This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk21: Welcome to the Iovance Biotherapeutics third quarter and year-to-date 2022 financial results and corporate updates conference call. My name is Andrew, and I'll be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session. During the question and answer session, if you have a question, please press star 11 on your touchtone phone. 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, Commercials. Dr. Frederick Zinkenstein, Chief Medical Officer. And John Mark Bellamy, our Chief Financial Officer. Dr. Madan Jagazia, our 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 30, 2022, as well as recent corporate updates. Before we start, I would like to remind everyone that statements made during this conference call will include forward-looking statements regarding Iovance's goals, business focus, business plan, pre-commercial activities, clinical trials and results, regulatory interactions, plans and strategies, research and preclinical 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 filing. Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward-looking data. With that, I will turn the call over to Fred.
spk20: Thank you, Sarah, and good afternoon, everyone. I am pleased to highlight some great momentum at iAdvance. We're getting ready to complete our Biologics License Application, or BLA, submission for our lead pill therapies, Lifolucil and Advanced Melanoma, while preparing for commercialization, developing our robust immuno-oncology pipeline. I'll begin today's introduction with a brief status update on the rolling BLA for Lifolucil, which we initiated in August. This remains our number one priority on behalf of our patients with Advanced Melanoma who are eager to see Lifolucil approved as soon as possible. A rolling BLA allows us to submit portions of the BLA to the FDA on an ongoing basis, so that the FDA may begin review as early as possible as documents are received, potentially allowing for earlier approval. We have continued to meet the submission schedule that we predetermined with the FDA and remain on track to complete the VLA submission this quarter. As a reminder, we previously received positive feedback from the FDA on the potency assay matrix. We also held a successful pre-VLA meeting in July where the FDA provided favorable feedback on clinical efficacy data from cohorts two and four, of our C14401 clinical trial, including duration of follow-up, and agreed that the clinical and safety data set was sufficient for a BLA review. The FDA remains engaged and supportive as we progress through the BLA submission process, and we look forward to continuing this level of collaboration. Bladpilucel, if approved, may address a significant unmet medical need for melanoma patients who progress on or after anti-PD-1 therapy, for which there are no FDA-approved treatment options. In addition, we are excited about the broader potential for lifeloosal as an earlier treatment for melanoma. We remain on track to begin a phase three trial of lifeloosal in combination with pembrolizumab and frontline advanced melanoma in late 2022, which is also designed to serve as a confirmatory study for our initial BLA submission. In anticipation of potential approval and launch of lifeloosal next year, our commercial readiness activities include medical education, treatment center onboarding, payer engagement, commercial manufacturing readiness, and near and long-term capacity planning. As part of our cross-functional effort to educate physicians about our clinical data and the unmet medical need in advanced melanoma, we are especially excited about the upcoming Society for Immunotherapy of Cancer, or CITC, annual meeting next week. We will present the detailed data from our C14401 trial cohorts 2 and 4 for the first time to the medical community in a rapid oral presentation at 1233 p.m. Eastern on November 10th. Earlier today, CITC issued a press release to announce the titles for the annual meeting press program. Our C14401 abstract was one of only eight abstracts selected out of more than 1,400 total abstracts to be part of the press conference. Following the presentation on November 10th, we will host an investor webcast and conference call with key opinion leaders, which will be accessible on our website. We look forward to having a high level of visibility at the meeting and encourage everybody on the call today to attend CITC and or participate in our investor event. In addition to the Lifolucel and melanoma, a growing TIL therapy pipeline has the potential to create significant value for cancer patients as well as our shareholders. We are treating patients in six Iovance clinical trials across multiple TIL treatment regimens and thalathemers, which Frederick will highlight on today's call. The strength of talent within Iovance also reflects tremendous enthusiasm for our TIL therapies and our global leadership within the field. We currently have more than 450 employees with deep expertise and successful track records in oncology, cell and gene therapy development and commercialization. I look forward to addressing your questions later during this call and will now ask Igor to address manufacturing updates.
