Good afternoon, and welcome to Iovance First Quarter 2020 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After the speaker’s presentation, there will be a question-and-answer session.

[Operator Instructions] Please be advised that this call consists of a recording of prepared remarks followed by a live question-and-answer session. 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, Howard. Good afternoon, everyone and thank you for joining us. Speaking on the call today, we have Maria Fardis, our President and Chief Executive Officer; Friedrich Finckenstein, our Chief Medical Officer; and Tim Morris, Chief Financial 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 first quarter ended on March 31, 2020 as well as a corporate update.

Before we start, I would like to remind everyone that statements made during this conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans, pre-commercial activities, clinical trial, plans and results potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, collaboration, impact of COVID-19 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'll turn the call over to Maria..

clinical site engagement in preparation for commercial launch, development of a close collaboration with health care professionals or HCPs who will be handling and administering our product, operational excellence by Iovance in provision of the product, and communication with payers.

We anticipate that centers with prior TIL experience and those with key opinion leaders for melanoma and cervical cancer will be the initial target for the launch of lifileucel and LN-145 subsequent to approval. In the United States, we currently work with over 20 clinical sites for melanoma and approximately the same number of sites for cervical.

Iovance is targeting to train and onboard well over 20 sites at launch and we expect to expand to additional sites over time. 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.

On the reimbursement and patient access front we have continued discussions with private payers and CMS to ensure timely access to TIL therapy for patients. And under a patient-centric model we intend to support the patient at every step of the process from initial resection to infusion.

We are developing a patient support hub with the mission to enable lifileucel patients and providers to create a seamless treatment journey by providing support through a single point of contact our hub case managers.

As our market research and commercial preparation continues we look forward to providing updates on our launch and throughout the year. I would like to now ask our Chief Medical Officer, Friedrich Finckenstein to provide an update about recent and upcoming data presentations as well as our other clinical programs at Iovance.

Friedrich?.

Thank you, Maria. I would first like to touch upon the recent American Association of Cancer Research AACR Virtual Meeting 1 where our collaborators at Moffitt Cancer Center presented data on TIL they have manufactured in non-small cell lung cancer.

As a reminder Moffitt TIL is not the same as Iovance's TIL but it uses a process similar to the Iovance Gen 1 manufacturing process and is expected to be a proof-of-concept for TIL in non-small cell lung cancer.

We were very pleased to see Moffitt's TIL show durable complete responses in non-small cell lung cancer which is such an unmet medical need indication. The initial data from Moffitt is the foundation for our strategy to investigate our own Iovance TIL in two cohorts of non-small cell lung cancer patients in our IOV-COM-202 basket study.

And the most recent data from AACR further reinforces this strategy. Looking ahead, we are pleased that ASCO has accepted the new updated data from cohort 2 from our C-144-01 clinical study of lifileucel in advanced melanoma in an oral session.

We submitted the abstract to further illustrate the durability in results of longer follow-up of metastatic melanoma patients treated with a one-time treatment of lifileucel. As a reminder, the most recent update on overall response rate or ORR was 36.4% in 66 patients as assessed by investigators.

These data were presented in November 2019, at the Society for Immunotherapy of Cancer or SITC Annual Meeting. As of our Iovance corporate update in January 2020, median duration of response or DOR for cohort 2 was still not reached at 15.5 months of median study follow-up.

Published data in similar late stage patient populations shows median overall survival may reach seven to eight months. So the results with lifileucel are highly encouraging. Moving on to our other studies. We continue to advance TIL in the clinic in additional indications, as well as in earlier lines of therapy.

All key activities across our clinical programs continue and we think that the one-time treatment approach may offer a particularly attractive option for patients and treating physicians.

These studies include, the IOV-COM-202 clinical study, which we also refer to as our basket study to evaluate the broader potential for TIL treatment in earlier lines of therapy for checkpoint naive melanoma, head and neck and non-small cell lung cancer.

