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

Well good afternoon, everyone. It's my pleasure to introduce Iovance Biotherapeutics, Maria Fardis, President and CEO. Maria, thanks for joining us here. And as I've been kind of starting off all the conversations with our cell therapy companies, we don't know exactly who's in the audience, whether they're familiar with Iovance, whether they're not, so would love to take maybe a couple of minutes, if you could give us an overview of Iovance.

Yes, absolutely. And thank you for the invitation, Reni. This is great to be here. Iovance is a cell therapy company for administering a product called tumor-infiltrating lymphocytes, or TIL, for solid tumors. The original concept for the product came from National Cancer Institute, or NCI. We took a license in 2011. We have developed a product into now a commercial-ready product. The manufacturing process initially was around 6 to 7 weeks, and we have optimized that to a much shorter manufacturing process. We are very much focused on melanoma, the first lead indication, as well as cervical cancer. We are late stage in our development. We are running 2 pivotal programs, one in melanoma and one in cervical. We have met with FDA for both indications as part of an end of Phase II meeting and have agreed on the patient population on the registration path for these products. Where we are from a corporate perspective is we expect to finish our work in melanoma and submit a BLA to FDA later part of this year, and that's one of our corporate goals this year. Thank you. In cervical cancer, we continue enrollment, and we expect to complete enrollment by around midyear, so in the next couple of months. And in other indications, we are very much interested in head and neck, where we have been introducing newer products into clinic for this specific indication as well as non-small cell lung cancer. That particular product is introduced as part of a basket study called IOV-COM-202. We also work very closely with our collaborative partners, including MD Anderson or Moffitt Cancer Center, when we have a new indication that we introduced. And we start with doing a sort of a evaluation of a new indication first through these collaborations. And once we find a proof of concept, then we bring that program in-house and run a study. You might have seen some preliminary data from lung at AACR that was presented through our collaborators at Moffitt, and that has triggered us to explore non-small cell in a more meaningful way. The collaboration with MD Anderson is focused on multiple indications, including ovarian, colorectal and pancreatic, as you see on this slide, and we have 2 different studies as part of that collaboration. I'm happy to answer any questions you might have, of course, beyond what is on the pipeline and very high-level brief overview of the company.

Yes. No, that's perfect. And maybe before we get into the data because this is a post-ASCO [ EI ] forum, and we're going to jump into the data a little bit. But before that, I'd love to kind of get your thoughts -- high-level thoughts on where -- the cell therapy space is advancing very, very quickly, right? We're evolving very quickly. And so I'm curious as to where you see Iovance, this platform, kind of 3 to 5 years from now, given the competition that's growing, right? There are CAR-T players that are going after solid tumors. There's iPSC players. There's a lot of people wanting to get to the Holy Grail of solid tumors, where I kind of feel Iovance is in the lead. We have 3 to 5 years from now, how do you see this unfold?

Yes. It's a great topic. Looking at our crystal ball of what do we think the future is going to look like in the next few years [indiscernible] driven field, so a lot of what I'm going to say would have to depend on data and what data we would have in the next year or 2 to be able to base on that and plan our next-generation product. But I think -- let me just step back in a sort of a broader overview. When we think about TIL therapy, the benefit of this particular therapeutic has to do with, twofold: one, as long as you don't know what is the target for the disease such as melanoma or cervical or head and neck, what exactly is that one or combination of multiple targets, the neoantigens that are creating and meeting the driver mutations that are causing the disease? As long as we don't know what those driver neoantigens are, it's best to rely on our own immune system, where the cells of the new system have recognized those specific neoantigens. So that's noteworthy because at this point in time, we still haven't figured out what is that one particular driver mutation or a combination of them that could cause the disease, and eradication of those would remove the disease. A second aspect, which is sort of correlated to the same thing, is the polyclonality. So the fact that a product like TIL is able to target multiple targets, multiple neoantigens. And we think that a disease like cancer is not extremely simple, although, in some cases, if you have a biomarker-driven mutation, maybe that biomarker can be targeted. But in the grand scheme of things, these diseases -- cancer, in general, is a result of multiple mutations, typically, leading to the disease. And particularly on the high mutational load diseases, the polyclonality is a key driver for response. So the combination of both of those from my perspective makes TIL a very attractive therapeutic option. Now fast forwarding into the next 3 to 5 years, where are we and where we are going, where we are right now is we are looking at TIL as a bulk product. This is unmodified. Even though it's unmodified, what it's doing is we are sort of amplifying the product ex vivo. We are rejuvenating the product, and we are putting it back into the patient. In the next future, 2 to 3 years, we are doing multiple things to change the product. We are genetically modifying the product. We are shortening the manufacturing process. We are selecting a subset of TILs, which we think has more potency in them. And any one or a combination of these could change the future direction of where we are going. A number of these are getting introduced into clinic this year, next year, the year after, and we think a lot of that may change our direction. But I don't think we are coming off of the TIL platform. We are on that TIL platform for 2 reasons, as I noted earlier, which is the polyclonality, and so long as we don't know the target, relying on the tumor or our own immune system to identify the neoantigens and bind to those neoantigens. Those 2 pivots are going to stay with TIL.

