Good afternoon, and welcome to the Iovance Biotherapeutics Fourth Quarter and Year-End 2019 Financial Results Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time.

[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 Sara Pellegrino, Vice President, Investor and Public Relations at Iovance. Please go ahead..

Thank you, Lorie. Good afternoon, everyone. And thank you for joining us. Speaking on today's call will be Maria Fardis, our President and Chief Executive Officer; Friedrich Finckenstein, our Chief Medical Officer; and Tim Morris, Chief Financial Officer.

This afternoon, we issued a press release that you can find on our website at iovance.com, which includes the financial results for the fourth quarter and year ended December 31, 2019 as well as the corporate update.

Before we start, I would like to remind everyone that statements made during this conference call will include forward-looking statements regarding Iovance’s goals, business focus, business plans, pre-commercial activities, clinical trial plans and results, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, licensing and collaboration agreements and future updates.

Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward-looking statements.

With that, I’ll pass the call over to Maria..

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

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

Our medical affairs team is in place to work with a network of treating HCPs and patient advocacy groups to assure that information about TIL is available to interested organizations.

We also continue optimizing our logistics and infrastructure to assure a patient focused organization is in place not only for our clinical program but also for commercialization. We have made great progress in identification of centers that we work with in the clinical program and expect to collaborate with them in commercializing TIL.

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

As our market research and commercial preparation continues, we look forward to providing updates on our launch plan throughout the year.

I would like to ask now our Chief Medical Officer, Friedrich Finckenstein, to provide an update about our other clinical programs and ongoing research at Iovance? Friedrich?.

Thank you, Maria. I would like to begin with the expansion of our ongoing C-145-03 clinical study in head and neck cancer, which remains an important indication for Iovance. We continue to enroll patients in our C-145-03 study, and recently added new cohorts to the study.

Patients in the first new cohort will be treated with LN-145 manufactured with our new proprietary 16-day, third generation TIL therapy process, which we call Gen 3. The second new cohort will evaluate a selected TIL product PD-1 select, designated as LN-145-S1.

We prevented preclinical inflammation on PD-1 selected TIL at SITC in November 2018, which demonstrated improved tumor cell killing properties for this product. This cohort is the first time we are testing selected TIL in the clinic, and we look forward to enrolling patients in this new cohort.

We have also made significant progress in evaluating the broader potential for TIL treatment in earlier lines of therapy for checkpoint naïve melanoma, head and neck, and non-small cell lung cancer. Patient dosing in the IOV-COM-202 clinical study, which we also refer to as our active study was initiated in May 2019.

Three cohorts will evaluate TIL plus pembrolizumab in patients who are immune checkpoint inhibitor naïve with melanoma, squamous cell carcinoma of the head and neck, and non-small cell lung cancer. And the fourth cohort, LN-145 monotherapy is offered to relapsed/refractory non-small cell lung cancer patients.

Enrollment across all four of these cohorts is proceeding well and we have plans to add a fifth cohort to investigate our selected TIL, LN-145-S1 in melanoma patients who have received prior anti-PD-1 and BRAF or BRAF MEK as indicated. This is the same selected TIL product that we have introduced into the head and neck study.

The additional cohort will also increase the overall target enrollment in the back of study. Moving on to our peripheral blood lymphocyte therapy or PBL therapy, we're very excited to be in clinic with our very first Iovance cell therapy for blood cancers.

I am happy to report that last week, we dosed the first patient in the clinical study of our PBL therapy, which we have designated IOV-2001. The Phase 1/2 study named IVO-CLL-0l is currently enrolling patients with relapsed or refractory CLL or small lymphocytic lymphoma, SLL into the Phase 1 dose escalation portion.

We generated a polyclonal population of PBL for therapeutic use from 50 milliliters of blood using a 9-day T-cell manufacturing process. Development of IOV-2001 PBL therapy is a result of internal research and development efforts at Iovance to translate our experience with killing solid tumors.

We think the study will provide important proof-of-concept to our PBL approach and look forward enrolling additional patients in this study. Before I turn the call to Tim, I would like to briefly mention our earlier stage research and development efforts.

As announced in January, we have obtained a license from Novartis to develop and commercialize an antibody cytokine engrafted protein, referred to as IOV-3001 as a targeted and selected IL-2 analog. IL-2 is a major component of our treatment.

So, the development of proprietary IL-2 analog is valuable opportunity to further optimize the beneficial properties of the IL-2 to improving pharmacokinetic and pharmacodynamic properties as compared to the currently available IL-2. We are also exploring genetically modified TIL with the potential to create an even more potent TIL.