Furthermore, this study has two additional cohorts for relapse/refractory melanoma and non-small cell lung cancer to receive TIL. The ongoing C-145-03 clinical study in head and neck cancer, which remains an important indication for Iovance.

This study also introduces new TIL product into the clinic including LN-145 manufactured with our new proprietary 16-day third-generation or Gen 3 TIL therapy process as well as LN-145-S1, which is our proprietary PD-1 selected TIL product. I will now hand the call over to Tim to discuss our financial results..

Thank you, Friedrich. My comments will reflect high-level financial results from our first quarter 2020. Additional details can be found in the press release that we distributed earlier as well as in our report on Form 10-Q to be filed shortly with the SEC.

Net loss for the first quarter ended March 31, 2020 was $69.6 million or $0.55 per share compared to a net loss of $37 million or $0.30 per share for the first quarter ended March 31, 2019.

Research and development expenses were $57 million for the first quarter 2020, an increase of $26.1 million compared to $30.9 million for the first quarter of 2019.

The increase in first quarter 2020 over the prior year period was primarily attributable to an increase in costs associated with the license to the IOV-3001 IL-2 analog from Novartis, higher clinical trial costs due to higher enrollment, the growth in the internal research and development team and increased manufacturing activities.

General and administrative expenses were $13.9 million for the first quarter 2020, an increase of $4.8 million compared to $9.1 million for the first quarter of 2019.

The increase in the first quarter 2020 over the prior year period was primarily attributable to the growth of internal general and administrative team and higher stock-based compensation expenses.

At March 31, 2020, the company held $251.2 million in cash, cash equivalents, short-term investments and restricted cash as compared to $312.5 million at December 31, 2019. The first quarter 2020 spend included one-time upfront license payments and the stocking of clinical materials to be used throughout 2020.

I will now hand the call back to Maria to review upcoming milestones and to kick off the Q&A session..

Thank you all for attending the call today. We look forward to an exciting and productive 2020. In closing, I would like to reiterate that our anticipated milestones all remain on track for this year including last patient to be dosed in the pivotal program for LN-145 for cervical cancer, pre-BLA meeting with U.S.

FDA, melanoma top line pivotal data and BLA submission. Overall, I'm very pleased with the progress we have made and our continued prospects to become the leaders in TIL development manufacturing and commercialization. I will now turn the call over to operator for questions.

Operator?.

[Operator Instructions] Our first question or comment comes from the line of Mara Goldstein from Mizuho. Your line is open..

Thank you very much for taking the question. If I could just return to the AACR data from Moffitt.

And I'm curious as to how you would characterize the similarities between the Moffitt trial and your own clinical program and the differences? And then just based on the potential timing of filings and FDA designations, is it possible to see a potential BLA approval in cervical before melanoma?.

Thank you, Mara..

Thanks..

Of course. From a difference perspective between Moffitt and Iovance program, there definitely is a difference in manufacturing method, the manufacturing method that is being utilized at Moffitt is a six-week manufacturing process, which is more similar to Iovance's Gen 1 manufacturing.

While Iovance's manufacturing method of course is the Gen 2 which is a 22-day manufacturing process. So there's definitely differences in the process of manufacturing product itself. There also is a difference in how we treat the actual TIL. They use a process which I call a tumor banking model.

The patient is seen and initially resected, the tumor that is resected then undergoes the process of initiation of pre-rep and rep for TIL manufacturing process. In the ,meantime the patient is treated with nivolumab at least four doses are administered.

And if the patient is progressing a confirmation of progression is conducted and then and only then they receive their TIL followed by nivolumab. We don't use that process. We are using a process by which TIL as well as KEYTRUDA in one cohort where we are doing TIL plus KEYTRUDA are given approximately concomitantly.

