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

And good afternoon, everyone. Welcome to the JMP Hematology & Oncology Summit. It's my pleasure to introduce the next presenting company, Iovance Biotherapeutics and here to talk about the company, Frederick Vogt, Interim CEO.

Just jumping right into it. We've talked about the full interim CEO title. I would love to just start off by asking what's happening there? How is the search going? And are there any updates you could provide?

Sure. Yes. Right now, the search is going. We're -- the Board is committed to getting candidates in and talking with them and seeing if we can find the right person. I don't have any updates for you. This is one of those things where, at the very end, you'll know. That's pretty much the best we can say about it. There's no real update you give during the process. But yes, it's active. Yes, we're doing it. In the meantime, I stress with everybody, as you know, Reni, that we have a full management team. Everybody is here and on board, the full C suite, Senior Vice Presidents. At our Investor Day yesterday that we held, a lot of the other SVPs that we have got to meet with investors and analysts extensively. And so you can see the full team is here, and there's really nothing at the company that slowed down even a nanosecond here as we continue towards the BLA because of the CEO search.

Got it. So why don't we jump right into it. As I've been telling all the companies that I'm talking to, I'm never privy to who exactly is listening in on this conversation whether they know the company or not. And so if you could spend maybe a couple of minutes summarizing the company and the technology platform before we dive into some of the details of some data, that would be great.

Absolutely. So Iovance is an immuno-oncology company. We're focused on polyclonal T cell products. Polyclonal, meaning products that can respond to multiple cancer neoantigens, even hundreds of thousands of cancer neoantigens. We're the leader in that space. We've been around the longest, and we've got the most advanced trials. On this slide Reni has got up here, it shows our pipeline. We've got a deep pipeline. You can see by the size of this slide. At the top, we've got our pivotal indication, which is melanoma, post-checkpoint, post-PD-1 melanoma, post-BRAF as well, BRAF/MEK. That's the indication that we talk most about publicly. It's got RMAT designation with FDA, which entitles us to accelerate a review in a lot of interactions with the FDA. And we've completed enrollment in that pivotal cohort some time ago. And it's -- at this point, we're -- that's the moment we talk about when we say we're going to file a BLA in the first half of 2022. Also at the top of this pipeline are some of our other key indications, starting with cervical cancer, and then moving down through lung and then head and neck. We presented on cervical cancer in the past and lung just recently at SITC. And post -- these are all post-Q1 indications. And again, on the left side of the slide, where it says TIL, that means TIL monotherapy. So TIL alone, just the TIL product alone without anything else besides the supportive care that we provide. As you go further down this pipeline chart, we've got TIL combinations, including lifileucel in combination with pembro, which is our principal combination that we use in our combo trials. This -- in these trials, we're trying to move earlier into earlier lines of therapy, where there's a really significant market opportunity to change the landscape of care. We've reported data on some of these combinations recently, including melanoma, cervical and head and neck combinations. At SITC, we combine those 2. And I think, Reni, you've got a slide coming on that to talk about that a bit. And then further down, we've got our other polyclonal T cell products, including PD-1 selective TIL, which is designed to be a little bit more selective for the cancer neoantigens of interest in a patient by looking for PD-1 expression, which is a marker that a T cell has seen tumor. Further down, we have the Gen 3 process, which is the extremely short process we have, the 16-day process for manufacturing TIL therapy that we've got in the clinic now. We've got PBL therapy in CLL. That's our polyclonal technology now applied to hematological cancers. And we've got PD-1 and activated TIL, which is our first gene-edited product, which we hope to have in clinic very soon, which is a -- will be the first large multicenter gene-edited TIL therapy trial when it's available. But finally, we've got our own IL-2 analog, which is a molecule we're developing as a potential alternative to aldesleukin, which is one of the molecules we use as supportive care for our indications. So the background of the company is basically pure IO. We're all about immuno-oncology. We're all about polyclonal T cell products, and we're all about solid tumor cancers.

