Iovance Biotherapeutics Inc (IOVA) 2020 Q2 法說會逐字稿

Good afternoon, and welcome to the Iovance Second Quarter 2020 Financial Results Conference Call. (Operator Instructions)

Now I would like to turn the call over to Sara Pellegrino, Vice President, Investor and Public Relations at Iovance. Please go ahead.

Thank you, operator. Good afternoon, and thank you for joining us. Speaking on today's call, we have Maria Fardis, our President and Chief Executive Officer; Friedrich Finckenstein, our Chief Medical Officer; and Michael Swartzburg, Vice President of Finance and Principal 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 second quarter and first half ended on June 30, 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 plan, precommercial activities, clinical trial plans and results, potential future applications of our technologies, manufacturing capabilities, regulatory 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 very pleased to lead today's conference call to summarize our achievements at Iovance during the second quarter and first half of 2020. We are moving closer toward commercializing Iovance TIL as we continue to execute our key priorities, including clinical, manufacturing and precommercial activities. We are driven because of our patience and by the dedication of internal team members and external partners.

In the second quarter of 2020, we continue to advance our tumor-infiltrating lymphocyte therapy or TIL in our lead pivotal programs in melanoma and cervical cancers. We reported updated Cohort 2 data and early Cohort 4 data in melanoma and recently completed enrollment in our pivotal cervical program.

We remain on track to submit our first planned Biologics License Application, or BLA, later this year, while preparing for potential commercial launch in 2021. Overall, we believe that the growing set of clinical data for TIL and advanced melanoma and cervical cancers, and more recently in lung cancer further support TIL as a broad technology platform of cell therapies across solid tumors.

With the successful completion of our June 2020 follow-on public offering, we are very well capitalized with approximately $777 million in cash to execute our initial commercial launch and expand our growing pipeline.

We also continue to make great strides with our research efforts. We will be disclosing some of our research and bioinformatics data as part of 3 abstracts accepted as e-posters in the upcoming European Society for Medical Oncology, or ESMO, virtual scientific weekend to be held September 19 to 21, 2020. They include data on persistence of TIL and cervical cancer patients, genetic modification of Iovance TIL using TALEN technology and reinvigoration of Iovance TIL during the Gen 2 manufacturing process. Further details of these posters are included in this afternoon's press release.

I would like to take a few minutes to highlight the significant progress across our pivotal TIL program, beginning with lifileucel for advanced melanoma. Metastatic melanoma is a common type of skin cancer, accounting for approximately 96,000 patients diagnosed annually and 7,200 deaths each year in the United States alone.

During the second quarter, we announced early pivotal Cohort 4 data and updated Cohort 2 data from our C-144-01 study of lifileucel. We believe that a combined data from Cohort 2 and 4 in our melanoma study continue to support the efficacy of lifileucel to address a very significant unmet medical need in metastatic melanoma.

As a reminder, lifileucel has also received both fast track and regenerative medicine advanced therapy or RMAT designation from the U.S. FDA, which were supported by the clinical data from Cohort 2 in the melanoma study. Iovance is an organization, is very focused on the advancement of this melanoma program. We anticipate to meet with FDA and expect at least submit the BLA for lifileucel in late 2020.

Our second pivotal program is investigating lifileucel, formerly known as LN-145 in this C-145-04 study in patients with metastatic cervical cancer. The United States Adopted Names or USAN council has accepted and published the use of the name lifileucel to describe Iovance TIL therapy for cervical cancer in addition to melanoma.

We recently completed enrollment in the pivotal Cohort 1 of the cervical study, and we are scheduled to dose our last patient in the coming weeks. As a reminder, the FDA has previously granted both breakthrough therapy and fast track designations for LN-145 now referred to as lifileucel.

Since we completed enrollment in our melanoma pivotal cohort, approximately 2.5 months ahead of the plan, the BLA submission for the 2 indications may be separate. We continue preparing for both submissions with the BLA submission for melanoma anticipated later this year and the BLA submission for cervical, most likely in the first half of 2021.

Transitioning to our manufacturing capabilities, we have established a solid track record in manufacturing TIL for patients as we prepare to launch lifileucel using our proprietary second-generation, or Gen 2, process. The Gen 2 process protected by 12 granted U.S. patents continues to be robust with a demonstrated success rate above 90% in over 300 patients.

For launch, our CMO partner, WuXi AppTec Philadelphia facility will provide initial commercial supply of lifileucel until we transfer to the Iovance Cell Therapy Center, now called ICTC. The ICTC is our own state-of-the-art 136,000 square-foot facility at the Navy Yard in Philadelphia. The location of the ICTC near Philadelphia airport also allows for shipment of TIL therapies to all states within the U.S. and throughout Europe, if necessary.

