Iovance Biotherapeutics, Inc. (IOVA) Q3 2022 Earnings Report, Transcript and Summary

Welcome to the Iovance Biotherapeutics Third Quarter and Year to-date 2022 Financial Results and Corporate Update Conference Call. My name is Andrew, and I will be your operator for today’s call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. [Operator Instructions] Please note that this conference is being recorded. I will now turn the call over to Sara Pellegrino, Senior Vice President, Investor and Public Relations and Corporate Communications at Iovance. Sara, you may begin.

Thank you, operator. Good afternoon and thank you for joining us. Speaking on today’s call, we have Dr. Fred Vogt, our Interim President and Chief Executive Officer; Dr. Igor Bilinsky, our Chief Operating Officer; Jim Ziegler, our Executive Vice President, Commercial; Dr. Friedrich Finckenstein, Chief Medical Officer; and Jean-Marc Bellemin, our Chief Financial Officer. Dr. Madan Jagasia, our Executive Vice President, Medical Affairs; and Dr. Raj Puri, our Executive Vice President, Regulatory Strategy and Translational Medicine are available for 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 plans, pre-commercial activities, clinical trials and results, regulatory interaction, plans and strategies, research and preclinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interaction, 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 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.

Thank you, Sarah, and good afternoon, everyone. I’m pleased to highlight some great momentum at Iovance. We are getting ready to complete our biologics license application or BLA submission for our lead cell therapies like lifileucel and advanced melanoma while preparing for commercialization developing our robust immune oncology pipeline. I will begin today’s introduction with a brief status update on the rolling BLA for lifileucel, which we initiated in August. This remains our number one priority on behalf of our patients with advanced melanoma who are eager to see lifileucel approved as soon as possible. One 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 BLA submission this quarter. As a reminder, we previously received positive feedback from the FDA on the potency assays matrix. We also had a successful pre BLA meeting in July where the FDA provided favorable feedback, clinical efficacy data from Cohorts 2 and 4 of our C-144-01 clinical trial, including duration of follow-up and agreed to the clinical and safety data set was sufficient for a BLA review. The FDA remains engaged in supportive as we progress the BLA submission process and we look forward to continuing this level of collaboration. Lifileucel approved may address significant unmet will need from 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 lifileucel as an earlier treatment for melanoma. We remain on track to begin a Phase 3 trial of lifileucel 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 lifileucel 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 needed advanced melanoma, who are especially excited about the upcoming Society for Immunotherapy of Cancer or SITC Annual Meeting next week. We will present the detailed data from our C-144-01trial Cohorts 2 and 4 for the first time in the medical community and a rapid oral presentation at 12:33 p. m. Eastern on November 10. Earlier today, SITC issued a press release to announce the titles for the Annual Meeting Press program. Our C-144-01 abstract is one of only eight abstracts, selected out of more than 1400 total abstracts to be part of the press conference. Following the presentation of November 10, 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 SITC and or participate in our investor event. Additional lifileucel on melanoma, our growing cell therapy pipeline has a 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 cell tumors, which Cedric 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 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 I will let Igor to address manufacturing updates.

Thank you, Fred. Iovance continues to prepare our manufacturing network to address patient needs and need demand at launch. We continue to achieve operational excellence with a consistent TIL manufacturing success rate of more than 90% in more than 500 patients treated with Iovance TIL therapy to-date. This success rate has been consistent across TIL manufactured at our internal facility, the Iovance Cell Therapy Center or iCTC and our contract manufacturing partners. We are currently supplying clinical studies from iCTC, our custom designed one 136,000 square foot internal manufacturing facility at Philadelphia and Navy Yard. Consistent with our overall manufacturing success rate, the success rate is more than 90% for TIL manufactured 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 preapproval inspections. The iCTC is expected to supply most of the commercial TIL therapies upon approval, while contract manufacturers provide additional flexibility to ultimately 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 are also planning future capacity needs as we look to establish TIL as the next paradigm shifting class of cancer therapy. As we have outlined on prior calls, the iCTC facility has currently built has annual capacity to supply more than 2000 patients with flexibility to build out existing shelf space to supply more than 5000 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 support our proprietary manufacturing processes and knowhow and to further solidify our leadership in TIL 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 expect to provide exclusivity into [2038] (Ph). I would now like to hand the call to Jim Ziegler to highlight our commercial launch preparations. Jim.

