Iovance Biotherapeutics, Inc. (IOVA) Q3 2020 Earnings Report, Transcript and Summary

Good afternoon, and welcome to the Iovance Third Quarter and Year-to-date 2020 Financial Results Conference Call. [Operator Instructions]. 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 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 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 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 toward 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 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 FDA to better define TIL. Reaching agreement with 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 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 end of 2020. We anticipate clinical activities in these rooms to be initiated in 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 which can address the need 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 head count prior to the BLA submission. A core team with extensive cell therapy experience is currently focused on site training, TIL awareness, patient access or 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 health care professionals, or HCPs, 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 and they have reached the process. Our medical affairs team works with a network of treating HCPs 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. Friedrich?

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 is 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 overall response rate to docetaxel that is approximately 9%. We believe that proof-of-concept in 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 of start of 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 a significant unmet need, we will look at 4 different cohorts. Cohort 1 will include patients whose tumors did not express PD-L1 with TPS score less than 1%. Cohort 2 will have tumors that express PD-L1 with TPS score greater than 1%. Cohort 3 patients also had 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 patient populations they enroll. The Simon's two-stage design is used in LUN-202 study, allowing for expansion if the strength of the signal supports that. The primary efficacy end point 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, or SITC, 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, overall response rate, or ORR, was 44%, and 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 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 2020, an increase of $5.9 million compared to $10 million for the third quarter 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 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.

[Operator Instructions]. And our first question comes from the line of Peter Lawson with Barclays.

Just on the new assays, how long do you think they take? And is there any way of -- again understanding the complexity of those and if that kind of creates almost like a barrier of entry into the space.

Peter, thank you for your question. We haven't given specific guidelines because it obviously is subject to discussion with 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. And 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 time frame. It requires further dialogue with FDA, but we are working on a number of different fronts to assure that we address any questions that they might have.

And is there any way to kind of explaining the level of complexity of those assays? How long they would -- if it requires more external resources to develop those.

We do have the resources to develop them. So it's not an issue of lack of resources. Our gold standard assay is a cytokine assay that has been provided to the agency. It's very well known in characterizing TIL. And again, a lot of work has been done. Validation data has been provided to the agency, and we are in the stage of refinement of the data. There's one assay that we have provided -- again has been provided to the agency and we are validating additional assays to provide to FDA. And then there's additional assays. So there's 3 waves of assays that we are working on to assure that each one of them is appropriate for FDA's request. They have different time frames. Some are very advanced, and some are more sort of our research assays that we are developing for commercial release assay.

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 to be 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 given that both products -- the lifileucel for cervical is the same as lifileucel for melanoma. They have the same manufacturing process and the same release. We had anticipated that the same potency assays will be used 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. Great question. So if I may just reword your question whether there would be -- one would be an sBLA, which is subsequent to the original BLA, or whether each one of them would be separate BLAs. It is subject to discussion to FDA. They would have the discretion to be able to ask for each one of them to have a separate independent filing or one being a supplement to the other one. From an operational perspective, both are very feasible from Iovance's side. We certainly can do whichever we reach agreement 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. Another good set of questions, and it starts again with Maria. So as Maria said, our goal was to identify a population with high unmet medical need with limited prior therapy, with basically a limited therapy history from diagnosis. The challenge with the mutation-positive patients is that these patients will -- depending on the driver mutation they have, they undergo at least 1 round of TKI therapy. And then they have available therapy, which is platinum doublet chemotherapy. So we would probably have to define the population as having exhausted all TKI options, all approved TKI options and platinum doublet therapy, which leads to quite an extensive prior therapy history. That's what we wanted to stay away from for this study. The second question was about the cohort sizes. So the two direction -- the registration-directed cohorts or Cohorts 1 and 2, each of those are currently sized with a sample size of 40. Then we have the core biopsy cohort, which is really a signal generation proof-of-concept objective that is sized at an equal 15 And then Cohort 4 is not defined with a subject size because these are patients who fail on either Cohort 1 through 3. So that's not really a statistically powered affair. This is basically again signal searching and enrolled from patients that are coming from the study. I hope that makes sense.

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 time line for our lung data to be released.