Got it. So if we get through nothing else, let's at least chat briefly about the validation assay, which is what's on top of everybody -- everyone's mind. Seems to be the late limiting step before a lot of these things can move forward, especially to commercialization. Because as you just mentioned, the melanoma BLA is front and center. Could you just summarize briefly for us kind of where we stand right now and when you think the earliest might be that we'll have an assay to submit to the regulatory agency?

Well, we're -- right now, where we are as of today is we're way into the assay process here. So we've been engaged in discussions with the regulator. We've been working on a new assay technology for quite some time. So this is not something that's new by any stretch. What we're still waiting for is we're still waiting for the regulatory process to finish and for us to be able to talk a little bit more about what we've said with the regulator and what they've said back, that's still ongoing right now. That's not slowing us down, though. We're very comfortable when we reiterated our guidance to filing in the first half of next year the BLA, which tells you that we've got to have everything lined up. The assay has to be completed. It has to be qualified. It has to be validated. It has to be used to test historical batches. And those historical batches need to be filtered out, whether those become the Cohort 4 pivotal data set once they're filtered out by the assay in terms of which ones pass and which ones fail. The only thing -- the assay is not going to do much filtering, but we still have to test it and run it through that process. So all that's ongoing right now. It's happening in real time. The first half timing for next year is tied to all that.

Got it. And I think one of the things just briefly before starting to jump into the data, some people suggest that competitors must already have an assay in hand since they have INDs that have been cleared and they're in the clinical studies. But you guys also have multiple clinical trials that are underway, right?

These have been cleared and are in clinical studies with assays. So that's the rationale. I would question the logic behind that.

Right, right. So I mean what do you think about just the notion that the competitors, I guess, have an assay in hand?

I mean competitors are working on all sorts of stuff, and that's why they're competitors. They design their own products and their -- you see there's a whole number of companies now coming into the TIL space. I don't think at the IND stage, at a pre-IND meeting, which is the meeting you have before you file an IND, you can have any kind of substantive discussion of this kind of thing. I think what you can do is make some proposals. The FDA may make some very quick comments. But there is a night and day difference between having a discussion before an IND and having discussions as you lead up to a BLA. If you've been in drug development long enough, you'll know what I'm talking about. But if you haven't been, it's like -- it's less than 1% of the interaction. I don't know what it is, but it's very low. And again, the FDA, when you come to market, is at their highest attention levels. I mean that's -- this is where they ask all the questions. It's where everything comes out. This is where they want to have the discussions with you. When they're at the IND stage, they're -- more than anything, they're concerned about safety.

Got you. So let's dive right into it. You guys had a nice update, of course, at SITC. You had this very nice combination with TIL and pembro. Would love to get, just for investors, your key takeaways from the data that was presented. But then also, what are the next steps for the program? And I think one of the things that you highlighted in the pipeline, which I really like, is really where TIL by itself, TIL in combination can fit within a particular paradigm, right, whether it's melanoma, whether it's earlier lines, later lines and the like. And you have quite the opportunity here. This data set, I think, really help investors kind of understand how this could move further front line or into the front lines of therapy. But would love to kind of hear your thoughts.