spk19: Thank you, Fred. i-Events continues to prepare our manufacturing network to address patient needs and meet demand at launch. We continue to achieve operational excellence with a consistent till manufacturing success rate of more than 90% in more than 500 patients treated with IFN's TIL therapy to date. The success rate has been consistent across TIL manufacturers at our internal facility, the IFN Cell Therapy Center, or ICDC, and our contract manufacturing partners. We are currently supplying clinical studies from ICDC, our custom-designed 136,000 square foot internal manufacturing facility at Philadelphia Navy Yard. Consistent with our overall manufacturing success rate, the success rate is more than 90% for till manufacturers at ICTC. The ICTC is operating flex suites for clinical manufacturing and core suites for BLA readiness activities. Manufacturing is critical for any commercial launch, particularly for autologous cell therapies, so our top priority is to prepare for commercial supply to meet patient needs. In addition, we are on track in preparing the ICTC and our contract manufacturers facility for FDA pre-approval inspections. The ICTC is expected to supply most of the commercial TIL therapies upon approval, while contract manufacturers provide additional flexibility to optimally manage capacity and fully meet patient demand. As noted in our press release this afternoon, This includes a recently signed commercial manufacturing and supply agreement for two GMP manufacturing suites at our contract manufacturing partner. We're also planning future capacity needs as we look to establish TIL as the next paradigm shifting plot of cancer therapy. As we have outlined on prior calls, the ICDC facility, as currently built, has annual capacity to supply more than 2,000 patients. with flexibility to build out existing shell space to supply more than 5,000 patients. Longer term, we plan to supply more than 10,000 patients annually by adding new facilities, as well as streamlining and automating manufacturing processes. To supplement our proprietary manufacturing processes and know-how, and to further solidify our leadership in till therapy, we are also growing our intellectual property, or IT, 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. I would now like to hand the call to Jim Ziegler to highlight our commercial launch preparations. Jim?
spk02: Thank you, Igor. Our cross-functional teams are making steady progress with our launch priorities for Life Elusel. I will highlight the onboarding of our authorized treatment centers or ATCs, payer engagement, and commercial operational readiness activities. First, our teams continue to have structured interactions and work with the leading U.S. cancer centers to build their TIL service line capabilities. Our goal is to onboard and train at least 40 ATCs within the first 90 days of launch. For lipolucel administration, the ATCs can leverage existing workflows within prevalent cell therapy service lines, and we are facilitating the development of new workflows that are unique to TIL cell therapy. Our ATC onboarding program includes a training curriculum that ensures multidisciplinary teams at each center can administer the lipolucel treatment regimen upon approval. The timing and execution of key onboarding activities and training are aligned to our regulatory milestones to ensure just-in-time training and readiness. To support timely patient access and appropriate reimbursement for life elusive upon approval, our market access team continues to engage with national and regional payers. We are pleased that the Centers for Medicare and Medicaid Services, or CMS, continues to recognize novel cell therapies, including lifelucel, in the expanded MS-DRG018 for Medicare patients. Mapping lifelucel to DRG18 ensures that more appropriate payment is available at launch for hospitals treating Medicare patients. In closing, I want to acknowledge our core cross-functional teams in continuing to build a strong foundation for life elusive commercialization. We are well positioned to scale our efforts heading into launch. I will now pass the call to Friedrich Finckenstein, 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 technologies to address more cancer patients and new tumor types at various stages of disease. First, as Fred mentioned, we are looking forward to an oral presentation at SITC next week. The presentation will include detailed clinical data from 153 patients across cohorts two and four in the C14401 trial in advanced melanoma. This is the largest single clinical study ever conducted for cell therapy in post-ICI melanoma. As a reminder, the top line analysis of the trial was previously announced. and has been summarized on our prior investor calls and investor conferences. The pivotal