Thank you, Igor. Our cross functional teams are making steady progress with our launch priorities for lifileucel. Today, 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 lifileucel 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 lifileucel 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 lifileucel 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 lifileucel in the expanded MS DRG 01A for Medicare patients. Mapping lifileucel 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 and continuing to build a strong foundation for lifileucel 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.

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 2 and 4 in the C-144-01 trial in advanced melanoma. This is the largest single clinical study ever conducted for a 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 4 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 Cohort 2 and 4 that represent meaningful improvements over available care for our clinical trial population. As we have shared previously, FDA has given us positive feedback on the clinical data for Cohorts 4 and 2 and that Cohort 2 may be supportive of approval. The Cohort 2 safety data and the efficacy data are part of the BLA submission and potentially the label for lifileucel, 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 our first medical meeting to present the C-144-01 Cohort 4 data and the pooled analysis of Cohort 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 2 and 4 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 2 and 4. This approach is appropriate because patients in both Cohorts 2 and 4 met the same primary eligibility criteria had the same study assessments and received the same treatment regimen and lifileucel that was produced using the same Gen 2 cryopreserved TIL manufacturing process. Together, the 2 Cohorts are representative of the real world advanced melanoma patient population. The contents of the presentation are on the 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 lifileucel in advanced melanoma patients. To recap the progress with our pipeline, we continue to develop TIL in combination with pembrolizumab in checkpoint inhibitor naïve patients with various tumor types to expand upon the initial opportunity for lifileucel monotherapy after anti-PD-1 therapy. We are committed to starting a Phase 3 study in frontline melanoma later this year, which is also designed to serve as confirmatory study for a potential accelerated approval of our BLA submission for lifileucel. We are also excited about initiating the first clinical trial of our first genetically modified PD-1 inactivated TIL therapy candidate IOV-4001. We are making great progress in the IOV-GM1-201 first-in-human study to assess safety and potential for increased potency from the genetic modification in IOV-4001. During the third quarter, we treated the first patients with IOV-4001 and continue to recruit patients with previously treated advanced melanoma or non-small cell lung cancer. Preclinical data supporting the rationale for IOV-4001 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 GM1-201 at SITC to further educate the medical community about IOV-4001 as a potential option for that patient. We also continue to prioritize our non-small cell lung cancer pipeline at Iovance. We have multiple shots on goal with a total of six Cohorts across three Iovance studies now enrolling patients at various stages of disease and using multiple treatment regimens. In cervical cancer, we have expanded our ongoing C-145-04 study to enroll additional Cohort 2 patients. Cohort 2 is intended to be pivotal to support regulatory submissions for the treatment of cervical cancer after chemotherapy and immune checkpoint inhibitor therapy. Looking towards next generation TIL therapy approaches, we have a robust research pipeline advancing towards the clinic. Following the progress of IOV-4001 into the clinic, additional research and preclinical studies focused on optimizing TIL therapy consist of several targets for genetic modification using the gene editing talent technology, including double genetic knockout programs. We are also exploring approaches to increase TIL potency using CD39/69 double negative TIL and gene knockout targets that incorporate other enhancements such as Teva cytokine. IND enabling studies also continue for our novel interleukin-2 analog IOV-3001. I’m 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.

Thank you, Fred. My comments will reflect the higher level financial results of our third quarter and year to-date 2022. More details can be found in the subsequent press release as well as in our SEC filings. And we are beginning with an overview of our cash position. As of September 30, 2022, Iovance held $366.6 million in cash, cash equivalents investments and restricted cash compared to $602.1 million on December 31, 2022. As a late stage oncology company approaching potential commercialization, we continue to make prudent investments in commercial loan preparation, internal manufacturing and pipeline expansion. Moving to the income statement, net loss for the third quarter ended September 30, 2022 was $99.6 million or $0.66 per share. This compared to a net loss of $86.1 million or $0.55 per share for the third quarter ended September 30, 2021. Net loss for the nine-months ended September 30, 2022 was $290.6 million or $1.85 per share compared to a 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 first quarter ended September 30, 2022, an increase of $7.1 million dollars 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-months 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 program costs. These higher costs were partially offset 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 ended September 30, 2022, 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 internal general and administrative and commercial teams, including stock based compensation expense as well as cost associated with the build out of the new corporate headquarter and pre-commercialization activities. As of September 30, 2022, there were approximately 157.8 million common shares outstanding. With a cash position that continues to support our prudent 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.

Thank you. [Operator Instructions] Our first question comes from the line of Michael Yee with Jefferies.

