Iovance Biotherapeutics, Inc. (IOVA) Earnings Call Transcript & Summary

Good afternoon, everyone. My name is Kelly Shi, one of the biotech research analysts at Jefferies. Thank you, everyone online, for attending our Virtual London Healthcare Conference. Today, we are very pleased that we have Ms. Maria Fardis, the Chief Executive Officer of Iovance Biotherapeutics, joining us for this fireside chat session. And at the end of the session, if time allows, we will have a Q&A. [Operator Instructions] And thank you for joining us, Maria.

Before we get into some of the more detailed questions, maybe we can touch on the high level and then your vision or your [indiscernible] for TIL therapies. You've made significant strides since becoming CEO. Do you see TILs as a therapy for earlier lines? Or do you expect these therapies will be relegated to last in line?

Thank you, Kelly, for the invitation and Jefferies team. Yes, thank you. That's an excellent question in the sense that it allows us to sort of think about the strategy around development of TIL. Of course, any sort of therapy, one before administration, the risk/benefit has to be considered, so I want to be upfront about that. Now in terms of our positioning of TIL, we have started targeting late-line patient population because this allows for a potential single arm to be supportive of registration and it allows for a possibly shorter, faster path to registration of the product. However, when we think about where else a product like TIL may be beneficial is adjuvant therapy as well as in early line is strictly positions that we have been thinking about from a clinical perspective. In an adjuvant setting, a tumor is resected, and if it has been resected at therapy, may be initiated subsequent to such resection. In fact, checkpoint inhibitors have been moving into this space very well, and one can imagine utilization of TIL in combination with checkpoint therapy in that setting may be an option. In addition, we feel that moving into early line of therapy where patients are checkpoint-naive and it allowing for a combination of TIL plus a checkpoint inhibitor, I'm going to refer to it as ICIs, might have really great promise as well. Again, the patient's immune system has not been exposed to significant pressure through various lines of therapy that may be prior ICIs. In fact, we presented some very preliminary data at SITC where we combined TIL plus KEYTRUDA in head and neck cancer. And granted the number of patients is very small, but we are seeing some encouraging results in terms of the responses. And so that may be a setting that one could pursue for additional indications.

And I want to add a little bit on this. From our cell therapy conference hosted like 1 month ago, we invited 2 patients who experienced the TIL therapies. And they strongly advocate to actually moving TIL into front line to benefit the patients. I want to ask, is this view also shared by physicians? What have you heard so far? Is it consistent from patients to physicians?

As a matter of fact, it is. And in fact, it's been -- really the pressure has been coming from physicians that we would really like to have access to TIL in earlier lines of therapy. I think they recognize that it really is never good when we have a cancer patient that ultimately is treated and once they recur, they're so much harder to treat. So if we can offer anything to patients that is sort of once and done, don't allow them to recur, give them the best opportunity for a long, durable response, even though that may be more complex in a front line, that may be more beneficial. So yes, absolutely. A number of our physicians have been asking us what do you have planned to move TILs into earlier lines in adjuvant setting, as a matter of fact.

That's very informative. And we have -- let's talk about the regulatory path of the 2 programs in pivotal phase. We have heard about the U.S. regulatory process recently, and you are clearly working towards that to meet the FDA requirements. And how will investors know why you are there as it relates to the potency assays you mentioned? And you have a second assay that have been developed but not validated yet. And how long will this take together? And is there a regulatory precedent for the current assay and for the second assay? Yes, we can start from there.

Excellent. Thank you. So I would expect that we would be able to communicate if we have clear alignment with FDA and more clarity on the BLA submission time line, but I don't think I can commit to that specific time line right now. The reason we haven't communicated a specific month for filing is we continue the dialogue with FDA, but we don't have specific alignment in terms of when exactly we are able to share information. And to a degree, that alignment also will depend on the timing of the review of the documents, which is not always in our control. So we are providing documents to FDA to address their questions and comments, but we certainly cannot commit until we have absolute clarity from them. In terms of your subsequent questions in terms of duration of time for validation of assays, it's usually a 2- to 4-month duration, assuming no major issues come up as you're validating an assay. And your subsequent question also was whether there is -- these assays have been provided to the agency and sort of how we are thinking about them, we -- the way we are thinking about it is we're thinking our first and second assays are great. We continue on working on additional assays. We felt that the approach of multiple shots on goal may be very beneficial, and the goal being provision of a potency program or a matrix that FDA ultimately accepts. And we feel that this should yield to a submission in 2021.

