Iovance Biotherapeutics, Inc. (IOVA) CEO Maria Fardis on Q1 2021 Results - Earnings Call Transcript

Iovance Biotherapeutics, Inc. (NASDAQ:IOVA) Q1 2021 Earnings Conference Call May 6, 2021 4:30 PM ET

Company Participants

Maria Fardis - Chief Executive Officer & President

Friedrich Finckenstein - Chief Medical Officer

Jean Marc Bellemin - Chief Financial Officer

Sara Pellegrino - Vice President, Investor and Public Relations

Jim Ziegler - Senior Vice President, Commercial

Conference Call Participants

Michael Yee - Jefferies LLC

Peter Lawson - Barclays Bank

Mark Breidenbach - Oppenheimer

Boris Peaker - Cowen & Co., LLC

Mara Goldstein - Mizuho Securities

Avi Dahan - Truist Securities

Nick Abbott - Wells Fargo Securities

Carolina Ibanez Ventoso - Stifel Financial Corp.

Operator

Hello and welcome to the Iovance Biotherapeutics First Quarter 2021 Financial Results Conference. My name is Michelle and I will be the operator on today’s call. [Operator Instructions]

I will now turn the call over to Ms. Sara Pellegrino. Ma'am, you may begin.

Sara Pellegrino

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 Jean-Marc Bellemin, our Chief Financial Officer. We are also joined by Jim Zigler, Senior Vice President, Commercial. 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 months ended on March 31, 2021, 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 trials and regulatory plans and results, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interaction, 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 intro, I will turn the call over to Maria.

Maria Fardis

Thank you, Sara, and good afternoon, everyone. I’m pleased to highlight our first quarter 2021 progress at Iovance during today’s conference call. During 2021, we have continued to advance and expand our Iovance tumor infiltrating lymphocytes or TIL platform across multiple indications including metastatic melanoma, cervical, head and neck and non-small cell lung cancers.

For our lead TIL product candidate lifileucel and metastatic melanoma, we completed the submission of additional information related to our potency assays to FDA in support of a planned biologics license application, or BLA submission. Resolution of the potency assay with FDA is our top priority for 2021.

We also reported new and updated data from our ongoing C-144-01 clinical study demonstrating durable responses in our Cohort 2 for one-time treatment with lifileucel. The Cohort 2 data was presented at AACR 2021 and as we show on data updates, we will be presented at ASCO 2021. And additional indications, as we completed patient dosing in Cohort 2 for lifileucel in advanced cervical cancer.

For our registration-directed study of LN-145 in non-small cell lung cancer, we continue to activate sites for IOV-LUN-202 and consented multiple patients. We believe that the growing body of Iovance TIL clinical data across multiple late stage cancers coupled with results from combination of our TIL and anti-PD-1 therapy and earlier stages of the disease validate the significance and broad potential for Iovance TIL therapy.

We also continue to execute toward all manufacturing and pre-commercial activities and furthering our commitment to address the critical need of cancer patients. I am very confident in the quality of our internal team to deliver towards this mission. An impressive 76% of our more than 250 employees have at least a year of cell therapy experience.

On the call today, I would like to spend a few minutes highlighting our lead indications and manufacturing progress. Then I will let Friedrich review our recent clinical data updates.

I will begin with our first pivotal program lifileucel for advanced melanoma. As discussed in our previous calls, metastatic melanoma is a common type of skin cancer. In the U.S alone metastatic melanoma account for approximately 100,000 patients diagnosed and 7,000 deaths each year in the United States.

We are focused on the growing population of metastatic melanoma patients that have exhausted their most commonly used available care options and need alternative therapies in our C-144-01 study. At the American Association for Cancer Research or AACR annual meeting, the updated data for Cohort 2 from C-144-01 clinical study was presented at a clinical trial plenary session. The long-term follow-up data showed that median duration of response was not reached at 28.1 months of median study follow-up. Furthermore, overall response rates remain at 36.4% and we saw a continued deepening of response in 17% of the patients.

