Good afternoon, and welcome to the Iovance Third Quarter and Year-to-date 2020 Financial Results Conference Call. Now I would like to turn the call over to Sara Pellegrino, Vice President, Investor and Public Relations at Iovance. Please go ahead.

Thank you, Operator. Good afternoon, and thank you for joining us. Speaking on today's call, we have Maria Fardis, our President and Chief Executive Officer; Friedrich Finckenstein, our Chief Medical Officer; and Michael Swartzburg, Vice President of Finance and Interim Principal Financial and Accounting Officer. This afternoon, we issued a press release that can be found on our website at iovance.com, which includes the financial results for the 3 and 9 months ended on September 30, 2020, as well as a corporate update. 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 trial plans and results, potential future applications of our technologies, manufacturing capabilities, regulatory plans, feedback and guidance, 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 Maria.

Thank you, Sara, and good afternoon, everyone. I am pleased to highlight our third quarter progress at Iovance during today's conference call. Our recent accomplishments reflect our efforts to bring our tumor-infiltrating lymphocyte, or TIL, to patients while broadening its potential across multiple indications. For our lead TIL product candidate, lifileucel in metastatic melanoma, we are in the process of refining the existing assays as well as developing new assays in pursuit of our biologics license application, or BLA, that we plan to submit to the FDA in 2021. An additional indication, we have initiated our registration-directed study of LN-145 in non-small cell lung cancer and look forward to the upcoming presentation of clinical data for LN-145 in combination with KEYTRUDA in head and neck cancer. We continue to execute towards all of our key priorities, including CMC, clinical, manufacturing, and pre-commercial activities, and furthering our commitment to address the critical needs of cancer patients. I would like to spend a few minutes highlighting our lead indications, and then I will let Friedrich highlight our updates in non-small cell lung and head and neck cancers. I will begin with lifileucel for advanced melanoma. Metastatic melanoma is a common type of skin cancer, accounting for approximately 96,000 patients diagnosed annually and 7,200 deaths each year in the United States alone. We are focused on a metastatic melanoma patient population that is a serious unmet need. Chemo is the only currently available therapeutic option, offering a 4% to 10% response rate and a short duration of response. As previously announced, we held a Type B meeting with the U.S. FDA, where we reached agreement on the duration of clinical data follow-up for our pivotal cohort 4 to support the BLA. We have further work to do to refine existing potency assays and develop new assays. We are actively working on a matrix of assays to offer to the FDA to better define TIL. Reaching agreement with the FDA on the potency assay is a top priority for Iovance. While the length of time until BLA submission depends on future dialogue with the agency, we plan on the BLA submission in 2021 and may provide updates when available. Our second pivotal program is investigating LN-145, now also known as lifileucel, in the C-145-04 study in patients with metastatic cervical cancer. We dosed the last patient in the pivotal Cohort 1 during the third quarter, and we anticipate top line pivotal data approximately in mid-2021, pending future discussions with the FDA on clinical data follow-up for this indication. As a reminder, the FDA has previously granted both breakthrough therapy and Fast Track designations for lifileucel and for cervical cancer. Turning to our manufacturing facility or ICTC. The first set of clean rooms are expected to be ready for the Iovance employees to move in by the end of 2020. We anticipate clinical activities in these rooms to be initiated in the first half of 2021. Commercial manufacturing is on track for 2022 with capacity to meet the demand for thousands of patients. Iovance has transformed TIL manufacturing from a lengthy academic process to a shorter, scalable centralized GMP process, yielding a cryopreserved product that can address the needs of thousands of cancer patients. To date, more than 400 patients have received TIL manufactured at Iovance with a continuing success rate above 90%. We have also built and continue to augment our intellectual property surrounding the Gen 2 process, which is covered by 20 granted or allowed U.S. patents. Turning to our commercial launch preparation. We are taking a gated approach to commercial readiness expenses and headcount prior to the BLA submission. A core team with extensive cell therapy experience is currently focused on site training, TIL awareness, patient access, and other readiness activities. A core commercial team continues to partner with the leading U.S. centers to build TIL service line capabilities, and we intend to scale our training and onboarding upon BLA submission. The engagement and feedback remain very positive as healthcare professionals recognize the high unmet need in metastatic melanoma. Our market access team continues to meet with private payers and the Centers for Medicare and Medicaid Services, or CMS, to ensure patients have appropriate and timely access to lifileucel. We believe that CMS and payers recognize the unmet need and clinical value of lifileucel, as well as the potential benefit for patients with metastatic melanoma. We are also pleased with the development and progress of our IOVANCECares program. Our goal is to deliver a best-in-class cell ordering and patient support system that assists the patient as they navigate the process. Our medical affairs team works with a network of treating healthcare professionals and patient advocacy groups to assure that information about TIL is available to interested organizations. Our work continues in developing our novel IL-2 analog, IOV-3001, as well as our genetic modification of TIL using TALEN technology. We presented some of our preclinical data at ESMO 2020. I will now pass the call to Friedrich to outline our new clinical study in non-small cell lung cancer and to highlight the TIL opportunity in head and neck cancer.

