 2021. The increase in research and development expenses in the fourth quarter and full year 2022 over the prior year periods were primarily attributable to costs associated with the growth of the internal research and development team including stock-based compensation expense, as well as facility-related expenses and internal research programs. These increased expenses were partially offset by lower clinical and manufacturing costs, driven by completion of enrollment in typical cohorts of a clinical trial. General and administrative expenses were $26.5 million for the fourth quarter of 2022, an increase of $2.7 million compared to $23.8 million for the fourth quarter of 2021. General and administrative expenses were $104.1 million for the full year 2022, an increase of $20.4 million compared to $83.7 million for full year 2021. The increase in general and administrative expenses in the fourth quarter and full year 2022 compared to the prior year periods, were primarily attributable to costs associated with the growth of the internal general and administrative and commercial teams, including stock-based compensation expense, the build-out of the new corporate headquarters, as well as pre-commercial activities. As of December 31st, 2022, there were approximately 187.8 million common shares outstanding. I will now arm the call back to the operator to kick off the Q&A session.

spk32: Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Peter Lawson from Barclays.

spk13: Great. Thanks so much for taking the question. Fred, you sounded confident around the BLA submission by the end of 1Q, kind of what needs to be done there, what's left?

spk08: Yeah, Peter, we're really confident that we're going to get this done. We have essentially a lot of activities we talk about relating to the assay work, CMC work, validation work, and stuff like that that we were completing. We've talked about it before. It's relatively routine work, but it's It's very important to the FDA, and that's kind of what we're getting done here so we can complete the rolling VLA submission.

spk13: Gotcha. Okay. And then I know some time is off, but just on the launch of Life of Lucille, are you expecting to see a bonus of patients on launch and kind of any way you can kind of quantify that?

spk08: Yeah. Jim, do you want to take that one?

spk17: Sure. Sure. Given our experience in dialogue and with the KOLs at many of these sites and even our clinical trial experience, there's a high unmet need. And this translates into a number of patients who are in need of therapy after checkpoint inhibitors. So we are expecting a bolus of patients at launch given that high unmet need.

spk08: And, Peter, we do run an EAP program in order to stay in close contact with the site so that we're making sure that we have a good feel for what's out there, providing care for patients as FDA wants you to do.

spk01: Thank you.

spk32: Thank you. One moment for our next question. Our next question comes from the line of Mark Breedenback from Oppenheimer.

spk19: Hey, guys, thanks for taking the question. Two quick ones for me. First, I'm wondering if you can just comment on remaining barriers before you can begin recruitment into the Tovance 301 study. And then I'm also wondering, aside from the cohort 3A lung data that Friedrich mentioned, are there plans for additional clinical data presentations in 2023? Thanks for taking that question.

spk06: Frederick, do you want to talk a little bit about the startup activities for 301?

spk08: And you can probably talk a little bit about the potential for lung data later this year, too, if you want.

spk16: Sure, happy to. Thanks for the question. So we have spoken about being in startup on Togon 301. So that basically means submission of the protocol. to sites, reviews at sites, site startup, site initiation, and then startup enrollment. There are no specific additional hurdles that would be kind of like one hurdle that would apply to all sites. It's now really activities at individual sites. And much of that work is basically going on in parallel and will continue as we are adding a meaningful number of sites both in the U.S. as well as ex-U.S., Europe, and beyond Europe to the sites that were enrolled to this trial. So really no specific hurdles of site startup activities at individual sites. Does that make sense?

spk19: Sure. I guess I'm trying to get a sense for when you would expect the first patient to be enrolled.

spk16: Yeah, we haven't guided to when exactly the first patient will be enrolled. What we have said, though, is that we expect enrollment to be well underway at the time of approval of the relapse refractory indication, and I think that's the main point here.

spk08: Yeah, Mark, we would certainly advise everyone when we do randomize the first patient.

spk19: Got it. And with respect to other clinical presentations besides the cohort 3A lung data?

spk08: Yeah, I mean, I can cover that one. We have additional lung studies running right now, including the OUN202 study, which could potentially read out this year. Plus, we already put out just a few weeks ago the 3A data, and we do want to get to a medical conference and drill into that data a little bit more deeply. So that'll be, I think, a very important presentation for the company when that comes.

spk19: Okay, but all the presentations will be in lung is what you're implying?

spk08: No, not necessarily. I thought you were just asking about lung.

spk19: No, no, I'm trying to get for all other indications as well.

spk08: Oh, yeah, there's other, well, I can't say for sure what we're going to do, but we've got a pretty thick pipeline, and there could be other presentations and other indications for sure.

spk23: All right, thanks.