We, as well as KOLs, including the physicians who highlighted the data at AACR continue to be very enthusiastic about the durability of response, following one-time treatments with lifileucel in very difficult to treat metastatic melanoma patients. For the post-anti-PD-1 patient population and growth in Cohort 2, chemotherapy is the only currently available option and offers a 4% to 10% response rate and overall survival of only 7 to 8 months.

Further updates for Cohort 2 will be highlighted at the upcoming American Society of Clinical Oncology or ASCO annual meeting in June. Detailed Cohort 2 data has also been accepted for publication in a forthcoming manuscript in a peer-reviewed high impact oncology journal.

Turning to TIL in earlier lines of therapy at the upcoming ASCO 2021 meeting, we are excited about sharing clinical data for lifileucel in combination with pembrolizumab and anti-PD-1 naive metastatic melanoma patients. Combination of Iovance TIL with available therapies and anti-PD-1 naive patients is one of Iovance's main clinical goals toward moving TIL into earlier treatment settings. Melanoma is the second clinical setting and with such combination is tested and data are being provided.

As previously mentioned, reaching agreement with FDA on the potency assays for lifileucel is a top priority for Iovance. While the length of time until BLA submission depends on feedback from the agency, we continue staying prepared for a BLA submission in 2021. We plan to provide updates when available. Our second pivotal program is investigating LN-145 now also known as lifileucel, in this C-145-04 study to support a BLA submission in metastatic cervical cancer.

During the first quarter, Cohort 2 patient dosing with lifileucel was completed in post-anti-PD-1 cervical cancer patients. We believe that a BLA submission that includes both co-pivotal Cohort 1, which is evaluating lifileucel post chemotherapy, in addition to Cohort 2 may strengthen the potential label and reflects the expected upcoming treatment landscapes in cervical cancer.

As we have mentioned before, the resolution of the potency assay for lifileucel in melanoma and dialogue with FDA around the amount of clinical data follow-up are key steps toward our BLA submission in the cervical cancer indications. As a reminder, the FDA has previously granted both breakthrough therapy and Fast Track designation for lifileucel and cervical cancer.

Turning to our manufacturing facility, Iovance cell therapy center, or ICTC, we have completed construction of the exterior core and shell as well as initial clean room and we have moved in. Process equipment and necessary utilities are now in place in the available clean rooms and activities have commenced to support the start of TIL clinical manufacturing in late 2021.

Commercial manufacturing of Iovance TIL remains on track for 2022 with capacity to meet the demand for up to 1,000s of patients in multiple indications. Iovance has transformed TIL manufacturing from a lengthy academic process to a shorter, scalable, centralized GMP process yielding a cryopreserved product. Our Gen 2 process is 22 days. To date, more than 450 patients have received Iovance TIL with a continuing success rate above 90%.

We are also looking forward to the potential to further improve the TIL manufacturing timelines and efficiencies. A shorter 16 day third generation Iovance TIL manufacturing process or Gen 3 is being explored in two of our clinical studies. The patients receiving Gen 3 TIL include a cohort of metastatic melanoma patients in the IOV-COM-202 clinical study where patient dosing has initiated as well as a cohort of a non-small cell lung cancer patients in the IOV-LUN-202 study.

We’ve also built and continued to augment our intellectual property which is covered by more than 25 granted or allowed U.S and international patents. Granted patents include composition and methods of treatment in a broad range of cancers relating to the Gen 2 manufacturing process with expected exclusivity through 2038.

Iovance patent applications and granted patents are also directed towards Gen 3 manufacturing, selected TIL products, stable and transient genetic modification of TIL, tumor digest and fragment composition and methods including cryopreservation and combination of TIL with checkpoint inhibitors.

In addition, as noted in this afternoon's press release, we have licensed additional patent rights from National Institutes of Health, or NIH for cytokines tethered TIL technology including IL-15 and IL-21 and similar technology. We also expanded our worldwide field of use to all cancers. We believe that this expanded license and relationship with NIH may further solidify our leadership in the advancement of TIL and related intellectual property.

Turning to our pre-commercial launch preparations, we remain disciplined in our gated approach to commercial readiness. Our core commercial team continues to build the foundation for site training, patient access, payer coverage and other commercialization readiness activities. We are well-positioned to rapidly scale and expand efforts across these areas pending alignment with the FDA on our potency assay.