Great. And we also understand the challenge here is, at the FDA side, that there's no prior examples for the assays like already there to define TIL products. So I wonder -- so with your internal effort, do you have other resources or maybe like a KOL network you can rely on to help FDA to form a view how to define a TIL product?

That's an excellent topic. Thank you so much for the question. You're correct. I think this is the pros and cons of being first in class, to a degree. When you are bringing a new product to the agency, there's no precedent, so we can't just rely on that precedent. So we are in a bit of a unique landscape in providing information to FDA. We do have a network of KOLs. In fact, many of them had reached out after we press-released it, offering to want to talk to us and make sure that FDA has appropriate information just to kind of put the -- sort of a perspective on what we did with the agency. The assay that we have used, as I noted, is the gold standard. We have talked to KOLs as well as a number of different investigators who have worked with TIL therapy, and we certainly take advantage of their wisdom and their years of development of assays. So yes, there certainly is additional resources, additional KOLs who are very familiar in the topic. We certainly talk to them. And of course, the agency is welcome to consult with them if that becomes something that they're interested in. But we do talk to most people who have been doing TILs for decades to make sure that we understand how they're thinking about defining the product, absolutely.

This is a very helpful discussion for investors. What is the regulatory process for Europe? And when do you plan to meet with EMA? And do you anticipate similar questions from EMA as well as from FDA?

Absolutely. So we are intending to engage the EU health authorities once the potency matter is settled with FDA. We have prioritized the U.S. FDA interactions to assure we have a clear alignment on the CMC topic before approaching EU in terms of a centralized procedure, having possibly the same expectation as you do, Kelly, which is they may be asking the same type of questions. So we want to make sure that we address that with FDA before we start a dialogue with -- in a centralized procedure with EU.

I see. Let's turn to the clinical side of 2 pivotal trials. So for the melanoma trials, the data gathered from Cohort 4 suggests equivalent efficacy to Cohort 2. Can you discuss the -- where there are any significant shifts in baseline patient characteristics across the 2 cohorts? And when do you hope to present those data? And when can we expect a follow-up on the duration of response for the Cohort 2 data? And we know it's already gathered, but we just want to know how much longer it can go.

Again, fair question. Yes, you're correct that our data from Cohort 4 suggested that the efficacy was pretty comparable with Cohort 2, very similar in the amount of follow-up that we had, which was approximately 5 months at the time we had initially cut the data to provide to FDA. We haven't reported baseline patient characteristics for Cohort 4, but the inclusion criteria was very much the same between Cohort 2 and Cohort 4. And the majority of the sites that enrolled patients in Cohort 4 were overlapping with Cohort 2. We have previously said that we plan on presenting the pivotal data at a medical meeting. We want to make sure that we provide this data of course for submission. The data cuts typically have to be contemporaneous for submission, so the timing of presentation is not entirely clear. It somewhat would depend on when we end up cutting the data to provide to FDA. So for that reason, I cannot give you a very accurate time frame. It really is somewhat connected to the FDA and the submission to the agency. We are not providing of course any specific guidance in terms of the next data cut for cohort 2. But I am, as much as you are, encouraged if we still see a median DOR not reached at the next data cut for Cohort 2. It would be highly encouraging if that's in fact the case.

Okay, we'll stay tuned. In terms of cervical cohort, how many patients are PD-L1 active versus inactive -- positive? And also, is there a difference on response rate to impede PD-L1 activity in the positive patients? And also, what is the breakdown of HPV-positive and inactive status? What should we expect regarding duration of response in cervical? And when can we expect those data?

Yes. So when we decided that the cervical program is going to be pivotal, similar to our other cohorts, when we agree with the agency that a cohort or a study can be pivotal, typically we don't cut the data anymore. We don't compile the data. So I actually don't have visibility to -- beyond the 27 patients that we presented at ASCO 2019. We did not necessarily break the data down by sort of specific subgroups of PD-L1 expression level or otherwise. Once we have the data, again, it requires an agreement with FDA in terms of amount of follow-up to start compiling the data. We might have better visibility. But at the moment, we don't have visibility to the pivotal cohort.

I see. Let's talk about the commercial launch preparation. Given the time line probably now pushed out until 2022, how are you going to utilize those extra time to help you to prepare for a market launch or 2 market launches in '22?

