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spk05: Welcome to the Iovance Biotherapeutics third quarter and year-to-date 2023 financial results and corporate updates conference call. My name is Abigail, and I will be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we'll conduct a question and answer session. To ask a question, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. 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.
spk06: Thank you, operator. Good afternoon, and thank you for joining us. Speaking of today's call, we have Dr. Fred Voth, our Interim President and Chief Executive Officer, Dr. Igor Belinsky, our Chief Operating Officer, Jim Ziegler, Executive Vice President, Commercial, Dr. Frederick Finkenstein, our Chief Medical Officer, and John Mark Bellaman, our Chief Financial Officer. Dr. Brian Gassman, Executive Vice President, Medical Affairs, and Dr. Raj Puri, our Executive Vice President, Regulatory Strategy and Translational Medicine are 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 nine months ended on September 30th, 2023, 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 IOMAS's goals, business focus, business plans and transactions, revenue, 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 collaboration, cash position and expense guidance, and future updates. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filing. 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.
spk02: Thank you, Sarah, and good afternoon, everyone. I'm pleased to highlight several recent important milestones for I-Advance. We continue to make significant progress towards U.S. commercialization while pursuing opportunities for our TIL therapies and additional geographies in solid tumor cancers. Our top priority is to secure FDA approval and launch like Volusil in the U.S., the new class of treatment for advanced melanoma patients with limited options. Overall, the BLA process continues under priority review with several positive status updates. We remain engaged with the FDA to complete the review as efficiently as possible. As a reminder, the FDA reiterated in September that there are no major review issues and no plans to hold an advisory committee meeting. In addition, all pre-approval inspections of all clinical sites and internal and external manufacturing and testing facilities have been successfully completed. The FDA is also engaged and has no concerns with the status of the Tobance 301 confirmatory trial which remains on track to be well underway by the PDUFA data. We appreciate the FDA review team's efforts to expedite the remaining review. We are confident in the potential for Lifolucel to redefine the treatment paradigm for these patients who have no approved options after current standard of care. With the strength of our clinical data, manufacturing capabilities, and commercial readiness efforts, IVAN is ready to rapidly serve the U.S. melanoma community immediately following approval, including the potential scenario for approval earlier than the February 24, 2024 PDUFA Beyond the US, we plan to submit additional marketing applications for Lake Volusia in Europe and other geographies. Based on positive feedback from the European Medicines Agency on codes two and four of the C14401 clinical trial, we plan to submit a marketing authorization application in the first half of 2024, with a potential European launch in 2025. We're also engaged with regulatory authorities in the United Kingdom and Canada. We plan to submit marketing applications in both countries in the second half of next year, again with potential launches in 2025. Key markets such as Germany, France, and the UK have mechanisms for early access and reimbursement that can begin to drive significant additional near-term revenue by the end of 2025. Next year, we expect to have additional regulatory updates about our expansion plans for life-reducing Australia and other countries with a significant number of advanced melanoma patients. Collectively, the advanced melanoma population in Germany, France, the UK, and Canada is slightly larger than the US patient population, with the same unmet medical need. Our geographic expansion, when complete, can more than double the total addressable patient population for Lefluso and advanced melanoma. We plan to leverage existing resources to serve the melanoma community in these new geographies without incurring significant additional expenses. For example, our IVAN Cell Therapy Center, or ICTC, has sufficient capacity for these new countries, and we already have an existing office in Amsterdam and field medical support in the region. As we prepare to launch Lifolucyl, we are also integrating Prolucan, a currently marketed IL-2 product used as part of the Tilt Therapy regimen. By owning Prolucan, we can offer it alongside Lifolucyl and have full control of the IL-2 supply chain. We also expect to lower clinical trial expenses and future cost of goods for Lifolucyl. Beyond our regulatory and commercial readiness activities, our robust Tilt Therapy pipeline continues to advance with seven active clinical trials. These include two registrational trials, IVANCE and frontline melanoma, and LUN202 in previously treated advanced lung cancer, which Frederick will highlight in a moment. Completing enrollment in LUN202 in 2024 is a top priority towards a potential supplemental VLA filing. Additional clinical trials include the IOV COM202 trial in solid tumors, and our first in-human trial of our genetically modified TIL therapy, IOV4001. Lastly, we are excited to introduce a new I-Advanced TIL therapy program in endometrial cancer. Checkpoint inhibitors are moving into earlier lines of therapy, leaving an unmet medical need for patients who request on or after immunotherapy and chemotherapy. Frederick will provide more details on this new program later in this call. Turning to our organization, we have more than 500 people with experience in developing and commercializing oncology and cell and gene therapy products. They are ready for our initial US launch, ex-US expansion, and ongoing pipeline developments. We have recently completed headcount growth and significant one-time investments in commercial manufacturing readiness activities. to prepare for launch and expand our pipeline. Following these one-time investments in strategic portfolio prioritization, we can reduce quarterly and annual operating expenses in the remainder of 2023 and full year 2024, while continuing all key clinical programs and internal manufacturing capabilities. In addition, our September 30th cash position of roughly $428 million is expected to fund our operating plan into 2025. John Mark will provide additional color on the expense guidance and cash runaway assumptions on today's call. We're excited about the near-term future at IVANS as we advance and broaden our mission to be the global leader in innovating, developing, and delivering tilt therapies for people with cancer across multiple cell tumors. I look forward to addressing your questions later in this call, and will now ask Igor to present our manufacturing updates.