Our medical affairs team maintains clinical site engagement in preparation for commercial launch. This team continues to work with key opinion leaders and patient advocacy groups until awareness and educational program and to ensure scientific communication at major conferences and in peer reviewed publications. Commercial team is partnering with the leading U.S cancer centers to build their TIL service line capabilities.

Our training and onboarding program, which we will further expand upon BLA submission is designed to ensure cross the supplier team can administer the lifileucel treatment regimen upon FDA approval. Our market access team continues to engage payers to ensure patients have access to lifileucel. Very recently the centers for Medicare and Medicaid Services, or CMS, proposed two new international classification of diseases, 10th revision, procedure coding system or ICD 10 codes for lifileucel.

Additionally, CMS proposed to map lifileucel to existing MS-DRG 18. CMS also proposed to expand MS-DRG 18 from CAR T cell immunotherapy to CAR T cell and other immunotherapies including Iovance TIL. We believe that CMS's proposal to include lifileucel in existing MS-DRG 18 is recognition of the value of Iovance TIL and cell therapies for patients and the need to ensure appropriate reimbursement for providers beyond CAR T. The proposal, if finalized, has the potential to strengthen hospital reimbursement for lifileucel therapy at the time of launch. We appreciate CMS's leadership and commitment to access to care.

The Iovance team is also developing our IOVANCECares program which remains on track. Our goal is to deliver a best-in-class chain of custody and chain of identity system, cell ordering platform and patient support capabilities. IOVANCECares is designed to be both customer and patient centric throughout the lifileucel treatment journey.

I will now pass the call to Friedrich to outline our clinical update. Friedrich?

Friedrich Finckenstein

Thank you, Maria. I am pleased to highlight recent and upcoming clinical data updates for Iovance TIL alone and in combination with pembrolizumab in melanoma, as well as the status of four ongoing clinical studies. Our drug development strategy focuses on cancer populations with high unmet need, with substantial opportunity for TIL to make a meaningful impact.

First, as Maria mentioned, we provided an update for Cohort 2 and our C-144-01 clinical study at AACR at approximately 28.1 months of median study follow-up and longer term updates have been accepted for oral presentation at ASCO. We are also looking forward to an upcoming peer reviewed publication of detailed Cohort 2 data.

At the upcoming ASCO meeting, we are also looking forward to the poster presentation of initial clinical data in the IOV-COM-202 study from Cohort 1A which is evaluating lifileucel in combination with pembrolizumab in melanoma. This will represent a second indication with clinical data for Iovance TIL in combination with pembrolizumab in earlier treatment settings following the encouraging data and head and neck cancer presented at last year's Society for the Immunotherapy of Cancer or SITC meeting.

While pembrolizumab yields 33% response rate, 6% of which are complete responses in patients with melanoma, 40% to 65% of patients still progress on or after treatment. Therefore, in anti-PD-1 naive metastatic melanoma there remains a need to increase the overall response rate and then in particular, the complete response rate. We also continue to recruit patients across four clinical studies with Iovance TIL.

Our C-145-04 clinical study in advanced cervical cancer has completed patient dosing in the first two cohorts. We continue to recruit a third cohort of anti-PD-1 naive patients to receive Iovance TIL plus pembrolizumab. We have now activated a total of 10 sites and consented multiple patients for our registration supporting study IOV-LUN-202 in second line non-small cell lung cancer.

We believe that the patient population in IOV-LUN-202 as well as the three non-small cell lung cancer cohorts in the basket study allow us to broadly address the unmet needs in non-small cell lung cancer. Recruitment also continues in our IOV-COM-202 study of Iovance TIL and TIL combinations across melanoma, head and neck and non-small cell lung cancers, in addition to the IOV-CLL-01 study in CLL/SLL.

As the impact of the COVID-19 pandemic on hospitals results, following the rollout of the COVID-19 vaccines and as the virus abate, we hope to be able to provide additional data at future medical meetings.

I will now hand the call over to Jean Marc, to discuss our first quarter 2021 financial results.

Jean Marc Bellemin

Thank you, Fred. My comments will reflect the high level financial results from our first quarter of 2021. Additional details can be found in this afternoon's press release as well as in our SEC filings.