We have been in active dialogue with the U.S. FDA during construction of the ICTC facility. In advance of a scheduled meeting with the Division of Manufacturing and Product Quality, or DMPQ, I am pleased to report that we reached full alignment with the division on commercial manufacturing facility design and capacity. Clean rooms at the ICTC are expected to be completed in late 2020 with clinical activities expected to initiate in early 2021. Commercial manufacturing is on track for 2022 with capacity to meet the demand for thousands of patients.

In anticipation of the launch of lifileucel in melanoma and cervical cancers, we continue to build a strong team at Iovance with more than 200 employees across multiple locations, including a commercial team with extensive cell therapy experience. The commercial and medical affairs groups remain focused on ensuring a positive patient experience with lifileucel during commercialization.

Toward that, we are working on the following areas of operational excellence: clinical site engagement in preparation for commercial launch; development of a close collaboration with health care professionals or HCPs, who will be administering lifileucel; operational excellence by Iovance in provision of lifileucel; and communication with payers.

First, we are partnering with the leading U.S. cancer centers to build their service-line capabilities. Among these centers, we anticipate that sites with prior TIL experience and those with key opinion leaders for melanoma and cervical cancers will be the initial target for our launch. Our comprehensive training program is designed to ensure cross-disciplinary teams can administer the lifileucel treatment regimen upon FDA approval.

Iovance is targeting to train and onboard well over 40 sites at launch and expand over time. The longer-term goal is to bring on enough sites so that most patients can be within a few hours drive to site offering lifileucel TIL therapy.

Based on our current market research, we estimate the addressable market for TIL therapy to be over 7,000 post PD-1 melanoma patients per year within U.S. In addition, our medical affairs team works with a network of treating HCPs and patient advocacy groups to assure that information of that TIL is available to interested organizations.

We have also continued discussions with private payers and Centers for Medicare and Medicaid's reimbursement, or CMS, to ensure patients have appropriate and timely access to lifileucel. Thus far, we have met with or are scheduled to meet with commercial and Medicare payers responsible for approximately 50% of covered lives. We believe that CMS and payers appreciate the unmet need and clinical value of lifileucel as well as the potential benefits for patients that both have metastatic melanoma and metastatic cervical cancers.

And under a patient-centric model, we intend to support the patient at every step of the process from initial resection to infusion. At Iovance, being patient-centric means understanding, anticipating and addressing our patients' need and removing barriers to treatment.

In today's press release, we introduced IovanceCares, a program that reflects our commitment to provide individualized support for personalized therapy. IovanceCares will allow communication and coordination of patient care with HCPs throughout the lifileucel journey. All elements of the system will be managed by dedicated Iovance case managers to handle the needs of HCPs and patients.

Through IovanceCares, HCPs can place order for lifileucel, while Iovance will monitor and track patients cell through manufacturing process until delivery to the hospitals. The dedicated case managers will also provide reimbursement support for sites and patients. As our market research and commercial preparation continues, we look forward to providing updates on our launch plans throughout the year for you.

I would like to now ask our Chief Medical Officer, Friedrich Finckenstein, to summarize the recent data as well as our other clinical studies at Iovance. Friedrich?

Thank you, Maria. I would like to spend some time walking through the most recent data from our C-144-01 clinical study of lifileucel, our TIL therapy for metastatic melanoma. These new data sets include an update from Cohort 2 and early data from Cohort 4.

Both Cohorts 2 and 4 have similar patient characteristics in that they are heavily pretreated with high baseline disease burden and significant unmet need. Chemotherapy is the available care for these patients who have progressed on immune checkpoint inhibitors reported to offer at best only a 4% to 10% response rate and median overall survival of only 7 to 8 months.

The updated Cohort 2 data was presented at the ASCO 2020 virtual scientific meeting. Following onetime treatment in 66 patients, lifileucel showed a 36.4% ORR, and duration of response was still not reached at 18.7 months of median study follow-up.

The new sensitivity analysis also showed that durable responses have been observed across the wide age range in metastatic melanoma patients who may have received prior anti-CTLA-4 and BRAF-targeted treatment regardless of the BRAF mutation studies and equally in patients with PDL-1 high and low status. We believe that these Cohort 2 data further demonstrate the durability of response to TIL for all subgroups of patients as well as the value proposition for lifileucel as a onetime treatment in metastatic melanoma.

Turning to Cohort 4. We recently conducted an early data analysis. As a reminder, the primary endpoint for Cohort 4 is ORR by independent review committee and a key secondary endpoint is ORR by investigator. The early analysis included an investigator assessment in 68 patients with 2 available radiological assessments at the time of our March 2020 data cutoff.