Thank you, Maria. I would like to provide an overview of our registration-directed study in non-small cell lung cancer. Despite significant advances in first-line treatment for non-small cell lung cancer, there are clear unmet needs in patients who have progressed on prior anti-PD-1 therapy. Patients who progress after checkpoint inhibitor and chemotherapy are expected to achieve an overall response rate to docetaxel that is approximately 9%. We believe that proof-of-concept in the use of TIL in non-small cell lung cancer was well established through the Moffitt TIL data, showing an overall response rate of 25%, including 2 durable complete responses and 1 confirmed partial response in 12 evaluable patients. We finalized the protocol for our IOV-LUN-202 study and began activating sites in preparation for starting the study by year-end. This is a Phase II study to investigate our Iovance TIL therapy, LN-145, in recurrent or metastatic non-small cell lung cancer patients without driver mutations who previously received a single line of approved systemic therapy with a checkpoint inhibitor and chemotherapy. Within this patient population with significant unmet need, we will look at 4 different cohorts. Cohort 1 will include patients whose tumors did not express PD-L1 with a TPS score less than 1%. Cohort 2 will have tumors that express PD-L1 with a TPS score greater than 1%. Cohort 3 patients also had a TPS score less than 1%, in which we will grow TIL from core biopsies to infuse back to the patients. And finally, Cohort 4 will offer retreatment for patients who progress in Cohorts 1 through 3. The cohorts in the LUN-202 study are distinct from the 2 cohorts in our ongoing IOV-COM-202 basket study in the patient populations they enroll. The Simon's two-stage design is used in the LUN-202 study, allowing for expansion if the strength of the signal supports that. The primary efficacy endpoint will be objective response rate, or ORR, assessed by Independent Review Committee, or IRC. Head and neck cancer also remains an important indication for Iovance in 2 of our ongoing studies. In our ongoing IOV-COM-202 basket study in solid tumors, Cohort 2A is evaluating LN-145 in combination with pembrolizumab in head and neck cancer. We are particularly excited about the upcoming clinical data presentation at the Society for Immunotherapy of Cancer annual meeting next week, as this is the first time we are presenting TIL in combination with KEYTRUDA in checkpoint-inhibitor-naive patients in any indication. We are highly encouraged by what we see so far in head and neck cancer, as well as the potential for the same combination in other solid tumors. The abstract of the poster presentation from our IOV-COM-202 basket study highlights 9 patients with head and neck squamous cell carcinoma, or HNSCC, who have not previously received treatment with checkpoint inhibitors but may have received prior chemotherapy. Following LN-145 in combination with pembrolizumab, the overall response rate, or ORR, was 44%, and the median duration of response had not been reached at 6.9 months of median study follow-up, as noted in the abstract. While these are small patient numbers, we find the results to be very promising since ORR with approved therapies in checkpoint-naive head and neck cancer patients ranges from 15% to 18% in the literature. We look forward to presenting updated head and neck cancer clinical data at SITC next week. I will now hand the call over to Michael to discuss our third quarter and year-to-date 2020 financial results.