I will begin with our cash position. As of March 31, 2021, Iovance held $610.2 million in cash, cash equivalents, investments and restricted cash compared to $635 million on December 31, 2020. A strong cash position is expected to be sufficient into 2023 to deliver on our pipeline programs.

Moving on to the income statement, our net loss for the first quarter ended March 31, 2021 was $75.4 million or $0.51 per share, compared to a net loss of $69.6 million or $0.55 per share for the first quarter ended March 31, 2020. Research and development expenses were $55.9 million for the first quarter ended March 31, 2021, a decrease of $1 million compared to $57 million for the first quarter ended March 31, 2020. The year-over-year decrease in research and development expenses was primarily attributable to a decrease in manufacturing and clinical costs following the completion of enrollment in the pivotal costs for melanoma and cervical cancer.

General and administrative expenses were $19.6 million for the first quarter ended March 31, 2021, an increase of $5.8 million compared to $13.9 million for the first quarter ended March 31, 2020. The year-over-year increase in general and administrative expenses was primarily attributable to growth of the internal general and administrative team and higher stock-based compensation expenses. As of March 31, 2021, there were approximately 149.3 million common shares outstanding.

Looking ahead, we remain focused on investment in four key areas to ensure the growth and strength of our value creation. First, advancing our current clinical programs and indication. Second, scaling up our manufacturing capacity to support our clinical manufacturing, while preparing for expected commercial supply in 2022. Third, ensuring launch readiness; and fourth, maintaining a strong balance sheet and cash position. I remain confident that by managing our investments across these four priorities, we will continue to stay focused and aligned on our spending with our corporate priorities.

I will now hand the call back to the operator to kick off the Q&A session.

Question-and-Answer Session

Operator

[Operator Instructions] The first question in the queue comes from Peter Lawson. Sir, your line is open. Please proceed. Okay. We'll go to the next question. Michael Yee, your line is open. Please proceed.

Michael Yee

Okay, thank you. Can you hear me okay, Maria?

Maria Fardis

Yes, we can. Hi, Michael.

Michael Yee

Hey. Hey, guys. Thanks and appreciate the update. In the interest of I guess one question, our question was regarding the commentary around the progress and submitting additional data for assays. And the question was around your confidence level that things are absolutely moving on a pace to get an agreement. And if there was an agreement, you would just be able to come out and say that? And if that was not going along the right path, the mechanisms to be able to either engage with the broader ODAC team, or do other things to just be able to go ahead and push a little harder. Sorry for the different questions here. But it's all kind of related to the confidence level in the time lines. Thank you.

Maria Fardis

Understood. Thank you so much, Michael. We have submitted as we noted, we have submitted our prior responses to the agency, to the questions that were issued as part of the type B meeting. We also have now provided the validation data that we had committed to provide to FDA as part of our responses in Q1 of 2021. We have not heard back from the agency, and I think a degree of confidence would depend on feedback from that we really do need to hear from them. In terms of mechanism of escalation, there are definitely mechanisms by which we can escalate. We have been talking to FDA management to assure that we're able to at least get a response in a timely manner. So, yes, there are venues and we certainly have considered them.

Michael Yee

Thank you very much.

Maria Fardis

Thank you.

Operator

Okay. And Peter Lawson, your line is open. Please proceed.

Peter Lawson

Great. Thank you so much. Sorry, I joined late. So I apologize if you run through this. But when -- in lung cancer, when you think about the subset kind of post-TKI and PD-1 high and low and failed, where do you think TIL therapy could potentially fit in? Where do you think you've got the best shot at generating efficacy over both existing and emerging therapies coming through?

Maria Fardis

Hi, Peter. Thank you for the question. The study that was conducted by Moffitt and was published at AACR 2020 was incredibly helpful in showing that really didn't seem to be a particular sub population that was responding to TIL or not responding to TIL. What you might have seen is patients who had a PDL-1 lower expression level, we're still among the responders, or patients that were post-TKI if they had an oncogene driver mutation. So that's highly encouraging. It's quite consistent with the [indiscernible] of TIL where there's not a specific sub population that may not respond to TIL.