In these Cohort 4 patients, like lifileucel showed a 32.4% ORR at 5.3 months of median study follow-up. Overall, we were very pleased that these preliminary results suggest significant improvement over available care for this patient population as well as remarkable consistency with prior Cohort 2 data that showed ORR of 33%, at 6 months of median study follow-up as presented at SITC in 2018. We will present the detailed pivotal data at a future medical meeting in 2021.

Turning toward our development of Iovance TIL therapy, LN-145. In lung cancer, we continue to dose 2 cohorts of non-small cell lung cancer patients in our ongoing basket study, which we call IOV-COM-202. We were highly encouraged by our collaborator of Moffitt's recent data update at AACR Virtual Meeting I, which showed durable complete responses in non-small cell lung cancer patients treated with Moffitt's TIL.

The Moffitt data provided the foundation for us to investigate our own in Iovance TIL in non-small cell lung cancer in the 2 baskets: early cohorts as well as a potentially registration-enabling study, which we call IOV-LUN-202. Like our approach in both melanoma and surgical, we believe that the single-arm study of our TIL therapy LN-145 has the potential to support approval in a well-defined lung cancer patient population with significant unmet medical need. We plan to begin the pivotal IOV-LUN-202 study by the end of 2020.

Moving on to our other studies. We continue to advance Iovance T-cell-based therapies in the clinic in additional indications as well as earlier lines of therapy. 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 combination with pembrolizumab in earlier lines of therapy for checkpoint-naive melanoma, head and neck and non-small cell lung cancer.

Furthermore, this study has 2 additional cohorts of TIL alone and relapsed/refractory melanoma and non-small cell lung cancer. The ongoing C-145-03 clinical study in head and neck cancer, which also introduces LN-145 manufactured with our new proprietary 16-day third-generation or, Gen 3, TIL therapy process as well as our proprietary PD-1-selected TIL product, which we call LN-145-S1.

We are also activating additional sites for the IOV-CLL-01 study of our peripheral blood lymphocytes, or PBL, therapy in relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma, CLL and SLL.

I will now hand the call over to Michael to discuss our second quarter and first half 2020 financial results.

Thank you, Friedrich. My comments will reflect the high-level financial results from our second quarter and first half 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. At June 30, 2020, Iovance held $777.4 million in cash, cash equivalents, short-term investments and restricted cash compared to $312.5 million at December 31, 2019. Our current cash position includes net proceeds of $567.4 million from our June 2020 common stock public offering. We anticipate year-end balances of cash, cash equivalents, short-term investments and restricted cash may be over $630 million.

Moving to the income statement. Our net loss for the second quarter ended June 30, 2020, was $63 million or $0.47 per share compared to a net loss of $47.6 million or $0.38 per share for the second quarter ended June 30, 2019.

Net loss for the 6 months ending June 30, 2020, was $132.6 million or $1.02 per share compared to a net loss of $84.5 million or $0.68 per share for the same period ended June 30, 2019. Research and development expenses were $49.3 million for the second quarter ended June 30, 2020, an increase of $10 million compared to $39.3 million for the second quarter ended June 30, 2019. Research and development expenses were $106.2 million for the 6 months ended June 30, 2020, an increase of $36 million compared to $70.2 million for the same period ended June 30, 2019.

The increase in research and development expenses in the second quarter 2020 over the prior year period was primarily attributable to an increase in costs associated with multiple clinical trials and growth of the internal research and development team. The increase in research and development expenses in the first half of 2020 over the prior year period was primarily attributable to the higher patient enrollment in clinical trials, licensing fees and growth of the internal research and development team.

General and administrative expenses were $13.9 million for the second quarter 2020, an increase of $4.8 million compared to $9.1 million for the second quarter of 2019. The increase in the second quarter of 2020 over the prior year period was primarily attributable to growth of the internal general and administrative team and higher stock-based compensation expenses.

General and administrative expenses were $14.4 million for the second quarter ended June 30, 2020, an increase of $3.5 million compared to $10.9 million for the second quarter ended June 30, 2019. General and administrative expenses were $28.2 million for the 6 months ended June 30, 2020, an increase of $8.3 million compared to $19.9 million for the same period ended June 30, 2019.

The increase in general and administrative expenses in the first quarter and first half of 2020 compared to the prior year periods were primarily attributable to the growth of the internal general and administrative team and higher stock-based compensation expenses. As of June 30, 2020, inclusive of the recent financing, there were approximately 146 million common shares outstanding.

Looking ahead, we expect operating expenses in the second half of 2020 to be in the same range as the first half of the year with a shift from certain clinical related expenses to commercial-readiness expenses.