spk24: thank you one moment for our next question our next question comes from the line of tyler van buren from cowan hi guys it's tara um for tyler um so i guess staying on the the same topic of the lung data so i know that you know when you just closed it a few weeks ago or back in january that it was too early to comment on response duration um but what do you kind of expect to see when the full results are presented? And then how are your discussions with the FDA going following that positive feedback that you received on study 202? Like, is there anything new to report there since January? Thanks.

spk08: On the, I assume you mean the LUN202 study? Yes. Yeah, that's one where we're engaging with discussions with the FDA. I don't have any updates for you on that right now. On 3A, we are, like we said when we released the data, the durability is something we're going to watch closely and it will certainly be part of our medical meeting presentation on that. I can't really say much more about that ahead of time. That's obviously an important thing to the content of the medical presentation when we do it, but we're very comfortable that what we're seeing should support a potential registrational trial like the one we described in January. And we're doing our best to get back to FDA with that proposal as soon as we can.

spk32: Thank you. One moment for our next question. Our next question comes from the line of Michael Yee from Jefferies.

spk26: Hi, guys. Thanks so much for taking the question. This is Dina Ahn for Michael. Given that you guys are reiterated, you know, the BLA submission for Q1, I just kind of wanted to get a better sense on, you know, I know you guys spoke about this slightly, but just if you can add an additional color on like the progress you guys made since the last update and what are just the remaining dating factors to getting that BLA submitted. And also if you had any further interactions with the FDA since that last update as well. And, you know, based on the commentary that you guys have had with them, you know, is there any color that you can share on a potential ad comp? or priority review. That would be helpful. Thank you.

spk08: Now, we haven't had any additional interactions with them. We do expect to have priority review for this, and we'll know more about an adcom at some point. We've spoken before about whether an adcom is likely here. It's possible we may not get an adcom because FDA is familiar with T cell therapies at this point. Raj has talked about that a few times on calls like this. With respect to the work and a little bit more color on the work, it's Like I said earlier, it's largely validation activities relating to some of the CMC stuff that we do that's part of our filings. I can tell you the bulk of the work for the BLA is done and submitted. So we're on the home stretch now, and we're just completing some of these key tasks. It takes a lot of effort from the company. We have a lot of people here working very hard to get this done. And really, it's not the kind of thing where... It's extremely technical in nature. It would be very difficult to communicate with the street on this, but it's basically a lot of additional CMC validation activities, like we've spoken about before.

spk26: Okay.

spk32: Thank you. Thank you. One moment for our next question. Our next question comes from the line of Ben Burnett from Stiefel.

spk18: Great. Thank you. I want to just ask about the launch preparations for Lipoleucel. Can you remind us just how many melanoma treatment centers in the U.S. you have already sort of onboarded, wherein sort of you feel that you've sufficiently trained all the necessary stakeholders at a particular clinical site? So, like, how many clinical sites have you onboarded as per all of your clinical trial activities to date?

spk17: Thanks, Ben. This is Jim. Go ahead, Jim. Great. So the onboarding process is exactly that. It's a process. We've engaged a number of key sites across the country to ensure that we have sufficient geographic coverage as well as access. I won't give you the specific numbers, but what we have stated in the past is based upon our own assessment, looking at analogs like CAR-Ts, we know that there's a heavy concentration of care at these top centers. In the CAR-T market, about 10 centers drive about 50%. of all the treated patients and the top 40, about 80% of all the treated patients. So we're focused on getting the right sites up and are targeted and up ready for a launch. We want to train them in the final phases of launch. You know, if we train them too soon, there could be staff turnover, there could be the recency. So what we're really doing is lining everyone up now And as soon as we have the BLA acceptance, well, BLA filing and acceptance, then we'll start to really accelerate that final onboarding process.

spk18: Okay. Understood. That makes sense. And then I want to ask just another question about the timing of data from the CRC program. In particular, the expanded CRC program in the post-chemo, post-Pembro program. I guess, number one, do you have line of sight as to when we could get data? And then have you said how many additional patients needed to be enrolled there to kind of support a BLA in that setting?

spk08: I think, Ben, you're not talking about colorectal. You're talking about non-small cell lung, right? You said CRC.

spk09: Yeah, you meant NSCLC, right? So I assume you meant non-small cell lung.

spk08: Yeah, cut off there.

spk18: Sorry. Yeah, we have ovarian cancer. My apologies. I said the wrong indication.

spk08: Yeah, we don't have an ovarian indication, Ivan, right now, although it's certainly something we're very interested in, and we've explored through ISPs.

spk18: Okay. My bad. I mistook that for a different program.

spk05: Too many earnings calls today.

spk18: All right. I appreciate the help. Thanks, guys.

spk32: Thank you. One moment for our next question. Our next question comes from the line of Rennie Benjamin from JMP Securities.