In Iovance's study, there's two cohorts that we administer TIL in. One is a cohort 3A and that's patient population which is PD-1 naive and a Cohort 3B, which is PD-1 relapse or refractory. So in Cohort 3A, we administered TIL plus KEYTRUDA. In Cohort 3B, we administered TIL alone. Let me pause there.

There are a few other modifications that are different between the Moffitt study as well as Iovance's, but those are the high-level indications sort of in terms of modifications.

From an indication perspective, I believe we likely would be either submitting melanoma ahead of cervical or concomitantly and both of them are on the table in terms of discussions with FDA..

Thank you very much..

Thank you, Mara..

Thank you. Our next question or comment comes from the line of Peter Lawson from Barclays. Your line is open..

Hi. Thanks for taking my question. Just as we think about these differences between your manufacturing and Moffitt's manufacturing.

Do you have any evidence from your Gen 1 versus Gen 2 about the kind of the depth of responses you could potentially get or how it could change the broadness of the response rates that we could be thinking about with your data? And then I guess the follow-up around that would be when would we see the next lung cancer data from you?.

Sure. Thanks Peter. We -- since we are not utilizing Moffitt's manufacturing process, it's very hard for me to compare. But allow me to speak to our Gen 1 versus our own Gen 2. We did publish differences between these two manufacturing methods at SITC 2017. We showed youth markers being different in our Gen 2 versus Gen 1.

Gen 2 having better youth markers and activity markers as well as better potency as measured by interferon gamma production. So we believe our Gen 2 is maybe possibly slightly a better product compared to our own Gen 1. In terms of data from our own basket study, we had initially thought about releasing data earlier on.

But as it's very noticeable from the Moffitt study, the heterogeneity of the non-small cell cancer patients is quite broad. So we are currently thinking that we might really want to have five -- at least 10 patients maybe before we release the data. But we have not committed to when that would be. This study is, obviously, open and enrolling.

And so, when we have adequate amount of data and follow-up, we're able to present that. But we have not committed to a time frame for presentation..

Thanks so much for taking the question..

Thank you. Our next question or comment comes from the line of Jim Birchenough from Wells Fargo. Your line is open..

Yes. Hi, guys. Congrats on all the progress. A quick question and follow-up.

One you might not be able to answer, but just on the ASCO presentation from Cohort 2 for melanoma, should we assume that a median duration of response has been reached? I'm not asking for the number, but just whether the presentation of this updated data suggests a median has been reached.

And then, just in terms of your own cohorts in non-small cell lung cancer, anything that you've learned from the Moffitt in terms of mutational burden and whether you think skewing towards a high mutational burden makes sense over a low mutational burden. Just wondering if there's any differences along those lines in your lung cohort. Thanks..

Sure. Thank you, Jim, for the question. In terms of ASCO presentation and thank you for recognizing that, of course, the abstract itself -- the title has only released. The abstract itself is still under embargo. But all I can say is that we're very excited that ASCO has accepted updated Cohort 2 data as an oral session.

We submitted the abstract, obviously, back in February time frame with a longer follow-up data that we had and we believe that this product offers great benefit as a one-time treatment to the patients. And so, I'm not confirming in any way that a median DOR has been reached, but we are very excited about the data as a matter of fact.

In terms of the non-small cell data. From the response perspective, what we saw was, as we had seen before, it seems like TIL is able to generate a response for patients regardless of their mutational load.

It's able to create a response for patients that have received their TKI, or tyrosine kinase inhibitors, and these patients have had an actionable mutation. So we are really pleased to see that a broad patient population is very much available to TIL therapy, similar to what we had seen in the setting of melanoma, as well as cervical, frankly.

So we are not quite changing our direction for our non-small cell program. We have a broad patient population defined, although, I can say that potential registrational patient populations are beginning to emerge, as we are seeing data for a broad set of patient populations. So, I'm very pleased to see that we don't have to select as a population.

We have a number of different options for the registration program..

Sure. Thanks, Maria..

Thank you..