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

Thank you all for attending the call today. We have already achieved many of our 2020 milestones, and we look forward to continued execution towards our pre-BLA meeting, BLA submission and remaining goals of the year, including initiation of a registration-enabling study in non-small cell lung cancer. Overall, I'm very pleased with our progress in expanding our leadership in TIL development, manufacturing and commercialization.

I will now turn the call over to the operator for questions. Operator?

(Operator Instructions) Our first question comes from Peter Lawson with Barclays.

Maria, just on lung cancer, how should we be thinking about the subsets that you target, whether it's lines of therapy, where the tumor is located? And how should we think about potential data from that, whether it's from the basket study or the pivotal study?

Yes, of course. Peter, thank you for the question. We have thought about the patient population a little bit differently for the LUN-202 study. When you were writing the basket study, we basically thought about relapsed/refractory patient population. While -- when we were thinking about LUN-202 study, we were more thinking about the pivotal cohorts that can possibly support a registration. So that's a difference between the 2 programs, the one for LUN-202 is better defined toward registration.

Got you. And then just the timing around the data from, I guess, either the basket or the pivotal itself.

Right. So the pivotal program is not expected to start until later part of the year and against registration supporting study. And the basket study, we have not committed to a specific data flow for that program. I have noted that we started that program, the basket study, around a year ago, although there was not a guarantee that the cohort for non-small cells start at the same time. So we wanted to make sure we have some patients into that program with some degree of follow-up so we have a better understanding of Iovance TIL in non-small cell lung cancer patient population. So we have not really committed to a specific data flow.

I also note that there's not a particularly good venue in the remaining part of the year for solid tumor indications in a conference setting to be able to present. So all of those considerations have gone into our decision to hold back until we have more data, and we have a better value to present our data.

And then just finally on cervical cancer. There seems a potential to kind of you must co-submit BLA with melanoma. And did cervical cancer slow down? Or was that COVID-related? Or was it just kind of better pacing driven by the FDA?

I think we always thought that our melanoma program is going to enroll by around March time frame. That program sort of sped up. I think that's what happened. That program came in about 2.5 months ahead of schedule.

The cervical program, we always thought it would end by around midyear, and it has, in fact, consented our last patient. Patient dosing always depends on the patient's clinical status. So the difference between the 2 of them has to do more on the melanoma being sped up to a degree because we managed to get the enrollment closed and all the patients got dosed by around mid-January.

From a timing perspective, we have been sort of on point saying that the 2 BLAs could go together or they can be separate. Our best estimate at this point is possibly a degree of follow-up may be necessary for the cervical indication. And given that we continue dosing patients, we have enrolled our last patient, but we haven't dosed our last patient. Our best estimate was perhaps this submission is likely going into early part of 2021. So we gave that guidance today.

Our next question comes from Jim Birchenough with Wells Fargo.

Congrats on all the progress. A couple of questions. Just first on a pre-BLA meeting. Could you speak to what the focus of that meeting will be on, what sort of areas you expect to touch on? Or do you feel like you already have agreement on most aspects with this filing?

Jim, thank you for the question. Typical pre-BLA meetings have 2 components. They have a structural component discussion that we have with FDA as to how we intend to compile the document itself. It is a large document. And then the second one is usually around data and amount of follow-up.

So just kind of trying to answer your question as part of the second part. So from a data perspective, usually, there's at least 3 different sets of questions. There's clinical questions. There's CMC questions, and there's usually nonclinical, and there may be a bucket of regulatory questions that are usually asked. So all of those are part of the potential dialogue as part of the pre-BLA with FDA.

And then, Maria, just in terms of thinking about the initial launch and the 40 sites that you're initially targeting, could you speak to what proportion of the late-stage melanoma patients, those 40 sites treat, if there's a number or proportion?

Yes, absolutely. I'm going to ask our Head of Commercial, Jim Ziegler, who's in the room with us, to address that question. Jim?

Jim, thank you very much for your question. First, we based the selection of our sites based upon prior clinical trial experience, KOL experience, status of whether they have existing cell therapy, service lines, et cetera.

What Maria said earlier is that we plan to launch with at least 40 sites. And based upon our estimates, we think that we'll cover the majority of patients in the community. But of course, as we expand, the number of sites over time will look to include more geographies that allow greater access to care.

Great. And maybe one final question, just following up on Peter's question on non-small cell lung cancer. What were your takeaways, Maria, from the Moffitt data? And can you say whether those learnings have been confirmed to some extent with the early experience in the basket study? And if that's what's supporting the move to a registration study?