spk20: Hey, good afternoon, guys. Thanks for taking the questions. I guess just to start off maybe for Friedrich, you know, the PD-1 selected TIL studies, the PBL therapy, and the PD-1 inactivated TILs, can you give us a sense as to how those studies are progressing and Kind of off Mark's question, do you think this is something that we might see some initial data for at the end of this year? I guess that would be question number one. Question number two would be, you know, the pro-lucan revenues are supposed to be, I think, near-term or imminent, right, like once the deal is done. I think you've talked about it in the past, but can you just remind us what sort of near-term revenues you expect from pro-lucan this year?

spk08: Yeah, why don't I take the first one, then I'll have Jean-Marc cover the revenues. We can't give you guidance on revenues, Rennie, but we can tell you historically what revenues have been for that product. And, you know, you can figure out how it will look, particularly upon launch of Lifeloosal. For the PD-1 Selected and PD-1 Knockout, the PD-1 Selected program, both of those programs are running, and we could be putting data out on those this year at some point. PD-1 knockout in particular is of high interest to us. That's why it's on the highlights of our portfolio because that, particularly in lung and in melanoma, should, we think, give us additional efficacy. So we're very excited about that. That's one that when we have data, we'll be putting it out pretty quickly. PD-1 Select is something we've been running for a while, and at some point we'll discuss that further. John Mark, do you want to cover the revenue? Sure.

spk14: Yeah, thank you, Fred, and thank you, Remy, for the question. I mean, as Fred mentioned, we're not giving any kind of revenue guidance. First of all, we need to close the deal first, and then we can talk and be more specific about the potential in the future. What we have publicly communicated is the revenue that was generated by ClinGen, which probably came in the past, and we were mentioning 2021 was close to £30 million or $35 million. So that's the the only indication that we were giving in terms of past revenue.

spk20: Got it. Okay. And just one final one, you know, this really just has to do with mainly the CEO search. Is that still going? Brad, are you dying to move your interim, you know, status to something more permanent? You know, and I'll throw it out there. Christy Shaw has left Kite Gilead. Is someone, you know, close to that name joining anytime soon? That's it for us.

spk08: Thanks. I can't say specifics like that, but the search is ongoing, and no, it won't be me. So at some point, we'll be able to talk more about that, and the board is definitely interested in finding somebody. Who knows? Thanks, Fred.

spk32: Thank you. One moment for our next question. Our next question comes from the line of Mara Goldstein from Mizuho Group.

spk30: Great. Thanks so much for taking the question. I did have a quick follow-up on Prolucan, and I respect you're not giving guidance, but I'm just curious around your expectations about working capital and how the ATM figures into that as you onboard that product. And then secondarily, can you speak to the TILVANCE trial and how we should think about the primary endpoint in terms of the delta improvement looking for given the number of patients in the trial and Secondarily, the presence of the crossover arm, how do you account for pressure on the OS secondary endpoint there?

spk07: John Mark, do you want to take the first part of that and Frederick get the second part?

spk14: Yeah, sure. Yeah, I'm trying to try to think about the best way to answer your question. So I think our goal is to integrate polluting in a way that we will keep it as a profitable activity. Again, it will be separate in a way from life also. So we will still sell polluting outside of our own usage. So currently I would say polluting is profitable and we intend to do the same in the future after integration. I'm not too much concerned around, you know, working capital as itself, because again, we're not talking about large amounts. We will not carry a lot of amount of inventory and everything should be pretty much managed correctly. So no concern on that. ATM related, I mean, we've commented about the activity that we've just done. And I think what's the most important there is to keep in mind we have enough cash, including the acquisition of Polo King into the second half of 2024.

spk30: OK. Thank you for that. And then the Tillvance question?

spk16: Yeah, sure. Thanks for the question, Frederic, here. So I think that was a two-part question. One of them was about how do we think about deltas that we're trying to achieve in the context of the study design and sample size. And the second question was about .. So the first question, just I mean, I'm just stating the obvious here. The design of the study is a randomized comparative study, right? So we're not shooting for specific deltas to an existing benchmark. We're shooting for a difference or a hazard ratio between the two arms. What you usually do when you design a study like that, you do look at the best available information about what you might be expecting in your control arm. And then you're powering in order to be able to get the difference or the hazard ratio. So it's a little different from how we would have done this or are doing it in our single arm design. The information that we're pulling in for that is pretty straightforward. It's available information on what you're seeing in a frontline population of patients. treated with Pembrolizumab monotherapy and the information is available in the USPI for Pembro or in publications. So that's probably as much as I can say here. The confidence here comes from our knowledge of what we are currently seeing in our COM202 cohort 1a, where the response rate is is 66.7% with our last update, and that would compare to something that's in the low 30% for pembrolizumab monotherapy. So that gives you an idea around VORR. The crossover, So, yes, obviously the crossovers are something that you have to keep in mind as you are thinking about an overall survival endpoint, but that is exactly the reason for why overall survival is not a primary endpoint here. It's fairly typical to, in that situation, then go with a non-overall survival endpoint, and we are particularly happy about having gotten an agreement of being able to use ORR and PFS as dual endpoints in our discussion with the FDA. And that's exactly the reason for it. The value of the crossover arm in this case is outweighing potential impacts on the overall survival of secondary endpoints.