Yes. It fits with the general strategy in oncology drug development of getting an approval. In a late-line indication, sometimes like in our case, an accelerated approval, then running a confirmatory trial in an earlier line indication, that would serve to confirm the late-line indication but also massively broaden your label at that point in your patient population. So we're always -- like everybody else, we're always following that general approach in our drug development. But really, if you just want me to summarize the messages of the data, both at SITC and ASCO, in melanoma, post checkpoint, we're -- we've got what we think are very good numbers in terms of response rate, durability. This is something that is addressing a significant unmet medical need. There's nothing else for these patients right now, anything comparable to this, that we think this is really something that is sort of the center of our thesis as Iovance's investment. When you talk about melanoma beyond post PD-1, the data that we had at SITC most recently shows what we're thinking. There, we've got, again, small numbers, doing 10 patients total. But you've got 3 CRs and 3 more PRs. So you got a 30% CR rate, 60% overall response rate. Pembro alone only gives you 33% ORR and well under 10% CR rate, so you know TILs are adding significantly to it, if not doubling, or in the case of CR rate, tripling it. These are significant increases for an immuno-oncology combination. There aren't any other agents out there that can do that right now in combination with pembro. The closest thing that can do anything in this area is CTLA-4. But we are -- we've got something here that -- although it's a cell therapy and it's a bit more complicated to handle, combines fantastically well with PD-1, PD-L1 antibodies that are out there. And that extends across the entire portfolio. As you got on the slide here, Reni, you got down the bottom, melanoma, head and neck and cervical together. So you can see that effect working across 3 different indications now, which is nice. That further validates the platform. This is in total across all 3 of those, it's 42 patients worth of combo data with pembro plus TIL therapy. And again, we're seeing significant increases in response rates over what you would expect from the monotherapy alone.

Yes. The data, as we saw, I thought was very impressive. And I guess one question that we always get is, okay, this is great. How many -- these trials continue to enroll, I'm assuming, correct me if I'm wrong. But how many more additional patients do you think we'll see from each of these programs? And when might we see that updated data?

We're continuing to enroll in many of these programs, like, for example, in melanoma. I can't tell you when we're going to see the updated data. I think we'd have to have a meaningful -- depends on enrollment stuff that is not straightforward to predict right now. But at some point in the future, we'll probably put out more information on these cohorts or in other cohorts that then we think it's meaningful and we think it matters from both the scientific communication and investor communication perspective. I do 2022 -- 2021, we put out more data than we ever had before. So we'll try to keep that up in '22.

Excellent. The -- one of the other programs that we're, of course, very interested in is the non-small cell lung cancer program. Would love to just have you kind of walk us through that data. The Moffitt IST is kind of what got a lot of people interested. I think that the data continue to show very well, but I'm kind of curious as to what you're hearing from investors as well as how you are thinking about next steps for this program.

Absolutely. So we think this is a fantastic indication for TIL therapy with a 21% response rate in post-checkpoint patients who have seen -- heavily pretreated, seen chemo and checkpoint, all responders in this study saw heavily pretreated. We have a new slide up on our deck actually just for this, Reni. You get a chance to take a look at it, up on the website, which is more of the pretreatment that we gave each patient. But a 21% response rate is really meaningful in this population. If you remember, checkpoints themselves got approved in the post-chemo setting at 20% response rate. So this is a significant. The durability -- we've got durability here. Yes, the median durability in this study is not something that we're -- that would be, from a regulatory perspective, something that we would point to. What we have here is strong signs of durability that should work in a well-designed study like LUN-202, where we've narrowed down the patient population post checkpoint. So in the LUN-202 study, we're focusing on earlier line post-PD-1 patients. Nevertheless, we still have one very long CR and another shorter PR that's still quite long, if you look up there in the upper right. And then the Moffitt IST, which is a patient population that had progressed on nivo and then was given nivo plus TIL therapy showed 2 very long CRs out past 15 months. The Nature Medicine paper, if you look, that's the IST that we funded with Moffitt. So we've got all the signs here that we need to say we've got an ORR that's reasonable and we can achieve an mDOR that's reasonable in this patient population. That's why we're running LUN-202 or aiming to make that a new registrational study and talk more about that as soon as we can.

And so it seemed like there was -- I don't know if it was investor disappointment or something that investors were harping on. I thought it was just maybe that the response rate didn't improve when the study results were read out. Is there anything else that we should be kind of thinking about? And then to the same vein of combinations, right, like in melanoma, you're combining with TIL and pembro. Unless I missed it here, how should we be thinking about it with this program?