Thank you. Our next question or comment comes from the line of Joe Catanzaro from Piper Sandler. Your line is open..

Hey, guys. Thanks for taking my question. Maybe sticking with the Moffitt AACR presentation. So the presenting investigator there noted that the trial was designed by taking the tumors first and then putting on to Nivo, because of potential concerns about exhausting the T cells with PD-1 treatment.

I'm wondering if you could just speak to that and whether you've seen any indication of that across your entire clinical program, melanoma, cervical and all the other studies? Thanks..

Thanks, Joe. We certainly see that in our TIL growth process a sample of a TIL that comes from a tumor that might have had exhaustion markers can get rejuvenated by the end of the process.

So, I recognize that concern, our entire program as you noted, for -- as a bulk is positioned for a post PD-1 landscape, given that that's more of a regulatory path. But from a procedural process in terms of what our TIL looks like. We do see rejuvenation markers at the end of our 22-day growth process.

So whether that makes up for the tumor microenvironment impact, it's unclear. We haven't done the randomized study to sort of control for that potential variable. But we are very pleased to see that the TIL seem to be doing better after our 22-day growth process. So it's unclear whether a tumor banking would offer any benefit.

It certainly doesn't appear that way to me as of now..

Okay. Got it. Thanks. And maybe just one quick follow-up here at the ASCO update. Can we expect another update from independent central review? And then maybe one for Tim. Maybe if you could just speak to runway with current cash on hand? Thanks..

Sure. So we were not planning on necessarily giving specific details in terms of whether we are going by investigator or by IRC. In terms of ASCO presentation, it is always easier to report an investigator data just because it's more live available.

So, the viewers can see a more accurate view of things just because investigators read the data very much in real time. In terms of runway, I'll answer for Tim as well. We have not given a cash guidance. We have plenty of cash in hand to complete our pivotal program and submit our BLA.

We're certainly still evaluating our total year spend and we will provide guidance when we have it available to us. But we are very comfortable with the strong financial position that we have. And we have had a really strong track record of being able to do financing. So, we will provide additional guidance when we have it available..

Okay. Got it. Thanks for taking my questions..

Thank you, Joe..

Thank you. Our next question or comment comes from the line of Madhu Kumar from Baird. Your line is open..

Hey guys. Thanks for taking our questions. So first one relates to the ASCO presentation. So kind of following on from Jim's question. So you mentioned the idea of the median duration of response being reached.

But there are other kind of material events that could impact disclosures such as additional complete response events, would that be a reasonable basis for updating the melanoma Cohort two in ASCO?.

Hi Madhu, thank you for the question. I think from just perspective of drug development, a drug developer always gives regular updates at any opportunity given just to make sure that particularly if the DOR continues that this is something that is of interest, both to the investor community as well as the scientific community.

So I wouldn't necessarily think about why would you want to go to ASCO or do you have additional CRS. I'm not disclosing anything that you probably are not aware of this is obviously still under embargo.

But a scenario where the DOR continues is from my perspective an incredibly favorable scenario, considering the last time that we read the data was for JPMorgan and we had 15.5 months of median study follow-up. So, I'm not necessarily confirming or declining whether there -- the responses got deeper or not.

But just the median you are continuing or not would have been read enough to go to ASCO..

And then stepping back kind of philosophically, thinking about some of the other programs like head and neck, like non-small cell. What kind of a data set would you feel comfortable with presenting at a medical conference be it online or in person..

I don't know if there's necessarily a specific item. I think that if -- and a lot of this is a bit subjective if drug developers who have been around 20-some years such as myself. You look at the data and you decide something is striking and it's time to put it out. I think one of the key pieces for me always is not to disclose too little data.

If it's extremely new, it's a brand-new indication then I can understand that. But given that the Moffitt data for us shows efficacy of TIL in non-small cell, I think the next question is how would you position TIL and what does Iovance's TIL do in these indications specifically non-small cell.

