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Edited Transcript of IOVA.OQ earnings conference call or presentation 4-Nov-19 9:30pm GMT

Q3 2019 Iovance Biotherapeutics Inc Earnings Call

SAN CARLOS Nov 9, 2019 (Thomson StreetEvents) -- Edited Transcript of Iovance Biotherapeutics Inc earnings conference call or presentation Monday, November 4, 2019 at 9:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Friedrich Graf Finckenstein

Iovance Biotherapeutics, Inc. - Chief Medical Officer

* Maria Fardis

Iovance Biotherapeutics, Inc. - CEO, President & Director

* Timothy E. Morris

Iovance Biotherapeutics, Inc. - CFO, Principal Accounting Officer, Corporate Secretary & Treasurer

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Conference Call Participants

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* Benjamin Jay Burnett

Stifel, Nicolaus & Company, Incorporated, Research Division - Associate

* Biren N. Amin

Jefferies LLC, Research Division - MD and Senior Equity Research Analyst

* Charles A. Frantzreb

Piper Jaffray Companies, Research Division - Research Analyst

* James William Birchenough

Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst

* John Thomas Scott

Cowen and Company, LLC, Research Division - Associate

* Joseph Pantginis

H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst

* Madhu Sudhan Kumar

Robert W. Baird & Co. Incorporated, Research Division - Senior Research Analyst

* Mark Alan Breidenbach

Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst

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Presentation

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Operator [1]

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Good afternoon, and welcome to the Iovance Biotherapeutics Third Quarter 2019 Financial Results Conference Call. (Operator Instructions)

Please be advised that the call is being recorded at the company's request.

Now I would like to turn the call over to Tim Morris, Chief Financial Officer at Iovance. Sir, please go ahead.

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Timothy E. Morris, Iovance Biotherapeutics, Inc. - CFO, Principal Accounting Officer, Corporate Secretary & Treasurer [2]

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Thank you, operator. Good afternoon, everyone, and thank you for joining us. With me on the call is Maria Fardis, our President and Chief Executive Officer; and Friedrich Finckenstein, our Chief Medical Officer. This afternoon, we issued a press release that you can find on our website at iovance.com, which includes the financial results for the third quarter and 9 months ended September 30, 2019, as well as the company 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, clinical trial plans and results, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, licensing and collaboration agreements, future updates and cash guidance.

Forward-looking statements are subject to numerous risk and uncertainties, many of which are beyond our control, including the risk 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 pass the call over to Maria.

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [3]

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Thank you, Tim. Good afternoon. Iovance continues to make excellent progress in development of T cell-based therapies for treatment of cancers. We believe we are in a position of leadership in advancing cell therapies for the treatment of solid tumors.

I'd like to briefly highlight a few recent accomplishments. First, our studies in melanoma and cervical cancer continue to enroll patients with the expectation of completion of enrollment of the melanoma pivotal cohort in early 2020 and for the pivotal cervical cohort before mid-2020. We continue to be on track with our plans to submit a BLA for registration of lifileucel and for LN-145 in late 2020. These TIL therapies have the potential to impact the lives of thousands of patients that have experienced disease progression despite treatment with currently available options.

Second, we continue to follow patients in our Cohort 2 of our melanoma program. One of the 4 abstracts accepted for presentation at the upcoming Society for Immunotherapy of Cancer, or SITC meeting, provides results as read by Independent Review Committee, or IRC, for this cohort. We will provide an update on investigator-assessed response as part of the SITC presentation as well.

Third, we are pleased to announce today that our investigational new drug application, or IND application for our newly developed peripheral blood lymphocytes, or PBL therapy, named IOV-2001, has been cleared by FDA. Development of IOV-2001 PBL product is a result of internal research and development efforts at Iovance and represents our first program in developing a cell therapy for blood-borne cancers. This product is polyclonal and is manufactured in 9 days from 50 milliliters of blood. We expect to begin the clinical trial with IOV-2001 for the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma by the end of 2019.

Now I would like to discuss our development programs in more detail. I'll also provide an update on our corporate activities as we work to make TIL therapy broadly accessible to the many patients who may benefit from this approach. The pivotal study cohort, Cohort 4 of our C-144-01 study of lifileucel in the treatment of metastatic melanoma is progressing well with complete enrollment expected before March of 2020 and a submission of the biological license application, or BLA for lifileucel planned in late 2020.