spk29: Okay. Thank you very much.

spk32: Thank you. One moment for our next question. Our next question comes from the line of Kelsey Goodwin from Guggenheim Partners.

spk22: Hey, guys. Thanks for taking my questions. I guess first regarding manufacturing, I guess how do you think about kind of initial launch capacity and then the timing for step-ups if we're kind of thinking about it similarly to what we've been seeing with the autologous CAR-T therapies? maybe just a bit more granular than kind of the phase one, phase two that you lay out for the ICTC. And then secondly, maybe just a quick one, are you able to provide any more color on your plans for potentially expanding into Europe for melanoma? Great, thank you so much.

spk08: Yeah, let me take the last one, and then Igor can give you some more color on the manufacturing. Yes, Europe is something we're very interested in. We haven't publicly spoken much about Europe, but... We are active there. Obviously, our trials have been run there, and we continue to run them there until VANS 301 is going to have a significant European presence. We are engaged with European regulators, and I think you'll hear more from us in 2023 on that. But that is an important market, we think, for melanoma, as well as other markets around the world where we have a high incidence rate of melanoma. Igor, do you want to answer the manufacturing question?

spk04: Happy to, Kelsey. Thanks for the question. So as I mentioned earlier, we have built the capacity because the facility is built can support more than 2000 patients per year. And we are now hiring the manufacturing team to meet the demand that we anticipate at launch. We're not sharing the exact demand numbers, but as Jim mentioned, actually in response to an earlier question, we expect there may be a bolus. So we're taking that into consideration as we're planning the initial launch capacity. Beyond that, We can continue hiring the staff as needed and then also build out the shell space that we have within the existing ICTC facility that can bring us to over 5,000 patients per year to increase the capacity stepwise. There's a process that's similar across cell therapy, similar to CAR T that requires capacity demo submissions to the agency, and we're planning those as well.

spk21: Okay, great. Thank you so much.

spk32: Thank you. One moment for our next question. Our next question comes from the line of Astika Goonwarden from Truist.

spk31: Hi, this is Karina for Astika.

spk02: Question, my question is for TIL and 301 study. How long do you anticipate it will take for you to finish recruitment? And given that the study is open label, do you plan to report interim data? And if so, at what point? Thank you.

spk16: Frederick, do you want to take that? Yeah, so the projection of accomplishing the analyses is hard, particularly when you are in the early phases of startup. I think we'll better understand that once we're in and make progress on enrollment and site activation. Also keep in mind that ultimately these endpoints, particularly the TFS endpoints, are event-driven. And a true and exact projection is never really truly possible because of that. So stay posted on that. Repeat the second question about the study, please. Oh, yeah. You were saying that this is an open-label study. It's actually not. It's a blind study. So meaning we are blinded to the treatment assignments as you would in any other study design. The assessments are done by a blinded independent radiology committee. So there's probably no update in between other than if the final decision is being made by the DMC.

spk02: Okay. And also, I have another question. You said that you did not expect to get a REMS. Is that still the case?

spk08: Yeah, that's the, we don't see any reason why we would get a REMS. The pill treatment regimen, Syflu and IL-2 don't have a REMS today. So, pills don't really carry any safety issues themselves. So, we don't see, we don't have the issues that you see with some of the CAR Ts that triggered the REMS in those cases.

spk32: Okay, thank you. Thank you. One moment for our next question. Our next question comes from the line of Madhu Kumar from Goldman Sachs.

spk11: Hi, guys. This is Rob. I'm from Madhu. Thanks for taking our question.

spk10: Just how should we think about the timing of data from cervical cancer cohort? And then on the genetically edited pill project, products? What are you guys thinking in terms of efficacy? Or like, where do you expect to be better?

spk08: Yeah, the genetically edited TIL products, to take that one first, that combines a PD with a TIL product. So we're hoping to get something that would look like additive efficacy between the two modes, the TIL response and then the blockade of the inhibitory mechanism directly within the cell now. And then as we add additional immune checkpoint targets to our gene editing, we can hopefully add on top of that too. So that's the basic theory behind it. We're testing that now in humans and we'll know more about how that works. It's similar in many respects to how you see a lot of people developing bispecific antibodies right now that blockade PD-1 and something else. I mean, this is the kind of thing that we want to do within the cell. And so the PD-1 knockout is the first one that's in humans right now. We'll have more updates on that for you later on this year. Cervical, we just restarted enrollment in that study, and that's a pivotal study. We intend that to be a pivotal study. And so we don't have an update for you today on that. The post-PD-1 cervical population is large enough that we think we can enroll it reasonably well, but we'll know more later this year on that.

