Iovance Biotherapeutics Inc (IOVA) 2022 Q3 法說會逐字稿

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.

(Operator Instructions)

Please note that this conference is being recorded. I will now turn the call over to Sara Pellegrino, Senior Vice President, Investor 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; James 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 Management 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 3 and 9 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 interactions, plans and strategies, research and preclinical 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 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, Sara, and good afternoon, everyone. I am pleased to highlight some great momentum at Iovance. We're getting ready to complete our biologics license application, or BLA, submission for our lead TIL therapy, lifileucel, in advanced melanoma, while preparing for commercialization, developing a robust immuno-oncology pipeline.

I'll begin today's introduction with a brief status update on the rolling BLA for lifileucel which we initiated in August. This remains our #1 priority on behalf of our patients with advanced melanoma who are eager to lifileucel approved as soon as possible. Our own 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 post-SITC metrics. We also had a successful pre-BLA meeting in July, where the FDA provided favorable feedback on the clinical efficacy data from Cohorts 2 and 4 of our C-144-01 clinical trial, including duration of follow-up and agreed to clinical and safety data set that was sufficient for a BLA review.

The FDA remains engaged and supportive as we progress the BLA submission process, and we look forward to continuing this level of collaboration. Lifileucel, 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 lifileucel as an earlier treatment for melanoma. We remain on track to begin a Phase III trial of lifileucel in combination with pembrolizumab in frontline advanced melanoma in late 2022, which is also designed to serve as the 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 efforts 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 SITC, annual meeting next week.

We will present the detailed data from our C-144-01 trial Cohorts 2 and 4 for the first time in the medical community in 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 was one of only 8 abstracts selected out of more than 1,400 total abstracts to be part of the press conference.

Following the presentation on 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 of the meeting and encourage everybody on the call today to attend the SITC and/or participate in our investor event.

In addition to lifileucel on 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 6 Iovance's clinical trials across multiple TIL treatment regimens in solid tumors, which Friedrich will highlight on today's call.

The strength of TALEN within Iovance also reflect 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 record in oncology, cell and gene therapy development and commercialization. I look forward to addressing your questions later during this call. We'll now ask Igor to address manufacturing updates.

Thank you, Fred. Iovance continues to prepare our manufacturing network to address patient needs and meet 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 design 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 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 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 2 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 as currently built has annual capacity to supply more than 2,000 patients with flexibility to build out existing shelf 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 (technical difficulty) proprietary manufacturing processes and know-how and to further solidify our leadership in TIL therapy, we are also growing our intellectual property or IP. 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?

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-018 for Medicare patients.

Mapping lifileucel to DRG 18 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 in 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 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 prespecified 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 improvement 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 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 option.

For patients and physicians, SITC will hold 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 cryopreserve TIL manufacturing process.

Together, the 2 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 lifileucel 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 lifileucel monotherapy after anti-PD-1 therapy. We are committed to starting a Phase III 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 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 patient 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 in progress poster on GM1-201 at SITC to further educate the medical community about IOV-4001 as a potential option for the 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 6 cohorts across 3 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 in 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 consists of several targets for genetic modification using the gene-editing TALEN technology, including double genetic knock-out programs. We are also exploring approaches to increase TIL potency using CD39/69 double-negative TIL and gene knock-in targets that incorporate other enhancements such as cytokines.

IND-enabling studies also continue for our novel interleukin 2 analog IOV-3001. 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.

Thank you, Fred. 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 SEC filings. I will begin 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, 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 ended September 30, 2022, was $99.6 million or $0.63 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 9 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 9 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 9 months as of 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 year 3- and 9-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 plain 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 9 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 9 months ended September 30, '22, 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 year 3- and 9-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 headquarter and 3 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.

(Operator Instructions)

Our first question comes from the line of Michael Yee with Jefferies.

This is [Jana] on for Michael. Two questions from us. One what increments will we have to expect to present at SITC? Would it be additional follow-up? And would you stratify between Cohorts 2 and 4? 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 can we hear more about this?

Yes. Thanks. So SITC will include detailed data on full Cohorts 2 and 4. There will be some individual Cohorts 2 and 4 data as part of that -- that will be part of that you can look at as a part of the presentation. You mentioned stratification. There's not going to be any stratification like cohorts.

Cohorts are pulled together and our analyzing data set and then separately in occasion to highlight some of these differences and similarities as stated. Regarding the FDA in non-small lung, we haven't provided any updates on that yet, and hopefully, we can do that in the near future.