As I mentioned at the beginning, at SITC, we will have results from Cohort 2 as read by an Independent Review Committee or IRC. We expect that the late-breaking abstract detailing IRC data from Cohort 2 will become available tomorrow on the SITC website.

To provide further detail on our cervical cancer program, I would like to ask Friedrich to speak to the changes made to the protocol. Friedrich?

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Friedrich Graf Finckenstein, Iovance Biotherapeutics, Inc. - Chief Medical Officer [4]

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Thank you, Maria. Hello, everyone. We are also pleased with the continued progress of our pivotal study of TIL therapy in patients with advanced cervical cancer. Further expand on evaluating TIL for broader cervical patient populations, such as earlier line patients as well as post-PD 1 patients, we have amended this protocol and added new cohorts. This amendment is the result of collaboration with key opinion leaders from the Gynecologic Oncology Group Foundation, or GOG, in offering TIL to broader cervical patient populations.

The pivotal study cohort, which is now known as Cohort 1, will treat 75 second and higher line metastatic cervical cancer patients who have progressed following systemic chemotherapy. Cohort 1 is the pivotal cohort for registration. The amendment of the protocol has no impact on the sample size or timing of completion of the registration program in cervical cancer.

We have added new cohorts to the C-145-04 study of LN-145 that address additional patient populations. These cohorts are intended to help evaluate the potential of broadening treatment to include earlier lines of therapy.

Two new cohorts added will enroll 2 distinct populations of patients. Patients who have experienced disease progression following treatment with pembrolizumab and first-line metastatic patients who have not received any therapies other than prior chemoradiation or surgery, to be treated with LN-145 in combination with pembrolizumab.

In addition, we have created 2 other cohorts, which are part of transforming the study into a pivotal program by separating nonregistrational patients into other cohorts, patients who have been previously enrolled but are not considered within the registration population such as patients treated with Gen 1 product and patients who may benefit from retreatment with LN-145.

To summarize, the additional study cohorts reflect our commitment to make TIL therapy broadly accessible to a broader patient population. Back to Maria.

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [5]

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Thank you, Friedrich. Beyond solid tumors, we also see potential for our TIL technology platform in the treatment of hematologic cancers and are pleased to have received U.S. FDA clearance of the IND application for IOV-2001. We are proceeding with an Iovance-sponsored study of the IOV-2001 in chronic lymphocytic leukemia and small lymphocytic lymphoma. We expect to dose the first patient in this IOV-CLL-01 Phase I/II study before the end of 2019. The clinical study for IOV-2001 is a dose-escalation program. We expect to be enrolling in the Phase I portion during 2020.

To further expand the investigation of PBL and heme, Iovance intends to expand its hematologic research to include mantle cell lymphoma as well. We're also pleased to engage with multiple research partners that help us evaluate additional applications of TIL and cell therapy of TIL. Recently, we entered into a collaboration with Lytix Biopharma to study the activity of LTX-315, an oncolytic peptide in conjunction with TIL therapy. Lytix Biopharma is developing oncology molecules able to disintegrate intercellular components of tumor cells resulting in exposure of tumor antigens and danger signal. The oncolytic peptide, LTX-315, has demonstrated proof of concept in patients.

In other solid tumor indications, Iovance has established an investigator-initiated study with Yale University to investigate LN-145 in triple-negative breast cancer. Iovance had previously shown successful growth of TIL in this indication. Toward that, an IND from Yale has been cleared by FDA to initiate investigation of LN-145 in patients with TNBC. This trial is expected to begin enrollment in 2020.

In addition to late-breaking clinical results, 3 preclinical abstracts highlighting Iovance cell therapy will be presented at the upcoming SITC meeting. These presentations will include abstracts covering expansion of TIL from core biopsies, transient genetic modification of PD-1 and TIL and Gen 2 manufacturing results from several solid tumor types. We continue to see favorable results from our manufacturing progress, and I'm pleased to report that our manufacturing success rate continues to exceed 93%. The construction of our Philadelphia manufacturing facility continues, and we are on target to open the facility for commercial manufacturing production in 2022.

