Good afternoon, 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 in 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 three and nine months ended on September 30th, 2020, as well as 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 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 candidates, 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. In additional indications, 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 in furthering our commitment to address the critical needs of cancer patients. I would like to spend a few minutes highlighting our lead indications. 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 U.S. 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%-10% response rates 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. 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 headcount 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. We intend to scale our training and onboarding upon BLA submission. The engagement and feedback remain very positive as healthcare 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 & 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 Iovance Cares program. Our goal is to deliver a best-in-class cell ordering and patient support system that assists the patient at every step of 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, IOVA-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 Frederich to outline our new clinical study in non-small cell lung cancer and to highlight the TIL opportunity in head and neck cancer. Frederich?
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 need in patients who have progressed on prior anti-PD-1 therapy. Patients who progressed 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 two durable complete responses and one 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 four 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 have TPS score less than 1%, in which we will grow TIL from core biopsies to infuse back to the patients. Finally, Cohort 4 will offer retreatment for patients who progress in cohorts one through three.
The cohorts in the IOV-LUN-202 study are distinct from the two cohorts in our ongoing IOV-COM-202 basket study in patient populations they enroll. The Simon's 2-stage design is used in IOV-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 two 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 the 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-naïve 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 nine patients with head and neck squamous cell carcinoma, or HNSCC, who had not previously received treatment with checkpoint inhibitors but may have received prior chemotherapy. Following LN-145 in combination with pembrolizumab, overall response rate, 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-naïve head and neck cancer patients ranges from 15%-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 30th, 2020, Iovance held $719.7 million in cash equivalents, short-term investments, and restricted cash, compared to $312.5 million on December 31st, 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 equivalents, short-term investments, and restricted cash maybe over $630 million. Moving to the income statement. Our net loss for the third quarter ended September 30th, 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 30th, 2019. Net loss for the nine months ended September 30th, 2020, was $191.2 million or $1.40 per share, compared to a net loss of $134 million or $1.08 per share for the same period ended September 30th, 2019.
Research and development expenses were $43.1 million for the third quarter ended September 30th, 2020, an increase of $1.5 million compared to $41.6 million for the third quarter ended September 30th, 2019. Research and development expenses were $149.3 million for the nine months ended September 30th, 2020, an increase of $37.5 million compared to $111.8 million for the same period ended September 30th, 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 nine 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 nine months ended September 30th, 2020, an increase of $14.1 million compared to $30 million for the same period ended September 30th, 2019. The increase in general and administrative expenses in the third quarter and first nine 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 30th, 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.
Thank you. As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from the line of Peter Lawson with Barclays.
Hey, thanks so much. Thanks for taking the questions. Just on the new assays, how long do you think they take, and is there any way of getting an understanding of the complexity of those and if that kind of creates almost like a barrier of entry into the space?
Hi, Peter. Thank you for your question. We haven't given specific guidelines because it obviously is a subject of 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 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 aspect of the first or the second or a combination of those two assays. We're not able to give you a specific timeframe. It requires further dialogue with FDA, but we are working on a number of different fronts to ensure that we address any questions that they might have.
Is there any way of you kind of explaining the level of complexity of those assays? How long 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. 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. The cytokine assays that we have provided, again, has been provided to the agency, and we are validating additional assays to provide to FDA. There's the additional assays. There's three waves of assays that we are working on to ensure that each one of them is appropriate for FDA's request.
They have different time frames. Some are very advanced, and some are more our research assays that we are developing for commercial release assay.
Thank you. Just on the IL-2, what's the timing around a new analog for IL-2? Will you need that to move into other settings?
Are you referring to IOVA-3001?
Yes.
Okay. Thank you. Yes, as you might recall, we have licensed this particular product, IOVA-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 IOVA-3001 in 2020, we anticipate to be initiating IND-enabling activities in early 2021. We remain on target for those.
Great. Okay. Thank you so much. Good luck with everything.
Thank you.
Thank you. Our next question comes from the line of Mara Goldstein with Mizuho.
Thanks so much for taking the question. Maybe if I could just ask, with respect to the cervical cancer filing also expected in 2021, what from 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. Good afternoon. 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 would be used for both products.
Okay. 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?
Yeah, great question. If I may just reword your question, whether they would be, one would be an sBLA, which is a subsequent to the original BLA, or whether each one of them would be separate BLAs. It is a 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.
When is the likelihood that you would know something like that?
Typically, a pre-BLA meeting is a good time to be discussing this. A pre-BLA meeting for cervical, for example, would be a good venue to discuss this topic.
Okay. Thank you.
Thank you.
Thank you. Our next question comes from the line of Mark Breidenbach with Oppenheimer.
Hey, good afternoon, thanks for taking the questions. I think I heard Frederich mention that patients in the 202 lung study would not overlap with those who are currently enrolled in the basket study lung 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. Hi, Mark. Good afternoon. I will turn this over to Frederich. 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. That's how we thought about it. Maybe I can ask Frederich to talk about the difference between COM 202 and LUN 202 cohorts.