And you touched upon this but would love to expand. The manufacturing process is obviously key to this, right? Like normally, when people think of TILs, right away, the first word that comes to mind is cumbersome. But I think you guys have really cracked this nut, if you will. You have a couple of processes. I guess I'd love to just quickly understand maybe the difference between them. And then more importantly, from an investor perspective, does it become a situation where the final products ultimately have one process? Or do all the products have their own process?

Excellent. Thank you. You're correct. So the first-generation product that we started evaluating was what we have licensed from National Cancer Institute, from NCI, from Dr. Rosenberg's lab. We called that a Gen 1. That product had about a 6- to 7-week duration. And while that was probably adequate for patient population that did not have alternative therapies, which was the case back in 2011 and '12 even, that is not [indiscernible] in today's landscape. Today's landscape, we have significantly better therapeutic options. Immune checkpoint inhibitors have been developed. Multiple of those have been offered. BRAF/MEK-targeted therapies have been developed. So a patient really cannot wait for 6 to 7 weeks to get their therapy. And so that's where we started. So our Gen 1 manufacturing product had very much the features from NCI. It was a non-cryopreserved product with about 6- to 7-week duration. For our Gen 2, given that we didn't know whether there is a specific proprietary behavior of these cells, we actually targeted to keep the product the same as Gen 1. Our Gen 2 product was a 22-day manufacturing process that we developed in late 2016 and early 2017, but we wanted a cryopreserved product. So it's frozen so that we can store, we can ship and we can deliver out to the site where the patient is ready. And we -- our goal was to keep the same profile as our Gen 1, which have license from Dr. Rosenberg's lab. So our Gen 2 is what we intend to take into the commercial landscape. We think it's very robust. The manufacturing success rate is well over 90%, and we have dosed well over 300 patients. So this is what we are preparing for commercialization. At the same time, we think about what is our life cycle strategy, and we have introduced what we call a Gen 3 into clinic. The Gen 3 process is a 16-day manufacturing process, and we have learned that we don't have to keep the profile of the products perhaps the same. So we started thinking what else could we do for these products so that their portfolio doesn't have to be completely identical to the previous generation. So Gen 3 has a younger profile. It has better use markers. It is a 16-day manufacturing process and we just -- we have introduced it into head and neck indication earlier part of this year. We know we can shorten the manufacturing process. I think we still are trying to understand whether the distribution of the cells can or should be different, and again, this is part of our life cycle management strategy. But in minimum, to think about a Gen 3, there's potentially 2 benefits. There could be clinical benefits, but there also certainly could be a COG reduction benefit, cost of goods reduction benefits, and to optimize our manufacturing process. So that's how we have been thinking about it. Does that answer your question, Reni?

It does. It does. So maybe we can jump right into the -- to some of the data. It -- you had an update this year at ASCO, like you mentioned there was the partners that you have, Moffitt, who gave an update with non-small cell at AACR. Could you just take us through what's the latest here and what we should be, in particular, paying attention to?

Sure. So the slide you have is on the melanoma data. Would you like me to speak to the melanoma data for a second?

Yes.

Yes. Thank you. Okay. You're correct. Cohort 2 is the study that we have and the cohort that we have been conducting. So we have nice, long-term follow-up data for Cohort 2, which is on the slide you're looking at. In Cohort 2, we showed at ASCO that at 18.7 months of median study follow-up, a median duration of response has not been reached. The response rate remained at previously reported response rate of 36.4%. So we are highly encouraged by the durable responses that we are seeing in the Cohort 2. Cohort 4 is our pivotal cohort, which we started after a discussion with FDA. The patient population is identical between Cohort 2 and Cohort 4, and the sites that have administered are almost identical between Cohort 2 and Cohort 4. Cohort 4 only has as a primary endpoint IRC read or as a primary outcome. And so in about a month ago, [ Reni has that on the slide ], we presented data that we had submitted to FDA as part of a pre-BLA interaction where they requested for us to cut the data for Cohort 4. At the time, we only had 68 patients who had had 2 radiologic assessments and so that's the data that we provided to them. And we also discussed that Cohort 2 plus Cohort 4 is available should that be acceptable by the agency, and that data is also noted on this slide. What we noticed on Cohort 4 was with about 5.3 months of median study follow-up, so very short study follow-up, we're seeing a 32.4% response rate, which was really comparable to Cohort 2 when we had a similar amount of follow-up. The combination cohort, Cohort 2 and Cohort 4, had a response rate of 34.3%. What was remarkable was at a nice long follow-up, around 10 months as an average for the 2 cohorts, we still hadn't reached the median DOR. So that's the data we press-released before ASCO, and we presented at ASCO just to tell you of the data.

And I think one of -- it's funny. Sometimes when we're talking to investors, they say, "Well, we kind of expect those to work in melanoma." That's where the initial data came out of, right? And it's not in any sort of an immune-privileged tumor. And then you guys generated some very interesting data in cervical. And so -- and kind of backing up the fact that, hey, look, it's more than just melanoma. There are other indications. And of course, you've gone on to the basket study. So the cervical data, what's the key things that we should be focused on in here? And I guess, more importantly, from a development perspective, I think you mentioned enrollment will be complete by the middle of this year. We'll probably see the data 6 months to 7 months after enrollment is complete. Maybe just fill us in on how that's going to unfold.