Now I would like to ask Tim to share an overview of our financial results. Tim?

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Timothy E. Morris, Iovance Biotherapeutics, Inc. - CFO, Principal Accounting Officer, Corporate Secretary & Treasurer [6]

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Thank you, Maria. My comments will address a few highlights from our financial results. Additional details can be found in the third quarter news release that we distributed earlier.

Net loss for the third quarter ended September 30, 2019, was $49.5 million or $0.40 per share compared to $33.8 million or $0.36 per share for the third quarter of 2018.

Research and development expenses were $41.6 million for the third quarter of 2019, an increase of $13.7 million when compared to $27.9 million for the third quarter of last year. The increase was primarily attributable to higher manufacturing costs resulting from increased capacity added to support enrollment in the pivotal and other clinical studies. The increase is also due to higher R&D personnel costs, including stock-based comp, resulting from an increase in headcount as compared to the third quarter in 2018.

General and administrative expenses were $10 million for the third quarter of 2019, an increase of $2.9 million when compared to the $7.1 million for the third quarter of 2018. The increase was primarily attributable to the increased personnel costs due to additional G&A employees added in 2019.

Net loss for the 9 months ended September 30, 2019, was $134 million or $1.08 per share as compared to a net loss of $91 million or $1.01 per share for the same period in 2018.

Research and development expenses were $111.8 million for the 9 months ended September 30, 2019, an increase of $39.4 million when compared to $72.4 million for the same period in 2018. The increase was primarily attributable to the reasons stated above for the quarter, namely additional manufacturing and clinical trial costs resulting from higher enrollment and increased personnel costs due to increase -- due to an increase in employees as compared to the same period in 2018.

General and administrative expenses were $30 million for the 9 months ended September 30, 2019, an increase of $9.1 million compared to the $20.9 million for the same period in 2018. Again, the increase was primarily attributable to the reasons stated above, namely higher personnel costs including stock-based comp, resulting from an increase in the number of G&A employees.

At September 30, 2019, the company held $367.3 million in cash, cash equivalents, short-term investments and restricted cash as compared to $468.5 million at December 31, 2018. For the third quarter, the change in cash was $42.3 million mainly from cash used in operations. At the year-end, the company anticipates that the balance of cash, cash equivalents, short-term investments and restricted cash may be between $310 million and $320 million.

This month, in addition to SITC, we look forward to presenting at the Crédit Suisse Healthcare Conference in Phoenix, the Stifel 2019 Healthcare Conference in New York and the Jefferies Healthcare Conference in London.

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

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Questions and Answers

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Operator [1]

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(Operator Instructions) Your first question comes from the line of Benjamin Burnett of Stifel.

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Benjamin Jay Burnett, Stifel, Nicolaus & Company, Incorporated, Research Division - Associate [2]

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Congrats on the progress. Two quick questions for me. Just one quickly on the cervical cancer updates. I appreciate the color on this, but I just wanted to clarify one thing. So I understand that these changes don't impact the registrational cohort, the addition of these other cohorts. But does this at all change your strategy for filing for approval? Like would you want to wait for these other cohorts to complete to maybe seek a broader label? Or is the strategy still to file with just Cohort 1?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [3]

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Ben, thank you for the question. No, it does not change our strategy for filing. We will be filing based on Cohort 1 data.

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Benjamin Jay Burnett, Stifel, Nicolaus & Company, Incorporated, Research Division - Associate [4]

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Okay. Perfect. And then also, I just wanted to ask, what are your plans for providing future updates to the melanoma Cohort 2 patients? And I guess, specifically, the investigator-assessed responses, will there be future updates with, I guess, based on the investigator-assessed responses? Or is the messaging going forward going to be all about the Independent Review Committee?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [5]

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We will provide an update on duration of response by investigator at SITC as well as overall response rate, which we have disclosed before. So there will be updates at SITC based on investigator-assessed data from Cohort 2.

Just to kind of make sure that I sort of closed the loop, the update may be a number or maybe just not reached, either one of them is considered an update.

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Operator [6]

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Your next question comes from the line of Jim Birchenough from Wells Fargo.