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

Just a follow-up on the SITC presentation. Will the correlation between duration of response and prior PD-1 treatment that we've shown very clearly with the Cohort 4 patients in the presentation? And can we expect a patient-level detail by swim-lane plot?

I guess, Tyler, you'll see patient-level detail on swim-lane plots. The correlations and there will be an analysis of everything that we could include in the presentation. Remember that we've -- we also want to stress the importance of age levels in patients as well as tumor burden, disease burden across patients, too -- stressed at our recent disclosures on this topic, too. So you'll see some of that in the presentation as well.

And our next question comes from the line of Colleen Kusy with RW Baird.

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've already submitted?

Yes, Colleen, they've been very responsive. So it's possible that we're going to get the data, but they don't really provide that sort of update during rolling-BLA submission. We haven't disclosed the detail of exactly where we are in the rolling BLA and what we submit and what we have submitted. But I can tell you though we've made substantial progress on this, and we're still on our time line to complete in the fourth quarter.

Great. That's helpful. 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?

Igor, would you like to take that one?

Happy to. Thanks for the question. So we're not disclosing the exact capacity because 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 provide additional flexibility in our capacity utilization. That's the purpose of signing that agreement for commercial manufacturing at the CMO.

Great. 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?

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.

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 III study in frontline melanoma. Can you give us a little more information about the trial protocol in terms of size and end points and maybe what time frame the FDA would want you to complete that by to support full approval?

And then the second question is just how soon we could see IOV-3001 enter the clinic? And how would that most likely enter the clinic? Would it be kind of layered on to an existing trial like the basket study? Or would it need its own separate protocol?

Yes, thanks. So on the Phase III study, we -- 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're financially -- will it be incorporating FDA feedback as well, of course.

The confirmatory nature of the study will also be included some of that discussion. So stay tuned and we'll have some more (inaudible) 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're going to be fine there.

For 3001, we haven't really talked a lot about the clinical design yet publically. We don't necessarily assume it's going to be part of basket study (inaudible) study. But the idea, of course, is to swap and look at 3001 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 will start to progress towards the clinic. The pace that you guys will -- I think we'll appreciate once we talk more about it.

Our next question comes from the line of Madhu Kumar with Goldman Sachs.

This is [Omar] on for Madhu. So we have 2 questions. First, what is the non-small cell lung cancer population should we be considering for a registrational population for lifileucel? And then second, how should we think about PD-1 in activated TILs in melanoma in non-small cell versus non-inactivated TILs?

It depends on -- sorry, did I -- did you catch that? I got cut off there. Sorry, can you guys hear me -- can -- operator, can you hear me okay?

Yes, sir. Loud and clear.

I think I got cut off there. So I'll start over on [Omar's] question with -- so non-small cell lung population, you can look at our deck and see the populations on corporate deck. But if you think about the post-PD1 population, you're talking many, many thousands of patients a year in the United States were failing checkpoint they could potentially be accessible with the TIL therapy, and that's our target population for at least some of our studies.

We're also working in the frontline as well in combination with (inaudible) for the PD-1 knock-out product, the way you should think about that is -- think about an internal knock-out of the PD-1, the gene PD-CD1 that goes for PD-1 such that, that cell can really be inhibited by PD-L1 on the tumor side.

So it functions in many ways. It's having an antibody permanently, attach the cell or embedded the cells, we think it could potentially be superior in terms of how penetrated the tumor and how it works. We have some data at ASCR this year. A few months ago that we put at ASCR website and a poster that compares the PD-1 knock-out TILs to non-knockout-TILs as well as non-small combination with the PD-1 antibody in the (inaudible) model knock-out as well. If you take a look at that, and you'll see how we're thinking about it. Again, that enters the clinic right now.

And our next question comes from the line of Ben Burnett (technical difficulty)

This is actually Carolina Ibanez-Ventoso for Ben Burnett. Would you show any analysis at the SITC update highlighting the effects of TIL therapy in relation to how long it's been sufficient -- has finished in IO? If I recall well, there was an early signal that lifileucel look better in patients who basically came off IO?

Madan, do you want to answer that one?

Yes, 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 lifileucel and 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 SITC is as long as the patient is responding, they go on to really benefit in the long term. So again, I can't say more to the data as it's under embargo at this time.

And our next question comes from the line of James Shin with Wells Fargo.

Can you hear me?