spk03: Thank you.

spk32: Thank you. At this time, I would now like to turn the conference back to Fred Vogt for closing remarks.

spk08: Thank you again for joining the I-Advanced Biotherapeutics fourth quarter and full year 2022 financial results conference call. We've had an exciting start to 2023 with the pro-leukin agreement and new clinical data, and we look forward to completing the BLA this quarter and delivering on our regulatory commercial manufacturing pipeline activities, and milestones throughout the year. I am grateful for the patients, physicians, and regulators, as well as our employees and cross-functional teams who have worked in close collaboration to advance our mission to be the global leader in pill therapy. I would also like to thank our shareholders and covering analysts for their support. Please feel free to reach out anytime to our investor relations team for any follow-up. Thank you.

spk32: This concludes today's conference call. Thank you for participating. You may now disconnect.

spk25: The conference will begin shortly. To raise and lower your hand during Q&A, you can dial star 1 1. The conference will begin shortly. To raise and lower your hand during Q&A, you can dial star 1 1. Thank you. you I'm sorry. Thank you. you you

spk32: Welcome to the IOVAN's Biotherapeutics fourth quarter and full year 2022 financial results and corporate updates conference call. My name is Gigi and I'll be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session. Please note that this conference is being recorded. I will now turn the call over to Sarah Pellegrino, Senior Vice President, Investor Relations, and Corporate Communications 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 Vogt, our Interim President and Chief Executive Officer, Dr. Igor Belinsky, our Chief Operating Officer, Jim Ziegler, our Executive Vice President Commercial, Dr. Frederick Finkenstein, our Chief Medical Officer, and John Mark Belleming, our Chief Financial Officer. Dr. Raj Puri, our Executive Vice President, Regulatory Strategy and Translational Medicine, is also available for the Q&A session. This afternoon, we issued a press release that can be found on our corporate website at iovance.com, which includes the financial results for the three and 12 months ended on December 31st, 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 and transactions, pre-commercial activities, clinical trials and results, regulatory interactions, plans and strategies, research and pre-clinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interactions, licenses and collaborations, cash position and expense guidance, and future updates. Forward looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward looking statements. With that, I will turn the call over to Fred.

spk08: Thank you, Sarah, and good afternoon, everyone. I am pleased to highlight the positive milestones and significant progress that I advanced in 2022 and into the beginning of 2023. We are close to completing our biologics license application, or BLA, for our lead TIL therapy, lifelucel, and advanced melanoma before the end of this quarter. We are also preparing for commercialization, developing our robust immunology pipeline and integrating Prolucan upon the close of our planned acquisition. The BLA for Lefalucil remains our number one priority on behalf of patients with advanced melanoma who progress on or after anti-PD-1 therapy. This represents a significant unmet medical need given that there are currently no FDA-approved treatment options in this setting. I feel very confident going into the BLA review process given the strength of our clinical data and unmet need, as well as several positive interactions with and feedback from the FDA during 2022. These included FDA alignment on the potency assay matrix last April and a successful pre-BLA meeting in July where the FDA provided favorable feedback on the clinical efficacy data from cohorts two and four of our C14401 clinical trial, including duration of follow-up and that the clinical and safety data set was sufficient for a BLA review. In the fourth quarter, we also reached agreement with the FDA on our recently started Tilvance 301 phase three trial, frontline advanced melanoma, to serve as a registrational trial on that indication, as well as a confirmatory study supporting full approval of lifelucel in post-anti-PD-1 advanced melanoma. We expect TILVANS 301 to be well underway at the time of potential approval, and Frederick will talk about additional details of the trial on today's call. Overall, the FDA continues to be engaged and supportive. We look forward to continuing this level of collaboration in 2023. We're also preparing to integrate Prolucan upon the close of our planned acquisition of this product. As a reminder, we announced last month that we have entered into a strategic transaction with Clinogen to acquire worldwide rights to Prolucan, an IL-2 product with currently approved indications that is importantly also used to promote T cell activity following TIL infusions. We have a strong strategic fit and rationale for this transaction, which provides immediate and future revenue and full control of the IL-2 supply chain and logistics surrounding TIL therapy. and is expected to lower clinical trial expenses and future cost of goods for Lifolucel. In addition to Lifolucel and melanoma, we are building a deep and diverse till therapy pipeline of multiple solid tumor types that has the potential to create significant value for cancer patients as well as our shareholders. We are conducting six active clinical trials, preparing the randomized patients in the frontline melanoma treatment setting in our first phase three study, and advancing several genetically modified TIL therapies, which Frederick will also highlight on today's call. As we grow our organization to prepare for our first potential launch, we currently have more than 500 iAdvance employees who have expertise in developing and commercializing oncology and cell and gene therapy products. I look forward to addressing your questions later during this call and will now ask Igor to address our manufacturing updates and preparations to supply commercial TIL therapies upon potential approval.