Thank you, Friedrich. My comments will reflect the high-level financial results from our third quarter and year-to-date 2020. Additional details can be found in this afternoon's press release as well as in our quarterly report on Form 10-Q to be filed shortly with the SEC. I'll begin with our cash position. As of September 30, 2020, Iovance held $719.7 million in cash, cash equivalents, short-term investments, and restricted cash compared to $312.5 million on December 31, 2019. Our cash position includes net proceeds of $567 million from our June 2020 common stock public offering. Our financial strength is expected to support the commercial launch and pipeline programs, including the IOV-LUN-202 study in non-small cell lung cancer. We anticipate year-end balances of cash, cash equivalents, short-term investments, and restricted cash may be over $630 million. Moving to the income statement, our net loss for the third quarter ended September 30, 2020, was $58.6 million or $0.40 per share compared to a net loss of $49.5 million or $0.40 per share for the third quarter ended September 30, 2019. Net loss for the 9 months ended September 30, 2020, was $191.2 million or $1.41 per share compared to a net loss of $134 million or $1.08 per share for the same period ended September 30, 2019. Research and development expenses were $43.1 million for the third quarter ended September 30, 2020, an increase of $1.5 million compared to $41.6 million for the third quarter ended September 30, 2019. Research and development expenses were $149.3 million for the 9 months ended September 30, 2020, an increase of $37.5 million compared to $111.8 million for the same period ended September 30, 2019. The increase in research and development expenses in the third quarter 2020 over the prior year period was primarily attributable to growth of the internal research and development team and higher stock-based compensation, partially offset by a decrease in manufacturing costs. The increase in research and development expenses for the first 9 months of 2020 over the prior period was primarily attributable to higher patient enrollment in clinical trials, licensing fees, and growth of the internal research and development team. General and administrative expenses were $15.9 million for the third quarter of 2020, an increase of $5.9 million compared to $10 million for the third quarter of 2019. The increase in third quarter 2020 over the prior period was primarily attributable to growth of the internal general and administrative team and higher stock-based compensation expenses. General and administrative expenses were $44.1 million for the 9 months ended September 30, 2020, an increase of $14.1 million compared to $30 million for the same period ended September 30, 2019. The increase in general and administrative expenses in the third quarter and first 9 months of 2020 compared to the prior year periods were primarily attributable to growth of the internal general and administrative team and higher stock-based compensation expenses. As of September 30, 2020, there were approximately 146.6 million common shares outstanding. Looking ahead, we expect operating expenses in the fourth quarter of 2020 to be higher compared to the third quarter of 2020 as we activate more sites and prepare to dose patients in our lung cancer study. At the same time, we are employing a measured and gated approach to commercial readiness expenses and continue to anticipate a year-end cash balance above $630 million. I will now hand the call back to the operator and kick off the Q&A session.

Our first question comes from Peter Lawson with Barclays.

Regarding the new assays, how long do you expect them to take? Also, can you help us understand their complexity and whether that might create a barrier to entry in the market?

Peter, thank you for your question. We haven't given specific guidelines because it obviously is subject to discussion with the FDA. We have existing assays that have been provided to the agency, and we are refining the data and providing that information to the agency. We also have additional assays that we have developed, and we are compiling further data, including validation, and we are providing that also to the FDA. In addition to those, we have what we call additional assays that we are developing in case we don't have agreement with the agency on some aspects of the first or the second or a combination of those two assays. So we are not able to give you a specific timeframe. It requires further dialogue with the FDA, but we are working on a number of different fronts to assure that we address any questions that they might have.

Is there a way to explain the complexity of those assays and how long they might take if they require more external resources for development?

We have the resources needed for development, so resource availability is not a concern. Our gold standard assay is a cytokine assay that has been submitted to the agency and is well-recognized for characterizing TIL. A significant amount of work has already been completed, and validation data has been shared with the agency. We are currently refining this data. We have provided one assay to the agency and are in the process of validating more assays for FDA submission. Additionally, we are working on three waves of assays to ensure that each meets the FDA’s requirements. These assays have different timelines; some are highly advanced, while others are more exploratory and being developed for commercial use.

And just on IL-2, what's the timing around a new analog for IL-2? And will you need that to kind of move into other settings?

Are you referring to IOV-3001?

Yes.