I think the most important thing to think about is that the response rate that we've achieved in the signal-finding study is meaningful in this patient population. And the durability, if we run the study the way we intend to run it, should be meaningful as well. We think that's supportive of a potential registrational strategy for TILs in a very large lung population here. And this is something that we think we can do. And this is -- of course, we're breaking into an area that's completely untapped, the thoracic surgery community. And we had to educate them heavily to get this trial run, and we had to do a lot of work to even be able to run in lung in a multicenter trial. Now we've broken that ground and we can go to the next level and run a big registrational study here. So I would be thinking about this as another leg of the TIL platform that we have at Iovance. It provides further support for the broad applicability that we always talk about when we say that 90% of cancers are solid tumor cancers, this is a huge chunk of that. And it's really a major part of the value of this technology.

And combination wise, Fred, how should we be thinking about that?

Yes. With combinations, I mean, with -- in all cases right now, we're working towards earlier lines of combination. So you can see across -- back on the pipeline slide, I kind of hit on this. Across all 4 of our big indications, we're pushing in that direction. I think you should think that Iovance would develop from late lines to early lines in all cases. I mean that's something we would try to do pretty much across the board once we have the resources to do it and the time to do it. Obviously, we're focused on melanoma first. But after that, I think lung is pretty hot for us and we still got cervical and we still have head and neck. So I would think about it as a sort of a continuous process of moving from late line to early line.

So before we touch on the milestones, you guys had an Investor Day or a day to go through the manufacturing facility. How did that -- I was just kind of curious, how did that go? And what were the key take-homes there?

Yes. So we had a day here, I'm actually at the facility right now. So in Philadelphia, our manufacturing facility, where we gave tours to the investor community, the analyst community and showed them the capacity of this operation. I think it's very important sometimes for investors and analysts to actually see it, see the size of it and the scale of it and how well done it's been, how well designed the facility is to the extent we can show it to you. And I think a lot of them got that out of it. You saw some of the -- if you read the other notes from your colleague, Reni, you can see all the notes that are out there about it. I also wanted to highlight the commercial preparations we have at the company as well. So we talked about both commercial manufacturing. There's a lot of discussion about scale. Can you handle the scale for all these indications? How do you expand? How do you make this -- how do you optimize cost of goods sold or COGS? Big important questions we spent a lot of time talking about. But also about the commercial launch preparations, what we're doing there to address treatment centers, try to reach into community setting, our proprietary chain of custody, chain of identity quality control system that we have called IovanceCares and so on.

Excellent. So at the last kind of 30 seconds, if we can just talk about 2022 and milestones.

Yes. So this is a nice number, you got here, Reni. Yes, we're working on the FDA -- I wouldn't say FDA meeting. We're having multiple interactions with the FDA. So it's RMAT, let's you have as many interactions as you need. They can be formal or informal, so don't assume there's one meeting or some kind of discrete event. It's been pretty clear publicly that we're at it. It's an ongoing process. And that's a good thing, actually. You want to have a lot of engagement. The submission of the BLA for lifileucel, we're still guiding towards the first half of '22, and we think we can do that. We think we're on track for that right now. Cervical cancer is still something that's dependent on a couple of things. We have to have a discussion with FDA about the fact that KEYNOTE-826 changed the landscape in cervical. Now you've got 240 plus pembro in the frontline and the [ likely ] full approval of pembro in second line after chemo. So with that setting, we have to go back to the FDA and talk more about Cohort 2 of our study, which is the post-PD-1 population. We're the only ones that have a significant amount of data in post-PD-1 cervical patients right now. Other people are moving and starting to enroll in that area with Seagen. But we've got a lot of data already, so we want to talk to them about whether that could support an approval in combination with the earlier Cohort 1 or in some other setting that they find agreeable. And then the potency assay has to be resolved for that as well, too. But when we get that resolved for melanoma, we think we'll be able to resolve this for all indications.

Terrific. Well, Fred, thank you very much for the time, as always, and very much appreciate all the answers.

Thank you, and please reach out with any questions.

You got it. Take care.

All right. Thanks. Bye-bye.