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James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [7]

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Let me add my congratulations on the progress. A, if you could just remind us when the abstract was submitted for melanoma? And if we should expect an appreciable change from what we see tomorrow and what we see Friday?

And then secondly, could you maybe comment on any expected erosion from investigator-assessed to central view that we see in other studies just to maybe set the frame of reference of what happens in melanoma, typically between investigator-assessed and central review? And then I've got a follow-up.

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [8]

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Sure. Thank you for the question. So the data which you might see tomorrow will be updated for the Friday poster. We are cutting the data with updates. There also will be additional information regarding investigator DOR sort of assessment because we have committed to The Street that any time we have an update, we'll provide it. We are obviously very pleased with the data. This is part of why we are putting it out. And needless to say, in terms of the concordance that we see, we do want to remind everyone for a very metastatic disease the opportunity for an investigator to choose different lesions than IRC is quite high. There's abundance of literature that says that these 2 data are very discordant. We felt that this data was very strong and further confirms the observation we have had in Cohort 2, and that's the data you're going to see at SITC.

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James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [9]

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And then maybe just separately, Maria, on the PBL opportunity, could you maybe speak to why a great indication initially with CLL, SLL, but any thoughts of broader blood cancers, hematologic malignancies like myeloma? What's -- I guess what makes you choose CLL to start with? And at what point do you move more broadly into things like myeloma?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [10]

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Yes, great question. Thank you. We recognize that the cells that are target of these T cells for expansion are not very frequently found in blood. This has been sort of a bit of a holy grail, what everybody is trying to find the cells in blood, and they're just not present in blood. However, if the patient has received ibrutinib as prior therapy, the cells are, in fact, found in higher frequency circulating in blood. So we started with patients that are post ibrutinib. This finding was presented at ASH a couple of years ago. And once we started with that process, we realized that these patients are specifically either on ibrutinib and they're progressing or they have already progressed. So we started CLL because we know ibrutinib was very well adopted in CLL. And I noted today that we are also interested in expanding this type of work in mantle cell. So we are interested in particularly post-ibrutinib patients and hematologic indications, which is quite a broad patient population to begin with.

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James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [11]

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And maybe just a final question. Just on implications of the core biopsy data we'll get at SITC, Maria, how could that impact your ability to treat patients in terms of making the process easier, getting some more patients where you might not be able to get as invasive a biopsy? Just trying to get a sense of the implications of the core biopsy data?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [12]

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Yes, absolutely. Thank you. Indeed. And I would expect that the process of excisional biopsy would become simpler. A core biopsy leading to sufficient TILs is certainly something that a lot of patients would be much more enthusiastic about, and we believe that our addressable market would be significantly impacted.

In the late-line metastatic disease, I think that there is ample amount of tumor in a disease such as melanoma and even cervical. But as we go into earlier line, I think these are exploratory work that is critical for our earlier-line patient population where the tumor bulk may not be as large. That's what we went after for.

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Operator [13]

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Your next question comes from the line of Mark Breidenbach.

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Mark Alan Breidenbach, Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst [14]

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Congrats on the progress. Maria, I was wondering if you could elaborate on the sizes of the new cervical cohorts and maybe speak about any prior data on TIL efficacy in either very early line or very late-line cervical cancer settings, either from the NCI or other academic centers?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [15]

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Well, maybe why don't I ask Dr. Finckenstein to speak to this?

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Friedrich Graf Finckenstein, Iovance Biotherapeutics, Inc. - Chief Medical Officer [16]

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Sure. Happy to. So I'll take the first part of your question. This was about the size of the additional cohorts. Both of those are exploring the efficacy and safety profile in up to 24 patients in the settings that we described. The other 2 cohorts that are really a clarification don't have a defined sample set because we're not actively enrolling into these.

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Mark Alan Breidenbach, Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst [17]

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Got it. And with regard to prior experience with TIL in, say, newly diagnosed cervical patients, have we seen any of that before?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [18]

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Not in absolute treatment-naive patients. Even when NCI was exploring TIL therapy, the patients, the bulk of the patients were post chemoradiotherapy. So the patient population has always been relapsed/refractory. I don't believe I've seen anyone having offered TIL in front line to the degree I'm aware of.