So is that correct then to assume that regardless of what the data you're going to see with your lung data -- with your own lung study, you're going to 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.

Sure. Our launch preparations continue as we have started earlier this year along three major fronts: first is site preparation and onboarding; second is ensuring that our IOVANCECares cell ordering and patient system -- support system is ready for launch; and then third working with payers. So on the first, we continue to meet with KOLs and sites. As we mentioned on the last earnings call, we're targeting at least 40 sites for commercial launch, and we have not slowed down. Every week, we continue to meet with KOLs and sites, and they remain very enthusiastic about the potential for delivering lifileucel to patients with high unmet need. On the payer front, we continue our engagements. We've had over payer -- 80 payer engagements. Year-to-date, we also meet with CMS and the Medicare administrative contractors or the MACs. So we feel very confident in about -- in our approach to creating access for lifileucel once it's approved. And then on the final front, the chain of identity, chain of custody, cell ordering and patient support programs were progressing nicely, and we feel, again, very confident that once we have FDA approval, we'll be firing on all cylinders on all 3 of those fronts. I won't comment too much about CAR-T, but yes, we absolutely do a competitive assessment. We look at the trend lines, potential barriers that they're facing. And I don't have to tell you with the recent earnings call that you can estimate the number of patients and the trends. So we're thinking about potential challenges like -- at least in their case, not just other CAR-T in terms of competition from a commercial perspective but also from the clinical trial perspective. And we also know that between the two, they're exchanging market share. So there's a lot of things that we're learning at the site level, the payer level and at the patient level.

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

So the first one kind of relates really on [indiscernible] as well as the lung cancer. What -- we recently say that the composite with Moffitt data proves that your [indiscernible] basket data are kind of the basis for [indiscernible] being this lung cancer trial [indiscernible] PD-1 low patient?

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 [indiscernible] beyond objective response rate, how is the duration of response of that [indiscernible] checkpoint plus chemo TIL 1 low [indiscernible] ever 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 [indiscernible] end point in non-small cell lung cancer [indiscernible] second-line setting beyond your [indiscernible]

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, given the abstract submission deadline was moved out really just a little bit of a longer follow-up is what we are going to present at SITC, and I think abstracts are being -- or the posters are getting released on Monday, so a longer 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. Great question. I think a little bit more additional patients and certainly a little bit of a longer follow-up so we have an understanding of median DOR would be very helpful. So we continue enrolling into this cohort. And hopefully, with -- once we have a little bit more patients sort of added and follow-up durations a little longer, we can decide exactly 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. So typically, we don't disclose our point estimate or the exact sort of number of patients for each of the stages for Simon’s two. Once we cross it -- traditionally, we have announced that we have crossed it and we are continuing. So that has been our sort of communication strategy.

And our next question comes from the line of Reni Benjamin with JMP Securities.

This is Justin Walsh on for Reni. So I have a couple of questions. The first one is on the assay. So if you resolve this -- and we're assuming that you will resolve this for lifileucel, do you expect that you could encounter similar roadblocks for later products like your genetically modified TILs? Or do you think that once you figure out how the FDA wants to define TILs that you'll be more or less in the clear for later products?

Justin, thank you for the question. I don't know if I can answer it for a product that we haven't fully developed yet. I know we are working and we have released data at ESMO 2020 for genetically modified products, but we haven't really quite defined it ourselves in the sense that usually in an IND, we define the product fully. So I don't know if I can answer that question today because we haven't filed the IND and we are still in the exploratory stages of the PD-1 knockout genetic modified product. So I don't know quite how the -- what assays we're going to develop and whether that would be adequate. I don't know if I can answer that question today.

Okay. And I guess the other one is on your plan for the Navy Yard and commercial production. I think it said that you're -- you'll be ready commercially in 2022 for the Navy Yard. If you end up having lifileucel approval before then, what would that transition look like from -- and how much capacity do you have before you get that facility up and running?

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 Jim Birchenough with Wells Fargo.

It's Nick on for James. First question, Maria, in your prepared comments, you noted the Type B meeting defined the duration of treatment -- sorry, duration of follow-up. So is this 6 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 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 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?