Now our study designs such as the specific IOV-COM-202 or LUN-202 is more designed with a registration-program in mind. So LUN-202 specifically is a -- potentially supportive of registration. And so the sub population that we selected there is trying to identify a patient population that is both an unmet medical need, and yet early enough in lines of therapy that the patients have an opportunity to benefit from TIL. It's not selected based on where we think TIL may be active or not active. It's really what we see is TIL seems to be active, regardless of the subpopulations to the degree we have data in non-small cell.

Peter Lawson

Got you. Thank you. And then this may be addressed, but when was the last time you spoke to the FDA? I know the FDA is kind of not on a time clock with you. But when was the last time you spoken about the BLA? And when do you anticipate speaking again? And do you think things are moving forwards or they paused or just your sense around that dialogue?

Maria Fardis

Sure. So FDA is a pretty large body. The review team or formal meetings is one venue for communication. There certainly are informal other ways of talking to FDA through either regulatory project managers or other venues. But the dialogue with agency is very much ongoing. It doesn't necessarily mean this is a -- [indiscernible] sort of a new type of a meeting, like a type B meeting. But there definitely is dialogue between our regulatory team and FDA to make sure that they have received the package at the satisfied time to review it and they will respond to us in a timely manner.

Peter Lawson

Great. Thank you.

Operator

The next question in the queue comes from Mark Breidenbach. Your line is open. Please proceed.

Mark Breidenbach

Hey, good afternoon, and thank you for taking our question. Just switching over to the upcoming data from lifileucel combined with pembrolizumab in frontline melanoma, I'm curious how many patients we're likely to see in that presentation. Maybe ballpark how much follow-up we can expect. And Maria I'm also curious to hear your thoughts on what you see as likely next steps for development in an early line setting with this basket trial cohort potentially balloon into a randomized study versus single agent pembro? Or what do you have in mind assuming these initial data look good?

Maria Fardis

Sounds good. Thank you, Mark. The number of patients has not quite been disclosed once the abstract come out away from embargo, we can certainly discuss how many patients are in there. What I can say is that the cohort itself was designed for 12 patients and the cohort is still open. So it's still continuing to enroll into the cohort. In terms of what the next steps would be, it is important for us to understand with larger number of patients and longer follow-up what the real data is. These early looks are really helpful for us to understand what the potential maybe, but at the same time, we recognize that we want to make sure we have a large enough sample size that we understand what the product is or is not doing.

In terms of next step, I think once the data is visible, it's a little bit easier to speak to it. In general, speak -- I'll answer your question is general sense. Typically, when you have a combination in early line, the next step typically is a randomized study that would show the contribution of elements. I do not rule out single arm in general, if the contribution of elements is extremely high in that single arm. There may be possibilities of talking to the agency and defining the registration path with a single arm. It's not very common, though. So typically around a whitespace, three type would be a next step to take.

Mark Breidenbach

Got it. Thanks for taking the question.

Maria Fardis

Thank you.

Operator

And the next question in the queue comes from Boris Peaker. Your line is open. Please proceed.

Boris Peaker

Great. Just wanted to ask in terms of the lung cancer cohorts. When should we be expecting updates from those? And what are some of the factors that go into kind of deciding the timing of those updates?

Maria Fardis

Hi, Boris. Good afternoon. Yes, absolutely. So we have really two cohorts that have lung cancer patients. One is in our basket study. The COM-202 study has two cohorts, cohorts 3A and 3B. Cohort 3A which is early line patients with treatment naive or actually PD-1 naive patients. It has been a little bit slower to enroll during COVID and this may very well be the impact of hospitals haven't been impacted by COVID as well as the fact that these patients obviously have available therapies to receive at their local institutions.

In Cohort 3B, we do have some patients. We have not committed to a specific data flow timeline. We drew the conclusion that patients that are second line are certainly much better in terms of non-small cell. The activation [ph] from first-line to second-line in non-small cell lung cancer is quite large. Unfortunately, many patients, around 70% of the patients don't make it to second line. So we are trying to limit our subsequent upcoming cohorts to second line non-small cell. But we do have some patients in that Cohort 3B, which once we have long enough follow-up we could disclose the data. We haven't committed to a specific venue or a timeframe yet.