Under research collaboration and exclusive worldwide license agreement with Cellectis, we have licensed certain TALEN technology to develop genetically edited TIL in several cancer indications. The worldwide exclusive license enables us to use TALEN technology to address multiple gene targets to modify TIL for therapeutic use.

I will now hand the call over to Tim to discuss our financial results..

Thank you, Friedrich. My remarks will address the high level financial results from our fourth quarter and full year 2019. Additional details can be found in the press release that we distributed earlier, as well as our Annual Report on Form 10-K to be filed shortly with the SEC.

Net loss for the fourth quarter ended 2019 was $63.6 million or $0.50 per share as compared to a net loss of $32.6 million or $0.27 per share for the fourth quarter 2018. Net loss for the full year 2019 was $197.6 million, or $1.59 per share, compared to a net loss of $123.6 million, or $1.27 cents per share for 2018.

Research and development expenses were $54.2 million for the fourth quarter 2019, an increase of $26.8 million, compared to the $27.4 million for the fourth quarter 2018. Research and development expenses were $166 million for the full year 2019, an increase of $66.2 million, when compared to $99.8 million for the prior year.

The increases in the fourth quarter and the full year over the prior periods were primarily attributable to an increase in costs associated with manufacturing activities and increased capacity, clinical trials due to higher enrollment and the growth of the internal research and development team.

General and administrative expenses were $10.9 million for the fourth quarter 2019, an increase of $3.4 million when compared to $7.5 million for the fourth quarter 2018. General and administrative expenses were $40.8 million for the full year 2019, an increase of $12.4 million compared to $28.4 million for 2018.

Increases in the fourth quarter and the full year over 2018 were primarily attributable to the growth of internal general and administrative team as well as higher IP legal costs and market research activities and preparation for commercialization.

At December 31, 2019, we held $312 million in cash, cash equivalents, short-term investments and restricted cash compared to $468.5 million at December 31, 2018. In addition, as Maria mentioned, we are building our own Iovance manufacturing facility. We expect to invest approximately $85 million over three years for equipment and construction.

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

Thank you all for attending the call today. We look forward to an exciting and productive 2020. In closing, our anticipated milestones for this year include last patient to be dosed in the pivotal program for LN-145 for cervical cancer; pre-BLA meeting with U.S. FDA; melanoma top-line pivotal data; and BLA submission.

Before we begin the Q&A session, I would like to remind everyone that Iovance does not comment on speculation in the media and will not answer questions related to any articles circulating in the press. I will now turn the call over to operator for any questions.

Operator?.

[Operator Instructions] We have a question from the line of Jim Birchenough from Wells Fargo. .

Hi., guys. Congratulations on all the progress.

I guess, thinking ahead to the commercial opportunity, just wondering if you think about the 7,200 patients that die each year of melanoma and if you thought about the addressable population that could benefit in cervical cancer, could you talk about the initial target population of 20 plus centers for each and what capacity they have to treat these patients? And then, I guess the second part of it is, one of the gating items to really making this more broadly available and how you’re going to go about accessing that?.

Sure. Hi, Jim. Thank you for the question. From a commercial opportunity perspective, although unfortunately 7,200 patients die in the melanoma landscape, and one can consider TIL certainly an option for these patients, we are actually thinking about second and third line. And that patient population is broader than 7,200 that is currently recorded.

So that's how you're thinking about sort of positioning the products, and that's the patient population that our current protocol allows. In terms of the centers, I just want to make sure that I'm clear. We're not targeting just 20 centers.

The comment I made was, we start with the sites that have been participating in a clinical program and those have been around 20 melanoma and cervical. We certainly intend to expand that by the time we’re getting ready to take off the product in the commercial landscape..

And I guess, the question, Maria, just a follow-up. When you think about those initial center that have had the most experienced with TIL therapies, give a sense of what proportion of the melanoma patients they treat.

And how many more centers do you think you need to gain experience to get more broad access to that second third line opportunity?.

Yes. We do know exactly what is the distribution of patients in terms of where the bulk of them are. We certainly have an internal math. We consider where they typically go to receive their care. I don't know if I'm quite ready to speak about that specific plan. But, we certainly think about it in the same way as you're approaching it..

And just a quick one, Maria.

Is the cervical filing, the LN-145 filing something you expect to get done in 2020 or does that really depend on when midyear you close out enrollment and could that slip into 2021?.

Right. We recognize that the timing of cervical and melanoma are slightly apart. We currently continue to plan for cervical submission by year-end. And you're correct that some of that would depend on exactly when cervical enrollment will complete, as well as a dialogue with FDA.

But, the current plans remain to go ahead and submit, assuming of course, all of the milestones are met around later part of 2020, as of now..