Thank you, Jim. I think that the lesson, one of our strategies -- maybe I'll step back for a second. One of our strategies has always been to look into new indications through collaborations with academic institutions as signal-seeking. And so we felt that the program we had with Moffitt was a great proof-of-concept signal-seeking program, where it showed that TIL in non-small cell can be a very powerful potential therapy.

Now the patient population may or may not be representative of today's patients. The TIL from -- manufactured by Moffitt may or may not be representative of Iovance's TIL, so the purpose of our COM-202 study is to do that, to get patients that are currently in community or academic institutions that are in -- seeking, sort of, clinical trials. And we are trying to look at Iovance's Gen 2 manufacturing process in the COM protocol.

So I think that we learned a few things from that study. What was remarkable was a broad patient population responded. Patients who might have had a biomarker therapy, so they had received their therapies in kinase inhibitors, followed by nivolumab. They still responded, and they were able to reach a CR as a matter of fact. We also noticed that patients that are PDL-1 low or even 0% have certainly an opportunity to respond to TIL.

So those are great lessons for us, and this is how we define the patient population in LUN-202 based on the lessons that we learned from that study.

Our next question comes from Ben Burnett with Stifel.

I wanted to just follow up on that and ask for just a little bit more color around this registrational non-small cell lung cancer study. I guess, what are you thinking in terms of study size? And did I hear you right? Did you -- are you focusing on leveraging the Gen 2 manufacturing process?

Ben, thank you for the question. Yes, we are definitely using Gen 2 going forward in most of our studies, although we have introduced other manufacturing methods into clinic as exploratory manufacturing methods. But given that we still are very much interested in Gen 2 in the commercial landscape, we will continue with Gen 2 and our LUN-202 study.

In terms of patient population, we really are looking at unmet medical need patient population. That's our strategy. Does that answer your question? Do you have a further question in terms of the patient population for that study?

Well, to the extent that you're prepared to disclose it, I guess I was wondering if you could provide any color on kind of the size of the study that would get the support registration here.

Yes. I think we will look to make sure that we first identify the patient population with the unmet need, and we feel that we have done that. And two, we have always been interested in a stage program such as a Simons two-stage program, where we explore a signal, the strength of a signal in a certain population, and then we can always expand.

We -- I believe that this study is very smartly designed, and we think that there's a potential if the signal is strong enough for registration. But our general strategy is find and define unmet medical need very well and ideally use a single-arm strategy.

Okay. Okay. That's great. Understood. And maybe just one follow-up question on the melanoma pivotal study. So you provided an update on the secondary endpoint, the investigator assessment, which was, I think, something like 68 patients. Do you plan on providing another update with a fuller data set this year before we get the primary endpoint?

I think what we are going to do, Ben, is to make sure that we have full agreement with FDA in terms of the size of the package. And then ideally, we always want to release our data in a medical conference. There was a question earlier about this, that there's not a lot of very good venues left in the year. Where we have the data, we can reach the timing of submission and then present in those medical conferences.

So I'm not committing necessarily to presenting the melanoma registrational program in the 2020 time frame. This likely would be a 2021 event. By the time we read the data, the full of the data, make sure we have agreement with FDA and then go to a medical conference.

Our next question comes from Mara Goldstein with Mizuho.

Great. So I have a question around the manufacturing. And when you are able to fully have the Iovance cell therapy center up and running, when it's fully operational. Will there be a perceptible change for you from a cost perspective?

And then I just had a question around capital allocation for the completion of manufacturing and your start-up costs now that you've been able to kind of top-up your coffers. And how should we think about cash spend over the next 12, 18, 24 months?

Sure. Sounds good. Thank you, Mara. Yes, we think that our manufacturing facility would ultimately yield a lower COGS. Not because of necessarily raw material, but as part of COGS, we certainly have a component of human capital and how much we pay for the time. And that's always something that you increase that payment when you're working with the CMO. So we think that once we have our own facility and our own team, we should be able to further reduce our COGS.

I'm going to ask Michael Swartzburg to speak to the capital allocation. Michael?

Yes. Thank you. So as we talk about spend, I had mentioned that our operating expenses in the second half of the year will look similar to the first half of the year. And we also mentioned that construction is ongoing for our Iovance cell therapy center, which the clean rooms are expected to be completed in 2020. And the rest, as you imagine, will continue ongoing.

As it relates to 2021, we haven't given any guidance of that yet. We also stated that we believe our cash position of $777.4 million is sufficient for us to execute commercial launch and pipeline activities, including our existing programs.

Our next question comes from Mark Breidenbach with Oppenheimer.

Congrats on the progress. Maria, since I've heard you say a couple of times that you don't think there are any good venues left in the year for solid tumor data, I'm just wondering if that implies that Iovance won't have much of a presence here at SITC.