Boris Peaker

Great. Thank you very much for taking my question.

Maria Fardis

Thank you, Boris.

Operator

And the next question in the queue comes from Mara Goldstein. Please proceed.

Mara Goldstein

Great. Thanks so much for taking the questions. Just a couple of things. First, I just wanted to circle back to make sure that I understood correctly on the submission that was made to the FDA around the assay that the FDA is not obligated to respond to you within a specific timeframe for that submission. And on the cervical program, can you give us a bit more background on how the decision was made to combine the two cohorts? And was that made based on discussions with FDA? And where does that leave a potential filing timeline? And then the last thing I had was just a curiosity more than anything on the reimbursement fund and the determinations that have been made around cohorts and whatnot. Is there a specific time limit in which those must be made active such that you don't have to reapply back to the agencies?

Maria Fardis

Mara, just with your first two questions, let me answer them, but I didn't catch quite your third question. Let me try and answer the first two and then I'll ask you to repeat number three. In terms of the assay, you're correct. The agency is not on a PDUFA clock to answer in a given timeline. However, when a CMC IND amendment is submitted to the agency, there's guidelines that typically limit the duration of IND review. It's usually 1 to 2 months. And so that guideline is what we are sort of referring to and waiting for the agency to respond within that window of opportunity.

In terms of cervical, we have been quite committed to combining the cohorts. I just want to be sure that we're clear. We gave the visibility to investors that we have the possibility of combining Cohorts 1 and 2. It's certainly subject to discussion with FDA. Cohort 1 were patients that were posed chemotherapy in a metastatic setting, and Cohort 2 were patients that also could have received anti-PD-1 in a metastatic setting.

Now, the reason we kind of went down that path is we wanted to make sure that the investors are aware that there's a possibility, given the potential change in the landscape of cervical cancer, there's a possibility that the agency may request Cohort 2 and/or Iovance may want to include that data. So it's very much subject to discussion with FDA. If that addresses your questions one and two, do you mind repeating your question three?

Mara Goldstein

Sure. On question two, if you do -- if the determination is that those cohorts will be combined from a potential filing perspectives, is that -- what does that do to sort of the internal timeline that you have, or the one that you shared?

Maria Fardis

Understood. Understood. From a timing perspective, just to kind of lay out what is required to reach a cervical BLA, let me just sort of lay out the steps that are needed. First and foremost, we absolutely want to make sure that our potency assay issue is resolved with the melanoma team, which is right now the dialogue that is ongoing. As a next step, you still do need to meet with the cervical review team to discuss the amount of follow-up you’re going to request and whether Cohort 1 plus Cohort 2 is something they want, or they want to stay just with Cohort 1. And subsequent to that we can think about sort of the BLA timeline. A scenario during which this submission can happen later part of this year is still in the picture from my perspective. It really depends on when we get the potency assay results.

Mara Goldstein

Okay. That's great. And then I was just curious, as you were discussing in the top of the call around having determinations from CMS and whatnot around potential codes such that you could get reimbursed. I know, typically, those needs to be in the books, I believe, by August. And so I'm just curious, do you have to have a commercialized product within a certain amount of time, as those are still valid. So would you have to go through this exercise again next year?

Maria Fardis

Sure. Let me ask, Jim, to actually address that question. He's in the room with me.

Jim Ziegler

Thanks, Maria. Hi, Mara.

Mara Goldstein

Hi.

Jim Ziegler

With respect to the DRG, if it's approved, be approved upon product approval, I think your real question is around N-CAM [ph]. So for products or technologies that are approved by 1 July, they would be implemented in the next fiscal year, beginning 1 October. So in this case, 2022. For products that don't meet that 1 July approval date would have to be resubmit with a N-CAM. There are two separate processes, right. So one is with the DRG, the other one [indiscernible].

Mara Goldstein

Okay. I appreciate the clarification on that. Thank you.

Operator

Thank you. And the next question in the queue comes from Asthika Goonewardene. Your line is open. Please proceed.

Avi Dahan

Hi. This is Avi for -- on for Asthika. Can you hear me?

Maria Fardis

Yes, we can.