cohort four met the pre-specified primary endpoint, which was objective response rate, or ORR, assessed by independent review committee, or IRC. The ORR endpoint has been the basis for FDA approval of many cancer agents in single-arm studies. In addition, We previously provided various results for secondary endpoints and supportive measures of durability for cohorts two and four that represent meaningful improvements over available care for our clinical trial population. As we've shared previously, FDA has given us positive feedback on the clinical data for cohorts four and two, and that cohort two may be supportive of approval. The cohort two safety data and the efficacy data are part of the BLA submission and potentially the label for Lifilucel if approved. We are confident in the potential for approval in advanced melanoma on or after anti-PD-1 therapy where there are no FDA-approved treatment options. For patients and physicians, SITC will have our first medical meeting to present the C14401 Cohort 4 data and the pooled analysis of Cohorts 2 and 4 to the medical community. Feedback from key opinion leaders who have seen the comprehensive data across the full spectrum of patients in cohorts two and four with post-anti-PD-1 melanoma has been very enthusiastic. For the medical community at SITC, we will focus on a detailed pooled analysis of cohorts two and four. This approach is appropriate because patients in both cohorts two and four met the same primary eligibility criteria, had the same study assessments, and received the same treatment regimen and that was produced using the same Gen 2 cryopreserved till manufacturing process. Together, the two cohorts are representative of the real-world advanced melanoma patient population. The contents of the presentation are under embargo, but you can expect a level of detail in line with our prior cohort 2 presentations at prior medical meetings. We are confident that the SITC presentation will add to the positive top line results that we previously shared, as well as a comprehensive and relevant data set supportive of adoption of lifeluzole in advanced melanoma patients. To recap the progress with our pipeline, we continue to develop TIL in combination with pembrolizumab in checkpoint inhibitor naive patients with various tumor types to expand upon the initial opportunity for lifeluzole monotherapy after anti-PD-1 therapy. We are committed to starting a phase three study in frontline melanoma later this year, which is also designed to serve as a confirmatory study for a potential accelerated approval of our BLA submission for Lifilucel. We are also excited about initiating the first clinical trial of our first genetically modified PD-1 inactivated chill therapy candidate, IOV4001. We are making great progress in the IOVGM1-201 first in human study to assess safety and potential for increased potency from the genetic modification in IOV4001. During the third quarter, we treated the first patient with IOV4001 and continue to recruit patients with previously treated advanced melanoma or non-small cell lung cancer. Preclinical data supporting the rationale for IOV4001 and trial and progress updates have been presented at several medical meetings and are available on our corporate website. We plan to share a trial and progress poster on GM-1201 at SITC to further educate the medical community about IOB-4001 as a potential option for their patients. We also continue to prioritize our non-small cell lung cancer pipeline at IOVAN. We have multiple shots on goal with a total of six cohorts across three IOVAN studies now enrolling patients at various stages of disease and using multiple treatment regimens. In cervical cancer, we have expanded our ongoing C14504 study to enroll additional cohort two patients. CORE2 is intended to be pivotal to support regulatory submissions for the treatment of cervical cancer after chemotherapy and immune checkpoint inhibitor therapy. Looking toward next-generation TIL therapy approaches, we have a robust research pipeline advancing towards the clinic. Following the progress of IOV4001 into the clinic, additional research and preclinical studies focused on optimizing TIL therapy consists of several targets for genetic modification using the gene editing talent technology, including double genetic knockout programs. We are also exploring approaches to increase till potency using CD39-69 double negative till and gene knock-in targets that incorporate other enhancements, such as tethered cytokines. IND enabling studies also continue for our novel interleukin-2 analog, IOV3001. I am available during the question and answer session. For now, I will hand the call over to Jean-Marc to discuss our third quarter and year-to-date 2022 financial results.
spk00: Thank you, Fred.