spk20: Thank you, Fred. We are committed to operational excellence. and to date have provided TIL therapy to more than 600 patients with a consistent manufacturing success rate of more than 90%. As part of the BLA review process, the FDA completed successful pre-licensing sections of our Iovansil Therapy Center facility, or ICDC, and our contract manufacturer's facility. Both sites are prepared with sufficient capacity and staffing to supply our commercial launch and clinical trials. Our manufacturing network strategy supports our vision to establish TIL therapy as the next paradigm shifting class of cancer therapy in the U.S. and beyond. The ICDC is currently built to supply TIL products for more than 2,000 patients annually in the U.S. and our planned geographic expansion. By building out additional existing shell space, ICDC may ultimately supply two products for more than 5,000 patients annually. Longer term, our vision is to build capacity for more than 10,000 patients annually by adding new facilities, as well as streamlining and automating manufacturing processes. Intellectual property, or IP, is also a critical component at IVANCE. We currently own at least 60 granted or allowed U.S. and international patents, including Gen 2 patent rights that we expect to provide exclusivity into 2038. Extensive detail on Iovance's owned IP is available 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.
spk16: Jim? Thank you, Igor. At Iovance, We have the potential to transform the practice of medicine in advanced melanoma and additional solid tumors. In the U.S., approximately 8,000 people die of melanoma annually, and the World Health Organization reports higher mortality in Europe. Lifolucel has the potential to be standard of care for patients who have no currently approved treatment options after standard of care frontline therapies. We have a sense of urgency to deliver Lifolucyl to these advanced melanoma patients upon approval. Our commercial and cross-functional teams are on track as we approach our PDUFA date. Today, I will highlight onboarding for authorized treatment centers, or ATCs, payer engagement, and commercial operational readiness activities. First, onboarding is a strong indication of ATC commitment and Lifolucyl demand. Today's press release provided our first status update on ATC onboarding. Approximately 30 centers have completed pre-approval onboarding steps to establish their TIL service line capabilities. These centers are educated in all aspects of the lipoleucine treatment regimen with staff and processes to begin treating patients pending the approval. Previously, we shared our goal to onboard 40 ATCs within 90 days of the PDUFA date. Based on our onboarding progress, we now expect to onboard approximately 50 centers within 90 days of the PDUFA date. We are also planning a disciplined approach to organize and schedule each ATC for their first treatments with full IOVAN support. We believe a positive initial experience will drive long-term success and peak revenues. Reimbursement is also essential for patient access and provider adoption. Our market access team continues to engage the key national and regional payers to accelerate timely access and appropriate reimbursement for lifeloosal upon approval. We believe payers appreciate the high unmet need, lack of treatment options, and clinical value of lifeloosal and advanced melanoma. We expect strong reimbursement for lifeloosal with a payer mix that includes a favorable, commercially-insured population. More than three-quarters of advanced melanoma patients are currently insured through commercial, Medicare Advantage, and Medicare IPPS-exempt segments. Based on our payer interactions, we expect coverage similar to CAR T's requiring prior authorization with coverage consistent with label, medical coverage policies issued within about 90 to 180 days, and single case agreements for commercially insured patients. Although pricing will be disclosed after approval, we believe the life elusive value proposition supports pricing in the higher range of CAR T cell therapies. The CAR T prices range from $424,000 to $508,000 based on current and reported price increases with additional price increases expected in early 2024. In addition to Lifolucel, we will receive incremental revenue from the sales of Prolucan for each patient. As a reminder, revenue recognition for Lifolucel occurs upon infusion, like other cell therapies. As we approach the U.S. launch, I would like to highlight the extensive cross-functional launch preparations underway. Our commercial and cross-functional teams are on track as we approach our PDUFA date, and we remain confident in our ability to deliver a successful launch. I will now pass the call to Friedrich Finckenstein, our Chief Medical Officer, to highlight our clinical progress.