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Mark Alan Breidenbach, Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst [19]

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Okay. And finally, just one on another TIL trial that we're expecting to see data from at SITC. I know there's a group at Moffitt that's evaluating TIL in non-small cell lung cancer. I was wondering if you could just remind us of the major manufacturing differences between your Gen 2 product and what Moffitt is doing? And if you think there can be any meaningful read through between that Moffitt lung trial and your ongoing basket trial that has some lung cohorts in it?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [20]

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Thank you, Mark. Yes. So Moffitt has been conducting a non-small cell lung cancer patient study. The study design allows for patients to come in, get excisional biopsy for generation of TIL. A pre-rapid expansion protocol, which is approximately 3 weeks or so is conducted. The patient, in the meantime, is exposed to nivolumab. And upon progression, or if they see no clinical benefit, the patient is then treated with their own TIL.

The differences between the Moffitt study and Iovance studies is both are in manufacturing process. Their manufacturing process is more involved, associated based on NCI manufacturing process for longer as well as the fact that the study from Moffitt is using what is called a tumor banking model, where they excise the tumor, they expose the patient to nivolumab. Upon progression or no clinical benefit, they allow the patient to receive their TIL. And last point of differentiation between what Iovance does and what Moffitt does is the amount of IL-2 that is administered. Moffitt study uses what is called a decrescendo IL-2, which is a lower-dose IL-2 and we use what is called high-dose IL-2 after 6 administration.

So with this 3 points of differentiators between our studies and theirs, we remain very excited about what we see with Moffitt. Moffitt really showed the proof of concept for TIL in non-small cell for the first time. There was no data up to that point that's showing TIL may do something in non-small cell. Based on that data, we have started now 2 cohorts of studies in our basket study, the COM -- COM-202 study, where we are offering TIL for earlier-line patients in combination with KEYTRUDA, and in a second cohort, where we are offering TIL in relapsed/refractory patients as a monotherapy or mono sort of a treatment option. So we see that this is maybe somewhat representative as the proof of concept, but it's not exactly the same manufacturing process and product. So those are sort of the pros and cons.

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Operator [21]

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Your next question comes from the line of Biren Amin from Jefferies.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [22]

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Maria, on the cervical and melanoma time lines, I think you mentioned that the BLA is expected to be submitted at year-end. But for cervical enrollment, it completes before midyear and for melanoma, it finishes in early 2020. So should we assume that the follow-up on cervical will be shorter by at least a quarter compared to the melanoma trial?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [23]

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Biren, thank you for the question. We are really excited about the enrollment rates in the melanoma program. And so we think we had initially thought that we might be looking at around March time frame, we think it's possible to potentially have an earlier time frame. So that's sort of the distinction between them.

In terms of amount of follow-up, we don't know quite how much follow-up exactly the agency would be open to receiving. There is 2 ways of thinking about follow-up, a median follow-up versus last patient last evaluation follow-up. We recognize that we have breakthrough designation in the cervical landscape. So there's a possibility that FDA may be open to different follow-up periods between melanoma and cervical. So to kind of short -- give you a shorter answer, we don't know quite exactly how much time they're going to ask for. But we are planning on our BLA submission for late 2020 for both indications.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [24]

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Maria, I guess, have you had any discussions with the agency regarding this topic of median fall versus last patient follow up? And then, I guess, on -- in the cervical trial, you had additional cohorts that you've added, what drove the addition of those cohorts? Was it investigator feedback? Was it regulatory feedback?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [25]

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Sure. So from a follow-up perspective, yes, we've had some preliminary discussion and what we're offering right now is based on that discussion. Having said that, it's important to go to a pre-BLA meeting and discuss with the agency exactly what is acceptable and what is not with them. So what we are offering is quite aligned with our prior dialogue with FDA.

In terms of additional cohorts, do you want to maybe add a comment to this or should I address? So Biren, you were wondering whether we wanted to expand the patient population, is that your question for cervical?