spk04: Thank you, Fred. Manufacturing is critical for any commercial launch, particularly for autologous TEL therapies. So our top priority is to prepare for commercial supply to meet patient needs while continuing to scale up our internal capabilities and staffing. We're focused on operational excellence and maintain a consistent TEL manufacturing success rate of more than 90% in more than 600 patients treated with IVAN TEL We are currently supplying clinical studies from ICTC, which is operating flex suites for clinical manufacturing and core suites for BLA readiness activities in preparation for commercial manufacturing. We have done significant work to ensure that ICTC and our contract manufacturers facility are well prepared for launch with many of our current efforts focused on the FDA pre-approval inspections that we expect to occur during the BLA review process. The ICTC is expected to supply most of the commercial TIL therapies upon approval with contract manufacturers to provide additional flexibility to optimally balance capacity and patient demand. Beyond our initial launch of Lifolucil, we are planning for future capacity needs as we look to establish TIL as the next paradigm shifting class of cancer therapy. The ICDC is currently built as annual capacity to supply TIL products for more than 2,000 patients with available shell space that we can build out to supply products for more than 5,000 patients annually from this facility. Longer term, by adding new facilities as well as streamlining and automating manufacturing processes, our vision is to build capacity for more than 10,000 patients annually. Our intellectual property or IP is also a critical component to support and protect our proprietary manufacturing processes and know-how and to further solidify our global leadership in till therapy. We currently own at least 60 granted or allowed U.S. and international patents, including Gen 2 patent rights that are expected to provide exclusivity into 2038. Extensive detail on IVAN OID IP is highlighted on our corporate website and within our annual report on Form 10-K. I would now like to hand the call to Jim Ziegler to highlight our commercial launch preparations.

spk17: Thank you, Igor. Throughout 2022, the commercial team made steady progress towards launch. With the ongoing BLA submission, our launch priorities include onboarding of our authorized treatment centers, or ATCs, securing appropriate access, and achieving operational readiness. Our cross-functional teams continue to partner with and onboard ATCs to develop new workflows that are unique to till therapy while leveraging workflows within existing cell therapy service lines at these centers. Our ATC operations and regional account director teams have structured interactions to support an efficient ATC onboarding process And we have developed a training curriculum to ensure multidisciplinary teams can administer the Lifolucel treatment regimen upon FDA approval. The timing and execution of key onboarding activities and training at each center are aligned to our regulatory timelines. We support each center in developing their TIL service line, and we plan just-in-time training to ensure launch readiness. Our reimbursement strategies are focused on securing coding, coverage, and payment. Our market access team continues to engage the key national and regional payers. As we transition from the clinical trial to commercially approved setting, our goal is to ensure patients have appropriate and timely access to Lipoleucine. Our cross-functional team is also assessing our needs and capabilities and developing our implementation plan for Prolucan. We are also fortunate to have several cross-functional team members with prior Proleukin leadership experience who are leading and developing our end-to-end integration processes. We are preparing for a smooth transfer and operational readiness for Proleukin upon the close of our planned acquisition. We understand that launching an autologous cell therapy requires sustained operational excellence, and I want to acknowledge the critical thinking problem-solving, and tireless efforts of our cross-functional team. Our team has set a high bar for themselves to ensure the highest quality of operational excellence. We are well positioned to scale our efforts to ensure commercial launch readiness. I will now pass the call to Friedrich Finckenstein, our Chief Medical Officer, to highlight our clinical progress. Thank you, Jim.