Okay. Thank you. Yes, as you might recall, we have licensed this particular product, IOV-3001, a novel IL-2 analog from Novartis. It is an IL-2 CDR graft, which is targeting, binding to IL-2 beta-gamma receptors. We had disclosed previously that we are focusing on GMP manufacturing of IOV-3001 in 2020, and we anticipate initiating IND-enabling activities in early 2021, and we remain on target for those.

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

Maybe if I could just ask with respect to the cervical cancer filing also expected in 2021. What, from sort of the current discussions and activities around the potency assays and the work that you're doing, is required for the cervical cancer filing?

Thank you, Mara. We expect that both products, lifileucel for cervical cancer and lifileucel for melanoma, are the same. They share the same manufacturing process and release. We had anticipated that the same potency assays would be utilized for both products.

Okay, but will you be required? I'm just curious about this, but are you able to leverage one filing into the other? Or will they be separate?

Yes, that's a great question. To rephrase, you are asking whether there will be one subsequent biologics license application, or if each product will require separate applications. This is a matter that we will discuss with the FDA, who has the authority to determine if a separate independent filing is necessary for each product, or if one can be a supplement to the other. From our operational standpoint, both options are feasible for Iovance, and we can proceed based on what we agree upon with them.

And when is the likelihood that you would know something like that?

Typically, a pre-BLA meeting is a good time to be discussing this. So a pre-BLA meeting for cervical, for example, would be a good venue to discuss the topic.

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

I think I heard Friedrich mention that patients in the 202 lung study would not overlap with those who are currently enrolled in the basket study on cohorts. Maybe you could elaborate a little bit on the differences between those patient populations and maybe give us some confidence on why you would expect LN-145 to work in a population where it hasn't been first tested in a smaller study?

Sure. Mark, I will turn this over to Friedrich. I just want to make a comment about how we thought about the LUN-202. The way we thought about the patient population is we wanted to make sure that these are earliest possible patients yet unmet medical needs. So that's how we thought about it. But maybe I can ask Friedrich to talk about the difference between COM-202 and LUN-202 cohorts.

Yes. Thanks for the question. Good question. I think it's really based on what Maria just said. Our goal was to, number one, define the population so that we are actually setting ourselves up for potential for registration-directed cohort. So the cohort in the LUN study is more narrowly defined. The numbers of prior therapies is lower than in the COM study, where we are doing more of a signal-finding study. So really, this is the follow-up step after the COM-202 study with a better defined narrow and more narrowly and better defined population. I think that's probably the best way to say it. The confidence really is based on the proof of concept as I had also laid out in the Moffitt study, where the proof of concept for activity after failure of checkpoint inhibitor therapy was shown with a 25% response rate in the 12 evaluable patients in that study. So that's where the confidence is driven from.

Okay. Got it. And we also saw in that Moffitt sort of proof-of-concept studies, some responses in patients who had driver mutation. So can you maybe talk a little bit about why they're being excluded from this new study? And also, can you tell us what kind of the estimated cohort size would be for each of the 4 cohorts that you outlined?

Sure. Those are good questions. To start, our goal was to find a population with significant unmet medical needs who have had limited previous therapy from their diagnosis. The issue with mutation-positive patients is that they typically undergo at least one round of TKI therapy depending on their specific driver mutation, and then they can receive platinum doublet chemotherapy. Therefore, we need to define the population as those who have exhausted all available TKI options and platinum doublet therapy, resulting in a considerable prior therapy history, which we wanted to avoid for this study. Regarding cohort sizes, the registration-directed cohorts, Cohorts 1 and 2, each have a sample size of 40. The core biopsy cohort, which aims for signal generation and proof of concept, consists of 15 participants. Cohort 4 does not have a specific size, as it includes patients who have failed on any of Cohorts 1 through 3, and this is not statistically powered. Essentially, this cohort is more about searching for signals and will include patients coming from the study. I hope that clarifies things.

And our next question comes from the line of Boris Peaker with Cowen.

I mean maybe first on the lung. Can you comment when we're going to be seeing your lung cancer data?

Boris, Yes, we have not committed to a specific timeline for our lung data to be released.

So is it correct to assume that regardless of the data you gather from your lung study, you will proceed with the pivotal trial?

I don't know if that's necessarily the correct statement. Just the fact that we haven't released it doesn't mean we haven't seen it. So obviously, we have enthusiasm behind the indication to start the study.