Your next question comes from the line of Ben Burnett from Stifel..

I have a question on the IOV-COM-202 that's the basket trial. Looking at TIL plus pembro as well as the fourth cohort monotherapy.

I guess, do you have an expectation as to when we might get data for these first four cohorts?.

Hi, Ben. Thank you for the question. We started patient dosing in May of 2019. Given that the study is a basket study, the patients may be distributed between the cohorts. We really would like to make sure we have a handful of patients in each cohort before we can report them.

So, we have not committed to a specific timing for data flow from the study yet..

If I could just ask one more on the -- regarding the recent Novartis collaboration. Can you talk more about the non-Treg activating IL-2 antibody that’s being developed, I guess. How is the antibody been engrafted? And I guess what makes this a more selective IL-2? Thank you..

Sure. Yes, of course. So, you might know IL-2 binds to three different subunits alpha, beta and gamma subunits on various T cells. The beta gamma sub units is what we are interested in; the alpha subunit is more prevalent in binding toward Treg. We're trying to rule that binding out.

So, the CDR that we have does not allow for this particular IL-2 to bind to the alpha subunit. It in fact focuses it better on the beta gamma subunit. That's why we expect it to be better..

Okay.

And I guess, at this point, you comment on just kind of the architecture of helping antibodies engraft it or is that -- at this point, is that proprietary?.

It’s certainly proprietary. And thank you for understanding..

Okay. Makes sense. Thanks so much..

Thank you..

Your next question comes from the line of a Joe Pantginis from H.C. Wainwright..

Thanks for taking the question. Maria, I was just curious if you could provide a little more detail with regarding your strategy for the evolution of your manufacturing facilities. As you mentioned in your prepared comments, you have WuXi right now and looking to have your new facility come on line in 2022.

How do you look to sort of share responsibilities between these two facilities? And also, when your facility comes on line, do you anticipate that that will start off with Gen 3?.

Joe, to correct your statement, it will start off with Gen 2, correct? Is that what you said?.

Yes. And when it would evolve to Gen 3. Sorry, yes..

Right. So, we -- currently, our commercial plan is very much locked and loaded for Gen 2. The facility is very much designed around Gen 2. Of course, they can support other manufacturing properties, should there be a need for them. But right now, we very much are planning on our commercialization for Gen 2 process.

In terms of rules and responsibilities, we already have started building our team out in Philadelphia. Certainly, the building of -- the building itself requires a number of staff who are familiar with the process.

We have great expertise in-house, starting from our engineering team, as well as people who are very familiar with the process, and in terms of process development and optimization. So, we already have a team that is slowly ramping up to what is going to be needed by the time the commercial activities roll out.

In addition to the local team members in Philadelphia, we have additional team members such as quality or otherwise, and some partners [ph] who are supporting the activities for the facility. So, I don't foresee any sort of a switch on where everybody then -- hundred people are hired and they go into the facility.

I see a rollout, and the rollout has already been started..

That's really helpful. Thank you. And if I could just ask a quick follow-up on your research front.

With regard to the PBL program, obviously, it's exciting that it's a much shorter process and how you can identify the TIL? Just curious, is there any major difference once you extract T cells from the blood, are there any major differences between Gen 2 and the TIL identification process before you expand them in the PBL versus Gen 2?.

We have a very different process that we use for PBLs. And again, some of those proprietary and bulk of it has not been sort of shared already. So, yes, there's rather significant differences, the cells, the T cells that we usually harvest from tumor are not in very high concentration in blood. We are already familiar with that.

We know that they are difficult to find. So, we had to implement different procedures in order to fix T cells out and we were very successful obviously in doing so. But yes, there's differences in how we get the cells from the source, one being a tumor, one being blood..

Your next question comes from the line of Mark Breidenbach from Oppenheimer..

Maria, I noticed that the pivotal cohort in melanoma enrolled a little bit faster than maybe you had initially projected and the pivotal cohort in cervical maybe more or less on the timeline you had initially projected. I'm just wondering if you can point any specific factors that are contributing to that discrepancy.

And also, is it safe to assume we would want a minimum of six months follow-up once the pivotal cervical cancer completes enrollment before we see top-line data from that?.

Thank you, Mark, for the questions. Yes, you're correct. Melanoma enrolled faster than we expected. And I think that definitely shows a clear unmet medical need. The cervical landscape is definitely changing. As you're aware, there's earlier line, Keytruda studies coming into the space, both in terms of clinical trials as well as just the commercial use.

And so, the patients that we're enrolling into our cohort 1 is certainly -- the nature of the patients that are out there is changing. So, it's really due to the change in landscape.