spk16: Today, I would like to summarize our TIL therapy pipeline and next-generation technology. I'll begin with our multi-pronged strategy in advanced melanoma. Our ongoing rolling BLA submission for lifelucid and post-anti-PD-1 advanced melanoma is based on the results from our C14401 trial, the largest single clinical study ever conducted for TIL therapy in post-ICI melanoma. In the fourth quarter, we presented positive data from C14401 cohorts two and four to the medical community for the first time at the Society for Immunotherapy of Cancer, or SITC, annual meeting last November, and published results from the study in the Journal of Immunotherapy of Cancer, or JITC, in December. We are confident that the strength of the clinical data from 153 patients in the C14401 trial, including our Pivotal Cohort 4 and Supportive Cohort 2 support approval. Following the recent posting of our Phase III TIL-VANCE 301 trial and frontline advanced melanoma on clinicaltrials.gov, I would like to highlight additional detail on this trial today. We reached agreement with the FDA for TIL-VANCE 301 to serve as our registrational trial for accelerated and full approvals of Lifolucel in combination with Pembrolizumab in frontline advanced melanoma, as well as a confirmatory trial to support full approval of Lifolucel in post anti-PD-1 advanced melanoma. Notably, we were very pleased that the FDA agreed to dual primary endpoints of Blinded Independent Review Committee, or BIRC, Assessed Objective Response Rate, or ORR, and progression-free survival, or PFS. TIL-BANS 3.1 also includes several secondary endpoints, such as overall survival and duration of response. In terms of trial design, we plan to randomize 670 patients who are naive to therapy in the advanced setting, equally to either life-elucidant combination of pembrolizumab in the experimental arm or pembrolizumab monotherapy in the control arm. We are including an appropriate number of global sites such as many large U.S. and European cancer centers and numerous other countries where we expect strong involvement. In the control arm, patients will have the option to receive TIL monotherapy upon confirmed disease progression verified by BIRC. Additional information on trial design, outcome measures, and eligibility criteria are available on clinicaltrials.gov. Our confidence in the success of TIL-VAMP3A1 is based on results from cohort 1A in our IOV COM202 trial of lifelucidin combination with pembrolizumab in ICI-naive advanced melanoma. In addition to prior data at the NCI for TIL monotherapy in anti-PD-1-naive melanoma generated in the pre-ICI era. We look forward to advancing our frontline melanoma strategy through our 2023 including site activation and patient randomization in TILVANS301. As Fred mentioned, TILVANS301 is expected to be well underway at the time of potential BLA approval for lysoleucine-posed anti-PD-1-advanced melanoma. We continue to execute on our non-small cell lung cancer, or NSCLC, pipeline at IOVANS, with six cohorts across three IOVANS studies to investigate multiple treatment regimens in various populations at various stages of disease. We recently shared top-line initial data from cohort 3A of the IOV COM202 trial, which we highlighted in a press release and investor conference call last month. Based on initial cohort 3A positive results in patients with advanced NSDLC who are naive to ICI treatment, particularly within the treatment naive and post-chemotherapy subsets, We plan to meet with FDA in 2023 to discuss data and a potential registration path for Liferleucine frontline advanced and SELC patients. Enrollment to Cohort 3A is ongoing, and we plan to present details and updated results at a medical meeting this year. Our IOV LUN202 trial is investigating LN145 monotherapy in patients who have received prior anti-PD-1 and chemotherapy in combination or sequentially and includes an option for pre-progression tumor harvest. We enroll patients for 2022 and expect to continue enrollment this year. Moving to cervical cancer, enrollment is underway in our expanded cohort two in the ongoing C14504 trial in patients who have progressed after chemotherapy and anti-PD-1 therapy. As a reminder, cohort two is intended to be pivotal to support regulatory submissions following dialogue and feedback from the FDA, and we look forward to continuing cohort two enrollment during the year. We are excited about our next-generation TIL therapy We are developing several genetically modified TIL therapies that utilize the gene editing talent technology licensed from Selectis to optimize TIL therapy by inactivating immune checkpoint proteins that inhibit anti-tumor response. IOV4001 is our first genetically modified PD-1 inactivated TIL therapy candidate. In the third quarter of last year, we treated the first patient with IOV4001 in our first in-human IOV GM1-201 trial in patients with previously treated advanced melanoma, or NSCLC. Additional programs using the TAB talent technology are expected to enter clinical development in 2024, including genetically modified TIL therapy with multiple inactivated immune checkpoint targets. Earlier stage research in preclinical studies include additional approaches to increase tilt potency, including the selection of CD39-69 double negative tilts and enhancements such as tethered cytokines. As part of our strategy to optimize the tilt treatment regimen, we also continue IND-enabling studies of our novel interleukin analog IOB3001. I am available during the question and answer session. For now, I will hand the call over to Jean-Marc to discuss our fourth quarter and full year 2022 financial results.