Avi Dahan

Hi. Good afternoon. So one quick question about license agreement with the NIH. Can you just give a little color on -- so this -- these are exclusive agreements and every time there's a BLA approval, you're subject to paying out a low single-digit $1 million payment, right?

Maria Fardis

That's correct.

Avi Dahan

Okay, got it. And one last thing, just circling back with the FDA, a lot of clarity today. Thank you. But one -- so you mentioned that it was a 1 to 2 month general guidelines, but it's not required by the typical PDUFA date. So your last -- when -- can you give a little more clarity on like, the day or the week you guys submitted the most recent data back to them?

Maria Fardis

Thank you, Avi, for the question. So we didn't disclose the exact date, but we did say that we have submitted the validation package to the agency in Q1. We had committed to investors to do and that was completed on time.

Avi Dahan

All right. Thanks. Thanks for our questions.

Maria Fardis

Sure. Thank you so much.

Operator

The next question in the queue comes from Madhu Kumar. Your line is open. Please proceed.

Unidentified Analyst

Hey everyone. Can you guys hear me okay?

Maria Fardis

Hi, Madhu. Yes, we can.

Unidentified Analyst

Okay, great. So, kind of thinking about the frontline melanoma trial a little bit, I guess kind of in a very simple question where do you think are the gaps in frontline melanoma on PD-1 blockade where TILs can provide specific benefit like duration of response, complete response? Where do you think there's a kind of window for TILs plus PD-1 to give edge?

Maria Fardis

That's a great question, Madhu. So melanoma is a disease that is fairly well addressed with checkpoint inhibitors. However, I think that it really depends on the data itself. And I think we can comment a little bit more once the data for TIL plus pembro shows up at ASCO. There's certainly -- there's always room for improvement if the patients are not reaching a complete response, or that their duration of response could be improved. So from my perspective, a patient that experiences a deep durable response in frontline, he offers a lot of benefits to the patients. The clear second unmet need is exactly what we have been doing, which is the post PD-1 patient population. I'm going to ask Friedrich to comment, if he has anything to add. Did you want to add to this?

Friedrich Finckenstein

I agree, Maria. What we shouldn't forget that although a lot of progress has been made with the checkpoint inhibitors and various indications, the majority of patients still will progress either primarily or secondarily because of resistance mechanisms, you will make that less likely and you will increase benefit by pushing down the responses even deeper and complete responses are a real, real good goal here. So I think I totally agree with Maria that is really where there's room for improvement.

Unidentified Analyst

Okay, great. And kind of the follow-up on some of the questions around the cell potency assay issues. I mean, I guess kind of ultimately to what extent is this whole situation about kind of educating the FDA about the differences between TILs and kind of earlier generation cancer cell technologies like CAR T. And to what extent is about kind of you mentioned, having a panel of cytokines type factors that demonstrate kind of T cell potency beyond just a single type of factor assay to demonstrate T cell potency?

Maria Fardis

It's a great question, Madhu. I don't know if I can comment on educating the agency. I mean, the agency is certainly on our review team, there are members who have been at NCI before. Now how much internal communication there is, it's a little hard for me to sort of comment on that. I can tell you that the request that they have made so far have been reasonable in the sense that they're not asking for example, for a go find yourself an antigen specific aspect, that would have told me that, well, for TIL it's going to be very difficult to do. But that type of a request hasn't come through. So which tells me that they do understand the power of TIL is the fact that it ultimately addresses multiple neoantigens, and it is highly, highly polyclonal. So I think that maybe education is not the right word, maybe the way is to better define it first-in-class product with this sponsor. There definitely is some time that needs to be spent between both the agency and the sponsor and trying to define how do we define such a complex product. I think that that's probably the true statement.

Unidentified Analyst

Okay, great. Thanks, guys.

Maria Fardis

Thank you.

Operator

Thank you. And the next question in the queue comes from Nick Abbott. Your line is open. Please proceed.

Nick Abbott

Hey. Good afternoon. Thanks for taking my question. Maria [indiscernible], so in the current JCO, Jason Luke and colleagues report encouraging data for the combination of PD-1 and CTLA-4 in patients who really considered primary PD-1 failures acknowledging these are largely second line CTLA-4 naive patients. And so clearly not apples to apples with lifileucel registration cohort. Do you think these data change the use of that tablet in sort of second line setting and does it create a barrier for lifileucel use? Thanks.