Now, we anticipated that this is going to happen, and I made a comment about it, added to the cohorts into our LN-145 study for cervical call in anticipation with the change in landscape. So, we have thought through this and we have some alternative strategies, if this continues. And your second question in terms of the six months of follow up.

We thought about six months of follow-up for melanoma just because enrollment closed so early, and it allows us to do a six months follow-up. There has not been really a request, either from agency or otherwise, for certain amount of follow-up. So, I think that this is really a subject to discussion with U.S.

FDA in terms of how much follow-up they might be asking for. But, I do want to note that the six months is a Iovance proposal in the melanoma case..

Understood. And maybe just a quick follow-up on the Gen 3 process. I'm curious why this is really initially being focused in head and neck. Maybe you could elaborate a little bit on why it's important to have a manufacturing timeline in head and neck.

And I'm also curious with regard PD-1 select version of TIL, what is that -- what was the impact of that on manufacturing timelines, does that add several days to the process?.

Yes. We had recognized earlier on that the patients in head and neck cancer have a fairly short survival unfortunately. So, we felt that a shorter manufacturing process really could benefit a patient population that doesn't -- many times, they don’t make it to the first assessment or a second assessment.

So, that's why we implemented that initially into the head and neck study. The PD-1 selected process does not add additional day to the manufacturing process. It is - in fact, we have optimized the process so that it is not longer than our Gen 2. So, it's the same duration as our Gen 2 process..

All right. Thank you for answering questions and congrats again. .

Thank you, Mark..

Your next question comes from the line of Reni Benjamin from JMP Securities..

Maria, can you just talk a little bit about how many patients do you think are required per cohort before you feel pretty comfortable with disclosing results, not just from the basket, but maybe some of your other studies? And you mentioned duration in answer to Mark's question, but what other kind of gating items need to be discussed with the FDA prior to filing?.

Thank you, Ben. I don't think there's a magical number for us to disclose, but I prefer, for example, at least 5 patients per cohort would be kind of nice to talk about it. But there's not a magical number. I think it depends on what we see. But that's my mental note.

But if you asked me what is your mental number, somewhere between 4, 5, 6, 7 would be really good numbers. But again, I do emphasize, there's not a magical number by which we want to disclose something, the data for that study.

In terms of -- did you ask about the duration? Can you repeat your question on what you were asking on the duration front?.

No, sorry. Just in regards to your discussions with the FDA prior to filing. I think, you mentioned, duration would be one of the things that you'll be talking about, since they don't have a particular mandate.

But, what are other items that you think are worthy of discussion prior to filing?.

Sure. So, just to make sure that I clarify the question, the specific item that we’d be asking to agency is duration of follow-up, another duration of response, the duration of response is the property of the product. But the duration of follow-up that they will make to see is typically a subject of discussion as part of a BLA dialogue.

The BLA pre-meeting typically has a component of logistics involved in it. It usually has a component of how you're going to build your BLA. BLA is a very large document, exactly where to find something. And then there's other components that we ask questions about. It's a bit of a logistics meeting as well as guidelines for next step.

Sometimes the other topics, scientific topics also pomp up. I won't go into too much detail, obviously, that's something that's proprietary for each company as to what they discuss at the pre-BLA meeting..

Got it. And I guess just one final question from us is, really the cadence of data, seems like it will be primarily second half focused from kind of all the programs that are running.

Are we thinking about that correctly? Would you release kind of top-line data for melanoma, then a filing and then kind of full data sometime in '21? Is that how we should be thinking about it, or is there a different cadence of results -- or reporting results?.

I wouldn't rule out any specific patterns in any shape or form. Just specifically talking about the melanoma top-line data, the way I’m thinking about it right now is possibly just disclosing very high level top-line data, and then submission to FDA and maybe disclosing more information at a medical conference.

That's sort of how we're thinking about it right now..

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

Hi, great. Thanks for taking our questions. So, I guess our first one is, what is the ex-U.S.

regulatory path in melanoma in cervical cancer?.

Sure. Thanks, Madhu. We do have plans to initiate a broader dialogue with EMA health authorities called CHMP, potentially in later part of 2020. It's not that there has been no dialogue. We obviously have a number of clinical sites that are active in EU and as part of that we submit what is called a clinical trial authorization, it has to be submitted.

And preliminary dialogue has been had with local health authorities. We do intend on starting a sort of more of a centralized procedure later part of the year in 2020..

Okay. And just a more practical question about the PD-1 combination studies.

So, [indiscernible] TIL, do the IL-2 treatment? And then, is there like a washout period before you start at PD-1, like how much a gap is there between the TIL procedure and the beginning of PD-1 administration in the combination studies?.