spk14: Thank you, Frederic. My comments will summarize our planned acquisition of Proloquin, as well as the high-level financial results from our fourth quarter and full year ended on December 31st, 2022. More details can be found in this afternoon's press release, as well as in your SEC findings. Last month, we announced that we have entered into an agreement to require polluting from Clinigen. Terms of the agreement include an upfront payment of £167.7 million British Pounds, the £41.7 million British Pounds milestone payment upon first approval of lipolucel in advanced melanoma, and double-digit polluting global sales royalties from AirAvance to Clinigen. The transaction will be financed with existing cash and is expected to close after all conditions are met, including regulatory approvals and clearance and other customary closing conditions. As a late stage oncology company approaching potential commercialization this year, we are also investing in launch preparations, internal manufacturing, and pipeline activities. As of December 31st, 2022, We held $478.3 million in cash, cash equivalents, investments, and restricted cash, compared to $602.1 million at December 31, 2021. Taking into account proceeds raised in 2023 from our at-the-market or ATM facility, our unaudited cash position is approximately $670 million as of February 24, 2023, which includes approximately $450 million in net proceeds raised through the ATM during the fourth quarter of 22 and into the first quarter of 23. This current and transcend cash position is expected to fund our operating plan into the second half of 2024, including the product acquisition, manufacturing activities, launch readiness and execution, plan clinical trial and pipeline advancements. Transitioning to the financial results for the fourth quarter and full year on December 31st, 2022. Our net loss for the fourth quarter of 2022 was $105.3 million, or $0.64 per share, compared to net loss of $99.3 million, or $0.63 per share, for the fourth quarter of 2021. Net loss for the full year of 2022 was $395.9 million, or $2.49 per share, compared to net loss of $342.3 million or $2.23 per share for the full year of 2021. Research and development expenses were $80.6 million for the fourth quarter of 2022, an increase of $5 million compared to $75.6 million for the fourth quarter of 2021. Research and development expenses were 294.8 million dollars for the full year 2022, an increase of 35.8 million dollars compared to 259.0 million dollars for the full year 2021. The increase in research and development expenses in the fourth quarter and full year 2022 over the prior year periods were primarily attributable to costs associated with the growth of the internal research and development team including stock-based compensation expense, as well as facility-related expenses and internal research programs. These increased expenses were partially offset by lower clinical and manufacturing costs, driven by completion of enrollment in typical cohorts of a clinical trial. General and administrative expenses were $26.5 million for the fourth quarter of 2022, an increase of $2.7 million compared to $23.8 million for the fourth quarter of 2021. General and administrative expenses were $104.1 million for the full year 2022, an increase of $20.4 million compared to $83.7 million for full year 2021. The increase in general and administrative expenses in the fourth quarter and full year 2022 compared to the prior year periods, were primarily attributable to costs associated with the growth of the internal general and administrative and commercial teams, including stock-based compensation expense, the build-out of the new corporate headquarters, as well as pre-commercial activities. As of December 31st, 2022, there were approximately 187.8 million common shares outstanding. I will now arm the call back to the operator to kick off the Q&A session.

spk32: Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Peter Lawson from Barclays.

spk13: Great. Thanks so much for taking the question. Fred, you sounded confident around the BLA submission by the end of 1Q, kind of what needs to be done there, what's left?

spk08: Yeah, Peter, we're really confident that we're going to get this done. We have essentially a lot of activities we talk about relating to the assay work, CMC work, validation work, and stuff like that that we were completing. We've talked about it before. It's relatively routine work, but it's It's very important to the FDA, and that's kind of what we're getting done here so we can complete the rolling VLA submission.

spk13: Gotcha. Okay. And then I know some time is off, but just on the launch of Life of Lucella, are you expecting to see a bonus of patients on launch and kind of any way you can kind of quantify that?

spk08: Yeah. Jim, do you want to take that one?

spk17: Sure. Sure. Given our experience in dialogue and with the KOLs at many of these sites and even our clinical trial experience, there's a high unmet need. And this translates into a number of patients who are in need of therapy after checkpoint inhibitors. So we are expecting a bolus of patients at launch given that high unmet need.

spk08: And, Peter, we do run an EAP program in order to stay in close contact with the site so that we're making sure that we have a good feel for what's out there. Right. I didn't care for patients as FDA wants you to do.

spk01: Thank you.

spk32: Thank you. One moment for our next question. Our next question comes from the line of Mark Breedenback from Oppenheimer.

spk19: Hey, guys, thanks for taking the question. Two quick ones for me. First, I'm wondering if you can just comment on remaining barriers before you can begin recruitment into the Tovance 301 study. And then I'm also wondering, aside from the cohort 3A lung data that Friedrich mentioned, are there plans for additional clinical data presentations in 2023? Thanks for taking that question.

spk06: Frederick, do you want to talk a little bit about the startup activities for 301?

spk08: And you can probably talk a little bit about the potential for lung data later this year, too, if you want.

spk16: Sure, happy to. Thanks for the question. So we have spoken about being in startup on Tobin 301. So that basically means submission of the protocol. to sites, reviews at sites, site startup, site initiation, and then startup enrollment. There are no specific additional hurdles that would be kind of like one hurdle that would apply to all sites. It's now really activities at individual sites. And much of that work is basically going on in parallel and will continue as we are adding a meaningful number of sites both in the U.S. as well as ex-U.S., Europe, and beyond Europe to the sites that were enrolled to this trial. So really no specific hurdles of site startup activities at individual sites. Does that make sense?