spk18: Thank you, Jim. This afternoon's press release highlighted several pipeline updates. On the call today, I would like to focus on our recent data presentations, which are available on our corporate website, as well as selected registrational programs in frontline advanced melanoma and non-small cell lung cancer. I will also discuss our new TIL program in endometrial cancer. We are pleased that several recent posters and presentations from our C14401 trial continue to support the potential benefit of lifeloosal as a one-time treatment that is differentiated from other immunotherapies for advanced melanoma. In October, during the European Society for Medical Oncology, or ESMO, Congress, and at this week's Society for Melanoma Research, or SMR, we highlight clinically meaningful and durable activity for life elusive from a subgroup analysis of patients with the rare and difficult to treat mucosal melanoma subtype. During the Society of the Immunotherapy of Cancer, or SATC, annual meeting last week, we highlighted the durable efficacy shown in a now four-year analysis of cohorts two and four of the C14401 trial. Our poster reported the longest follow-up data on live elusal treatment outcomes in the largest population of patients with anti-PD-1 refractory advanced melanoma treated with TIL therapy. Our registrational trials continue to advance in additional indications. TILVANS-301 is designed to support accelerated and full approvals of lifelucel in combination with pembrolizumab in frontline advanced melanoma. This randomized trial remains on track to be well underway at the time of potential approval and is designed as the confirmatory trial to support full approval for lifelucel in post-anti-PD-1 advanced melanoma. We continue to randomize patients and activate global sites in SILBANS 301 in key geographies with a large presence of melanoma patients and the potential for strong enrollment. We recently activated new sites in the US and the first site in Australia. We also have regulatory clearances to open sites in the United Kingdom and Canada. In non-small cell lung cancer, we have also made significant progress with our registrational strategy. IOV LUN202 is our registrational single-arm phase 2 trial in post-anti-PD-1 lung cancer. Following the positive preliminary data analysis from LUN202, physician interest and momentum for center participation is strong and remain actively activated with the site. We also have FDA regulatory feedback that the trial design may be acceptable for an accelerated approval of TIL therapy in post-anti-PD-1 non-small cell lung cancer. The preliminary analysis included data from the registrational population in cohorts 1 and 2, which enroll EGFR ROS or ALK mutation negative patients who have progressed on or after chemotherapy and anti-PD-1 therapy. Six patients had a confirmed objective response, representing an ORR of 26.1%. All six responses, including one complete response and five partial responses, remained ongoing at the time of the data analysis and ranged from 1.4 plus to 9.7 plus months. We remain on track to complete enrollment in LUN202 in the second half of 2024. Based on this trial, we intend to submit a supplemental DLA for U.S. accelerated approval in post-anti-PD-1 non-small cell lung cancer. We are proposing a phase 3 registrational trial in frontline lung cancer, which is intended to serve as the confirmatory trial for full approval in the post-anti-PD-1 setting and to support an approval in frontline treatment settings. We plan to meet with FDA early next year to discuss the phase three registrational trial, where our goal is to improve frontline non-small cell lung cancer therapy by adding TIL therapy to standard of care pembrolizumab maintenance therapy administered after completion of the initial chemoimmunotherapy. Our confidence in this frontline trial design is supported by the encouraging responses and response duration that we have observed with the TIL pembrolizumab combination compared to standard of care benchmarks, even without chemotherapy.
spk08: Turning toward our new program in endometrial cancer, as Fred mentioned,
spk18: We are starting an IOVAN still therapy program in endometrial cancer. The standard of care frontline treatment is shifting, and there is a lack of approved treatment options for patients who progress on or after immune checkpoint inhibitor containing treatment regimen. Analogous to other tumor types, our one-time TIL therapy may offer benefit in this setting. Based on the TIL mechanism of action, the benefit of TIL therapy is likely to extend across patients with tumors that are mismatch repair mechanism deficient and proficient, and our clinical program will include patients from both subgroups. We look forward to providing more details as we work towards initiating the study in the first half of 2024. I am available during the question and after session. For now, I will hand the call over to Jean-Marc to discuss our year-to-date 2023 financial results.