So, for that information I would like to make sure that we have enough number of patients and some degree of follow-up before we disclose it. So, there's not a specific number. It really has to do with patient population, the settings by which the product is being administered and how unmet the medical need for that patient population is..

Okay. Great. Thank you..

Thank you, Madhu..

Thank you. Our next question or comment comes from the line of Boris Peaker from Cowen. Your line is open..

Congrats on all the progress you guys made so far. I guess, I just want to talk a little more on the Moffitt lung cancer versus yours. I mean we've talked about the differences in trial designs. I'm just curious to understand the differences in manufacturing process.

Why does there take about three times longer than your Gen two process? Or kind of what is it that they're doing in their process that you're not doing in your Gen 2?.

Thank you, Boris. Sure. So, this is again I can only speak to our own Gen 1, which is Iovance's process, so that's a better sort of description on our end. Bear in mind that the 6-week manufacturing process initially has a -- there's a couple of steps in there. One is the TIL growth conditions is not as optimized as we have now developed at Iovance.

This is precisely why we have a proprietary method. This is precisely why we have 12 allowed or granted patents for our manufacturing method because we have certainly learned how to grow TILs very well at this point. But there's also a second step that is in process for our Gen 1 and that's a selection of a subpopulation of TIL.

This selection was part of the original NCI process and what we have learned from NCI and they have published this data since then, is that the selection does not lead to an improvement in clinical response in any way. This is not the same method of selection as for example a PD-1 selection, it's just based on an assay that is in process.

So one of the things that we decided earlier on at the company was not to utilize an assay which is in process and yet does not seem to have a correlation with clinical response and we dropped that specific step. We run it in parallel. We don't run it in sequence.

So that's one of the things I can speak to and I've spoken before that that has shortened our process. But significant shortening really comes from our proprietary method of growth as well as various conditions and optimizations that we have undertaken..

Great. And if I could squeeze in one more. I'm just curious in terms of -- on the manufacturing side as you're approaching your BLA, as well as building your own manufacturing facility.

What are some of the things that the FDA wants to see from the CMC perspective? Have you had the discussion with them? Just want to understand what you need to do for new TIL therapy approval?.

Sure. Absolutely. So we continue having a dialogue with FDA through the course of the years. It's not -- on the CMC front even more particularly in cell therapy than even clinical dialogue. So every time we make a modification we submit that modification to the agency and the agency is very aware of what we are doing.

Both in terms of absolute clarity around their process as well as what we intend to file with. This dialogue is ongoing. And on a regular basis we submit documents with agency or we receive their feedback. So very much an active dialogue still..

Great. Thank you very much for taking my questions..

Thank you, Boris..

Thank you. Our next question or comment comes from the line of Mark Breidenbach from Oppenheimer. Your line is open..

Hey good afternoon and thanks for taking the question. Maria, maybe sticking with the general theme of manufacturing, can you just remind us what efficiencies are being introduced in the Gen three manufacturing process to bring the time down to 16 days.

And when we do eventually see updated results in head and neck cancer will we be able to see side-by-side comparison between patients treated with Gen 2 versus Gen 3 versus the PD-1 selected Gen 3 TIL?.

Sure. Hi Mark. Thank you for the question. So what we did our initial goal when we were optimizing for Gen 2 was to keep the product profile fairly consistent with our Gen 1 product. We had also done some optimization on Gen 1 and our goal was to keep a very similar profile.

For our Gen 3, we changed our direction a little bit and we didn't necessarily keep the exact same product profile. So the process is not very -- it's not a follow-on to Gen 2. We changed the process fairly extensively allowing for us to get to a 16-day manufacturing process.

In terms of the data presentation when we get to head and neck, I suppose so, we haven't really thought about what would that data presentation look like during different cohorts. The patient population is fairly similarly defined.

So when and if we decide to present it, I presume we can present them side-by-side and people can draw their own conclusions..