Got you. Okay. Maybe lastly, I'm curious what commercial preparations are you making for lifileucel ahead of the launch and maybe what you've learned from CAR-Ts. Any mistakes that were made there to make sure they are not made again?

Absolutely. I'm going to pass the question to Jim.

Our launch preparations are progressing as planned this year across three main areas: site preparation and onboarding, ensuring our IOVANCECares cell ordering and patient support system is ready, and working with payers. Firstly, we continue to engage with key opinion leaders and sites. As noted in our last earnings call, we aim to have at least 40 sites ready for commercial launch, and our efforts have not slowed. We meet with key opinion leaders and sites weekly, and there is strong enthusiasm for delivering lifileucel to patients in need. On the payer side, we've conducted over 80 engagements and have also met with CMS and Medicare administrative contractors this year. We are confident in our strategy for accessing lifileucel once it's approved. Lastly, we are making good progress in areas like the chain of identity, chain of custody, cell ordering, and patient support programs, and we believe that once we receive FDA approval, we will be ready to operate effectively on all fronts. While I won’t discuss CAR-T in detail, we do assess competition and monitor trends and barriers they face. We are aware of patient trends from the recent earnings calls and recognize the challenges, particularly regarding market and clinical trial competition. We're learning a lot from our engagement at the site, payer, and patient levels.

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

The first point is closely related to lung cancer. We recently observed that the composite data from Moffitt supports that your basket data forms the basis for this lung cancer trial.

Madhu, I'll try and answer the question. It was not very easy to hear. You're getting cut off. I believe what you're wondering about is whether the collective experience of the data we had from Moffitt as well as what we may be observing internally was the basis for our selection of the patient population in LUN-202. The answer to that is yes.

Okay. And then about beyond objective response rate, how is the duration of response of that TIL likely to be a value in the non-small cell basket trial?

We're having a really hard time hearing you. Do you want to try one more time back in? Or do you want to try to repeat the question?

Sure. Sorry. So basically, to what extent is duration of response an endpoint in non-small cell lung cancer?

So I'm not able to hear Madhu, but I think he was talking about median duration of response and to what extent that might have had an impact on our patient selection. The best set of data in terms of durability did come from Moffitt. So it's very encouraging to see the two complete response patients continued in response past 12 months, and one of their PR patients had a response for approximately 18 months. So that was highly encouraging for us in terms of median DOR.

And our next question comes from the line of Biren Amin with Jefferies.

Maria, so at SITC, you talked about the abstract having 9 patients. How much more data will we have next week?

Biren, since the abstract submission deadline has been extended, we will present a slightly longer follow-up at SITC, and I believe the abstracts or posters are scheduled for release on Monday, which will allow for this extended follow-up.

Okay. So I mean you had some pretty encouraging responses. I think 4 out of 9 patients. And if you look at historical pembro, it's about 14%, 15% ORR. So I guess when would you have sufficient data where you feel comfortable moving this into a pivotal study?

Yes. That's a great question. Having a few more patients and extending the follow-up period to better understand the median duration of response would be very beneficial. We are still enrolling in this cohort, and once we have more patients and longer follow-up times, we can better determine how to position the product.

Got it. And then maybe just a last question on LUN-202, the lung study. Can you just talk about the thresholds for Cohort 1 and 2 in terms of the first phase? What type of a response rate would you need to see to move it into the second phase?

Right. Typically, we don't disclose our point estimate or the exact number of patients for each of the stages for Simon’s two. Once we reach it, we traditionally announce that we have crossed it and are continuing. So that has been our communication strategy.

And we have a follow-up question from the line of Justin Walsh with JMP Securities.

This is Justin Walsh speaking on behalf of Reni. I have a couple of questions. The first one is about the assay. If you manage to resolve this for lifileucel, do you anticipate facing similar challenges with later products like your genetically modified TILs? Or do you believe that once you determine how the FDA defines TILs, you will be relatively clear for subsequent products?

Thank you for the question, Justin. I'm not sure I can provide a clear answer regarding a product that isn’t fully developed yet. We are actively working on it and have shared data at ESMO 2020 about genetically modified products, but we haven't completely defined it ourselves as we typically do in an IND. Therefore, I'm unable to answer your question right now since we haven't filed the IND and are still exploring the PD-1 knockout genetic modified product. I'm uncertain about the assays we will develop and whether they will meet the requirements. So, I can't fully address that question today.