spk01: My comments will reflect the high-level financial results of our third quarter and year-to-date 2022. More details can be found in this afternoon's press release as well as in our ICC filings. I will begin with an overview of our cash position. As of September 30, 2022, IRAMS held $366.6 million in cash, cash equivalents, investments, and restricted cash, compared to $602.1 million on December 31, 2021. As a late-stage oncology company approaching potential commercialization, we continue to make prudent investments in commercial launch preparation, internal manufacturing and pipeline expansion. Moving to the income statement, our net loss for the third quarter under September 30, 2022 was $99.6 million or 63 cents per shares. This compared to net loss of $86.1 million or 55 cents per shares for the third quarter under September 30, 2021. Net loss for the nine months ended September 30, 2022 was $290.6 million or $1.85 per share compared to net loss of $242.9 million or $1.60 per share for the first nine months of 2021. Research and development expenses were $72.5 million for the third quarter ended September 30, 2022 An increase of $7.1 million compared to $65.4 million for the same period ended September 30, 2021. Research and development expenses were $214.2 million for the nine months ended September 30, 2022. An increase of $30.8 million compared to $183.4 million for the same period ended September 30, 2021. The increase in research and development expenses over the prior three and nine-month period was primarily attributable to the growth of the internal research and development team, including stock-based compensation expense, to support our ongoing and planned pipeline activities, as well as increased facility-related and internal research programs. This higher cost were partially upset by lower clinical and manufacturing costs in the first nine months of 2022, driven by completion of enrollment in pivotal clinical trials. General and administrative expenses were $27.9 million for the third quarter and the September 30, 2023 an increase of $7 million compared to $20.9 million for the same period ended September 30, 2021. General and administrative expenses were $77.6 million for the nine months ended September 30, 2022, an increase of $17.8 million compared to $59.8 million for the same period ended September 30, 2021. The increase in general and administrative expenses compared to the prior three and nine-month periods were primarily attributable to the growth of the internal general and administrative and commercial teams, including stock-based compensation expense, as well as costs associated with the build-out of the new corporate headquarters and pre-commercialization activities. As of September 30, 2022, approximately 157.8 million common shares outstanding. With a cash position that continues to support our present investments in commercial launch preparations, internal manufacturing, and pipeline expansion, we are well positioned to execute our operating plan into commercial launch and beyond. I will now hand the call back to the operator to kick off the Q&A session.
spk21: Thank you. As a reminder, ladies and gentlemen, to ask a question, you will need to press star 11 on your telephone. Once again, to ask a question, please press star 11. One moment, please. Our first question comes from the line of Michael Yee with Jefferies.
spk10: Hi, good afternoon. This is Jenna for Michael. Thanks for taking our questions. Two questions from us. One, what incremental data do you expect to present at CT? Would it be additional follow-up, and would you stratify between cohort two and four? Second question, what are you discussing with the FDA on pivotal for lung cancer? Any feedback you are able to share with us, whether the focus is still on ORR, and when can we hear more about this? Thank you.
spk20: Yeah, thanks. The data at CINCI will include detailed data on full cohorts two and four. There will be some individual cohorts two and four data as part of that that you can look at as part of the presentation. You mentioned stratification. There's not going to be any stratification by cohorts. The cohorts are pulled together and are analyzed in a data set and then separately in some cases to highlight some of these differences and similarities in data. Regarding the FDA and non-small cell lung, we haven't provided any updates on that yet and hopefully can do that in the near future.
spk10: Got it. Thank you. Thank you.
spk21: And our next question comes from the line of Tyler Van Buren with Cowan.
spk17: Hey, guys. Thanks very much for the updates. Just a follow-up on the CISI presentation. correlation between duration of response and prior PD-1 treatment be shown very clearly with the cohort for patients in the presentation? And can we expect a patient-level detail by a swim lane plot?
spk20: Yes, Tyler, you'll see patient-level detail on swim lane plots. The correlations and there'll be an analysis of everything that we could include in the presentation. Remember that we've We also want to stress the importance of LEH levels in patients, as well as tumor burden, disease burden across patients, too. And we stress that in our recent disclosures on this topic, too. So, you'll see some of that in the presentation as well.
spk17: Great. Thank you.
spk21: Thank you. And our next question comes from the line of Colleen QC with RW Bayer.