Hi. Good afternoon. This is [Jenna] on for Michael. Thanks for taking our questions. Two questions from us. One, what incremental data do you expect to present at 2Q, would it be additional follow-up and would you stratify between Cohort 2 and 4? Second question, what are we discussing with the FDA on pivotal for lung cancer? Any feedback you are able to share with us, whether the focus through ORR and when can we hear more about this? Thank you.

Yes, thanks. So, David Fisci will include detailed data on pulled Cohorts 2 and 4, there will be some individual Cohorts 2 and 4 data as part of that, that will be part of you that you can look at as part of the presentation. And then the stratification is not going to be stratification going forward. Cohorts are pulled together and are analyzing the data set and then separately in some cases to highlight some of these differences in 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 near future.

Got it. Thank you.

Thank you. Our next question comes from the line of Tyler Van Buren with Cowen.

Hey, guys. Thanks very much for the updates. Just a follow-up on the SITC presentation, will the correlation between duration response in prior PD-1 treatment, they have shown very clearly, with the Cohort 4 patients in the presentation? And can we expect patient level detail by a short lane plot?

Yes. Tyler, you will see his patient level detail on short lane plots. The correlations and there will be an analysis of everything that we could include in the presentation. Remember that, we also want to stress the importance of age levels in patients as well as tumor burden disease burden across patients too and stress, that is in our recent disclosures on this topic too. So you will see some of that in the presentation as well.

Great. Thank you.

Thank you. And our next question comes from the line of Colleen Kusy with R.W. Baird.

Hi, good afternoon. Thanks for taking our questions. Could you comment what items are still outstanding to completing the rolling BLA? And do you have any sense if the FDA has already started reviewing some of the data that you have already submitted?

Yes. Colleen, they have been very responsive, so it is possible that we are getting the data, but they don’t really provide that sort of update during the rolling billing submission. We haven’t disclosed the details exactly where we are in the rolling BLA and what we submitted, but hoping and what we have submitted. But I can tell you that we have made substantial progress on this and we are still on our timeline to complete it in the fourth quarter.

Great. That is helpful. Thank you. And I understand iCTC as built today has capacity for about 2000 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?

Igor, would you like to take that one?

Happy to, thanks for the question. So we are not disclosing the exact capacity would help one is to help the capacity satisfy demand. And we are not commenting on the exact expectations for demand, but 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 is the purpose of signing that agreement for commercial manufacturing and the CMO.

Great. Thank you. And then one follow-up if I can. Just as you have 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?

Hi, Colleen. It is Jim Ziegler here. Yes, given the high unmet need and the lack of available treatments 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.

Great. Thanks for taking our questions.

Thank you. And our next question comes from the line of Mark Breidenbach with Oppenheimer.

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 to support full approval? And then the second question is just how soon we could see IOV-3001enter 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 needed based on separate protocol? Thanks for taking the questions.

Yes, thanks. So on the Phase 3 study, as we noted in our press release, we are still on track to begin that by the end of the year. We haven’t shared details that is been designed yet, but that is something that we hope to do in the near future. And that will include end points and more details about how we are going to study and it will be incorporating NPA 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 will have some more. The impact time frame too, all I can say at this point is that we anticipate the study will be well underway in time for BLA to support the accelerated BLA approval. So we think that we are going to be fine there. For 3001, we haven’t really talked a lot about the - on that yet publicly. They don’t necessarily assume it is going to be part of a rapid study of - done study. But the idea of course is to swap out those who can’t look at 3001 natural agent dependent support [Indiscernible] and expansion. So we are going to have - in 2023, you should hear a lot more about 3001, because it will start to progress towards the clinic and a pace that we will - you guys will - I think we will appreciate once we talk more about it.

Okay. Thank so much.

Thank you. And our next question comes from the line of Madhu Kumar with Goldman Sachs.

This is [Omar] (Ph) on for Madhu, So we have two questions. First, what is the non small cell lung cancer population should be considering for registrational population for like muscle? And then second, how should we think about PD-one inactivated pills in melanoma and non small cell versus non-inactivated pills?

So not small cell lung population, you can look at our deck and see the populations corporate death. But if you think about the post PD-1 population, you are talking many, many thousand patients a year in the United States. We are filling checkpoint potentially be accessible with the TIL therapy and that is the target population. For at least some of our studies that we are also working in the frontline as well a combination of that. 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 PD-1 that codes for PD-1 such that that cell can’t really be inhibited by PD-L1 tumor side. So functions in many ways of having an antibody permanently attached the cell or embedded the cells. We think it could potentially be superior in terms of how penetrating the tumor and how it works. We had some data at AACR this year, a few months ago that we put at AACR on our website in the poster that compared to PD-1 knockout pills to non- knockout pills combination with the PD-1 antibody in the mouse model superiority to knock out there as well. So take a look at that and you will see how we are thinking about it. Again, that is into the clinic right now. I will go back to Las Vegas momentarily soon.