spk12: Jean- Thank you, Frédéric. I will summarize the high-level financial results for the three and nine months ended on September 30, 2023. More details can be found in this afternoon's press release, as well as in our ICC findings. Beginning with the balance sheet, I advance add $427.8 million in cash, cash equivalents, investment and restricted cash as of September 30, 2023, compared to $478.3 million as of December 31, 2022. The current cash position includes approximately $203.2 million in combined net proceeds from our public offering in July 2023 and the at-the-market equity financing facility. We expect our cash position and anticipated 2024 revenue from LIFO and Proloquing to be sufficient to fund current and planned operations into 2025. As Fred described earlier, we continue to internally prioritize and optimize our operation and completed many one-time investments. As we carefully manage our operating expenses, we are guiding towards 2024 cash burn in the range of $320 to $340 million, excluding one-time expenses, and will continue to look for opportunities to further streamline spending and drive revenue. Transitioning to financial results, net loss for the third quarter ended September 30, 2023 was $113.8 million, or 46 cents per share, compared to a net loss of $99.6 million, or 63 cents per share, for the third quarter ended September 30, 2022. Net loss for the 9 months under September 30, 2023 was $327.7 million or $1.44 per share compared to a net loss of $290.6 million or $1.80 per share from the same period under September 30, 2022. We began recording revenue from product sales following the Prolooking acquisition in May 2023 and anticipate significant revenue after the launch of LifeAlooso. Revenue for the third quarter and nine months under September 30, 2023 was $469,000 and $707,000 respectively. There were no revenue for the third quarter and nine months under September 30, 2022. Cost of sales for the third quarter and nine months ended September 30, 2023 was $4.3 million and $6.4 million respectively. The cost of sales includes cost of inventory associated with sales of as well as $4 million and $5.9 million, respectively, of non-cash amortization expenses of the acquired intangible assets for developed technology in the three and nine months period ended September 30, 2023. There was no cost of revenues for the third quarter and nine months ended September 30, 2023. Research and development expenses were $87.5 million for the third quarter of September 30, 2023, an increase of $15 million compared to $72.5 million for the same period under September 30, 2022. Research and development expenses were $256.6 million for the nine months ended September 30, 2023, an increase of $42.4 million compared to $214.2 million for the same period ended September 30. The increases in research and development expenses in the third quarter and the nine months ended September 30, 2023, over the prior year periods, were primarily attributable to growth of the internal research and development team, as well as higher costs related to facilities and the initiation of new clinical trials, including the Phase III TIL VANS trial, which were partially offset by a decrease in stock-based compensation expenses. Selling general and administrative expenses were $27.0 million for the third quarter and the September 30, 2023, a decrease of $0.9 million compared to $27.9 million for the same period and the September 30, 2022. Selling general and administrative expenses were $77.0 million for the nine months and the September 30, 2023, a decrease of 0.6 million dollars compared to 77.6 million dollars for the same period under September 30, 2022. The decrease in selling general and administrative expenses in the third quarter and the nine months ended September 2023 compared to prior year periods was primarily attributable to the decrease in stock-based compensation expenses and other costs related to the timing of spend compared to the prior year period, including marketing, advertising, and legal costs, partially offset by costs associated with the growth in the overall business. As of September 30, 2023, there were approximately 255.8 million common share outstanding. Before I link the call back to the operator to kick off the Q&A session, I want to reiterate our 2024 cash-run guidance in the range of $320 to $340 million, excluding one-time expenses. as we will carefully manage your operating expenses in the coming months and quarters. Operator, we can now start the Q&A session.
spk05: Thank you. At this time, we'll conduct the question and answer session. As a reminder, to ask a question, you will need to press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again.
spk09: One moment while we compile the Q&A roster. Our first question comes from Peter Lawson with Barclays.
spk05: Your line is open.
spk11: Great. Thank you so much. Thanks for taking my questions. Just as we think about a potential EU filing, if you can talk about the impact of a single-arm study on an EU approval and if that kind of changes the way you think about reimbursement as well in the EU. And then I've got a follow-up. Thank you.
spk02: Sure, Peter, yes. You're thinking of the CAR T products and what they did to get approval there. And obviously, we have the TILBAN 301 study already running, which could provide us that randomized control trial that we could use to, and it will read out right around the time, potentially, where we could use it to drive reimbursement in Europe. So yes, that's correct. We think, as you know, there's early access programs in all the major countries. The single arm data should be good enough for that. The EMA seems fine with the single arm data. And then you get through the early access program and then until Vance is reading out and potentially you're on to more longer-term public reimbursement programs in Europe. Great. Thank you. And then, sorry.
spk11: And I had a follow-up just around the number of authorized treatment centers that seem to increase. I'm just curious about what drove that increase, whether it was kind of demand driven, essentially, or if it was the benefit of the FDA delay.