Okay. I also wanted to ask about your plans for the Navy Yard and commercial production. It seems you will be commercially ready in 2022 for the Navy Yard. If you receive lifileucel approval before that, what would the transition look like, and what is your capacity before getting that facility operational?

Thank you for that question. Excellent. Thank you. We certainly have been working very closely with WuXi, our CMO provider for our manufacturing to date, and there's ample capacity secured at WuXi for us to initialize our commercial manufacturing and then switch over to ICTC. So we do have a number of different options, and we work on all fronts to make sure that we are completely ready.

And our next question comes from the line of Nicholas Abbott with Wells Fargo.

It's Nick on for James. First question, Maria, in your prepared comments, you mentioned that the Type B meeting defined the duration of follow-up. Is this six months after an unconfirmed partial response? And why would it be different for cervical cancer?

Right. I think you're referring to the comment on the timing of data release for cervical. And we did say that we really want to make sure that we meet with the FDA to make sure that the duration of follow-up is defined. I'm not necessarily saying that it would be different. I'm just saying that because we haven't talked to the FDA about the follow-up, that step needs to take place. But it doesn't necessarily mean that it's going to be any different than melanoma. Does that answer your question, Nick?

Yes, partially. I was thinking from the Type B meeting from the melanoma data, you said that you've defined what the duration of follow-up is. Is this 6 months? And is that after an unconfirmed PR or after a confirmed PR?

It's six months from the time of the partial response as assessed by the IRC. We have defined this for melanoma, but I want to clarify that the two products are under different investigational new drug applications. As a result, the review teams are different. We want to ensure that we are respectful to the FDA and meet with the review team that will be handling the cervical submission before we confirm what the follow-up duration will be.

Okay. Just to clarify on LUN-202, the clinical trial description for Cohorts 1 and 2 indicates that a tumor sample must be obtained through surgical resection or biopsy. Based on the prepared comments, it appears that a core biopsy would not be permitted in Cohorts 1 and 2.

That's correct. So Cohorts 1 and 2 have excisional biopsy, which is our traditional method of collection of tumor. Cohort 3 allows for a core biopsy, which is a much smaller amount of tumor.

Great. In terms of the commercial prospects for lifileucel in melanoma, how many surgeons involved in surgical resection or biopsy procedures are credentialed to administer chemotherapy? How common is that?

For the surgeon to give chemotherapy, are you referring to the...

Credentials for chemotherapy are somewhat unclear. One of the main investigators in the melanoma trial is a surgeon instead of a medical oncologist, which is typically the case. However, this surgeon is also credentialed in chemotherapy. If the surgeon is responsible for patient access and they have chemotherapy credentials, does that influence their interest in a TIL product?

Understood. Let me provide some clarity on this, and I'll ask Jim to comment as well. It's important to note that there is usually a team involved in patient care. When a patient reaches a late stage post-therapy, surgeons and oncologists, among others, are part of the support team that assesses the best way to assist the patient. This is exactly why our commercial team is preparing sites, as a significant amount of coordination takes place there. Now, I'll have Jim elaborate on this. The surgeon isn't necessarily the one administering the chemotherapy that is needed as part of non-myeloablative chemotherapy. Jim, would you like to add anything?

Thanks, Maria. You're exactly right. That's the reason why we're focusing on these top sites. It's because lifileucel, like other cell therapies, are delivered in a coordinated fashion across multiple people. It begins with, let's say, the surgical oncologists, as you point out, to do the tumor tissue procurement process. It involves the medical oncologists, obviously, and consult with the community in many cases. And then there's the care team that surrounds this. Every site is a little bit different as we're learning in our engagements in many cases because many of the same sites that we're targeting also deliver CAR-T therapy. There's the cell therapy or the BMT or other aspects of care that may have slight variations from site to site, but that's essentially the care team.

Our next question comes from the line of Kailie Briza with Stifel.