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [26]

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Yes, for cervical, clearly, you've gone into post PD-1 into the first-line setting. And so I'm just interested to hear what drove that? Was it regulatory feedback? Or was it investigator feedback?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [27]

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Actually both. Regulators were certainly excited about broadening our footprint in TIL therapy in cervical. As Friedrich noted, we also had a dialogue with GOG, which is Gynecological Oncology Group, which is a very large key opinion leader, sort of a setting where they decide sort of what sort of studies they can offer for patients in the gyn setting, and they were very excited about earlier-line patients as well. So we definitely took advice from both health authority as well as GOG into consideration in proposing these additional cohorts.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [28]

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Got it. And then just one maybe last question on the cervical cohort. I think the company mentioned that patients that have already been enrolled, but would not be eligible for Cohort 1, such as those that received the Gen 1 manufacturing process could be enrolled into these additional cohorts that you started. So I guess my question is, how many of the 27 patients presented at ASCO would not be eligible for Cohort 1?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [29]

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So this new cohort is, for example, Gen 1 manufacturing, which was not part of what we presented at ASCO. So Biren, the effort really here is to clean up this study and as showed at Cohort 1 is a unanimously defined patient population, which supports the registration. So I don't know how to answer the question a little bit because we did not mix Gen 1 in our ASCO presentation. Gen 1 was presented before as part of the financing, but was not part of ASCO.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [30]

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Got it. So the ASCO data was strictly Gen 2? And I guess all of those 27 patients would still be counted towards Cohort 1?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [31]

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We did -- as you see FDA feedback, we did say that most of the patients in the enrolled 27 patients would fulfill the criteria and that's in our previous July press release. So we did talk about that.

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Operator [32]

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Your next question comes from the line of Joseph Pantginis from Wainwright.

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Joseph Pantginis, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [33]

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Maria, I was just curious, I'm very glad to see the progress now for 2001, so good luck with the heme programs. I was wondering if you could provide any nuances since you said this is obviously internally developed, about maybe some differences between what you're working on with Ohio State?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [34]

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Joe, thank you for the question. This is very much the same collaboration. This has always been a collaboration with Ohio State University. The process, however, has been entirely developed by Iovance researchers. It's based on the data, however, that OSU showed where the T cells were more in circulation subsequent to treatment with ibrutinib. So there's different aspects of this collaboration. The manufacturing method development was entirely done at Iovance. The data, however, where to find the TILs in the blood was based on findings at OSU. The study that will use this product into clinic is a company-sponsored study, though.

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Operator [35]

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Your next question comes from the line of Madhu Kumar from Baird.

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Madhu Sudhan Kumar, Robert W. Baird & Co. Incorporated, Research Division - Senior Research Analyst [36]

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So one question is, what do you guys think of the path for approval for TILs in Europe? What is the kind of regulatory interactions you've had with the EMA regarding kind of path forward for TILs for melanoma or cervical? And then secondly, you mentioned maybe you have a transient knockdown study that you'll present at SITC. How are you thinking about the potential for either transient or permanent gene inactivation in TILs ex vivo as a means to kind of do the next step for a TIL production?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [37]

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Sure. Madhu, thank you for the question. In terms of TIL in EU, we obviously have had interactions with regional health authorities as we have been either filing for CTAs and the CTAs are active. So we've had a number of different dialogues that way as well as just regional meetings, but we have not spoken to EMA as a central procedure, and that's something we intend to do in part of 2020. So that dialogue is expected to be had. We are very clear that various countries are very aware of this product coming.

In terms of transient knockdown versus potential permanent genetic modification, we are very excited about the data that we have. We hope to take at least one of these products into clinic in 2020, and you're going to see some of the knockdown data in terms of sort of the properties of the cells, subsequent to knockdown as part of our SITC poster.

I do think they might have a different safety profile. One of them is transient and one is permanent. So we might just find out in clinic, whether they behave the same or differently.

I guess I do want to add another point Madhu, that we wanted to have multiple shots on goal from both a safety and efficacy perspective. So we consider a transient modification as well as both permanent genetic modification as viable routes.

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Operator [38]

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Your next question comes from the line of Joseph Catanzaro from Piper Jaffrey.