spk09: Hi, good afternoon. Thanks for taking our questions. Could you comment, what items are still outstanding to completing the rolling VLA? And do you have any sense if the FDA has already started reviewing some of the data that you've already submitted?
spk20: Yeah, Colleen, they've been very responsive, so it's possible they're reviewing the data, but they don't really provide that sort of update during the rolling VLA submission. We haven't disclosed in detail exactly where we are in the rolling VLA and what we've submitted and what we haven't submitted. But I can tell you that we've made substantial progress on this, and we're still on our timeline to complete it before the quarter.
spk09: Great. That's helpful. Thank you. And I understand that ICTC, as built today, has capacity for about 2,000 patients. What do you expect the capacity to be at launch, and kind of what drove the decision to sign the new agreements with the contract manufacturers?
spk20: Igor, would you like to take that one?
spk19: Happy to. Thanks for the question. So we're not disclosing the exact capacity. Our plan is to have the capacity satisfy demand, and we're not commenting on the exact expectations for demand, but the general plan is to have full capacity to meet patient demand at launch. Regarding our agreement with the contract manufacturer, we expect ICTC, our internal facility, to meet most of the commercial demand And we are intending to use contract manufacturing capacity to better manage demand and to provide additional flexibility in our capacity utilization. That's the purpose of signing that agreement for commercial manufacturing at the CMO.
spk09: Great. Thank you. And then one follow-up, if I can. Just as you've done more work with the top 40 centers ahead of launch, do you have a better sense if you expect a bolus of patients at launch?
spk02: Hi, Colleen. It's Jim Ziegler here. Yes, given the high unmet need and the lack of available treatments, we're expecting a bit of a bolus. We haven't quantified that, but the goal from a commercialization standpoint is to make sure that we can support those patients.
spk09: Great. Thanks for taking your questions.
spk21: Thank you. And our next question comes from the line of Mark Breedenbach with Oppenheimer.
spk03: Hey, guys, thanks for taking the questions. First of all, since you must be getting close to initiating the potentially confirmatory phase 3 study in frontline melanoma, can you give us a little more information about the trial protocol in terms of size and endpoints and maybe what timeframe the FDA would want you to complete that by to support flu approval? And then the second question is just how soon we could see IOV3001 enter the clinic, and how would that most likely enter the clinic? Would it be kind of layered onto an existing trial, like the basket study, or would it need its own separate protocol? Thanks for taking the questions.
spk20: Yeah, thanks. So, on the phase three study, we've, as we noted in our press release, we're still on track to begin that by the end of the year. We haven't shared details of that study design yet, but that's something that we hope to do in the near future. And that will include endpoints and more details about how we do that study. And it will be incorporating FDA feedback as well, of course. The confirmatory nature of the study will also be included in some of that discussion. So stay tuned, and we'll have some more. The end of that timeframe, too, all I can say at this point is that we anticipate the study will be well underway in time. for VLA to support the accelerated VLA approval. So we think we're going to be fine there. For 3001, we haven't really talked a lot about the clinical design yet publicly. Don't necessarily assume it's going to be part of a basket study. It might get its own study. But the idea, of course, is to swap out all those we can and look at 3001 as a potential agent that can support telegraph and expansion. So we're going to have, in 2023, you should hear a lot more about 3001 because it'll start to start to progress towards the clinic at a pace that you guys will, I think, will appreciate once we talk more about it.
spk21: Okay. Thanks so much. Thank you. And our next question comes from the line of Madhu Kumar with Goldman Sachs.
spk06: Good afternoon. This is Omari on Madhu. So, we have two questions. what is the non-small cell lung cancer population should we be considering for a registrational population for lactamucil? And then second, how should we think about PD-1 inactivated pills and melanoma in non-small cell versus non-inactivated pills?
spk20: The lung, it depends on, sorry, did I, did you catch that? I might've gotten cut off there. Sorry. Can you guys hear me? Operator, can you hear me okay?
spk21: Yes, sir.