Okay. Thank you.

Thank you. And our next question comes from the line of Ben Burnett.

Hi good afternoon. This is actually [Carolina Vanessa on for Ben Burnett] (Ph). Thank you for taking our question. We do show any analysis of the safety update, highlighting the effects of TIL therapy in relation to long it is been since the patient has finished in IO. If I recall well, there was an earlier signal that we feel like also look better in patients who recently came off IO.

Madan, do you want to answer that one?

Yes, absolutely. Thank you for the question. It is a very valid question. So the data, as I said, is under [embargo] (Ph). And I think what you may be also referring to is the differential effect of lifileucel patients who have primary refractory when we had published the data in JCO in May of 2021, 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 will be able to see at this year as long as a patient is responding, they go on to really benefit in the long-term. So again, can’t say more on to the data as it is under embargo at this time.

Okay, understood. Thank you.

Thank you. And our next question comes from the line of James Gin with Wells Fargo.

Fantastic. When, like we said, BLA is completed, will you issue a press release? And then one for Igor, for the 2000 patient capacity that is SITC currently. Can you say how much of that is fully automated and free of human interaction and is this continuous at this point?

Yes. So, I will take the first one and Igor can hit the second one. Yes, I think we will likely issue a press release, very likely issue a press release on BLA. Igor.

James, thanks for the question. So our current 22-day Gen 2 manufacturing process is still largely manual and automation in closing the process is something that we are working on to get to the next level of capacity. We expect that in order to reach 5000 patients per year, we can build existing shell at iCTC and then to get to 10,000 patients per year, we are looking at new facilities potentially and automating and further streamlining the process that will be part of that effort.

I appreciate the color. Thanks guys.

Thank you. And our next question comes from the line of Geulah Livshits with Chardan.

Hi. This is [indiscernible] Thanks for taking the question. So, we want to bring an update on data in your BOC1 cancer and head and neck cancer program where you are activated by. We want ready to just provide some color on additional progress in those Phase 2 indicate in sort of enrollment in data that is being back over the next few months? And a short follow-up on the PD-1 inactivated cell program. So it you previously showed a mean knockout efficiency of about 50% in the - and manufacturing one. Do you think that is an outbound opportunity to increase that number? Thanks for taking the questions.

Yes. Let me see if I can understand the first question. You were asking about updates to the head and neck trials on the clinical trial back up, because it was pretty hard to hear you there.

Oh, sorry, yes, in both the lung cancer and the head and neck, you could speak to additional progress there and the cadence of enrollment in use flow that we can expect.

I think, Frederic, you might have to help me out here. But I think you may be referring to changes in the COM-202 study, maybe for total enrollment. Fred, can you answer that question or help with that?

Yes. So I also have problems acoustically hearing the question. So we do have - if this is a question about the head and neck cancer trials, C-145-03, ct.gov currently for that trial, so 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 and enrollment or speed of enrollment on any of those specific cohorts. Does that answer your question?

Yes, it does. Then I have a quick follow-up for the PD-1 activated.

I heard that question. I heard that before. U.S. was a 50% of that, but we report values in that range. We can do a little bit better than that sometimes, but we think that is adequate to treat patients. Remember, we are giving patients many billion cells and 50% of that is still quite a large number, usually the billions. And so we are giving patients some products that contain both knockout cells and cells that are still having tax - PD-1 gene. So that is basically where the technology is these days for knockout. If you look at the literature, it is some of the early work the knockout percentages, for example. So the early Phase 1 knockout studies like coming out of the University of Pennsylvania were like 20%. So we are comfortable with that amount. We think that is going to be useful in the clinic.

Okay, thank you.

Thank you. And our next question comes from the line of Kelsey Goodwin with Guggenheim.

I just have two forms, I think. First, now that the BLA submission is nearing completion, I guess can you provide any additional color on ex-U.S. procedures? I think, you have said that because your facilities on the East Coast of the U.S. that could possibly produce some products 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.