Okay. Thank you..

Thank you, Mark..

Our next question or comment comes from the line of Ben Burnett from Stifel. Your line is open. .

Thanks very much and good afternoon. Also trying to understand the Moffitt data from ACR and I guess I was hoping that maybe you could just speak to the efficacy that we would expect from the standard of care for nivo treatment from patients in that setting.

And I guess what would in your mind be a clear signal of efficacy over and above standard of care from your lung studies?.

Hi Ben. Thank you for the question. It's a complex question to answer. So I'm going to try and summarize it. Just because there's a lot of different subpopulations that are present in a non-small cell lung cancer indication, so let me say really high level. There's probably 3 big subpopulations.

It's a population which is biomarker-driven so they have an actionable mutation sort of EGFR, BRAF, ROS and others are part of that cohort. They're typically treated with their TKI at frontline. Checkpoints have not done very well in the patient population as a second line.

The response rate is quite low in that patient population and some of these were in the Moffitt study. And you could see that of course, there are primary refractory patients and they immediately progressed on anti-PD-1 as one would expect. So that's one patient population.

There's not very good literature in anti-PD-1 in this setting, just because they are not very good. The investigators believe that somewhere around 5% response maybe at best 10% response is what is expected from nivo in that second line and that's a best-case scenario.

A second subpopulation is patients that do not have an actionable mutation and their PD-L1 level is high. Those patients are expected to respond really well in the front-line setting. And in fact Ben Creelan had shown that, he had some of those patients.

And in fact they were responders one of them being ACR, having had a PD-L1 expression level of 100%. So that patient population is expected to respond well to PD-1s in the front line. And in the second line, they have a number of options. They might receive other PD-anti-ICIs such as PD-L1 combinations or otherwise.

And by third line, they would have to resort to chemotherapy. Standard of care in third-line is around 9% response rate and a DOR of around 6% for taxol-based products.

The third bucket of patients in non-small cell are PD-L1-low patients, and these patients are typically treated with anti-PD-1 plus chemotherapy just because they don't have a very good chance of responding necessarily to immune checkpoint inhibitors.

So this bucket of patients typically receives chemo plus anti-PD-1, so chemo immunotherapy as frontline. By second or third line, they are out of options. And again, they have to resort back to chemotherapy, which as I noted is around 9% to 10% response rate and a DOR of around at best maybe six, seven months.

So they're in different settings when they reach chemotherapy, but just about all of the patients in non-small cell will reach that point fairly quickly.

Does that answer your question?.

That's really helpful. I appreciate that..

Thank you, Ben..

That's great. And if I could just ask one follow-up question. Just with regards to the IL-2 analog program the IOV-2001. Just what are the steps to bring this to the clinic? And I guess could you also just talk about how you plan on developing this? And by that, I mean, Iovance's has a couple of different TIL programs.

Which TIL programs do you seek to leverage the 3001 analog first?.

Sure. Yes. So right now, we are still in early preclinical stage and we thought that we would be an IND-enabling activity mode around 2021. We haven't completely disclosed our development program, but we certainly have a plan internally that, we are executing too, when we are ready to get into clinic.

We are excited about this program of course that has very favorable – the product has favorable PK, PD and IP landscape. That's why we license that product in. But I haven't disclosed in detail sort of what our development program would look like. And I think probably 2021 would be a better time to disclose more information about that..

Okay. Excellent. Thanks very much..

Thank you, Ben..

Thank you. Our next question or comment comes from the line of Reni Benjamin from JMP Securities. Your line is open..

Hi. Good afternoon. Thanks for taking the question and congratulations on the progress. Maria you might have touched upon this, but I'm kind of curious as to your guys choice of combining KEYTRUDA with TIL versus with Moffitt and with nivolumab.

Are there learnings from this data that might make you start evaluating other checkpoints? And when we think about the market even if we look at the end stage non-small lung cancer patient population it's significant. And now in combination with checkpoints it can clearly move up.