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Charles A. Frantzreb, Piper Jaffray Companies, Research Division - Research Analyst [39]

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This is Charles on for Joe. I wanted to ask about the ongoing cohort in head and neck cancer and whether you could specifically say, if we can expect any data update from that cohort in 2020? Or if not, more generally speaking, whether you had noticed any change in enrollment since the approval of pembrolizumab in first-line head and neck? Or if you had a sense of how quickly pembrolizumab is being adopted there?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [40]

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Thank you so much for the question. Yes, I actually agree, we do see a change in enrollment rate, I think, because the landscape for care of these patients has changed, in fact. It used to be that the patients would receive chemotherapy. Upon progression, they would receive anti-PD-1. Anti-PD-1s would offer around 13% to 15% response rate. And subsequent to anti-PD-1s, the patients had a fairly short median OS. But it has been very difficult to get these patients and make sure that we are able to offer something to them that allows us to have a follow-up with the patients and see benefits of potential TIL therapy. Today's landscape is definitely changing. And we do see a slowdown in enrollment, perhaps because a lot of these patients are now changing the path by which they come to clinical trials. They're receiving pembro plus chemo in front line, and then ultimately, when they progress, and they're beginning to -- we're beginning to see them, they're coming into our trials. So that's a very great observation. The change in the landscape for head and neck, we do see that.

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Charles A. Frantzreb, Piper Jaffray Companies, Research Division - Research Analyst [41]

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Okay. And then as for when we can expect to see updated data, do you have any guidance for that? Is it possible in 2020? Or is it too early to say at this point?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [42]

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I think it's a little too early to say. We have not committed to a time frame for data flow for that study yet.

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Charles A. Frantzreb, Piper Jaffray Companies, Research Division - Research Analyst [43]

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Okay. And then, Tim, I have a question on operating expenses going forward. Should we expect OpEx for R&D and SG&A to continue to increase? Or should we expect it to level off at some point?

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Timothy E. Morris, Iovance Biotherapeutics, Inc. - CFO, Principal Accounting Officer, Corporate Secretary & Treasurer [44]

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Yes, we haven't given any guidance yet for 2020, but when you're going into precommercial mode and continuing to build up your plants and are preparing to file the BLAs, I think it'd be hard-pressed to say that they'll go down. So -- but we'll give some guidance on the year-end call for cash in 2020.

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Operator [45]

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Your next question comes from the line of Boris Peaker from Cowen.

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John Thomas Scott, Cowen and Company, LLC, Research Division - Associate [46]

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This is John Scott on for Boris. On manufacturing costs, you mentioned the R&D rose because of increased capacity. Can you comment on the cost per patient now versus previous quarters, if you saw that change? And then secondly, can you give a rough estimate on what proportion of your manufacturing capacity is being used? And do you anticipate a need to further scale up given the study cohorts you've discussed?

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Timothy E. Morris, Iovance Biotherapeutics, Inc. - CFO, Principal Accounting Officer, Corporate Secretary & Treasurer [47]

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Sure, John. This is Tim. Yes, we don't break down the cost per patient. What we have done, though, is we had to make sure we had enough capacity, both in the U.S. and in Europe to ensure we can enroll these pivotal studies on time. But the cost per patient, remember, there's 2 components to the CMOs. There's a fixed cost for a given suite. We had disclosed earlier that we'd added some additional capacity at Wuxi. And so you could probably assume that there was a fixed cost associated with that. The cost per patient still remains relatively consistent in terms of the materials and the labor component of that.

In terms -- I think your second question if additional capacity is needed or not, I think given the timing and the suggestion for the pivotal is finishing up essentially in the first half or the first part of 2020, I think we have sufficient capacity right now. I don't see a need to scale up any additional capacity, at least as it relates to the pivotal.

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Operator [48]

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As we have no more questions, we would now like to turn the call over to Maria Fardis for closing remarks. Maria?

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Maria Fardis, Iovance Biotherapeutics, Inc. - CEO, President & Director [49]

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Thank you, operator. We are pleased to have this opportunity to reflect on our progress and the hard work that has allowed us to achieve a position of leadership in this industry. We would like to acknowledge the many individuals who have helped us reach this point, including our employees, our shareholders, patients, the investigators in our ongoing studies and the researchers at our partner institutions. We would not be able to reach our goals without the invaluable, coordinated efforts from the supporters of these groups. Finally, we would like to thank you for joining us on the call today and look forward to providing future updates of our progress at the future dates. Have a good day.

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Operator [50]

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Ladies and gentlemen, thank you for your participation in today's conference. This concludes today's program. You may now disconnect.