This is Kailie Briza on for Ben Burnett. I was wondering if you could provide a little bit of color as to which clinical indications you expect to leverage IOV-3001 first. And then my second question was if you guys are planning on implementing the Gen 3 manufacturing process for the new IOV-LUN-202 study.

Thank you so much for the questions. We have not finalized our indications for IOV-3001 program, so I likely won't be able to speak to that today. We obviously look at multiple indications, and there's quite a bit of history with IL-2 analogs in terms of which indications they have been approved or they have been investigated in. In terms of whether we would use Gen 3 and LUN-202, we would. That Cohort 3 may be subject to Gen 3.

And we have a follow-up question from the line of Madhu Kumar with Baird.

Yes. Can you guys hear me okay?

Yes, much better. Thank you, Madhu.

I wanted to follow up on head and neck cancer. The data you have so far mainly involves patients who received PD-1 after chemotherapy. As Biren mentioned, there appears to be a significant difference in response rates between the frontline PD-1 population for head and neck cancer and the PD-1 after chemotherapy population. So ultimately, how do you view the positioning of PD-1 plus TILs in head and neck cancer? Is it intended as a post-chemotherapy treatment or a frontline therapy? What would you need to observe to be confident that TILs plus PD-1 can offer additional benefits in patients who are truly treatment-naive?

Yes, thank you for the question, Madhu. I'll provide my perspective, and then I'll ask Friedrich to add his comments if there's more to discuss. We haven't finalized the exact product positioning yet. It's crucial for us to fully understand the product, which requires a larger sample size and extended follow-up. The median duration of response is a significant factor here, especially considering that many previous therapies, such as chemotherapy and immunotherapy in frontline head and neck cases, typically show a very short median duration of response of around 5 to 6 months. Therefore, the median duration of response will be vital for us, along with additional patients to validate the responses we are observing. Friedrich, do you have anything to add regarding the product positioning?

No, I think it's important to mention that the positioning right now is that the patients we are exploring in this cohort are essentially post an NCCN approved first-line therapy, which is the extreme setting. This includes chemotherapy or chemotherapy plus EGFR antibody. This is significant as it remains an approved and utilized first-line therapy. Although the sample size is small, the response rate is encouraging and appears comparable to what you would observe in first-line treatments. We have some options here, but our current position is already quite meaningful.

Okay. And one more, and I'm sure this is a question you get and think about all the time. Given these head and neck cancer data, what about a frontline melanoma trial with PD-1 kind of upfront? Like what do we need to see there and then get that going? I know Rosenberg for years has kind of wanted to do that study. So like how are you thinking about that?

Madhu, thanks again. So our Cohort 1A and our COM-202 study is exactly that. It's TIL plus KEYTRUDA in frontline patients or immune anti-PD-1 naive patients. So I think that, that data would be quite meaningful in terms of their ORR and median DOR before we decide what the next steps would be.

And we have another follow-up question from the line of Mara Goldstein with Mizuho.

You just mentioned a few times on the call around manufacturing capacity on the order of thousands of patients. Would you care to sort of, I suppose, put some colors around what thousands mean?

Thank you for your question, Mara. The reason we aren't providing a specific number regarding how many thousands we're capable of is because, as you may remember, we discussed a butterfly design for the manufacturing facility. We're currently focused on building the core of the facility, but only about half of it will be operational initially. Once we achieve a larger capacity, we will finish the remaining half. This design allows us to expand capacity as needed, which is why we're not sharing a precise figure; it's flexible based on demand. As demand increases, we will expand the facility and can add staff to accommodate multiple shifts.

And we have another follow-up from the line of Jim Birchenough with Wells Fargo.

Maria, can you give us an update on the CLL trial, please?

Jim, yes, of course. Our CLL program had dosed our first patient in the earlier part of the year. The program was mainly active in one clinical site, which was impacted by COVID. They have recently sort of gotten reactivated, and we also added clinical sites as well. So enrollment has recently sort of resumed. I won't be able to give you much further information beyond that.

And I'm showing no further questions. So with that, I'll turn the call back over to President and CEO, Maria Fardis, for any further remarks.

Thank you, Operator. Thank you, everyone, for joining Iovance's third quarter and year-end 2020 results conference call. Please feel free to reach out to our IR team if you wish to follow up in any way. Have a good afternoon.

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