So I'm kind of curious, how you guys are thinking about or where you feel the TIL will fit best?.

Sure. Thank you for the question. You're correct. We started with KEYTRUDA. I presume your question is why KEYTRUDA versus nivo.

Is that correct? Is that what you're asking?.

Correct. Yeah, yeah..

Okay. All right. At the time, when we started the program or at least we started putting the concept together, we expected KEYTRUDA plus chemotherapy to be a standard of care in frontline. And it has. In fact, that is exactly what has happened. So, we wanted to make sure that, we are combining what is called a standard of care.

Of course, we were replacing chemotherapy with TIL for the early-on patient population. So recall that, we have two cohorts Cohort 3a allows for KEYTRUDA plus TIL and Cohort 3b allows for TIL alone in the relapsed/refractory non-small cell cancer patients. That was the reason for selection of KEYTRUDA the post nivolumab. The market is quite large.

And I think in terms of placing TIL one sort of at a very, very high level can think about two strategies.

The one strategy we have selected for melanoma and cervical, at least our initial strategy has been to go into a late-line patient population, so relapsed/refractory with unmet medical need that allows us to do a single-arm strategy for registration. And that certainly has worked out really well for us.

A second broader strategy would be not to go to late-line and in fact go to earlier line in combination with checkpoint. So this is our rationale for having the two cohorts that we have. It allows exploration of both potential approaches going forward..

And just as a follow-up kind of based on this Moffitt data, is there any thoughts in expanding even this basket study to evaluate something like nivolumab.

And I think in the study, they looked at patients who would progress while on nivolumab versus in combination? Any thoughts regarding that kind of a design versus just a straight combo?.

Before thinking about sort of what next, I certainly would want to see our own data for TIL plus KEYTRUDA and just to see whether earlier line and concomitant administration would add a benefit or not. So I think it will be very much data-driven.

And I think we don't have quite sufficient amount of data for me to speak to that but I understand what your question is and thank you for that..

Okay. Thank you..

Thank you. Our next question or comment comes from the line of Joe Pantginis from H.C. Wainwright. Your line is open..

Hi, Maria. Thanks. Just curious, I know my question might be a little bit of a reach at this point but hoping to get some broad strokes.

I guess first what can you say has been the nature of the talks you've had thus far with payers? And secondly, maybe can you take any broad strokes with regard to pricing structure? Are you looking at potential flexible types of pricing, indication based or what have you? Just want to get some ideas of what you might be thinking at this point?.

Hi, Joe. Thank you for great question. Yes, we have had initial dialogue with payers. And so far they've been quite open. This is a slightly different cell therapy product on what is already out there in the market. We are also dealing with a different patient population. The products that are in the market are for hematologic malignancies.

And this is really the first cell therapy product for solid tumor. So the initial dialogue really has been to educate to assure that a differentiated safety profile is clear to the payers, as well as the potential benefit for the existing patient population. In terms of pricing, we certainly haven't quite nailed down our own pricing position.

And I think part of this has always been that as the median DOR for the melanoma program continues or continued and as you will see in ASCO where we are with this. We're very encouraged to see the value of the product. So I think that that by itself has been playing a role into thinking about the positioning of the product itself.

And then we certainly haven't disclosed whether we are going to have a different indication-specific position for the pricing position of the product. We're still evaluating the patient populations and we're evaluating sort of how we should administer TIL in terms of different sites and different indications.

And so I think we can probably update the market when we have better information to provide. But we continue being very excited about the product and the payers have been very open to the dialogue and have been very welcoming and in fact invited us to come talk to them. So this has been – it's been a great start to the payer discussion so far..

That’s very helpful actually. Thank you very much..

Thank you..

Thank you. Our next question or comment comes from the line of Geulah Livshits from Chardan. Your line is open..