spk02: Jim, do you want to take this?
spk16: Hi, Peter. It's Jim. Yes, it's a combination of both. There's a high sense of urgency and demand from our treatment centers, so we've had a few extra weeks, months to prepare, and we're just increasing the number. We're very confident to share that number publicly, the demand is so high right now for these centers to be able to offer lipolucel. Great.
spk11: Thank you. I'll get back into the queue.
spk09: One moment for our next question. Our next question comes from Colleen Cousy with Baird. Your line is open.
spk07: Hi. Good afternoon. Can you hear me okay? Hello? Can you hear me okay?
spk02: Colleen, we can hear you.
spk07: Okay, great. So thanks for taking the question. Congrats on all the progress and on the launch prep. So clarifying question, on the 30 centers who have completed the ATC preparation, theoretically, if Lifolucil were approved today, could those centers start preparing to dose a patient today? Or kind of what else needs to be done for those patients to start using Lifolucil once it's approved, once they're through the training?
spk02: Yeah, Jim can answer this in more detail, Colleen, but yes, basically these guys are ready to go. Jim, do you want to give a little bit more detail here?
spk16: Sure. Thanks, Colleen. Just real quickly, what we've done to date on the pre-approval onboarding is, you know, we've worked with the centers to develop their TIL service line, which includes the clinical end-to-end education and training with med-on surgeons, cell therapy. We've operationalized the tumor journey in terms of building out workflows, SOPs, coordination and procedures on all of the logistics from OR, chain of identity, chain of custody to product handling and logistics. And we've worked extensively on the reimbursement front. So when we say that these centers are ready to go, they're ready to go. The last step in all of this will be for us to use the final label, make sure that all of our training and initiatives are consistent with label. And then we'll roll out a very abbreviated update based upon the label, and centers will be ready to enroll their first patients.
spk07: Great. That's really helpful. Thank you. And you had some commentary around the size and the mortality rate in some of the ex-U.S. territories. Can you just talk a little bit more about the differences in the cell therapy market as you see it in Europe versus the U.S., and talk about what the manufacturing plans would be in those regions?
spk02: Sure. The manufacturing plant we mentioned earlier, we're going to use our ICT facility there. So I want to make it absolutely clear we're not talking about building a new facility there right now. We're focused on using our existing facility that's already built out to make efficient use of our capital. The CAR-T launches in Europe provide a pretty good yardstick for what's available there and what can be done in Europe. You can see from there's six CAR-T products that have been approved in Europe at this point. in different jurisdictions, and you've seen sales figures, you've seen from the European sales of these things that range anywhere from tens of millions up into the low hundreds of millions at this point. So we see this as a pretty good upside opportunity here. Again, it increases the market significantly. We've got more than 3,000 patients a year in Germany dying from melanoma right now, and equally bad numbers in France and the UK and elsewhere. And then we've also got Canada in play here, and we're going to look at Australia as well, as we've mentioned, too, where We have well over 1,000 patients here dying in Australia of melanoma. The demand for TIL therapy in these jurisdictions is very high. We have clinical sites there. We know the physicians very well, and we're very comfortable with launching the product there. We think it can be successful, just like the CAR T's are.
spk07: Great. Thanks for taking our questions.
spk05: One moment for our next question. Our next question comes from Yanin Zhu with Wells Fargo. Your line is open.
spk15: Great. Thanks for taking our questions. Could you give us a sense of how the review is going? Have you had the late cycle meeting? Have you had any labeling discussion? And also, could you talk about your perception of the agency's resources allocated to the review and whether the previous constraint has improved? And then I have a follow-up. Thanks.
spk02: Raj, would you like to take Jan's question? I think Raj is on the line.
spk17: Yeah, no, I'll take that question first. Thank you, Jan, and thank you for the question. The review is coming along very well. We have been getting IRs and providing all the responses to the agency. Our late cycle meeting is planned. We will announce when that has happened. There are no other additional issues currently. The resource issues seem to be under control, and we are expecting that our VLA would be approved perhaps before the PDUFA date in January. Sometimes in January. The PDUFA date is February 2024.
spk15: Great. Great. And could you elaborate on the estimate of January? Is there anything for us to further understand here? Yeah.
spk17: So the FDA likes to approve products with the unmet medical needs at least four to six weeks prior to the PADUFA date, as they have done with all CAR T-cell products. and other products as well. So with that, keeping that in mind, FDA will like to, they like to approve the product sooner before the PDUPA date. So we are expecting the same for the live lucid.