Yes, I will take the first one, and then maybe Jim can talk about community referrals. So, yes, manufacturing facility is located in a place actually both lots of the manufacturing facility we own as well as our CMO partner located on these East Coasts. It can reach all the way into Eastern Europe as well as that is the United States and beyond. We do have an ex-U.S. strategy. We haven’t talked about that much publicly, because we have been focused on the U.S. FDA. But we have ongoing collaborations and we are active in places ranging from all over Europe to Canada to Australia and beyond. And those are all countries that we will be in the future for melanoma launches in particular and for non-small cell lung and other indications, we are looking beyond that as well. Jim, do you want to talk about the community referral.

Thanks, Fred and Kelsey, thanks for the question. Yes, as you know, about 60% 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 will have our sales team working with the top community practices going to your education and outreach initiatives. And then we will also augment all of our efforts with non-personal promotions to expand our region frequency.

Okay, great. Thank you so much.

Thank you. Our next question comes from the line of Asthika Goonewardene with Truist.

Hello. This is [Indiscernible] on for us. A few questions here. You guys said that you would be able to dose about 2000 patients at launch just wondering where you would be getting into contract manufacturers and also potentially where those centers are administering high dose access to would be if you got more of them online. And then secondly, in terms of IOV-4001, you have mentioned the one patient dose already, and we are just wondering how enrollment was progressing in that trial and back to the initial look at the data?

Igor, would you like to take the first part of that question, Maybe Jim could talk about high dose too and Friedrich to cover the enrollment for 4001.

Yes happy to. Thank you for the question. So as I mentioned earlier on the call, the ICTC capacity of our internal facility has built is to supply more than 2000 patients annually. We are not commenting exactly about the demand we expect in year one, but does 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 are fully meet patient demand at launch.

On IL-2, as, high dose IL-2, use has decreased significantly over the years. In fact, we have data to identify each of the sites where they are currently using IL-2. And we know most of our target sites, while they have experience, the uses of Wayne rather significantly. We have a very efficient training program to make sure that sites are trained on appropriate use for IL-2 and side effect management. So I don’t expect it to be a barrier for launch.

As regarding the IOV-4001 and one trial, there was a question around how this 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 is going really nicely. And there is a lot of interest in this study. Thanks for the question.

Thank you. And our next question comes from the line of Mara Goldstein with Mizuho.

This is [Jerry Gong] (Ph) on for Eric 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 a 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 RT products? Thank you.

Sure. We haven’t disclosed the details of cervical maximum enrollment just yet, but we will have some more details on that hopefully soon. Jean-Marc, can you talk about the cash and maybe Jim could comment on pricing.

Sure. Yes, about the cash flow $56 million at end of this quarter. I mean, we are confirming that we have in a runway to 2024. So definitely, a strong position as led stage company with de risk lead programs and also internal manufacturing now up and running and ready to supply the demand from the commercialization. So we are not giving any specific guidance around the 2024 cash burn. But again, we do have enough cash into 2024 at this stage.

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.

Got you. Thanks for the color.

Thank you. And our next question comes from the line of [Alex Spoolow] (Ph) with Barclays.

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 have made a few protocol amendments a couple months ago. Any color around that would be helpful. Thank you.

Yes, Frederic. I think if you talk about IOV-LUN-202 study. Could you comment on?

Yes, sure. Happy to and thanks for the question. Yes, so you rightly we will refer to some of the adjustments that we have made lately. We are actually really happy about how we were able to activate sites and how these sites are enrolling to the trial. We haven’t shared any exact and concrete numbers, but we are 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.

Thank you. I will now turn the call back over to Interim President and CEO, Fred Vogt for any closing remarks.

Thank you again for joining the Iovance Biotherapeutics third quarter year-to-date 2022 financial results conference call. We are heading into an exciting end-to-year with Iovance including the SITC Annual Meeting Next week as well as our upcoming expected completed BLA submission. As a preview, we expect that on November 7th, the SITC abstract for oral presentation will be released and we will include detailed look at the full data from Cohorts 2 and 4 of our C-144-01 trial. On November 8th, there will be a press program for members of the media covering the data and the abstract. Finally, on November 10, our oral presentation will be presented with an updated clinical additional follow-up on the four individual cohorts. I’m grateful for the patient, physicians and regulators as well as our employees and cross functional teams who have worked in close collaboration to advance our mission is a global leader in TIL therapy. I would also like to thank [indiscernible] please feel free to reach out to our Investor Relations team for any follow-up. Thank you.

Ladies and gentlemen, this concludes today’s conference call. Thank you and you may now disconnect.