I think that was in light of -- thank you, Mark. It was in light of the pivotal program for melanoma. And given that the timing of the abstract submission is literally in a couple of weeks and you have to have read all the data and have the abstract ready, I don't consider SITC a good venue for melanoma program.

It doesn't mean we will have nothing else. I was just not committed to what that could be. But from a pivotal data program, I think we probably would look into 2021 for data release.

Okay. And in terms of your peripheral blood lymphocyte program, I know that's something that you've been working on for a while now. Is there a chance we'd see early data from that at ASH later this year?

Thank you for the question. Our sites for PBL were, in fact, affected by COVID, and we are looking into expanding our additional sites to be able to expedite enrollment, but chances of being able to get data this year is extremely low, given that patients have to be enrolled, the very first set of patients are typically safety, and this is a different study design in the sense that efficacy is pretty hard to see in early stages.

I'm going to ask our Chief Medical Officer, Friedrich Finckenstein to speak to maybe just at a high level, the study design for the PBL program. So you have an understanding and appreciation of when data may be available.

Yes. So thank you, Maria, and thank you for the question. At a very high level, I think it's sufficient to describe the design as, first, a dose-finding part, which is really by regimen, a dose-escalation design with small cohorts of patients that are being treated sequentially after confirmation of the safety profile at that dose level.

So by definition, that goes basically small cohort by small cohort, and it takes a while to be done with that and to have a sufficient sample size that might be worth presenting the data. And then it would be really mostly focused on safety. Maybe that gives you an idea around the design.

And only when that is available, would we be going into an expansion at a dose level that we find appropriate that then would be more focused on describing the efficacy profile. And that's probably most relevant for what we would be showing.

I hope that addresses the question.

Next question comes from Reni Benjamin with JMP Securities.

This is Justin Walsh on for Reni. Based on your agreement with Avid Biosciences (sic) [Avid Bioservices] with IOV-3001. I was wondering if you could comment on what you're trying to or what you're hoping to achieve with that. And how you're trying to improve over native IL-2?

Yes, absolutely. Justin, I don't know if you have seen, but we had an earlier press release around I think it was right around JPMorgan, when we announced that we had taken a license from Novartis to commercialize a novel IL-2 analog. This was an IL-2 CDR-grafted, which targets really IL-2 receptor beta-gamma units. So it's a novel IL-2 that we are pursuing, and it's in a preclinical stage.

So the agreement with Avid was really to try and go through the process development and manufacturing GLP as well as GMP material for preclinical program that supports the IND-enabling program.

Does that answer your question?

Yes. That makes sense. So how would you -- I guess you would -- in the preclinical exploration, you would actually look at how you would consider incorporating that into your treatment programs.

Yes. So on IL-2 analog, particularly this one, which was, as I noted, is a CDR graft. It allows a better PK. It has better CMC profile. It certainly has very favorable IP characteristics and expectedly a differentiated safety profile compared to available IL-2. The idea around this is to explore a potentially better product as we administer and co-administer with TIL therapy. But there certainly are plenty of opportunities to develop something of this nature on its own as well.

We have now committed one way or the other. What I have commented is we expect to be an IND-enabling program in 2021.

Our next question comes from Madhu Kumar with Baird.

So I'll start micro and then go more macro as we go along. So on a micro basis, so you've completed enrollment in a cervical cohort. That's 75 patients, correct?

Approximately, approximately, typically, when we close enrollment, we don't always know exactly how many patients because there may be screen failures. So approximately 75 is what we had defined in the protocol, yes.

Okay. And then second question, what is it going to take to get lifileucel in melanoma and cervical approved in Europe?

I think that really depends on the dialogue with the European health authorities. The same way that we have been talking to FDA, we need to parallel that dialogue with the EU health authorities to make sure that they might be supportive of the existing program.

The first dialog typically, Madhu, that I have with health authorities is, do they appreciate the unmet medical need? And do they agree with our definition? And do they think that if the answer is yes, then do they agree that a single-arm can be supportive of registration? It usually starts with that discussion.

And when and if they agree with those dialogues, then I think it's appropriate to talk about what is the size of the package. What do they think is available care in that region? What percent of response we need to see and what could be a successful package for submission to EU? So that entire dialogue needs to be had with the EU health authorities, which we've had with FDA for some time now.

Does that answer your question?

I mean -- so I guess my question is, when will you have those discussions, given that you're pretty far along into the clinical development of lifileucel in melanoma and cervical?

Yes. So we have been planning on a potential interaction to get initiated later part of the year. There are EU-specific requirements, and we are going through the list of items that we need to have on the ground in EU to assure support of the program with assumption of success. And that's a list that every sponsor has to sort of review, particularly one that has not had a commercial product in EU. We need to make sure that we have those in place before starting the dialogue with the agency.