spk15: Got it. That's very, very helpful. And then my follow-up is about the number of centers and manufacturing capacity. So great to hear that you have 30 centers virtually ready to go. And by the time of approval, I assume you might have additional centers ready to go. And the question is, would you have any capacity limit that you might place a cap on the number of manufacturing slots at each of these early centers? And my other question is whether you can foresee that you might onboard more than 50 by 90 days after the approval, and would your capacity allow that? Thank you.
spk02: Yeah, Jan, let me start, and then maybe Igor can help out here. Yes, obviously you're aware of our facility. It's a very large facility. It's got capacity. It's built today for up to 2,000-plus patients. FDA is the final decider of capacity with cell therapy, so we can't really say what's going on until we Got the feedback from FDA as part of the approval process at the very end. We'll find out more about that. We did announce, as you saw, that we anticipate 50 EATCs within nine days of the Zufa date. It's possible we can go beyond that. We have to see. Right now, that's a pretty large launch. It'd be the largest launch ever for cell therapy, so it's pretty aggressive. But let me turn it over to you for just some comments on the capacity and our ability to scale up between our own facility as well as our contract manufacturer.
spk20: Yeah, thanks for the question. So first of all, as I mentioned earlier, the FDA completed pre-license inspections at both sites at our ICTC facility and contract manufacturing facility. Both went very, very well. And so both were successful. So both sites, our ICTC site and the contract manufacturer's site are preparing for the launch and also producing clinical material. The exact capacity, as Fred mentioned, will be determined by what capacity the FDA allows. We've been hiring and training the personnel at what we have been and our contract manufacturing partner has been as well in preparation for launch. But again, the exact capacity of launch we'll know hopefully in the next several weeks as we get to approval.
spk15: Great. Super helpful. Thank you for all the comments.
spk05: One moment for our next question. Our next question comes from Michael Yee with Jefferies. Your line is open.
spk01: Hi, thanks for the question. This is Dina Ahn for Mike. Congrats on all the progress. I just wanted to ask about lung. I know that there was a previous disclosure about potentially seeing some second line updated lung data, maybe in a medical conference that's coming up by year end. Is that still on track, or what are you guys thinking about the lung strategy? Thank you.
spk02: Yeah, Deanna, we're looking to put data out on lung when we think we have meaningful additional numbers available. So, we would really like to see more patients, I think, in the study, and then we will get that to a medical meeting. I don't know if we're going to get it by the end of the year at this point, or it could be next year, but it's important to have that data be more significant once we have more patients in the study. Remember, we put out data with 23 patients on a 26.1% ORR with good signs of durability, so it could use a dose of additional patients here to help bolster the case. Meanwhile, we're just executing on a study right now and running hard to make sure we can complete enrollment in 2024.
spk05: Perfect. Thank you so much. One moment for our next question. Our next question comes from Rene Benjamin with JMP Securities. Your line is open.
spk13: Hey, good afternoon, guys. Thanks for taking the questions, and congratulations on all the progress and a very informative call. A couple of quick ones. You know, you mentioned following a strategic portfolio prioritization. I typically think, you know, anytime that's mentioned, there have been programs that have been backburnered. Are there any programs that have been backburnered? Because you mentioned that there are seven clinical studies that are still ongoing. And as part of that, can you just give us an update as to what's happening with the ovarian study? Or do you think the endometrial one that you're going to start will kind of take that one over?
spk02: Yeah, Randy, I think you're referring to cervical, I think, instead of ovarian, right? I said we don't have an ovarian program at iAdvanced.
spk13: Oh, sorry, yeah, cervical.
spk02: Yeah, so all those studies continue to run, and we actually think we can continue to run these studies in the budget we're on. When we say prioritization, we may focus more on enrolling one particular study or putting our efforts on, for example, the LUN202 study where we need to enroll fast. That doesn't mean we're closing the cervical study. The endometrial study, when it does hit, will hit later, and so we don't foresee a near-term impact on cash. We could always reevaluate the program to that point. What we're basically saying, though, is we're focusing on particular studies that are of high importance, like LUN202 and Telvan 301, as well as the VLA approvals and the XUS filings at this point so we can drive revenues.
spk13: Got it. Okay. Then just switching gears to the asthma data that Friedrich mentioned, you know, as of the latest long-term follow-up, can you talk a little bit, I guess, about the PFS for the pooled cohorts of, you know, two and four? What kind of, can you just remind us what kind of subsequent therapies these patients got? And if I'm remembering right, correct me if I'm wrong, The 26% of patients that are surviving four years, right, their overall survival is 26% of patients are out four years. Does that, you know, suggest that patients who have been treated with Lifolucel are not in any way detrimentally impacted by any post therapies? Or is there another way to look at that data? Yeah.