Right. It's 6 months from the time of PR as assessed by IRC. So we did define it for melanoma, but I think that -- let me maybe clarify something. The 2 products are under two different INDs. So the review teams are different. So we just want to make sure that we are respectful to FDA and we meet with the review team that's going to be reviewing the cervical submission before we sort of confirm what the duration of follow-up would be.

Okay. And then just a clarification on LUN-202. The clinical trial description for Cohorts 1 and 2 says a tumor sample via surgical reception -- resection or biopsy. So from the prepared comments, it sounds like a core biopsy would not be allowed 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. And then just in terms of thinking about commercial prospects for lifileucel in melanoma. And how many is -- with surgical resection or biopsy procedure, how many of those surgeons are credentialed for giving chemotherapy? How comment is that, I guess, is the question.

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

Credentials for chemotherapy. They're sort of -- I'm not sure if it's the same, dual-certified, but I mean one of the principal investigators in the melanoma trial is a surgeon rather than a medical oncologist, which most of them are. But it turns out they're also credentialed in chemotherapy. And so if the surgeon is the gatekeeper of patients, if they're credentialed in chemotherapy, then does that make a difference as to their interest in a TIL product?

Understood. Let me try and shed some light and I'm going to ask Jim to comment on this as well. I just want to make sure that it's clear that usually, there's a team involved in caring for patients. When a patient becomes such late line post therapy, there are surgeons involved. There's oncologists involved. There is a number of different -- support team is involved in assessing how to best support the patient. This is precisely why our commercial team is preparing sites because there is a great degree of coordination that happens at the site. But let me ask Jim to speak to that. So the surgeon is not necessarily the person who's administering chemotherapy that is required as part of non-myeloablative chemotherapy. Jim , do you want to add something to this?

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 Ben Burnett 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 analog 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.

Awesome. Great. So I wanted to follow up on head and neck cancer. So the data you have so far is largely patients who received PD-1 after chemo. And as Biren mentioned, there's seems to be a really material difference in response rate between -- in the frontline PD-1 population with head and neck cancer and the PD-1 after chemo population. So ultimately, how do you think about the positioning of PD-1 plus TILs in head and neck cancer? Like is it a post-chemo drug? Is it a -- some frontline drug? And what do you need to see if it's the latter to kind of make you confident that TILs plus PD-1 can provide additive benefit in the truly previously untreated population?

Yes. Great question. Thank you, Madhu. I'll give you my best assessment, and then I'm going to ask Friedrich to comment as well if there's more to -- for us to share. I think exact product positioning is not something we have quite done. We really want to be sure that we understand the product, a larger sample size and longer follow-up. So I think median duration of response is an important player here given that a lot of prior therapies, including chemotherapy or immunotherapy in frontline head and neck, really offer a very short median duration of response of approximately 5 to 6 months. So median duration of response in this setting would be very important to us as well as additional patients to confirm the responses that we are seeing. Friedrich, do you want to add anything in terms of how to position the product?

No, I think it's important to mention that the positioning right now -- so the patients that we are exploring in this cohort are basically post an NCCN and approved first-line therapy, which is the extreme setting, right? So the chemotherapy or chemotherapy plus EGFR antibody. So this is meaningful. That is still an approved and used first-line therapy. And although the sample size is small, the response rate is encouraging and shows basically something that's comparable to what you would be seeing in first line. So I think that's indicating the potential here in what is a chemo-free regimen. So I think there's -- we have some options here, but where we are right now 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 like 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?

Mara, thank you for the question. Yes, the reason we are not giving the exact number of how many thousands -- presumably, I think that's what you're asking...

Yes.

Is you may -- thank you. You may recall that for the manufacturing facility, we talked about a butterfly design, where we are building the core for the facility but the internal manufacturing facility itself is really half of the manufacturing facility almost, is going to be ready. And when we have larger capacity, we will complete the remaining half of the facility. So we have a lot of opportunities to increase capacity as necessary, which is why we are not trying to give a specific number because it is a flexible number depending on the need. So it would be very much supply and demand. As the demand goes up, we will expand the facility and we can add staff to go to 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 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.