Okay. And then how are you thinking about moving up the line of therapy in both melanoma and cervical cancer? And what's it going to take to kind of get a clinical trial program starting to really kind of in-depth pursuits, either frontline melanoma or frontline cervical cancer?

Yes, excellent question. So in order to define -- going to earlier line requires a couple of things: one, one has to understand the magnitude of the effect of the given product, lifileucel; and two, there's standard of care usually available for these patients.

So typically, the first step is to go on top of standard of care. Because the patients have the standard of care available, usually the sponsors have to add to it. And once you see the magnitude of the effect, you might be able to peel off or -- and do a single agent and/or go into a registration study where you have to randomize to see what is the magnitude of the effect.

So the first step toward that is to run the combination in early line, which is exactly what we are doing in our basket study for melanoma. And in our own cervical study, as our Cohort 3 is offering TIL plus pembrolizumab in early line patients.

So you're completely correct, and we have already triggered these steps in order to see what is the magnitude of the effect in early line patients in combination with available care.

Okay. And then kind of finally, how are you thinking about combining TILs with agents beyond PD-1 blockade? Like how would you want to pursue that? How are you envisioning that in the next, like, say, 1 to 5 years?

Yes. Excellent question as well. It is part of our strategy to think about what is in scope for our clinical development program and what is out of scope in our clinical development program, but it may be very well in scope for our investigator-sponsored program.

So when we think about some of these combinations, which, of course, are of high interest to Iovance, we put those typically in investigator-sponsored studies. As you might know, we choose our resources very carefully. And our focus typically is in new indications as well as a pivotal program. So things that may be non-pivotal, yet very relevant in the treatment landscape are part of our IST strategies.

So then kind of following from that, how much of that could be -- beyond being just an investigator-sponsored trial, positioning be a business development positioning where you see -- look to collaborate with other companies that have interesting assets as compared to just having an investigator run a trial with drug A plus TILs?

Absolutely. We are definitely open to that alternative as well. The one consideration for that scenario is most of these drugs are out in the public market already. And so if the collaboration ends up with Iovance having to give up either a portion of its intellectual property or anything of that sort of financial sort of commitments on our side, then I would rather redo an IST. If it's pure collaboration with a sponsor who is bringing a product to market and it's a win-win for everybody, then we're certainly very open to that.

But those considerations go into our decision-making as to we don't want to give up Iovance IP. We certainly don't want to ideally have financial commitments to other sponsors, particularly if the drug is already a commercial product.

Our next question comes from Joe Catanzaro with Piper Sandler.

Maybe just 2 quick ones for me. So in your pre-BLA meeting later this year, would you also look to receive alignment around cervical cancer? And if so, would you need a data cut from the pivotal cohort to frame that discussion?

An excellent question as well. We have been debating this, and I don't know if I can necessarily give you the best answer possible. I think that it really would be dependent on what the division wants to discuss as part of the meeting. However, just to kind of clarify, the cervical program is under a different IND as is the melanoma program. And therefore, the division that we usually request the meeting with is a division that is that IND -- responsible for the review of that IND. So the cervical team members may or may not be in the room when we have our pre-BLA meeting.

So it's a little unclear whether this topic is going to come up. It's because the cervical review team may or may not be in the meeting.

Okay. Got it. And then just one quick follow-up, Karen, how should we read into the fact that you're committing to a registration program in lung cancer but not head and neck cancer, where you've seen an early 30% response rates. And what that means about the kind of activity you're seeing in lung cancer? Or is this maybe more reflective of how you're thinking about head and neck cancer?

Yes. I think that they're not necessarily opposing each other. Let's just take them one at a time. In the non-small cell, once we are ready to distribute and provide the study design, you'll see the study design. But assignments to stage allows for the sponsors to make a decision. While we are committing to the indication, we certainly have the opportunity to make decisions along the way.

In head and neck, we have a slightly different landscape. While we have a response, the duration of response has not been particularly something that we had -- we felt that we want to pursue in a very large way with Gen 2. In head and neck, we introduced 2 other products into clinic earlier part of the year. We introduced the Gen 3, which was a 16-day manufacturing process; and we introduced a PD-1-selected TIL, which we thought based on literature should be a more potent product. So we are trying to solve slightly different problems for each one of them.

Does that make sense?

Yes. No, that's helpful. I'm wondering if we should read into the fact that you are committing that if you've seen any responses in lung cancer that they've been durable. But I guess, I'm assuming you won't answer that.