spk18: Rene, I can take this one. So as you know, collecting data, collecting subsequent data is always something that you have to take with a grain of salt. We haven't put out a comprehensive summary of what we are seeing in the study. But again, I think what you're seeing in this long-term follow-up data is really the promise that TIL cell therapy has for patients treated in a setting where there's really no available care, right? So I don't actually think there's going to be a pattern here in regards to what these patients would be seeing after. We certainly don't see any signals for detriment. What we think is really fascinating in this data is the fact, is the long-term durability. the fact that we now have patients who have completed the study in a response, meaning a five-year follow-up, which equals to cure, and that we see late deepening of responses and conversions to complete response, which is speaking to the mechanism of action of a living drug. That, I think, is the importance of this data.
spk13: Yep, yep, fair enough. I guess just one final question regarding the label. Is there any possibility of a blue sky sort of scenario for a labeling discussion where you get more than what you want? Or really, when we're looking at this data, accelerated approval and the like, do you think the base case scenario based on the trial results from cohort two and cohort four is the best that we can hope for?
spk02: Well, actually, let me say something, Rajen, that you can add in because we didn't answer Jan on this fully either. But on the label front, if we get cohort four followed by pooled cohort two plus four, which is what we think FDA is leaning towards right now based on our conversations, we think that's the home run, the best option, because that allows promotion on the back of both the cohort four data, the pivotal data, as well as the 153 patient data set with with MDOR not reached, it's a large data set. It just gives you a lot of different promotional opportunities for the product. Raj can tell you more about sort of the nitty-gritty of the details of when the timing for labels and that kind of discussion comes up if you want.
spk17: Yeah, I think some of Fred covered pretty well. Some of the labeling discussion actually has begun. We have received a few IRs and we have responded to them. So I'd be concerned that the labeling has started, and we're going to have more discussions regarding that in the next couple of weeks or so. First, guys, thanks for taking the questions, and good luck.
spk09: One moment for our next question. Our next question comes from Mara Goldstein with Mizzou.
spk05: Your line is open.
spk14: Great, thanks so much for taking the next question. If I could just return to the strategic portfolio prioritization as well as the completion of a number of activities. You mentioned that that is likely to reduce the quarterly and annual operating expenses. So I'm wondering if you can provide us with some guidance, at least directionally, as to what that is. And then on the ATM program, how much capacity is left there?
spk02: Jean-Marc, do you want to take that?
spk12: Yeah, definitely. Thank you, Mark, for the question. So I'm not going to be really specific, but you can imagine that this year as we were preparing for launch, there was a lot of one-time expenses related to manufacturing readiness, even on the CAPEX and OPEX front. also wrapping up on the commercial, all the activities and medical. So there is a lot of spend that occurred in 2023 that will be considered again one time and not happen next year. So prioritization means also managing investment over time. And that's why we're confident about our ability to reduce our spend both quarterly and annually as we announce during the call. On the ATM, we still have a large amount available because we have a 500 million ATM on which we only do a partial amount in Q3. All right.
spk14: Thank you very much.
spk05: One moment for our next question. Our next question comes from Asika Gunawardin with Truist. Your line is open. Hi, this is Karina for ASTICA.
spk03: I had a question. If you could share some color on the manufacturing success rate, whether you had any discussions with the FDA on this and the potential for specs to be tighter in the commercial setting, as has been previously seen with other parties. Thank you.
spk02: Igor, do you want to get that?
spk20: I'm sorry. Could you repeat the question, please? My audio is broken up.
spk03: So on the manufacturing success rate, whether you had any discussions with the FDA and for the potential for the specs to be tighter in the commercial setting?
spk20: Yes. So as you know, in case of CAR-T, we've seen that happen in some cases to an extreme extent. In our case, we've had the manufacturing success rate maintained in the clinic at more than 90% consistently, and in the pivotal cohorts, it was 94.7%. The final specs will be set very late at approval, so we cannot comment on the final specs right now, but that's certainly been part of the discussions with the agency and part of the information requests that have been ongoing. But we don't expect, I mean, right now we don't expect anything as anywhere close as draconian as you've seen in some cases of CAR-T in terms of tightening the specs.
spk09: One moment for our next question. Our next question comes from Ben Burnett with Stiefel.
spk05: Your line is open.