Yeah. 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. The cohort in the LUN study is more narrowly defined. The numbers of allowed prior therapies is lower than in the COM study, where we are doing more of a signal finding study. Really, this is the follow-up step after the COM 202 study with a better defined, 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. That's where the confidence is driven from.
Okay, got it. We also saw in that Moffitt sort of proof of concept study some responses in patients who had driver mutations. Can you maybe talk a little bit about why they're being excluded from this new study? Also, can you tell us what kind of the estimated cohort size would be for each of the four cohorts that you outlined?
Sure. Another good set of questions. It starts again with Maria. 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 one round of TKI therapy. Then they have available therapy, which is platinum doublet chemotherapy. 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. The two registration-directed cohorts are Cohorts 1 and 2. Each of those are currently sized with a sample size of 40.
We have the core biopsy cohort, which is really a signal generation proof of concept objective that is sized at N equals 15. Cohort 4 is not defined with a subject size because these are patients who fail on either cohort 1 through 3. 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.
Yeah, super helpful. Thanks for taking the questions.
Sure.
Thank you. Our next question comes from the line of Boris Peaker with Cowen.
Great. Thanks for taking my questions. Maybe first on the lung. Can you comment when we're going to be seeing your lung cancer data?
Hi, Boris. Good afternoon. Yeah, we have not committed to a specific timeline for our lung data to be released.
Is that correct then to assume that regardless of what the data you're going to see 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. Obviously we have enthusiasm behind the indication to start the study.
Got you. Okay, maybe lastly, just curious, what commercial preparations are you making for lifileucel ahead of the launch? Maybe what you 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 Iovance Cares cell ordering and patient support system is ready for launch. Third, working with payers. 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 needs. On the payer front, we continue our engagements. We've had over 80 payer engagements year to date. We also meet with CMS and the Medicare Administrative Contractors or the MACs.
We feel very confident in our approach to creating access for lifileucel once it's approved. On the final front, the chain of identity, chain of custody, cell ordering, and patient support programs, we're progressing nicely, and we feel, again, very confident that once we have FDA approval, we'll be firing on all cylinders on all three 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. 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.
We also know that between the two, they're exchanging market share. There's a lot of things that we're learning at the site level, the payer level, and at the patient level.
Great. Thank you very much for taking the questions.
Thanks.
Thank you. Our next question comes from the line of Madhu Kumar with Baird.
Hey, everyone. Thanks for taking our questions. The first one kind of briefly on small cell lung cancer, would we reasonably say that the composite of the Moffitt data, let's say your own basket study data, are the basis for starting this lung cancer trial in PD-L1 low patients?
Hi, Madhu. Good afternoon. I'll try and answer the question. It was not very easy to hear you. 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 LUN202. The answer to that is yes.
Okay. Beyond objective response rate, how is duration of response in that kind of close checkpoint plus chemo PD-L1 look real driver of value in the non-small cell 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. Basically, to what extent is duration of response against an endpoint in non-small cell lung cancer, second-line setting, beyond just straight objective response?
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. It's very encouraging to see that two complete response patients continued in response past 12 months, and one of their PR patients had a response for approximately 18 months. That was highly encouraging for us in terms of median DOR.
Thank you. Our next question comes from the line of Biren Amin with Jefferies.
Yeah. Hi, guys. Thanks for taking my questions. Maria, at SITC, you talked about the abstract having nine patients. How much more data will we have next week?
Hi, Biren. Good afternoon. 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. Longer follow-up.
Okay. You had some pretty encouraging responses, I think four out of nine patients, and if you look at historical pembro, it's about 14%, 15% RR. I guess, when would you have sufficient data where you feel comfortable moving this into a pivotal study?
Yeah, 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. We continue enrolling into this cohort and, hopefully, once we have a little bit more patients sort of added and follow-up duration's a little longer, we can decide exactly how to position the product.
Got it. Maybe just the last question on LUN202, 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 estimates, or the exact sort of number of patients for each of the stages for Simons 2. Once we cross it, traditionally, we have announced that we have crossed it, and we are continuing. That has been our sort of communication strategy.
Great. Thanks for taking my questions.
Thank you, Biren.
Our next question comes from the line of Reni Benjamin with JMP Securities.
Hi, this is Justin Walsh. I'm for Reni. I have a couple questions. The first one is on the assay. 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? 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?
Hi, 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. 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. I don't know quite what assays we are going to develop and whether that would be adequate. I don't know if I can answer that question today.
Okay, thanks. I guess the other one is on your plan for the Navy Yard and commercial production. I think it said that 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. We do have a number of different options, and we work on all fronts to make sure that we are completely ready.
Perfect. Thank you for taking the questions.
Of course. Thank you.