spk20: Loud and clear. I think I got cut off there, so I'll start over on Mari's question a little bit. So the non-small cell lung population, you can look in our deck and see the populations in our corporate deck. But if you think about the post-PD-1 population, you're talking many, many thousands of patients a year in the United States who are failing checkpoint that could potentially be accessible with the TIL therapy. And that's our target population for at least some of our studies. And we're also working in the front line as well in combination with the non-small cell For the PD-1 knockout product, the way you should think about that is think about an internal knockout of the PD-1, the gene PDCD1 that codes for PD-1, such that that cell can't really be inhibited by PD-L1 on the tumor side. So it functions in many ways like having an antibody permanently attached to the cell or embedded in the cells. We think it could potentially be superior in terms of how it penetrates into the tumor and how it works. We have some data at ACR this year, a few months ago, that we put at ACR. It's on our website in a poster. It compares P1 knockout pills to non-knockout pills, as well as to non-knockout pills in combination with a P1 antibody in a mouse model, and the superiority of the knockout there as well. So take a look at that, and you'll see how we're thinking about it. Again, that's active in the clinic right now. We hope to ask a lot of people.
spk21: All right. Thank you. Thank you. And our next question comes from the line of Ben Burnett.
spk15: Hi, good afternoon. This is actually Carolina Ibanez for Ben Burnett. Thank you for taking our question. Will you show any analysis of the CIPSE update highlighting the effects of field therapy in relation to how long it's been since a patient has finished IO? If I recall well, there was an early signal that Lifilacil looked better in patients who recently came off IO.
spk20: Madan, do you want to answer that one?
spk18: Yeah, absolutely. Thank you for the question. It's a very valid question. So the data, as I said, is under embargo, and I think what you may be also referring to is the differential effect of Lifilacil in patients who have primary refractory When we had published the data in JCO in May of 21, numerically, the patients who had primary refractory had a slightly higher ORR compared to patients with acquired resistance. That does not necessarily translate into a statistically superior outcome for these patients. So I think what you'll be able to see at CITC is as long as the patient is responding, they go on to really benefit in the long term. So again, can't say more to the data as it's under embargo at this time.
spk15: Okay, understood. Thank you.
spk21: Thank you. And our next question comes from the line of James Shin with Wells Fargo.
spk05: Hey guys, can you hear me?
spk21: Yes, go ahead.
spk05: Fantastic. When life elusive BLA is completed, will you issue a press release? And then one for Igor. For the 2,000 plus patient capacity that's at the ITC, ICTC currently, Can you say how much of that is fully automated and free of human interaction? And is this continuous at this point?
spk20: Yeah, so I'll take the first one. Igor can get the second one. Yes, I think we will likely ensure press release, very likely ensure press release when the rolling BLA is completed. Igor?
spk19: James, thanks for the question. So our current 22-day Gen 2 manufacturing process is still largely manual and automation and closing the process is something that we're working on to get to the next level of capacity. We expect that in order to reach 5,000 patients per year, we can build out the existing shell at ICDC and then to get to 10,000 patients per year, we're looking at new facilities potentially and automating and further streamlining the process that will be part of that effort. Appreciate the call.
spk21: Thanks, guys. Thank you. And our next question comes from the line of Eula Liveschitz with Chardon.
spk08: Hi. This is Chloe from Eula. Thanks for taking the question. So we want to address an update from td.gov in your book on cancer and the next cancer program where you're activating sites. We're wondering if you could provide some color and additional progress in those phase IIs and the cadence of enrollment and data that's been in effect over the next few months. And a short follow-up on the PD-1 inactivated SIL program. So, you previously showed a mean knockout efficiency of about 60% in your development in Magimetric 1. Do you think that's enough, and what could you do more to increase that number? Thank you for taking the question.
spk20: Yeah, let me see if I can understand the first question. You were asking about updates to the head and neck trials on clinicaltrials.gov? It was pretty hard to hear you there.
spk08: Oh, sorry. Yeah, in both the lung cancer and the head and neck, if you could speak to additional progress there and the cadence of enrollment and use flow that we can expect.