Yes, absolutely. We are actually very excited about our commercial activities. We continue very much preparing our clinical sites to become commercial sites. We expect that there will be well over 40 sites that we are preparing and addressing -- bringing the product to the commercial landscape. We continue our discussions with payers, trying to make sure that the payers, both commercial as well as CMS, are comfortable with our product. So the dialogue in terms of the commercial landscape continues at full speed, and we feel that we just got a little bit more time to prepare. And so that actually is a welcome opportunity for our commercial team. That's how they are looking at it.

Great to hear. And do you expect approval of melanoma and cervical come at the same time? And also, how should we think about the pricing for TIL if it's approved? Do you benchmark to CAR T or are there any other factors you will consider for the pricing strategy?

Certainly. We -- although we have done extensive market research for pricing, we haven't quite finalized our pricing. And typically you want to make sure that you understand the product very well. And we are very encouraged with Cohort 2 data, seeing that the median duration of response had not been reached the last time we cut the data. So it's important that we make sure that we understand the product as to how much durability would it offer to patients. And that certainly has an impact in terms of pricing. In terms of approval of both melanoma and cervical, it's a little difficult for us from a submission time frame to decide are they going to be on top of each other or are they going to be sort of staggered a little bit? The discussion with -- on melanoma really of course has to do with the potency assay. We have the amount of clinical follow-up they're looking forward to see, so that's great. But we want to make sure that the order of events are, one, the potency assay has to be resolved with FDA, and then this allows for the melanoma submission. The cervical submission would have still 2 questions, making sure that they don't have any further questions on the CMC front, and then how much clinical follow-up do they want from cervical. So right now, we're still very much focused on melanoma. But it's true that if the discussion continues through the course of 2021, we may start engaging the FDA also on cervical program and the amount of follow-up. But right now, we still are very focused on melanoma and melanoma submission for now.

Okay. Well, we'll wait for your update. And if you are able to launch 2 products at the same time, would you anticipate some synergy? Or it's not necessarily the case?

I do expect a lot of synergy, as a matter of fact. So the sites -- many of the sites that we have used across the program are the same clinical sites. The investigator may be different because their expertise may be different, but their -- the site itself and the infrastructure work that we put in, in preparing the site is the same. So for example, we understand what is the orchestration of the cell therapy within a site, how our chain of identity and chain of custody system will connect to the staff at the site and all of that is the same regardless of the indication. So there certainly is significant synergy once we prepare a site. Going from one indication to the next is significantly easier.

I see. And are there any challenges you foresee in the launch of TILs since it is a brand-new therapeutic module? And how are you going to remove those challenges? If you have done marketing research in both melanoma and the cervical space, would you mind like sharing with us and investors?

Yes. There are unique things that are associated with TIL. From a touch point perspective, TIL has a broader touch point set at a clinical site. So if we compare to CAR Ts for example, CAR T therapy is mostly associated with hematology/oncology because that's where the patients are, and then possibly cell therapy. As we think about TIL, and you brought up cervical indication, that's a great introduction to this, the melanoma patients are coming from different units than the cervical patients may be coming through. So the touch points that we have at the hospital are very broad. And that's -- but that's why we spend a lot of time preparing and understanding what does the hospital do, what is their routine and how do we integrate into their system without disturbing their process. So it is quite time-consuming to make sure that we understand their system, we integrate into their system. We make it easy and convenient for them to receive our product and administer it. Those are important goals for us. And really ultimately at the end of the day, we want to make sure that it's a patient-friendly approach in terms of the infrastructure as well as the system that we put in place in communicating the patients and patient care system. So you're correct that it is a bit more complex. This is why we -- you were asking what is unique about it? You got to start early. Planning early and preparing the sites is probably the most important thing. And I do want to remind many of these sites were participating in our clinical program. And I might have said before that we didn't necessarily meet every single site in a clinical setting, but we started with a very broad footprint in terms of our clinical sites, both in U.S. and EU, for that reason. That if we touch the product, if we go into a contract with them, if we understand their infrastructure, that all will be helpful ultimately when we come into the commercial landscape. So this preparation for us started some time ago and it continues. In addition to the clinical sites, we're going to additional sites. But it is critically important to understand the sites and what their routines are.

What percentage of overlapping between the started sites and your targeted sites for commercial launch?

There is good degree of overlap between them. However, we have a lot more commercial sites that we had initially used in a clinical setting. So we are going into sites that they have not been part of our clinical program, and we are really walking in for the first time for commercialization.