I think that this sign from what we have seen from Moffitt study has been really promising from my perspective. Seeing 2 CRs that had continued past 12 months and a PR that went out to 18 months is really quite, quite promising. So not only do we see an ORR, which is well above available care, but we also see the DOR in that indication, which is well above available care. And I think that's maybe how we are thinking about it.

Our next question comes from Biren Amin with Jefferies.

Congrats on all the progress. Maria, maybe I'll start with the melanoma indication, given the follow-up from Cohort 2 and the interim data from Cohort 4. Have you had discussions with payers regarding pricing for lifileucel?

Biren, let me ask Jim to speak to the pricing comment.

Yes. We have engaged payers, Biren, but we have not set a price nor discussed the price for lifileucel. As you know, there are many factors to consider in establishing both price and value, which we will continue to evaluate until product approval.

As you know, these potential indications are in areas of high unmet need for which there are no viable treatment, and we believe that lifileucel will support compelling value.

Okay. And then I guess on cervical, I understood that you've had, I guess, or you're going to have a pre-BLA meeting on the melanoma side. But do you plan to have a separate second discussion with FDA regarding cervical? And what type of follow-up period FDA would like to see? And is this driving the BLA submission early 2021?

And I just want to clarify, I guess, from the Cohort 1 cervical cancer, is that data going to be released in 2021? Or can we expect that at the end of 2020?

Yes. I think a lot of that is dependent on the interactions with FDA, you're completely correct. So cervical, as I noted earlier, is under a different IND. And I think it depends on if the review division ends up participating in our melanoma discussions, then we can have a potentially similar dialogue around the follow-up.

If they end up staying in their own -- under their own IND, then we absolutely need a separate meeting with them, which then defines the amount of follow-up. This is precisely why we thought it's safer to move the expected BLA time line to early 2021 because by the time we dose the patients, we approach the agency. We have a dialogue with them regarding the follow-up. Chances are pretty good that it might be a BLA in 2021.

Got it. And then just maybe a couple more for me. Can we expect an additional update from Moffitt at SITC? And given the announcement regarding the posters at ESMO, should we expect anything from late breakers at ESMO? I think late breaker are going to be out in August 17.

I am not aware whether Moffitt is submitting something to SITC. So I can't comment on that. I think from an ESMO perspective, let me not comment what might be in late-breaking or not. I think that we have not really committed to any clinical data flow for 2020 beyond what we already presented. Just want to remind ourselves.

Got it. And then just on the -- with regards to the ESMO poster in terms of the PD-1 knockout, what's the difference between the PD-1 knockout and the PD-1 silencing approach that you presented last year at SITC? I think you used Phio's compound PH-762?

Yes. There's a difference in the method of knocking something out. The Phio product was using an RNAi technology, and that's a transient knockout. The one that is being expected to be presented at ESMO is a TALEN product, which is a permanent genetic knockout.

Our next question comes from Geulah Livshits with Chardan.

Congrats on the progress. So maybe following up on the pricing question. In regards to your discussions with payers and other stakeholders, can you speak to how you might be thinking about pricing considerations for different indications, i.e., melanoma and cervical? In particular, how that might relate to response durations in the different settings potentially?

Yes. Thanks, Geulah. Let me ask Jim to comment on the pricing.

Yes. Thank you, Maria. There are many factors, as we mentioned earlier, that go into setting pricing, and we're continuing to evaluate pricing individually for both metastatic melanoma as well as metastatic cervical. We're looking at the unmet need, the clinical profile, as you point out, efficacy measures around ORR, DOR the safety profile. We're also considering other factors as well in our pricing decision.

And we look forward as we approach launch to having more dialogue with you specifically on pricing and value. But at this point, we're not prepared to talk about pricing.

Got it. And then just a follow-up on maybe the strategy for Europe. It may be kind of an early time to be thinking about that, but in terms of the potential commercial launch planning and infrastructure, do you envision some of those needs to be similar or structured differently towards the versus strategy in the U.S.?

Thank you. That's a great question and one that the team is working on right now as we are evaluating both the best practices and approaches in the U.S. and what will be scalable in ex U.S.

We're considering, as you might imagine, 3 real scenarios: one, going it alone; two, potentially partnering; or three, out licensing. But we're still very much early in the process. And again, we'll look forward to finalizing the assessment and making our go-to-market strategy based upon the data and the market dynamics.

I'm not showing any -- sorry, I'm not showing any further questions at this time. I'd like to turn the call back over to Maria.

Thank you, operator. Thank you again for joining the Iovance quarter end call and first half of 2020. Please feel free to reach out to our IR team if you wish to follow-up on any item. We look forward to address the second half of the year as we further solidify our leadership and TIL development, manufacturing and commercialization.

Ladies and gentlemen, this does conclude today's presentation. You may now disconnect, and have a wonderful day.