spk20: I think, Frederick, you might have to help me out here, but I think you may be referring to changes in the COMP2A2 study, maybe for total enrollment. Frederick, can you answer that question or help with that?
spk16: Yes, I also have problems acoustically hearing the question, but so we do have, if this is a question about the head and neck cancer trial C145-03, ct.gov currently for that trial shows that that trial is completed. And we are currently in the process of summarizing the data. In the COM-202 trial, we have recently made updates to the cohort sizes, but we haven't shared any additional details around the progress in enrollment or speed of enrollment on any of those specific cohorts. Does that answer your question?
spk08: Yes, it does. Then I had a quick follow-up for the PD-1 inactivated program. Did you hear that question?
spk20: I heard that part. Okay. So you asked whether 50% is adequate. We report values in that range. We can do a little bit better than that sometimes, but we think that's adequate to treat patients. Remember, we're giving patients many billion cells, so 50% of that is still quite a large number, usually in the billions. So we're giving patients a product that contains both knockout cells and cells that are are still have intact PCC1 genes. So that's basically where the technology is these days for knockout. If you look in the literature, some of the early work that was done in knockout percentages, for example, some of the early P1 knockout studies like coming out of University of Pennsylvania were only 20%. So we're comfortable with that amount. We think that's gonna be useful in clinic.
spk08: Okay, thank you.
spk21: Thank you. And our next question comes from the line of Kelsey Goodwin with Guggenheim.
spk07: Hey, thank you so much for taking my question. I just had two quick ones, I think. First, now that the BLA submission is nearing completion, I guess can you provide any additional color on ex-U.S. pursuers? I think you've said that because your facility is on the east coast of the U.S., you could possibly produce some product there for an EU launch, but maybe just a little more color. And then secondly, bigger picture question, I guess, what steps can be taken to increase the referral rate of community physicians to the academic centers? Thanks so much.
spk20: Yeah, well, I'll take the first one, and then maybe Jim can talk about community referrals. So, yes, the manufacturing facility is located in a place, actually, both the manufacturing facility we own as well as our CMO partner are located on the East Coast and can reach all the way into Eastern Europe, as well as, That's the United States and beyond. We do have an ex-U.S. strategy. We haven't talked about that much publicly because we've been focused on the U.S. FDA, but we have ongoing collaborations, and we're active in places ranging from all over Europe to Canada to Australia and beyond, and those are all countries that we would be interested in in the future for melanoma launches in particular, and then for non-small cell lung and other medications, we're looking well beyond that as well. Do you want to talk about the community referral?
spk02: Thanks, Brad and Kelsey. Thanks for the question. Yes, as you know, about sixty percent of our patients are dispersed in the community and currently the referral patterns are not as strong as we would like. So we are using data driven approaches to identify the patients in the community practices. We'll have our sales team working with the top community practices, doing your education and outreach initiatives. And then we'll also augment all of our efforts with non-personal promotions to expand our region frequency.
spk07: Okay, great. Thank you so much.
spk02: Thanks.
spk21: Thank you. Our next question comes from the line of Astika Gunawardin with Truist.
spk04: Hello. This is Anj Kaner on for Astika. A few questions here. You guys said that you'd be able to dose about 2,000 patients at launch. Just wondering where you would be getting your contract manufacturers and also potentially where those centers administering high-dose ICU would be if you got more of them online. And then secondly, in terms of IOB-4001, you mentioned the one-patient dose already, and we're just wondering how enrollment was progressing in that trial and whether back to initial look at the data.
spk20: You know, Igor, would you like to take the first part of the question? Maybe Jim could talk about HIDOSYL2 and Frederick could cover the enrollment for 4001.
spk14: Yes.
spk19: Yes, happy to. Thank you for the question. So, as I mentioned earlier on the call, the ICTC capacity of our internal facility as billed is to supply more than 2,000 patients annually. We're not commenting exactly about the demand we expect in year one, but that's the capacity we have in the currently constructed facility. The plan is to meet most of the commercial demand out of ICTC, and then the role of the contract manufacturing partner is to provide additional flexibility to optimally manage capacity and ensure that we fully meet patient demand at launch.