Our next question comes from the line of Jim Birchenough with Wells Fargo.
Good afternoon. It's Nick on for Jim this afternoon. Thanks for taking our questions. First question, Maria, in your prepared comments, you noted that the Type B meeting defined the duration of treatment, sorry, duration of follow-up. Is this six months after an unconfirmed partial response? 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. 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. It doesn't necessarily mean that it's going to be any different than melanoma. Does that answer your question, Nick?
Yeah, partially. I was thinking from the Type B meeting from the melanoma data, you said you've defined what the duration of follow-up is. Is this six months, and is that after an unconfirmed PR or after a confirmed PR?
Right. It's six months from the time of PR as assessed by IRC. We did define it for melanoma, but I think that, let me maybe clarify something. The two products are under two different INDs, so the review teams are different. 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, thank you. Just a clarification on LUN-202. The clinical trial description for Cohorts 1 and 2 says, "The tumor sample via surgical resection or biopsy." From the prepared comments, it sounds like a core biopsy would not be allowed in Cohorts 1 and 2.
That's correct. Cohorts 1 and 2 have incisional biopsy, which is a traditional method of collection of tumor. Cohort 3 allows for a core biopsy, which is a much smaller amount of tumor.
Great. Thank you. Just in terms of thinking about the commercial prospects for lifileucel in melanoma. With the surgical resection or biopsy procedure, how many of those surgeons are credentialed for giving chemotherapy? How common is that, I guess, is the question.
For the surgeon to give chemotherapy? Are you referring to the-
Credentialed for chemotherapy. They're sort of, I'm not saying they're dual certified, but 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. 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. Let me ask Jim to speak to that. 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 is because lifileucel, like other cell therapies, are delivered in a coordinated fashion across multiple people. It begins with, let's say, the surgical oncologist, as you point out, to do the tumor tissue procurement process. It involves the medical oncologist, obviously, in consult with the community in many cases. 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.
Great. Thank you.
Thank you, Nick.
Our next question comes from the line of Benjamin Burnett with Stifel.
Hi, this is Kailie Briza on for Benjamin Burnett. Thanks for taking our question. I was wondering if you could provide a little bit of color as to which clinical indications you expect to leverage IOV-3001 first. 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.
Thank you so much for the questions. We have not finalized our indications for IOV-3001 program. I likely won't be able to speak to that today. We obviously look at multiple indications. 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 in IOV-LUN-202, we would. That Cohort 3 may be subject to Gen 3.
Thank you.
Thank you.
We have a follow-up question from the line of Madhu Kumar with Baird.
Yeah. Can you guys hear me okay?
Yes, much better. Thank you, Madhu.
Awesome. Great. I wanted to follow up on head and neck cancer. The data you have so far is largely in patients who received PD-1 after chemo. As Biren mentioned, there seems to be a really material difference in response rate in the frontline PD-1 population in head neck cancer and the PD-1 after chemo population. Ultimately, how do you think about the positioning of PD-1 plus TILs in head neck cancer? Is it a post-chemo drug? Is it a true frontline drug? 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?
Yeah, 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 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 with larger sample size and longer follow-up. 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 five to six months. 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 entity and approved first-line therapy, which is the extreme setting, right? It's chemotherapy or chemotherapy plus EGFR antibody. This is meaningful. That is still an approved and used first-line therapy. 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. I think that's indicating the potential here in what is a chemo-free regimen. I think we have some options here, but where we are right now is already quite meaningful.
Okay. One more, and I'm sure this is a question you get and think about all the time. Given this head neck cancer data, what about a front-line melanoma trial with PD-1 kind of upfront? What do we need to see there to kind of get that trial going? I know Rosenberg for years has kind of wanted to do that study. How are you thinking about that?
Hi, Madhu. Thanks again. Our Cohort 1A in our COM 202 study is exactly that. It's TIL plus KEYTRUDA in front line patients or immune, anti-PD-1 naive patients. I think that data would be quite meaningful in terms of their ORR and median DOR before we decide what the next steps would be.
Okay, great. Thank you.
Thank you.
We have another follow-up question from the line of Mara Goldstein with Mizuho.
Great. Thanks so much for taking the question. Iva's 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 collars around what thousands mean?
Hi, Mara. Thank you for the question. Yes, the reason we're not giving the exact number of how many thousands, presumably, I think that's what you're asking, is.
Yes.
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. When we have larger capacity, we will complete the remaining half of the facility. 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. 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.
All right. Thank you.
Thank you, Mara.
We have another follow-up from the line of Jim Birchenough with Wells Fargo.
Hi. Thanks for taking the follow-up. Maria, can you give us an update on the CLL trial, please?
Hi, Jim. Good afternoon. 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. Enrollment has recently sort of resumed. I won't be able to give you much further information beyond that.
Great. Thank you very much.
Thank you, Jim.
I'm showing no further questions. 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 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.