Hi. Good afternoon. Thanks for taking my questions. I wanted to follow up about some of the question is about the Gen 3 process and the selected TIL cohorts that have been added.

So based on the experience thus far, can you elaborate a bit more about how you think about the path forward there and expanding to other cancer types potentially? And also more specifically in terms of manufacturing, in terms of the process and the equipment and the overall setup data.

How different is Gen 3 from Gen 2 as you think about setting up the internal manufacturing facility?.

That's great. Thank you, Geulah. Yes, we are quite excited about being able to potentially offer Gen 3 and other indications as well. We chose head and neck as our first indication because these patients are particularly sick with a fairly short life. It seems like their life expectancy is not very long.

So we were trying to see, if we can offer something that is expectedly shorter and may be more potent. So, that was our intent for both Gen 3 and selected TIL. From equipment perspective, we are using the same equipment for Gen 3 as we're using for Gen 2.

The method by which we're using them order of events may be different, but it's the same equipment. So, a commercial manufacturing facility can easily be reconfigured for Gen 3 should we decide to go in that direction..

Great. Thanks..

Thank you..

Thank you. Our next question or comment comes from the line of Biren Amin from Jefferies..

Hi guys. Thanks for taking my questions. Maybe one more question on the ASCO oral melanoma data Maria. Are you planning to present data from the PD-1 primary refractory cohort as it relates to the median DOR.? I think you enrolled about 42 patients from this cohort and presented these data last fall.

And maybe if you could also contextualize this population in terms of what's the typical MPFs and median OS in these patients versus the PD-1 relapsed population?.

Sure. Hi Biren, thank you for the question. I don't know if we necessarily were planning on breaking the primary refractory apart. I think we were -- we had a lot of content for ASCO and we felt that that content is probably really important and we didn't necessarily think about a subpopulation presentation.

So, not for any other reason except that we have a lot of content and we were excited to share all of that. As of now, we weren't necessarily pinpointing the primary refractory patient population. From an OS perspective, we have disclosed that metastatic patients in Stage IV disease have a median OS of approximately six to seven months.

That's the best information we can find in literature for our patient population. I really haven't seen a very good PFS in that patient population. It's actually not an easy patient population to find reports on. Unfortunately, they're particularly ill and they don't make it very far.

But I think that that OS of six to seven months is a great benchmark to show what is expected from a Stage IV metastatic melanoma patient population..

Okay. And maybe one more.

As you look to filing the BLA, what are your thoughts on the size of the commercial team that you would need?.

Sure. We've been having that discussion internally and we certainly have internal plans in terms of how to outreach how many sites and what is our footprint going to be.

I'm not quite ready to share that today with you but we have our plans nail down and it's -- we think that we have a really broad outreach both for academic settings as well as community settings and we have plans as to how to broaden that even further subsequent to launch. So, both of those are in progress and proceeding.

We already have a commercial presence inside the company of course. I mentioned that we have been expanding our commercial and medical affairs teams and we are very excited about expanding them further by year end..

Okay. And then maybe just the last one.

What are your thoughts on filing in Europe? Have you had discussions with the EMA in terms of what they would require?.

Yes. Really good topic as well. Over the course of development as you're probably aware we have opened a number of CTAs in various countries in EU and Canada. So, we have had initial discussion as part of the CTA process and we have had also local health authority discussions.

Our centralized procedures for EU engagement is planned for later part of 2020 and we are beginning to initiate that discussion with the centralized CHMP body of European Health Authority..

Okay, great. Thank you..

Thank you..

Thank you. I'm showing no additional questions in the queue at this time. I'd like to turn the conference back over to management for any closing remarks..

Thank you, Howard. I think we just want to thank everyone for participating today and we thank our patients and patient families for contribution that they make to our internal program and stay tuned. We're very excited about progress in 2020..

Ladies and gentlemen, thank you for participating in today's conference. This concludes the program. You may now disconnect. Everyone have a wonderful day. Stay safe..