spk02: Thanks, Igor. On IL-2, as you know, high-dose IL-2 use has decreased significantly over the years. In fact, we have data to identify each of the sites where they're currently using IL-2, and we know most of our target sites, while they have experience, the use is weighing rather significantly We have a very efficient training program to make sure that sites are trained on appropriate use for aisle 2 and side effect management. So I don't expect it to be a barrier for launch.
spk16: As we go to. Regarding the IOV-4001 trial, there was a question around how the study is progressing. That is working very nicely. Just as a reminder, we had previously shared the design of the study. The study does include a safety lead-in with sequential dosing of patients, and we are able to optimize that avoiding any sort of delays between the patients. So that's going really nicely, and there's a lot of interest in this study. Thanks for the question.
spk21: Thank you. And our next question comes from .
spk13: Hi, this is Jerry Gong-Gong from Mayor Goldstein. Thanks for taking our questions. I did lose connection for a short portion, so I apologize if any of my questions were already asked. So for cohort two of the cervical cancer trial, can you share if you have settled on a target enrollment number? And on cash burn, what is your current thinking on how it may look like through the regulatory approval process and then through launch? And lastly, on pricing, is it fair to think about perhaps pricing in line with current RTE products? Thank you.
spk20: Sure. We haven't really – we haven't disclosed the details of the cervical maximum enrollment just yet, but we'll have some more details on that hopefully soon. John-Marc, can you talk about the cash, and maybe Jim can comment on pricing?
spk00: Sure. Sorry, pushing the unmute button. Yes, about the cash, $366 million at the end of this quarter. I mean, we are confirming that we have enough runway to 2024, so definitely a strong position as a late-stage company with de-risked lead programs. And also, you know, our internal manufacturing now are up and running and ready to supply the demand from the commercialization. So we are not giving any specific guidance around the 2024, you know, cash burn. But again, we do have enough cash into 2024 at this stage.
spk02: And this is Jim. On pricing, we haven't disclosed pricing, but I think it is fair to think about the CAR T pricing as a good analog and good range.
spk13: Gotcha. Thanks for the color.
spk21: Thank you. And it comes from the line of Alex Spulo with Barclays.
spk11: Hey, good afternoon. Thanks for taking my question. This is Alex on for Peter Lawson. I just had a quick one on the lung cancer study and was wondering if you could comment a little bit on how enrollment has been going after you've made a few protocol amendments a couple months ago. Any color around that would be helpful. Thank you.
spk20: Yeah, Frederick, I think he's talking about study. Could you comment on that?
spk16: Yeah, sure, happy to, and thanks for the question. Yes, so you rightly referred to some of the adjustments that we've made lately. We're actually really happy about how we were able to activate sites and how these sites are enrolling to this trial. We haven't shared any exact and concrete numbers, but we're really, really pleased with the progress on that study. What we can share is that we have more than 40 active sites at this point, which is a really healthy number for a study design like this.
spk21: Thank you. I'll now turn the call back over to Interim President and CEO, Fred Vogt, for any closing remarks.
spk20: Thank you again for joining the I-Advanced Biotherapeutics Third Quarter Year-to-Date 2022 Financial Results Conference Call. We're heading into an exciting end to the year at I-Advance, including the CISI annual meeting next week, as well as our upcoming expected completion of the VLA submission. As a preview, we expect that on November 7th, the CISI abstract for our oral presentation will be released, and we'll include a detailed look at the pooled data from cohorts two and four of our C14401 trial. On November 8th, there will be a press program for members of the media covering the data in the abstract. Finally, on November 10th, our oral presentation will be presented with an update, including additional files on the pooled individual cohorts. I'm 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 a global leader in health therapy. I would also like to thank our sharing panelists. Please feel free to reach out to our investor relations team for any follow-up. Thank you.
spk21: Ladies and gentlemen, this concludes today's conference call. And you may now disconnect.
Disclaimer