Yes, absolutely. And then a comment on whether melanoma is the only indication that TIL would work on or not. This is, basically, our immune system, again, amplified and rejuvenated. So I would expect that it would work in [indiscernible] no guarantee the exact same manufacturing method is going to work for every single product. But there's a good chance because it is, again, based on our own immune system principles that TIL actually works. You're correct. We showed at ASCO last year, we showed data that is on the side on the left-hand side, from 27 patients, we had a response rate of 44%. We had showed that 10 out of 12 responders were still in response at 6 months of follow-up from the TIL infusion. We were highly encouraged to see this data. This is quite maybe similar to what Dr. Rosenberg had also showed, a fairly small set of patients, around 9 patients that had initially presented, and later on, they had expanded and they were seeing very similar type of responses with durable CRs in a cervical setting. So they had 2 patients that had been in follow-up for 5 and 6 years in cervical cancer with durable CRs. So we felt that, that signature of TIL is very much consistent between cervical as well as melanoma. We -- you have the competitive landscape on this slide, which is really helpful. Thank you. I think it is important to understand that the landscape of patients is changing, particularly in cervical as well. With entry of immune checkpoint inhibitors, I do feel that the patient population may be changing. It's really remarkable to see responses in post-PD 1 patients in both indications. So we did discuss -- obviously, we have showed our data heavily in melanoma. In the cervical setting, we only have 4 patients with prior immune checkpoint inhibitors.

Got it. And just maybe before we talk about what's upcoming, you have this basket study that's ongoing. It's clearly to expand, right, and look at all these other indications. But non-small cell appears to be getting an interesting signal. Kind of your thoughts there, ways to maybe accelerate that program and when might we see some data from that basket study.

Yes. So we saw some preliminary data from our collaboration with Moffitt at AACR. There is a couple of points to think about. Of course, it's noteworthy to say that they use their own manufacturing process. There's other points of differentiation between their study and ours. But at the same time, I think it was really remarkable to see durable CRs with TIL therapy with a non-small cell lung cancer indication. So this is the basis for our own 2 cohorts in our COM protocol and our basket protocol, IOV-COM-202. We continue enrolling patients. It is a broad patient population still that we are enrolling into our 2 cohorts. And answering your question, Reni, about what other studies are we doing in non-small cell. There's certainly registration targeted path that we're thinking about, not too dissimilar to what we did in melanoma or cervical. We first think about what is an unmet medical need patient population and how do we address that patient population better. We design a study where we target that specific patient population, and we think about maybe assigning 2 types of the design where you expand if you see the acceptable response. And if you don't see acceptable response, that's fine. We can rethink about our strategy or consider a combination strategy. So that general strategy is something we're thinking through for non-small cell as well as the 2 cohort studies that we are conducting.

Got it. So everyone in our world is not what you've done for me, but what have you done for me lately, but kind of what's coming up. Clearly, you guys have an action-packed sort of second half, right? You have BLA filings. We assume that with those BLA filings, there's data, top line data releases. Can you just take us through kind of the cadence of how we should be expecting data to flow over the next 6 to 12 months?

Yes, sure. Very first, at this point, given that our interaction with FDA is expected to be sort of heavy in the second part of the year, a lot of this depends on the interactions we have with the agency, and I want to make sure that I emphasize that. Now even our BLA planning and submission, the follow-up amount of time all depend on our interaction with the agency and a clear agreement with them as to how much follow-up is adequate. We are very encouraged with the fact that melanoma program enrolled well in advance of its time line. So we have quite a number of opportunities in terms of follow-up to provide as long as a follow-up as the agency might request. The cervical study is expected to enroll by around mid-year, as I noted earlier. And the data flow from that and the follow-up is very much subject to discussions with FDA, of course, as I noted earlier. So we absolutely are preparing for both BLAs. We have already started putting modules of the BLA together for melanoma and cervical. And we hope that subsequent to the interaction with the agency that we are able to submit at least 1, maybe 2 by the end of this year, and we're very focused on building our commercial and commercial manufacturing organization in anticipation of support of commercialization of TIL.

And just in terms of data, I typically think of ESMO or SITC and the like. Should we be thinking about those conferences for the rest of the pipeline? Or is that really kind of a 2021 type of event?

Yes. I think that the timing would depend on the agreement with the agency a little bit. I want to make sure that we don't cut the data prematurely. Even the 68 patients that we cut was based on their request. They wanted to see the data and as part of a pre-BLA sort of a dialogue that we have ongoing with them. So we have not committed to a specific data flow. I have committed that we would like to present our data in a scientific conference, as you noted. But from a timing perspective, I want to be sure that we have agreement with the agency as to when we expect to cut.

Got it. Thank you very much for your time. I know I've gone over by a couple of seconds, and I have to run down the virtual hallway. So thank you, Maria, for your time.

Thank you as well.