Maria Fardis

Hi, Nick. Thank you for the question. I'll do my best to give you preliminary answers. I'm going to invite Friedrich to also comment. I do -- we have seen the manuscripts. I'm glad you're -- its getting noticed. I highlight a few differences between the manuscripts in terms of the patient population the endpoint with what Iovance is doing. The endpoint that is reported at the manuscript is IR resist, not resist 1.1. Resist 1.1 is a regulatory endpoint that has been very well understood and requested by FDA. IR resist is an immune mediated type of endpoint and has not been really accepted by the agency as an appropriate endpoint.

In terms of the patient population, this is strictly speaking, second line and in some cases frontline metastatic patients because they could have had adjuvant therapy, and subsequent to that they would have entered the study. I highlight a couple of other points. There amount of time on prior anti-PD-1 as the median was reported at 4.8 months. That's a pretty short duration of time. It probably looks like a primary refractory patient population.

What was also remarkable from my perspective, was the time from prior anti-PD-1, which was quite short. And that may yield to the previous products still being on board given the long [indiscernible] CD-1. The median duration of response had been lately [ph] reported. And some of the patients, as I noted, were coming from an adjuvant setting. So I think that there's meaningful differences both between the endpoints as well as the patient population making it very difficult to compare. Friedrich, did you want to add any comments to this?

Friedrich Finckenstein

I think maybe a couple of comments kind of compare and contrast also. This is an academic paper, this was generated in seven U.S sites. The data that we are presenting for our program is a global multicenter study, I think that is relevant in this context as well. And maybe one -- just one quick comment on the nature of the therapy. The treatment that was explored and this [indiscernible] still requires continuation of pembrolizumab for up to 2 years, which is a big contrast to a one-time treatment with the lifileucel regimen. And that is meaningful as well. And other than that, I think Maria summarized the differences very well.

Maria Fardis

Yes. Just maybe add one more point, Nick, that I was reminded. Again, strictly speaking, they're stuck in line at the latest. Many of the patients, a percent of the patients were first line sort of systemic therapy, and then -- some of them were second line. The patients had not received for anti-CTLA-4 or other therapeutics, which is pretty much a reality of life for these patients nowadays and outpatients [indiscernible] system.

Nick Abbott

Okay. Thank you.

Maria Fardis

Thank you.

Operator

And we have one more question in the queue. And that question comes from Ben Burnett. Your line is open Mr. Burnett.

Carolina Ibanez Ventoso

Hi. Good afternoon. This is Carolina Ibanez Ventoso on for Ben Burnett. My call drop here, so my apologies if you already touch on this. We were wondering if you could talk a bit more on the Cohort 3 arm of the cervical cancer study. And did you expect these will be needed for approval?

Maria Fardis

Hi, Carolina. If I understand -- let me make sure I understand the question. Were you asking about Cohort 3 of cervical?

Carolina Ibanez Ventoso

Yes, correct.

Maria Fardis

So Cohort 3 is patients that are PD-1 naive and they get [indiscernible] PD-1. Is that the cohort you're asking? Or are you asking about Cohort 2?

Carolina Ibanez Ventoso

No, I'm asking about Cohort 3, and if you find that this will be needed for approval?

Maria Fardis

Great questions. I don't believe so. That was really an exploratory cohort that we started trying to understand what a combination of TIL plus pembro in PD-1 naive patients would yield. So this has not been subject to any regulatory discussion. The patient population is an earlier line patient compared to Cohort 1 and 2. Cohort 1 was discussed with FDA. Cohort 2 is the patient population which is post-PD-1 as well as post chemotherapy and we think this is a landscape of patients that is coming, so we have added the cohort into the program and we think it might be also important in submission of the BLA.

Carolina Ibanez Ventoso

Okay, perfect. Thank you.

Maria Fardis

Thank you.

Operator

Okay. We have no further questions at this time. Thank you ladies and gentlemen, this will conclude today's teleconference. Thank you for participating. You may now disconnect.