Yes, go ahead.

Fantastic. When lifileucel BLA is completed, will you issue a press release? And then one for Igor. For the 2,000-plus patient capacity that's ICTC 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'll take the first one. Igor will take the second one. Yes, I think we will likely issue a press release -- very likely issue a press release when the BLA is completed. Igor?

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 ICTC.

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.

And our next question comes from the line of Yevgeniya Livshits with Chardan.

This is (inaudible). So we noted recent update about both lung cancer and head and neck cancer program where you're activating (inaudible)? We want to have -- just provide some color and additional progress in the Phase IIs and the cadence of enrollment in data that can impact over the next few months? And a short follow-up on the PD-1 inactivated cell program. So you previously showed a mean knockout additions that came about 60% in development of [matrix-1]. Do you think that's enough (inaudible) number?

Yes. Let me see if I can understand the first question. You were asking about updates to the head and neck trials on trials.gov? It was pretty hard to hear you there.

Sorry, yes, in both the lung cancer and the head and neck, you could speak to traditional progress there and the cadence of enrollment and useful that we can expect.

I think -- Friedrich, 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. Friedrich, can you answer that question or help with that?

Yes. So 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, 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 like, the progress in enrollment or speed of enrollment on any of those specific cohorts. Does that answer your question?

Yes, it does. I had a small -- a quick follow-up to the PD-1 inactivated question.

I heard that one. So you asked whether 50% is adequate? We report values in that range, we could do a little bit better at sometimes. But we think that's adequate to treat patients. Remember, we're giving patients many billion sales of 50%, that is still quite a large number, usually in the billions. So we're giving patients a product that contains both knock-out cells and cells that are still having intact PD-1 gene.

So that's basically where the technology is these days for knockout. If you're looking in literature and some of the early work that was done, the knockout percentages, for example. Some of the early knockout studies like coming out of -- maybe more like 20%. So we're comfortable with that amount. We think that's going to be useful in...

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

I just had 2 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. procedures? I think you've said that because of 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?

Yes. 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 a lot of the manufacturing facility we own as well as our CMO partner, located on the East Coast and we can reach all the way into Eastern Europe as well as 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 will be interested in the future for melanoma launches in particular, and then for non-small lung and other indications, we're looking well beyond that as well. Jim, do you want to talk to 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'll have our sales team working with the top community practices doing education and outreach initiatives and then we'll also augment all of our efforts with nonpersonal promotions to expand our region frequency.

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

This is (inaudible) on for Asthika. 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 contract manufacturers and also potentially where those centers are administering high-dose IL-2 would be if you've got more of them online? And then secondly, in terms of IOV-4001, you mentioned the 1 patient dosed already, and we're just wondering how enrollment was progressing in that trial at initial look at the data?

Igor, would you like to take the first part of that question? Maybe Jim could talk about high-dose IL-2, and Friedrich will 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 2,000 patients annually. We're not commenting exactly about the demand we expect in year 1, 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.

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 uses of weighing 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.

Regarding the IOV-4001 trial, and there was 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 the study. Thanks for the questions.

And our next question come (inaudible).

This is Jerry (inaudible). I did lose connection for a short portion, so I apologize if any of my questions were already asked. So for Cohort 2 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 CAR-T product?

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

Sure. Yes -- so about the cash (technical difficulty) at the end of this quarter, I mean, we are confirming that we have enough runway into 2024. So definitely a strong position as a late-stage company with derisked lead programs and also our 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.

The next question comes from the line of Alex (inaudible) with Barclays.

This is Alex on for Peter Lawson. I just had a quick one on the lung cancer study, and I 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 of months ago? Any color around that would be helpful.

Yes. Friedrich, I think you talked earlier about the COM-202 study.

Yes, 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 what we were able to activate sites and how these sites are enrolling to the trial. We haven't shared any exact and concrete numbers. We're really, really pleased with the progress on that study. What we had shared 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'll 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're heading into an exciting end to the year at Iovance, including the SITC Annual Meeting next week as well as our upcoming expected completion of BLA submission.

As a preview, we expect on November 7 the SITC will hold for oral presentation will be released and will include a detailed look at the full data from Cohorts 2 and 4 of our C-144-01 trial.

On November 8, there will be a press program for members of the media covering the data in the abstract. Finally, on November 10, oral presentation will be presented with an update including additional follow-up on the 4 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, the global leader in cell therapy.

I would also like to thank our (technical difficulty) 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.