So, the PD-1 is administered prior to TIL. And that information to the degree I can speak to is available on clinicaltrials.gov. But, I won't be able to go into details of the study design, Madhu..

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

Thanks for taking my questions. And it was great to see you earlier today. So Maria with the melanoma cohort 4 fully enrolled, how do you think about the baseline characteristics of this cohort compared to cohort 2 in terms of median prior lines, as well as in terms of PD-1 refractory status? Thanks..

Hi, Biren. Thank you for your question. We have not been analyzing cohort 4. We actually have a data integrity document in place where we don't compile the data for cohort 4. So, I won't be able to speak to the patient population in cohort 4.

I did note that we designed a protocol the same way, the patient population definition is the same between cohort 2s and 4s, and we try to keep the participating sites to the degree we could control it the same..

And then, can you just talk a little bit about the PD-1 selected TIL.

What are you hoping to gain from this program in terms of activity? And I guess, what are you currently seeing in the head and neck cohort that allowed you to decide to move forward with not just the Gen 3, but the PD-1 selected TIL?.

So, some of the data for PD-1 selected TIL was presented at I think it was 50 2018. The criteria for that program was there was some preliminary data around T-cells that are -- ultimately recognize the tumor, because they have seen the PDL-1 of the tumor.

So, it's TIL that is expressing PD-1 high, they recognize the tumor, not only beyond what TIL initially identified, but they have really touched the tumor, the tumor cells. So, that was the idea around the selection process. And again, there was literature showing that these are more potent TILs, they have better activity and so killing capability.

When we presented this at SITC in 2018, we showed in fact that the TILs that are PD-1 selected have enhanced autologous melanoma cell killing capability. And it was quite remarkable. So, we decided to move that product into clinic.

In terms of what the bar would be, we have disclosed for Gen 2 a very, very preliminary set of data back maybe a couple of years ago now that its median DOR was around 2 to 7 months for our head and neck patients. So, we are looking to try and elongate the median DOR. That would be our goal for the additional cohort. .

And then, maybe just a last question Maria, in terms of the landscape of TILs, and how you think about new antigens. Do you view this as a competitive approach or a complementary approach? Because it seems there's some pharma companies that are investing in this.

And if you feel that some of these could potentially be synergistic to TILs?.

Thank you for that question. I think they make me cover slightly different landscapes. In my opinion, when we have diseases that are high mutational load, such as possibly melanoma, we're thinking head and neck, lung. These are diseases that there's multiple targets and there needs to be multiple cells that will hit those targets.

So, the challenge with them would be identifying that specific new antigen that a T-cell could target. And if you don't have that then it's really hard to hit them. So, I do think that they would occupy different spaces.

I think new antigen targeted therapies would -- could be beneficial for lower mutational load, while TIL are maybe more beneficial for higher mutational load. And this would last as long as you don't know exactly what targets you’re are trying to hit with various cell therapies. So yes, I see them complementary, maybe..

So, are there any pharma Companies that you think complement those?.

I don't know if I can address that. There's a number of companies who are interested in that particular landscape. And we of course monitor them very closely..

Your next question comes from the line of Joe Catanzaro from Piper Sandler..

Just maybe one quick one for me. So, Maria, you had mentioned that as part of your commercial preparation, clinical side engagement is a main area of focus.

Now that cohort 4 of melanomas is closed, what are the opportunities from now until potential approval to continue to maintain and expand that clinical site engagement, the current ongoing studies, allow you to do that? Would you potentially expect an extended access program that would allow you to do that? How are you thinking about that?.

As a matter of fact that is something that is very much front of mind. This is why Friedrich’s commented about this. For the, IOV-COM-202 study, we’re adding a core part into that study that will enroll melanoma patients with the selected TIL product 145-S1.

That's exactly the purpose, allow access to TIL product, while you're bringing this -- the LN-144 lifileucel to market..

There are no further questions at this time. I will now turn the call over back to Maria for her closing remarks..

Thank you, operator. Overall, I'm really pleased with the progress we have made on our prospects of becoming the leader in the TIL development, manufacturing and commercialization. Indeed, in just four years, we have gone from our first patient in the clinic to preparing our first regulatory submission for approval.

We have the potential to impact lives of thousands of patients with melanoma, cervical cancers who have exhausted current treatment options.

Work is possible, thanks to the valuable contribution of many individuals including committed shareholders, hardworking employees, clinical investigators, collaboration partners and patients and patients families who motivate us. We look forward to realizing this shared vision for this product with the individuals that are in need of therapy.

Thank you..

This concludes the call today. You may now disconnect..