spk19: Hey, great. Thanks so much. I wanted to go back and ask another question about just the capacity. I understand that the FDA will sort of help define the capacity at launch just in terms of the number of slots that are available for commercial use. But I guess, can you frame for us just maybe like an upper limit of the capacity that you feel like you can handle now?
spk02: Yeah, Ben, the facility right now is actually constructed to go even beyond 2,000 patients a year at our facility. And then on top of that, we have our CDMO WUSHI that has considerable capacity, too. We haven't disclosed exactly what that is, but it's quite large. It could represent a good portion of our capacity at lunch. So that's really the max that we've got constructed today without the need for additional capital.
spk19: Okay, that's helpful. And does that include, like, the personnel required to sort of run that type of capacity at that level?
spk02: Yeah, the majority of that personnel is in place, and the rest of it can be put in place very quickly. Obviously, we don't just sit the personnel there as a fixed cost if we don't need to, but we are very well skilled in bringing on manufacturing and QC personnel quickly and know how to do that, both I-Advanced and CDMO.
spk19: Okay, that's great. And then maybe just one other question. Can you frame for us when one would expect the labeling discussions to start? Would this be something at the late cycle meeting as being the first ever sort of till approval? Just any color you can provide on that.
spk17: Yeah, as I mentioned earlier, thanks for asking this question. That labeling discussion had actually begun. We have received a couple IRs clarifying things in the label. So, and it's going to continue until the perhaps earlier approval date. So, it's a good news for us that we have already engaged with the agency, the labeling discussion. Okay, that's great. Thanks so much.
spk05: One moment for our next question. As a reminder, to ask a question, you will need to press star 11 on your telephone and wait for your name to be announced. Our next question comes from Kelsey Goodwin with Guggenheim. Your line is open.
spk04: Oh, hey, thanks for taking my question. Just a couple quick ones from me. I guess maybe just on XUS, is this still something that you're looking to pursue on your own? And I guess is there any appetite to maybe partner in specific regions or just more broadly XUS? And then moving on to the endometrial cancer trial, I guess maybe could you just remind us what kind of the efficacy benchmark is in the post-PD-1 setting here? Thank you.
spk02: Yeah, I can answer the first one, Kelsey, and then Frederick can jump in on the second part on the individual benchmarks. So we're always looking for opportunities, and yes, we would consider things like partnerships, strategic alliances, and things like that. But right now, we do have the ability to go into these jurisdictions ourselves as needed, and we can do that with minimal capital investments right now, as we discussed on the earlier part of the call. We don't need to build a facility there. We don't need to do a whole lot of hiring there we can get in there and generate revenues relatively quickly now if it turns out there's a partnership that would be uh a value to our shareholders certainly we would consider that in those jurisdictions but right now we're looking to do it ourselves as well uh and then frederick can you answer the individual benchmark question yeah a really good question and i love getting a question about the material program thank you um
spk18: So as you know, what we're seeing happening right now with the checkpoint inhibitors moving from a second-line treatment setting into frontline, the data on what's being used and efficacy after use of checkpoint inhibitors is really not available. So I think probably the best benchmark, the best starting point of what you can look at as a potential benchmark would be data that have been used when Pembrol and Lenvadanum was brought into the second-line setting. There, the control arm of study Keynote 775 was investigators' choice of doxorubicin alpaclitaxel monotherapy, and those showed an ORR of about 15%. median duration of response of 5.7 months in patients with MMR-proficient tumors. The results in DMMR patients were a little lower with ORR of 12% and medium DOR of 4.1 months. So I think that's probably where you can start, given that we would be exploring populations that have seen both chemo, frontline chemo, which was the M5, but also either concomitant or sequential checkpoint inhibitor therapy, I think it's fair to say that we would choose to beat an ORR of about 10% to 15%.
spk05: Okay, great. Thank you so much. That concludes the question and answer session. At this time, I would like to turn the call back to Fred Vogt for closing remarks.
spk02: Thank you again for joining the iAdvanced Biotherapeutics Third Quarter 2023 Financial Results and Corporate Updates Conference Call. We've had a productive year to date with the priority review of the BLA, the close of the Prolucan transaction, important milestones in lung cancer, and delivering on our key regulatory, commercial, manufacturing, and pipeline activities. I am grateful for the patients, physicians, and regulators, as well as for our employees and cross-functional teams who have collaborated on our BLA submission while advancing our mission to be the global leader in tilt therapy. I'd also like to thank our shareholders and covering analysts for their support. Please feel free to reach out to our investor relations team for follow-up. Thank you.
spk05: Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.
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